Cuticular Lipid Topology on Insect Body Surfaces Studied by Synchrotron Radiation FTIR ATR Microspectroscopy.
The cuticular lipid covering the integument of insects is exposed to the environment and involved in a variety of functions offered by insect body surfaces, ranging from protection against the environment, such as the control of water transpiration, the reduction of abrasive damage, and the prevention of pathogen intrusion, to the communication between insects from intraspecific to interspecific interactions. In comparison with the importance of their physiological functions, there is remarkably little information on the structure and physical property of cuticular lipids on insect body surfaces. The lipid layer on the outer exoskeleton is very thin, estimated on the order of 0.01-1 μm or less, and this has led to a lack of practical methodologies for detailed structural analyses. To fill this devoid, we have exploited the characteristics of Fourier transform infrared (FTIR) attenuated total reflection (ATR) spectroscopy, which allows us to conduct a chemical analysis on insect body surfaces and also to investigate depth-dependent structural changes. We have applied a combination of FTIR ATR microspectroscopy with IR radiation provided by a synchrotron facility to obtain in situ two-dimensional (2D) information of the cuticular lipid layer on the surface of the integument. The 2D FTIR spectra measured on the two-spotted cricket and the American cockroach show that the IR bands due to the cuticular lipid, such as CH2 symmetric and antisymmetric stretch, νa(CH2) and νs(CH2), change in intensity significantly, depending on the location of measurements. As if to keep pace with this, the bands of the amide group for the underlying cuticular layer also change in intensity significantly, although the changes are in the opposite direction; as the lipid bands increase in intensity, the amide band decreases, and vice versa. The ATR spectral analysis, which takes into account the characteristics of the evanescent wave, points out that the lipid layer would vary tens of times in the range of 0.01-1 μm significantly. The νa(CH2) and νs(CH2) bands show frequency shifts, which correlate to some extent with their intensity changes, suggesting that the drastic uneven distribution of the cuticular lipid would be related to the solid-liquid phase separation and also the coarsening of the solid phase domains. The formation of such topological features, significant heterogeneity in the lipid layer thickness, and solid-liquid phase ratios would be accompanied by the partitioning of lipid components according to molecular structures and physicochemical properties. Considering that each lipid component in insect body surface lipids is involved in various physiological roles, the segregation of lipid components during the formation of such heterogeneous structures is thought to have a significant impact on the functionality of the insect body surface.


Total Synthesis of (-)-Principinol C.
We have achieved the first total synthesis of (-)-principinol C, which possesses an intriguing and complex 5/7/6/5 tetracyclic skeleton with eight contiguous stereocenters. The 5/7/6/5 tetracyclic skeleton of principinol C was assembled using an intramolecular Pauson-Khand reaction as the key step. This synthetic route represents the first application of the intramolecular Pauson-Khand reaction of enyne to construct the 7,5-bicyclic ring system in natural product synthesis.


EPR studies of recombinant horse L-chain apoferritin and its mutant (E 53,56,57,60 Q) with haemin.
Structural similarities between ferritins and bacterioferritins have been extensively demonstrated. However, there is an essential difference between these two types of ferritins: whereas bacterioferritins bind haem, in-vivo, as Fe(II)-protoporphyrin IX (this haem is located in a hydrophobic pocket along the 2-fold symmetry axes and is liganded by two axial Met 52 residues), eukaryotic ferritins are non-haem iron proteins. However, in in-vivo studies, a cofactor has been isolated from horse spleen apoferritin similar to protoporphyrin IX; in in-vitro experiments, it has been shown that horse spleen apoferritin is able to interact with haemin (Fe(III)-protoporphyrin IX). Studies of haemin incorporation into horse spleen apoferritin have been carried out, which show that the metal free porphyrin is found in a pocket similar to that which binds haem in bacterioferritins (Précigoux et al. 1994 Acta Cryst D50, 739-743). A mechanism of demetallation of haemin by L-chain apoferritins was subsequently proposed (Crichton et al. 1997 Biochem 36, 15049-15054) which involved four Glu residues (E 53,56,57,60) situated at the entrance of the hydrophobic pocket and appeared to be favoured by acidic conditions. To verify this mechanism, these four Glu have been mutated to Gln in recombinant horse L-chain apoferritin. We report here the EPR spectra of recombinant horse L-chain apoferritin and its mutant with haemin in basic and acidic conditions. These studies confirm the ability of recombinant L-chain apoferritin and its mutant to incorporate and demetallate the haemin in acidic and basic conditions.


Surface double phase network modified lithium rich layered oxides with improved rate capability for Li-ion batteries.
Poor rate capability and cycling performance are the major barriers to the application of lithium rich layered oxides (LLOs) as the next generation cathodes materials for lithium-ion batteries. In this paper, a novel surface double phase network modification has been applied to enhance the rate property of Li1.2Co0.13Ni0.13Mn0.54O2 (LR) via flexible electrostatic heterocoagulation and thermal treatment. The template action of multiwalled carbon nanotubes (MWCNTs) network on LR clusters results in the spinel phase network formation at the interface between the LR and MWCNTs. The phase transformation process from layered component toward spinel phase is identified through the detailed investigation of the interface using high-resolution transmission electron microscopy, fast Fourier transformation, and the detailed analysis on the transformation of simulated diffraction patterns. The double phases stretch two sets of networks with both fine Li ion and electron conductivity onto and within the clusters of LR, lowering the surface resistance, reducing the electrochemical polarization, and as a result, significantly enhancing the rate capability of LR. The double phase network modification, combining MWCNT coagulation and spinel phase modification, has profound potential in accelerating kinetics for LLOs.


Structure formation and surface chemistry of ionic liquids on model electrode surfaces-Model studies for the electrode | electrolyte interface in Li-ion batteries.
Ionic liquids (ILs) are considered as attractive electrolyte solvents in modern battery concepts such as Li-ion batteries. Here we present a comprehensive review of the results of previous model studies on the interaction of the battery relevant IL 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide ([BMP]+[TFSI]-) with a series of structurally and chemically well-defined model electrode surfaces, which are increasingly complex and relevant for battery applications [Ag(111), Au(111), Cu(111), pristine and lithiated highly oriented pyrolytic graphite (HOPG), and rutile TiO2(110)]. Combining surface science techniques such as high resolution scanning tunneling microscopy and X-ray photoelectron spectroscopy for characterizing surface structure and chemical composition in deposited (sub-)monolayer adlayers with dispersion corrected density functional theory based calculations, this work aims at a molecular scale understanding of the fundamental processes at the electrode | electrolyte interface, which are crucial for the development of the so-called solid electrolyte interphase (SEI) layer in batteries. Performed under idealized conditions, in an ultrahigh vacuum environment, these model studies provide detailed insights on the structure formation in the adlayer, the substrate-adsorbate and adsorbate-adsorbate interactions responsible for this, and the tendency for chemically induced decomposition of the IL. To mimic the situation in an electrolyte, we also investigated the interaction of adsorbed IL (sub-)monolayers with coadsorbed lithium. Even at 80 K, postdeposited Li is found to react with the IL, leading to decomposition products such as LiF, Li3N, Li2S, LixSOy, and Li2O. In the absence of a [BMP]+[TFSI]- adlayer, it tends to adsorb, dissolve, or intercalate into the substrate (metals, HOPG) or to react with the substrate (TiO2) above a critical temperature, forming LiOx and Ti3+ species in the latter case. Finally, the formation of stable decomposition products was found to sensitively change the equilibrium between surface Li and Li+ intercalated in the bulk, leading to a deintercalation from lithiated HOPG in the presence of an adsorbed IL adlayer at >230 K. Overall, these results provide detailed insights into the surface chemistry at the solid | electrolyte interface and the initial stages of SEI formation at electrode surfaces in the absence of an applied potential, which is essential for the further improvement of future Li-ion batteries.


Static metrics of impact for a dynamic problem: The need for smarter tools to guide suicide prevention planning and investment.
This study investigates two approaches to estimate the potential impact of a population-level intervention on Australian suicide, to highlight the importance of selecting appropriate analytic approaches for informing evidence-based strategies for suicide prevention. The potential impact of a psychosocial therapy intervention on the incidence of suicide in Australia over the next 10 years was used as a case study to compare the potential impact on suicides averted using: (1) a traditional epidemiological measure of population attributable risk and (2) a dynamic measure of population impact based on a systems science model of suicide that incorporates changes over time. Based on the population preventive fraction, findings suggest that the psychosocial therapy intervention if implemented among all eligible individuals in the Australian population would prevent 5.4% of suicides (or 1936 suicides) over the next 10 years. In comparison, estimates from the dynamic simulation model which accounts for changes in the effect size of the intervention over time, the time taken for the intervention to have an impact in the population, and likely barriers to the uptake and availability of services suggest that the intervention would avert a lower proportion of suicides (between 0.4% and 0.5%) over the same follow-up period. Traditional epidemiological measures used to estimate population health burden have several limitations that are often understated and can lead to unrealistic expectations of the potential impact of evidence-based interventions in real-world settings. This study highlights these limitations and proposes an alternative analytic approach to guide policy and practice decisions to achieve reductions in Australian suicide.


Does the histology of nodal metastasis predict systemic relapse after retroperitoneal lymph node dissection in pathological stage B1 germ cell tumors?
We evaluated the prognostic significance of the histology of metastatic lymph nodes to predict postoperative relapse in pathological stage B1 nonseminomatous germ cell tumor (NSGCT). A retrospective review of the testicular cancer database was performed to identify all patients with clinical stage A NSGCT who underwent primary retroperitoneal lymph node dissection and were found to have pathological stage B1 disease. No patient received adjuvant chemotherapy and minimal followup was 24 months. A total of 118 patients were identified with a 5-year disease-free survival (DFS) of 68% and a median followup of 43 months. Embryonal cell carcinoma was identified in 92 of 118 (77%) surgical specimens, which was significantly greater than the presence of teratoma (22%), seminoma (16%) and yolk sac (14.4%, p < or = 0.001) with no difference in 5-year DFS comparing the presence or absence of each histology. Solitary histology was noted in 88 of 118 patients (74.5%). Embryonal cell carcinoma was the most common single histology identified at surgery at 64 of 88 (73%), with the incidence of seminoma, teratoma and yolk sac being 12.5%, 9.0% and 5.5%, respectively (p < or = 0.001). There was no statistical difference in DFS for each of the solitary histological subtypes (p=0.67). Recurrence rates were similar for pure embryonal cell carcinoma (69%), mixed embryonal cell carcinoma (63%) and no embryonal cell carcinoma (73%) in the retroperitoneum (p=0.63). Retroperitoneal histology does not appear to predict outcome in patients with pathological stage B1 NSGCT.


[Tumor-secreted vascular endothelial growth factor A increases the pulmonary metastasis from nasopharyngeal carcinoma].
Objective: Vascular endothelial growth factor A (VEGFA) was investigated as the key protein which might promote the specific metastasis progress of nasopharyngeal carcinoma. Methods: Sixteen specimens of pulmonary metastasis carcinoma and counterparts in primary nasopharyngeal carcinoma tissue were collected from patients. The expression of VEGFA through immunohistochemistry was investigated.VEGFA was knocked down by siRNA in two cell lines of nasopharyngeal carcinoma (CNE-1 and 5-8F), MTT and Transwell test were used to explore the role of VEGFA in praxiology. Then shRNA was used to cultivate the stable CNE-1 cell line with down-regulated-expression of VEGFA. The nude mice models were built through tail vein injection of specific nasopharyngeal carcinoma cells, and lungs were collected to perform further metastasis analysis. Results: Previous genetic studies showed that VEGFA had higher expression in metastasis tissue, and the result was validated in the present study using immunohistochemistry. The percentage of positive cells was 84.8% in pulmonary metastasis group, 51.5% in primary tissue group (t=8.639, P<0.05), average optical density was 0.154 in pulmonary metastasis group, 0.061 in primary tissue group (t=18.791, P<0.05). Low expression of VEGFA inhibited cell viability of optical density value of CNE-1 in siRNA gourp was 0.715, 0.902 in control group (t=7.274, P<0.05); 5-8F in siRNA group was 0.715, 0.935 in control group (t=7.751, P<0.05). Number counting suppressed migration of CNE-1 in siRNA group was 52 per high-power lens, 124 per high-power lens in control group (t=29.380, P<0.05), 5-8F in siRNA group was 65 per high-power lens, 155 per high-power lens in control group (t=18.181, P<0.05). Number counting invasion of CNE-1 in siRNA gourp was 38 per high-power lens, 86 per high-power lens in control group (t=27.665, P<0.05), 5-8F in siRNA group was 52 per high-power lens, 116 per high-power lens in control group (t=40.972, P<0.05) in vitro. Furthermore, knock-down of VEGFA in nasopharyngeal carcinoma reduced the pulmonary metastasis in vivo. Number counting of tumor volumes in shRNA group was 2.4, and 11.0 in control group (t=6.143, P<0.05); average optical density of immunohistochemistry in shRNA group was 0.033, and 0.176 in control group (t=15.734, P<0.05). Conclusions: Results above reveal the overexpression of VEGFA in nasopharyngeal carcinoma can facilitate the pulmonary metastasis. Targeting VEGFA may provide a new biomarker of clinical study.


TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia.
Genetic variants of TREM2, a protein expressed selectively by microglia in the brain, are associated with Alzheimer's disease (AD). Starting from an unbiased protein microarray screen, we identified a set of lipoprotein particles (including LDL) and apolipoproteins (including CLU/APOJ and APOE) as ligands of TREM2. Binding of these ligands by TREM2 was abolished or reduced by disease-associated mutations. Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells, whereas TREM2 disease variants were impaired in this activity. Trem2 knockout microglia showed reduced internalization of LDL and CLU. β-amyloid (Aβ) binds to lipoproteins and this complex is efficiently taken up by microglia in a TREM2-dependent fashion. Uptake of Aβ-lipoprotein complexes was reduced in macrophages from human subjects carrying a TREM2 AD variant. These data link three genetic risk factors for AD and reveal a possible mechanism by which mutant TREM2 increases risk of AD. VIDEO ABSTRACT.


[Nd YAG laser microsurgery for pupil centering and improvement of visual acuity].
To define the use of Nd YAG laser treatment for centering the pupil--coreoplasty and improvement of the visual acuity. We used Nd YAG laser for coreoplasty in 29 eye of the patient, aged between 6 and 90. The eyes were classified in four groups using the disposition of the pupil according to the optic axis criteria. We used our own methods for centering the pupil. The average power was 3 +/- 0.2 mj, and the average number of applications--5 +/- 2. The Nd YAG laser coreoplasty succeeded in all 29 eyes. In 96.55% of the eyes the visual acuity was very good and excellent. The dislocation of the pupil according to the optic axis due to trauma or surgery complication always decreases the function of the damaged eye. The Nd YAG laser helps to improve the visual acuity--an excellent effect, produced in several minutes in dispensary conditions.


[Vaginal metastasis of renal carcinoma (author's transl)].
Four cases of vaginal metastases of renal carcinoma are reported. This is an incidence of 1.3% in 313 operated patients (from 1/1/70 to 12/31/76). A surgical treatment of primary renal carcinoma and vaginal metastasis seems to be reasonable in there cases. Since in accordance with the literature metastatic involvement of vagina and vulva seems not to be a very rare finding, the diagnostic in renal carcinoma should imply a gynecologic examination. Although in carcinoma of the left kidney metastatic spreading into the external female genitalia most probably occurs by a retrograde venous pathway (left ovarian vein), the way of dissemination in carcinoma of the right side is unclear.


SARS-CoV-2 strain-specific anti-spike IgG ELISA utilizing spike protein produced by silkworms.
A cost-effective and eco-friendly method is needed for the assessment of humoral immunity against SARS-CoV-2 in large populations. We investigated the performance of an ELISA that uses silkworm-produced proteins to quantify the strain-specific anti-Spike IgG (anti-S IgG) titer. The OD values for the anti-His-tag antibody, a standard material of ELISA quantification, were measured. Correlations between the ELISA for each strain and the Abbott SARS-CoV-2 IgG II Quant assay for the wild type were evaluated with serum samples from nine participants with various infection and vaccination statuses. Linear dose-responses were confirmed by high coefficients of determination: 0.994, 0.994, and 0.996 for the wild-type, Delta, and Omicron (BA.1) strain assays, respectively. The coefficient of determination for the wild-type and Delta strain assays was high at 0.959 and 0.892, respectively, while the Omicron strain assay had a relatively low value of 0.563. Booster vaccinees showed similar or higher titers against all strains compared to infected persons without vaccination. The Omicron-infected persons without vaccination had lower antibody titers against wild type than did the vaccinated persons. This study provides data indicating that the ELISA with silkworm-produced proteins makes it possible to discriminate and quantify the strain-specific anti-S IgG antibody induced by vaccination or infection.


Novel CFTR missense mutations in Brazilian patients with congenital absence of vas deferens: counseling issues.
Screening for mutations in the entire Cystic Fibrosis gene (CFTR) of Brazilian infertile men with congenital absence of vas deferens, in order to prevent transmission of CFTR mutations to offspring with the use of assisted reproductive technologies. Specific polymerase chain reaction (PCR) primers were designed to each of the 27 exons and splicing sites of interest followed by single strand conformational polymorphism and Heteroduplex Analysis (SSCP-HA) in precast 12.5% polyacrylamide gels at 7 masculineC and 20 masculineC. Fragments with abnormal SSCP migration pattern were sequenced. Two novel missense mutations (S753R and G149W) were found in three patients (two brothers) together with the IVS8-5T allele in hetrozygosis. The available screenings for CF mutations do not include the atypical mutations associated to absence of vas deferens and thus, when these tests fail to find mutations, there is still a genetic risk of affected children with the help of assisted reproduction. We recommend the screening of the whole CFTR gene for these infertile couples, as part of the work-up before assisted reproduction.


Structure-Performance Relationships of Covalent Organic Framework Electrode Materials in Metal-Ion Batteries.
Covalent organic frameworks (COFs) have shown great potential as high-performance electrode materials for metal-ion batteries in view of their relatively high capacity, flexibly designable structure, ordered porous structure, and limited solubility in electrolyte. To develop more attractive COF electrode materials, it is necessary to understand their structure-performance relationships. This Perspective focuses on discussing the relationships between structure (molecular structure, micro structure, and electrode structure) and performance (voltage, capacity, cycling stability, and rate performance) of COF electrode materials in metal-ion batteries. Among the reported COF electrode materials, those with all linkages being redox active based on C═O and C═N groups would be the most promising cathode materials because of their high capacity (∼500 mAh g-1), moderate working voltage (∼2 V vs Li+/Li), and good cycling stability. To accelerate practical application of COF electrode materials in metal-ion batteries, future work should pay more attention to function-oriented molecular structure design via theoretical simulations, as well as full-cell fabrication and evaluation. This Perspective will stimulate high-quality research that might lead to future commercialization.


The Draft Genome of Hop (Humulus lupulus), an Essence for Brewing.
The female flower of hop (Humulus lupulus var. lupulus) is an essential ingredient that gives characteristic aroma, bitterness and durability/stability to beer. However, the molecular genetic basis for identifying DNA markers in hop for breeding and to study its domestication has been poorly established. Here, we provide draft genomes for two hop cultivars [cv. Saazer (SZ) and cv. Shinshu Wase (SW)] and a Japanese wild hop [H. lupulus var. cordifolius; also known as Karahanasou (KR)]. Sequencing and de novo assembly of genomic DNA from heterozygous SW plants generated scaffolds with a total size of 2.05 Gb, corresponding to approximately 80% of the estimated genome size of hop (2.57 Gb). The scaffolds contained 41,228 putative protein-encoding genes. The genome sequences for SZ and KR were constructed by aligning their short sequence reads to the SW reference genome and then replacing the nucleotides at single nucleotide polymorphism (SNP) sites. De novo RNA sequencing (RNA-Seq) analysis of SW revealed the developmental regulation of genes involved in specialized metabolic processes that impact taste and flavor in beer. Application of a novel bioinformatics tool, phylogenetic comparative RNA-Seq (PCP-Seq), which is based on read depth of genomic DNAs and RNAs, enabled the identification of genes related to the biosynthesis of aromas and flavors that are enriched in SW compared to KR. Our results not only suggest the significance of historical human selection process for enhancing aroma and bitterness biosyntheses in hop cultivars, but also serve as crucial information for breeding varieties with high quality and yield.


Investigating the association of atopy and aeroallergen sensitization and chronic spontaneous urticaria.
Chronic spontaneous urticaria (CSU) is a common skin allergic reaction with an unknown mechanism. There is inadequate evidence to support the role of aeroallergen sensitization in CSU. The present study was conducted to investigate the association between the aeroallergen sensitivity and CSU. In this cross-sectional study, 91 patients with CSU were recruited. Information on demographic characteristics was collected. The skin prick test (SPT) for most prevalent aeroallergens and pulmonary function test (PFT) were performed and the results were clinically matched to investigate the allergic rhinitis (AR) and asthma. Total serum immunoglobulin E (IgE) concentration was analysed in the subjects for the presence of atopy. Ninety one patients (75 of them were females) were enrolled in the study (with a mean age of 36.90 ±12.93 years). SPT result was positive in 75 (82.4%) subjects. Weeds (67 cases, 73.6%), trees (61 cases, 67%), and dust mites (55 cases, 60.4%) were the most common pollens in the positive SPT samples. Thirty-seven (40.7%) of the patients had allergic rhinitis. There was a statistically significant association between the presence of AR and positive SPT result (p = 0.002). Eight patients had allergic asthma and 45 (49.4%) of the patients had a total serum IgE level of more than 100 IU/ml. Our results indicated a clear association between the presence of aeroallergen sensitivity and development of CSU. AR exists as a co-morbidity of CSU.


Optimal Combinations of AT(N) Biomarkers to Determine Longitudinal Cognition in the Alzheimer's Disease.
Background: National Institute on Aging-Alzheimer's Association (NIA-AA) proposed the AT(N) system based on β-amyloid deposition, pathologic tau, and neurodegeneration, which considered the definition of Alzheimer's disease (AD) as a biological construct. However, the associations between different AT(N) combinations and cognitive progression have been poorly explored systematically. The aim of this study is to compare different AT(N) combinations using recognized biomarkers within the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Methods: A total of 341 participants were classified into cognitively unimpaired (CU; n = 200) and cognitively impaired (CI; n = 141) groups according to the clinical manifestations and neuropsychological tests. Cerebrospinal fluid (CSF) Aβ42 and amyloid-PET ([18F]flutemetamol) were used as biomarkers for A; CSF phosphorylated tau (p-tau) and tau-PET ([18F]flortaucipir) were used as biomarkers for T; CSF total tau (t-tau), hippocampal volume, temporal cortical thickness, [18F]fluorodeoxyglucose (FDG) PET, and plasma neurofilament light (NfL) were used as biomarkers for (N). Binary biomarkers were obtained from the Youden index and publicly available cutoffs. Prevalence of AT(N) categories was compared between different biomarkers within the group using related independent sample non-parametric test. The relationship between AT(N) combinations and 12-year longitudinal cognition was assessed using linear mixed-effects modeling. Results: Among the CU participants, A-T-(N)- was most common. More T+ were detected using p-tau than tau PET (p < 0.05), and more (N)+ were observed using fluid biomarkers (p < 0.001). A+T+(N)+ was more common in the CI group. Tau PET combined with cortical thickness best predicted cognitive changes in the CI group and MRI predicted changes in the CU group. Conclusions: These findings suggest that optimal AT(N) combinations to determine longitudinal cognition differ by cognitive status. Different biomarkers within a specific component for defining AT(N) cannot be used identically. Furthermore, different strategies for discontinuous biomarkers will be an important area for future studies.


Plasma hormone concentrations during the menstrual cycle of normal Chinese women.
The concentrations of progesterone, estrogens, luteinizing hormone and follicle stimulating hormone were measured in samples of plasma taken frequently during normal menstrual cycles in fourteen Chinese women. Each of the menstrual cycles was characterized by hormonal changes which were comparable to those previously reported in Caucasian subject.


[Changes in humoral and cellular immunity in patients operated on due to esophageal cancer].
The aim of this paper was to analyze changes in immune system in patients operated on due to esophageal carcinoma. A special interest was paid to selected parameters of humoral and cellular immunity in peripheral blood as well as local changes in the immune system. A practical aspect of changes in immune system in the diagnosis of postoperative complications was taken into account. Results of the analyzed studies show that in patients with esophageal carcinoma occur significant changes in humoral and cellular immunity which increase the risk of postoperative complications. A high rate of postoperative complications in patients after esophagectomy due to esophageal carcinoma is caused predominantly by preoperative immunocompromised and malnutrition. The extent of operative stress as well as increased activity of immune cells in the early postoperative period, are other factors which increase the risk of severe, especially respiratory complications. It seems that early diagnosis and correction of compromised immunity (for example with nutrition) can significantly improve the results of the treatment.


Lymphoma of the thyroid. An unusual clinical course in a patient possessing a 14/21 translocation.
The unusual course of a lymphoma in a woman with a chromosome abnormality is reported. When aged 30 years, the right lobe of her thyroid gland was found to be infiltrated by a follicular lymphoma. Two years later, poorly differentiated diffuse lymphoctic lymphoma recurred locally, grew rapidly, and infiltrated the adjoining muscles. It was treated by widefield irradiation of the upper trunk and neck, and disappeared completely. The patient remained sympton-free for 22 years. Unequivocal Hodgkin's disease then developed in a left cervical lymph node; the patient received radiotherapy. Eighteen months later the right inguinal nodes were infiltrated by similar tumor and further treatment was given. Massive abdominal involvement followed and the patient died 28 years after developing the thyroid lymphoma. The tumor at necropsy was pleomorphic and contained Reed-Sternberg cells. The significance of the constitutional chromosome abnormality, a Robertsonian translocation of the No. 14 chromosome, is discussed.


Structure-Activity Relationship Analysis of the Thermal Stabilities of Nitroaromatic Compounds Following Different Decomposition Mechanisms.
The decomposition behavior of energetic materials is very important for the safety problems concerning their production, transportation, use and storage, because molecular decomposition is intimately connected to their explosive properties. Nitroaromatic compounds, particularly nitrobenzene derivatives, are often considered as prototypical energetic molecules, and some of them are commonly used as high explosives. Quantitative structure-activity relationship (QSAR) represents a potential tool for predicting the thermal stability properties of energetic materials. But it is reported that constructing general reliable models to predict their stability and their potential explosive properties is a very difficult task. In this work, we make our efforts to investigate the relationship between the molecular structures and corresponding thermal stabilities of 77 nitrobenzene derivatives with various substituent functional groups (in ortho, meta and/or para positions). The proposed best MLR model, developed by the new software QSARINS, based on Genetic Algorithm for variable selection and with various validation tools, is robust, stable and predictive with R(2) of 0.86, QLOO (2) of 0.79 and CCC of 0.90. The results indicated that, though difficult, it is possible to build predictive, externally validated QSAR models to estimate the thermal stability of nitroaromatic compounds.


Fracture Risk Assessment in Patients With Diabetes Mellitus.
Diabetes mellitus, both type 1 and type 2 (T2DM), is associated with decreased bone strength as well as increased fracture risk. Bone mineral density is decreased in type 1 diabetes but increased in T2DM, compared with controls. This suggests alterations in bone quality are a major player in the pathogenesis of fragility fractures in patients with diabetes. The link between diabetes and bone appears to be mediated by complex pathways, including the insulin-insulin growth factors system, accumulation of advanced glycation end-products in bone collagen, microangiopathy, and increased bone marrow fat content. Bone fragility in T2DM, which is not reflected by bone mineral density and bone mass reduction, depends on deterioration of bone quality. Also, at least in T2DM, the classical diagnosis of osteoporosis by dual-energy X-ray absorptiometry and the fracture risk estimation by FRAX (fracture risk assessment tool) are only partially useful in assessing fracture risk. Trabecular bone score and trabecular bone score-adjusted FRAX offer an enhanced estimation of fracture risk in these patients. Specific risk stratification criteria are needed in the future. The development of improved methods to assess the material properties of bone to better characterize fracture risk is also a priority. Adequate glycemic control is generally associated with decreased fracture risk, with the exception of specific antidiabetics (thiazolidinediones, canagliflozin) that have been shown to have a detrimental effect. Most currently used antiosteoporotic treatments seem equally effective in diabetic patients as compared with patients without diabetes, but clinical data regarding the reduction in fracture risk specifically in patients with diabetes mellitus are lacking.


[A case of primary pulmonary artery sarcoma].
A 39-year-old male was admitted with persistent cough, palpitations and dyspnea on exertion. Chest X-ray showed cardiomegaly, left pleural effusion and left hilar mass shadow. Echocardiogram revealed dilatation and hypertrophy of the right atrium and ventricle. Perfusion lung scintigram disclosed a complete defect of the left lung and a partial defect of the right upper lobe. CT scan showed an intravascular tumor mass in the bilateral main pulmonary arteries. Digital subtraction angiography of the pulmonary artery revealed complete obstruction of the left pulmonary artery and stenosis of the right pulmonary artery. MR image showed intravascular tumor infiltrating the mediastinum and surrounding tissue. Sarcoma was highly suspected, but a histopathological diagnosis could not be made. The patient died of heart failure two months after admission to our hospital. Postmortem examination showed that the pulmonary trunk and left main pulmonary artery were markedly dilated and completely occluded by the tumor. Tumor infiltrated into the left upper lobe and mediastinal lymph nodes. The tumor was histologically diagnosed as undifferentiated sarcoma.


The economics of imperialism and health: Malta's experience.
The thesis of this article is that the prevalence of disease and premature death depends more on national, class, and gender relationships than on medical and biological factors. The political and economic realities of life in the British Colony of Malta revealed here clearly determined the severity of both infant mortality rates and the attacks of brucellosis. A brief history sets the background for an in-depth study of the interaction between socioeconomic conditions and disease in the first half of the 20th century. Britain's adherence to imperialist "free" trade policies and refusal to consider Malta's economy beyond its use as a military base had resulted in the "underdevelopment" of Malta's traditional cotton agroindustry and the erosion of household economic stability. Persistently high infant mortality rates and the absence of preventive disease measures were a clear manifestation of continuing exploitative imperialist policies. In this scenario, the devastation of the Second World War became a catalyst for change.


Patterns of severe abdominal wall defects: insights into pathogenesis, delineation, and nomenclature.
During the last decade, descriptions of malformation complexes involving an abdominal wall defect (AWD) have repeatedly appeared in the literature, and there has been frequent confusion regarding nomenclature, definitions, and delineations. The aims of this work were to evaluate possible embryological relationships among AWD cases, review the related nomenclature, identify patterns involving AWDs, and stress the importance of complete clinical descriptions. METHODS Cases diagnosed as AWD complexes were selected from live--and stillborn infants of the Hospital Materno Infantil Ramón Sardá, Buenos Aires, and from the Laboratory of Perinatal Pathology, Buenos Aires, Argentina. They were sorted by the location of the AWD, the umbilical cord length, and the presence or absence of a persistent cloaca. The findings in 26 cases were described, according to proposed definitions. Three patterns could be identified: 1) the AWD involving the umbilical ring, a persistent or exstrophic cloaca, and a spinal cord anomaly; 2) the AWD extending laterally to the umbilical ring, severe unilateral limb defects, and same-sided agenesis of abdominal organs; and 3) the AWD not involving the umbilical ring, clefts, exencephaly, and amputations. Furthermore, overlapping among these patterns was observed, and possible involved mechanisms are discussed. The observed overlapping among patterns suggested that malformation complexes involving AWDs might not be independent conditions but rather belong to a common and broader spectrum of anomalies. Complete clinical descriptions, the avoidance of synonyms and generalizations, and strictly defined inclusion criteria are proposed for a better understanding of pathogenetic pathways in, and relationships among, AWD complexes.


Characteristics of FDG-PET findings in the diagnosis of systemic juvenile idiopathic arthritis.
To examine and delineate inflammatory focus in patients with juvenile idiopathic arthritis (JIA), (18)F-Fluoro-deoxy-glucose (FDG)-positron emission tomography (PET) ((18)F-FDG-PET) was applied to patients with JIA, and the images of these patients were compared. Sixty-eight children (59 with systemic JIA (s-JIA) and 9 with polyarticular JIA) were included. The diagnosis of JIA was done to meet the International League of Associations for Rheumatology (ILAR) criteria. After 6-h fasting, whole-body positron emission tomography (PET) scans were acquired 60 min after intravenous injection of 3-5 MBq/kg (18)F-FDG. The interpretation of (18)F-FDG uptake was based on visual characteristics. Two types of PET images were outstanding in s-JIA; one was (18)F-FDG uptake in red bone marrow, such as the spine, pelvis, and long bones as well as spleen (12 cases), and other type was the uptake in the major joints, such as hips, elbows, wrists, knees, and ankles (8 cases). The former findings were correlated with elevated levels of inflammatory markers, while the latter were with significantly increased levels of MMP-3 (p < 0.05). There was a noticeable accumulation of (18)F-FDG uptake in bone marrow of s-JIA patients which may indicate the inflammatory focus of this disease and play an important role in the pathogenic basis of arthritis and systemic inflammation of s-JIA.


[Clinical and radiological results of non-fusion by static interspinous spacer].
The aim of this paper is to demonstrate the clinical and radiological results of non-fusion in patients with degenerative disc disease and lumbar by placing static interspinous spacer. A retrospective study was made in the period between January 2010 and January 2013, 130 patients were treated by placing static interspinous spacer. Patients were divided into: Group 1 (treated for diagnosis of degenerative lumbar spinal stenosis), and group 2 (those diagnosed with lumbar disc herniation). It is improving pain by visual analog scale (VAS), functional improvement based on the Oswestry scale (ODI) and radiological outcome at 6,12 and 24 months was evaluated. 57 female patients and 73 male were included. The most affected segments were L4 - L5 and L5 - S1. In Group 1, there was improvement in pain (VAS) at 6 months to 2 points which was maintained through 12 months and 24 months was found in 4 points. Functional improvement (ODI) at 6 and 12 months remained 13 points and 24 points and 21 months in group 2: VAS 2.7, 3, 3.5 and ODI 15 respectively at 6 and 12 months; at 24 months was found in 20 points. There were no fatal complications in 1.5% in both groups. Regarding radiological changes increased the diameter foraminal which was held at the 6, 12 and 24 month follow-up. The interspinous device is an effective alternative treatment for lumbar degenerative disc disease and because it was associated with significantly improved lumbar pain and return to work activity.


Combining acellular nerve allografts with brain-derived neurotrophic factor transfected bone marrow mesenchymal stem cells restores sciatic nerve injury better than either intervention alone.
In this study, we chemically extracted acellular nerve allografts from bilateral sciatic nerves, and repaired 10-mm sciatic nerve defects in rats using these grafts and brain-derived neurotrophic factor transfected bone marrow mesenchymal stem cells. Experiments were performed in three groups: the acellular nerve allograft bridging group, acellular nerve allograft + bone marrow mesenchymal stem cells group, and the acellular nerve allograft + brain-derived neurotrophic factor transfected bone marrow mesenchymal stem cells group. Results showed that at 8 weeks after bridging, sciatic functional index, triceps wet weight recovery rate, myelin thickness, and number of myelinated nerve fibers were significantly changed in the three groups. Variations were the largest in the acellular nerve allograft + brain-derived neurotrophic factor transfected bone marrow mesenchymal stem cells group compared with the other two groups. Experimental findings suggest that chemically extracted acellular nerve allograft combined nerve factor and mesenchymal stem cells can promote the restoration of sciatic nerve defects. The repair effect seen is better than the single application of acellular nerve allograft or acellular nerve allograft combined mesenchymal stem cell transplantation.


Effects of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) on Fetal Pulmonary Circulation: An Experimental Study in Fetal Lambs.
Background: Persistent pulmonary hypertension of the newborn (PPHN) causes significant morbidity and mortality in neonates. n-3 Poly-unsaturated fatty acids have vasodilatory properties in the perinatal lung. We studied the circulatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fetal sheep and in fetal pulmonary arterial rings. Methods: At 128 days of gestation, catheters were placed surgically in fetal systemic and pulmonary circulation, and a Doppler probe around the left pulmonary artery (LPA). Pulmonary arterial pressure and LPA flow were measured while infusing EPA or DHA for 120 min to the fetus, to compute pulmonary vascular resistance (PVR). The dose effects of EPA or DHA were studied in vascular rings pre-constricted with serotonin. Rings treated with EPA were separated into three groups: E+ (intact endothelium), E- (endothelium stripped) and LNA E+ (pretreatment of E+ rings with l-nitro-arginine). Results: EPA, but not DHA, induced a significant and prolonged 25% drop in PVR (n = 8, p < 0.001). Incubation of vascular rings with EPA (100 µM) caused a maximum relaxation of 60% in the E+ (n = 6), whereas vessel tone did not change in the E- (n = 6, p < 0.001). The vascular effects of EPA were significantly decreased in LNA E+ (n = 6). Incubation with DHA resulted in only a mild relaxation at the highest concentration of DHA (300 µM) compared to E+. Conclusions: EPA induces a sustained pulmonary vasodilatation in fetal lambs. This effect is endothelium- and dose-dependent and involves nitric oxide (NO) production. We speculate that EPA supplementation may improve pulmonary circulation in clinical conditions with PPHN.


[Iatrogenic kidney diseases].
Iatrogenic kidney diseases may appeared as the consequence of medical mistakes or as the result of drug side effects. Present paper is dedicated mainly to this second group of disorders. Spectrum of different syndromes caused by the undesirable drug effects is very long and varied. There are among them water and electrolyte, disorders, tubulo-interstitial nephritis, glomerulopathies or acute renal failure. Also list of potentially nephrotoxic drugs is very long and including many different medicines. Additionally it is important to take into account existence of many risk factors enabling appearance of drug nephrotoxicity. Most important seen to be advanced age and deterioration of renal function. Main prophylactic method preventing development of drug induced nephropaties is strict drug dosage, their adjustment according glomerular filtration rate and monitoring of water- electrolyte balance. Common automatic estimation of eGFR by diagnostic laboratories have to be useful tool in this matter. It is also important to avoid combinations of potentially nephrotoxic drugs. In case of the appearance of first symptoms of toxic renal injury specific activities dependent from the character and severity of pathological changes are necessary. Nevertheless most important issue is consciousness of this danger in both sides: physician and patients enabling avoid drug nephrotoxicity.


[Priority directions of specialized neurological care of patients in a hospital].
The article presents main stages of becoming and improvement of specialized neurological aid in the 3rd CMCH of Vishnevsky A.A. since its opening (1968) to now-day. Also in the article could be found data about the first-time created neurological center in the system of military health protection, about the center as a multifield clinical institute, its functional subdivisions: 2 psycho-neurological, 3 neurological and reanimation-intensive therapy discharges. Author shows foreground directions of improvement of different types of specialized neurological aid and of scientifically-practical work of the center.


Empirical or microbiologically guided systemic antimicrobials as adjuncts to non-surgical periodontal therapy? A systematic review.
It is unclear whether patients with specific subgingival microbiological profiles benefit more from adjunctive systemic antibiotics. To answer the question: "What is the clinical benefit in periodontitis patients taking adjunctive systemic antimicrobials to non-surgical therapy, depending on pre-treatment detection of periodontopathogenic bacteria?" A search was conducted in four electronic databases for randomized controlled trials reporting clinical outcomes following adjunctive antibiotic therapy for patients divided by baseline microbiological profiles. The initial search resulted in 643 papers, reduced to five after screening and author contact. Four of these studies were suitable for a fixed effects two-stage individual participant data meta-analysis adjusted for baseline data. Collectively, adjunctive amoxicillin and metronidazole yielded superior clinical results (measured as reduction of PPDs) compared to placebo. No significant differences were detected for the effect of adjunctive antibiotics by the detection of Aggregatibacter actinomycetemcomitans on PPDs ≥ 5 mm (WMD = 1.16, 95% CI [-5.37, 7.68], I2 = 37.8%) or other clinical outcomes. All included studies had low risk of bias. There is no evidence to suggest that baseline detection of periodontopathogenic bacteria should be used as criterion for prescribing adjunctive antibiotics, although only limited information on microbial data and specific antimicrobials was available for analysis.


Multiple sclerosis and related challenges to young women's health: Canadian expert review.
Multiple sclerosis (MS) is among the most common chronic neurological diseases, with a highly variable degree of disability during its long-term course. The majority of patients develop significant permanent disability later in life. MS is often diagnosed in women of childbearing age, with a 3:1 ratio of young women to young men with MS. Comorbidities such as depression, anxiety, migraines and reproductive, urological and bowel issues are common and negatively impact patients' quality of life. The objective of this supplement is to review the most common comorbidities occurring in young women with MS, and to propose a multidisciplinary, holistic approach to management.


[Clinical aspects of occupational asthma].
Although on the increase overall, the actual prevalence of occupational asthma is difficult to assess because of variations seen according to periods, countries, jobs, and the agents responsible. In the authors' experience, this prevalence is slightly less than 10%. Three principal mechanisms, sometimes present together, not always elucidated: immunological, reflex and irritative, are responsible for such asthma. Whilst a positive diagnosis raises few problems, the aetiological diagnosis is difficult and involves two stages: recognition of the occupational characteristic of the asthma and attribution of this asthma to an allergen or substance in the occupational environment. Skin tests and in vitro tests, but above all exposure tests, make an important diagnostic contribution. Personal examples are used to illustrate the principal aetiological factors in occupational asthma of animal, vegetable or chemical origin.


Paper vs. practice: How legal and ethical frameworks influence public sector data professionals in the Netherlands.
Recent years have seen a massive growth in ethical and legal frameworks to govern data science practices. Yet one of the core questions associated with ethical and legal frameworks is the extent to which they are implemented in practice. A particularly interesting case in this context comes to public officials, for whom higher standards typically exist. We are thus trying to understand how ethical and legal frameworks influence the everyday practices on data and algorithms of public sector data professionals. The following paper looks at two cases: public sector data professionals (1) at municipalities in the Netherlands and (2) at the Netherlands Police. We compare these two cases based on an analytical research framework we develop in this article to help understanding of everyday professional practices. We conclude that there is a wide gap between legal and ethical governance rules and the everyday practices.


[Employee assistance program].
Recently the EAP has received much attention in Japan. The first EAP service in the US was conducted by employees who had recovered from alcohol problems. In the early days EAP providers focused on addiction, but mainly after 1980 they expanded their service areas to include mental health, marital problems, legal problems and financial problems. In Japan the EAP was first received attention as a counseling resource outside the workplace where employees could seek professional help confidentially, but the main reasons why this system now interests employers are as a risk-management tool and an outsourcing of mental health services, since the growing number of mental health cases in the workplace has been a big issue for employers. Two movements have also contributed to more recognition of the EAP: one is guidelines on compensation for mental health cases in the workplace and the other is guidelines on mental health promotion in the workplace. There are four types of EAP systems: internal EAP, external EAP, combination EAP, and consortium EAP. EAP core technology consists of 8 functions including problem identification, Crisis intervention, Short-term intervention, Consultation with work organization leader. The literature on cost-benefit analysis of the EAP is very limited. Although the available data suggest that the EAP is highly cost-effective, further studies are needed with the sufficient statistical quality. In Japan the most important issues in the EAP are the standardization and quality assurance of EAP services. For this purpose development of a good educational system for EAP professionals is needed.


Robotically Assisted Sonic Therapy as a Noninvasive Nonthermal Ablation Modality: Proof of Concept in a Porcine Liver Model.
Purpose To determine the feasibility of creating a clinically relevant hepatic ablation (ie, an ablation zone capable of treating a 2-cm liver tumor) by using robotically assisted sonic therapy (RAST), a noninvasive and nonthermal focused ultrasound therapy based on histotripsy. Materials and Methods This study was approved by the institutional animal use and care committee. Ten female pigs were treated with RAST in a single session with a prescribed 3-cm spherical treatment region and immediately underwent abdominal magnetic resonance (MR) imaging. Three pigs (acute group) were sacrificed immediately following MR imaging. Seven pigs (chronic group) were survived for approximately 4 weeks and were reimaged with MR imaging immediately before sacrifice. Animals underwent necropsy and harvesting of the liver for histologic evaluation of the ablation zone. RAST ablations were performed with a 700-kHz therapy transducer. Student t tests were performed to compare prescribed versus achieved ablation diameter, difference of sphericity from 1, and change in ablation zone volume from acute to chronic imaging. Results Ablation zones had a sphericity index of 0.99 ± 0.01 (standard deviation) (P < .001 vs sphericity index of 1). Anteroposterior and transverse dimensions were not significantly different from prescribed (3.4 ± 0.7; P = .08 and 3.2 ± 0.8; P = .29, respectively). The craniocaudal dimension was significantly larger than prescribed (3.8 ± 1.1; P = .04), likely because of respiratory motion. The central ablation zone demonstrated complete cell destruction and a zone of partial necrosis. A fibrous capsule surrounded the ablation zone by 4 weeks. On 4-week follow-up images, ablation zone volumes decreased by 64% (P < .001). Conclusion RAST is capable of producing clinically relevant ablation zones in a noninvasive manner in a porcine model. © RSNA, 2018.


Clinical, hemodynamic, and intracardiac echocardiographic characteristics of secundum atrial septal defects-related paradoxical embolism in adulthood.
Paradoxical embolism associated with secundum atrial septal defect (sASD) is a relatively rare but well-known occurrence. The purpose of our study is to report the clinical, hemodynamic, and anatomical features assessed by intracardiac echocardiography (ICE) of sASD as related to paradoxical embolism. Five hundred thirty-seven patients (mean age 48 ± 19.0 years) admitted for transcatheter repair of interatrial shunts were enrolled in a prospective registry over a 10-year period (September 2003-September 2013). All patients underwent transesophageal echocardiography, complete right and left catheterization, prior to the device-based procedure. ICE was performed in all patients in order to investigate the interatrial septum anatomy and to monitor device implantation. These results were compared with the data of patients with patent foramen ovale (PFO) patients and nonemboligenous sASD admitted at the same time period. Twenty-four patients (6.2%) out of 386 who underwent transcatheter repair for paradoxical embolism had a secundum ASD. The defects were cribrosus in 41.6% (10/24). All single sASD (58.3%) had a peculiar anatomical feature a so-called flat elliptical shape with a major axis of 7.6 ± 2.4 and minimal axis of 2.5 ± 1.6 mm. Patients with sASD-related paradoxical embolism had a higher frequency of deep venous thrombosis compared to PFO patients. In comparison to nonemboligenous sASD, such patients had lower mean pulmonary pressure and smaller defects. sASD related to paradoxical embolism had peculiar clinical, hemodynamic, and anatomical characteristics, which classified such defects in the middle of the spectrum between nonemboligenous secundum ASD and PFO.


Reductions in blood lead levels among school children following the introduction of unleaded petrol in South Africa.
Epidemiological studies have indicated that in the 1980s and early 1990s (a period in which petrol lead concentrations in South Africa ranged from 0.836 to 0.4 g/L), large proportions of urban South African children were at risk of excessive exposure to environmental lead. In 1991, when the maximum permissible petrol lead concentration in the country equaled 0.4 g/L, a study determined that the mean blood lead level among children attending inner city schools in the Cape Peninsula equaled 16 microg/dL, with well over 90% of children having blood lead levels equaling or exceeding the internationally accepted guideline level of 10 microg/dL. Socio economic status, housing conditions, and proximity of children's schools and homes to heavily trafficked roads were among the factors significantly associated with blood lead concentrations. In 1996, unleaded petrol was introduced in South Africa. A study undertaken in 2002 (at the same schools as in 1991), when unleaded petrol constituted around 30% of the market share of petrol in the country, has shown significant reductions in the mean blood lead concentration among Cape Peninsula inner city children and in the proportion of children with elevated blood lead levels. The mean blood lead level for the total sample (n = 429) of children whose mean age equaled 7 years (range: 5-11 years) was 6.4 microg/dL (range: 1.0-24.5 microg/dL) and 10% of children had blood lead levels equalling or exceeding 10 microg/dL. The mean blood lead levels among children attending schools in an inner city and in a less heavily trafficked periurban suburb were 6.9 and 4.8 microg/dL, respectively.


Practice and perception of first aid among lay first responders in a southern district of India.
Injuries rank among the leading causes of morbidity and mortality worldwide, and are steadily increasing in developing countries like India. However, it is often possible to minimize injury and crash consequences by providing effective pre-hospital services promptly. In most low-and middle-income countries (LMICs), transportation of road traffic victims, is usually provided by relatives, taxi drivers, truck drivers, police officers and other motorists who are often untrained. The current study was conducted to understand the current practice and perception of first aid among lay first responders in a rural southern district of India. The current cross sectional descriptive study was conducted in the southern district of Tumkur in India within three months from January to March 2011 and covered the population including all police, ambulance personnel, taxi drivers, bus and auto drivers, and primary and middle school teachers within the study area. Nearly 60% of the responders had witnessed more than two emergencies in the previous six months and 55% had actively participated in helping the injured person. The nature of the help was mainly by calling for an ambulance (41.5%), transporting the injured (19.7%) and consoling the victim (14.9%). Majority (78.1%) of the responders informed that they had run to the victim (42.4%) or had called for an ambulance. The predominant reason for not providing help was often the 'fear of legal complications' (30%) that would follow later. Significant number (81.4%) of respondents reported that they did not have adequate skills to manage an emergency and were willing to acquire knowledge and skills in first aid to help victims. Regular and periodical community-based first aid training programs for first care responders will help to provide care and improve outcomes for injured persons.


Rumen-protected methionine a feed supplement to low dietary protein: effects on microbial population, gases production and fermentation characteristics.
The present study was performed to evaluate the effects of different concentration of rumen-protected methionine (RPMet) with a low level of crude protein (CP) using rumen simulation technology on many parameters. The experiment was assigned randomly into four treatments: (1) high protein diet (163.39 g/kg CP) without RPMet (HP); (2) low protein diet (146.33 g/kg CP) without RPMet (LP); (3) low protein diet, supplement with low RPMet (RPMet: 0.11 g/kg) (LPLMet); and (4) low protein diet, supplement with high RPMet (RPMet: 0.81 g/kg) (LPHMet), mixed with 20 g basal diet in each fermenter. Based on National Research Council (NRC) (Nutrient requirements of dairy cattle, National Academies Press, Washington, DC, 2001) recommendation for dairy ruminants HP diet was formulated as positive normal control and LP as a negative control. Results demonstrated that CP disappearance was found significantly higher (P < 0.05) in supplement groups compared with HP and found similar (P > 0.05) with LP. However, neutral detergent fiber (NDF) and gross energy (GE) were found a parallel among supplement groups compared to HP and higher than LP. Furthermore, microbial crude protein, total and short chain fatty acids were found similar in LPHMet and HP and found significantly higher than LPLMet and LP. The R. albus population of LPHMet found parallel to HP and pointedly higher than LP in a solid and liquid fraction. Daily production of ammonia nitrogen, total gas, and methane were higher in HP than LP, LPLMet, and LPHMet. Overall, results concluded that values of digestibility, rumen fermentation, microbial crude protein, and R. albus population were similar of LPHMet to that of HP group. However, production of ammonia-N, total gas, and methane volume were significantly higher in the HP group than LPLMet, LPHMet, and LP groups. In conclusion, rumen-protected methionine is a good feed supplement to low dietary protein in the level of 0.81 g/kg.


[Premenstrual syndrome].
The Premenstrual Syndrome (PMS) is defined as the repeated occurrence of psychic disability accompanied by physical symptoms such as weight-gain, mastodynia and edema during the luteal phase. Irritability, depressive mood, lack of concentration and anxiety are the dominant psychiatric features. These symptoms culminate during the premenstrual period and disappear at the onset of menstrual bleeding. The symptomatology is of variable degree. About 2 to 3% of all women of reproductive age are severely impaired by these symptoms. The etiology of PMS is unknown. Disturbance of serotonin metabolism in the central nervous system is discussed. Furthermore abnormalities of the metabolism of sex-steroids in the brain could be involved, since these metabolites are able to modulate the GABA-ergic system. This applies in particular to progesterone-metabolites. Other etiologic concepts favour the ideas of elevated aldosterone activity, variations of endogenous opiod-levels or transient hyperprolactinemia. Thus the unknown etiology and the complex pathophysiology explain the polypragmatic therapeutic strategies including psychotherapy, treatment with psychopharmacologic agents, administration of aldosterone-antagonists, GnRH-analoga and finally prescription of oral contraceptives. The management of PMS requires individualized care by primarily treating the leading symptoms.


Simultaneous quantification of estrogens, their precursors and conjugated metabolites in human breast cancer cells by LC-HRMS without derivatization.
Liquid chromatography-mass spectrometry (LC-MS) is the state of the art technique for quantification of steroid hormones. Currently used methods are typically limited by the need of pre-column derivatization to increase ionization efficiency; however, this causes hydrolysis of conjugated metabolites. Our newly established LC-HRMS method is able to simultaneously quantify conjugated and unconjugated steroids without prior derivatization using deuterated internal standards and solid-phase extraction. This assay was validated according to ICH Q2(R1) guidelines for the analysis of the 10 main steroids of the estrogenic pathway, namely 4-androstene-3,17-dione, dehydroepiandrosterone (DHEA), DHEA-3-sulfate, estrone, 17β-estradiol, estriol (16α-OH-17β-estradiol), estrone-3-sulfate, 17β-estradiol-3-(β-d-glucuronide), 17β-estradiol-3-sulfate and testosterone. Assay performance characteristics were excellent with results for accuracy (98.8-101.2%), precision (mean: 2.05%, all ≤2.80%), stability over five freeze-thaw-cycles (95.7-100.4%) and SPE accuracy (96.9-102.0%), as well as suitable lower and upper limits of quantification for cell culture experiments (LLOQ 0.005-2ng/ml, ULOQ 3-2000ng/ml). Furthermore, we demonstrated the functionality of our method for the monitoring of steroid levels in the human breast cancer cell line MCF-7. This sensitive assay allows for the first time detailed investigations on estrogen metabolomics in breast cancer cells and may also apply to other estrogen-dependent tumor entities.


The Geomagnetic Field Is a Contributing Factor for an Efficient Iron Uptake in Arabidopsis thaliana.
The Earth's magnetic field, defined as the geomagnetic field (GMF), is an unavoidable environmental factor for all living organisms. Variation in the GMF intensity was found to affect the content of some nutrients and their associated channels and transporters in Arabidopsis thaliana. In this work, we observed that reduction of the GMF to near null magnetic field (NNMF) affects the accumulation of metals in plant tissues, mainly iron (Fe) and zinc (Zn) content, while the content of others metals such as copper (Cu) and manganese (Mn) is not affected. Accordingly, Fe uptake genes were induced in the roots of NNMF-exposed plants and the root Fe reductase activity was affected by transferring GMF-exposed plant to NNMF condition. Under Fe deficiency, NNMF-exposed plants displayed a limitation in the activation of Fe-deficiency induced genes. Such an effect was associated with the strong accumulation of Zn and Cu observed under NNMF conditions. Overall, our results provide evidence on the important role of the GMF on the iron uptake efficiency of plants.


Targeting connexin43 expression accelerates the rate of wound repair.
The repair of tissue damage is a key survival process in all organisms and involves the coordinated activation of several cell types. Cell-cell communication is clearly fundamental to this process, and a great deal is known about extracellular communication within the wound site via cytokines. Here we show that direct cell-cell communication through connexin 43 (Cx43) gap junction channels also plays a major role in the wound healing process. In two different wound healing models, incisional and excisional skin lesions, we show that a single topical application of Cx43 antisense gel brings about a transient downregulation of Cx43 protein levels, and this results in a dramatic increase in the rate of wound closure. Cx43 knockdown reduces inflammation, seen both macroscopically, as a reduction in swelling, redness, and wound gape, and microscopically, as a significant decrease in neutrophil numbers in the tissue around the wound. One long-term consequence of the improved rate of healing is a significant reduction in the extent of granulation tissue deposition and the subsequent formation of a smaller, less distorted, scar. This approach is likely to have widespread therapeutic applications in other injured tissues and opens up new avenues of research into improving the wound healing process.


[Whole rehabilitation: a new goal of erectile dysfunction therapy].
Phosphodiesterase type 5 (PDE5) inhibitors effectively enhance the erectile function of the patients with erectile dysfunction (ED). The use of sildenafil citrate is expanding to a broader extent. Pulmonary artery hypertension has become a new indication of sildenafil. Sildenafil could improve the epithelial function in several vascular conditions in clinical trials. This article reviews the recent advances on basic and clinical studies of ED and sildenafil. On animal models, sildenafil could resume the cavernous epithelial function, up-regulate the protein expression of phosphorylated endothelial NO synthase (eNOS), reverse the decreased intracavernosal pressure (ICP) induced by pudendal artery blood flow restriction or hypoxia. In clinical studies, over 50% of ED patients receiving sildenafil got a fully rigid erection (grade 4 erection). And the same percentage of post-nerve-sparing radical prostatectomy patients receiving sildenafil obtained penile rehabilitation and spontaneously resumed erection sufficient for sexual intercourse. Sildenafil treatment has contributed to the normalization of self-esteem, confidence and sexual harmony in men with ED. All this suggests that a whole rehabilitation from erectile to psychosocial function may become a new goal of ED therapy.


Genetic characteristics of Coxsackievirus A6 from children with hand, foot and mouth disease in Beijing, China, 2017-2019.
To investigate the evolution and genetic characteristics of Coxsackievirus A6 (CVA6) which acted as the predominant pathogen of hand, foot and mouth disease (HFMD) in children in Beijing, China, 2017-2019. Throat swab specimens were collected for general Enterovirus (EV), enterovirus A71 (EV-A71) and CVA16 detection by Real-time PCR. These general EV-positive samples were identified by semi-nested RT-PCR method and sequencing. The CVA6 VP1 gene and genome sequences were amplified and sequenced. The phylogenetic, variation and recombination analyses were performed. A total of 1721 HFMD patients were enrolled in this study, with the male to female ratio of 1.62:1. The majority of cases were less than five years, which accounted for 73.50%. The overall detection rate of EV was 88.32% (1520/1721). A total of 8 EV types were identified, including CVA6 (55.86%), CVA16 (26.32%), EV-A71 (2.24%), CVA10 (2.04%), CVA4 (1.05%), CVA5 (0.59%), CVA2 (0.33%), and CVA8 (0.07%), while 175 (11.51%) EV were untyped. The main pathogen of HFMD was CVA6 from 2017 to 2018, while CVA6 and CVA16 were the main causative pathogens in 2019. The nucleotide and amino acid sequence identities of the 120 CVA6 complete VP1 gene sequences in this study were 91.2%-100.0% and 97.7%-100.0%, respectively. Compared with the prototype strain (Gdula) of CVA6, the nucleotide and amino acid sequence identities were 81.7%-84% and 94.7%-96.3%, respectively. The phylogenetic tree indicated that all 120 CVA6 sequences belonged to sub-genotype D3, while 119 CVA6 sequences belonged to evolutionary branch D3a, except one from 2017 belonged to D3b. Recombination analysis based on the complete genome sequences showed that potential multiple recombination may have occurred in 2B and 3D protein coding regions with EV-A114. The main pathogens of HFMD were CVA6 and CVA16 in Beijing, China, 2017-2019; while these CVA6, as recombination strains, belonged to the D3a evolutionary branch.


Gravidic Intrahepatic Cholestasis With Concurrent COVID-19 Infection.
The most usual pregnancy-specific liver condition that commonly exhibits in the third trimester is intrahepatic cholestasis (IHC). Maternal non-pruritic rash and jaundice are clinical signs; and abnormal liver function tests, especially elevated blood bile acids, are the laboratory findings. Pregnancy-related IHC is linked to a higher risk of unfavorable perinatal consequences including stillbirth, meconium-stained amniotic fluid, and spontaneous premature delivery especially when combined with COVID-19 infection. The treatment for it typically involves ursodeoxycholic acid. There is mounting evidence that IHC during pregnancy may have long-term effects on the health of both the mother and the fetus. Therefore, to have a better understanding of the etiology, management and consequences on maternal and fetal wellbeing, with concurrent COVID-19 infection; here is a case of a 25-year-old second gravida with IHC with concurrent COVID-19 infection in the discussion.


Comprehensive Lipidomic Analysis of Three Edible Brown Seaweeds Based on Reversed-Phase Liquid Chromatography Coupled with Quadrupole Time-of-Flight Mass Spectrometry.
A comprehensive lipidomic analysis was performed onto three edible brown seaweeds, namely Laminaria japonica, Undaria pinnatifida, and Scagassum natans, using reversed-phase liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (RPLC-Q-TOF-MS/MS). In total, 675 lipid molecules, including glycolipids (GLs), phospholipids, sphingolipids (SLs), betaine lipids, and glycerolipids, were identified and semiquantified. With the exception of the high content of diacylglycerols found in L. japonica (54.6% of total lipids), GLs were the dominant component in the three brown seaweeds (27.7-56.7% of total lipids), containing a high proportion of eicosapentaenoic acid. Interestingly, SLs represented by ceramide and hexosylceramide containing phytosphingosine and α-hydroxy fatty acid structures were detected in the three brown seaweeds. A large number of acylated GLs were identified and reported for the first time in these seaweeds, including acylated monogalactosyldiacylglycerol and acylated digalactosyldiacylglycerol containing nonoxidized fatty acids. The bioactive lipids identified herein could be considered potential biomarkers for identifying these seaweeds, evaluating their nutritional value and further promoting their utilization.


The problem family and community medicine.
The characteristics of problem families are described and especially their dependency upon the social services. They are of increasing importance to community medicine since as shown by the literature their members form 5--10% of the total population and use from 50--80% of the total social and corrective services. The social pathology of 16 root and 110 sub-families was investigated; enquiries have also been made into the family dynamics and especially child rearing, learning problems and ill health. Infections, injuries and childhood disorders are particularly frequent. There are administrative advantages in regarding these families as socially handicapped.


Oxygen Reduction Reaction Activity of Microwave Mediated Solvothermal Synthesized CeO2/g-C3N4 Nanocomposite.
Electrocatalytic active species like transition metal oxides have been widely combined with carbon-based nanomaterials for enhanced Oxygen Reduction Reaction (ORR) studies because of the synergistic effect arising between different components. The aim of the present study is to synthesize CeO2/g-C3N4 system and compare the ORR activity with bare CeO2. Ceria (CeO2) embedded on g-C3N4 nanocomposite was synthesized by a single-step microwave-mediated solvothermal method. This cerium oxide-based nanocomposite displays enhanced ORR activity and electrochemical stability as compared to bare ceria.


Using Cooperatively Folded Peptides To Measure Interaction Energies and Conformational Propensities.
The rates and equilibria of the folding of biopolymers are determined by the conformational preferences of the subunits that make up the sequence of the biopolymer and by the interactions that are formed in the folded state in aqueous solution. Because of the centrality of these processes to life, quantifying conformational propensities and interaction strengths is vitally important to understanding biology. In this Account, we describe our use of peptide model systems that fold cooperatively yet are small enough to be chemically synthesized to measure such quantities. The necessary measurements are made by perturbing an interaction or conformation of interest by mutation and measuring the difference between the folding free energies of the wild type (in which the interaction or conformation is undisturbed) and the mutant model peptides (in which the interaction has been eliminated or the conformational propensities modified). With the proper controls and provided that the peptide model system in question folds via a two-state process, these folding free energy differences can be accurate measures of interaction strengths or conformational propensities. This method has the advantage of having high sensitivity and high dynamic range because the energies of interest are coupled to folding free energies, which can be measured with precisions on the order of a few tenths of a kilocalorie by well-established biophysical methods, like chaotrope or thermal denaturation studies monitored by fluorescence or circular dichroism. In addition, because the model peptides can be chemically synthesized, the full arsenal of natural and unnatural amino acids can be used to tune perturbations to be as drastic or subtle as desired. This feature is particularly noteworthy because it enables the use of analytical tools developed for physical organic chemistry, especially linear free energy relationships, to decompose interaction energies into their component parts to obtain a deeper understanding of the forces that drive interactions in biopolymers. We have used this approach, primarily with the WW domain derived from the human Pin1 protein as our model system, to assess hydrogen bond strengths (especially those formed by backbone amides), the dependence of hydrogen bond strengths on the environment in which they form, β-turn propensities of both natural sequences and small molecule β-turn mimics, and the energetics of carbohydrate-protein interactions. In each case, the combination of synthetic accessibility, the ease of measuring folding energies, and the robustness of the structure of the Pin1 WW domain to mutation enabled us to obtain incisive measurements of quantities that have been challenging to measure by other methods.


[Identification and evaluation of a new nucleic acid amplification test target for specific detection of Mycobacterium tuberculosis complex].
To identify and evaluate a new nucleic acid amplification (NAA) test target for specific detection of Mycobacterium tuberculosis (MTB) complex (MTC). MTC-specific fragment was obtained by ISSR genotyping technology. Primer pairs were designed based on the sequences of MTC-specific fragment and tested in 211 mycobacterial strains including 107 MTC strains and 104 nontuberculous mycobacteria (NTM) strains. IS6110 element (specific identification of MTC strains) and 16s rRNA gene (specific identification of Mycobacterium) amplification were used as a control to evaluate the efficacy of the NAA test target in the detection of MTC strains. One MTC-specific fragment with the length of 588 bp, located in 315947 - 316534 of the genome from MTB reference strain H(37) Rv, were obtained, cloned and sequenced. MTC-specific primer pairs MTCF/R were designed based on these sequences. All 211 mycobacterial strains accurately produced the genus-specific 16s rRNA amplicon. All MTC strains were positive in the MTCF/R PCR amplification while 99% MTC strains (106/107) were positive in the amplification of IS6110 sequences. All NTM strains were negative in both IS6110 and MTCF/R PCR amplification. The MTC-specific fragment developed in this study can be used as a new NAA test target to correctly distinguish MTC from NTM.


Elevated Levels of the Reactive Metabolite Methylglyoxal Recapitulate Progression of Type 2 Diabetes.
The molecular causes of type 2 diabetes (T2D) are not well understood. Both type 1 diabetes (T1D) and T2D are characterized by impaired insulin signaling and hyperglycemia. From analogy to T1D, insulin resistance and hyperglycemia are thought to also play causal roles in T2D. Recent clinical studies, however, found that T2D patients treated to maintain glycemia below the diabetes definition threshold (HbA1c < 6.5%) still develop diabetic complications. This suggests additional insulin- and glucose-independent mechanisms could be involved in T2D progression and/or initiation. T2D patients have elevated levels of the metabolite methylglyoxal (MG). We show here, using Drosophila glyoxalase 1 knockouts, that animals with elevated methylglyoxal recapitulate several core aspects of T2D: insulin resistance, obesity, and hyperglycemia. Thus elevated MG could constitute one root cause of T2D, suggesting that the molecular causes of elevated MG warrant further study.


Chemokine receptor expression in the human ectocervix: implications for infection by the human immunodeficiency virus-type I.
Human immunodeficiency virus-type 1 (HIV-1) is a sexually transmitted pathogen that can infect cells in the female reproductive tract (FRT). The mechanism of viral transmission within the FRT and the mode of viral spread to the periphery are not well understood. To characterize the frequency of potential targets of HIV infection within the FRT, we performed a systematic study of the expression of HIV receptors (CD4, galactosyl ceramide (GalCer)) and coreceptors (CXCR4 and CCR5) on epithelial cells and leucocytes from the ectocervix. The ectocervix is a likely first site of contact with HIV-1 following heterosexual transmission, and expression of these receptors is likely to correlate with susceptibility to viral infection. We obtained ectocervical tissue specimens from women undergoing hysterectomy, and compared expression of these receptors among patients who were classified as being in the proliferative or secretory phases of their menstrual cycle at the time of hysterectomy, as well as from postmenopausal tissues. Epithelial cells from tissues at early and mid-proliferative stages of the menstrual cycle express CD4, although by late proliferative and secretory phases, CD4 expression was absent or weak. In contrast, GalCer expression was uniform in all stages of the menstrual cycle. CXCR4 expression was not detected on ectocervical epithelial cells and positive staining was only evident on individual leucocytes. In contrast, CCR5 expression was detected on ectocervical epithelial cells from tissues at all stages of the menstrual cycle. Overall, our results suggest that HIV infection of cells in the ectocervix could most likely occur through GalCer and CCR5. These findings are important to define potential targets of HIV-1 infection within the FRT, and for the future design of approaches to reduce the susceptibility of women to infection by HIV-1.


Microtubule self-organisation during seed germination in Arabidopsis.
Upon water uptake and release of seed dormancy, embryonic plant cells expand, while being mechanically constrained by the seed coat. Cortical microtubules (CMTs) are key players of cell elongation in plants: their anisotropic orientation channels the axis of cell elongation through the guidance of oriented deposition of load-bearing cellulose microfibrils in the cell wall. Interestingly, CMTs align with tensile stress, and consistently, they reorient upon compressive stress in growing hypocotyls. How CMTs first organise in germinating embryos is unknown, and their relation with mechanical stress has not been investigated at such an early developing stage. Here, we analysed CMT dynamics in dormant and non-dormant Arabidopsis seeds by microscopy of fluorescently tagged microtubule markers at different developmental time points and in response to abscisic acid and gibberellins. We found that CMTs first appear as very few thick bundles in dormant seeds. Consistently, analysis of available transcriptome and translatome datasets show that limiting amounts of tubulin and microtubule regulators initially hinder microtubule self-organisation. Seeds imbibed in the presence of gibberellic acid or abscisic acid displayed altered microtubule organisation and transcriptional regulation. Upon the release of dormancy, CMTs then self-organise into multiple parallel transverse arrays. Such behaviour matches the tensile stress patterns in such mechanically constrained embryos. This suggests that, as CMTs first self-organise, they also align with shape-derived tensile stress patterns. Our results provide a scenario in which dormancy release in the embryo triggers microtubule self-organisation and alignment with tensile stress prior to germination and anisotropic growth.


Susceptibility to diet-induced atherosclerosis in transgenic mice expressing a dysfunctional human apolipoprotein E(Arg 112,Cys142).
Transgenic mice expressing apolipoprotein (apo) E(Cys 142), a human defective variant of apo E, have elevated levels of plasma cholesterol, triglycerides, and very-low-density lipoproteins (VLDL); beta-VLDL, the biochemical hallmark of the human genetic disease type III hyperlipoproteinemia (HLP), is also present in these mice. This study was designed to determine whether these type III HLP mice have an increased susceptibility to spontaneous or diet-induced atherosclerosis. Three 4-month-old male transgenic mice and three male nontransgenic littermates were assessed for the presence of atherosclerotic lesions in the proximal aorta. No lipid-stained microscopic lesions were visible in the aortas of nontransgenic mice, whereas minimal lesions were observed on the aortic valve stumps of transgenic mice. To magnify the effect of the mutant apo E on the susceptibility of the transgenic animals to atherosclerosis, 8 transgenic and 8 nontransgenic mice were fed a synthetic diet containing 1% cholesterol, 16% fat, and 0.5% cholic acid for 3 months. The diet induced an increase in plasma cholesterol level in both transgenic and nontransgenic mice. However, the increase in plasma cholesterol level in the transgenic mice was all in the VLDL fraction, whereas in nontransgenic mice it was due to increases in both VLDL and high-density lipoprotein (HDL) fractions. Plasma triglyceride levels fell in both groups of mice. After 3 months on the diet, there were compositional changes in the VLDL of both groups, characterized mainly by higher cholesteryl ester content, that resulted in beta-migration on agarose gel electrophoresis. Despite similar VLDL lipid compositions, the extent of atherosclerosis differed markedly in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Horizontal transfer of carbohydrate metabolism genes into ectomycorrhizal Amanita.
The genus Amanita encompasses both symbiotic, ectomycorrhizal fungi and asymbiotic litter decomposers; all species are derived from asymbiotic ancestors. Symbiotic species are no longer able to degrade plant cell walls. The carbohydrate esterases family 1 (CE1s) is a diverse group of enzymes involved in carbon metabolism, including decomposition and carbon storage. CE1 genes of the ectomycorrhizal A. muscaria appear diverged from all other fungal homologues, and more similar to CE1s of bacteria, suggesting a horizontal gene transfer (HGT) event. In order to test whether AmanitaCE1s were acquired horizontally, we built a phylogeny of CE1s collected from across the tree of life, and describe the evolution of CE1 genes among Amanita and relevant lineages of bacteria. CE1s of symbiotic Amanita were very different from CE1s of asymbiotic Amanita, and are more similar to bacterial CE1s. The protein structure of one CE1 gene of A. muscaria matched a depolymerase that degrades the carbon storage molecule poly((R)-3-hydroxybutyrate) (PHB). Asymbiotic Amanita do not carry sequence or structural homologues of these genes. The CE1s acquired through HGT may enable novel metabolisms, or play roles in signaling or defense. This is the first evidence for the horizontal transfer of carbohydrate metabolism genes into ectomycorrhizal fungi.


Hepatitis C virus subtype 3a was introduced in the USSR in the early 1980s.
A total of 2120 nucleotide sequences of the NS5b region of HCV subtype 3a were analysed, including 310 strains derived from former republics of the USSR (Azerbaijan, Estonia, Lithuania, Russia, Tajikistan and Uzbekistan). Among the viral isolates collected from former regions of the Soviet Union, 294 strains formed 3 sustained phylogenetic clusters, with each having a common origin. Phylodynamic analysis demonstrated that the most recent common ancestors of the current strains inside the three clusters were introduced into the USSR population in 1981±1, 1984±2 and 1985±2, respectively (the confidence intervals were calculated using Student's t-distribution, P<0.05). The time estimation obtained for HCV subtype 3a correlated well with the historical and epidemiological context of this period, and in particular with the start of widespread injection drug use in the USSR in the first half of the 1980s.


[Multidrug resistant Acinetobacter baumannii].
Acinetobacter baumannii is a well recognized cause of nosocomial infections, particularly in intensive care units. Strains of this species can be resistant to multiple antimicrobial agents, leaving limited therapeutic options. It has been shown that multidrug resistance in A. baumannii is, although not exclusively, associated with some lineages (EU clones) spread in many European countries. Since 1991, the population structure and antimicrobial resistance of Acinetobacter hospital isolates in the Czech Republic have been systematically studied in our laboratory. It has been shown that the vast majority of Czech multidrug resistant isolates from 1991 to 2006 belonged to EU clone I or II. While clone I largely predominated among the isolates in the 1990s, a prospective study 2005-2006 has shown a recent shift towards clone II. This change was associated with the emergence of resistance to carbapenems in the Czech Acinetobacter population. As similar observations have been recently reported from other European countries, EU clone II is likely to play an important role in the spread of carbapenem resistance.


Neosynthesis of cardiolipin in Rhodobacter sphaeroides under osmotic stress.
The phospholipid composition of Rhodobacter sphaeroides cells resuspended in various hypertonic solutions has been examined by thin-layer chromatography and ESI mass spectrometry. R. sphaeroides responds to hyperosmotic stress by increasing the amount of cardiolipin in the membranes; this phenomenon occurs in spheroplasts also. Cardiolipin increases quickly and continuously during the time when the cells are resuspended in hypertonic medium. The optimum of stimulation of the neosynthesis of cardiolipin during osmotic stress was found to be at external 1 osm. ESI-MS analyses allowed the identification of two different cardiolipins in R. sphaeroides: the tetravaccenylcardiolipin ([M - H](-), m/z 1456.9) and the trivaccenylmonopalmitoylcardiolipin ([M - H](-), m/z 1430.0).


Photodissociation and radiative association of HeH+ in the metastable triplet state.
We investigate the photodissociation of HeH(+) in the metastable triplet state as well as its formation through the inverse process, radiative association. In models of astrophysical plasmas, HeH(+) is assumed to be present only in the ground state, and the influence of the triplet state has not been explored. It may be formed by radiative association during collisions between a proton and metastable helium, which are present in significant concentrations in nebulae. The triplet state can also be formed by association of He(+) and H, although this process is less likely to occur. We compute the cross sections and rate coefficients corresponding to the photodissociation of the triplet state by UV photons from a central star using a wave packet method. We show that the photodissociation cross sections depend strongly on the initial vibrational state and that the effects of excited electronic states and nonadiabatic couplings cannot be neglected. We then calculate the cross section and rate coefficient for the radiative association of HeH(+) in the metastable triplet state.


Postnatal Outcomes and Risk Factors for In-Hospital Mortality among Asphyxiated Newborns in a Low-Resource Hospital Setting: Experience from North-Central Nigeria.
Birth asphyxia accounts for a third of global newborn deaths and 95 percent of these occur in low-resource settings. A key to reducing asphyxia-related deaths in these settings is improving care of these newborns and this requires an understanding of factors associated with adverse outcomes. In this study, we report outcomes and risk factors for mortality among newborn infants with birth asphyxia admitted to a typical low-resource hospital setting. We prospectively followed up 191 asphyxiated newborn infants admitted to a referral tertiary hospital in North-central Nigeria. At baseline, care-givers completed a structured questionnaire. Using univariable analysis, we compared baseline characteristics between participants who died and those who survived till discharge. We also fitted a multivariable logistic regression model to identify risk factors for mortality among the cohort. Majority (60.7%) of the study participants presented to the hospital within the first six hours of life. Despite this, mortality among the cohort was 14.7% with a third dying within the first 24 hours of admission. The presence of respiratory distress at admission increased the risk for mortality (AOR = 3.73, 95% CI 1.22 to 11.35) while higher participant weight at admission decreased the risk (AOR = 0.11, 95% CI 0.03 to 0.40). Intrapartum factors such as duration of labour and maternal age, although significant on univariable analysis, were not significant on multivariable analysis. Hospital mortality among newborns with birth asphyxia is high in North-central Nigeria and majority of deaths occur during acute care. Respiratory distress at presentation and admission weights were identified as key risk factors for asphyxia mortality. Intrapartum factors on the other hand might have indirect effects on mortality through an increased risk for neonatal complications.


Effect of the antiphagocytic agent cytochalasin B on macrophage invasion by Leishmania mexicana promastigotes and Trypanosoma cruzi epimastigotes.
Unstimulated mouse peritoneal exudate cells were cultured on coverslips in Medium 199 containing 10 per cent (v/v) calf serum. Cytochalasin B dissolved in dimethyl sulphoxide (DMSO) and diluted in Medium 199 was added to cultures to give final concentrations of 1, 5 and 10 mug/ml. Equal numbers of Leishmania mexicana promastigotes, Trypanosoma cruzi epimastigotes and sheep red cells were added to 24 hr cultures incubated at 37 C. The macrophage monolayers were fixed and stained at various time intervals. L. mexicana promastigotes sheep red blood cells were found to attach to macrophages in the presence of the drug but did not enter the cells. When the medium containing the cytochalasin was replaced with normal medium phagocytosis of the adherent parasites and red cells followed rapidly. T. cruzi epimastigotes were found inside macrophages in both drug-treated and drug-free cultures although the number found to be intracellular in the latter was significantly greater. This study suggest that L. mexicana promastigotes enter macrophages by being phagocytosed, whereas T. cruzi epimastigotes can actively penetrate these cells.


Urinary NO2- and NO3- evaluation by an ion chromatography system.
We describe an ion chromatography system using a Dionex AS4A-SC column with carbonate-bicarbonate buffer (1.8-1.7 mM) as eluent for the evaluation of urinary NO2- and NO3-. This chromatographic system gives an accurate measurement of NO2- and NO3- in the urine as an index of NO production in vivo, making also possible to evaluate their relative proportion and providing useful tools to investigate the NO system.


Prediction of Drug-Target Interactions From Multi-Molecular Network Based on Deep Walk Embedding Model.
Predicting drug-target interactions (DTIs) is crucial in innovative drug discovery, drug repositioning and other fields. However, there are many shortcomings for predicting DTIs using traditional biological experimental methods, such as the high-cost, time-consumption, low efficiency, and so on, which make these methods difficult to widely apply. As a supplement, the in silico method can provide helpful information for predictions of DTIs in a timely manner. In this work, a deep walk embedding method is developed for predicting DTIs from a multi-molecular network. More specifically, a multi-molecular network, also called molecular associations network, is constructed by integrating the associations among drug, protein, disease, lncRNA, and miRNA. Then, each node can be represented as a behavior feature vector by using a deep walk embedding method. Finally, we compared behavior features with traditional attribute features on an integrated dataset by using various classifiers. The experimental results revealed that the behavior feature could be performed better on different classifiers, especially on the random forest classifier. It is also demonstrated that the use of behavior information is very helpful for addressing the problem of sequences containing both self-interacting and non-interacting pairs of proteins. This work is not only extremely suitable for predicting DTIs, but also provides a new perspective for the prediction of other biomolecules' associations.


Dispersive liquid-liquid microextraction followed by high-performance liquid chromatography-ultraviolet detection to determination of opium alkaloids in human plasma.
A novel, simple, rapid and sensitive dispersive liquid-liquid microextraction method based on the solidification of floating organic drop (DLLME-SFO) combined with high-performance liquid chromatography-ultraviolet detection (HPLC-UV) was used to determine opium alkaloids in human plasma. During the extraction procedure, plasma protein was precipitated by using a mixture of zinc sulfate solution and acetonitrile. Some effective parameters on extraction were studied and optimized. Under the optimum conditions (extraction solvent: 30.0 μl 1-undecanol; disperser solvent: 470 μl acetone; pH: 9; salt addition: 1%(w/v) NaCl and extraction time: 0.5 min), calibration curves are linear in the range of 1.5-1000 μgl(-1) and limit of detections (LODs) are in the range of 0.5-5 μgl(-1). The relative standard deviations (RSDs) for 100 μgl(-1) of morphine and codeine, 10.0 μgl(-1) of papaverine and 20.0 μgl(-1) of noscapine in diluted human plasma are in the range of 4.3-7.4% (n=5). Finally, the method was successfully applied in the determination of opium alkaloids in the actual human plasma samples. The relative recoveries of plasma samples spiked with alkaloids are 88-110.5%. The obtained results show that DLLME-SFO combined with HPLC-UV is a fast and simple method for the determination of opium alkaloids in human plasma.