[Usefulness and necessity of the andrologist in assisted reproductions units].
In this issue we make a review of our experience in the management of the sterile men: protocols used for the study of men's sterility, causes and specific treatments, surgical recovery of spermatozoa and screening before IVF or IVF-ICSI. We concluded that with an adequate protocol, it's possible to establish the aetiology of men's infertility in a 78.8% of the cases and it's also possible to initiate a specific treatment in almost a 47.8% of men. Results of specific treatment, with a previous selection of patients, could be better than those of assisted reproduction techniques. Best results are obtained in cases of vaso-vasostomy (vasectomy reversal) and obstruction of ejaculatory duct. It's also needed a study of genetics causes and bad prognostic circumstances in those men whose partner is going on with an IVF or IVF-ICSI cycle.


Substituted benzamides containing azaspiro rings as upregulators of apolipoprotein A-I transcription.
Apolipoprotein A-I (Apo A-I) is the principal protein component of high density lipoprotein (HDL), which is generally considered as a potential therapeutic target against atherosclerosis. The understanding of the Apo A-I regulation mechanism has fuelled the development of novel HDL targeted therapeutic approaches. To identify novel agents that can upregulate Apo A-I expression, we performed a cell-based reporter assay to screen 25,600 small molecules. Based on the dataset obtained from screening, a series of novel analogs of substituted benzamides containing azaspiro rings were assessed for their ability to induce the transcription of the Apo A-I gene, and the structure-activity relationship (SAR) around these analogs was also proposed. The results indicated that the trifluoromethyl substituted benzamide containing an azaspiro ring is a promising backbone for designing Apo A-I transcriptional upregulator and could be viable leads for development of new drugs to prevent and treat atherosclerosis in the future.


Bcl-2 protection of islet allografts is unmasked by costimulation blockade.
One major limitation in pancreatic islet transplantation is availability of donor tissue. Donor shortage is exacerbated by islet apoptosis from the stresses of islet isolation and transplantation. Furthermore, the side effects of immunosuppressive drugs preclude transplants into patients whose diabetes is controlled by parenteral insulin. We hypothesised that over-expressing anti-apoptotic Bcl-2 or secretion of immunomodulatory CTLA4Ig molecules in islet beta cells would enhance survival of transplanted islets while minimizing systemic side effects. Over-expression of Bcl-2 neither significantly increased preservation of islet cell mass after transplantation into immunocompromised recipients nor decreased cytokine-mediated apoptosis in vitro. Although Bcl-2 over-expression alone was insufficient in protecting islet allografts from rejection, its beneficence was shown by the enhancement of protection when the adaptive immune response was inhibited by locally produced CTLA4Ig. Thus, the combination of anti-apoptotic and immunosuppressive intervention has additive or synergistic efficacy and may reduce the level of systemic immunosuppression or quantity of donor tissue required.


Thermal shift assays of marine-derived fungal metabolites from Aspergillus fischeri MMERU 23 against Leishmania major pteridine reductase 1 and molecular dynamics studies.
Marine-derived fungi are a promising source of bioactive molecules, especially species from extreme habitats. Although several secondary metabolites such as meroterpenoids and alkaloids have been isolated from cultures of Aspergillus fischeri, obtained from terrestrial habitats, there is no report on compounds isolated from marine-derived strains. Many metabolites isolated from marine-derived fungi exhibited a myriad of biological activities. Marine natural products have shown to be an important source of bioactive compounds and can assist in the discovery of molecules with affinity against validated targets from exclusive strains of parasites of medical importance such as pteridine reductase 1 (PTR1), from Leishmania major, which is essential for cell growth. Leishmaniasis is responsible for approximately 65,000 annual deaths. Despite the mortality data, drugs available for the treatment of patients are insufficient and have moderate therapeutic efficacy in addition to serious adverse effects, which make the development of new drugs urgent. The previously described aszonalenin (ASL), aszonapyrone A (ASP), acetylaszonalenin (ACZ), and helvolic acid (HAC) were isolated from the ethyl acetate extract of the culture of a marine sponge-associated A. fischeri MMERU 23 and their affinities against PTR1 were determined by ThermoFluor®. Among the tested compounds, only ACZ showed dose-dependent affinity against PTR1. Moreover, complementary molecular dynamics studies (t = 100 000 ps) have showed that this molecule performs hydrogen bonds with key residues at the active site for more than 60% of the productive trajectory time. The results indicate that ACZ could be a promising PTR1 inhibitor and a potential candidate for development of antileishmanial drug.Communicated by Ramaswamy H. Sarma.


Jacalin, a lectin that inhibits in vitro HIV-1 infection, induces intracellular calcium increase via CD4 in cells lacking the CD3/TcR complex.
The lectin jacalin interacts with the CD4 cell surface antigen; this lectin inhibits in vitro infection by human immunodeficiency virus type 1 without preventing virus binding on the host cell. The infection process is known to involve cellular events triggered by the binding of the viral external glycoprotein gp120 to CD4. Herein we demonstrate that jacalin induces cell signaling directly through the CD4 antigen and that independently of the CD3/TcR complex. The capacity of jacalin to trigger cell signals through the CD4 molecule is discussed in relation to its ability to inhibit HIV infection.


The impact of antibody/epitope affinity strength on the sensitivity of electrochemical immunosensors for detecting small molecules.
A displacement immunoassay involves having a labelled analogue of the analyte (the epitope) already bound to the antibody. The presence of the analyte causes a competition for antibodies, and some of the antibodies dissociates from the epitope so that it can bind with the analyte. Herein, the influence of the affinity of the surface-bound epitope for the antibody on the sensitivity and selectivity of a displacement immunosensor is explored both theoretically and experimentally. An electrochemical immunosensor described previously, where the dissociation of antibodies from an electrode surface causes an increase in current from surface-bound ferrocene species, is used for this purpose. As expected, the ease and effectiveness of the bound antibody being displaced is inversely related to the affinity of the antibody to the surface-bound epitope relative to the analyte in solution as expected. However, if the affinity constant is too low, selectivity and/or sensitivity are compromised. Experimental results are qualitatively compared with a simple mass-action model.


CSF in Epileptic Prodromal Alzheimer's Disease: No Diagnostic Contribution but a Pathophysiological One.
Objective: To study whether cerebrospinal fluid (CSF) analysis may serve as a diagnostic test for the screening of epilepsy in sporadic prodromal Alzheimer's disease (AD). Methods: A total of 29 patients with epileptic prodromal sporadic AD patients (epADs) were included and were retrospectively compared with 38 non-epileptic prodromal AD patients (nepADs) for demographics, clinical features, Mini-Mental Status Examination (MMSE) results, CSF biomarkers, and electro-radiological features. Results: Our study did not show any significant differences in CSF biomarkers regarding neurodegeneration, albumin levels, and inflammation between epADs and nepADs. The epADs were significantly older at diagnosis (p = 0.001), more hypertensive (p = 0.01), and displayed larger white matter hyperintensities on brain magnetic resonance imaging (MRI; p = 0.05). There was a significant correlation between the CSF Aβ-42 and Aβ-40 levels with interictal epileptiform discharges and delta slowing on EEGs recordings, respectively (p = 0.03). Conclusions: Our study suggests that CSF may not serve as a surrogate marker of epilepsy in prodromal AD and cannot circumvent the operator-dependent and time-consuming interpretation of EEG recordings. In humans, AD-related epileptogenesis appears to involve the Aβ peptides but likely also additional non-amyloid factors such as small-vessel disease (i.e., white matter hyperintensities).


Plants, diet, and health.
Chronic disease is a major social challenge of the twenty-first century. In this review, we examine the evidence for discordance between modern diets and those on which humankind evolved as the cause of the increasing incidence of chronic diseases, and the evidence supporting consumption of plant foods as a way to reduce the risk of chronic disease. We also examine the evidence for avoiding certain components of plant-based foods that are enriched in Western diets, and review the mechanisms by which different phytonutrients are thought to reduce the risk of chronic disease. This body of evidence strongly suggests that consuming more fruits and vegetables could contribute both to medical nutrition therapies, as part of a package of treatments for conditions like type 2 diabetes, heart disease, cancer, and obesity, and to the prevention of these diseases. Plant science should be directed toward improving the quality of plant-based foods by building on our improved understanding of the complex relationships between plants, our diet, and our health.


[Chromosomal aberrations in a subfertile cotton-top tamarin].
The present case report describes a female cotton-top tamarin which was taken over by the Zoo Basel to form a new breeding pair. The animal demonstrated increased marking behavior without any obvious medical reasons, dominant behavior, failure to become pregnant and its external genitals were ambiguous. A disorder of the sexual development (DSD) was suspected by the zoo veterinarians and in a first step, the chromosomes of the monkey were analyzed. Six cell lines with different karyotypes were observed. The two most frequent cell lines had a 46,XX or a 46,XY karyotype which are normal chromosome complements of female and male cotton-top tamarins, respectively. The other much less frequent cell lines showed numerical aberrations with and without a marker chromosome. Specific biological features of the Callitrichidae, such as natural twinning and genetic chimerism impeded the clarification of the pathogenesis and prevented a reliable prognosis on the fertility of the cotton-top tamarin.


[Isolated symplasts and stromal syncytial buds of the normal human placenta at 6 to 14 weeks of pregnancy].
Formation of isolated symplasts (IS) ("deported trophoblast", according to English nomenclature) and stromal syncytial buds (SSB) has been studied in 10 normal patients at pregnancy of 6-14 weeks by means of the indirect immunoperoxidase method. Monoclonal antibodies against beta-subunit of the human chorionic gonadotropin (beta-HCG), serial paraffin slices, stained with hematoxylin-eosin, semithin slices, stained with toluidin blue-pyronine and scanning electron microscopy have been used. A great amount of syncytiotrophoblastic processes and IS, analogous by their structure to syncytiotrophoblast are revealed. Presence of beta-HCG in the syncytiotrophoblast and its absence in the cytotrophoblast are proved. Concentration of beta-HCG in the IS is higher than in the syncytiotrophoblast of the villi. Maximal concentration of beta-HCG in the SSB is described for the first time. The functional role of the IS and SSB is discussed in the system mother-placenta-fetus.


VR-ACS6 is an auxin-inducible 1-aminocyclopropane-1-carboxylate synthase gene in mungbean (Vigna radiata).
We have isolated four cDNA clones of ACC synthase from etiolated mungbean seedlings treated with auxin. pVR-ACS2, pVR-ACS3 and pVR-ACS6 contained the same sequences as the previously reported DNA fragments, pMAC2, pMAC3 (Botella et al. 1992b) and pMBA1 (Kim et al. 1992), respectively. pVR-ACS1 was identical with pAIM-1 (Botella et al. 1992a). VR-ACS6 was specifically induced in response to the auxin signal. The IAA-induction of VR-ACS6 was very rapid (within 30 min) and insensitive to cycloheximide treatment at concentrations up to 100 microM. Significant accumulation of VR-ACS6 mRNA was detected at 1 microM IAA. The IAA-induced expression of VR-ACS6 was suppressed by ABA and ethylene, but enhanced by BA. These characteristics of VR-ACS6 expression were well correlated with the physiological data of auxin-induced ethylene production in mungbean hypocotyls. VR-ACS1 was strongly induced by cycloheximide, but was found to be not auxin-specific. Inhibitors of either ethylene biosynthesis (AOA) or action (NBD) increased the basal level of VR-ACS1 mRNA.


Usefulness of high-frequency ultrasonography in the assessment of alopecia areata - comparison of ultrasound images with trichoscopic images.
Trichoscopy allows us to distinguish between different types of alopecia and to determine the stage of the disease. High-frequency ultrasonography (HF-USG) enables the evaluation of structures that are not available for clinical and trichoscopic examination, but it has not been widely used to date in the evaluation of patients with alopecia areata (AA) and other scalp disorders. To characterise the ultrasound images of patients with AA, including different stages of the disease, and to compare them with trichoscopic images and other scalp diseases. Twenty-five patients with AA, on the basis of trichoscopic examination, were qualified to three groups: with active, inactive, and regrowth phase. Next, HF-USG (20 MHz) with qualitative and quantitative evaluation of various elements of the images was performed: entrance echo (EE), dermis (dermal background; DB), follicular structures (FS), dermal/ subdermal border (D/SB). The results were compared with 10 healthy volunteers, 10 patients with androgenic alopecia (AGA), and 12 with seborrhoeic dermatitis (SebD). Active AA was characterised by FS with distinct borders, drop-like shaped, with a widened distal end located in the lower layers of DB. Inactive AA was characterised by a smaller number of FS without distinct borders. In the regrowth phase, FS of different widths, elongated, and with widened distal parts located at different DB depths were observed. HF-USG (20 MHz) may be a valuable diagnostic method in patients with AA. Ultrasound images of AA vary according to the stage of the disease and in comparison with AGA, SebD, and healthy individuals.


Pharmacogenomics variants are associated with BMI differences between individuals with bipolar and other psychiatric disorders.
Aim: Regardless of the plethora of next-generation sequencing studies in the field of pharmacogenomics (PGx), the potential effect of covariate variables on PGx response within deeply phenotyped cohorts remains unexplored. Materials & methods: We explored with advanced statistical methods the potential influence of BMI, as a covariate variable, on PGx response in a Greek cohort with psychiatric disorders. Results: Nine PGx variants within UGT1A6, SLC22A4, GSTP1, CYP4B1, CES1, SLC29A3 and DPYD were associated with altered BMI in different psychiatric disorder groups. Carriers of rs2070959 (UGT1A6), rs199861210 (SLC29A3) and rs2297595 (DPYD) were also characterized by significant changes in the mean BMI, depending on the presence of psychiatric disorders. Conclusion: Specific PGx variants are significantly associated with BMI in a Greek cohort with psychiatric disorders.


Identification and characterization of novel fusion genes in prostate cancer by targeted RNA capture and next-generation sequencing.
Gene fusions play critical roles in the development and progression of prostate cancer, and have been used as molecular biomarkers for diagnosis of the malignant disease. To further explore the novel fusions in prostate cancer, we performed targeted RNA capture and next-generation sequencing in a cohort of 52 prostate cancer patients, identified and validated 14 fusion events (7 types of fusion genes) in 12 cases, including three novel fusion genes. We characterized a chromosome rearrangement-induced trigenic KLK2-DGKB-ETV1 fusion, which may function as a non-coding RNA to upregulate the expression of the wild-type ETV1 protein in the tumor tissue. Additionally, we detected two novel fusion forms of HNRNPA2B1-ETV1 and SLC45A2-AMACR fusions, respectively. Interestingly, fusion events participated by kinase genes, which frequently occurred in other human cancers, were not present in these prostate cancer cases, suggesting discrepant gene fusion patterns in different cancers. These findings expand the genetic spectrum of prostate cancer and provide insight into diagnosis of this prevalent disease.


Bevacizumab combined with apatinib enhances antitumor and anti-angiogenesis effects in a lung cancer model in vitro and in vivo.
Angiogenesis is involved in the proliferation and metastasis of solid tumours; hence, it is an attractive therapeutic target. However, most patients who undergo anti-angiogenic drug treatment do not achieve complete tumour regression, resulting in drug resistance. The objective of this research is to explore the therapeutic effect of combining bevacizumab (Bev), an anti-vascular endothelial growth factor (VEGF)-A antibody, with apatinib (Apa), a VEGR receptor (VEGFR)-2-targeting tyrosine kinase inhibitor, in non-small cell lung cancer (NSCLC). In vitro, we assessed the influence which Bev + Apa treatment exerts upon the proliferation as well as apoptosis of Lewis lung carcinoma (LLC) cells in virtue of the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide as assay as well as Annexin V staining, respectively. For in vivo assessment, we established a tumour-bearing mouse model with LLC cells and investigated the anti-angiogenic and antitumor effects of Bev + Apa by 18F-FDG PET/CT imaging, immunohistochemistry and TUNEL staining. Bev + Apa treatment significantly inhibited LLC cell growth and proliferation in a larger scale compared to therapy of either of the only agent. Bev + Apa inhibited tumour growth and extended the median survival time of tumour-bearing mice. Mechanistically, Bev + Apa reduced angiogenesis by inhibiting VEGF and VEGFR-2 expression and reducing glucose metabolism in tumour tissues. Thus, Bev and Apa inhibited tumour angiogenesis synergistically, indicating their potential clinical utility for NSCLC treatment.


Does Television Viewership Predict Presidential Election Outcomes?
The days of surprise about actual election outcomes in the big data world are likely to be fewer in the years ahead, at least to those who may have access to such data. In this paper we highlight the potential for forecasting the Unites States presidential election outcomes at the state and county levels based solely on the data about viewership of television programs. A key consideration for relevance is that given the infrequent nature of elections, such models are useful only if they can be trained using recent data on viewership. However, the target variable (election outcome) is usually not known until the election is over. Related to this, we show here that such models may be trained with the television viewership data in the "safe" states (the ones where the outcome can be assumed even in the days preceding elections) to potentially forecast the outcomes in the swing states. In addition to their potential to forecast, these models could also help campaigns target programs for advertisements. Nearly two billion dollars were spent on television advertising in the 2012 presidential race, suggesting potential for big data-driven optimization of campaign spending.


Abietane diterpenoids from Coleus xanthanthus.
Eight new abietane diterpenoids, coleon U 11-acetate (1), 16-acetoxycoleon U 11-acetate (2), and xanthanthusins F-K (3-8), together with five known analogues, coleon U (9), 16-O-acetylcoleon C (10), coleon U-quinone (11), 8alpha,9alpha-epoxycoleon U-quinone (12), and xanthanthusin E (13), were isolated from the aerial parts of Coleus xanthanthus. The structures of 1-8 were elucidated on the basis of spectral methods. Compounds 1, 5, and 11-13 were evaluated for their cytotoxicity against K562 human leukemia cells.


Biotechnological applications of research on animal pigmentation.
The implications of primary research on pigmentation for the colour manipulation of animal species of economic importance, and the facilitation of specific processes in biotechnology are discussed. Pigment technologists, especially poultry and fish nutritionists, are concerned with achieving the often specific type and degree of coloration demanded by consumers of various products (notably egg yolk, eggshell, broiler skin and salmon flesh). In most instances involving melanin (pelage, plumage and integument) and porphyrin (eggshell) pigments, the desired coloration is achieved through the use of alternate alleles at gene loci controlling the characters of interest. In contrast, coloration involving carotenoids is controlled primarily through pigment supplementation in the diet. The difference between carotenoids and other pigments involves the strict dietary origin of the former. Factors other than pigment availability, such as body condition, hormonal status and genetic constitution, also affect coloration. Although day-old chicks can be sexed by visual inspection of their genitalia, matings resulting in sex-associated phenotypes are in wide use. The genetic markers involved affect the colour of the plumage. The cloning of genes involved in pigmentation offers the prospect of deciphering the genetic control of animal pigmentation and modifying it to meet specific pigmentation needs.


Unique oestrogen receptor ligand-binding domain sequence of native parrots: a possible link between phytoestrogens and breeding success.
The New Zealand (NZ) native parrots kākāpō, kākā and kea are classified as critically endangered, endangered and vulnerable respectively. Successful reproduction of kākāpō and kākā is linked to years of high levels of fruiting in native flora (mast years). To assess a possible hormonal link between native plants and reproductive success in these parrots in mast years, we examined the ligand-binding domains (LBD) of the progesterone receptor (PR), androgen receptor (AR), estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2) in NZ native (kākāpō, kākā, kea and kākāriki) and non-native (Australian cockatiel) parrots and compared them with those in the chicken. The amino acid sequences for PR, AR, ESR1 and ESR2 shared >90% homology among the NZ parrots, the cockatiel and, in most cases, the chicken. The exception was for the ESR1 LBD, which contained an extra eight amino acids at the C-terminal in all the parrots compared with the chicken and with published sequences of non-parrot species. These results support the notion that the ESR1 LBD of parrots responds differently to putative oestrogenic compounds in native trees in NZ during times of intermittent masting. In turn, this may provide important information for generating parrot-specific bioassays and linkages to steroidogenic activity in native plants.


Short-term desensitization of G-protein-activated, inwardly rectifying K+ (GIRK) currents in pyramidal neurons of rat neocortex.
Whole cell recordings from acutely isolated rat neocortical pyramidal cells were performed to study the kinetics and the mechanisms of short-term desensitization of G-protein-activated, inwardly rectifying K+ (GIRK) currents during prolonged application (5 min) of baclofen, adenosine, or serotonin. Most commonly, desensitization of GIRK currents was characterized by a biphasic time course with average time constants for fast and slow desensitization in the range of 8 and 120 s, respectively. The time constants were independent of the agonist used to evoke the current. The biphasic time course was preserved in perforated-patch recordings, indicating that neither component of desensitization is attributable to cell dialysis. Desensitization of GIRK currents displayed a strong heterologous component in that application of a second agonist substantially reduced the responsiveness to a test agonist. Fast desensitization, but not slow desensitization, was lost in cells loaded with GDP, suggesting that the hydrolysis cycle of G proteins might underlie the initial, rapid current decline. Hydrolysis of phosphatidylinositol biphosphate is an unlikely candidate underlying short-term desensitization, because both components of desensitization were preserved in the presence of the phospholipase C inhibitor U73122. We conclude that short-term desensitization does neither result from receptor downregulation nor from altered channel gating but might involve modifications of the G-protein-dependent pathway that serves to translate receptor activation into channel opening.


Variance and covariance of actual relationships between relatives at one locus.
The relationship between pairs of individuals is an important topic in many areas of population and quantitative genetics. It is usually measured as the proportion of the genome identical by descent shared by the pair and it can be inferred from pedigree information. But there is a variance in actual relationships as a consequence of mendelian sampling, whose general formula has not been developed. The goal of this work is to develop this general formula for the one-locus situation,. We provide simple expressions for the variances and covariances of all actual relationships in an arbitrary complex pedigree. The proposed method relies on the use of the nine identity coefficients and the generalized relationship coefficients; formulas have been checked by computer simulation. Finally two examples for a short pedigree of dogs and a long pedigree of sheep are given.


An automated system for the study of pulsatile hormone secretion in the immature rat.
A procedure is described for prolonged sampling of blood from unrestrained immature rats which overcomes some of the problems associated with contemporary techniques. 1 or 2 days before sampling, the animal is fitted with two indwelling catheters, one inserted into the right jugular vein and the other into a femoral vein. On the day of the experiment blood is continuously withdrawn from the jugular vein (30 microliter/min) using a peristaltic pump and is dispensed into sample tubes every 5 min by means of an automatic fraction collector. A second channel of the same pump continuously infuses a blood replacement mixture (at 37 degrees C) into the femoral vein thereby keeping the animal's blood volume constant. In the present study this technique was used to sample blood from both ovariectomized and immature, intact female rats for as long as 5-7 h. The procedure did not appear to disturb the normal locomotion, feeding, drinking and sleeping behavior of the animals. Plasma luteinizing hormone (LH) profiles obtained from the ovariectomized rats showed a normal pulsatile pattern of LH secretion. The frequency and amplitude of the pulses was not affected, even when the animals were bled on 2 consecutive days. Moreover, the procedure permitted accurate detection and characterization of pulsatile LH release in intact, immature rats although the episodes of LH secretion were more variable and much less pronounced. It is believed that this novel sampling technique could prove to be a valuable tool in the study of pulsatile hormone secretion in small laboratory rodents.


Optimization of Triarylpyridinone Inhibitors of the Main Protease of SARS-CoV-2 to Low-Nanomolar Antiviral Potency.
Non-covalent inhibitors of the main protease (Mpro) of SARS-CoV-2 having a pyridinone core were previously reported with IC50 values as low as 0.018 μM for inhibition of enzymatic activity and EC50 values as low as 0.8 μM for inhibition of viral replication in Vero E6 cells. The series has now been further advanced by consideration of placement of substituted five-membered-ring heterocycles in the S4 pocket of Mpro and N-methylation of a uracil ring. Free energy perturbation calculations provided guidance on the choice of the heterocycles, and protein crystallography confirmed the desired S4 placement. Here we report inhibitors with EC50 values as low as 0.080 μM, while remdesivir yields values of 0.5-2 μM in side-by-side testing with infectious SARS-CoV-2. A key factor in the improvement is enhanced cell permeability, as reflected in PAMPA measurements. Compounds 19 and 21 are particularly promising as potential therapies for COVID-19, featuring IC50 values of 0.044-0.061 μM, EC50 values of ca. 0.1 μM, good aqueous solubility, and no cytotoxicity.


Maternal adiposity, smoking, and thyroid function in early pregnancy.
A high activity of the deiodinase type 2 has been proposed in overweight, obese, and smoking pregnant women as reflected by a high triiodothyronine (T3)/thyroxine (T4) ratio. We speculated how maternal adiposity and smoking would associate with different thyroid function tests in the early pregnancy. Cross-sectional study within the North Denmark Region Pregnancy Cohort. Maternal thyroid-stimulating hormone (TSH), total T4 (TT4), total T3 (TT3), free T4 (fT4), and free T3 (fT3) were measured in stored blood samples (median gestational week 10) by an automatic immunoassay. Results were linked to nationwide registers, and live-birth pregnancies were included. The associations between maternal adiposity (overweight or obese), smoking, and log-transformed TSH, fT3/fT4 ratio, and TT3/TT4 ratio were assessed using multivariate linear regression and reported as adjusted exponentiated β coefficient (aβ) with 95% CI. The adjusted model included maternal age, parity, origin, week of blood sampling, and diabetes. Altogether 5529 pregnant women were included, and 40% were classified with adiposity, whereas 10% were smoking. Maternal adiposity was associated with higher TSH (aβ 1.13 (95% CI 1.08-1.20)), whereas maternal smoking was associated with lower TSH in the early pregnancy (0.875 (0.806-0.950)). Considering the T3/T4 ratio, both maternal adiposity (fT3/fT4 ratio: 1.06 (1.05-1.07); TT3/TT4 ratio: 1.07 (1.06-1.08)) and smoking (fT3/fT4 ratio: 1.07 (1.06-1.09); TT3/TT4 ratio: 1.10 (1.09-1.12)) were associated with a higher ratio. In a large cohort of Danish pregnant women, adiposity and smoking showed opposite associations with maternal TSH. On the other hand, both conditions were associated with a higher T3/T4 ratio in early pregnancy, which may reflect altered deiodinase activity.


Experimental investigation of supertransmission for an intrinsic localized mode in a cyclic nonlinear transmission line.
In this experimental study of the nonlinear loss mechanism between traveling localized excitation and the underlying extended normal mode spectrum for a 1D lattice, three types of cyclic, electric, nonlinear transmission lines (NLTLs) are used. They are nonlinear capacitive, inductive, and capacitive+inductive NLTLs. To maintain a robust, steady-state traveling intrinsic localized mode (ILM), a traveling wave driver is used. The ILM loses energy because of a resonance between it and the extended NLTL modes. A wake field excitation is detected directly from ILM velocity experiments by the decrease in ILM speed and by the observation of the wake. Its properties are quantified via a two-dimensional Fourier map in the frequency-wavenumber domain, determined from the measured spatial-time voltage pattern. Simulations support and extend these experimental findings. We find for the capacitive+inductive NLTL configuration, when the two nonlinear terms are theoretically balanced, the wake excitation is calculated to become very small, giving rise to supertransmission over an extended driving frequency range.


How x-rays inhibit amphibian limb regeneration.
The effects of an inhibiting dose of 2,000 rad of X-rays on the regenerating limbs of axolotl larvae have been examined in a histological and cytological study. Particular attention was paid to the mitotic indices of normal and irradiated epidermal and blastemal cells. Both the characteristic pattern of epidermal mitotic stimulation which normally follows amputation and the later increase in blastemal mitoses are suppressed by irradiation. In most cells the effects are permanent, but in a small proportion a mitotic delay is induced and upon subsequent division chromosome damage in the form of micronuclei is revealed. Thus irradiated cells which do divide almost certainly die. These results are discussed in relation to other theories of X-ray inhibition of regeneration with particular reference to the view that irradiated cells can be reactivated.


ELectrophysiologic properties of bretylium tosylate on atrial myocardium.
The antifibrillatory property of bretylium tosylate was first observed in experimental atrial fibrillation, yet the cellular basis for this phenomenon has not been explored. The purpose of this study was to determine the electrophysiologic properties of bretylium tosylate on guinea pig atrial myocardium in the presence and absence of cholinergic influence. Bretylium (10(-6) M - 10(-4) M) produced a concentration-dependent prolongation of atrial action potential duration with a threshold concentration of 10(-5) M. This direct effect of bretylium was unaltered by blockade of beta-adrenergic receptors with propranolol (10(-6) M) or blockade of alpha-adrenergic receptors with phentolamine (10(-6) M). In a second series of experiments the muscarinic receptor blocking properties of bretylium were determined. Acetylcholine produced a concentration-dependent shortening of action potential duration in paced (200 ms) left atrial muscle strips. This well-recognized muscarinic effect was unaltered in the presence of bretylium (10(-6) M - 10(-3) M). These data indicate that bretylium tosylate physiologically exerts direct effects on the atrial myocardium to prolong action potential duration. This compound does not appear to physiologically antagonize the effects of acetylcholine and therefore its reported atrial antiarrhythmic properties cannot be explained by muscarinic receptor blockade.


2-(4-Iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25I-NBOMe): clinical case with unique confirmatory testing.
2C designer drugs have been in use since the 1970s, but new drugs continue to develop from substitutions to the base phenethylamine structure. This creates new clinical profiles and difficulty with laboratory confirmation. 2-(4-Iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25I-NBOMe) is a relatively new 2C drug that is more potent than structural 2C analogs; exposure reports are rare. Testing for 2C drugs is developing; specific testing for new analogs such as 25I-NBOMe is a challenge. These drugs do not reliably trigger a positive result on rapid drug immunoassays. Additionally, most facilities with confirmatory testing capabilities will not identify 25I-NBOMe; methods for detecting 25I-NBOMe in biological samples have not been clearly described nor have optimal metabolic targets for detecting 25I-NBOMe ingestion. An 18-year-old female presented following use of 25I-NBOMe. She had an isolated brief seizure, tachycardia, hypertension, agitation, and confusion. She improved with intravenously administered fluids and benzodiazepines and was discharged 7 h postingestion. Urine was analyzed using quantitative LC-MS/MS methodology for 25I-NBOMe, 2-(4-chloro-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)-methyl]ethanamine (25C-NBOMe), and 2-(2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25H-NBOMe). 25I-NBOMe was found at a concentration of 7.5 ng/mL, and 25H-NBOMe was detected as well. Additional testing was pursued to characterize the metabolism of 25I-NBOMe; the sample was reanalyzed with UPLC-time-of-flight mass spectrometry to identify excreted metabolites. The sample was additionally analyzed for the presence of 2,5-dimethoxy-4-iodophenethylamine (2C-I), 4-bromo-2,5-dimethoxyphenethylamine (2C-B), and 1-(2,5-dimethoxy-4-ethylphenyl)-2-aminoethane (2C-E). This is a report of a patient presenting following exposure to 25I-NBOMe, a dangerous member of the evolving 2C drug class. The exposure was confirmed in a unique manner that could prove helpful in guiding further patient analysis and laboratory studies.


High prevalence of antibodies against canine adenovirus (CAV) type 2 in domestic dog populations in South Africa precludes the use of CAV-based recombinant rabies vaccines.
Rabies in dogs can be controlled through mass vaccination. Oral vaccination of domestic dogs would be useful in the developing world, where greater vaccination coverage is needed especially in inaccessible areas or places with large numbers of free-roaming dogs. From this perspective, recent research has focused on development of new recombinant vaccines that can be administered orally in a bait to be used as adjunct for parenteral vaccination. One such candidate, a recombinant canine adenovirus type 2 vaccine expressing the rabies virus glycoprotein (CAV2-RG), is considered a promising option for dogs, given host specificity and safety. To assess the potential use of this vaccine in domestic dog populations, we investigated the prevalence of antibodies against canine adenovirus type 2 in South African dogs. Blood was collected from 241 dogs from the Gauteng and KwaZulu-Natal provinces. Sampled dogs had not previously been vaccinated against canine adenovirus type 1 (CAV1) or canine adenovirus type 2 (CAV2). Animals from both provinces had a high percentage of seropositivity (45% and 62%), suggesting that CAV2 circulates extensively among domestic dog populations in South Africa. Given this finding, we evaluated the effect of pre-existing CAV-specific antibodies on the efficacy of the CAV2-RG vaccine delivered via the oral route in dogs. Purpose-bred Beagle dogs, which received prior vaccination against canine parvovirus, canine distemper virus and CAV, were immunized by oral administration of CAV2-RG. After rabies virus (RABV) infection all animals, except one vaccinated dog, developed rabies. This study demonstrated that pre-existing antibodies against CAV, such as naturally occurs in South African dogs, inhibits the development of neutralizing antibodies against RABV when immunized with a CAV-based rabies recombinant vaccine.


Optoelectromechanical phase shifter with low insertion loss and a 13π tuning range.
We present an on-chip optoectromechanical phase shifter with low insertion loss and low half-wave voltage using a silicon nitride platform. The device is based on a slot waveguide in which the electrostatic displacement of mechanical structures results in a change of the effective refractive index. We achieve insertion loss below 0.5 dB at a wavelength of 1550 nm in a Mach-Zehnder Interferometer with an extinction ratio of 31 dB. With a phase tuning length of 210 µm, we demonstrate a half-wave voltage of Vπ = 2.0 V and a 2π phase shift at V2π = 2.7 V. We measure phase shifts up to 13.3 π at 17 V. Our devices can be operated in the MHz range and allow for the generation of sub-µs pulses.


Mangiferin for the Management of Liver Diseases: A Review.
The liver is a digestive and metabolic organ, and several factors can induce liver damage, which is a severe threat to human health. As a natural polyphenolic compound, mangiferin belongs to xanthone glucoside and mainly exists in many plants, such as mango. It is notorious that mangiferin has remarkable pharmacological activities such as anti-inflammatory, anti-tumor, antioxidative stress, antiviral and so on. Emerging evidence indicates the therapeutic benefits of mangiferin against liver disease, including liver injury, nonalcoholic fatty liver disease, alcoholic liver disease, liver fibrosis, and hepatocellular carcinoma. This review aims to summarize the possible underlying signaling mediated by mangiferin in liver disease treatment and the available findings of mangiferin, which can be used to treat different liver diseases and may contribute to mangiferin as a therapeutic agent for liver disease in humans.


Factors associated with access blood flow in native vessel arteriovenous fistulae.
Access blood flow (Qa) identifies stenosis in patients with native vessel AV fistulae (AVF), but data on factors that are associated with Qa in normally functioning accesses are sparse. Such factors could be used in conjunction with Qa to improve the diagnostic performance of screening. We examined the relationship between Qa and certain clinical characteristics in a large group of patients with AVF. This was a retrospective study of incident and prevalent haemodialysis patients treated at a single institution, all of whom had a functioning AVF during the study period. Qa was measured bimonthly using ultrasound dilution in all subjects. Mixed models were used to explore the relationship between Qa and a group of independent variables, including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), diabetes mellitus, patient age, sex, height, body mass index (BMI) and AVF location (forearm vs upper arm). A total of 4084 Qa measurements was made in 294 patients. Univariate analysis found that younger patient age, non-diabetic status, higher blood pressure (SBP, DBP, MAP, all at the time of Qa measurement), upper arm AVF location and overweight status (BMI >/=25) were significantly associated with Qa. SBP appeared to be more strongly associated with Qa than either DBP or MAP. Patient sex, height and interval between access creation and Qa measurement were not significantly associated with Qa. Tests for interaction suggested that the association between SBP and age and Qa varied significantly by access location. In a multivariate model, SBP, overweight status and diabetic status were independently associated with Qa. The strength of the association between these characteristics and Qa appeared to be clinically relevant. Our findings suggest that a single Qa threshold for angiography in all patients may be simplistic, and that the optimal threshold might vary by patient subgroup. The strong association between SBP and Qa suggests that adjusting Qa for SBP may improve the specificity of access screening. Further work is required to determine whether such modifications to current practice would improve the predictive power of Qa measurements for detection of stenosis in AVF.


Introducing the Twitter Impact Factor: An Objective Measure of Urology's Academic Impact on Twitter.
Social media use in academia and urology is rising. Specifically, individual journals now have Twitter accounts (Twitter Inc, San Francisco, CA, USA) and regularly tweet academic content. To present and evaluate the Twitter impact factor (TIF), a novel means of measuring a journal's academic influence in the realm of social media. Journal Citation Reports (JCR; Thomson Reuters, New York, NY, USA) for 2014 was queried for urologic academic journals. English-language journals with active Twitter accounts since 2013 were included. The total number of followers, tweets, and retweets over a 2-yr period were collected. Each journal's TIF was calculated based on the number of retweets per original relevant tweet. Comparisons between the TIF and the journal impact factor (JIF) as well as the Klout score were made using the Pearson correlation. Of 33 journals listed in the JCR for 2014, 7 (21%) had a Twitter presence as of 2013. The number of JCR-listed journals with a Twitter handle increased by 29% in 2014. There was an increase in the mean number of relevant tweets per journal during the study period and a 130% increase in the number of retweets over 1 yr. European Urology (1.80) and BJU International (1.46) had the highest TIFs. The journals with the highest number of Twitter followers were European Urology (5807) and the Journal of Urology (4402). The journals with the highest numbers of relevant tweets were European Urology (1159) and BJU International (1090). There was a positive but statistically insignificant association between the TIF and the JIF (r=0.64, p=0.12). There was a strongly positive linear correlation between the TIF and the Klout score (r=0.84, p=0.0086). With the increasing use of social media by individuals and academic journals, the TIF can be a useful tool to measure the academic reach and impact of a journal on Twitter. Social media is an increasing part of the way in which practitioners and academicians communicate. The TIF can be used to analyze the impact of journal Twitter feeds and their social media content.


Serum Vitamin A Levels May Affect the Severity of Ocular Graft-versus-Host Disease.
Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established therapeutic option for a range of inherited and acquired hematological disorders. However, graft-versus-host disease (GVHD) remains the leading cause of non-relapse mortality in allogeneic HSCT recipients. Ocular involvement occurs in up to 80% of chronic GVHD patients. In our cases, the diagnosis of vitamin A deficiency was suspected for GVHD patients. Serum vitamin A measurements were conducted to confirm clinical suspicions. Our study revealed significant decrease in serum levels of vitamin A in chronic liver GVHD patients. Although there have been many studies evaluating ocular manifestations in patients with GVHD, the present study is, to our knowledge, the first to study the relationship between vitamin A and ocular manifestations of GVHD in humans. Our data suggest that vitamin A deficiency affects the severity of ocular GVHD in adults.


An analogous wood barrel theory to explain the occurrence of hormesis: A case study of sulfonamides and erythromycin on Escherichia coli growth.
Hormesis has aroused much attention during the past two decades and may have great implications on many fields, including toxicology and risk assessment. However, the observation of hormesis remains challenged under laboratory conditions. To determine favorable conditions under which to observe hormesis, we investigated the hormetic responses of Escherichia coli (E. coli) upon exposure of different concentrations of sulfonamides and erythromycin at different time points and in different culture media: Luria-Bertani (LB) broth and Mueller Hinton (MH) broth. Our results reveal that the antibiotics, both individually and combined, produce hormetic effects on E. coli growth in MH broth at the stationary phase, with the maximum stimulatory response increasing with time. However, in LB broth, the hormetic response was not observed, which can be explained by an analogous "wood barrel theory". Our study suggests that the culture medium and time should be taken into consideration in hormetic studies, and compound mixtures should also receive more attention for their potential to induce hormesis.


The C-Terminal Effector Domain of Non-Structural Protein 1 of Influenza A Virus Blocks IFN-β Production by Targeting TNF Receptor-Associated Factor 3.
Influenza A virus non-structural protein 1 (NS1) antagonizes interferon response through diverse strategies, particularly by inhibiting the activation of interferon regulatory factor 3 (IRF3) and IFN-β transcription. However, the underlying mechanisms used by the NS1 C-terminal effector domain (ED) to inhibit the activation of IFN-β pathway are not well understood. In this study, we used influenza virus subtype of H5N1 to demonstrate that the NS1 C-terminal ED but not the N-terminal RNA-binding domain, binds TNF receptor-associated factor 3 (TRAF3). This results in an attenuation of the type I IFN signaling pathway. We found that the NS1 C-terminal ED (named NS1/126-225) inhibits the active caspase activation and recruitment domain-containing form of RIG-I [RIG-I(N)]-induced IFN-β reporter activity, the phosphorylation of IRF3, and the induction of IFN-β. Further analysis showed that NS1/126-225 binds to TRAF3 through the TRAF domain, subsequently decreasing TRAF3 K63-linked ubiquitination. NS1/126-225 binding also disrupted the formation of the mitochondrial antiviral signaling (MAVS)-TRAF3 complex, increasing the recruitment of IKKε to MAVS; ultimately shutting down the RIG-I(N)-mediated signal transduction and cellular antiviral responses. This attenuation of cellular antiviral responses leads to evasion of the innate immune response. Taken together, our findings offer an important insight into the interplay between the influenza virus and host innate immunity.


CXCL1 Derived from Mammary Fibroblasts Promotes Progression of Mammary Lesions to Invasive Carcinoma through CXCR2 Dependent Mechanisms.
With improved screening methods, the numbers of abnormal breast lesions diagnosed in women have been increasing over time. However, it remains unclear whether these breast lesions will develop into invasive cancers. To more effectively predict the outcome of breast lesions and determine a more appropriate course of treatment, it is important to understand the underlying mechanisms that regulate progression of non-invasive lesions to invasive breast cancers. A hallmark of invasive breast cancers is the accumulation of fibroblasts. Fibroblast proliferation and activation in the mammary gland is in part regulated by the Transforming Growth Factor beta1 pathway (TGF-β). In animal models, TGF-β suppression of CCL2 and CXCL1 chemokine expression is associated with metastatic progression of mammary carcinomas. Here, we show that transgenic overexpression of the Polyoma middle T viral antigen in the mouse mammary gland of C57BL/6 mice results in slow growing non-invasive lesions that progress to invasive carcinomas in a stage dependent manner. Invasive carcinomas are associated with accumulation of fibroblasts that show decreased TGF-β expression and high levels of CXCL1, but not CCL2. Using co-transplant models, we show that decreased TGF-β signaling in fibroblasts contribute to mammary carcinoma progression through enhancement of CXCL1/CXCR2 dependent mechanisms. Using cell culture models, we show that CXCL1 mediated mammary carcinoma cell invasion through NF-κB, AKT, Stat3 and p42/44MAPK dependent mechanisms. These studies provide novel mechanistic insight into the progression of pre-invasive lesions and identify new stromal biomarkers, with important prognostic implications.


[Cylindrical cancer of the lung. Analysis of a series of 191 cases].
The authors analyse 191 cases of cylindrical carcinoma of the lung. Study of the clinical and radiological characteristics, as well as the course, revealed the following: the reduced male predominance of this type of lesion, the often distal site and the primary pulmonary nature. The prognosis is identical to that for squamous forms: 31% survivors at 5 years.


Evaluation of Dissolution in the Lower Intestine and Its Impact on the Absorption Process of High Dose Low Solubility Drugs.
The purpose of this article was two-fold: first, to optimize a recently proposed two-stage single-compartment in vitro test for the evaluation of dissolution in the lower intestine with the mini-paddle apparatus in the fasted and fed state using two model high dose, low solubility drugs [sulfasalazine (Azulfidine) and micronized aprepitant] and one mesalamine colon targeting product (Asacol, 400 mg/tablet); second, to evaluate the impact of passive absorption from the lower intestine on the overall absorption process using three model high dose, low solubility drugs [micronized aprepitant, SB705498, and albendazole (Zentel)]. The intensity of agitation and the physicochemical characteristics of fluids simulating the environment in the distal ileum and the proximal colon were optimized and the importance of solid particles was evaluated. Dissolution data collected under conditions simulating the upper and lower intestine were coupled with physiologically based oral absorption modeling to simulate the average plasma levels or the average absorption process. Reliability of the modeling approach was evaluated based on previously collected data in adults. The impact of solid particles on dissolution in the lower intestine was found to be clinically insignificant for Asacol tablets, as well as for sulfasalazine (Azulfidine) and micronized aprepitant. Average plasma levels (micronized aprepitant and SB705498) and cumulative amount absorbed (albendazole) could be adequately simulated by referring only to events in the upper gastrointestinal lumen, indicating that the impact of absorption from the lower intestine on actual plasma levels was minimal. Dissolution of Asacol tablets and immediate release formulations in the lower intestine can be adequately evaluated by employing Level II biorelevant media. However, simulation of actual drug particle dissolution in the lower intestine is not typically necessary for adequate prediction of oral absorption from immediate release formulations containing discrete, dispersed particles of lipophilic drugs.


COEVOLUTION IN BACTERIAL-PLASMID POPULATIONS.
Evolutionary changes are described in plasmid-containing strains isolated after approximately 800 generations of growth in glucose-limited chemostat culture. The reproductive fitness increased dramatically over this period. Genetic changes associated with the increases in fitness were localized to both the bacterial and the plasmid chromosomes. In addition, some of the genetic changes on the bacterial and the plasmid chromosomes interact to minimize the deleterious effect of the plasmid. Thus, the changes observed may be considered coevolutionary. Reductions in the deleterious effects of the plasmid were shown to be associated with a decrease in plasmid copy number and an increase in the rate of segregational loss of the plasmid.


First Detection of a Fosfomycin Resistance Gene, fosA7, in Salmonella enterica Serovar Heidelberg Isolated from Broiler Chickens.
We previously described Salmonella enterica serovar Heidelberg isolates harboring a chromosomal gene cluster similar to the glutathione S-transferase gene, a putative fosA gene conferring resistance to fosfomycin. Here, we show that this new gene, named fosA7, confers resistance to fosfomycin. The introduction of fosA7 into the fosfomycin-susceptible Salmonella enterica serovar Enteritidis resulted in a substantial increase in the fosfomycin MIC. This finding increases the awareness of antibiotic resistance in Salmonella Heidelberg from broilers as related to the food safety and public health.


Association of proteinuria and incident atrial fibrillation in patients with diabetes mellitus: a population-based senior cohort study.
Diabetes mellitus (DM) is considered an independent risk factor for atrial fibrillation (AF). The excess risk in relation to the presence of proteinuria has not been well elucidated. Our aim was to determine the association between the incidence of AF and proteinuria in diabetic population. A total of 240,499 individuals aged ≥ 60 years from the Korea National Health Insurance Service-Senior cohort from 2004 to 2014 were included. 4.2% of individuals with DM and 3.7% of controls were diagnosed with AF during a median follow-up period of 7.2 years. Amongst controls (participants without proteinuria and DM), DM only, proteinuria only, and DM with proteinuria groups, the crude incidences of AF were 0.58, 0.70, 0.96, 1.24 per 100 person-years respectively. Compared with controls, the weighted risk of AF was increased by 11% (hazard ratio = 1.11, 95% confidence interval = 1.02-1.20, P = .001), 48% (hazard ratio = 1.48, 95% confidence interval = 1.30-1.69, P < .001), and 66% (hazard ratio = 1.66, 95% confidence interval = 1.26-2.18, P < .001) in the DM only, proteinuria only, and DM with proteinuria groups, respectively (P for trend < .001). Degree of proteinuria in diabetic patients was associated with a significantly higher rate of incident AF in dose dependent manner. Thus, assessing proteinuria by a simple urine dipstick test could provide a useful adjunct to risk assessment for AF in elderly population with DM.


iTRAQ-Based Proteomic Analysis of Sublethally Injured Escherichia coli O157:H7 Cells Induced by High Pressure Carbon Dioxide.
High pressure carbon dioxide (HPCD) could cause sublethally injured cells (SICs), which may cause food poisoning and spoilage during food storage and limit its application. Therefore, the formation of SICs of Escherichia coli O157:H7 was investigated by isobaric tag for relative and absolute quantification (iTRAQ) proteomic methods in this study for better controlling the SICs induced by HPCD. A total of 2,446 proteins was identified by iTRAQ, of which 93 and 29 were significantly differentially expressed in the SICs compared with live control cells (CKL) and dead control cells (CKD), respectively. Among the 93 differentially expressed proteins (DEP) in the SICs compared with CKL, 65 proteins showed down-regulation and 28 showed up-regulation. According to the comprehensive proteome coverage analysis, the SICs survived under HPCD by reducing carbohydrate decomposing, lipid transport and metabolism, amino acid transport and metabolism, transcription and translation, DNA replication and repair. Besides, the SICs showed stress response, DNA damage response and an increased carbohydrate transport, peptidoglycan synthesis and disulfide bond formation to HPCD. Among the 29 DEP in the SICs compared with CKD, 12 proteins showed down-regulation and 17 showed up-regulation. According to the comprehensive proteome coverage analysis, the SICs survived under HPCD by accumulation of cell protective agents like carbohydrates and amino acids, and decreasing transcription and translation activities. Results showed that the formation of the SICs with low metabolic activity and high survival ability was a survival strategy for E. coli O157:H7 against HPCD.


Transition-Metal-Free ipso-Functionalization of Arylboronic Acids and Derivatives.
Arylboronic acids and their derivatives have been widely exploited as important synthetic precursors in organic synthesis, materials science, and pharmaceutical development. In addition to numerous applications in transition-metal-mediated cross-coupling reactions, transition-metal-free transformations involving arylboronic acids and derivatives have recently received a surge of attention for converting the C-B bond to C-C, C-N, C-O, and many other C-X bonds. Consequently, a wide range of useful compounds, e.g., phenols, anilines, nitroarenes, and haloarenes, have been readily synthesized. Amongst these efforts, many versatile reagents have been developed and a lot of practical approaches demonstrated. The research in this promising field is summarized in the current review and organized on the basis of the type of bonds being formed.


A novel reticular stromal structure in lymph node cortex: an immuno-platform for interactions among dendritic cells, T cells and B cells.
For efficient adaptive immunity, the lymph nodes (LNs) are equipped with a strategically organized microarchitecture, which is largely supported by the reticular network (RN). The RN can be clearly visualized by fluorescence immunohistochemistry coupled with confocal imaging using a monoclonal antibody, ER-TR7, and can be subdivided into four structurally distinct regions, each of which correlates well with the location of distinct immune cell subsets. In addition, we noticed a characteristic reticular structure designated the 'cortical ridge' at the boundary of the T and B zone, in which dendritic cells are preferentially accumulated. In vitro adhesion assays of frozen sections demonstrated a preference of dendritic cells for the cortical ridge rather than the deeper cortex. Adoptive transfer experiments also demonstrated that antigen-bearing dendritic cells migrated to this region from peripheral tissues, especially in the vicinity of the high endothelial venules, and were anchored on the reticular fibers waiting to interact with the antigen-specific T cells. Taken together, the findings obtained in this study provide new insights into how the LN stromal reticulum works as a specialized 'immuno-platform' for tissue compartmentalization and the immune response.


Acantholytic cells exfoliated from pemphigus vulgaris of the uterine cervix. A case report.
Pemphigus vulgaris of the uterine cervix is rare and almost always associated with cutaneous or mucosal lesions elsewhere on the body. Without a history of pemphigus, acantholytic cells in cervical smears may be misdiagnosed as malignant ones. A 52-year-old female presented with a vaginal discharge, and a routine cervical smear was collected for cytology. The smear displayed atypical cells lying singly and in loose clusters, having vesicular nuclei, a thin nuclear membrane, prominent nucleoli and well-defined cytoplasmic margins. These were labeled atypical glandular cells of undetermined significance, and colposcopic examination and biopsy were advised. On colposcopy vesicular lesions and erosions were noticed on the cervix. The biopsy revealed typical intact as well as denuded suprabasal bullae of pemphigus vulgaris. On reevaluation of the cytologic smear, the cytomorphologic features correlated well with the acantholytic cells of pemphigus. Thorough reexamination of the patient revealed 2 tiny vesicles on the oral mucosa that, on biopsy, confirmed the diagnosis of pemphigus vulgaris. Cytopathologists should be aware of the typical cytomorphologic features of pemphigus vulgaris and, in an appropriate clinical setting, should be able to diagnose or at least suspect this entity in even rare sites like the cervix. A false positive diagnosis of malignancy can be avoided if the cytologic findings are judiciously correlated with the history and with clinical and colposcopic examinations.


Diagnosis and treatment of accessory parotid gland masses.
Accessory parotid glands are true parotid tissue lying distinctly separate from the parotid gland proper. They lie along and drain into Stensen's duct. Although literature describing the accessory parotid gland is limited, its anatomy and pathology have been described. Controversies exist in the literature regarding the diagnosis and management of pathological changes seen in these glands. We have found magnetic resonance imaging to be extremely helpful in their diagnosis and treatment. A review of the literature and an illustrative example are presented.


Using pressure-volume curves to set proper PEEP in acute lung injury.
The evolution of respiratory care on patients with acute respiratory distress syndrome (ARDS) has been focused on preventing the deleterious effects of mechanical ventilation, termed ventilator-induced lung injury (VILI). Currently, reduced tidal volume is the standard of ventilatory care for patients with ARDS. The current focus, however, has shifted to the proper setting of positive end-expiratory pressure (PEEP). The whole lung pressure-volume (P/V) curve has been used to individualize setting proper PEEP in patients with ARDS, although the physiologic interpretation of the curve remains under debate. The purpose of this review is to present the pros and cons of using P/V curves to set PEEP in patients with ARDS. A systematic analysis of recent and relevant literature was conducted. It has been hypothesized that proper PEEP can be determined by identifying P/V curve inflection points. Acquiring a dynamic curve presents the key to the curve's bedside application. The lower inflection point of the inflation limb has been shown to be the point of massive alveolar recruitment and therefore an option for setting PEEP. However, it is becoming widely accepted that the upper inflection point (UIP) of the deflation limb of the P/V curve represents the point of optimal PEEP. New methods used to identify optimal PEEP, including tomography and active compliance measurements, are currently being investigated. In conclusion, we believe that the most promising method for determining proper PEEP settings is use of the UIP of the deflation limb. However, tomography and dynamic compliance may offer superior bedside availability.


Interactions between season of birth, chronological age and genetic polymorphisms in determining later-life chronotype.
Human chronotype, the temporal pattern of daily behaviors, is influenced by postnatal seasonal programming and ageing. The aim of this study was to investigate genetic variants that are associated with season of birth programming and longitudinal chronotype change. Longitudinal sleep timing and genotype data from 1449 participants were collected for up to 27 years. Gene-environment interaction analysis was performed for 445 candidate single nucleotide polymorphisms that have previously been associated with chronotype. Associations were tested using linear mixed model. We identified 67 suggestively significant genomic loci that have genotype-ageing interaction and 25 genomic loci that may have genotype-season of birth interaction in determining chronotype. We attempted to replicate the results using longitudinal data of the UK Biobank from approximately 30,000 participants. Biological functions of these genes suggest that epigenetic regulation of gene expression and neural development may have roles in these processes. The strongest associated gene for sleep trajectories was ALKBH5, which has functions of DNA repair and epigenetic regulation. A potential candidate gene for postnatal seasonal programming was SIRT1, which has previously been implicated in postnatal programming, ageing and longevity. Genetic diversity may explain the heterogeneity in ageing-related change of sleep timing and postnatal environmental programming of later-life chronotype.


Daytime Atmospheric Halogen Cycling through Aqueous-Phase Oxygen Atom Chemistry.
Halogen atoms are important atmospheric oxidants that have unidentified daytime sources from photochemical halide oxidation in sea salt aerosols. Here, we show that the photolysis of nitrate in aqueous chloride solutions generates nitryl chloride (ClNO2) in addition to Cl2 and HOCl. Experimental and modeling evidence suggests that O(3P) formed in the minor photolysis channel from nitrate oxidizes chloride to Cl2 and HOCl, which reacts with nitrite to form ClNO2. This chemistry is different than currently accepted mechanisms involving chloride oxidation by OH and could shift our understanding of daytime halogen cycling in the lower atmosphere.


Differential expression of melatonin receptor subtypes MelIa, MelIb and MelIc in relation to melatonin binding in the male songbird brain.
Previous autoradiography studies illustrated that several areas of the avian brain can bind the pineal hormone melatonin. In birds, there are three melatonin receptor (MelR) subtypes: MelIa, MelIb and MelIc. To date, their brain distribution has not been studied in any passerine bird. Therefore, we investigated mRNA distribution of MelR subtypes in adjacent sections of the brain of two songbirds, the blackcap and the zebra finch, in parallel with that of 2-[¹²⁵I]-iodomelatonin (IMEL) binding sites in the same brains. The general pattern of receptor expression shown by in situ hybridization of species-specific probes matched well with that of IMEL binding. However, the expression of the three subtypes was area specific with similar patterns in the two species. Some brain areas expressed only one receptor subtype, most brain regions co-expressed either MelIa with MelIb or MelIa with MelIc, whereas few areas expressed MelIb and MelIc or all three receptor subtypes. Since many sensory areas, most thalamic areas and subareas of the neopallium, a cortex analogue, express MelR, it is likely that most sensory motor integration functions are melatonin sensitive. Further, the area-specific expression patterns suggest that the regulatory role of melatonin differs among different brain areas. Since subareas of well-defined neural circuits, such as the visual system or the song control system, are equipped with different receptor types, we hypothesize a diversity of functions for melatonin in the control of sensory integration and behavior.


Preliminary evaluation of foetal liver volume by three-dimensional ultrasound in women with gestational diabetes mellitus.
The aim of the study was to assess the standard foetal biometric measurements and foetal liver volume (FLV) in pregnancies complicated by gestational diabetes mellitus (GDM) at the time of GDM screening and to compare the results with foetuses in normal pregnancies. Ninety-seven pregnant women with normal singleton uncomplicated pregnancies between 24 and 28 weeks of gestation were allocated into GDM (+) (n: 33) and GDM (-) (n: 64) groups based on their 75 g oral glucose tolerance test results. Foetal biometric measurements and FLV measurements of the groups were compared. Although there were no significant differences in the standard biometric measurements between the two groups, FLV was significantly higher in the women with GDM (p < .01). The ROC analysis implied that with a cut-off value of FLV of 32.72 cm3 for GDM prediction, the sensitivity was 78.8% and specificity was 56.3%. We suggest that FLV measurements during the second-trimester ultrasound scanning may be a tool for the prediction of GDM in the obstetric population. Impact statement What is already known on this subject? GDM is an important pregnancy disease, because of its possible foetal and maternal complications. Besides the standard biometric measurements, some other foetal body dimensions such as the anterior abdominal wall thickness, skinfold thickness, adipose tissue thickness, Wharton's jelly thickness, foetal liver length and foetal liver volume (FLV) have been evaluated as ultrasound parameters of glycaemic control. While the evaluation of foetal liver dimensions has a role in identifying foetal growth acceleration, previous studies addressed patients with insulin-dependent diabetes mellitus rather than gestational diabetes mellitus, utilised two-dimensional ultrasound and did not argue the diagnostic value of these findings. What do the results of this study add? In our study, besides the standard biometric measurements, the FLV measurements were evaluated by a three-dimensional ultrasound. Although there were no significant differences in the standard biometric measurements between the GDM (+) and GDM (-) groups, the FLV was significantly higher in women with GDM. The FLV was found to be a potential predictive factor for GDM. The ROC analysis implied that as a cut-off value of FLV of 32.72 cm3 for GDM prediction, the sensitivity was 78.8% and the specificity was 56.3%. What are the implications of these findings for clinical practise and/or further research? Screening for GDM with oral glucose tolerance test within the limited weeks of gestation may not always be feasible. On the other hand, the mid-trimester ultrasound scanning is done almost in all pregnancies. Accordingly, FLV measurement might be an alternative method for the GDM diagnosis.


The political economy of health policy in Sub-Saharan Africa.
This paper discusses the health status of Sub-Saharan Africa focusing on infectious and parasitic diseases, HIV/AIDS, maternal and child health, famine, and political instability. Its contention is that Africa is stuck in the second stage of the demographic transition (high birth rate, low death rate) and the first stage of the epidemiological transition (deaths related to pestilence, famine, and war). Africa's lack of sustainable development is attributed to ineffective governmental policy and leadership. The prognosis is that the health and well-being of Africa's most vulnerable population, women and children, will improve when government shifts its attention from external funding and affairs to internal and concentrates on retaining Africa's 'talented tenth'; that the 'brain drain' and political instability has robbed Africa of its most talented young people, medical and science professionals, who are needed to provide primary care and development to a region with a high mortality rate, a low life expectancy, and a low per capita income.


In Situ Formation of Co9 S8 /N-C Hollow Nanospheres by Pyrolysis and Sulfurization of ZIF-67 for High-Performance Lithium-Ion Batteries.
Co9 S8 is considered a promising candidate as the anode material in lithium-ion batteries (LIBs) because of its remarkable electrical conductivity, high theoretical capacity, and low cost. However, the practical application of Co9 S8 is greatly restricted because of its poor cycling stability and rate performance, which result mainly from the large volume expansion and dissolution of the polysulfide intermediates during the charge/discharge process. In this report, Co9 S8 embedded in N-rich carbon hollow spheres are successfully designed and synthesized through an in situ pyrolysis and sulfurization process, employing the well-known ZIF-67 as the precursor and ethanethiol as the sulfur source. Co9 S8 nanoparticles embedded in the N-rich hollow carbon shell exhibit excellent lithium storage properties at a high charge/discharge rate. A discharge capacity of 784 mAh g-1 is obtained upon battery testing at a current density of 1 C (544 mA g-1 ). Even upon cycling at a current density of 4 C, the as-prepared Co9 S8 /N-C can still deliver a discharge capacity of 518 mAh g-1 . The excellent battery performance can be attributed to the hollow structure as well as the N-rich carbon encapsulation. Moreover, this metal-organic framework sulfurization route also shows good generality for the synthesis of other metal sulfide-carbon composites such as ZnS/N-C and Cu2 S/C.


[The establishment of the museum of Hôpital Saint-Louis: chronological milestones and important elements].
Created in 1865, by Alphonse Devergie, physician and head of one of the medical departments in Saint-Louis hospital, the first iconographic collection of the museum was made by water-colours, photographs from the atlas by Hardy and Montméja. Financially supported by the assistance Publique in Paris, thanks to the interest of its manager, Armand Husson, the museum was then enriched by the wax moulages produced by Jules Baretta, from 1867 onwards. Due to the development of the collection, the erection of a specific building was soon regarded as a necessity. The attention given to the project, by Bourneville, City Councellor in Paris, made it possible. First managed by Charles Lailler, physician in Saint-Louis, the museum was definitely located, with the medical library (later called Bibliothèque Henri Feulard), in an independent building, inaugurated August 5th 1889 on the opening of the first International Congress of Dermatology and Syphilology. This new museum, still existing in its original condition, was a part of the restoration of the international influence of the French school of dermatology.


Identification and Quantification of Tylosin in Animal Feed by Liquid Chromatography Combined with Electrospray Ionisation Mass Spectrometry.
The authorisation of tylosin as feed additive was withdrawn for reasons of human health concerning resistance of pathogenic bacteria. An analytical method for the identification and quantification of tylosin in animal feed was developed and validated. The samples were extracted using an acidified methanol:water mixture and solid-phase extraction was employed for the isolation of the antibiotic from diluted feed samples. Tylosin was analysed by liquid chromatography with electrospray ionisation mass spectrometric detection. The method's performance was evaluated in adherence to the Commission Decision 2002/657/EC. The recovery of the analyte from spiked samples was determined to be in the range from 78.9% to 108.3% depending on tylosin concentrations. The CCα and CCβ values for tylosin in feeds were determined at 0.085 mg kg-1 and 0.091 mg kg-1, respectively. The method detection limit was found to be 0.035 mg kg-1 and the quantification limit 0.05 mg kg-1. The applicability of the developed method was tested by analysing real feed samples. A reliable LC-MS method was developed to identify and quantify tylosin in animal feed with a good repeatability and a high specificity and sensitivity. Because of these characteristics, the proposed method is applicable and could be deemed necessary within the field of feed control and safety.


How adolescents construct their future: the effect of loneliness on future orientation.
This study examined the effect of loneliness, gender, and two dimensions of prospective life domains on adolescent future orientation. Future orientation was studied in four prospective domains: social relations, marriage and family, higher education and work and career. These domains are described in terms of two dimensions: theme (relational vs. instrumental) and distance (near vs. distant future). Data collected from Israeli Jewish adolescents (11th graders) were analysed by repeated measures ANOVAs and ANCOVAs (covariate: depressive experiences) for seven future orientation variables: value, expectance, control (motivational variables), hopes, fears (cognitive representation variables), exploration, commitment (behavioural variables). As predicted, lonely adolescents scored lower than socially embedded adolescents on future orientation variables applied to the relational and near future domains and lonely boys scored lower than lonely girls. However, effects were found only on the three future orientation motivational variables and not on the cognitive representation and behavioural variables. Contrary to prediction controlling for the effect of depressive experiences did not reduce the effect of loneliness on the future orientation variables, but reduced the tendency of adolescents to score higher on all future orientation variables in the instrumental than in the relational prospective domains. The contribution of these findings to the understanding of adolescent loneliness and future orientation was discussed and directions for future research were suggested.


Extracranial aneurysms of the carotid artery.
Aneurysms of the extracranial carotid artery represent a serious disease because of possible cerebral embolism and aneurysm rupture. Between 1960 and 1979, 28 aneurysms of the extracranial carotid artery were seen in 27 patients at our institution. Twenty-six of these patients noticed a pulsating tumor, 12 patients had neurological symptoms; 2 aneurysms were ruptured. Five times the external carotid artery, and 3 times the internal carotid artery were ligated without neurological symptoms. After aneurysm resection, the carotid artery was reconstructed in 4 cases by direct suture, and in 2 cases by patch angioplasty. Reconstruction was accomplished with a tube-graft in 9 instances, once an extra-intracranial shunt had to be performed in advance. Two patients developed neurological deficiencies after the operation (8.7%), in one of them these were permanent. In the follow-up, 20 patients were without symptoms (87%), 3 patients died after the operation (peri-operative mortality 13%). Out of the 5 non-operated patients 2 died after a short time: one of an acute myocardial infarction and one of an extensive cerebro-vascular infarction. Two patients with asymptomatic internal carotid aneurysm refused the operation and are without symptoms for 2 and 40 years respectively. Because of the potential risks of cerebro-vascular infarction and aneurysm rupture, good results of operative treatment call for an aggressive surgical approach in dealing with extracranial carotid aneurysms.


Characteristics of COVID-19 and mortality-associated factors during the first year of the pandemic in southeast Mexico.
Aim: The present study was designed to evaluate the clinical characteristics of COVID-19 and mortality-associated factors during the first year of the pandemic in patients from southeastern Mexico. Patient & methods: A total of 953 records from patients with COVID-19 were cross-sectionally studied in a primary care hospital in southeast Mexico between 2020 and 2021. Results: The prevalent symptoms were fever (78.6%), cough (80.5%) and headache (82.8%) and dyspnea reached 13.5%. The mortality rate was 7.63% and the clinical variables associated with it were age >60 years, hypertension, severe disease, radiographic pneumonia, days to diagnosis and having two Mayan surnames. Conclusion: Future health strategies should consider age, comorbidities, disease severity, clinical manifestations and possessing ethnicity of risk (i.e., Mayan genetic background).


The miR-203/SNAI2 axis regulates prostate tumor growth, migration, angiogenesis and stemness potentially by modulating GSK-3β/β-CATENIN signal pathway.
Dysregulation of microRNA expression plays a pivotal role in the initiation and progression of a variety of human carcinomas including prostate cancer. Our previous studies have demonstrated that the silence of miR-203 contributes to the invasiveness of malignant breast cancer cells by targeting SNAI2. However, the effects and underlying mechanisms of miR-203/SNAI2 axis in prostate cancer have not been elucidated. The aim of this study is to explore the effects of miR-203/SNAI2 axis on the biological characteristics of prostate carcinomas both in vitro and in vivo. We found that miR-203 was significantly downregulated in prostate cancer cell lines compared with immortalized prostate epithelial cells using semi-quantitative PCR and real-time PCR, as well as in clinical prostate cancer tissues compared to normal tissues using TCGA analysis. Functionally, miR-203 inhibited prostate cancer cell proliferation, migration, endothelial cell tube formation and cancer stemness in vitro. Meanwhile, overexpression of miR-203 suppressed SNAI2 expression both in DU145 and PC3 cells. In addition, the in vivo study showed that miR-203 suppressed tumorigenicity, metastasis and angiogenesis of DU145 cells. Ectopic expression of SNAI2 rescued the inhibitory effects of miR-203 both in vitro and in vivo. Importantly, the EMT markers CDH1 and VIMENTIN were modulated by the miR-203/SNAI2 axis. Furthermore, the GSK-3β/β-CATENIN signal pathway was suppressed by miR-203 and could be reactivated by SNAI2. Taken together, this research unveiled the function of miR-203/SNAI2 axis in tumorigenesis, angiogenesis, stemness, metastasis and GSK-3β/β-CATENIN signal pathway in prostate cancer and gave insights into miR-203/SNAI2-targeting therapy for prostate cancer patients. © 2018 IUBMB Life, 70(3):224-236, 2018.


Prevalence of Escherichia coli O157:H7 in surface water near cattle feedlots.
Between April 2009 and July 2011, 311 surface water samples in 48 cattle feedlots distributed in an area of about 67,000 km(2) were analyzed to examine the environmental dissemination of Escherichia coli O157:H7. Samples were taken inside and outside the pens, exposed and not exposed to runoff from corrals, near the feedlots. Two types of samples were defined: (1) exposed surface waters (ESW; n=251), downstream from cattle pens; and (2) nonexposed surface waters (NESW; n=60), upstream from cattle pens. By multiplex PCR, 177 (70.5%) ESW samples were rfb(O157)-positive, and 62 (24.7%) E. coli O157, and 32 (12.7%) Shiga toxin-producing E. coli (STEC) O157:H7 strains were isolated. In the NESW samples, 36 (60.0%) were rfb(O157)- positive, and 9 (15.0%) E. coli O157, and 6 (10.0%) STEC O157:H7 strains were isolated. These results showed that the environmental surface waters exposed to liquid discharges from intensive livestock operations tended to be contaminated with more STEC O157:H7 than NESW. However, no significant difference was found. This fact emphasizes the relevance of other horizontal routes of transmission, as the persistence of E. coli in the environment resulting from extensive livestock farming. By XbaI-PFGE, some patterns identified are included in the Argentine Database of E. coli O157, corresponding to strains isolated from hemolytic uremic syndrome and diarrhea cases, food, and animals, such as AREXHX01.0022, second prevalent pattern in Argentina, representing 5.5% of the total database. In the study area, characterized by the abundance of waterways, pathogens contained in feedlot runoff could reach recreational waters and also contaminate produce through irrigation, increasing the potential dissemination of STEC O157:H7 and the risk of human infections. The control of runoff systems from intensive livestock is necessary, but other alternatives should be explored to solve the problem of the presence of E. coli O157 in the aquatic rural environment.


Cognitive Training in Parkinson's Disease Induces Local, Not Global, Changes in White Matter Microstructure.
Previous studies showed that cognitive training can improve cognitive performance in various neurodegenerative diseases but little is known about the effects of cognitive training on the brain. Here, we investigated the effects of our cognitive training paradigm, COGTIPS, on regional white matter microstructure and structural network topology. We previously showed that COGTIPS has small, positive effects on processing speed. A subsample of 79 PD patients (N = 40 cognitive training group, N = 39 active control group) underwent multi-shell diffusion-weighted imaging pre- and post-intervention. Our pre-registered analysis plan (osf.io/cht6g) entailed investigating white matter microstructural integrity (e.g., fractional anisotropy) in five tracts of interest, including the anterior thalamic radiation (ATR), whole-brain tract-based spatial statistics (TBSS), and the topology of the structural network. Relative to the active control condition, cognitive training had no effect on topology of the structural network or whole-brain TBSS. Cognitive training did lead to a reduction in fractional anisotropy in the ATR (B [SE]: - 0.32 [0.12], P = 0.01). This reduction was associated with faster responses on the Tower of London task (r = 0.42, P = 0.007), but this just fell short of our statistical threshold (P < 0.006). Post hoc "fixel-based" analyses showed that this was not due to changes in fiber density and cross section. This suggests that the observed effect in the ATR is due to training-induced alterations in neighboring fibers running through the same voxels, such as intra-striatal and thalamo-striatal fibers. These results indicate that 8 weeks of cognitive training does not alter network topology, but has subtle local effects on structural connectivity.


Erythrocyte Autoantibody Positivity in Serological Cross-matching.
To investigate the erythrocyte autoantibody positivity detected in the serological cross-matching (XM), and its possible effects on salient hemogram parameters. A descriptive study. Balıkesir Atatürk City Hospital's Blood Transfusion Centre, Faculty of Medicine, Department of Anesthesiology and Reanimation, Balıkesir University, Turkey, from 2017 to 2018. Erythrocyte autoantibody positivity, which was detected in the traditional serological cross-matching for a pre-transfusion laboratory test were analysed retrospectively. Later, hemogram changes in the previous (no erythrocyte autoantibodies) and following (erythrocyte autoantibodies present) transfusions were investigated using statistical methods. Erythrocyte autoantibody positivity rate was 10.16% (342/3,365). There was no statistically significant difference in the increase of hemoglobin, hematocrit, and red blood cell between the period when erythrocyte autoantibodies were detected or not, (p = 0.27, 0.13, and 0.09, respectively). Erythrocyte autoantibodies positivity found on routine cross-match exmination, which must be considered together with parameters such as previous transfusion history, other pre-transfusion laboratory test results, and clinical presentation and management. Key Words: Transfusion, Erythrocye autoantibody, Alloantibody, Hemogram, Cross-matching.


Massive venous injuries associated with penetrating wounds of the liver.
The management of eleven patients with major venous and associated liver injuries has been summarized. Aggressive resuscitation includes early operative intervention. Repair of venous injury can be effected if hemorrhage is contained and stepwise exposure instituted. The critical steps in management include: 1) thoraco-abdominal exposure; 2) intermittent occlusion of the porta hepatis; 3) total liver mobilization; 4) judicious use of cava-hepatic bypass.


Automated quantification of choriogonadotropin: analytical correlation between serum and urine with creatinine correction.
We evaluated the Boehringer Mannheim Diagnostics ES 600 automated immunoassay system for measuring choriogonadotropin (hCG) in human serum, plasma, and urine. The ES 600, an automated sample-selective, multibatch analyzer, is based on immunoenzymometric coated-tube technology. Interassay CVs for assay of both serum and urine ranged from 2% to 16%. The analytical sensitivity was 0.5 int. unit/L. Results for serum correlated well with qualitative "Icon" and quantitative "Tandem" assays (Hybritech). In addition, results for serum and urinary hCG correlated well when the latter was expressed in terms of creatinine excretion. These results suggest that determination of hCG in urine can be correlated with those in serum for use as a marker for chorionic tumors or for screening abnormal pregnancies, where the rate of hCG production may be important.


Development of an LC-MS/MS method for the detection of traces of peanut allergens in chili pepper.
The recent detection of nuts (including peanut) in spices across the globe has led to enormous recalls of several spices and food products in the last two years. The lack of validated detection methods specific for spices makes it difficult to assess allergen presence at trace levels. Because of the urgent need for confirmation of possible peanut presence in chili peppers, an LC-MS/MS method was optimized and developed for this particular food matrix. Although several studies optimized LC-MS detection strategies specific for peanuts, the presence of complex components in the spices (e.g., phenolic components) makes method optimization and validation necessarily. Focus was laid on validation of the method with real incurred chili peppers (whereby a known amount of peanut is added) at low concentrations, to deal with possible matrix interferences. LC-MS/MS proves to be a good alternative to the currently most applied methods (ELISA and RT-PCR) and can be used as a complementary method of analysis when results are unclear. Peanut marker peptides were selected based on their abundancy in digested incurred chili peppers. The limit of detection was determined to be 24 ppm (mg peanut/kg), a level whereby the risk for potential allergic reactions is zero, considering the typical portion size of spices. The chili pepper powder under investigation proved to contain low levels of peanuts after LC-MS/MS, ELISA, and RT-PCR testing. Graphical abstract Standard curve of the detected peanuts in chili pepper samples using the novel LC-MS/MS method.


Development and use of a microdissected swine chromosome 6 DNA library.
To facilitate the identification of microsatellite genetic markers from a single swine chromosome, chromosome microisolation and microcloning have been used to generate a swine chromosome 6-specific DNA library. Ten copies of swine chromosome 6 were scraped from metaphase spreads, ligated to custom-prepared adaptors, and amplified by PCR. The purity of the amplified product was verified by fluorescent in situ hybridization. The utility of the chromosome painting probe for heterologous painting was demonstrated and confirmed that swine chromosome 6 is syntenic to human chromosomes 1p and 19q. A small insert genomic library of 1.39 x 10(6) clones was generated from the PCR-amplified chromosome 6 genomic DNA and screened for (GT)n microsatellite genetic markers. Nine (GT)n microsatellite markers were developed and genotyped on a Yorkshire x Meishan swine reference family. All nine markers genetically mapped to chromosome 6, confirming the purity of the microisolation method. The method used here should be adaptable to the microdissection of subchromosomal regions of not only the swine genome but also other livestock genomes.


Traumatic injury of the cervicothoracic trachea and major bronchi.
Interstate highways and crowded urban areas have become the "battlefields" of the 1990s. The weapons are motor vehicles, handguns, and knives. This article relates the historical perspective, diagnosis, and management of traumatic injury to the cervicothoracic trachea and major bronchi. The etiologic factors are explained in depth. Examples of the current management of cervicothoracic tracheal injuries, including resection, primary repair, and the use of autogenous tissue to buttress or wrap the repair, are explained and illustrated.


Pigment epithelium-derived factor attenuates angiogenesis and collagen deposition in hypertrophic scars.
Scar forming wounds are often characterized by higher levels of vascularity than non-scarring wounds and normal skin, and inhibition of angiogenesis has been shown to inhibit scar formation in some model systems. The rabbit ear hypertrophic scar (HS) model has been widely used to study the mechanisms that underlie the development of HS as well as the effectiveness of various treatments. Although the rabbit ear HS model is well characterized in terms of scar formation, the rate and level of angiogenesis has not been investigated in this model, and the cause-effect relationship between angiogenesis and rabbit HSs has not been examined. In the current study, full-thickness excisional wounds were created on the ventral side of New Zealand White rabbit ears to induce HS formation, and the dynamic pattern of angiogenesis and the expression of angiogenic regulatory factors were examined over time. Blood vessel density was found to peak at 2.7% on day 14 post-wounding, decreasing to 1.7% by day 28. mRNA levels of the proangiogenic factor VEGF-A peaked at day 14, while the expression of the antiangiogenic factors pigment epithelium-derived factor (PEDF) and thrombospondin 1 (TSP1) peaked at day 28 post-wounding. To examine whether inhibition of angiogenesis influences HS formation in this model, wounds were treated with exogenous soluble antiangiogenic agents including recombinant PEDF (rPEDF) and a functional PEDF peptide (PEDF-335). rPEDF and PEDF-335 were administered intradermally from day 4 post-wounding every 3 days until day 19. Intradermal injection of rPEDF or PEDF-335 both led to decreased angiogenesis and decreased collagen deposition at the wound site. The results support the utility of antiangiogenic therapies, including rPEDF/PEDF-335, as a potential new strategy for the prevention or treatment of HSs.


Enhancing the Nutritional Profile of Tenebrio molitor Using the Leaves of Moringa oleifera.
Nowadays, more and more research is being carried out on various feeds of Tenebrio molitor larvae, in order to increase their nutritional value and render them a valuable component of the human diet. In this study, Moringa oleifera leaves were used in different proportions (up to 50%) to substitute wheat bran (the usually employed feed), in order to evaluate their effect on the growth and development of the larvae, as well as on their composition in crude protein, fat and fatty acids, ash, vitamins, and antioxidants. It was found that the addition of M. oleifera leaves in the feed had no negative impact on the development and survival of the insects, while an increase in their nutritional value was recorded. More specifically, an increase in the crude protein of up to 22.61% and vitamin C and A contents of up to 40.74% and 491.63%, respectively, was recorded. Therefore, the use of M. oleifera leaves as a feed additive is highly recommended for rearing T. molitor larvae to enhance the nutritional value of the insects.


Suicide and the rural adolescent.
The rural family, with its particular stressors, is increasingly vulnerable to overwhelming crises. Adolescent suicide, although rare, may result from or add to that stress. The intent of this study was to identify and examine specific stressors with which a rural adolescent must deal, the coping mechanisms utilized, and when these fail, how it leads to suicidal behavior. Therapeutic modalities available to the troubled adolescent were examined and additional services suggested.


Mechanism of miR-204-5p in exosomes derived from bronchoalveolar lavage fluid on the progression of pulmonary fibrosis via AP1S2.
Exosomes are nanoscale vesicles secreted by various types of cells that are responsible for intracellular communication. Despite that bronchoalveolar lavage fluid (BALF) has been proven to involve in tumor development, more efforts are required to investigate the impact of BALF on pulmonary fibrosis (PF). This study aimed to investigate the mechanism of how exosomal miR-204-5p from BALF facilitates PF progression in rats. PF rat model was established by intratracheal injection of bleomycin. BALF-derived exosomes (Exo) were extracted from normal and PF rats. PF-Exo (BALF-derived Exo from PF rats) and miR-204-5p antagomir were injected into rats to investigate the effect of exosomal miR-204-5p on PF. Collagen content in lung tissues of rats was assessed by Masson staining, hydroxyproline (HYP) content assay and immunohistochemistry (IHC). Primary lung fibroblasts were isolated, and treated by TGF-β1. After co-transfection of PF-Exo, miR-204-5p inhibitor and sh-AP1S2, cell proliferation, levels of miR-204-5p, fibrotic markers α-SMA and collagen 1 (Col 1), and proteins of autophagy markers LC3II, LC3I and P62 were measured. The interaction between miR-204-5p and AP1S2 was determined by bioinformatics online software TargetScan and dual-luciferase reporter assay. miR-204-5p was abundantly expressed in the PF-Exo group. PF-Exo injection potentiated PF progression and proliferation ability of lung fibroblasts in vivo and in vitro. Injection with PF-Exo and miR-204-5p antagomir significantly increased the LC3II/I ratio and decreased the HYP content, proteins of α-SMA, Col 1 and P62, collagen content in rat lung tissues of PF rats. TGF-β1 induction elevated the LC3II/LC3I ratio, suppressed the cell proliferation rate, and decreased the levels of α-SMA, Col 1 and P62. Additionally, AP1S2 was a direct target of miR-204-5p. miR-204-5p inhibitor can counteract the effect of PF-Exo in proliferation of lung fibroblasts, while sh-AP1S2 eliminated the effect of miR-204-5p inhibitor. Exosomal miR-204-5p from BALF inhibits autophagy to promote the progression of PF rats by targeting AP1S2.