Molecular beam scattering of NO+Ne: a joint theoretical and experimental study.
The collision dynamics of the NO+Ne system is investigated in a molecular beam scattering experiment at a collision energy of 1055 cm(-1). Employing resonance enhanced multiphoton ionization of NO, we measured state-resolved integral and differential cross sections for the excitation to various levels of both spin-orbit manifolds. The dependence of the scattered intensity on the laser polarization is used to extract differential quadrupole moments for the collision induced angular momentum alignment. The set of cross section data is compared with results of a full quantum mechanical close coupling calculation using the set of ab initio potential energy surfaces of Alexander et al. [J. Chem. Phys. 114, 5588 (2001)]. In previous work, it was found that the positions and rotational substructures for the lowest bend-stretch vibrational states derived from these surfaces agree very well with the observed spectrum of the NO-Ne complex. For the same potential, we find that the calculated cross sections show a less satisfactory agreement with the experimental data. While the overall Jf dependence and magnitude of the integral and differential cross sections are in good agreement, noticeable discrepancies exist for the angle dependence of the differential cross sections. In general, the calculated rotational rainbow structures are shifted towards larger scattering angles indicating that the anisotropy of the potential is overestimated in the fit to the ab initio points or in the ab initio calculation itself. For most states, we find the measured alignment moments to be in excellent agreement with the results of the calculation as well as with predictions of sudden models. Significant deviations from the sudden models are observed only for those fine-structure changing collisions which are dominated by forward scattering. Results of the full quantum calculation confirm the deviations for these states.


Control of surface wettability and photomicropatterning with a polymorphic diarylethene crystal upon photoirradiation.
A photochromic diarylethene crystal of 1,2-bis(2-methyl-6-nitro-1-benzothiophen-3-yl)perfluorocyclopentene (1 a) was found to undergo a thermodynamic phase transition at 180 °C to form a needle-like crystal, designated as 1 a-γ. The phase transition involves melting of the initial α-crystal and growth of the γ-crystal. The phase transition temperature decreased with the presence of the closed-ring isomer (1 b) in the crystal because of the decrease in the melting temperature. Upon irradiation with ultraviolet (UV) light, compound 1 a in the α-crystal was converted into 1 b to an extent of 20 %. Consequently, the α-crystal containing 20 % of 1 b underwent the phase transition accompanied by melting of the crystal and growth of the γ-crystal even at 170 °C. Photomicropatterning by the phase transition upon irradiation with UV light using a photomask, followed by heating at 170 °C, was successfully accomplished with a resolution in the microcrystalline pattern of about 20 μm. The contact angle with water on the γ-microcrystalline phase on a glass substrate was larger than that on the α-microcrystalline phase by 20°. This can be ascribed to a difference in the roughness of the surface. Furthermore, the γ-microcrystal was also found to be formed upon heating an amorphous film of 1 a in poly(methyl methacrylate) for 2 min at 130 °C. The crystallized area exhibited a higher water contact angle than the amorphous area. Upon irradiation of the amorphous film with UV light, such crystallization did not take place because of the impurity effect of 1 b in 1 a. Photomicropatterning by the crystallization in the polymer showed a pattern with a higher resolution of about 4 μm, which was much better than that of the neat crystal. This photopatterning process represents a useful tool for controlling the surface wettability in relevant applications.


Disome and Trisome Profiling Reveal Genome-wide Targets of Ribosome Quality Control.
The ribosome-associated protein quality control (RQC) system that resolves stalled translation events is activated when ribosomes collide and form disome, trisome, or higher-order complexes. However, it is unclear whether this system distinguishes collision complexes formed on defective mRNAs from those with functional roles on endogenous transcripts. Here, we performed disome and trisome footprint profiling in yeast and found collisions were enriched on diverse sequence motifs known to slow translation. When 60S recycling was inhibited, disomes accumulated at stop codons and could move into the 3' UTR to reinitiate translation. The ubiquitin ligase and RQC factor Hel2/ZNF598 generally recognized collisions but did not induce degradation of endogenous transcripts. However, loss of Hel2 triggered the integrated stress response, via phosphorylation of eIF2α, thus linking these pathways. Our results suggest that Hel2 has a role in sensing ribosome collisions on endogenous mRNAs, and such events may be important for cellular homeostasis.


One half of the CD11b+ human peripheral blood T lymphocytes coexpresses the S-100 protein.
The expression of the CD11b antigen and the presence of the S-100 (and, specifically, its beta subunit) protein within the T4- subpopulation of normal human peripheral blood lymphocytes were investigated by panning techniques, immunofluorescence analysis and immunoelectronmicroscopy. Both antigens are known to be absent in the T4+ lymphocytes. However, CD11b+ T lymphocytes represented about 30% of the T4- population; a part of them (over 1/3) belonged to and completely filled up the T4- T8- subpopulation, whereas the remaining part (almost 2/3) shared the T8 positivity. Interestingly, S-100+ T lymphocytes, which always were CD11b+ too, represented about one half of the CD11b+ T cells, but were excluded from the T4- T8- CD11b+ subpopulation, whereas they represented up to 80% of the T4- T8+ CD11b+ subset. Such findings demonstrate that the S-100+ T lymphocytes are exclusively restricted to a discrete T cell compartment which shows the T8+ CD11b+ immunophenotype. Since such T8+ CD11b+ cells had been shown to possess suppressive capabilities, we herein propose that S-100+ lymphocytes might to some extent modulate the immune responses. However, the exact functional significance of the S-100 protein still remains unknown.


Autoxidation Mechanism and Kinetics of Methacrolein in the Atmosphere.
Elucidating the autoxidation of volatile organic compounds (VOCs) is crucial to understanding the formation mechanism of secondary organic aerosols, but it has been proven to be challenging due to the complexity of reactions under atmospheric conditions. Here, we report a comprehensive theoretical study of atmospheric autoxidation in VOCs exemplified by the atmospherically important methacrolein (MACR), a major oxidation product of isoprene. The results indicate that the Cl-adducts and H-abstraction products of MACR readily react with O2 and undergo subsequent isomerizations via H-shift and cyclization, forming a large variety of lowly and highly oxygenated organic molecules. In particular, the first- and third-generation oxidation products derived from the Cl-adducts and the methyl-H-abstraction complexes are dominated in the atmospheric autoxidation, for which the fractional yields are remarkably affected by the NO concentration. The present findings have important implications for a systematical understanding of the oxidation processes of isoprene-derived compounds in the atmospheric environments.


Amide proton back-exchange in deuterated peptides: applications to MS and NMR analyses.
Deuterium for hydrogen exchange at amide sites in proteins is a well-established means of probing the stability of certain proteins and the effects of interactions with ligands and other proteins. When deuterium content is analyzed by mass spectrometry (MS) of digested peptides, corrections frequently need to be made for back-exchange that occurs during digestion, separation, and analysis. The back-exchange process is actually complex and deserving of analysis in a sequence-specific manner. Here an analysis of back-exchange in the decapeptide, angiotensin I, and a hexapeptide derived by digestion of a 15N-labeled carbohydrate-binding protein, galectin-3, is presented. Nuclear magnetic resonance (NMR) data are used to study back-exchange at specific sites in typical solvents used for separation and analysis, and the derived rates are found to be predictable using methods established for aqueous solvents. The predictability provides potentially new means of improving site specificity of MS analysis and new means of assigning NMR resonances for deuterium content analysis in peptides.


Decreased health-related quality of life in patients with diabetic foot problems.
The aim of this study was to investigate health-related quality of life (HRQoL) in patients with diabetic foot problems and compare the HRQoL between diabetic patients with: 1) diabetic foot problems (DF), including diabetic foot ulcer (DFU) or amputation (AMPU); 2) other diabetic complications (COM), such as diabetic retinopathy (DR), end-stage renal disease (ESRD), or coronary artery disease (CAD); and 3) no diabetic complication (CON). A total of 254 diabetic patients were studied in a cross-sectional setting. HRQoL was evaluated using Thai version of the Euro Quality of Life Questionnaire (EuroQoL), with five dimensions and five-level scale (EQ-5D-5L). Utility scores were calculated using time trade-off methods. A total of 141 patients in the DF group (98 DFU and 43 AMPU groups), 82 in the COM group (27 DR, 28 ESRD, and 27 CAD groups), and 31 in the CON group were interviewed. The mean age was 63.2±12.1 years, body mass index was 24.9±4.7 kg/m2, mean hemoglobin A1c was 7.7±2.1%, duration of diabetes was 13.1±9.9 years, and the mean utility scores were 0.799±0.25. After having DF, 21% of patients had lost their jobs. The COM group had lower utility scores than the CON group. Among the diabetic complications, the DF group had the lowest mean utility scores as compared to the COM and CON groups (0.703±0.28 in the DF group, 0.903±0.15 in the COM group, and 0.961±0.06 in the CON group, P<0.01). There was no difference in the mean utility scores between DFU and AMPU groups. Patients in the DF group reported moderate-to-severe problem in all dimensions more than the other groups. DF have the greatest negative impact on HRQoL. Therefore, diabetic foot care should be emphasized in clinical practice to prevent foot complications.


Beauveria bassiana (Hypocreales: Cordycipitaceae) Reduces the Survival Time of Lutzomyia longipalpis (Diptera: Psychodidae), the Main Vector of the Visceral Leishmaniasis Agent in the Americas.
Visceral leishmaniasis caused by Leishmania infantum (Kinetoplastida: Trypanosomatidae) is a major neglected tropical disease and Brazil is the responsible for most cases reported in the Americas. In this region, L. infantum is primarily transmitted by Lutzomyia longipalpis and Migonemyia migonei (França) (Diptera: Psychodidae) is considered a permissive vector. We evaluated the susceptibility of Lu. longipalpis and Mg. migonei to Beauveria bassiana and to Eucalyptus globulus (Myrtales: Myrtaceae) essential oil. A spore suspension of B. bassiana was prepared and sand flies divided into five groups: test 1 (107 spores/ml of B. bassiana with E. globulus essential oil at 4 mg/ml), test 2 (107 spores/ml of B. bassiana), test 3 (E. globulus essential oil at 4 mg/ml), positive control (cypermethrin 0.1%), and negative control (sterile distilled water). Scanning electron microscopy (SEM) was performed on specimens from each group. A 50% reduction was recorded in the survival time of Lu. longipalpis in test 1 and 2, where hyphal adhesion and cuticle damage were observed by SEM. No significant differences in the survival time of Mg. migonei were found, probable due to the high mortality rate observed in the negative control group, which may be a result of the greater sensitivity of this species to laboratory conditions. The results obtained herein suggest that B. bassiana may be a potential biological control agent against Lu. longipalpis, the main vector of L. infantum in the Americas.


Parallel increases in [alpha-125I]bungarotoxin binding and alpha 7 nicotinic subunit immunoreactivity during the development of rat hippocampal neurons in culture.
Previous studies have shown that hippocampal neurons cultured at high density express alpha-bungarotoxin binding sites and have alpha 7 nicotinic acetylcholine receptor subunit immunoreactivity [Barrantes, G.E., Rogers, A.T., Lindstrom, J. and Wonnacott, S., Brain Res., 672 (1995) 228-236]. We now examine both of these parameters in well-characterized hippocampal neurons cultured at sufficiently low densities to resolve individual neurons and their processes. The specific binding of [alpha-125I]bungarotoxin is first detectable after 3 days in culture and increases during the next 12 days in culture, reaching a maximum of approximately 30,000 binding sites per cell. This is accompanied, over the same timecourse, by an increase in immunoreactivity for two antibodies that specifically bind to the alpha 7 subunit. Both cell bodies and processes were labelled by 9 days in culture. The timecourse of alpha 7-type nicotinic receptor expression resembles that previously described for synapse formation in hippocampal cultures.


A Guide for Undergraduates to the Society for Neuroscience Annual Meeting.
The annual meeting of the Society for Neuroscience (SfN) attracts over 30,000 attendees, including many of the world's most accomplished researchers. Although it can be intimidating to attend a conference of this scale, there are many rewards for undergraduates. Based on surveys of young neuroscientists, we provide planning strategies to ensure attendees maximize their exposure and retention of the breadth and depth offered by this large conference format without becoming overwhelmed.


Engineering of Organic Solvent-Tolerant Antibody to Sulfonamides by CDR Grafting for Analytical Purposes.
The use of organic solvents to extract chemical contaminants for an immunoassay is mostly inevitable. On this occasion, the intolerance of natural antibodies against organic solvent is detrimental to the performance of immunoassays in terms of sensitivity, assay time, accuracy, and precision. Few studies have focused on improving the low tolerance of natural antibodies to organic solvents for analytical purposes. In this study, we engineered the monoclonal antibody (mAb) 4D11 to sulfonamides through CDR grafting by using one proven highly stable humanized antibody (hAb) 4D5 for the first time. The engineered antibody hAb 4D11 showed significantly improved tolerance abilities to acetonitrile (2% to 20%) and methanol (10% to 20%), and retained the highly affinity and class-specificity to sulfonamides. This study provided a general strategy to improve antibody tolerance to organic solvents and was greatly beneficial to the robust development of immunoassays.


Erdosteine protection from cigarette smoke-induced loss of alpha 1-antitrypsin activity in rat lungs.
Acute inhalation of cigarette smoke induced alpha 1-antitrypsin inactivation in rat lungs. The elastase inhibitory capacity of the protein could be prevented by oral treatment with erdosteine (a mucoregulator endowed with free radical scavenging properties). A partial dose-dependent protection was observed with 500 and 1,000 mg/kg. The mechanism of its action might be related either to the inhibition of alpha 1-antitrypsin oxidation manifested by two SH groups liberated in vivo or to the anti-inflammatory and mucoregulator properties present in the substance.


[Protestant clergymen among Hahnemann's clientele. Patient histories in letters].
As part of the research project, developments in the history of science and in the regional and ecclesiastic history of the late feudal petty state of Köthen-Anhalt have been assessed and numerous documents of the Nagel and Mühlenbein family histories examined that place the transcribed patient letters of the two Protestant clergymen within the context of the Hahnemann Archives. These findings complement and extend previous insights into Hahnemann's Köthen clientele, especially when it comes to the structure and milieu of the local clerical elite. Inspired by the interpretive methods of sequential textual analysis, form and content of the letters of the two clergymen and their relatives were also investigated as methodically structured lines of communication. The body of sources published here presents--embedded in the body-image (of sickness and health) prevalent at the time--the medical cultures of educated patients as well as the increasingly professionalized medical practices of Samuel Hahnemann in a flourishing urban doctor's surgery. The correspondence between the pastors Albert Wilhelm Gotthilf Nagel (1796-1835) and August Carl Ludwig Georg Mühlenbein (1797-1866), presented here in a standard edition, has been investigated at Fulda University as part of the project 'Homöopathisches Medicinieren zwischen alltäglicher Lebensführung und professioneller Praxis' ('Homeopathic medicine between everyday use and professional practice'). Of the altogether 78 transcribed documents, 53 are letters written by either of the two pastors, 16 are patient journals by Samuel Hahnemann, 9 letters by the pastors' wives and Mühlenbein's mother. The two series of letters, originally composed between 1831 and 1833 in old German cursive script, can now be used as sources for research into the history of homeopathy.


[Snake as a symbol in medicine and pharmacy - a historical study].
The snake and snake venoms have stimulated the mind and imagination of humankind since the beginning of records about society. No animal has been more worshipped yet more cast out, more loved yet more despised than the snake. The essence of the fascination with fear of the snake lies within the creature's venom. Snakes have been used for worship, magic potions and, medicine, and they have been the symbol of love, health, disease, medicine, pharmacy, immortality, death and even wisdom. In the Sumer civilization (B.C. 2350-2150), designs with 2 snakes appeared. In Greek mythology (B.C. 2000-400), statues of Asclepius (God of Medicine), with "Caduceus" (made of two snakes and a staff), and his daughter Hygeia (God of Health), holding a snake and bowl, were created as symbols for medicine and health, respectively. A kind of Caduceus (1 snake and 1 staff) has been used as a symbol by the World Health Organization (WHO) and a snake and bowl as a symbol of pharmacies in Europe. Snakes have also been worshipped by old Indian peoples involved in Hinduism since 6-4th century B.C. In ancient Egypt, snake designs were used in hieroglyphs. In China, dried bodies of about 30 species of snakes are still using as Chinese medicines. In Japan, a painting of the symbol of "Genbu" (snake with tortoise) was found recently on the north wall of the Takamatsuzuka ancient tomb (7-8th century A.D.), however it is a symbol of a compass direction, and has probably less relation to medicine and pharmacy.


The selectivity of DG-5128 as an alpha 2-adrenoceptor antagonist.
DG-5128 (2-[2-(4,5-dihydro-1H-imidazol-2-yl)-1-phenylethyl]pyridine dihydrochloride sesquihydrate) at concentrations up to 10 microM inhibited [3H]clonidine binding more effectively than it did [3H]prazosin binding in rat cerebral cortex membranes. The mode of inhibition was homogeneous and consistent with the law of simple mass action. DG-5128 exhibited a 7.4 times higher affinity (pKi = 6.28) toward alpha 2-adrenoceptors than alpha 1-adrenoceptors. The results indicate that DG-5128 is a preferential alpha 2-antagonist.


Limited cross-variant immune response from SARS-CoV-2 Omicron BA.2 in naïve but not previously infected outpatients.
Omicron is currently the dominant SARS-CoV-2 variant and several sublineages have emerged. Questions remain about the impact of previous SARS-CoV-2 exposure on cross-variant immune responses elicited by the SARS-CoV-2 Omicron sublineage BA.2 compared to BA.1. Here we show that without previous history of COVID-19, BA.2 infection induces a reduced immune response against all variants of concern (VOC) compared to BA.1 infection. The absence of ACE2 binding in sera of previously naïve BA.1 and BA.2 patients indicates a lack of meaningful neutralization. In contrast, anti-spike antibody levels and neutralizing activity greatly increased in the BA.1 and BA.2 patients with a previous history of COVID-19. Transcriptome analyses of peripheral immune cells showed significant differences in immune response and specific antibody generation between BA.1 and BA.2 patients as well as significant differences in the expression of specific immune genes. In summary, prior infection status significantly impacts the innate and adaptive immune response against VOC following BA.2 infection.


Role of a novel immune modulating DDR2-expressing population in silica-induced pulmonary fibrosis.
Micro-injuries associated with chronic inhaled particle exposures are linked with activation of the immune response and are thought to contribute to progression of fibrotic disease. In the pulmonary environment, we have previously demonstrated a heterogeneous population of circulating fibroblast precursors (CFPs), which are defined by expression of the pan-leukocyte marker CD45 and the collagen receptor, discoidin domain receptor-2 (DDR2). This population is derived from the hematopoietic stem cell, expresses collagen, and has a fibroblastic morphology in vitro. Herein, we demonstrate a novel subset of CFPs expressing immune markers CD11b, CD11c, and major histocompatibility complex II (MHC II). The CFP population was skewed toward this immune marker expressing subset in animals with silica-induced pulmonary fibrosis. Data indicate that this CFP subset upregulates co-stimulatory molecules and MHC II expression in response to silica-induced fibrosis in vivo. Functionally, this population was shown to promote T cell skewing away from a Th1 response and toward a pro-inflammatory profile. These studies represent the first direct flow cytometric and functional evaluation of the novel immune marker expressing CFP subset in an exposure-induced model of pulmonary fibrosis. Elucidating the role of this CFP subset may enhance our understanding of the complex immune balance critical to mediating exposures at the pulmonary-host interface and may be a valuable target for the treatment of exposure-induced pulmonary fibrosis.


Adult Multipotent Cardiac Progenitor-Derived Spheroids: A Reproducible Model of In Vitro Cardiomyocyte Commitment and Specification.
Three-dimensional cell culture systems hold great promise for bridging the gap between in vitro cell-based model systems and small animal models to study tissue biology and disease. Among 3D cell culture systems, stem-cell-derived spheroids have attracted significant interest as a strategy to better mimic in vivo conditions. Cardiac stem cell/progenitor (CSC)-derived spheroids (CSs) provide a relevant platform for cardiac regeneration. We compared three different cell culture scaffold-free systems, (i) ultra-low attachment plates, (ii) hanging drops (both requiring a 2D/3D switch), and (iii) agarose micro-molds (entirely 3D), for CSC-derived CS formation and their cardiomyocyte commitment in vitro. The switch from a 2D to a 3D culture microenvironment per se guides cell plasticity and myogenic differentiation within CS and is necessary for robust cardiomyocyte differentiation. On the contrary, 2D monolayer CSC cultures show a significant reduced cardiomyocyte differentiation potential compared to 3D CS culture. Forced aggregation into spheroids using hanging drop improves CS myogenic differentiation when compared to ultra-low attachment plates. Performing CS formation and myogenic differentiation exclusively in 3D culture using agarose micro-molds maximizes the cardiomyocyte yield. A 3D culture system instructs CS myogenic differentiation, thus representing a valid model that can be used to study adult cardiac regenerative biology.


Influence of Number Fluctuation and Position Variation of Channel Dopants and Gate Metal Grains on Tunneling Field-Effect Transistors (TFETs).
The influence of number fluctuation and position variation on channel dopants and gate metal grains on tunneling field-effect transistors (TFETs) have been discussed in comparison with metal-oxide-semiconductor FETs (MOSFETs). Based on the simulation results of randomly generated device samples, the shape of the statistical threshold voltage (V(th)) distribution of TFETs associated with individual variation sources such as random dopant fluctuation (RDF) and work-function variation (WFV) have been found to be significantly different than that of MOSFETs. This analysis provides a detailed insight into the variation sources related to underlying physics of TFETs.


Ethnic and age variation of cancer of the reproductive system in women of Kyrgyzstan.
The purpose of this research was to assess the ethnic and age variation in the incidence rates of cancer of the female reproductive system (cancers of the breast, cervix uteri, corpus uteri and ovaries) in Kyrgyzstan. A retrospective approach was adopted covering the period from 1995 to 2002 with descriptive and analytical methods to estimated incidence rates in women of Russian and Kyrgyz nationalities. Values were found to be higher in Russian women but decreasing over time, while increase was observed for the Kyrgyz. Breast cancers were most common in Russian women and in their Kyrgyz counterparts cancer of the cervix uteri predominated. The data reveal age and ethnic variation in cancer localization.


Histopathological changes in morphea and their clinical correlates: Results from the Morphea in Adults and Children Cohort V.
Histopathological features in morphea (localized scleroderma) and their clinical correlates are poorly described. We sought to systematically describe histologic changes of morphea in a large, well-annotated cohort and determine the association between histopathology and clinical features. This was a cross-sectional study of 83 patients enrolled in the Morphea in Adults and Children cohort. The main outcome measure was the association of microanatomical location and degree of sclerosis and inflammation seen on histologic samples with patient-reported symptoms and physician-based measures of severity. Pattern of sclerosis was associated with morphea subtype, the presence of patient-reported symptoms, and functional limitation. A bottom-heavy pattern of sclerosis was associated with pain and tightness (P = .0039 and .001, respectively). These symptoms were not associated with a top-heavy pattern. Severe inflammation may be associated with pain and functional limitation (P = .073 for both). Small sample size limits ability to detect associations, particularly in subgroups. Histopathological examination of morphea may assist in identifying patients who may require additional monitoring and treatment. Features such as patterns of sclerosis and severity of inflammation should be included in pathology reports to help aid in clinical management.


Relevance of functional neuroimaging in the progression of mild cognitive impairment.
To assess whether combining neuropsychological tests and cerebral blood flow markers improves progression accuracy from mild cognitive impairment (MCI) to Alzheimer's disease (AD) than each of them on its own. Forty-two patients were investigated prospectively, undergoing baseline and 3-year follow-up neuropsychological tests and neuroimaging with Tc-ECD-SPECT. Twenty-one patients had developed AD while 21 retained their initial diagnosis. The relative blood flow and cognitive differences were studied. Validity parameters, multivariant analysis and logistic regression model were calculated. Patients who deteriorated showed lower scoring than stable subjects in some neuropsychological tests (p = 0.03-0.001) and in relative blood flow in selected regions (8-10%). Low cognitive test scoring and low relative blood flow in some regions showed sensibilities and specificities from 70% to 86% for the diagnosis of early Alzheimer's disease. The relative risk of progression to AD was up to 4.7 times higher for these patients (p = 0.0001). The left frontal relative blood flow, the CAMCOG and orientation scoring were the best data to predict the risk of progression to AD. The combination of functional imaging and neuropsychological tests can diagnose with high sensitivity and specificity if a patient is suffering cognitive impairment in its early stages, and may aid in predicting the risk of developing dementia.


Spectroscopic imaging as a triage test for cervical disease: a prospective multicenter clinical trial.
The objective of the study was to evaluate the potential safety and effectiveness of tissue spectroscopy for the diagnosis of cervical cancer in a prospective multicenter study of women scheduled for colposcopy on the basis of an abnormal Pap test or other risk factor. Five hundred seventy-two women underwent spectroscopy of the cervix during their colposcopy visit. Spectroscopy measurements taken over a scan period of 4 minutes and 30 seconds were integrated by a cross-validated pattern recognition model and compared with biopsy results to yield sensitivity and specificity of cervical spectroscopy. The median age of subjects enrolled in the study was 27.7 years. The sensitivity of cervical spectroscopy was 95.1% with a corresponding 55.2% specificity for benign lesions. Several potential confounding factors (eg, mucous, blood, patient motion, ambient light) were examined to determine their potential impact on the accuracy of the test. Ambient light seemed to have the greatest effect, but no single factor contributed significantly to the results. The subjects did not experience any adverse events from undergoing the test. Spectroscopy of the cervix has the potential to accurately detect cervical moderate and high-grade dysplasia while also reducing the false-positive rate for benign cervices. The test is relatively simple to implement and was well accepted by subjects enrolled in the study.


Cross-Cultural Validation of the Quality of Life in Hand Eczema Questionnaire (QOLHEQ).
The Quality of Life in Hand Eczema Questionnaire (QOLHEQ) is the only instrument assessing disease-specific health-related quality of life in patients with hand eczema. It is available in eight language versions. In this study we assessed if the items of different language versions of the QOLHEQ yield comparable values across countries. An international multicenter study was conducted with participating centers in Finland, Germany, Japan, The Netherlands, Sweden, and Turkey. Methods of item response theory were applied to each subscale to assess differential item functioning for items among countries. Overall, 662 hand eczema patients were recruited into the study. Single items were removed or split according to the item response theory model by country to resolve differential item functioning. After this adjustment, none of the four subscales of the QOLHEQ showed significant misfit to the item response theory model (P < 0.01), and a Person Separation Index of greater than 0.7 showed good internal consistency for each subscale. By adapting the scoring of the QOLHEQ using the methods of item response theory, it was possible to obtain QOLHEQ values that are comparable across countries. Cross-cultural variations in the interpretation of single items were resolved. The QOLHEQ is now ready to be used in international studies assessing the health-related quality of life impact of hand eczema.


Real-World Eligibility for Sacubitril/Valsartan in Heart Failure with Reduced Ejection Fraction Patients in Korea: Data from the Korean Acute Heart Failure (KorAHF) Registry.
Sacubitril/valsartan (SV, LCZ696), the first in class drug, called as angiotensin receptor-neprilysin inhibitor (ARNI) can reduce heart failure (HF) hospitalization and cardiovascular mortality. However, SV prescription rate remains still low despite current HF guideline recommendations. Considering the complex inclusion criteria of Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, the real-world eligibility for SV remains uncertain in Asian heart failure with reduced ejection fraction (HFrEF) patients. Therefore, we aimed to assess real-world HF population eligibility for SV in a large Korean acute HF registry. From March 2011 to February 2014, a total of 5,625 patients who were admitted for HF were enrolled in Korea. After excluding HF patients with left ventricular ejection fraction > 40% and in-hospital death, 2,941 patients were analyzed. Criteria for SV based on Korean Food and Drug Administration (KFDA) label and PARADIGM-HF were applied. Of 2,941 patients, KFDA label criteria excludes the absence of symptoms (New York Heart Association class I, 20%); PARADIGM-HF criteria excludes chronic kidney disease stage IV (9%), hyperkalemia (1%), hypotension (6%), and sub-optimal pharmacotherapy (52%, e.g. lower dose use of angiotensin converting enzyme inhibitor/angiotensin receptor blocker [ACEI/ARB], beta blocker use). When a daily requirement of ACEI/ARB ≥5 mg enalapril (instead of ≥10 mg) was used, the percent of eligibility for SV rose from 12% to 30% based on the PARADIGM-HF criteria. Among the Korean hospitalized HFrEF patients, 80% met KFDA label criteria, while only 12% met the inclusion criteria of PARADIGM-HF trial for SV if requiring ≥10 mg enalapril. Sub-optimal pharmacotherapy could be the main reason for ineligible SV use based on the PARADIGM-HF criteria.


Maternal Anemia during pregnancy and infant low birth weight: A systematic review and Meta-analysis.
Infant low birth weight is one of the major problems in different societies. Different reports have provided different results regarding the relationship between maternal anemia and infant low birth weight in different months of pregnancy. The aim of this study was to determine the relationship between maternal anemia during pregnancy and infant low birth weight. This systematic review was conducted using related keywords in national (Sid, Iran.doc, Iran medex and Magiran) and international (PubMed, Science Direct, Cochrane, Medline, Web of Science, Scopus, Springer, Embase, Google scholar) databases. Relative risks and confidence intervals were extracted from each study. The results were combined using random-effects model for meta-analysis. The I2 index was also used to measure heterogeneity between the studies. Overall, 17 studies with a total sample size of 245407 entered the final meta-analysis and demonstrated that the relative risk for maternal anemia in the first, second and third trimester of pregnancy were 1.26 (95% CI: 1.03-1.55), 0.97 (95% CI: 0.57-1.65), and 1.21 (95% CI: 0.84-1.76), respectively. The relationship between maternal anemia and infant low birth weight in the first trimester of pregnancy was significant. Maternal anemia, especially during the first trimester of pregnancy, can be considered as a risk factor for pregnancy outcomes. Therefore, one needs to take the necessary steps to cure this disease in order to reduce the incidence of infant low birth weight.


Circulating Tumor Cells in Esophageal Cancer.
Esophageal cancer (EC) is mostly diagnosed due to clinical symptoms such as dysphagia or anemia. Depending on the staging and the histological subtype, squamous cell carcinoma or adenocarcinoma, patients with non-metastasized disease mostly undergo neoadjuvant chemoradiation or perioperative chemotherapy followed by esophageal resection. Nearly 50% of the curatively treated patients develop distant metastasis within 5 years, although no metastases were clinically evident at time of treatment. More recently, the concept of circulating tumor cells (CTC) has also been introduced for EC. CTC are thought to be the means of systemic tumor spread, with the ability to set up metastases in distant organs. Much effort has been made to capture, enrich and detect these very rare cells from the blood stream of EC patients. CTC have been found to be independent risk factors for worse prognosis in patients with EC. Pre- and intra-therapeutic CTC enrichment and detection has the potential to improve preoperative staging, and provide a differential indication for neoadjuvant therapeutic modality and an indication for adjuvant therapy.


[Acrosyringium and follicular infundibulum: immunomorphologic aspects].
Acrosyringium and infundibulum are epidermal structures with different morphology, but functional similarities regarding re-epithelialization, transport of antigens, and attraction of infiltrates. Immunomorphologically, the infundibula revealed an immunoreactivity of Langerhans cells and keratinocytes comparable with that of the interfollicular epidermis, whereas the acrosyringia reacted differently because of the permanent expression of MHC class II antigens and reduced Langerhans cells in the perisyringial region. Our findings suggest that these epidermal compartments differ with regard to their individual immunologic situations. While the mechanisms of epidermal immunity known from the interfollicular epidermis are possibly the same in the infundibula, we have to expect a basically different immunologic situation in the acrosyringia.


Neuroendocrine targets of endocrine disruptors.
The central neuroendocrine systems are responsible for the control of homeostatic processes in the body, including reproduction, growth, metabolism and energy balance, as well as stress responsiveness. These processes are initiated by signals in the central nervous system, specifically the hypothalamus, and are conveyed first by neural and then by endocrine effectors. The neuroendocrine systems, as the links between the brain and peripheral endocrine organs, play critical roles in the ability of an organism to respond to its environment under normal circumstances. When neuroendocrine homeostasis is disrupted by environmental endocrine-disrupting chemicals, a variety of perturbations can ensue, particularly when endocrine disruption occurs during critical developmental time periods. This article will discuss the evidence for environmental endocrine disruption of neuroendocrine systems and the effects on endocrine and reproductive functions.


[Empiric antibiotic therapy in the treatment of postoperative abdominal abscesses. Clinical and microbiological data].
Abdominal abscesses arising postoperatively constitute a serious problem, particularly in the field of oncological surgery. The aim of our study was to interpret clinical and microbiological data relating to a population of oncological patients, undergoing ultrasound-guided drainage for postoperative abdominal abscesses, so as to be able to better plan empiric antibiotic therapy. We therefore retrospectively analysed the data of 24 patients operated on for neoplastic pathologies and treated with ultrasound-guided percutaneous drainage for abdominal abscesses during the postoperative period. Microbiological and clinical data showed that abscesses located in the lower abdominal regions almost always present a polymicrobial growth, though abscesses in the upper regions are more frequent. Moreover, the antibiotic assay results prompted us to consider the use of beta-lactamines, quinolones and glycopeptides more favourably, in view of their greater efficacy against the microbes tested. Thus, the planning of empiric antibiotic therapy should be based above all on the anatomical-topographic location of the abdominal abscess and on the type of operation performed, with thorough assessment of the use of the above-mentioned antibiotics.


Microwave permittivity, permeability, and absorption of Ni nanoplatelet composites.
The Ni nanoplatelets with an average diameter of 75 nm and an average thickness of 10 nm are coated with MnO2 by a simple solution phase chemical method. The MnO2-coated Ni nanoplatelets are dispersed in paraffin wax to form the composite samples of the magnetic filler dispersed in the nonmagnetic insulating matrix. The effect of the Ni nanoplatelet volume fraction on the complex permittivity, complex permeability, and microwave absorption of the composites has been studied in the frequency range of 0.1-10 GHz. The complex permittivity of the composites with different volume fractions of the Ni nanoplatelets is almost constant in the 0.1-10 GHz frequency range. The complex permeability of the composites shows several resonance peaks. Besides the natural resonance peak, the exchange resonance peaks are observed. The composite with 17% volume fraction of Ni nanoplatelets has excellent microwave absorption properties of a minimum reflection loss value -31 dB at 9.1 GHz for a thickness of 2 mm and a broad absorption bandwidth of 2.3-10 GHz (R < -10 dB). The Ni nanoplatelets are a possible candidate as high performance microwave absorption filler. For the Ni nanoplatelet composites, the magnetic loss is the dominant term for microwave absorption.


[Study on the preemptive analgesia effects of both the parecoxib sodium and the pentazocine in patients undergoing nasal endoscopic surgery].
To evaluate the preemptive analgesia effects of both the parecoxib sodium and the pentazocine in patients undergoing nasal endoscopic surgery. In the randomized, double blind, controlled study, 120 patients undergoing septoplasty were divided into 3 groups (n = 40): group A received parecoxib 40 mg by muscle injection 30 min before the operation; group B received pentazocine 30 mg; group C received an equal volume of saline. The preemptive analgesia effect was evaluated with VAS scores which recorded at different time points. The proportion of participants using rescue analgesia after the operation were recorded as additional measures of preemptive analgesia. Intra-operative as well as the postoperative pain scores were less in the group A and group B than in the control group. Fewer participants required rescue medication after operation with parecoxib as well as pentazocine than placebo. However there were no difference in the preemptive effects between the group A and group B. Administration of both the parecoxib and pentazocine before the nasal endoscopic surgery can provide preemptive analgesia without serious adverse side effects that deserves popularization in the clinic.


Myosin heavy chain accumulates in dissimilar cell types of the macromere lineage in the sea urchin embryo.
In this study, myosin heavy chain from sea urchin pluteus larvae was characterized by analysis of a 2.5-kb cDNA clone. DNA sequence of 1465 bp demonstrated a 71% similarity in the deduced amino acid sequence to the embryonic rat skeletal muscle sequence. Antibodies generated against a polypeptide encoded by the open reading frame of the cDNA clone specifically identified a 210-kDa myosin protein which accumulated in 8-12 muscle cells differentiating bilateral to the esophagus beginning at early larval stages. This same myosin also accumulated in cells of the endodermal epithelium that comprise the three sphincters of the larval gut. Thus, a gene encoding myosin heavy chain is expressed in dissimilar cell types of the macromere lineage, and the pattern of accumulation in the gut identifies functionally distinct cells of the endodermal epithelium.


Unusual association of SCN2A epileptic encephalopathy with severe cortical dysplasia detected by prenatal MRI.
We present an atypical association of SCN2A epileptic encephalopathy with severe cortical dysplasia. SCN2A mutations are associated with epileptic syndromes from benign to extremely severe in absence of such macroscopic brain findings. Prenatal MRI (Magnetic Resonance Imaging) in a 32 weeks fetus, with US (Ultrasonography) diagnosis of isolated ventriculomegaly showed CNS (Central Nervous System) dysplasia characterized by lack of differentiation between cortical and subcortical layers, pachygyria and corpus callosum dysgenesis. Postnatal MRI confirmed the prenatal findings. On day 6 the baby presented a focal status epilepticus, partially controlled by phenobarbital, phenytoin, and levetiracetam. After three weeks a moderate improvement in seizure control has been achieved with carbamazepine. Exome sequencing detected a de novo heterozygous mutation in the SCN2A gene, encoding the αII-subunit of a sodium channel. The patient findings expand the phenotype spectrum of SCN2A mutations to epileptic encephalopathies with macroscopic brain developmental features.


Total and Visceral Adiposity Are Associated With Prevalent Vertebral Fracture in Women but Not Men at Age 62 Years: The Newcastle Thousand Families Study.
Low body weight is an established risk factor for osteoporosis and fracture, but the skeletal risks of higher adiposity are unclear and appear sex-specific and site-dependent. The aim of this study was to investigate associations of total fat mass (TFM), visceral adipose tissue (VAT), and C-reactive protein (CRP) with bone mineral density (BMD) and prevalent vertebral fracture (VF) in men and women aged 62 years. A total of 352 men and women aged 62.5 ± 0.5 years from the Newcastle Thousand Families Study cohort received dual-energy X-ray absorptiometry (DXA) evaluations of femoral neck and lumbar spine BMD, of the lateral spine for vertebral fracture assessment, and of the whole body for TFM and VAT (GE Lunar CoreScan, Madison, WI, USA). Plasma CRP, FRAX scores, falls in the last 12 months, and occupation at age 50 years were also included in the analysis. Vertebral fractures were less prevalent in women than in men (odds ratio [OR] = 0.33, p < 0.001) and BMD or FRAX scores did not differ between participants with and without VF. Women with VF were heavier and had higher TFM, VAT, and CRP than women without (p < 0.001). In women, greater (+1 SD) TFM and VAT increased the odds of any grade VF (TFM: OR = 1.06, p = 0.001; VAT: OR = 2.50, p = 0.002), and greater VAT mass increased the odds of prevalent mild VF (OR = 2.60, p = 0.002). In contrast, there were no associations in men. In both sexes, after controlling for body weight, neither VAT nor CRP were associated with BMD. In conclusion, irrespective of BMD, total and visceral adiposity were associated with prevalent VF in women but not in men. High fat mass, particularly if visceral, should be considered when assessing VF risk in women. Risk factors for VF in men require further investigation, particularly given their high prevalence. © 2017 American Society for Bone and Mineral Research.


Solid-State Fluorescent Carbon Dots with Aggregation-Induced Yellow Emission for White Light-Emitting Diodes with High Luminous Efficiencies.
For practical applications of carbon dots (CDs), a major challenge is to prevent the notorious aggregation-caused quenching (ACQ) effect. Herein, a new type of CDs (CD1) has been developed that can transform from ACQ to an enhancement of fluorescence by aggregation-induced emission (AIE). The blue fluorescence of the CDs is suppressed by ACQ. However, this is accompanied by the phenomenon of AIE at a longer wavelength, resulting in the emergence and gradual enhancement of yellow fluorescence. The obtained CD1 solid powder shows a bright yellow emission with a photoluminescence quantum yield (PLQY) of 65%. The photoluminescence (PL) spectra, absorption spectra, and time-resolved PL decay curves indicate that Förster resonant energy transfer from dispersed CD1 particles to large CD1 agglomerations leads to the enhancement of yellow fluorescence. To exploit its high PLQY and strong AIE, CD1 is applied as a color-converting layer on blue light-emitting diode (LED) chips to fabricate white LEDs (WLEDs). The obtained devices show white light coordinates of (0.29, 0.38) and (0.32, 0.42), which are close to pure white light (0.33, 0.33), and luminous efficiencies of 97.8 and 93.9 lm·W-1 and show good stability. The low cost, easy fabrication, controllability, and favorable fluorescence properties signify that CD1 of AIE will have superior performance in a variety of applications.


Induction of human herpesvirus 8 gene expression in a posttransplantation primary effusion lymphoma cell line.
Human herpesvirus 8 (HHV-8 or Kaposi's sarcoma herpesvirus) is a gamma herpesvirus that is most likely the etiologic agent of both Kaposi's sarcoma and primary effusion lymphoma (PEL), a rare HIV-associated lymphoma. The role of HHV-8 in post-transplant lymphoma is less well characterized. We demonstrate that HHV-8 is constitutively present in LH5-21 cells, an atypical patient derived posttransplant PEL cell line. LH5-21 cells lack detectable Epstein-Barr virus, express T cell-associated surface markers and have undergone immunoglobulin heavy chain gene rearrangement. Incubation with 12-O-tetradecanoyl-phorbol- 13-acetate or butyrate induces high levels of several HHV-8 encoded genes that are associated with lytic replication. The patient from whom this cell line was derived demonstrated a dramatic clinical response to withdrawal of immunosuppressive therapy. While HHV-8 associated PELs in the post-transplant setting are rare, this study suggests that improvement in the host immunologic function might help in the management of some PELs.


Cations affect the rate of gating charge recovery in wild-type and W434F Shaker channels through a variety of mechanisms.
In this study we examine the effects of ionic conditions on the gating charge movement in the fast inactivation-removed wild-type Shaker channel and its W434F mutant. Our results show that various ionic conditions influence the rate at which gating charge returns during repolarization following a depolarizing pulse. These effects are realized through different mechanisms, which include the regulation of channel closing by occupying the cavity, the modulation of transitions into inactivated states, and effects on transitions between closed states via a direct interaction with the channel's gating charges. In generating these effects the cations act from the different binding sites within the pore. Ionic conditions, in which conducting wild-type channels close at different rates, do not significantly affect the rate of charge recovery upon repolarization. In these conditions, channel closing is fast enough not to be rate-limiting in the charge recovery process. In the permanently P-inactivated mutant channel, however, channel closing becomes the rate-limiting step, presumably due to weakened ion-ion interactions inside the pore and a slower intrinsic rate of gate closure. Thus, variations in closing rate induced by different ions are reflected as variations in the rate of charge recovery. In 115 mM internal Tris(+) and external K(+), Cs(+), or Rb(+), low inward permeation of these ions can be observed through the mutant channel. In these instances, channel closing becomes slower than in Tris(+)(O)//Tris(+)(I) solutions showing resemblance to the wild-type channel, where higher inward ionic fluxes also retard channel closing. Our data indicate that cations regulate the transition into the inactivated states from the external lock-in site and possibly the deep site. The direct action of barium on charge movement is probably exerted from the deep site, but this effect is not very significant for monovalent cations.


Evaluating the quality of shared decision making during the patient-carer encounter: a systematic review of tools.
The concept of shared decision making (SDM) has been developing in many countries since the 1990s. The main challenge of SDM, based on the principles of respect for the person's autonomy, is to improve patients' participation, should they so wish, in decisions concerning their personal health. To our knowledge, there is only one SDM evaluation tool validated in metropolitan French that does not measure the entire SDM construct. The aim of this review was to identify existing and validated SDM measurement tools to determine which of them could be adapted in French to cover all the dimensions of SDM. A systematic literature review was conducted based on articles found in the PubMed and PsycINFO bibliographic databases and published between 2010 and 2014. Studies were included if the main goal of the article was the development and psychometric validation of an SDM measurement tool, not specific to any given disease or situation, in English, French and Spanish. We used the nine essential elements of the Makoul and Clayman's integrative model to describe the different existing tools. Nineteen studies were included. Seven new tools had been published since Scholl's previous review in 2011. We observed a recent spread of the multi-appraiser approach, which combines points of view of patients, healthcare professionals and sometimes external observers. Several models were used for the development of the seven newly identified tools. None of the identified tools assessed the nine elements of the Makoul's model. Three of these elements, however, were systematically measured in each of the new tools: "defining/explaining the problem", "patient values/preferences", and "checking/clarifying understanding". We identified several potentially interesting tools for the French context which could cover the whole elements of Makoul's model. The next step will be the development of a French-language instrument based on these tools.


Striving for Better Medical Education: the Simulation Approach.
Medical simulation is a rapidly expanding area within medical education due to advances in technology, significant reduction in training hours and increased procedural complexity. Simulation training aims to enhance patient safety through improved technical competency and eliminating human factors in a risk free environment. It is particularly applicable to a practical, procedure-orientated specialties. Simulation can be useful for novice trainees, experienced clinicians (e.g. for revalidation) and team building. It has become a cornerstone in the delivery of medical education, being a paradigm shift in how doctors are educated and trained. Simulation must take a proactive position in the development of metric-based simulation curriculum, adoption of proficiency benchmarking definitions, and should not depend on the simulation platforms used. Conversely, ingraining of poor practice may occur in the absence of adequate supervision, and equipment malfunction during the simulation can break the immersion and disrupt any learning that has occurred. Despite the presence of high technology, there is a substantial learning curve for both learners and facilitators. The technology of simulation continues to advance, offering devices capable of improved fidelity in virtual reality simulation, more sophisticated procedural practice and advanced patient simulators. Simulation-based training has also brought about paradigm shifts in the medical and surgical education arenas and ensured that the scope and impact of simulation will continue to broaden.


Improving routine immunization data quality using daily short message system reporting platform: An experience from Nasarawa state, Nigeria.
Routine immunization (RI) delivery was declared a public health concern in Nigeria in 2017 because of persistently low immunization coverage rates reported in independent surveys. However, administrative coverage rates remain high, suggesting serious data quality issues. We posit that a shorter timespan between service provision and data reporting can improve the monitoring of RI data, and developed a short message system (SMS) text reporting strategy to generate daily RI data points from health facilities (HFs). The goal was to assess whether daily data collection produces complete, reliable and internally consistent data points. The SMS reporting platform was piloted between December 2017 and April 2018 in two Local Government Areas (LGAs, equivalent to districts) of Nasarawa state, Nigeria. The 145 healthcare workers from 55 HFs received one mobile phone and pre-configured SIM card, and were trained to send data through predefined codes. Healthcare workers compiled the data after each vaccination session and transmitted them via SMS. We analyzed completeness, number of weekly sessions, and supportive supervision conducted. During the pilot phase, we received data from 85% (n = 47) of the 55 HFs. We expected 66 fixed-post sessions and 30 outreach sessions per week, but received data for 33 fixed-post and 8 outreach weekly session on average. More HFs reported on Tuesdays compared to other days of the week. When assessing internal consistency, we observed that the reported number of children vaccinated was sometimes higher than the number of doses available from opening a given number of vaccine vials. When found, this discrepancy was noted for all antigens during fixed-post and outreach vaccination sessions. Despite these initial discrepancies, transmitting RI data sessions via texting is feasible and can provide real-time updates to the performance of the RI services at the HF level.


Control regions for chromosome replication are conserved with respect to sequence and location among Escherichia coli strains.
In Escherichia coli, chromosome replication is initiated from oriC by the DnaA initiator protein associated with ATP. Three non-coding regions contribute to the activity of DnaA. The datA locus is instrumental in conversion of DnaA(ATP) to DnaA(ADP) (datA dependent DnaA(ATP) hydrolysis) whereas DnaA rejuvenation sequences 1 and 2 (DARS1 and DARS2) reactivate DnaA(ADP) to DnaA(ATP). The structural organization of oriC, datA, DARS1, and DARS2 were found conserved among 59 fully sequenced E. coli genomes, with differences primarily in the non-functional spacer regions between key protein binding sites. The relative distances from oriC to datA, DARS1, and DARS2, respectively, was also conserved despite of large variations in genome size, suggesting that the gene dosage of either region is important for bacterial growth. Yet all three regions could be deleted alone or in combination without loss of viability. Competition experiments during balanced growth in rich medium and during mouse colonization indicated roles of datA, DARS1, and DARS2 for bacterial fitness although the relative contribution of each region differed between growth conditions. We suggest that this fitness advantage has contributed to conservation of both sequence and chromosomal location for datA, DARS1, and DARS2.


Resistant protein; its existence and function beneficial to health.
The remnants of proteins themselves or complexes with protein remaining no longer indigestible in the intestine are referred to as resistant proteins, which exert physiological functions similar to dietary fibers and are also better for health. In recent years, noticeable functions attributable to resistant proteins have become gradually apparent with regard to several proteinous items. Recent investigations have revealed that the relevant ingredients are either condensed in isolates or concentrates of vegetable proteins or causally brought about as a consequence of denaturation and/or entanglement in the process of preparation. Some protein components inherently insusceptible to mammalian digestive enzymes also belong to the group of resistant proteins in case of edibility irrespective of their sources. Among the medicinal benefits of several resistant proteins hitherto pointed out by animal experiments, there were preventive effects against hypercholesterolemia, constipation, corpulence, tumorigenesis (colon, liver, mammary gland), gallstone formation or poisoning, and wholesome improvements in enteric fermentation of short-chain fatty acids.


Association Between Fatty Liver Index, Controlled Attenuation Parameter, and Metabolic Syndrome Stages: A Community-Based Study.
BACKGROUND Controlled attenuation parameter (CAP) is a recent ultrasound-based method for measuring hepatic steatosis, which is common in patients with metabolic syndrome (MetS). The fatty liver index (FLI), an algorithm-based method, is frequently used to evaluate hepatic steatosis. This study assessed how FLI and CAP relate to the earlier MetS stage and their ability to identify it. MATERIAL AND METHODS A total of 170 community-based individuals were studied. Demographic information, body mass index, waist circumference, and blood pressures were collected. CAP was assessed by FibroScan. Fasting glucose, lipid tests, and γ-glutamyl transferase were measured. The CAP and FLI results were categorized into quartiles, with the MetS stages as the main outcomes. The odds ratio (OR) of the outcomes was calculated using logistic regression. The area under the curve in receiver operating characteristic analysis (AUC-ROC) was used to detect the stages of MetS. Sensitivity, specificity, and appropriate cut-offs based on ROC analysis are shown. RESULTS The higher the FLI or CAP category, the lower the proportion of non-MetS and the higher the proportion of moderate MetS. Each single-quartile increase in FLI and CAP was associated with an increased likelihood of being in the higher MetS stages - FLI: adjusted OR 3.1 (2.23-4.32); CAP: adjusted OR 1.96 (1.48-2.59). In the ROC analysis, FLI had a higher AUC-ROC than CAP in separating the stages of MetS, although findings were significant (P<0.001). FLI in detecting the stages of mild-to-severe versus non-MetS performed well (AUC-ROC [95% confidence interval]: 0.79 [0.72-0.87]), with high sensitivity (0.86) but low specificity (0.62). CONCLUSIONS FLI and CAP were positively associated with the MetS stage and its components, suggesting that they could be used as a MetS screening tool in community studies.


Examining coordination and equilibrium: an analysis of supply index and spatial evolution characteristics for older adult services in Zhejiang Province.
This study aims to analyze the spatial distribution and dynamic evolution of older adult service supply in Zhejiang Province from 2010 to 2019. Additionally, this research seeks to propose an optimized resource allocation strategy for older adult care services, promoting regional fairness and coordinated development. To evaluate the older adult service supply capacity, this research first constructed an evaluation index system based on the Chinese modernization development pattern. Then, an empirical analysis was carried out using a combination of the entropy-TOPSIS method, kernel density estimation, Markov chain analysis, Dagum Gini coefficient, and panel regression model. The results show an overall upward trend in the supply and service capacity of older adult care in the whole province. However, the spatial distribution of older adult service supply capacity in Zhejiang Province still exhibits a gradient effect, even in the most recent year of 2019. Furthermore, the supply capacity of older adult services shifted to a higher level in the whole province, and regions with high supply capacity had a positive spillover effect on adjacent regions. The overall difference in the older adult service supply capacity of the province showed a decreasing trend. The level of economic development, urbanization rate, transportation capacity, the level of opening up, and the proportion of employees in the tertiary industry had a significant impact on the supply capacity and spatial difference of older adult services. From the findings, this study puts forth countermeasures and suggestions to optimize the spatial distribution of older adult care services. This includes giving full play to the regional spatial linkage effect, promoting new-type urbanization construction, upgrading the transportation network, and expanding the opening up of the industrial structure. By implementing these measures, a more equitable and coordinated older adult services system can be developed in Zhejiang Province.


Translating to the Community (T2C): a protocol paper describing the development of Canada's first social epigenetic FASD biobank.
Translating to the Community (T2C) is a social biorepository designed to advance new diagnostic tools and realign community-clinical processes, with the aim to mitigate the short- and long-term impacts of fetal alcohol spectrum disorder (FASD) as well as prenatal alcohol exposure and its co-morbidities and behaviors. In this paper, we describe the evolution of this repository as a new translational partnership to advance a precision-medicine approach to FASD. Key to its evolution was a partnership between academic researchers, Indigenous communities, families, and a regional diagnostic clinic. We further describe the rationale for social biobanking, the type of banking, ethical engagement of families, communities, and clinics, their roles in repository design, governance, translation, and research activities, types of data collected from families, and how the study data are managed, reported, and accessed. The repository design includes biological samples, social-contextual health-survey data, and clinical data (which are linkable to administrative data) from community and clinical cohorts of diagnosed children, children prenatally exposed but not diagnosed, children suspected to have had a prenatal exposure, and related siblings, biological parents, and unrelated children and their parents. From these cohorts and families, potential studies drawing on this data will shed light on various risk factors, social and biological pathways, and service utilization issues, with the aim to implement primary and secondary prevention and intervention strategies.


Towards a low complexity carbon removal model for the optimal design of compact decentralised wastewater treatment systems.
On-site decentralised wastewater treatment systems can provide a financially attractive alternative to a sewer connection in locations far from existing sewer networks. Operational problems and shortcomings in the design of these systems still occur frequently. The aim of this paper is to provide a low complexity (i.e. easy to calibrate) but still accurate mathematical model that can be used to optimise the operational design of compact individual wastewater treatment systems. An integrated hydraulic and biological carbon removal model of a biofilm-based compact decentralised treatment system is developed. The procedure for drafting the model is generic and can be used for similar types of wastewater treatment systems since (i) the hydraulic model is based on an N-tanks-in-series model inferred from tracer test experiments and (ii) (biofilm) respirometry experiments are exploited to determine the biodegradation kinetics of the biomass. Based on the preliminary validation results of the integrated model, the carbon removal in the system can be predicted quite accurately. While some adjustments could further improve the modelling strategy, the here presented results can already assist the manufacturers of compact treatment systems in efficiently (re)designing their systems.


Recombinant respiratory syncytial virus (RSV) bearing a set of mutations from cold-passaged RSV is attenuated in chimpanzees.
A set of five missense mutations previously identified by nucleotide sequence analysis of subgroup A cold-passaged (cp) respiratory syncytial virus (RSV) has been introduced into a recombinant wild-type strain of RSV. This recombinant virus, designated rA2cp, appears to replicate less efficiently in the upper and lower respiratory tracts of seronegative chimpanzees than either biologically derived or recombinant wild-type RSV. Infection with rA2cp also resulted in significantly less rhinorrhea and cough than infection with wild-type RSV. These findings confirm the role of the cp mutations in attenuation of RSV and identify their usefulness for inclusion in future live attenuated recombinant RSV vaccine candidates.


Proteome analysis revealed the essential functions of protein phosphatase PP2A in the induction of Th9 cells.
Proteomic analysis identifies post-translational functions of proteins, which remains obscure in transcriptomics. Given the important functions of Th9 cells in anti-tumor immunity, we performed proteome analysis of Th9 cells to understand the involvement of proteins that might be crucial for the anti-tumor functions of Th9 cells. Here we performed a comprehensive proteomic analysis of murine Th0 and Th9 cells, and identified proteins that are enriched in Th9 cells. Pathway analysis identified an abundance of phosphoproteins in the proteome of Th9 cells as compared to Th0 cells. Among upregulated phosphoproteins, Ppp2ca (catalytic subunit of protein phosphatase, PP2A) was found to be highly enriched in Th9 cells. Although the role of PP2A has been shown to regulate the differentiation and functions of Th1, Th2, Th17 and Tregs, its role in the differentiation and functions of Th9 cells is not identified yet. Here we found that PP2A is required for the induction of Th9 cells, as PP2A inhibition leads to the suppression of IL-9 and expression of key transcription factors of Th9 cells. PP2A inhibition abrogates Th9 cell-mediated anti-tumor immune response in B16-OVA melanoma tumor model. Thus, we report that PP2A is essential for the differentiation and anti-tumor functions of Th9 cells.


Factors affecting recovery from anaesthesia with propofol-remifentanil target-controlled infusion in laparoscopic surgery.
Objective This study was performed to analyse factors influencing the effect-site concentration (Ce) of propofol at return of consciousness (ROC) with target-controlled infusion of propofol-remifentanil after laparoscopic surgery. Methods In total, 112 patients who underwent laparoscopic surgery under general anaesthesia were given propofol at the target concentration of 3.5 µg/ml. Remifentanil (Ce: 4.0 ng/ml) and 0.9 mg/kg of rocuronium were administered when the Observer's Assessment of Alertness/Sedation score reached 1. Two minutes after injection of rocuronium, tracheal intubation was initiated. The bispectral index (BIS) was maintained between 45 and 55. Results Ce values of propofol at loss of consciousness (LOC) and ROC were significantly correlated. Age was significantly correlated with Ce of propofol at ROC. At LOC, propofol Ce values of patients aged 65-80, 45-64, and 20-44 years were 1.8 ± 0.8, 2.2 ± 0.7, and 2.3 ± 0.8 µg/ml, respectively, and the BIS was 70 ± 10, 68 ± 7, and 69 ± 10, respectively. At ROC, the propofol Ce values of the three groups were 1.2 ± 0.3, 1.4 ± 0.3, and 1.5 ± 0.3 µg/ml, respectively, and the BIS was 80 ± 5, 82 ± 6, and 83 ± 6, respectively. Conclusions The concentration of propofol at ROC was significantly affected by age, and ROC of propofol-remifentanil anaesthesia after laparoscopic surgery was well predicted by the concentration at LOC.


Combined impacts of multimorbidity and mental disorders on frequent emergency department visits: a retrospective cohort study in Quebec, Canada.
Multimorbidity and mental disorders are independently associated with frequent visits to the emergency department (≥ 3 visits/yr), but their interaction has been little studied. We aimed to measure the interaction between mental disorders and physical multimorbidity with respect to frequent visits to the emergency department. We conducted a population-based cohort study of adults in Quebec from 2012 to 2016, using the Quebec Integrated Chronic Disease Surveillance System. We assessed multimorbidity as the number of physical illnesses and mental disorders as serious (psychotic or bipolar disorders), common or absent, using data from 2012 to 2014. We counted emergency department visits from 2014 to 2015. We used logistic regression to estimate interaction on frequent visits to the emergency department from 2 perspectives: of public health (additive scale as differences in risk) and of individual patients (multiplicative scale as odds ratios). Each additional physical illness was associated with a greater increase in the absolute risk of frequent visits to the emergency department for people with mental disorders. Between 0 and ≥ 4 physical conditions, the absolute risk increased more for individuals with serious mental disorders (16.2%) than common (15.3%) or no disorders (11.4%). On the relative scale, for people with no mental disorders and ≥ 4 physical conditions, odds of frequent visits to the emergency department were 6.2 (95% confidence interval [CI] 6.08-6.35) times the odds for people with no physical conditions. For individuals with common and serious mental illnesses, corresponding odds ratios were 4.75 (95% CI 4.60-4.90) and 3.7 (95% CI 3.18-3.57), respectively. Mental disorders interact with physical multimorbidity to increase the odds of frequent visits to the emergency department. More research is needed on interventions that promote high-quality care for mental illness, especially in the context of physical multimorbidity.


Making effective use of dashboards.
Sam Foster, Chief Nurse at Heart of England NHS Foundation Trust, considers some of the pitfalls users might encounter when collating and interpreting data.


N1-Selective alkenylation of 1-sulfonyl-1,2,3-triazoles with alkynes via gold catalysis.
A N1-selective alkenylation of 1-sulfonyl-1,2,3-triazoles with alkynes via gold catalysis is reported. N1-Vinyl substituted 1,2,3-triazoles were selectively prepared in up to 92% yield through the sulfonyl group of 1,2,3-triazole derivatives transformed to alkenyl groups in a "one-pot two steps" manner. This method provided a new method for the synthesis of potentially biological-active vinyl-triazole building blocks.


Complement activation and anaphylatoxin (C3a and C5a) formation in preeclampsia and by amniotic fluid.
The aim of this study was to determine whether the biologically active complement peptides C3a and C5a are formed in pregnancy and whether amniotic fluid can activate complement. C3a and C5a are formed when complement is activated. They increase smooth-muscle contraction, vascular permeability, and histamine release from mast cells and basophils. Thirty pregnant women were studied, 16 with uncomplicated and 14 with preeclamptic pregnancies. The plasma C3a and C5a concentrations before delivery were significantly higher in the preeclamptic than in the normal group. The concentrations returned to normal within 1 week. Plasma, serum, and amniotic fluid from 12 pregnant women (eight uncomplicated and four preeclamptic pregnancies) were drawn in connection with delivery. Amniotic fluid was incubated in fresh autologous serum at 37C for 15 minutes. A dose-dependent formation of C3a and C5a was registered with increasing amounts of amniotic fluid.


Naevoxanthoendothelioma (Synonym: Juvenile Xanthogranuloma).
A case of naevoxanthoendothelioma juvenile xanthogranuloma) is reported with rare features like late onset of the disease, involvement of liver and diffuse cutaneous lesions including cafe au lait spots and pigmented naevus. Final diagnosis could be achieved only on histopathology report.


Clinical and Genetic Characteristics of BRCA1/2 Mutation in Korean Ovarian Cancer Patients: A Multicenter Study and Literature Review.
We investigated the clinical relevance and spectrum of BRCA1/2 mutations in Korean ovarian cancer (KoOC) patients. Two hundred seventy-nine KoOC patients were enrolled from three university hospitals between 2012 and 2017. Their peripheral blood samples were obtained for BRCA1/2 mutation analysis by direct sequencing. Clinicopathological characteristics were retrospectively reviewed, and spectrum analyses of BRCA1/2 mutation were assessed by systematic literature review. Frequency of BRCA1/2 mutations was 16.5% in KoOC patients. BRCA1/2 mutations were significantly associated with family history of breast/ovarian cancer (p<0.001), serous histology (p=0.044), and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (III/IV, p=0.018) but not with early age-of-onset (age < 50, p=0.729). Literature review of BRCA1/2 mutations in KoOC patients found 111 (55 distinct) mutations with high proportion of Korean-specific mutations (24/55, 43.6%). Comparing the spectrum of BRCA1/2 mutation between KoOC and Korean breast cancer (KoBC) patients, the ratio of BRCA1-to-BRCA2 mutations was different, with BRCA1 (78.4%) being predominant in KoOC and BRCA2 in KoBC (59.2%). The most common mutation also differed between the two (c.3627insA of BRCA1 in KoOC and c.7480C>T of BRCA2 in KoBC). The clinical relevance of BRCA1/2 mutations in KoOC patients was confirmed but that of early age-of-onset was not. Possible inconsistency in the ratio of BRCA1-to-BRCA2 mutations and the most common mutation between KoOC and KoBC may probably suggest presence of mutation sequence-associated penetrance tendency in hereditary Korean breast and ovarian cancer. These data may provide insights for optimal genetic counseling and prophylactic treatment for at-risk relatives of KoOC patients.


Immunoglobulin and cytokine production from mesenteric lymph node lymphocytes is regulated by extracts of Cordyceps sinensis in C57Bl/6N mice.
Cordyceps sinensis, one of the well-known fungi used in traditional Chinese medicine, is recognized to play a role in the metabolic process of inflammation and immunity. The purpose of this study was to evaluate the effects of water extracts of C. sinensis on the immune function of mesenteric lymph node (MLN) lymphocytes in C57Bl/6N mice. C. sinensis-treated mice were administered the respective extract by oral gavage for 4 weeks. Immunoglobulin E concentrations in serum and MLN lymphocytes were significantly lower in C. sinensis-treated mice than in control mice. In contrast, the immunoglobulin A concentration from the C. sinensis group was higher than that in control mice. C. sinensis increased the proportion of CD4(+) and CD8(+) T cells in MLN lymphocytes. C. sinensis significantly decreased interleukin-4 and interleukin-10 cytokine concentrations. Therefore, water extracts of C. sinensis modulate immune parameters through regulation of immunoglobulin production resulting from decreased T-lymphocyte helper 2 cytokine secretion and reduce cytokine secretion in MLN lymphocytes.


Wear Characteristic of Stellite 6 Alloy Hardfacing Layer by Plasma Arc Surfacing Processes.
The microstructure and wear resistance of Stellite 6 alloy hardfacing layer at two different temperatures (room temperature and 300°C) were investigated by plasma arc surfacing processes on Q235 Steel. Tribological test was conducted to characterize the wear property. The microstructure of Stellite 6 alloy coating mainly consists of α-Co and (Cr, Fe)7C3 phases. The friction coefficient of Stellite 6 alloys fluctuates slightly under different loads at 300°C. The oxide layer is formed on the coating surface and serves as a special lubricant during the wear test. Abrasive wear is the dominant mechanism at room temperature, and microploughing and plasticity are the key wear mechanisms at 300°C.


Chemotactic behavior of the sperm of chitons (Mollusca: Polyplacophora).
Observations of sperm behavior in the vicinity of gradients of egg-water or alcohol extracts of whole freshly-spawned eggs of several chitons reveal what appear to be directed movements of sperm up the gradient, resulting in the aggregation of motile sperm at the gradient source. Plots of the tracks of the sperm approaching the gradient source show that the cells increase the time during which they move toward the source and decrease the time spent moving away. Although this resembles the kinesis behavior shown by bacteria in a gradient, the path directions are markedly non-random. The reorientation behavior of thigmotactic sperm involves enlargement of the normal circular path diameter in the direction of the source and an alternation of tight loops and wide circular arcs, with the latter made in the direction of the source. The form of the path of attracted chiton sperm is like that observed during chemotaxis of the sperm of the hydroid Tubularia and the tunicate Ciona and resembles the behavior of Ciona sperm in that there is no increase in velocity as the cells move up the gradient. However, unlike the cnidarian and urochordate cases, the attracting substances extracted from chiton eggs do not act species-specifically.


The association of Schistosomiasis mansoni and proteinuria in an endemic area. A preliminary report.
The association of Schistosoma mansoni infection and proteinuria was investigated by measuring quantitative urinary protein in a defined population in an endemic area in northeastern Brazil. Persons with schistosomiasis had higher mean urinary protein than those without. Two of 162 persons with schistosomiasis had clear evidence of renal disease (pathologic proteinuria, abnormal urinary sediment). These results seemed to be related neither to the intensity of S. mansoni infection as measured by fecal egg excretion nor to the presence of hepatic and splenic enlargement in schistosomiasis.


Regulation of information passing by synaptic transmission: a short review.
The largest part of information passed among neurons in the brain occurs by the means of chemical synapses connecting the axons of presynaptic neurons to the dendritic tree of the postsynaptic ones. In the present paper, the most relevant open problems related to the mechanisms of control of the information passing among neurons by synaptic transmission will be shortly reviewed. The "cross talking" between synapses, their mutual interactions and the control of the information flow between different areas of the dendritic tree will be also considered. The threshold mechanism based on the "reversal potential" will be considered for its role in the control of information transfer among neurons and also for its contribution to the information flow among different areas of the dendritic tree and to the computational ability of the single neuron. The concept of "competition for plasticity" will be proposed as a mechanism of competition based on the synaptic activation time.


β-Arabinofuranosylation using 5-O-(2-quinolinecarbonyl) substituted ethyl thioglycoside donors.
A new β-stereoselective D- and L-arabinofuranosylation method has been developed employing 5-O-(2-quinolinecarbonyl) substituted arabinosyl ethyl thioglycosides as glycosyl donors. The approach allows a wide range of acceptor substrates to be used; the β-selectivity is good-to-excellent. Stereoselective synthesis of a mannose-capped octasaccharide portion from a mycobacterial cell wall polysaccharide was then carried out to demonstrate the utility of this methodology.


In Situ Self Assembly of Nanocomposites: Competition of Chaotic Advection and Interfacial Effects as Observed by X-Ray Diffreaction.
The effects of chaotic advection on the in situ assembly of a hierarchal nanocomposite of Poly Amide 6, (nylon 6 or PA6) and platelet shape nanoparticles (NPs) were studied. The assemblies were formed by chaotic advection, where melts of pristine PA6 and a mixture of PA6 with NPs were segregated into discrete layers and extruded into film in a continuous process. The process assembles the nanocomposite into alternating pristine-polymer and oriented NP/polymer layers. The structure of these hierarchal assemblies was probed by X-rays as a processing parameter, N, was varied. This parameter provides a measure of the extent of in situ structuring by chaotic advection. We found that all assemblies are semi-crystalline at room temperature. Increasing N impacts the ratio of α to γ crystalline forms. The effects of the chaotic advection vary with the concentration of the NPs. For nanocomposites with lower NP concentrations the amount of the γ crystalline form increased with N. However, at higher NP concentrations, interfacial effects of the NP play a significant role in determining the structure, where the NPs oriented along the melt flow direction and the polymer chains oriented perpendicular to the NP surfaces.


Salt intake and Helicobacter pylori infection.
The chance finding of an association between Helicobacter pylori infection and hypertension and the known relationship between salt intake and blood pressure led us to speculate whether these two environmental factors might be related. A positive relationship between them might suggest that a high-salt diet could in some way facilitate gastric H. pylori infection. We have therefore conducted an ecological study of the national H. pylori infection rates in the EUROGAST study and national salt excretion levels with the INTERSALT project. Ten nations were included in both projects. Statistically significant correlation between H. pylori infection rates and salt excretion were found in older men and women (r = 0.728 and r = 0.827, respectively) and in younger men (r = 0.728), but not younger women (r = 0.519). Our findings raise the possibility that salt intake may in some way facilitate H. pylori infection. A dedicated population survey is now justifiable to investigate the role of salt intake in H. pylori infection with the measurement of all possible confounding variables including particularly socio-economic status


Effect of intrarenal renin-angiotensin-aldosterone system on renal function in patients after cardiac surgery.
The aim of the study was to investigate the influence of intrarenal RAS on the decrease of renal function in patients undergoing cardiac surgery with cardiopulmonary bypass. This observational study investigated the activation of intrarenal RAS in 24 patients with AKI after cardiac surgery with cardiopulmonary bypass. The activation of intrarenal RAS was determined by urinary angiotensinogen (uAGT), which was measured at 12 hours before surgery, 0 and12 hours after surgery. The results were compared with those of 21 patients without AKI after cardiac surgery with cardiopulmonary bypass. Clinical and laboratory data were collected. Compared with baseline, all patients with cardiac surgery had activation of intrarenal RAS at 0 and 12 hours after surgery. The activation of intrarenal RAS was found significantly higher at both 0 and 12 hours after surgery in AKI group versus non AKI group (6.18 ± 1.93 ng/mL vs 3.49 ± 1.71 ng/mL, 16.38 ± 7.50 ng/mL vs 6.04 ± 2.59 ng/mL, respectively). There was a positive correlation between the activation of RAS at 0 hour after surgery and the decrease of renal function at 48 hours after surgery (r = 0.654, P = .001). These findings suggest that uAGT might be a suitable biomarker for prediction of the occurrence and severity of AKI after cardiac surgery. Inhibition of intrarenal RAS activation might be one the path of future treatment for this type of disease.


Flavin supported fatty acid oxidation by the heme domain of Bacillus megaterium cytochrome P450BM-3.
Cytochrome P450BM-3 is a fatty acid hydroxylase that consists of a heme domain covalently attached to a diflavin (FMN+FAD) cytochrome P450 reductase domain. The heme and flavin domains can be separately expressed and purified from E. coli recombinant expression systems. Normally P450s require a protein redox partner as a source of electrons. We now have found that the P450BM-3 heme domain can be reduced by NADPH+FMN and that reduced FMN can support the P450 catalyzed hydroxylation of a fatty acid substrate, myristic acid. HPLC profiles show that the "artificial" FMN supported hydroxylation gives the same products as does holo-P450BM-3.


Identification and characterization of an insect homologue of the vertebrate Golgi apparatus protein 1 (MG-160/cysteine-rich fibroblast growth factor receptor/E-selectin ligand-1/latent transforming growth factor-beta complex protein-1) with a Golgi-specific monoclonal antibody.
A monoclonal antibody 14F10 was raised against Golgi fractions from Sf21 cells and selected as Golgi specific. Immunohistochemical stainings with the antibody localized the antigen in Golgi cisterns of the cells. The antigen was purified and shown to be a 130-K membrane protein with N-glycans and intrachain disulfide bonds. Amino acid sequencing of its peptide fragments revealed that the antigen contained homologous sequences to those encoded by CG7190 and CG7193 Drosophila melanogaster genes. No possible transmembrane domain existed in these deduced amino acid sequences, while one did in that encoded by CG7195, an adjacent gene to CG7193. Furthermore, 5' and 3' expression sequence tags of LD19434 had been mapped to CG7190 and a downstream region of CG7195, respectively. These findings supported that all of these genes actually composed a single gene, which encoded an orthologous protein to a vertebrate Golgi-resident protein, Golgi apparatus protein 1, also called cysteine-rich FGF receptor, E-selectin ligand-1, or latent TGF-beta complex protein-1. Our results suggested that the Golgi apparatus protein 1 played a critical role in the Golgi cisterns through the animal kingdom.


Civil Liberties in a Lockdown: The Case of COVID-19.
In response to the spread of COVID-19, governments across the world, with very few exceptions, have enacted sweeping restrictive lockdown policies that impede citizens' freedom to move, work, and assemble. This paper critically responds to the central arguments for restrictive lockdown legislation. We build our critique on the following assumption: public policy that enjoys virtually unanimous support worldwide should be justified by uncontroversial moral principles. We argue that the virtually unanimous support in favor of restrictive lockdowns is not adequately justified by the arguments given in favor of them. Importantly, this is not to say that states ought not impose restrictive lockdown measures, but rather that the extent of the acceptance of these measures is not proportionate to the strength of the arguments for lockdowns.


Direct nkx2-5 transcriptional repression of isl1 controls cardiomyocyte subtype identity.
During cardiogenesis, most myocytes arise from cardiac progenitors expressing the transcription factors Isl1 and Nkx2-5. Here, we show that a direct repression of Isl1 by Nkx2-5 is necessary for proper development of the ventricular myocardial lineage. Overexpression of Nkx2-5 in mouse embryonic stem cells (ESCs) delayed specification of cardiac progenitors and inhibited expression of Isl1 and its downstream targets in Isl1(+) precursors. Embryos deficient for Nkx2-5 in the Isl1(+) lineage failed to downregulate Isl1 protein in cardiomyocytes of the heart tube. We demonstrated that Nkx2-5 directly binds to an Isl1 enhancer and represses Isl1 transcriptional activity. Furthermore, we showed that overexpression of Isl1 does not prevent cardiac differentiation of ESCs and in Xenopus laevis embryos. Instead, it leads to enhanced specification of cardiac progenitors, earlier cardiac differentiation, and increased cardiomyocyte number. Functional and molecular characterization of Isl1-overexpressing cardiomyocytes revealed higher beating frequencies in both ESC-derived contracting areas and Xenopus Isl1-gain-of-function hearts, which associated with upregulation of nodal-specific genes and downregulation of transcripts of working myocardium. Immunocytochemistry of cardiomyocyte lineage-specific markers demonstrated a reduction of ventricular cells and an increase of cells expressing the pacemaker channel Hcn4. Finally, optical action potential imaging of single cardiomyocytes combined with pharmacological approaches proved that Isl1 overexpression in ESCs resulted in normally electrophysiologically functional cells, highly enriched in the nodal subtype at the expense of the ventricular lineage. Our findings provide an Isl1/Nkx2-5-mediated mechanism that coordinately regulates the specification of cardiac progenitors toward the different myocardial lineages and ensures proper acquisition of myocyte subtype identity.


Unroofed coronary sinus: update on diagnosis and treatment.
Unroofed coronary sinus (UCS) is among the rarest congenital heart malformations in pediatric practice. Often, they are associated with persistent left superior vena cava (PLSVC) draining into the left atrium, and in this situation, there is a double intracardiac shunt, right-to-left and left-to-right. They are asymptomatic in the majority of the cases. Each ordinary imagistic method (transthoracic echocardiography, contrast transesophageal echocardiography, angiography) can be helpful in finding the diagnosis, but enhanced computed tomography scan can give an irrefutable diagnosis. The surgical intervention may consist in the recreation of a roof for the coronary sinus, and anastomosis of the PLSVC to the right atrial appendage.


An integrated framework for examining groundwater vulnerability in the Mekong River Delta region.
The Mekong River provides water, food security, and many other valuable benefits to the more than 60 million Southeast Asian residents living within its basin. However, the Mekong River Basin is increasingly stressed by changes in climate, land cover, and infrastructure. These changes can affect water quantity and quality and exacerbate related hazards such as land subsidence and saltwater intrusion, resulting in multiple compounding risks for neighboring communities. In this study, we demonstrate the connection between climate change, groundwater availability, and social vulnerability by linking the results of a numerical groundwater model to land cover and socioeconomic data at the Cambodia-Vietnam border in the Mekong River Delta region. We simulated changes in groundwater availability across 20 years and identified areas of potential water stress based on domestic and agriculture-related freshwater demands. We then assessed adaptive capacity to understand how communities may be able to respond to this stress to better understand the growing risk of groundwater scarcity driven by climate change and overextraction. This study offers a novel approach for assessing risk of groundwater scarcity by linking the effects of climate change to the socioeconomic context in which they occur. Increasing our understanding of how changes in groundwater availability may affect local populations can help water managers better plan for the future, leading to more resilient communities.


Erratum.
In the report "A candidate magnetic sense organ in the yellowfin tuna, Thunnus albacares" by M. M. Walker et al. (18 May, p. 751), the standard error given on page 752 (3rd column, first full paragraph) for the sizes of the magnetite particles was instead the standard deviation. Use of the term "standard error" implies a far greater variance in the sizes of the particles than actually existed and could lead to the conclusion that the published electron micrograph is not typical but presents a biased sample of the particles.


Effects of therapeutic positioning on vital parameters in patients with central neurological disorders: a randomised controlled trial.
To investigate the effects of positioning on heart rate, breathing frequency and blood pressure in postacute, severely disabled patients with central neurological disorders. Positioning patients is part of the regular nursing routine in the care for severely disabled patients. Positioning can be done in a conventional way or in Lagerung in Neutralstellung (Engl.: positioning in neutral), which has recently been shown to have better effects on the passive range of motion and comfort than conventional positioning. While it is thought that positioning influences vital parameters, so far no study has investigated this for a clinically relevant observation period, and no study has compared different positioning concepts in this respect. A multicentre, randomised, controlled, single-blind clinical trial. Two hundred and eighteen patients were randomly assigned to positioning in neutral or conventional positioning. For two hours, they were lying in one of five positions (supine, 30° and 90° side lying on the right or left side) according to the respective positioning concept. Heart rate, breathing frequency and blood pressure were measured before and after positioning in a supine lying position (i.e. not positioned according to any concept). It was investigated if the interventions influence vital parameters and whether there are differences between positioning in neutral and conventional positioning, or between the different positions. In neither of the groups did heart rate, breathing frequency and blood pressure change significantly after the intervention compared to before (p ≤ 0·01). Positioning does not influence heart rate, breathing frequency and blood pressure when patients are lying for a clinically feasible length of two hours. This study shows that nurses can apply both positioning concepts according to their patients' preferences or to address problems like pressure sore prevention. There is no risk of influencing basic vital parameters.


Neuromuscular Involvement in Glycogen Storage Disease Type III in Fifty Tunisian Patients: Phenotype and Natural History in Young Patients.
Our aim was to describe the natural history of neuromuscular involvement (NMI) in glycogen storage disease type III (GSDIII). We conducted a longitudinal study of 50 Tunisian patients, 9.87 years old in average. NMI was diagnosed at an average age of 2.66 years and was clinically overt in 85% of patients. Patients with clinical features were older (p = 0.001). Complaints were dominated by exercise intolerance (80%), noticed at 5.33 years in average. Physical signs, observed at 6.75 years in average, were dominated by muscle weakness (62%). Functional impairment was observed in 64% of patients, without any link with age (p = 0.255). Among 33 patients, 7 improved. Creatine kinase (CK) and aspartate aminotransferase (AST) levels were higher with age.Electrophysiological abnormalities, diagnosed in average at 6.5 years, were more frequent after the first decade (p = 0.0005). Myogenic pattern was predominant (42%). Nerve conduction velocities were slow in two patients. Lower caloric intake was associated with more frequent clinical and electrophysiological features. Higher protein intake was related to fewer complaints and physical anomalies. Neuromuscular investigation is warranted even in asymptomatic patients, as early as the diagnosis of GSDIII is suspected. Muscle involvement can be disabling even in children. Favorable evolution is possible in case of optimal diet.


NEUTRAL GENE FLOW ACROSS SINGLE LOCUS CLINES.
We study the strength of the genetic barrier to neutral gene flow in a general one-locus, two-allele model that includes viability selection as well as fertility selection and premating isolation. We have separately considered adult migration and pollen migration. Our theoretical results suggest that selection against hybrid formation in the form of fertility selection or assortative mating is more effective in preventing introgression of neutral alleles than is reduction in hybrid viability. We argue that in experimental studies of introgression testing of F1 hybrids is as important as testing of parental forms. To illustrate the utility of this approach, we estimate the strength of the barrier to neutral gene flow between Piriqueta caroliniana and P. viridis, between Iris hexagona and I. fulva, and between Chorthippus brunneus and C. biguttulus.