Rabies awareness in eight Asian countries.
Rabies is a deadly zoonotic disease most often transmitted to humans through a dog bite. Human mortality from endemic canine rabies is estimated by WHO to be around 55,000 deaths annually, with over 31,000 deaths in Asia alone, mostly children. Most of these deaths could be prevented through post-exposure prophylaxis (PEP), including immediate wound washing, rabies immunoglobulin administration and vaccination. Unfortunately, at-risk populations are not well-informed of the risk of rabies and what to do in the event of an animal bite. In order to identify the main gaps in rabies information and better define the most urgent information actions to be undertaken, the Asian Rabies Expert Bureau (AREB) conducted a multicentre, multi-country survey of patients seeking rabies post-exposure prophylaxis in rabies prevention centres from 1 July 2007 to 31 January 2008, in Bangladesh, China, India, Indonesia, Pakistan, the Philippines, Sri Lanka, and Thailand. Questionnaires were completed for 4377 subjects in the eight countries. Data was collected regarding the patient, former rabies exposures, the present wound, rabies exposure management, and rabies awareness. Two major issues were identified where active information of the population could make a difference: the necessity to apply appropriate wound care and to consult the nearest rabies prevention centre as soon as possible.


Lack of mitogen-activated protein kinase phosphatase-1 protects ApoE-null mice against atherosclerosis.
Multiple protein kinases have been implicated in cardiovascular disease; however, little is known about the role of their counterparts: the protein phosphatases. To test the hypothesis that mitogen-activated protein kinase phosphatase (MKP)-1 is actively involved in atherogenesis. Mice with homozygous deficiency in MKP-1 (MKP-1(-/-)) were bred with apolipoprotein (Apo)E-deficient mice (ApoE(-/-)) and the 3 MKP-1 genotypes (MKP-1(+/+)/ApoE(-/-) ; MKP-1(+/-)/ApoE(-/-) and MKP-1(-/-)/ApoE(-/-)) were maintained on a normal chow diet for 16 weeks. The 3 groups of mice exhibited similar body weight and serum lipid profiles; however, both MKP-1(+/-) and MKP-1(-/-) mice had significantly less aortic root atherosclerotic lesion formation than MKP-1(+/+) mice. Less en face lesion was observed in 8-month-old MKP-1(-/-) mice. The reduction in atherosclerosis was accompanied by decreased plasma levels of interleukin-1alpha and tumor necrosis factor alpha, and preceded by increased antiinflammatory cytokine interleukin-10. In addition, MKP-1-null mice had higher levels of plasma stromal cell-derived factor-1a, which negatively correlated with atherosclerotic lesion size. Immunohistochemical analysis revealed that MKP-1 expression was enriched in macrophage-rich areas versus smooth muscle cell regions of the atheroma. Furthermore, macrophages isolated from MKP-1-null mice showed dramatic defects in their spreading/migration and impairment in extracellular signal-regulated kinase, but not c-Jun N-terminal kinase and p38, pathway activation. In line with this, MKP-1-null atheroma exhibited less macrophage content. Finally, transplantation of MKP-1-intact bone marrow into MKP-1-null mice fully rescued the wild-type atherosclerotic phenotype. These findings demonstrate that chronic deficiency of MKP-1 leads to decreased atherosclerosis via mechanisms involving impaired macrophage migration and defective extracellular signal-regulated kinase signaling.


Biodistribution of polyacrylic acid-coated iron oxide nanoparticles is associated with proinflammatory activation and liver toxicity.
Iron oxide nanoparticles (IONs) have physical and chemical properties that render them useful for several new biomedical applications. Still, so far, in vivo safety studies of IONs with coatings of biomedical interest are still scarce. The aim of this study, therefore, was to clarify the acute biological effects of polyacrylic acid (PAA)-coated IONs, by determining their biodistribution and their potential proinflammatory and toxic effects in CD-1 mice. The biodistribution of PAA-coated IONs in several organs (liver, spleen, kidneys, brain, heart, testes and lungs), the plasma cytokines, chemokine and aminotransferases levels, white blood cell count, oxidative stress parameters, adenosine triphosphate and histologic features of liver, spleen and kidneys were evaluated 24 h after a single acute (8, 20 or 50 mg kg(-1) ) intravenous administration of PAA-coated IONs in magnetite form. The obtained results showed that these IONs accumulate mainly in the liver and spleen and, to a lesser extent, in the lungs. Although our data showed that PAA-coated IONs do not cause severe organ damage, an inflammatory process was triggered in vivo, as evidenced by as evidenced by increased neutrophils and large lymphocytes in the differential blood count. Moreover, an accumulation of iron in macrophages of the liver and spleen was observed and hepatic lipid peroxidation was elicited, showing that the IONs are able to induce oxidative stress. The effects of these nanoparticles need to be further investigated regarding the mechanisms involved and the long-term consequences of intravenous administration of PAA-coated IONs. Copyright © 2016 John Wiley & Sons, Ltd.


Climate change is a major stressor causing poor pregnancy outcomes and child development.
The climate crisis is the existential threat of our times and for generations to come. This is no longer a threat but a reality affecting us, our children, and the generations that follow. Pregnant mothers, their fetuses, and their children are among those at greatest risk in every population and every jurisdiction. A timely consideration is the health of racialized groups who are particularly vulnerable owing to the confluence of several risk factors that are compounded by climate change. Included among these are Indigenous communities that are the most directly threatened by climate change. This review discusses the main health challenges faced by mothers, fathers, and their children during the climate crisis, focusing on mental health as a causal factor. Exploration of this topic includes the role of prenatal maternal and paternal stresses, allostatic load, and the effect of degradation of the environment and ecosystems on individuals. These will be examined in relation to adverse pregnancy outcomes and altered developmental trajectories of children. The climate crisis is a health threat multiplier that amplifies the health inequities of the most at-risk populations and individuals. It accelerates the increase in allostatic load of those at risk. The path of tragedy begins with an accumulating allostatic load that overwhelms both individual and socio-ecological resilience. This can lead to worse mental health including depression and anxiety and, in the case of pregnant women and their children, more adverse pregnancy outcomes and impaired developmental trajectories for their newborn children. We argue that there is an urgent need to develop new (or re-discover or re-purpose existing) tools that will predict communities and individuals who are experiencing the highest levels of climate-related hazards and intervene to reduce stress and increase resilience in pre-conceptual women and men, pregnant and post-partum women, and their young children.


Screening for pharmaco-toxicologically relevant compounds in biosamples using high-resolution mass spectrometry: a 'metabolomic' approach to the discrimination between isomers.
High-resolution mass spectrometry (HRMS) enables the identification of a chemical formula of small molecules through the accurate measurement of mass and isotopic pattern. However, the identification of an unknown compound starting from the chemical formula requires additional tools: (1) a database associating chemical formulas to compound names and (2) a way to discriminate between isomers. The aim of this present study is to evaluate the ability of a novel 'metabolomic' approach to reduce the list of candidates with identical chemical formula. Urine/blood/hair samples collected from real positive cases were submitted to a screening procedure using ESI-MS-TOF (positive-ion mode) combined with either capillary electrophoresis or reversed phase liquid chromatography (LC). Detected peaks were searched against a Pharmaco/Toxicologically Relevant Compounds database (ca 50,500 compounds and phase I and phase II metabolites) consisting of a subset of PubChem compounds and a list of candidates was retrieved. Then, starting from the mass of unknown, mass shifts corresponding to pre-defined biotransformations (e.g. demethylation, glucuronidation, etc.) were calculated and corresponding mass chromatograms were extracted from the total ion current (TIC) in order to search for metabolite peaks. For each candidate, the number of different functional groups in the molecule was automatically calculated using E-Dragon software (Talete srl, Milan, Italy). Then, the presence of metabolites in the TIC was matched with functional groups data in order to exclude candidates with structures not compatible with observed biotransformations (e.g. loss of methyl from a structure not bearing methyls). The procedure was tested on 108 pharmaco-toxicologically relevant compounds (PTRC) and their phase I metabolites were detected in real positive samples. The mean list length (MLL) of candidates retrieved from the database was 7.01 +/- 4.77 (median, 7; range, 1-28) before the application of the 'metabolomic' approach, and after the application it was reduced to 4.08 +/- 3.11 (median 3, range 1-17). HRMS allows a much broader screening for PTRC than other screening approaches (e.g. library search on mass spectra databases). The 'metabolomic' approach enables the reduction of the list of candidate isomers.


Audiological assessment of infants and children with preauricular tags.
A previous study found sensorineural hearing loss in 13% of 178 children with solitary preauricular tags. The present results are quite different. Audiological assessment was performed on 42 children (median age of 2 months) with preauricular tags as the sole anatomical malformation. Tests included behavioral audiometry and transient evoked otoacoustic emissions. Twenty-two subjects were also tested with auditory brainstem recording while under general anesthesia during surgical excision of the tag. None of the children had a sensorineural hearing loss, but 4 had a bilateral or unilateral conductive hearing loss due to secretory otitis media. It is concluded that solitary ear tags are not a high risk factor for sensorineural hearing loss if not associated with a family history of hearing loss.


An evaluation of the reliability and sensitivity of the London Chest Activity of Daily Living Scale (LCADL).
We have previously reported the validity of a new assessment tool; the London Chest Activity of Daily Living Scale (LCADL). This work investigates the reliability and responsiveness of that measure. Reliability was assessed in 19 patients with stable severe chronic obstructive pulmonary disease (COPD); median age (range) 66 (55-79) years, FEV1 mean (SD) 0.91 (0.29) l, by test-retest 4 weeks apart. Responsiveness was assessed in 59 patients; median age (range) 66 (38-84) years, FEV1 mean (SD) 0.87 (0.30) l, who had undergone at least 6 weeks of pulmonary rehabilitation. Test-retest scores of the LCADL showed a strong relationship with one another, Intraclass correlation coefficient Icc=0.93 95%CI (0.82-0.97) demonstrating evidence of good reliability. With the exception of the Domestic component, all domains of the LCADL showed a statistically significant reduction in dyspnoea during ADLs after pulmonary rehabilitation. There was a statistically significant improvement in the total LCADL score (mean difference (95% CI) -5.91 (from -9.23 to -2.60) after rehabilitation. These data support the use of the LCADL as an outcome measure in COPD which is valid, reliable and responsive to change.


Substrate Metabolism-Driven Assembly of High-Quality CdS xSe1- x Quantum Dots in Escherichia coli: Molecular Mechanisms and Bioimaging Application.
Biosynthesis offers opportunities for cost-effective and sustainable production of semiconductor quantum dots (QDs), but is currently restricted by poor controllability on the synthesis process, resulting from limited knowledge on the assembly mechanisms and the lack of effective control strategies. In this work, we provide molecular-level insights into the formation mechanism of biogenic QDs (Bio-QDs) and its connection with the cellular substrate metabolism in Escherichia coli. Strengthening the substrate metabolism for producing more reducing power was found to stimulate the production of several reduced thiol-containing proteins (including glutaredoxin and thioredoxin) that play key roles in Bio-QDs assembly. This effectively diverted the transformation route of the selenium (Se) and cadmium (Cd) metabolic from Cd3(PO4)2 formation to CdS xSe1- x QDs assembly, yielding fine-sized (2.0 ± 0.4 nm), high-quality Bio-QDs with quantum yield (5.2%) and fluorescence lifetime (99.19 ns) far exceeding the existing counterparts. The underlying mechanisms of Bio-QDs crystallization and development were elucidated by density functional theory calculations and molecular dynamics simulation. The resulting Bio-QDs were successfully used for bioimaging of cancer cells and tumor tissue of mice without extra modification. Our work provides fundamental knowledge on the Bio-QDs assembly mechanisms and proposes an effective, facile regulation strategy, which may inspire advances in controlled synthesis and practical applications of Bio-QDs as well as other bionanomaterials.


Role of probiotics/synbiotic supplementation in glycemic control: A critical umbrella review of meta-analyses of randomized controlled trials.
The evidence regarding the beneficial effects of probiotics/synbiotic supplementation have been revealed by several meta-analyses, however some of these studies have fielded inconsistent results and a conclusion has yet to be reached. Therefore, the aim of present umbrella meta-analyses was to assess relevant evidence and elucidate the efficacy of probiotics/synbiotic supplementation in glycemic control. A comprehensive search in four databases (Cochrane library, PubMed, Web of science and Scopus) was performed to collect relevant studies up to August 2022, the pooled effects were measured with the use of random/fix-effect model depends on the heterogeneity. A total of 47 eligible meta-analyses involving 47,720 participants were identified to evaluate the pooled effects. The overall results showed that probiotics/synbiotic supplementation delivered significant decreases in fast plasma glucose (ES = -0.408, 95% CI: -0.518, -0.298; P < 0.001; I2 = 82.996, P < 0.001), fast plasma insulin (ES = -1.165, 95% CI: -1.454, -0.876; P < 0.001; I2 = 89.629, P < 0.001), homeostasis model assessment of insulin resistance (ES = -0.539, 95% CI: -0.624, -0.454; P < 0.001; I2 = 56.716, P < 0.001), and glycosylated hemoglobin (ES = -0.186, 95% CI: -0.270, -0.102; P < 0.001; I2 = 59.647, P = 0.001). Subgroup analysis showed that patients with impaired glucose homeostasis might benefit the most from probiotics/synbiotic supplementation. In conclusion, current umbrella meta-analysis strongly supporting the beneficial health effects of probiotics/synbiotic supplementation in glycemic control.


Bioconjugation of ribonuclease A: a detailed chromatographic and mass spectrometric analysis of chemical modification by a cross-linking reagent.
The modification of ribonuclease A with the heterobifunctional cross-linker, 4-succinimdyloxycarbonyl-methyl-alpha-[2-pyridyldithio]-toluene (SMPT) is described. RNase A has 11 potential sites of modification by the SMPT reagent. Tracking the two-dimensional separation and proteolytic digestion of SMPT-modified RNase A with ESI/FTICR-MS and HPLC/ESI/QIT-MS demonstrates the detailed information about number of SMPT modifications and sites of modification that can be obtained by application of these techniques. Analysis of native and modified RNase A tryptic digests by ESI/FTICR-MS resulted in the identification of the sites of modification. Semiquantitative results of the reactivity of certain lysine residues toward the coupling reagent SMPT are presented. Two sites (lysines 1 and 37) are highly reactive, while three sites (lysines 41, 61, and 104) appear to be unreactive toward SMPT under the conditions used. Experimental results demonstrate that quantitative comparison of relative intensities of peptide sequences of different charge states is not possible. No correlation was found between number of basic residues and sensitivity to detection. Digestion of the modified and unmodified RNase A by subtilisin followed by examination by HPLC/ESI/QIT-MS and MS(n) enabled further investigation of modification on lysines 1 and 7, including modification at the epsilon- and alpha-amino positions on lysine 1.


Surgical treatment of primary disease for penile squamous cell carcinoma: A Surveillance, Epidemiology, and End Results database analysis.
Current guidelines recommend penile sparing surgery (PSS) for selected penile cancer cases. The present study described the use of PSS in a population-based cohort, and also examined the role of PSS on penile cancer-specific mortality (PCSM). Data from the Surveillance, Epidemiology, and End Results (SEER) database were used to identify individuals that were diagnosed with penile squamous cell carcinoma between 1998 and 2009 and treated with surgery. Patients were sorted into two groups: Local tumor excision (LTE) and partial/total penectomy (PE). Factors associated with the receipt of LTE and PCSM following LTE were examined. In addition, PCSM was compared between LTE and PE following propensity score matching. Of the 1,292 eligible patients, 24.2% underwent LTE. For stage T1 disease, the rates of LTE increased moderately from 29 to 40% over the last decade. Following multivariate analyses, young age, African descent, a tumor size of <3 cm and stage T1 disease were identified to positively influence the receipt of LTE. With a median follow-up period of 55 months, the four-year PCSM rate was 9.8% in patients treated with LTE. Older age, a tumor size of 3-4 cm and regional/distant disease (SEER stage) were significant predictors of PCSM. Furthermore, in matched cohorts with stage T1 disease, the four-year PCSM rates were 8.9 and 10.0% for patients that received LTE or PE, respectively (P=0.93). In conclusion, underuse of PSS is pronounced in the general community with significant age and ethnicity disparities. The current population-based study provides evidence supporting the oncological safety of PSS compared with PE in early-stage disease.


Sexual dysfunction in female adult children of alcoholics.
This study investigated sexual dysfunction and selected related characteristics attributed to female adult children of alcoholics (ACOAs). Using a variety of established measures, data were collected on 30 female ACOAs and 30 non-ACOA control subjects from the general population. The results indicated that female ACOAs manifested lower self-esteem, more distrust, and more sexual dysfunction, compared to the control subjects. These findings provide strong empirical evidence that female ACOAs may be at high risk for experiencing sexual problems.


Optic nerve head drusen.
Optic disc drusen are congenital and developmental anomalies of the optic nerve head seen commonly in clinical practice, often as an incidental ophthalmologic finding during routine exams. Optic disc drusen are a form of calcific degeneration in some of the axons of the optic nerve. Visual acuity is often not affected but the visual fields of these patients can be abnormal and deteriorate over time. Optic disc drusen are familial and are not uncommon. They are thought to be the result of pathology at the level of the optic nerve head itself. The diagnosis can be made with clinical findings combined with B scan ultrasound and computed tomography. In addition, newer modalities using optic nerve head tomography are proving to be very useful. Since children as well as adults are affected, it is important to consider optic nerve head drusen in the differential diagnosis of papilledema or optic nerve swelling.


Node counts in neck dissection: are they useful in outcomes research?
We studied the unilateral nodal yields for procedures reported as standard or modified radical neck dissection (RND) to determine their applicability in outcomes research. We analyzed the unilateral nodal yields for all procedures reported as RND for carcinoma of the oral cavity, pharynx, and larynx at our institution from 1985 to 1997 (n = 64, no prior treatment). These included both standard and modified techniques, encompassing levels I through V of the neck. Each side of a bilateral RND was treated as a separate case. This sample was compared with a similar population from the National Cancer Institute's Surveillance, Epidemiology, and End-Results (SEER) registry. Nodal yield was obtained for RND alone and for unspecified neck dissection with primary excision for the same diseases and time period (n = 1499). The mean nodal yield from 64 RND was 30 vs 27 in the SEER data. The standard deviation was 14.7 compared with 17.2 in the SEER data. Values ranged from 7 to 66 nodes whereas the SEER range was from 1 to 97 nodes. Although the SEER data contain nodal yields from regional or selective neck dissection, we corroborate our findings of large variance in nodal yield from our RND sample. Large variance in nodal yields from RND may have undefined effects on quality of life, cure rate, and survival. Until correlation of nodal yields with outcomes is examined, we cannot know how to relate RND to outcomes.


Delay in serum stimulation of Erk activity caused by oncogenic transformation.
Mitogenic growth factor stimulation activates several signal transduction pathways, including the well-characterized Ras-Erk pathway, resulting in transient activation of Erk1 and Erk2. Oncogenic transformation, however, causes constitutive activation of growth signalling pathways, resulting in an accelerated rate of cell division. We investigated the effects of transformation on serum and growth factor stimulation of Erk1 and Erk2, and show that stimulation of these MAP kinases, as well as the Erk activator Mek, is delayed in oncogene transformed cells. Possible mechanisms of this delay are explored. In addition, our data indicate that prolonged mitogenic stimulation does not necessarily result in constitutive activation of Erk1 and Erk2.


[A combined therapy for maxillary cancer].
Forty-three patients with cancer of the maxillary sinus were treated by surgery combined with radiation and regional chemotherapy as a series of treatment in 1978-1989. The combined therapy consisted of the followings: 1) Operation to reduce tumor-mass. 2) Irradiation of total dose of 16 Gy, that is, 8 Gy preoperatively and 8 Gy postoperatively. 3) Chemotherapy with arterial infusion of 1,000 mg fluorouracil (5-FU) and 2,000 mg broxuridine (BUdR) for 4 days after operation. Of the 16 patients with neck metastasis, 14 accepted extirpation of the metastatic cervical lymph nodes and upper neck dissection was performed in other 2 cases. Five-year survival was 87% in the 32 patients of stage II and III but 41% in the 11 of stage IV. The combined therapy for patients of stage II and III disease is recommended because of the satisfactory results. However, a further study is required in our therapeutic schema for the case of stage IV since the prognosis was poor.


Protease-activated receptor-2 induces myofibroblast differentiation and tissue factor up-regulation during bleomycin-induced lung injury: potential role in pulmonary fibrosis.
Idiopathic pulmonary fibrosis constitutes the most devastating form of fibrotic lung disorders and remains refractory to current therapies. The coagulation cascade is frequently activated during pulmonary fibrosis, but this observation has so far resisted a mechanistic explanation. Recent data suggest that protease-activated receptor (PAR)-2, a receptor activated by (among others) coagulation factor (F)Xa, plays a key role in fibrotic disease; consequently, we assessed the role of PAR-2 in the development of pulmonary fibrosis in this study. We show that PAR-2 is up-regulated in the lungs of patients with idiopathic pulmonary fibrosis and that bronchoalveolar lavage fluid from these patients displays increased procoagulant activity that triggers fibroblast survival. Using a bleomycin model of pulmonary fibrosis, we show that bleomycin induces PAR-2 expression, as well as both myofibroblast differentiation and collagen synthesis. In PAR-2-/- mice, both the extent and severity of fibrotic lesions are reduced, whereas myofibroblast differentiation is diminished and collagen expression is decreased. Moreover, fibrin deposition in the lungs of fibrotic PAR-2-/- mice is reduced compared with wild-type mice due to differential tissue factor expression in response to bleomycin. Taken together, these results suggest an important role for PAR-2 in the development of pulmonary fibrosis, and the inhibition of the PAR-2-coagulation axis may provide a novel therapeutic approach to treat this devastating disease.


Simultaneous determination of 24,25- and 25,26-dihydroxyvitamin D3 in serum samples with liquid-chromatography mass spectrometry - A useful tool for the assessment of vitamin D metabolism.
Vitamin D status is typically assessed by the measurement of 25-hydroxyvitamin D (25(OH)D). However, in selected patient groups the sole determination of 25(OH)D has been proven insufficient for this purpose. The simultaneous measurement of additional vitamin D metabolites may provide useful information for a better evaluation of the vitamin D status. Therefore, we developed and validated a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of 25(OH)D3, 25(OH)D2, 24,25(OH)2D3 and additionally 25,26(OH)2D3, which was identified with a synthesized pure substance. Pure and deuterated substances were used to prepare calibrators and internal standards for all target metabolites. Pre-analytical sample preparation comprised protein precipitation followed by liquid-liquid-extraction and derivatization with 4-Phenyl-1,2,4-triazole-3,5-dione (PTAD) using 50 µL sample volume. Samples were analyzed on an Agilent HPLC 1260 system equipped with a silica-based Kinetex® 5 µm F5 100 Å core-shell column (150 × 4.6 mm) coupled to a Sciex 4500 mass spectrometer. For all four metabolites, limit of detection (LoD) and limit of quantification (LoQ) ranged from 0.3 to 1.5 nmol/L and 1.0 to 3.1 nmol/L, respectively. Recovery varied between 76.1 % and 84.3 %. Intra- and inter-assay imprecision were <8.6 % and <11.5 %, respectively. The analysis of external and internal quality control samples showed good accuracy for 25(OH)D3, 25(OH)D2, 24(R),25(OH)2D3 and 25,26(OH)2D3. Method comparison studies with human samples that were also analyzed with two other LC-MS/MS methods showed close agreement. Finally, the present method has been shown capable of identifying patients with 24-hydroxylase deficiency, which proves its clinical utility.


Levels of analysis in psychiatric research.
Most of the major psychiatric disorders have been analyzed at each of several different levels. For example, at the broadest level, epidemiological studies have served to establish the incidence of disorders like schizophrenia and major depression in a number of different populations. Family and twin studies have been important in determining the heritability of certain mental illnesses, and chromosomal and linkage analyses have identified a number of discrete loci that appear to be implicated in disease susceptibility or, even directly, in the pathogenesis of some disorders. In a few cases, specific genes have been found to be mutated or polymorphic and proteins they encode are currently being analyzed. This article reviews how these different levels contribute to our understanding of a number of psychiatric disorders, including drug addiction, which has been the focus of much of our own work.


[Bacterial meningitis caused by Neisseria meningitidis. Prophylactic measures].
Meningitis caused by Neisseria meningitidis is one of the most frequent and most serious, with fatal rate between few up to 20%. Majority of cases are caused by Neisseria meningitidis of serological groups A, B, C, as well as Y and W 135. Vaccination is the most effective prophylactic measure against meningococcal meningitidis. Polysaccharide, not conjugated vaccines against Neisseria meningitidis serological groups A, C, W 135, Y effective for children over 2 years old, adolescents and adults as well as vaccine against serogroup C conjugated with protein carrier, effective for children over 2 months of life, adolescents and adults are used. Conjugated vaccine against serological group C was used in 1998/1999 in Great Britain in the mass vaccination of infants in 2, 3, 4 months of life, children and adolescents up to 17. In Poland as well as in other European countries serological group B is an etiological factor of majority of cases caused by Neisseria meningitidis. Intensive studies are performed in the field on effective, safety, cheap vaccine against all serological groups of Neisseria meningitidis.


Dual-Functional Implants with Antibacterial and Osteointegration-Promoting Performances.
Multifunctional antibacterial materials have great significance for treating biomedical device-associated infections (BAIs). In the present work, a facile and rational strategy was developed to produce dual-functional implants with antibacterial and osteointegration-promoting properties for the treatment of BAI. A titanium implant, as a representative demo of implants, was first functionalized with ethanediamine-functionalized poly(glycidyl methacrylate) (PGED) brushes. Then, low-molecular-weight quaternized polyethyleneimine (QPEI, a cationic antibacterial agent) and alendronate (ALN, a clinically used drug with high affinity for bone minerals) were covalently conjugated onto PGED brushes to produce dual-functional dental implants (Ti-AQ). The QPEI component imparted Ti-AQ with antibacterial abilities, and the ALN component could balance the cytotoxicity of a cationic antibacterial agent, improving the biocompatibility for osteoblast cells. The effective performances of anti-infection and osteointegration were demonstrated in a BAI animal model. The results indicated that Ti-AQ inhibited bacterial infection at the early stage and enhanced the osteointegration and biomechanical properties between the implants and bone tissues at the late stage. This study will provide one facile and universal strategy for the design and development of novel multifunctional antibacterial implants.


Naturalistic decision making.
This article describes the origins and contributions of the naturalistic decision making (NDM) research approach. NDM research emerged in the 1980s to study how people make decisions in real-world settings. The findings and methods used by NDM researchers are presented along with their implications. The NDM framework emphasizes the role of experience in enabling people to rapidly categorize situations to make effective decisions. The NDM focus on field settings and its interest in complex conditions provide insights for human factors practitioners about ways to improve performance. The NDM approach has been used to improve performance through revisions of military doctrine, training that is focused on decision requirements, and the development of information technologies to support decision making and related cognitive functions.


Global profiling of protein complexes: current approaches and their perspective in biomedical research.
Despite the rapid evolution of proteomic methods, protein interactions and their participation in protein complexes - an important aspect of their function - has rarely been investigated on the proteome-wide level. Disease states, such as muscular dystrophy or viral infection, are induced by interference in protein-protein interactions within complexes. The purpose of this review is to describe the current methods for global complexome analysis and to critically discuss the challenges and opportunities for the application of these methods in biomedical research. Areas covered: We discuss advancements in experimental techniques and computational tools that facilitate profiling of the complexome. The main focus is on the separation of native protein complexes via size exclusion chromatography and gel electrophoresis, which has recently been combined with quantitative mass spectrometry, for a global protein-complex profiling. The development of this approach has been supported by advanced bioinformatics strategies and fast and sensitive mass spectrometers that have allowed the analysis of whole cell lysates. The application of this technique to biomedical research is assessed, and future directions are anticipated. Expert commentary: The methodology is quite new, and has already shown great potential when combined with complementary methods for detection of protein complexes.


Growth hormone responses to multiple injections of a fragment of human growth hormone-releasing factor in conscious male and female rats.
The GH responses to single i.v. injections of GH-releasing factor (GRF) in conscious male rats are highly variable. Although normal male rats show a pulsatile secretory pattern of GH with pulses occurring at intervals of 3-3.5 h, the peaks occur at different times in individual animals. We have compared the GH responses of young conscious male and female rats to multiple i.v. injections of 1 microgram human (h) GRF1-29NH2. The peak GH responses occurred 3-5 min after hGRF1-29NH2 injection and were lower in female than in male rats. Both males and females responded uniformly to hGRF1-29NH2 injections given 180 min apart and the GH responses became entrained with no endogenous GH pulsing. Female rats produced consistent GH peaks in response to hGRF1-29NH2 injections at 90-min intervals, whereas male rats responded only to alternate injections, so that GH peaks occurred only every 180 min despite giving GRF every 90 min. When the frequency of hGRF1-29NH2 administration was increased to once every 40 min female rats again responded consistently to each injection. Male rats responded intermittently, being able to respond to two injections 40 min apart, after which they became refractory to hGRF1-29NH2. This cycle of varying sensitivity to GRF in male rats probably underlies their 3-hourly endogenous GH secretory rhythm. Female rats can respond uniformly to repeated GRF injections, consistent with their more continuous pattern of endogenous GH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)


Actinomycin D causes oocyte maturation failure by inhibiting chromosome separation and spindle assembly†.
Actinomycin D (ActD) has been considered as one of the most effective and safe chemotherapeutic medications for treating a number of cancers. Although ActD has been used in the treatment of gynecological tumors and pediatric tumors for more than 50 years, the toxic effects of ActD on mammalian oocytes remain unknown. In this study, the influence of ActD on mouse and human oocyte maturation and the possible mechanisms were investigated. Notably, ActD inhibited oocyte maturation and arrested oocytes at the metaphase I (MI) stage in a dose-dependent manner. In addition, ActD arrested oocyte maturation when the oocytes were treated at different successive stages, including the germinal vesicle (GV), germinal vesicle breakdown, and MI stages. In ActD-treated oocytes, disordered chromosome condensation and irregular spindle assembly occurred, resulting in incomplete chromosome segregation and oocytes arresting at the MI phase; these results possibly occurred because ActD triggered the formation of reactive oxygen species, resulting in DNA damage and decreased ATP in mouse GV oocytes. Besides, in vivo treatment with ActD also inhibited mouse oocyte maturation. Similar effects were seen in human oocytes. Collectively, our results indicated that ActD exposure disrupted oocyte maturation by increasing DNA damage, which is a finding that might help with optimizing future methods for female fertility preservation before undergoing chemotherapy.


Genetic analysis of factor V Leiden in a family with history of thrombosis and venous leg ulcers.
Inherited resistance to activated protein C has been recognized as a major risk factor for thrombosis. The factor V Leiden mutation, which is detectable by molecular DNA techniques, is responsible for 95% of cases of activated protein C resistance. In our study one patient with venous leg ulcers from a family with a history of thrombosis showed factor V Leiden mutation. Genotypic analysis demonstrated that the patient was homozygous for factor V Leiden. All family members of the index subject showed the same abnormalities. Two were homozygous and 3 were heterozygous for factor V Leiden mutation. The polymerase chain reaction was used to amplify exon 10 of the factor V gene, followed by enzymatic digestion with MnlI for mutation detection. Patients with a family history of thrombosis and factor V Leiden have an increased risk of venous leg ulcers. Screening for factor V Leiden may be indicated in patients with venous leg ulcers and their family members.


[Prostaglandins in the blood serum of patients with rheumatoid arthritis].
Radioimmunoassay was used to study the content of prostaglandins in blood plasma of patients suffering from rheumatoid arthritis (PGE in 133 and PGF2 alpha in 102 patients). It has been established that as compared to the control group subjects, it is appreciably elevated and reflects the degree of inflammatory process activity, being pronounced to a greater measure in persons not receiving glucocorticoids than in hormone-dependent patients. A relationship has been revealed between the content of PGE and PGF2 alpha and certain clinical and laboratory characteristics (disease standing, intensity of exudative component of inflammation, the presence of humoral and cellular immunity disorders, anemia, and some visceral lesions), which may be of definite importance in the assessment of the patient's status. The time-course of changes in blood plasma prostaglandins reflects on the whole the dynamics of the disease activity, being related to a greater degree to the application of nonsteroidal antiinflammatory agents than of glucocorticoids.


Post-surgical unilateral left pulmonary edema after mitral valve replacement - A diagnostic challenge.
Unilateral left pulmonary edema due to inadvertent surgical occlusion of left superior and inferior pulmonary veins is not only an exceedingly rare complication of mitral valve surgeries but also a diagnostic challenge in the postoperative recovery unit. Described here is a case of a 38-year-old male who developed progressively worsening unilateral left pulmonary edema after mitral valve replacement on postoperative day-1. The diagnosis was mostly by the exclusion of multiple possible differentials and was confirmed during reexploration surgery.


The trauma nurse coordinator in Australia and New Zealand: a progress survey of demographics, role function, and resources.
An initial profile of the demographics and current practice of Australian trauma nurse coordinators (TNCs) was conducted in 2003. The study identified common and differing role components, provided information to assist with establishing national parameters for the role, and identified the resources perceived necessary to enable the role to be performed effectively. This article compares the findings of the 2003 study with a 2007 survey, expanded to include New Zealand trauma coordinators. Forty-nine people, identified as working in a TNC capacity in Australia and New Zealand, were invited to participate in February 2007. The survey consisted of a 3-part questionnaire of respondents' demographics, the percentage of time allocated to 10 defined role functions (components), and the TNCs' perceived required resources to fulfill their role effectively. Feedback from the 2003 survey was incorporated in the redesign. Participation in the research enabled an update of the previously compiled Australia/New Zealand trauma network list. Thirty-six surveys (71.5% response rate) were returned. Descriptive statistics were undertaken for each item, and comparisons were made among states, territories, and countries. The mean age of respondents was 41+/-7.7, range 27 to 57, and 92% were female. They averaged 11.1 years of postregistration critical care or trauma experience, and 50% (n=18) reported working unpaid overtime (decreased from 56% (n=19) since 2003). Participants reported that most of their time was spent fulfilling the trauma registry component of the role (27% of total hours), followed by quality and clinical activities (19% of total hours), education, and administration. The component associated with the least amount of time was outreach (3% of total hours). Although the proportion of time has almost halved since 2003, TNCs still spend the most time maintaining trauma registries. Compared to the 2003 survey, Australian and New Zealand TNCs are working more unpaid overtime, spending more time performing quality and clinical activities and less time doing data entry. Despite where one works, the role components identified are fulfilled to a certain extent. However, trauma centers need to provide the TNC with adequate resources if trauma care systems are to be optimally effective.


On-surface synthesis of π-conjugated ladder-type polymers comprising nonbenzenoid moieties.
On-surface synthesis provides a powerful approach toward the atomically precise fabrication of π-conjugated ladder polymers (CLPs). We report herein the surface-assisted synthesis of nonbenzenoid CLPs from cyclopenta-annulated anthracene monomers on Au(111) under ultrahigh vacuum conditions. Successive thermal annealing steps reveal the dehalogenative homocoupling to yield an intermediate 1D polymer and the subsequent cyclodehydrogenation to form the fully conjugated ladder polymer. Notably, neighbouring monomers may fuse in two different ways, resulting in six- and five-membered rings, respectively. The structure and electronic properties of the reaction products have been investigated via low-temperature scanning tunneling microscopy and spectroscopy, complemented by density-functional theory calculations. Our results provide perspectives for the on-surface synthesis of nonbenzenoid CLPs with the potential to be used for organic electronic devices.


The diagnostic value of CSF amyloid-β(43) in differentiation of dementia syndromes.
Amyloid-β (Aβ) is known as the most prominent core protein in Alzheimer's Disease (AD) senile plaques. Although research has focused mainly on Aβ40 and Aβ42 as potential cerebrospinal fluid (CSF) biomarkers, a range of Aβ peptides with variable lengths has been demonstrated in the brains and CSF of AD patients. Recently, it has been found that the Aβ43 peptide may be more abundant than previously assumed, could therefore play an important role in AD pathophysiology, and hence also function as putative biomarker. In this study the value of CSF Aβ43 in AD diagnosis was investigated. Aβ43 levels in CSF were highly correlated with Aβ42 levels. Furthermore, in differentiation of AD from nondemented controls and from patients with Lewy body dementia and frontotemporal dementia, Aβ43 had an equal diagnostic value as Aβ42, both as a single biomarker and in combination with total and phosphorylated tau. In conclusion, quantification of Aβ43 in CSF does not add novel diagnostic information to the differential diagnosis of AD compared to existing biomarkers.


IgE myeloma: a case presentation and a review of the literature.
In the literature, fewer than 40 cases of IgE myeloma have been described. We report the first Norwegian case, an 80-year-old man presenting with progressive weakness, dyspnea and dizziness. With the exception of hypersedimentation, routine chemistry values were within reference limits. Plasma cells were not observed in the peripheral blood. Serum protein electrophoresis showed a monoclonal protein in the gammaglobulin fraction. Immunofixation confirmed the presence of an IgE kappa monoclonal protein. A bone marrow biopsy revealed an interstitial and nodular infiltration of abnormal plasma cells comprising 40% of nucleated cells present. Skeletal roentgenograms of this patient showed osteolytic lesions in the skull and in the left pubic arc. The findings for this patient were compared with the previous reports of IgE myeloma.


Pancreatic ascites as a powerful inducer of inflammatory cytokines. The role of known vs unknown factors.
To determine if pancreatic ascites will induce interleukin 1 beta (IL-1 beta) or tumor necrosis factor alpha (TNF-alpha) production outside the pancreas and examine the possible components responsible. Severe pancreatitis was induced in rats (n = 30) by pancreatic duct infusion with 4% glycodeoxycholic acid; pancreatic ascites was collected 18 hours later. In vitro studies used quiescent murine splenic or pulmonary macrophages (10(5)/mL) which were exposed to media alone (control), trypsin, chymotrypsin, cathepsin-B, 20% ascites (vol/vol), 50% ascites, or endotoxin (lipopolysaccharide, 10 micrograms/mL, positive control) for 4 hours. Subsequently, pancreatic ascites was cultured for bacteria and assayed for endotoxin and cytokines (interleukin 1, interleukin 6, interleukin 8, TNF-alpha, or interferon gamma). The experiments were then repeated using 20% and 50% ascites that was sterile and cytokine-free (SCF ascites). In vivo studies used 100% (n = 8) or 50% (n = 12) SCF ascites or normal rat serum (control, n = 12) for a 10-second pulmonary lavage (100 microL) in adult mice, with lungs collected at 6 hours for cytokine gene analysis. Surgical basic science research laboratory. Interleukin 1 beta and TNF-alpha gene induction was assessed by quantitative competitive reverse-transcription polymerase chain reaction and cytokine protein production was determined by enzyme-linked immunosorbent assay. Macrophages responded to untested and SCF ascites in a dose-dependent fashion, with a multifold increase in both IL-1 beta and TNF-alpha messenger RNA (mRNA) and protein, which was often more potent than lipopolysaccharide. Expression of IL-1 beta and TNF-alpha mRNA could not be induced by trypsin, chymotrypsin, or cathepsin-B. All animals undergoing lavage with 100% SCF ascites died within 2 hours, while those undergoing lavage with 50% SCF ascites showed a multifold increase in pulmonary IL-1 beta and TNF-alpha mRNA. Pancreatic ascites contains factors that are capable of inducing IL-1 beta and TNF-alpha production in vitro and in vivo. This effect cannot be reproduced by activated digestive enzymes and is propagated despite the absence of known inducers of cytokines such as bacteria, endotoxin, or other inflammatory cytokines.


Effects of the lipid bilayer phase state on the water membrane interface.
We performed 200 ns MD simulations of phosphatidylcholine (PC) bilayers in the liquid crystalline (L(α)) and gel (L(β)') states to compare the properties of the water-membrane interfaces in these two thermotropic bilayer phases. Our simulations show that the membrane phase determines the behavior of water, ions, and PC head groups. When the membrane was in the gel phase, we found partial dehydration (fewer PC-water interactions), particularly in the carbonyl groups region, as well as an almost complete lack of ionic penetration into this region as compared with the bilayer in the liquid-crystalline phase. In the latter case, there is an exchange of Na(+) ions between the water layer and the interfacial region. This is mainly due to the fact that the most stable binding of Na(+) in the liquid-crystalline bilayer is to the carbonyl groups. The lack of Na(+) binding to the carbonyl groups in the gel phase bilayer can be explained by the more compact structure of the bilayer in this phase.


[Radiologically isolated syndrome: prognosis and predictors of conversion to multiple sclerosis].
Increased sensitivity and availability of magnetic resonance imaging (MRI) in neurological routine practice led to the fact that more and more experts began to encounter changes typical for multiple sclerosis (MS) according to MRI in the absence of anamnestic and clinical indications of damage to the central nervous system (CNS). This nosological form has been defined as a radiologically isolated syndrome (RIS). More and more RIS cases convert to MS (up to 30% in the first 5 years after RIS diagnosis). At the moment, there are no biological markers that allow combining RIS and MS into one pathological process and early treatment with disease-modifying drugs (DMT). Prospective studies are actively being conducted to identify demographic, clinical, neuroimaging and biochemical conversion predictors. The identification of the molecular biological RIS features, combining these changes with MS, is an urgent scientific task and will allow timely initiation of therapy of the pathological process already at the subclinical stage.


Aminoacyl-tRNA synthesis and translational quality control.
Translating the 4-letter code of RNA into the 22-letter alphabet of proteins is a central feature of cellular life. The fidelity with which mRNA is translated during protein synthesis is determined by two factors: the availability of aminoacyl-tRNAs composed of cognate amino acid:tRNA pairs and the accurate selection of aminoacyl-tRNAs on the ribosome. The role of aminoacyl-tRNA synthetases in translation is to define the genetic code by accurately pairing cognate tRNAs with their corresponding amino acids. Synthetases achieve the amino acid substrate specificity necessary to keep errors in translation to an acceptable level in two ways: preferential binding of the cognate amino acid and selective editing of near-cognate amino acids. Editing significantly decreases the frequency of errors and is important for translational quality control, and many details of the various editing mechanisms and their effect on different cellular systems are now starting to emerge.


Asthma control, cost and race: results from a national survey.
Although interventions have been shown to alleviate symptoms in most patients suffering from asthma, only one-third of asthma patients have disease that is well-controlled. The purpose of this study is to investigate whether partly and uncontrolled asthmas are associated with increased costs for asthma-related healthcare utilization compared to well-controlled asthma and to determine whether these associations differed across racial groups. We classified respondents from the Asthma Insights and Management survey into those with well-, partly and uncontrolled asthma and compared utilization of healthcare services and costs among these groups, as well as between whites and non-whites. Respondents categorized as having asthma that was not well-controlled reported lower income levels, higher rates of unemployment and more trouble paying for healthcare; similar results were found in analyses stratified by race. Patients whose asthma was partly or uncontrolled had greater use of asthma-related medications and medical services compared to patients whose asthma was well-controlled. Total unadjusted and adjusted costs were greater in patients whose asthma was classified as partly and uncontrolled. Similar results were found in analyses stratified on race. Across all levels of asthma control, non-whites had higher rates of utilization of emergency rooms and urgent care facilities and had greater rates of hospitalizations compared to whites. Our findings indicate that patients with asthma that is not well-controlled utilized more healthcare resources and had greater medical costs, despite lacking of health insurance which may suggest less access to care.


The Bacillus subtilis sin gene, a regulator of alternate developmental processes, codes for a DNA-binding protein.
The sin gene of Bacillus subtilis encodes a dual-function regulatory protein, Sin, which is a negative as well as a positive regulator of alternate developmental processes that are induced at the end of vegetative growth in response to nutrient depletion. Sin has been purified to homogeneity by using a simple two-step procedure. It was found to bind to the developmentally regulated aprE (alkaline protease) gene at two sites in vitro. The stronger Sin-binding site (SBS-1) is located more than 200 bp upstream from the transcription start site. It is required for Sin repression of aprE expression in vivo, as strains bearing SBS-1 deletions were not affected by the sin gene. The second, weaker Sin-binding site lies on a DNA fragment that contains the aprE promoter. Results of DNase I, exonuclease III, and dimethyl sulfate footprinting analysis of SBS-1 suggested that Sin binding involves two adjacent binding sites which appear to contain two different partial dyad symmetries. An analysis of the predicted amino acid sequence of Sin revealed a potential leucine zipper protein dimerization motif which is flanked by two helix-turn-helix motifs that could be involved in recognizing two different dyad symmetries.


Occupation and lung cancer risk among New Jersey white males.
The association of occupation with lung cancer risk was examined in a case-control study conducted in six areas of New Jersey. The study included 763 white males with incident histologically confirmed primary cancer of the trachea, bronchus, and lung and 900 general population white male controls selected from driver's license and death certificate files. Altogether, 27 employment categories had a smoking-adjusted odds ratio (OR) of 1.3 or greater; five of these with significantly high OR contributed to an occupational population attributable risk of 13%. Masons and tilesetters; janitors and cleaners; printing workers; and trucking service, warehousing, and storage workers had significantly high risks overall and for longer durations of employment. Shipbuilding workers had significantly high risk overall and for short duration of employment. Although the excess risk for all shipbuilding workers was primarily among those with reported exposure to asbestos, the risk was also high among welders, burners, sheet metal workers, and boilermakers with no reported asbestos exposure.


Physiological responses to acute fasting: implications for intermittent fasting programs.
Intermittent fasting (IF) is a dietary strategy that involves alternating periods of abstention from calorie consumption with periods of ad libitum food intake. There is significant interest in the body of literature describing longitudinal adaptations to IF. Less attention has been given to the acute physiological responses that occur during the fasting durations that are commonly employed by IF practitioners. Thus, the purpose of this review was to examine the physiological responses - including alterations in substrate metabolism, systemic hormones, and autophagy - that occur throughout an acute fast. Literature searches were performed to locate relevant research describing physiological responses to acute fasting and short-term starvation. A single fast demonstrated the ability to alter glucose and lipid metabolism within the initial 24 hours, but variations in protein metabolism appeared to be minimal within this time frame. The ability of an acute fast to elicit significant increases in autophagy is still unknown. The information summarized in this review can be used to help contextualize existing research and better inform development of future IF interventions.


Categorization of Functional Constipation in Traditional Persian Medicine: A Descriptive Study.
Functional constipation (FC) is a common clinical condition without any specific physiological causes with economic cost and adverse effects on patients' quality of life. The present study aimed to evaluate the causes of nonobstructive constipation in traditional Persian medicine and its prevalence in patients with functional constipation by content analysis of patients' interviews and clinical exams. In this study, almost two thirds of the patients with functional constipation had mild to severe cold distemperament of the gastrointestinal system, and in almost half of them the signs and symptoms were compatible with dry distemperament of the gastrointestinal. This observational study reports high prevalence of gastrointestinal system distemperaments in patients with functional constipation. According to the results, we can consider the proposed management of distemperaments in traditional Persian medicine for functional constipation treatment and pathophysiology explanation. This project is a novel study that provides the opportunity for investigating the epidemiological aspects of these distemperaments and their relationship with functional constipation.


pep27 and lytA in Vancomycin-Tolerant Pneumococci.
Vancomycin therapy failure due to the emergence of tolerance in pneumococci is increasing. The molecular mechanism of tolerance is not clear, but lytA and pep27 are known to be involved. Our aim was to evaluate the expression of both genes in vancomycin-tolerant Streptococcus pneumoniae (VTSP) strains. Eleven VTSP strains from a total of 309 clinical isolates of S. pneumoniae from 1997 to 2006 were classified according to the criteria of Liu and Tomasz. All VTSP strains were evaluated for susceptibility according to CLSI criteria, serotype by the Quellung test, and clonality by PFGE. The expressions of lytA and pep27 were analyzed in different growth phases by RT-PCR with and without vancomycin. Eighty-two percent of VTSP strains showed resistance to penicillin, and 100% were sensitive to vancomycin and cefotaxime. The most frequent serotypes of VTSP strains were 23F (4/11) and 6B (3/11). Clonal relationship was observed in only two strains. No significant changes were observed in pep27 expression in the three phases of growth in VTSP strains with and without vancomycin. Interestingly, pep27 expression in the stationary phase in the non-tolerant reference strain R6 was significantly higher. However, no significant differences in lytA expression were observed between VTSP and R6 strains during the phases of growth analyzed. The absence of changes in pep27 expression in VTSP strains in the stationary phase may be related to their ability to tolerate high antibiotic concentrations, and thus, they survive and remain in the host under the antibiotic selective pressure reflected in therapeutic failure.


Expression of 5-Methyltryptophan Resistance in Plants Regenerated from Resistant Cell Lines of Datura innoxia.
Seventy-nine 5-methyltryptophan-resistant cell lines have been selected from haploid Datura innoxia Mill. cell cultures by plating suspensions in agar medium containing a growth inhibitory concentration of 5-methyltryptophan. Mutagen treatment increased the frequency of resistance. The eleven variants tested posses an altered anthranilate synthase less sensitive to feedback inhibition by tryptophan. All five of the variants which were analyzed for free amino acids contained elevated levels of free tryptophan (8 to 30 times the wild type level). None of the selected cell lines were auxin-autotrophic. Resistance to 5-methyltryptophan, altered anthranilate synthase, and high free tryptophan (4 to 44 times) were also expressed in leaves of plants regenerated from the variant lines and in cultures reinitiated from the resistant plants. These results show that the amino acid overproduction phenotype can be selected at the cellular level of organization and be expressed identically in whole plants regenerated from the selected cells.


2-(Hydroxyalkyl)estradiols: synthesis and biological evaluation.
Synthetic estrogens possessing hydroxyalkyl side chains at the C-2 position of the A-ring were designed in order to further elucidate the structural and electronic requirements of the estrogen receptor to A-ring modifications. Furthermore, these compounds were envisaged as being stable analogs of the estradiol metabolite 2-hydroxyestradiol. The homologous series of 2-(hydroxyalkyl)estradiols 1-3 has been prepared by chain extension of 2-formylestradiol 6, which, in turn, was prepared via ortholithiation of estradiol. The substituted estradiols 1-3 were assayed for their abilities to bind to the estrogen receptor in MCF-7 cells and induce estrogen-responsive gene expression. The estradiol homologs exhibited significantly weaker affinity than estradiol for the MCF-7 cell estrogen receptor, with relative binding affinities (estradiol = 100) ranging from 1.11 for 2-(hydroxymethyl)estradiol (1) to 0.073 for 2-(hydroxypropyl)estradiol (3). The relative activities for mRNA induction of the pS2 gene by the estradiol homologs closely parallel the relative binding affinities for the estrogen receptor in MCF-7 cells. 2-(Hydroxymethyl)-estradiol exhibited similar estrogen receptor affinity and pS2 gene induction to the catechol estrogen 2-hydroxyestradiol and may prove useful in examination of the further biological effects of 2-hydroxyestrogen homologs.


"Free full text articles": where to search for them?
References form the backbone of any medical literature. Presently, because of high inflation, it is very difficult for any library/organization/college to purchase all journals. The condition is even worse for an individual person, such as private practitioners. The solution lies in the free availability of full-text articles. Here, the authors share their experiences about the accessibility of free full-text articles.


Evaluation of commercially available diagnostic tests for the detection of dengue virus NS1 antigen and anti-dengue virus IgM antibody.
Commercially available diagnostic test kits for detection of dengue virus (DENV) non-structural protein 1 (NS1) and anti-DENV IgM were evaluated for their sensitivity and specificity and other performance characteristics by a diagnostic laboratory network developed by World Health Organization (WHO), the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) and the Pediatric Dengue Vaccine Initiative (PDVI). Each network laboratory contributed characterized serum specimens for the panels used in the evaluation. Microplate enzyme-linked immunosorbent assay (ELISA) and rapid diagnostic test (RDT formats) were represented by the kits. Each ELISA was evaluated by 2 laboratories and RDTs were evaluated by at least 3 laboratories. The reference tests for IgM anti-DENV were laboratory developed assays produced by the Armed Forces Research Institute for Medical Science (AFRIMS) and the Centers for Disease Control and Prevention (CDC), and the NS1 reference test was reverse transcriptase polymerase chain reaction (RT-PCR). Results were analyzed to determine sensitivity, specificity, inter-laboratory and inter-reader agreement, lot-to-lot variation and ease-of-use. NS1 ELISA sensitivity was 60-75% and specificity 71-80%; NS1 RDT sensitivity was 38-71% and specificity 76-80%; the IgM anti-DENV RDTs sensitivity was 30-96%, with a specificity of 86-92%, and IgM anti-DENV ELISA sensitivity was 96-98% and specificity 78-91%. NS1 tests were generally more sensitive in specimens from the acute phase of dengue and in primary DENV infection, whereas IgM anti-DENV tests were less sensitive in secondary DENV infections. The reproducibility of the NS1 RDTs ranged from 92-99% and the IgM anti-DENV RDTs from 88-94%.


Clinical analysis and strategy for liver transplantation in patients with pre-existing portal vein thrombosis.
Liver transplantation (LT) in patients with portal vein thrombosis (PVT) remains a challenge for transplant surgeons. In this study, we included a group of patients with PVT who underwent LT, and analyzed patient outcomes. A total of 356 patients who underwent LT consisting of 167 cases of deceased donor LT and 189 cases of live donor LT at Chang Gung Memorial Hospital Linkou Medical Center between September 1996 and June 2009 were retrospectively reviewed; 24 (6.7%) of these patients had PVT at transplantation. Their clinical features, surgical management, and outcomes were analyzed. Surgical management of patients with PVT included a thrombectomy followed by direct anastomosis between the recipient's and the liver graft portal vein (PV) (n = 13), interposition vein graft between the recipient's coronary vein (CV) and the liver graft PV (n = 3), direct anastomosis of the recipient's CV and the liver graft PV (n = 1), interposition jump graft from the recipient's superior mesenteric vein to the liver graft PV (n = 4), and transection of the thrombotic PV followed by interposition of a venous graft between the recipient's PV and the liver graft PV (n = 3). There were 7 hospital mortalities. The mean follow-up for the 17 surviving patients was 36.3 months (range, 3.4-105.1 months), and 14 patients were still alive at the end of the study. Four patients (16.7%) had rethrombosis of portal inflow after LT. Patients with PVT undergoing LT had a significantly higher mortality rate (p = 0.033) than patients without PVT undergoing LT. However, there was no significant difference in the cumulative survival rates (p = 0.0696). Further analysis of patient survival according to PVT grade, venous graft application, and reconstructed portal flow routes also exhibited no significant differences. LT for patients with PVT is clinically feasible and should not be considered a contraindication. However, a favorable outcome is achievable only with ideal surgical management to overcome PVT during LT.


The distinguishing features of urbanization in socialist countries.
Urbanization in developing socialist countries (DSC) is described and compared with urban growth in market-economy countries. The author finds that "the common characteristics of DSC urbanization are mainly composed of two...factors: firstly, they all use a similar set of economic development models. This set of models is different from the development models of capitalist countries. Secondly, compared with population movement in a so-called 'state of anarchy' in an urban economy, socialist countries stress that population movement, just like the deployment of other productive force elements, must submit to central economic planning, and population movement should occur in a 'planned' way."


Analysis of immunoglobulin heavy chain delta transcription termination in the production of delta S or delta M mRNA.
mRNA encoding secreted immunoglobulin is synthesized either by termination of transcription 3' to secreted terminus sequences and 5' to the membrane terminus sequences or by cleavage of a pre-mRNA transcript containing both secreted and membrane sequences at the appropriate polyadenylation site 5' to the membrane sequences. In vitro "run-on" transcription analysis was used to examine the delta transcription termination patterns in resting membrane IgD expressing B lymphocytes, in KWD2, an IgD-secreting hybridoma, and in TEPC 1017, an IgD-secreting plasmacytoma. In resting B cells, transcription terminated in a region 4 to 7 kilobases 3' to the delta M exons. Transcription in the secreting cells continued through the delta M exons, but terminated at more upstream sites. Additionally, an increased loading of polymerases in the region of the delta S exon and its 5' flanking sequence was detected in the secreting cells and was particularly pronounced in TEPC 1017. It is hypothesized that this peak correlates with high delta S mRNA production.


Postpartum haemorrhage.
Most cases of postpartum haemorrhage are caused by uterine atony, maternal soft-tissue trauma, retained placenta or its parts, and obstetric coagulopathy. The factors most significantly associated with haemorrhage include advanced maternal age, prolonged labour, pre-eclampsia, obesity of mother, multiple pregnancy, a birth weight of more than 4000g, and previous postpartum haemorrhage. It seems that multiparity itself is only a weakly associated factor. The prophylactic use of oxytocic drugs (oxytocin or its combination with ergometrine at the third stage of labour is always recommended for decreasing the bleeding. Prostaglandins should be used as a second line treatment if uterine atony cannot be abolished by uterine massage and oxytocin infusion. In the surgical management, the role of hypogastric artery ligation is decreasing. The stepwise uterine devascularization may be a reasonable method in the most severe uncontrollable postpartum bleeding. The uterine tamponade with gauze or specific tubes may also be a useful alternative in some cases. Selective arterial embolization is a promising new method that seems to have success in controlling the heavy postpartum bleeding unresponsive to more usual measures. However, the value of this method should be evaluated in bigger series.


Cell-type specific regulation of myostatin signaling.
The transforming growth factor (TGF)-β family member myostatin is an important regulator of myoblast, adipocyte, and fibroblast growth and differentiation, but the signaling mechanisms remain to be established. We therefore determined the contribution of myostatin type I receptors activin receptor-like kinase-4 (ALK4) and -5 (ALK5) and different coreceptors in C2C12 myoblasts, C3H10T1/2 mesenchymal stem cells, and 3T3-L1 fibroblasts, as well as in primary myoblast and fibroblasts. We performed siRNA-mediated knockdown of each receptor and measured signaling activity using Smad3-dependent luciferase and Smad2 phosphorylation assays with nontargeting siRNA as control. We find that myostatin utilizes ALK4 in myoblasts, whereas it has a preference for ALK5 in nonmyogenic cells. Notably, our results show that coreceptor Cripto is expressed in myoblasts but not in the nonmyogenic cells and that it regulates myostatin activity. More specifically, myostatin requires Cripto in myoblasts, whereas Cripto represses activin activity and TGF-β signaling is Cripto independent. Cripto-mediated myostatin signaling is dependent on both epidermal growth factor (EGF)-like and Cripto-FRL1-cryptic (CFC) domains, whereas activin signaling is solely conferred by the CFC domain. Furthermore, Cripto down-regulation enhances myoblast differentiation, showing its importance in myostatin signaling. Together, our results identify a molecular mechanism that explains the cell-type specific aspects of signaling by myostatin and other TGF-β family members.


Rupture of flexor tendons as a complication of a distal radius fracture.
Two cases are reported of flexor tendon rupture of ulnar side fingers as a complication after distal radius fracture. One was associated with a prominent distal volar lip of fracture site, the other with a relatively volarly displaced ulnar head due to the dorsally tilted distal radius due to malunion. These may be unique cases of flexor tendon rupture with conservatively treated patients.


Neurotrauma: the role of CT angiogram.
Cerebrovascular injuries can occur in blunt or penetrating head and neck trauma. A high index of suspicion based on mechanism of injury and clinical assessment warrants screening for intracranial and extracranial vascular lesions. Conventional angiogram has been and remains the gold standard for diagnosis of these injuries, but computerized tomography angiography offers a fast, noninvasive method of imaging for neurotrauma patients. Advantages and disadvantages of each modality are discussed.


Effect of Oxidized LDL on Platelet Shape, Spreading, and Migration Investigated with Deep Learning Platelet Morphometry.
Platelets are functionally versatile blood cells involved in thrombosis, hemostasis, atherosclerosis, and immune response. Platelet interaction with the immediate microenvironment in blood, vasculature, and tissues alters platelet morphology. The quantification of platelet morphodynamics by geometrical parameters (morphometry) can provide important insights into how platelets sense and respond to stimulatory cues in their vicinity. However, the extraction of platelet shapes from phase contrast microscopy images by conventional image processing is difficult. Here, we used a convolutional neural network (CNN) to develop a deep-learning-based approach for the unbiased extraction of information on platelet morphodynamics by phase contrast microscopy. We then investigated the effect of normal and oxidized low-density lipoproteins (LDL, oxLDL) on platelet morphodynamics, spreading, and haptotactic migration. Exposure of platelets to oxLDL led to a decreased spreading area and rate on fibrinogen, accompanied by increased formation of filopodia and impaired formation of lamellipodia. Haptotactic platelet migration was affected by both LDL and oxLDL in terms of decreased migration velocity and reduced directional persistence. Our results demonstrate the use of deep learning in investigating platelet morphodynamics and reveal differential effects of LDL and oxLDL on platelet morphology and platelet-matrix interaction.


Platinum-based drugs for cancer therapy and anti-tumor strategies.
Platinum-based drugs cisplatin, carboplatin, and oxaliplatin are widely used for chemotherapeutic eradication of cancer. However, the side effects of platinum drugs, such as lack of selectivity, high systemic toxicity, and drug resistance, seriously limit their clinical application. With advancements in nanotechnology and chemical synthesis, Pt-based anti-cancer drugs have made great progress in cancer therapy in recent years. Many strategies relied on the anti-cancer mechanism similar to cisplatin and achieved some success by modifying existing platinum drugs. Pt-based nanodrugs, such as platinum nanoclusters, have novel anti-cancer mechanisms and great potential in tumor-targeted therapy and have shown promising results in clinical application. In this review, we systematically explored the development of first-line platinum chemotherapy drugs in the clinic and their anti-cancer mechanisms. We also summarize the progress of Pt-based anti-cancer drug application in cancer therapy, emphasizing their modification to enhance the anti-tumor effect. Finally, we address challenges faced by platinum chemotherapy drugs, especially Pt nanocluster-based nanodrugs, in cancer treatment. The new platinum drugs and their targeted modifications undoubtedly provide a promising prospect for improving the current anti-cancer treatments.


Diversity-induced resonance in a globally coupled bistable system with diversely distributed heterogeneity.
A moderate degree of diversity, in form of quenched noise or intrinsic heterogeneity, can significantly strengthen the collective response of coupled extended systems. As yet, related discoveries on diversity-induced resonance are mainly concentrated on symmetrically distributed heterogeneity, e.g., the Gaussian or uniform distributions with zero-mean. The necessary conditions that guarantee the arise of resonance phenomenon in heterogeneous oscillators remain largely unknown. In this work, we show that the standard deviation and the ratio of negative entities of a given distribution jointly modulate diversity-induced resonance and the concomitance of negative and positive entities is the prerequisite for this resonant behavior emerging in diverse symmetrical and asymmetrical distributions. Particularly, for a proper degree of diversity of a given distribution, the collective signal response behaves like a bell-shaped curve as the ratio of negative oscillator increases, which can be termed negative-oscillator-ratio induced resonance. Furthermore, we analytically reveal that the ratio of negative oscillators plays a gating role in the resonance phenomenon on the basis of a reduced equation. Finally, we examine the robustness of these results in globally coupled bistable elements with asymmetrical potential functions. Our results suggest that the phenomenon of diversity-induced resonance can arise in arbitrarily distributed heterogeneous bistable oscillators by regulating the ratio of negative entities appropriately.


(-)-Adrenaline-induced, calcium-dependent phosphorylation of proteins in human platelets.
In human platelets, adrenaline stimulated, approximately four-fold, as compared with controls, the phosphorylation of primarily two proteins of apparent molecular weights of 20,000 and 40,000, respectively. Maximum phosphorylation occurred after incubation for 1 min and was inhibited by the addition of either yohimbine, prostaglandin E1, or EGTA. Phosphorylation of the two proteins was accompanied by diacylglycerol formation. The (-)-adrenaline-induced phosphorylation of proteins corresponds to the activation of a calcium-dependent protein kinase partially purified by DEAE-cellulose and Sephadex G150 column chromatography. The enzymatic activity was modulated by addition of (-)-adrenaline and CaCl2, by diolein, and in the presence of membranes or phosphatidylinositol but not phosphatidylethanolamine and phosphatidylcholine. A phospholipid-dependent reaction appears to be involved in the molecular mechanism of action of adrenaline.


[Characteristics of the biochemical properties of pseudomonads isolated from environmental objects].
Biochemical characteristics of 117 Pseudomonas cultures isolated from water bodies and washings off the hospital environment objects were under study, including the strains from patients' wound surfaces. Analysis of the strains' characteristics permitted referring 83.8 +/- 3.7% of them to typical ones as regards their biochemistry. 45.9 +/- 7.5% of these were P. putida, 21.4 +/- 4.8% were P. aeruginosa, 10.2 +/- 1.01% P. fluorescens strains, and the shares of P. cepacia and P. stutzeri strains were 11.2% each. 16.2% of the strains were found atypical because of lysine decarboxylase and growth at 42 degrees C; they were conditionally referred to P. putida. One third of these cultures were isolated in hospital. The detected differences may be helpful in identification of Pseudomonas.


Colonic haemorrhage: a technique for rapid intra-operative bowel preparation and colonoscopy.
We describe a new technique of operative orthograde colonic washout followed by colonoscopy for use in patients with severe colonic haemorrhage. We report its use in four patients in whom the exact source of bleeding was localized and treated. In two of these cases a policy of 'blind' hemicolectomy would have been incorrect. The technique is simple and safe, and we advocate its use during laparotomy for major colonic haemorrhage.


[Epidemiology of extrauterine pregnancy].
An epidemiological study of ectopic pregnancy shows an increased frequency, a diminution of mortality by ectopic pregnancy. This review of the literature points out the influence of several factors implicated in the increased incidence of ectopic pregnancy: pelvis inflammatory disease (PID), intrauterine device and other contraceptive methods tubal ligation, induced abortions, tubal microsurgery, proximal tubal disease, ovulation induction and in vitro fertilization, diethylstilboestrol (DES) syndrome.


Prevalence, Virulence, and Antimicrobial Resistance of Campylobacter spp. in Raw Milk, Beef, and Pork Meat in Northern Poland.
The purpose of this study was to determine whether raw milk, unpasteurized dairy products, pork, and beef available for sale in the Kujawsko-Pomorskie and Wielkopolska regions in Poland are contaminated with Campylobacter spp. bacteria and may be a potential source of infection. For isolated strains, antibiotic susceptibility and the presence of genes responsible for virulence were examined. Material for research included 1058 food samples collected between 2014 and 2018 with 454 samples of raw milk and unpasteurized dairy products (milk from vending machines, milk from owners of dairy cows, cheese, milk cream) and 604 samples of raw meat (pork, beef). The results indicated that 9.3% of the samples were positive for Campylobacter spp., and Campylobacter jejuni was predominant in this study. Campylobacter bacteria was not found in milk collected from vending machines, as well as cheese and milk cream samples. Campylobacter was noted in 12.7% of beef samples, 11.8% of raw milk purchased from individual suppliers, and 10.9% of pork samples. Resistance to erythromycin (2.0%), azithromycin (3.1%), gentamicin (4.1%), tetracycline (65.3%), and ciprofloxacin (71.4%) was determined using the disc diffusion method. Furthermore, the prevalence of racR, sodB, csrA, virB11, cdtB, iam, and wlaN genes were examined using the PCR method. The sodB, csrA, and cdtB genes exhibited the highest detection rate, but none of the genes were identified in 100% of the isolates. Statistically significant differences between the presence of virulence marker genes, including for iam, racR, and csrA markers, were noted among different sources of the isolates. Differences in the distribution of iam, wlaN, and virB11 were also shown between C. jejuni and C. coli strains. As a result of the analysis, it has been concluded that unpasteurized milk, beef, and pork could be a sources of Campylobacter pathogens. Moreover, this study revealed virulent properties of Campylobacter isolated from such food products and high resistance rates to fluoroquinolones, which may represent difficulties in campylobacteriosis treatment.


[Cell kinetics and radiosensitivity of Cercopithecus aethiops sabaceus lymphocytes stimulated by phytohemagglutinin].
The use of the BudR-Giemsa technique has shown that the peripheral blood lymphocytes of Cercopithecus aethiops sabaceus display a very fast answer to PHA-stimulation. At 32 h culture time numerous mitoses are already present and at 48 h more than 30% of the dividing cells are in second mitosis. Exposure to X-irradiation results in a higher incidence of unstable aberrations than in human lymphocytes.


Exopolysaccharide from Bacillus subtilis Induces Anti-Inflammatory M2 Macrophages That Prevent T Cell-Mediated Disease.
Commensal bacteria contribute to immune homeostasis in the gastrointestinal tract; however, the underlying mechanisms for this are not well understood. A single dose of exopolysaccharide (EPS) from the probiotic spore-forming bacterium Bacillus subtilis protects mice from acute colitis induced by the enteric pathogen Citrobacter rodentium Adoptive transfer of macrophage-rich peritoneal cells from EPS-treated mice confers protection from disease to recipient mice. In vivo, EPS induces development of anti-inflammatory M2 macrophages in a TLR4-dependent manner, and these cells inhibit T cell activation in vitro and in C. rodentium-infected mice. In vitro, M2 macrophages inhibit CD4+ and CD8+ T cells. The inhibition of CD4+ T cells is dependent on TGF-β, whereas inhibition of CD8+ T cells is dependent on TGF-β and PD-L1. We suggest that administration of B. subtilis EPS can be used to broadly inhibit T cell activation and, thus, control T cell-mediated immune responses in numerous inflammatory diseases.


Mammalian telomeres and their partnership with lamins.
Chromosome ends are complex structures, which require a panel of factors for their elongation, replication, and protection. We describe here the mechanics of mammalian telomeres, dynamics and maintainance in relation to lamins. Multiple biochemical connections, including association of telomeres to the nuclear envelope and matrix, of telomeric proteins to lamins, and of lamin-associated proteins to chromosome ends, underline the interplay between lamins and telomeres. Paths toward senescence, such as defective telomere replication, altered heterochromatin organization, and impaired DNA repair, are common to lamins' and telomeres' dysfunction. The convergence of phenotypes can be interpreted through a model of dynamic, lamin-controlled functional platforms dedicated to the function of telomeres as fragile sites. The features of telomeropathies and laminopathies, and of animal models underline further overlapping aspects, including the alteration of stem cell compartments. We expect that future studies of basic biology and on aging will benefit from the analysis of this telomere-lamina interplay.


Effects of Web-based instruction on learning behaviors of undergraduate and graduate students.
Web-based instruction requires transformation from traditional teaching strategies to directed independent learning. Careful attention must be given to the creation of effective interactive learning experiences that foster student-to-student and student-to-faculty interactions (l). How content is learned, the effects of the use of computers on learning, and perceived barriers to learning must all be evaluated. Students' responses to Web-based education must also be considered. This article describes the response of 58 undergraduate and 13 graduate students to their initial experiences with Web-based instruction (WBI). While the educational levels of the students and the courses in which the transition to WBI took place differed for the two groups, their computer expertise did not, and similar responses to Web-based learning were noted. Differences in the types of courses and the expertise of the two faculty with regard to WBI also contributed to the production of some dissimilar responses.


Functional results and the risk factors of reoperations after lumbar disc surgery.
Factors such as driving motor vehicles, sedentary occupations, vibration, smoking, previous full-term pregnancies, physical inactivity, increased body mass index (BMI), and a tall stature are associated with symptomatic disc herniations. Fitness and strength is postulated to protect an individual from disc rupture. The objective of our study was to determine the pain levels and differences of functional and economic situations of patients who had undergone one or more than one operation due to lumbar disc herniation and to put forward the effect of risk factors that may be potential, especially from the aspect of undergoing reoperation. Patients who had undergone one (n=46) or more than one operation (n=34) due to lumbar disc herniation were included in the study. It was a prospective study with evaluation on the day the patients were discharged and at second and sixth months after lumbar disc operation. The Oswestry Disability Index (ODI) was used in determining the functional disability associated with back pain; the Prolo Functional Economic Rating Scale (Prolo scale) was used in determining the effect of back pain on functional and economic situations. In the ODI measurements made in the postoperative second and sixth months, significant differences appeared in favor of patients who had undergone one operation (p<0.05). According to the Prolo scale, it was found that the economic situation was better in the sixth month and the functional situation was better in the second and sixth months in patients having undergone one operation (p<0.05). The logistic regression analysis demonstrated that the lack of regular physical exercise was a significant predictor for reoperation (OR, 4.595; CI, 1.38-15.28), whereas gender, age, BMI, occupation, or smoking did not indicate so much significance as regular exercise.


Separation of monoclonal antibody charge state variants by open tubular capillary electrochromatography with immobilised protein as stationary phase.
Monoclonal antibodies (mAbs) are highly heterogeneous and complex glycoproteins requiring powerful analytical tools for characterization and quality control. In this work, we utilize adsorbed bovine serum albumin (BSA) as a stationary phase in open tubular (OT) capillary electrochromatography for separation of charge state variants of mAbs. Poly(diallydimethylammonium chloride) (PDDA) was used to assist fabrication of BSA coated OT column by electrostatic self-assembly. Scanning electron microscopy and electroosmotic flow measurement were carried out to characterize the as-prepared BSA coated PDDA OT columns. The electrochromatographic performance of the OT columns was evaluated by separation of basic proteins and different charge state variants of mAbs. The effects of background solution pH and concentration on separation were investigated. A rapid separation of charge state variants of mAbs was successfully achieved in the BSA coated PDDA OT column. Separation of seven variants of the mAb cetuximab was achieved using the prepared column. Two basic variants and one acidic variant of rituximab, and two basic variants and four acidic variants of trastuximab were successfully distinguished from the main forms. In addition, the columns demonstrated good repeatability and stability with the run-to-run, day-to-day and batch-to-batch relative standard deviations of migration times less than 3.7%.


Lung adenocarcinoma with type II pneumocyte characteristics.
We report a case of primary lung adenocarcinoma with type II pneumocyte characteristics. Electron microscopic examination demonstrated that the tumour cells had well-developed microvilli and cytoplasmic lamellar inclusion bodies. These ultrastructural features are similar to those seen in type II pneumocytes of normal lung tissue. Western blot analysis, using monoclonal antibody against human surfactant protein A (SP-A), clearly demonstrated that the tumour cells expressed human SP-A, which is a major pulmonary surfactant protein produced by type II pneumocytes. These observations suggest that the tumour was derived from a type II pneumocyte.


Lack of evidence for improvement in internal mammary graft flow by occlusion of side branch.
Coronary steal due to unligated side branches of an internal mammary artery graft has been reported previously. Embolization of these side branches has been shown to result in symptomatic improvement, but objective evidence of improved flow to the coronary artery has been lacking. We studied intracoronary Doppler flow in a patient presenting with symptoms thought to be due to a large unligated side branch of mammary graft. There was no significant change in the mammary flow after balloon occlusion of the side branch. More objective data may be required to routinely prescribe side branch embolization for symptomatic patients with unligated side branches of a mammary graft.


Autocrine effects of transgenic resistin reduce palmitate and glucose oxidation in brown adipose tissue.
Resistin has been originally identified as an adipokine that links obesity to insulin resistance in mice. In our previous studies in spontaneously hypertensive rats (SHR) expressing a nonsecreted form of mouse resistin (Retn) transgene specifically in adipose tissue (SHR-Retn), we have observed an increased lipolysis and serum free fatty acids, ectopic fat accumulation in muscles, and insulin resistance. Recently, brown adipose tissue (BAT) has been suggested to play an important role in the pathogenesis of metabolic disturbances. In the current study, we have analyzed autocrine effects of transgenic resistin on BAT glucose and lipid metabolism and mitochondrial function in the SHR-Retn vs. nontransgenic SHR controls. We observed that interscapular BAT isolated from SHR-Retn transgenic rats compared with SHR controls showed a lower relative weight (0.71 ± 0.05 vs. 0.91 ± 0.08 g/100 g body wt, P < 0.05), significantly reduced both basal and insulin stimulated incorporation of palmitate into BAT lipids (658 ± 50 vs. 856 ± 45 and 864 ± 47 vs. 1,086 ± 35 nmol/g/2 h, P ≤ 0.01, respectively), and significantly decreased palmitate oxidation (37.6 ± 4.5 vs. 57 ± 4.1 nmol/g/2 h, P = 0.007) and glucose oxidation (277 ± 34 vs. 458 ± 38 nmol/g/2 h, P = 0.001). In addition, in vivo microPET imaging revealed significantly reduced (18)F-FDG uptake in BAT induced by exposure to cold in SHR-Retn vs. control SHR (232 ± 19 vs. 334 ± 22 kBq/ml, P < 0.05). Gene expression profiles in BAT identified differentially expressed genes involved in skeletal muscle and connective tissue development, inflammation and MAPK and insulin signaling. These results provide evidence that autocrine effects of resistin attenuate differentiation and activity of BAT and thus may play a role in the pathogenesis of insulin resistance in the rat.


Cohort profile: Actionable Register of Geneva Outpatients and inpatients with SARS-CoV-2 (ARGOS).
The Actionable Register of Geneva Outpatients and inpatients with SARS-CoV-2 (ARGOS) is an ongoing prospective cohort created by the Geneva Directorate of Health. It consists of an operational database compiling all SARS-CoV-2 test results recorded in the Geneva area since late February 2020. This article aims at presenting this comprehensive cohort, in light of some of the varying public health measures in Geneva, Switzerland, since March 2020. As of 1 June 2021, the database included 360 525 patients, among which 65 475 had at least one positive test result for SARS-CoV-2. Among all positive patients, 37.6% were contacted only once, 10.6% had one follow-up call, 8.5% had two and 27.7% had three or more follow-up calls. Participation rate among positive patients is 94%. Data collection is ongoing. ARGOS data illustrates the magnitude of COVID-19 pandemic in Geneva, Switzerland, and details a variety of population factors and outcomes. The content of the cohort includes demographic data, comorbidities and risk factors for poor clinical outcome, self-reported COVID-19 symptoms, environmental and socioeconomic factors, prospective and retrospective contact tracing data, travel quarantine data and deaths. The registry has already been used in several publications focusing on symptoms and long COVID-19, infection fatality rate and re-infection. The data of this large real-world registry provides a valuable resource for various types of research, such as clinical research, epidemiological research or policy assessment as it illustrates the impact of public health policies and overall disease burden of COVID-19.


GH3 cell-specific expression of Kv1.5 gene. Regulation by a silencer containing a dinucleotide repetitive element.
A silencer element (Kv1.5 repressor element; KRE) was characterized by deletion analyses in the promoter of Kv1.5, a voltage-gated potassium channel. The silencer element selectively decreases expression of Kv1.5- and thymidine kinase-chloramphenicol acetyl-transferase reporter gene constructs in cell lines that do not express Kv1.5 polypeptide. It contains a dinucleotide repetitive element (poly(GT)19(GA)1(CA)15(GA)16), and self-associates spontaneously in vitro to form complexes with slow electrophoretic mobility. Deletion of the repetitive element abolished self-association in vitro and the silencing activity in transient transfection experiments in vivo. Electromobility gel shift assays of KRE with GH3 cells nuclear extracts detected the formation of a unique DNA-protein complex, which was not detectable in Chinese hamster ovary and COS-7 cells. This complex does not react with an antibody against nonhistone high mobility group 1 protein, which binds KRE in gel retardation assays. These observations establish that a dinucleotide tandem repeat sequence, capable of self-association, forms part of a cell-specific silencer element in a mammalian gene.


Study of family clusters of COVID-19 in the Ústí nad Labem Region with a focus on children - clinical picture, secondary transmission, antibody response.
The article presents the results of a study of family clusters of COVID-19 whose aim was to describe the clinical course of the disease in children, to identify secondary transmission in households with infected children, and to find out the differences in the antibody response between children and adults. Data were collected from 3 March 2020 to 25 October 2020, that is at the time when the alpha or delta variants were not dominant. A retrospective analysis of data on infected children in the Ústí nad Labem Region collected by the Regional Public Health Authority along with questionnaire data reported by their families. Serological tests were performed in study volunteers. The most common symptoms in children were headache, runny nose, and loss of smell and taste. The hospital admission rates were 0.8% in children and 2.4% in adults. The secondary transmission rate in families where the index case was a child reached 22.6%. It was higher when the index case was a child 11-15 years of age or asymptomatic. The secondary transmission rate in families where the index case was an adult equalled 77.1%. Children had higher IgG antibody levels than adults at post-infection months 4 and 5, but their seropositivity rate was comparable to that of adults. Children have a nonspecific clinical course of the disease, which is quite similar as other viroses, and rarely require hospital admission. Secondary transmission in families where the index case was a child is not uncommon and is also possible through contact with an asymptomatic child. After recovery, children have higher levels of antibodies at post-infection months 4 and 5.


Safety and efficacy of chronic therapy with captopril in hypertensive patients: an update.
Captopril, an orally active angiotensin-converting enzyme inhibitor, has been administered to 81 patients with different types of clinical hypertension. Most of the patients had previously uncontrollable high blood pressure. In order to achieve a satisfactory blood pressure control during long-term captopril therapy, a concomitant decrease in total body sodium was required in more than half of the patients. During our first two years of clinical experience with this new antihypertensive agent, side effects developed in 46.9 per cent of the patients and necessitated the withdrawal of the drug in 23.4 per cent of all patients. Only a few side effects such as hypotensive or syncopal episodes and cold extremities appeared to be due to the chronic blockade of the renin-angiotensin system. The most frequent and the most serious adverse reactions such as skin rash, altered taste, pancytopenia, and pemphigus foliaceus seemed to be specifically drug related. The incidence of cutaneous and taste problems was markedly higher in patients with impaired renal function in whom retention of captopril has been previously demonstrated. This suggests that the occurrence of adverse reactions to captopril could be lowered in the future by using smaller daily doses and by titrating them according to the renal function.