Physiological Effects of Ergot Alkaloid and Indole-Diterpene Consumption on Sheep under Hot and Thermoneutral Ambient Temperature Conditions.
A controlled feeding study was undertaken to determine the physiological and production effects of consuming perennial ryegrass alkaloids (fed via seed) under extreme heat in sheep. Twenty-four Merino ewe weaners (6 months; initial BW 30.8 ± 1.0 kg) were selected and the treatment period lasted 21 days following a 14 day acclimatisation period. Two levels of two factors were used. The first factor was alkaloid, fed at a nil (NilAlk) or moderate level (Alk; 80 μg/kg LW ergovaline and 20.5 μg/kg·LW lolitrem B). The second factor was ambient temperature applied at two levels; thermoneutral (TN; constant 21-22 °C) or heat (Heat; 9:00 AM-5:00 PM at 38 °C; 5:00 PM-9:00 AM at 21-22 °C), resulting in four treatments, NilAlk TN, NilAlk Heat, Alk TN and Alk Heat. Alkaloid consumption reduced dry matter intake ( p = 0.008), and tended to reduce liveweight ( p = 0.07). Rectal temperature and respiration rate were increased by both alkaloid and heat ( p < 0.05 for all). Respiration rate increased to severe levels when alkaloid and heat were combined, indicating the short term effects which may be occurring in perennial ryegrass toxicosis (PRGT) areas during severe weather conditions, a novel finding. When alkaloid ingestion and heat were administered separately, similar physiological responses occurred, indicating alkaloid ingestion causes a similar heat stress response to 38 °C heat.


[Management of twin-to-twin transfusion syndrome].
Twin-to-twin transfusion syndrome (TTTS), also called twin oligoamnios polyhydramnios sequence (TOPS) complicates around 15% of monochorionic pregnancies irrespective of the mode of conception. It is a hemodynamic, and probably hormonal, discordance secondary to imbalanced blood flow through the vascular anastomoses aforementioned. During the last 15 years, a lot of progress has been made in the understanding, diagnosis and treatment of TTTS. Nevertheless, many questions remain unanswered and research is still active in this domain. Fetoscopic laser coagulation of placental vessels is the only treatment addressing the pathophysiology of the syndrome as proven through a randomized controlled study against amnioreduction. This technique has definitely improved overall survival as well as the rate of neurologically intact survival but it still lacks preoperative prognostic markers.


Glutamic acid decarboxylase-containing axons synapse on LHRH neurons in the rat medial preoptic area.
A double-label electron microscopic immunostaining procedure was employed to examine the interconnections of glutamic acid decarboxylase(GAD)- and LHRH-immunoreactive neurons in the medial preoptic area of the rat. The results provide ultrastructural evidence that GABA-ergic neurons establish symmetric (Gray II) synapses on LHRH neurons.


Neutrophil Gelatinase Associated Lipocalin (NGAL) - a biomarker of renal dysfunction in patients with liver cirrhosis: Do we have enough proof?
Renal dysfunction has a serious impact on the natural evolution of liver cirrhosis. Treatment and prognosis may be improved if an early diagnosis could be established, and specific therapeutic interventions would be applied. Although RIFLE and AKIN classifications have been successfully implemented in the clinical practice of Nephrology and Intensive Care Units, these did not provide major improvements in patients with liver cirrhosis. In the last decade, various biomarkers of kidney injury have been assessed, and Neutrophil Gelatinase-Associated Lipocalin (NGAL) is one of the most promising and most studied novel biomarker. To offer a brief evaluation on current data on the utility of this biomarker in patients with liver cirrhosis. We have searched through current literature and analyzed all significant full text articles on this topic. NGAL and other new kidney injury molecules may be useful in patients with liver cirrhosis, particularly in identifying structural kidney dysfunction, but larger validation studies to confirm this observation are needed.


A selective CuII complex with 4-fluorophenoxyacetic acid hydrazide and phenanthroline displays DNA-cleaving and pro-apoptotic properties in cancer cells.
The thin line between efficacy and toxicity has challenged cancer therapy. As copper is an essential micronutrient and is important to tumor biology, CuII complexes emerged as an alternative to chemotherapy; however, its biological properties need to be better understood. Thus, we report in vitro the antitumor effects of two CuII complexes named [Cu(4-fh)(phen)(ClO4)2] (complex 1) and [Cu(4-nh)(phen)(ClO4)2]·H2O (complex 2), in which 4-fh = 4-fluorophenoxyacetic acid hydrazide; 4-nh = 4-nitrobenzoic hydrazide and phen = 1,10-phenanthroline. Both complexes presented cytotoxic activity against tumor cells, but only complex 1 showed significant selectivity. Complex 1 also induced DNA-damage, led to G0/G1 arrest and triggered apoptosis, which was initiated by an autophagy dysfunction. The significant in vitro selectivity and the action mechanism of complex 1 are noteworthy and reveal this prodrug as promising for anticancer therapy.


Detection of FMDV RNA amplified by the polymerase chain reaction (PCR).
Molecular detection of foot-and-mouth disease virus (FMDV) using the polymerase chain reaction (PCR) is a rapid and accurate method. In this study we present PCR for the detection of FMDV RNA in infected BHK cells. Using PCR and two primers selected from the RNA polymerase gene, a conserved sequence in all types and subtypes of FMDV, we were able to detect FMDV RNA present in RNA extracted from the FMDV-infected cells. RNA from uninfected BHK cells gave negative results. Another set of primers selected from the nucleotide sequence of the variable VP1 gene permitted the demonstration of variations among different FMDV Israeli isolates by PCR. Two 01 type FMDV isolates out of a total of 6 FMDV field isolates (including 01 Geshur) gave a positive PCR while two other 01 isolates and two ASIA isolates were detected with the RNA polymerase gene primers but not with the VP1 primers. Serial dilutions of the RNA used in each reaction showed that a very small amount of RNA may be detected by PCR. The PCR products from the RNA polymerase and the VP1 genes were sequenced and the nucleotide sequences obtained were compared with a known nucleotide sequence of the FMDV 01 genome.


Current cellular immunological hurdles in pig-to-primate xenotransplantation.
In this review, we summarize the work published over the last few years relative to cellular immunological hurdles encountered specifically in pig-to-primate xenotransplantation models. The works summarized here cover both the innate and adaptative cellular immune response as well as strategies to overcome them and consequently prevent xenograft rejection.


Identification of a repeated domain within mammalian alpha-synemin that interacts directly with talin.
The type VI intermediate filament (IF) protein synemin is a unique member of the IF protein superfamily. Synemin associates with the major type III IF protein desmin forming heteropolymeric intermediate filaments (IFs) within developed mammalian striated muscle cells. These IFs encircle and link all adjacent myofibrils together at their Z-lines, as well as link the Z-lines of the peripheral layer of cellular myofibrils to the costameres located periodically along and subjacent to the sarcolemma. Costameres are multi-protein assemblies enriched in the cytoskeletal proteins vinculin, alpha-actinin, and talin. We report herein a direct interaction of human alpha-synemin with the cytoskeletal protein talin by protein-protein interaction assays. The 312 amino acid insert (SNTIII) present only within alpha-synemin binds to the rod domain of talin in vitro and co-localizes with talin at focal adhesion sites within mammalian muscle cells. Confocal microscopy studies showed that synemin co-localizes with talin within the costameres of human skeletal muscle cells. Analysis of the primary sequences of human alpha- and beta-synemins revealed that SNTIII is composed of seven tandem repeats, each containing a specific Ser/Thr-X-Arg-His/Gln (S/T-X-R-H/Q) motif. Our results suggest human alpha-synemin plays an essential role in linking the heteropolymeric IFs to adherens-type junctions, such as the costameres within mammalian striated muscle cells, via its interaction with talin, thereby helping provide mechanical integration for the muscle cell cytoskeleton.


Data on the peptide mapping and MS identification for phosphorylated peptide.
This article contains peptides mapping, mass spectrometry and processed data related to the research "Identification and quantification of the phosphorylated ovalbumin by high resolution mass spectrometry under dry-heating treatment" [1]. Fourier transform ion cyclotron mass spectrometry (FTICR MS) was used to investigate the specific phosphorylation sites and the degree of phosphorylation (DSP) at each site. Specifically, phosphorylated peptides were monitored through mass shift on the FTICR MS spectrum. DSP was evaluated through the relative abundance levels of the FTICR MS spectrometry. From these data, the calculation method of DSP was exemplified.


Unilateral breast enlargement 5 years after reduction mammaplasty.
A 26-year-old woman presented with unilateral breast enlargement 5 years after bilateral reduction mammaplasty. After careful physical examination combined with a clinical assessment, mammogram, and histologic tissue examination, the patient underwent bilateral reduction mammaplasty using an inferior wedge resection technique. Histologic examination confirmed the diagnosis of a fibrocystic breast disease in both breasts. The most common differential diagnoses are juvenile fibroadenoma, virginal hypertrophy, fibrocystic disease, and cystosarcoma phylloides.


Endoscopically Assisted Correction of Malpositioned Breast Implants Using Absorbable Barbed Sutures.
Breast implant malpositioning is the second most common reason for revisional breast surgery. Multiple correction methods are suggested, depending on the malposition, but most of the methods, such as the inframammary fold incision, result in additional scars. We performed transaxillary endoscopic breast implant bottoming out corrections and used V-Loc thread for capsulorrhaphy. Fourteen patients who underwent correction for breast implant bottoming out after transaxillary breast augmentation were included in this study. Transaxillary endoscopic correction was performed using a V-Loc thread. All the 14 patients were satisfied with the result immediately after surgery. One case of overcorrection and one with implant bottoming out occurred, but did not require additional surgery. Transaxillary endoscopic bottoming out correction is a useful technique for those individuals who underwent primary transaxillary incisional breast augmentation. V-Loc thread is useful for endoscopic capsulorrhaphy. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


On the differential responsiveness of males and females in the micronucleus assay.
The primary question asked was whether the increased sensitivity of female mice to the induction of micronuclei by ethyl methanesulphonate, compared to males, would vanish if the doses were adjusted for any difference in the LD50 between the sexes. The second question was whether the frequency of micronuclei after 4 daily treatments would differ from 2 daily treatments. We measured the LD50 in the two sexes separately and found the female value to be lower. We also repeated the micronucleus measurements in each sex separately. At any given dose expressed in mg/kg the response in females was greater than in males. This was still true when the dose was expressed as a fraction of the LD50, but the difference was reduced. The uncertainty in the LD50 measurements was such that there may be no meaningful difference between males and females when the dose is expressed in this way. The 2-day and 4-day results differed very little for ethyl methanesulphonate, but were quite different for the positive control, dimethylbenz[a]anthracene, being higher at 4 days than at 2 days. We argue that the results of our experiments, which confirm the results of others, demonstrate the advisability of using both sexes in the assay.


Oral and nonoral sensorimotor interventions facilitate suck-swallow-respiration functions and their coordination in preterm infants.
Preterm infants are at high risk of encountering oral feeding difficulties. Early sensorimotor interventions may improve oral feeding skills in preterm infants. To further explore the effects of an oral (O), tactile/kinesthetic (T/K), and combined (O+T/K) sensorimotor intervention on preterm infants' nutritive sucking, swallowing and their coordination with respiration. Seventy-five infants (29 [0.3, standard error of mean, SEM] weeks gestation, 49 males/26 females) were randomly assigned to an O group involving sensorimotor input to the oral structures; a T/K group involving sensorimotor input to the trunk and limbs; a combined (O+T/K) group; and a control group. Stage of sucking, suction and expression amplitudes (mmHg), suck-swallow ratio, stability of suck-swallow interval, and swallow-respiration patterns. The O group had significantly more advanced sucking stages, and greater suction and expression amplitudes than controls [p≤0.035, effect size (ES) >0.6]. The suck-swallow ratio and stability of suck-swallow intervals did not significantly differ among groups (p≥0.181, ES≤0.3). The three interventions led to fewer swallows bracketed by prolonged respiratory pauses compared to controls (pause-swallow-pause, p≤0.044, ES≥0.7). The T/K and combined (O+T/K) groups had greater occurrence of swallows bracketed by expiration than the control and O groups (expiration-swallow-expiration, p≤0.039, ES≥0.3). The O intervention enhanced specific components of nutritive sucking. All three interventions resulted in improved swallow-respiration coordination. Sensorimotor interventions have distributed beneficial effects that go beyond the specific target of input.


Dereplication for biotechnology screening: PyMS analysis and PCR-RFLP-SSCP (PRS) profiling of 16S rRNA genes of marine and terrestrial actinomycetes.
The search for exploitable biology is a major task for biotechnology-based industries. In this context, discrimination between previously tested or recovered micro-organisms (dereplication) is imperative, in order to reduce screening costs by sorting large collections of isolates, which are then subjected to further detailed evaluation. Pyrolysis mass spectrometry (PyMS) is a whole-cell fingerprinting technique that enables the rapid and reproducible sorting of micro-organisms, uses small samples and has the advantage of being fully automated. In this study, we compare chemometric fingerprinting with a ribotyping fingerprinting method, in order to investigate the extent to which pyrogroups formed by PyMS analysis relate to genetic diversity, using polymerase chain reaction-restriction fragment length polymorphism-single-strand conformational polymorphism (PRS). A mixture of environmental strains of mycolic acid containing actinomycetes was used to mimic the selection of colonies from primary isolation plates. The congruence found between the clusters defined by the chemometric and molecular fingerprinting techniques was very high and demonstrated the effectiveness of PyMS as a rapid sorting and dereplicating procedure for putatively novel strains, criteria that are critical for biotechnological screens. Moreover, PyMS analysis revealed significant variation within pyrogroups that contained strains with the same genotypic (PRS) characteristics, thus emphasising its discriminatory capacity at the infraspecies level.


Azide-functionalized ligand enabling organic-inorganic hybrid dielectric for high-performance solution-processed oxide transistors.
We propose a highly efficient crosslinking strategy for organic-inorganic hybrid dielectric layers using azide-functionalized acetylacetonate, which covalently connect inorganic particles to polymers, enabling highly efficient inter- and intra-crosslinking of organic and inorganic inclusions, resulting in a dense and defect-free thin-film morphology. From the optimized processing conditions, we obtained an excellent dielectric strength of over 4.0 MV cm-1, a high dielectric constant of ~14, and a low surface energy of 38 mN m-1. We demonstrated the fabrication of exceptionally high-performance, hysteresis-free n-type solution-processed oxide transistors comprising an In2O3/ZnO double layer as an active channel with an electron mobility of over 50 cm2 V-1 s-1, on/off ratio of ~107, subthreshold swing of 108 mV dec-1, and high bias-stress stability. From temperature-dependent I-V analyses combined with charge transport mechanism analyses, we demonstrated that the proposed hybrid dielectric layer provides percolation-limited charge transport for the In2O3/ZnO double layer under field-effect conditions.


Plasticity in life-history traits of Plantago major L. ssp. pleiosperma Pilger.
Plasticity in life-history characteristics was investigated in three populations of Plantago major L. ssp. pleiosperma (Pilger), a self-compatible, wind pollinated species with a high self-fertilization rate. The populations studied were selected for their marked differences in biomass accumulation and habitat characteristics such as nutrient availability and interspecific interaction. Plants, raised from seeds collected at three sites, were grown in a greenhouse at three nutrient levels. In addition, a reciprocal transplant experiment was carried out. In both experiments variances in variables of growth and reproduction were largely due to environmental factors. Besides this overall result, population and population x environment interaction effects existed for most of the variables. Differences in plasticity between populations were further analysed. In the greenhouse experiment plants from a river-side population showed a high degree of plasticity in reproductive effort, whereas plants from two other populations, one series from a beach plain and the other from a salt meadow, showed a high degree of plasticity in shoot-root ratio. Plasticity in biomass allocation to either vegetative or generative parts is suggested to be an important response to selective forces related to either interspecific competition or temporal variability.


Late right heart reconstruction following repair of tetralogy of Fallot.
Twenty-two symptomatic patients underwent a total of 28 reoperative procedures after initial surgical repair of tetralogy of Fallot. Sixteen of the patients were considered to have unfavorable anatomy of the right ventricular outflow tract (RVOT) or pulmonary artery at the time of initial repair. Pulmonary or tricuspid valve replacement, or replacement of both valves, utilizing a xenograft bioprosthesis was performed in 1 of the 22 initial repairs, 7 of the 22 first reoperations, and 5 of the 6 second reoperations. Ultimately, 14 patients received transannular RVOT patches. The interval between the first and second reoperations for 6 patients who required 2 late reconstructive procedures was 5.8 years. No operative deaths occurred. There were 2 late deaths (1 sudden and 1 due to aspiration). Actuarial survival probability (+/- standard error of the mean) 16 years after initial repair was 72 +/- 21%. Eighteen of the 20 current survivors in the present series are completely asymptomatic without physical restrictions; the other 2 are considered to be in New York Heart Association Functional Class II. No xenograft bioprosthetic dysfunction has occurred to date, but cumulative valve follow-up is limited (13 patient-years). In selected patients, earlier pulmonary or tricuspid valve replacement or replacement of both of these valves can provide some degree of protection against recurrent deterioration.


The effects of anti-CD4 and anti-CD8 antibody treatment on placental growth and function in allogeneic and syngeneic murine pregnancy.
During pregnancy, maternal immune recognition of paternal alloantigens has been shown to result in an increased influx of maternal T cells into the spleen, draining lymph nodes and decidua. In previous studies we have shown that polyclonal or monoclonal anti-T cell antibody treatment of allogeneically pregnant mice results in decreased placental proliferation and phagocytosis in vivo. In the present study we compare the effect of such antibody treatment during allogeneic and syngeneic pregnancy. We show that monoclonal anti-CD8 treatment of both types of pregnant females reduces placental proliferation and phagocytosis. Anti-CD4 antibody treatment, on the other hand, only affects placental proliferation, indicating that there is a complex network of immune interactions affecting placental growth and function.


Neutrophil elastase enhances IL-12p40 production by lipopolysaccharide-stimulated macrophages via transactivation of the PAR-2/EGFR/TLR4 signaling pathway.
Proteinase-activated receptor 2 (PAR-2) and toll-like receptor 4 (TLR4) are involved in innate immune responses and signaling cross-talk between these receptor molecules has the potential to augment an ongoing inflammatory response. The aim of this study was to evaluate the possible cooperative influence of PAR-2 and TLR4 on IL-12p40 production by macrophages after stimulation with lipopolysaccharide (LPS). During culture, GM-CSF upregulated PAR-2 expression by macrophages in a time-dependent manner. Stimulation with LPS enhanced IL-12p40 production by macrophages in a concentration-dependent manner. While human neutrophil elastase (HNE) did not induce IL-12p40 production, pretreatment of macrophages with HNE synergistically increased the IL-12p40 protein level after LPS exposure. Silencing of TLR4 with small interfering RNA blunted the synergistic enhancement of IL-12p40 by HNE combined with LPS. Silencing of β-arrestin 2, p22phox, or ERK1/2 also inhibited an increase of IL-12p40. Interestingly, transfection of macrophages with small interfering RNA duplexes for DUOX-2, EGFR, TLR4, or TRAF6 significantly blunted the increase of IL-12p40 in response to treatment with HNE plus LPS. U73122 and Rottlerin also inhibited the increased production of IL-12p40. In conclusion, HNE is involved in transactivation of TLR4 through activation of DUOX-2/EGFR and synergistically enhances IL-12p40 production by macrophages stimulated with LPS.


Characterization of the secondary structure and order-disorder transition of a β-(1 → 3, 1 → 6)-glucan from Aureobasidium pullulans.
This study revealed the secondary structures of the water-soluble Aureobasidium pullulans β-(1 → 3, 1 → 6)-d-glucan (APG) whose primary structural unit is a β-(1 → 3)-d-glucan backbone with four β-(1 → 6)-d-glucosyl branching units every six residues. Solid-state NMR spectroscopy, X-ray diffractometry (XRD), and small-angle X-ray scattering (SAXS) experiments involving samples prepared from lyophilized APG showed that APG forms a triple helix in H2O and a random structure in DMSO. In addition, it was revealed that the transformation from the triple helix of APG to the random structure occurs reversibly, and that the triple helix is recovered from the random structure in DMSO/H2O mixtures containing more than 30% H2O. Solid-state NMR and diffraction studies revealed that the triple helix of APG is more stable than that of schizophyllan (SPG) whose structure comprises a β-(1 → 3)-d-glucan backbone with one β-(1 → 6)-d-branching unit every three residues. The APG helical pitch is 1.82 nm, which is about 10% longer than that of the triple helix of SPG. These findings show that the β-(1 → 6) side-chain frequency strongly affects the stability and helical pitch of a β-(1 → 3, 1 → 6)-d-glucan.


EM-652 (SCH57068), a pure SERM having complete antiestrogenic activity in the mammary gland and endometrium.
In order to minimize the risks of endometrial cancer and the development of resistance to antiestrogen therapy, we have synthesized the orally active antiestrogen EM-652 which is the most potent of the known antiestrogens and exerts pure antiestrogenic activity in the mammary gland and endometrium. EM-652 inhibits the AF-1 and AF-2 functions of both ERalpha and beta while the inhibitory action of OH-TAM is limited to AF-2. EM-652, thus, inhibits Ras-induced transcriptional activity and blocks SRC-1-stimulated activity of the two receptors. The absence of blockade of AF-1 by OH-TAM could explain why resistance develops to Tamoxifen treatment. Not only the development, but also the growth of established DMBA-induced mammary carcinoma is inhibited by treatment with EM-800, the prodrug of EM-652. EM-652 is the most potent antiestrogen to inhibit the growth of human breast cancer ZR-75-1, MCF-7 and T-47D cells in vitro. When incubated with human Ishikawa endometrial carcinoma cells, EM-800 has no stimulatory effect on the estrogen-sensitive parameter alkaline phosphatase activity. When administered to ovariectomized animals, EM-800 prevents bone loss, and lowers serum cholesterol and triglyceride levels. EM-800 has shown benefits in women with breast cancer who had failed Tamoxifen. The above-summarized preclinical and clinical data clearly suggest the interest of studying this compounds in the neoadjuvant and adjuvant settings and, most importantly, for the prevention of breast and uterine cancer.


The long terminal repeat of VL30 retrotransposons contains sequences that determine retinoic acid-induced transcription in cultured keratinocytes.
The characterization of retinoic acid (RA)-regulated gene transcription in keratinocytes has important implications as to the function of retinoids in epidermal homeostasis and to the central role retinoids play in the pharmaco-therapy of a variety of skin disorders. We show that cultured mouse keratinocytes (Balb/MK) responded to RA with induced expression of VL30 retrotransposons. The induction was rapid, was present at nanomolar concentrations of RA, was independent of new protein synthesis, and occurred both in proliferating and differentiated keratinocytes. The long terminal repeat of a VL30 retrotransposon, expressed in mouse epidermis in vivo, was found to contain two RA-responsive elements (RREs) that independently conferred RA responsiveness on a heterologous promoter in both cultured Balb/MK cells and normal human keratinocytes. Functional characterization and in vitro binding analysis showed that the sequence requirement for binding of retinoid X receptor alpha (RXR alpha) and retinoic acid receptor (RAR, either alpha, beta, or gamma) heterodimers, correlated with the sequence requirement for RA-induced transcription in keratinocytes. The VL30 RREs differed functionally from the RA response element present in the RAR-beta 2 promoter, in that the VL30 RREs were non-responsive in fibroblasts cultured from human skin. The non-responsiveness correlated with a reduced complex formation between a VL30 RRE and endogenously expressed nuclear factors present in skin fibroblasts. The data suggest that a direct repeat of two half-sites, spaced by two base pairs, with the consensus sequence T(A/G)AACTTTT(T/C)ACC(T/C), bound RAR-RXR heterodimers and mediated, at constitutive receptor levels, a primary RA response on gene transcription specifically in keratinocytes.


Validation of criteria used to predict extraprostatic cancer extension: a tool for use in selecting patients for nerve sparing radical prostatectomy.
We have previously reported that a prostate biopsy core specimen with a tumor length of at least 7 mm plus any positive basal biopsy core is the best predictor of extraprostatic extension (EPE) in radical prostatectomy (RP) specimens. We present prospectively collected data to validate our results. The study included 270 patients who underwent RP for localized prostate cancer between January 2002 and December 2003 by a single surgeon. We correlated side specific biopsy data, pretreatment prostate specific antigen, clinical stage and RP type using pathological specimen data. Mean patient age was 59.6 years and median prostate specific antigen was 8.24 ng/ml. Of the patients 94 (35%) underwent unilateral and 114 (42%) underwent bilateral nerve sparing RP. The overall incidence of EPE was 16%. The incidence of EPE was 33% in patients who met our criteria vs 4.6% in those who did not. Of 538 evaluable sides 7.2% were positive at the surgical margin. The incidence of ipsilateral positive margins was 2.5% when the neurovascular bundle was spared according to our criteria vs 11.8% when the bundle was resected according to criteria. This series validates our finding that a prostate biopsy core with a tumor length of at least 7 mm plus a positive basal biopsy core of any length and tumor grade is predictive of ipsilateral EPE. In the absence of these criteria the incidence of ipsilateral positive margins is low. Thus, these criteria are valuable for predicting EPE and selecting patients for nerve sparing RP.


Immunization to prevent congenital cytomegalovirus infection.
A primary maternal cytomegalovirus (CMV) during pregnancy causes newborn disease that includes hearing deficit and/or mental retardation. Relevant published literature. There are no biologic obstacles to immunization against fetal/placental infection with CMV. CMV vaccine trials may be difficult due to a lack of public awareness of CMV. Vaccine trials that use fetal infection as an endpoint will be prolonged, since vaccination will need to occur preconception. Vaccines in preclinical development include antigens of the CMV gB glycoprotein and the gH/gL UL128, 130 and 131 pentameric complex. These antigens induce antibodies that block viral entry into fibroblasts and endothelial/epithelial cells. Vaccines immunogenic in animals include an inactivated virus with a wild-type UL131 gene, a DNA vaccine using a wild-type UL130 gene and peptide vaccines using peptides from UL130 and 131. In spite of these potential obstacles, successful evaluation of CMV vaccines is possible.


Immunocytochemical evidence for a distinct GFAP-negative subpopulation of astrocytes in the adult rat hippocampus.
In order to establish the relative distribution of a GFAP-negative population of astrocytes, and its change in gliotic tissue, sections of the stratum radiatum of the CA1 hippocampal layer of male, adult, Wistar rats were analyzed by immunocytochemical methods. Ten micrometer-thick sections were triple-stained to detect nuclei, glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS). In another set of experiments, the rats received a one-time intraperitoneal injection of kainic acid that caused epileptic seizures. With the use of a behavioral protocol, animals with substantial neuronal loss in the pyramidal layer were selected. Five days after the injection these rats were analyzed similarly to control rats. We find that GFAP-positive cells are a subpopulation of GS-positive cells and that the GFAP-negative subpopulation is quite large (40%). After gliosis the density of GFAP-negative, GS-positive cells stays stable, whereas the GFAP-positive population triples. These experiments confirm electrophysiological experiments showing a distinct, GFAP-negative subset of astrocytes that remains consistent even after injury-induced gliosis and accompanying up-regulation of GFAP.


Marcel Proust: genius and insomnia.
Marcel Proust is considered one the greatest novelists of all times. His life was characterised by a long list of diseases. We analyse an important illness suffered by Proust: insomnia. It began in childhood and continued throughout his life, worsening progressively, and leading to a complete reversal of the sleep-wake cycle in the last years of the novelist's life. Several factors may be involved in the pathogenesis of Proust's insomnia. The beginning of insomnia since childhood, its characteristics, and the lack of precipitating factors suggest a form of idiopathic insomnia. Psychological traits of his personality (severe anxiety and depression) may have played a central role in the onset of insomnia. Further factors such as asthma and intake of stimulating substances may have had an important role in the maintenance and worsening of his insomnia. This sleep disorder affected both the lifestyle and literary genius of Marcel Proust. Insomnia is the prominent figure in the first novel ("Swann's way") of Proust's masterpieces entitled "In search of lost time," in which the novelist begins his journey through involuntary memory starting from his insomnia.


Effect of the immobilisation of DNA aptamers on the detection of thrombin by means of surface plasmon resonance.
We report a multichannel surface plasmon resonance (SPR) sensor for detection of thrombin via DNA aptamers immobilized on the SPR sensor surface. A detailed investigation of the effect of the immobilisation method on the interaction between thrombin and DNA aptamers is presented. Three basic approaches to the immobilisation of aptamers on the surface of the SPR sensor are examined: (i) immobilisation based on chemisorption of aptamers modified with SH groups, (ii) immobilisation of biotin-tagged aptamers via previously immobilized avidin, neutravidin or streptavidin molecular linkers, and (iii) immobilisation employing dendrimers as a support layer for subsequent immobilisation of aptamers. A level of nonspecific binding of thrombin to immobilized human serum albumin (HSA) for each of the immobilisation methods is determined. Immobilisation of aptamers by means of the streptavidin-biotin system yields the best results both in terms of sensor specificity and sensitivity.


The current status of exposure-driven approaches for chemical safety assessment: A cross-sector perspective.
For the purposes of chemical safety assessment, the value of using non-animal (in silico and in vitro) approaches and generating mechanistic information on toxic effects is being increasingly recognised. For sectors where in vivo toxicity tests continue to be a regulatory requirement, there has been a parallel focus on how to refine studies (i.e. reduce suffering and improve animal welfare) and increase the value that in vivo data adds to the safety assessment process, as well as where to reduce animal numbers where possible. A key element necessary to ensure the transition towards successfully utilising both non-animal and refined safety testing is the better understanding of chemical exposure. This includes approaches such as measuring chemical concentrations within cell-based assays and during in vivo studies, understanding how predicted human exposures relate to levels tested, and using existing information on human exposures to aid in toxicity study design. Such approaches promise to increase the human relevance of safety assessment, and shift the focus from hazard-driven to risk-driven strategies similar to those used in the pharmaceutical sectors. Human exposure-based safety assessment offers scientific and 3Rs benefits across all sectors marketing chemical or medicinal products. The UK's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) convened an expert working group of scientists across the agrochemical, industrial chemical and pharmaceutical industries plus a contract research organisation (CRO) to discuss the current status of the utilisation of exposure-driven approaches, and the challenges and potential next steps for wider uptake and acceptance. This paper summarises these discussions, highlights the challenges - particularly those identified by industry - and proposes initial steps for moving the field forward.


Data on MRI brain lesion segmentation using K-means and Gaussian Mixture Model-Expectation Maximization.
The data in this article provide details about MRI lesion segmentation using K-means and Gaussian Mixture Model-Expectation Maximization (GMM-EM) algorithms. Both K-means and GMM-EM algorithms can segment lesion area from the rest of brain MRI automatically. The performance metrics (accuracy, sensitivity, specificity, false positive rate, misclassification rate) were estimated for the algorithms and there was no significant difference between K-means and GMM-EM. In addition, lesion size does not affect the accuracy and sensitivity for either method.


Speech and language disorders in patients with high grade glioma and its influence on prognosis.
One hundred and sixteen patients with high grade glioma were entered into a prospective phase two study and treated with accelerated radiotherapy from 1988 to 1993. In this cohort of patients we analysed speech deficit as a subdivision of global functional status in terms of incidence, category and prognosis for survival. Forty three patients (37%) had a speech deficit at presentation. Eighty percent of these had a component of expressive dysphasia, associated with considerable degree of awareness and distress. The overall median survival was 9.5 months. On univariate analysis, median survival in patients with speech difficulties (6 months) was worse than patients with normal speech (10.5 months) (log rang p = 0.005). Multivariate analysis established independent significance from age, Karnofsky Performance Status (KPS), gender, histological grade, extent of surgery and seizures. This paper highlights the importance of assessing individual categories of functional disability which in patients with high grade glioma include mobility, cognitive function and communication. Each of these factors may seriously affect an individual's activities of daily living, hence quality of life and separate analysis has a number of clinical implications. Firstly, with over a third of patients suffering speech difficulties, adequate speech therapy facilities should be freely available to score the degree of deficit, devise coping strategies and institute communication therapy. Secondly, an understanding of prognostic factors aids the critical analysis of phase two studies and the design and stratification of future prospective trials which should include an analysis of speech deficit. Thirdly, separating individual patients into good and bad prognostic groups can assist strategic management decisions.


Combined study of 1H-magnetic resonance imaging and depth-selected, EKG-gated 31P-magnetic resonance spectroscopy of the heart in vivo.
NMR is useful for both 1H-magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). We undertook to combine these two merits of NMR for in vivo characterization of living rat heart in wide bore (9 cm) superconducting magnet under high magnetic field (6.4 Tesla). Spatial resolution of 1H-MRI attained 0.1 mm by spin warp method. Then, depth-selected, EKG-gated 31P-MRS was performed, adjusting the detection area to cover the heart that was identified by the preceding 1H-MRI. Three evidences that 31P-SMR signal chiefly originated from the heart without cross talk of adjacent organs indicated that combination of 1H-MRI and in vivo 31P-MRS under high magnetic field in whole animal is promising for more accurate evaluation of cardiac muscle metabolism.


Advanced image-guided skull base surgery.
Tumors of the skull base frequently encase or extend into normal neural and vascular structures. Preoperative planning and intraoperative identification of anatomic landmarks is especially important in complex tumors since it helps avoid or minimize surgical morbidity. By creating a surgical plan the image guidance software offers help in the establishment of a surgical approach. During surgery, the neuronavigation system displays the location of anatomic landmarks of the skull base regardless of any erosion or displacement. A series of 10 patients with complex tumors in various skull base locations is reported. Osseous structures are easily identified using the CT-based image guidance since these landmarks do not shift due to CSF loss. Image fusion of CT and MRI data gives additional information on the displacement of soft tissue structures. Image fusion in a substraction mode is helpful when a tumor has invaded bony structures or when the encasement of major vessels has to be visualized. The preoperative data preparation (planning of the approach, image fusion) plays a vital role in modern neuronavigation and contributes useful information during surgery for complex skull base tumors. Such advanced neuronavigation increases the efficacy and safety of intraoperative maneuvers. Eroded and distorted anatomic landmarks are not subject to a significant amount of intraoperative shift throughout the surgical procedure.


Immunochemical characterization of a cytochrome P450 isozyme and a protein purified from liver microsomes of male guinea pigs and their roles in the oxidative metabolism of delta 9-tetrahydrocannabinol by guinea pig liver microsomes.
A protein (designated as protein-B) was purified from liver microsomes of adult male guinea pigs by an affinity chromatography with omega-aminooctyl Sepharose 4B, followed by HPLC using DEAE-5PW and hydroxyapatite columns which had been used to purify a cytochrome P450 (P450) isozyme (P450-A) from the same subcellular fraction (Narimatsu et al., Biochem Biophys Res Commun 172: 607-613, 1990). Protein-B had a molecular mass of 49 kDa in SDS-PAGE, but did not show absorbance at 417 nm for heme. Further, it did not show any oxidative activities towards aniline (AN), d-benzphetamine (d-BP), p-nitroanisole (p-NA) or delta 9-tetrahydrocannabinol (delta 9-THC) in a reconstituted system including dilauroylphosphatidylcholine, NADPH-P450 reductase, and cytochrome b5. However, antiserum against protein-B raised in rabbits suppressed liver microsomal oxidative activities towards d-BP and p-NA dose-dependently. The antibody decreased delta 9-THC oxidative activity most effectively, but did not decrease AN hydroxylation activity. Antiserum against P450-A suppressed all the activities towards these four substrates, especially towards delta 9-THC, in liver microsomes of male guinea pigs. Moreover, reconstitution with hemin made it possible for protein-B to produce some oxidative activity toward delta 9-THC. These results suggest that protein-B is also a cytochrome P450 isozyme which has lost a heme moiety during purification steps. Both P450-A and protein-B could have a role as cytochrome P450 isozymes in the oxidative metabolism of drugs, especially that of delta 9-THC by the liver microsomes of adult male guinea pigs.


Hemispheric asymmetry in the perception of emotional sounds.
Three experiments were conducted to investigate hemispheric asymmetry for the perception of emotional sounds. Pairs of human nonspeech sounds were presented dichotically in a forced choice recognition task. Under divided attention conditions (Experiments 1 and 2) an left ear advantage (LEA) emerged during the second block of trials. Performance accuracy for the left and right ears was equal during the first block of trials. Under selective attention conditions (Experiment 3) an LEA emerged during the first block of trials. The results suggest that attention influences the rate of development of the laterality effect but not the direction of the effect.


Culture filtrate ether extracted metabolites from Streptomyces levis ABRIINW111 increased apoptosis and reduced proliferation in acute lymphoblastic leukemia.
Despite the advances in the discovery of various types of anticancer drugs for curing acute lymphoblastic leukemia (ALL), their toxicity and unfavorable side effects remained as big limitations for therapeutical applications. In this regard, natural products such as Streptomyces -derived agents have shown potential applications as anticancer drugs. The present study deals with evaluating the anti-carcinogenic activity of the ether extracted metabolites derived from Streptomyces on nalm-6 and molt-4 ALL cell lines. MTT assay was performed to evaluate the cytotoxicity effect of Streptomyces sp on nalm-6 and molt-4 cell lines. Apoptosis and proliferation were evaluated by Flow cytometry. Quantitative real-time RT-PCR (qRT-PCR) and western blot were performed to investigate the effect of these metabolites on the mRNA and protein expression levels of P53, Bax, and Bcl2. In both cell lines, extracted metabolites significantly inhibited cell growth and increased apoptosis. Although P53, Bax mRNA and protein expressions were increased, Bcl-2 expression decreased in treated cells compared with control. In addition, the G0/G1 arrest of Nalm-6 cells was induced. These findings of this work show that the ether-extracted metabolites from Streptomyces levis ABRIINW111 can be used as an anti-carcinogenic for acute lymphoblastic leukemia cells.


Inhibition of basal and TGF beta-induced fibroblast collagen synthesis by antineoplastic agents. Implications for wound healing.
Antineoplastic drugs, given in the perioperative period, are thought to be a hazard to wound repair. Since fibroblast collagen synthesis is crucial to healing, we examined the effects of bleomycin, cisplatin and 5-fluorouracil on collagen synthesis in confluent cultures of fibroblasts from human colon and skin. The drugs were added in final concentrations between 0.1 and 50 microM. Bleomycin did not affect collagen synthesis in colon fibroblasts but inhibited synthesis in skin fibroblasts. Collagen synthesis in colon fibroblasts was strongly, and specifically, inhibited by cisplatin while synthesis in skin fibroblasts was affected only slightly. 5-Fluorouracil had no effect whatsoever on the collagen synthetic capacity in either colon or skin fibroblasts. If skin fibroblasts were cultured in the presence of transforming growth factor beta (TGF beta), the antineoplastic agents inhibited the TGF beta-stimulated collagen synthesis at far lower concentrations than those needed to suppress non-stimulated synthesis. This effect was not observed in fibroblasts from colon. The possible implications of these observations, as pertain to the use of perioperative chemotherapy, are discussed. Since 5-fluorouracil did not directly affect collagen synthesis in colon fibroblasts under any of the conditions tested it is suggested that the data support the contention that this drug is relatively harmless for intestinal healing.


Amino acid sequence of bovine protein Z: a vitamin K-dependent serine protease homolog.
The amino acid sequence of protein Z has been determined from sequence analysis performed on fragments obtained by chemical and enzymatic degradations. The polypeptide consists of a single chain containing 396 amino acid residues (Mr 43 677). Comparison with the vitamin K-dependent plasma proteins reveals an extensive homology. The N-terminal part, containing 13 gamma-carboxyglutamic acid and one beta-hydroxyaspartic acid residue, is extensively homologous to and of similar length to the light chain of factor X. The remainder of protein Z is homologous to the serine proteases and of similar size to the heavy chain of factor Xa, but of the active site residues only aspartic acid-102 is present. Histidine-57 and serine-195 are replaced in protein Z by threonine and alanine, respectively. The physiological function of protein Z is still uncertain.


Hyperoside: A review on its sources, biological activities, and molecular mechanisms.
Hyperoside is a natural flavonol glycoside in various plants, such as Crataegus pinnatifida Bge, Forsythia suspensa, and Cuscuta chinensis Lam. Medical research has found that hyperoside possesses a broad spectrum of biological activities, including anticancer, anti-inflammatory, antibacterial, antiviral, antidepressant, and organ protective effects. These pharmacological properties lay the foundation for its use in treating multiple diseases, such as sepsis, arthritis, colitis, diabetic nephropathy, myocardial ischemia-reperfusion, pulmonary fibrosis, and cancers. Hyperoside is obtained from the plants and chemical synthesis. This study aims to provide a comprehensive overview of hyperoside on its sources and biological activities to provide insights into its therapeutic potential, and to provide a basis for high-quality studies to determine the clinical efficacy of this compound.


Identification and characterization of transcriptional control region of the human beta 1,4-mannosyltransferase gene.
All asparagine-linked glycans (N-glycans) on the eukaryotic glycoproteins are primarily derived from dolichol-linked oligosaccharides (DLO), synthesized on the rough endoplasmic reticulum membrane. We have previously reported cloning and identification of the human gene, HMT-1, which encodes chitobiosyldiphosphodolichol beta-mannosyltransferase (β1,4-MT) involved in the early assembly of DLO. Considering that N-glycosylation is one of the most ubiquitous post-translational modifications for many eukaryotic proteins, the HMT-1 could be postulated as one of the housekeeping genes, but its transcriptional regulation remains to be investigated. Here we screened a 1 kb region upstream from HMT-1 open reading frame (ORF) for transcriptionally regulatory sequences by using chloramphenicol acetyl transferase (CAT) assay, and found that the region from -33 to -1 positions might act in HMT-1 transcription at basal level and that the region from -200 to -42 should regulate its transcription either positively or negatively. In addition, results with CAT assays suggested the possibility that two GATA-1 motifs and an Sp1 motif within a 200 bp region upstream from HMT-1 ORF might significantly upregulate HMT-1 transcription. On the contrary, the observations obtained from site-directed mutational analyses revealed that an NF-1/AP-2 overlapping motif located at -148 to -134 positions should serve as a strong silencer. The control of the HMT-1 transcription by these motifs resided within the 200 bp region could partially explain the variation of expression level among various human tissues, suggesting availability and importance of this region for regulatory role in HMT-1 expression.


Dietary methionine supplementation to a low-protein diet improved hair follicle development of Angora rabbits.
Angora rabbits fed a low-protein diet exhibit decreased hair production performance. This study was set out to evaluate the effects of methionine on hair properties and nitrogen metabolism in Angora rabbits fed a low-protein diet and to investigate the gene expression related to hair follicle development to determine the possible molecular mechanism of methionine effects on hair follicle development. An experiment was conducted to investigate the effects of DL-methionine addition on a low-protein diet on hair development in Angora rabbits. Angora rabbits were divided into 5 groups: fed a normal diet (control), fed a low-protein diet (LP), or fed an LP supplemented with 0.2%, 0.4%, or 0.6% DL-methionine (Met). The results showed that rabbits in the LP group had lower wool yield than the control rabbits, but the addition of 0.4% to 0.6% Met to LP attenuated these effects (p<0.05). Dietary addition of 0.4% to 0.6% Met to LP increased the apparent nitrogen digestibility, nitrogen utilization rate, and feed efficiency (p<0.05). Feeding LP decreased the insulin-like growth factor 1 (IGF1), keratin-associated protein (KAP) 3.1, and KAP 6.1 mRNA levels compared with the control, but the addition of 0.4% Met in LP attenuated these effects (p<0.05). Relative to the LP or control group, dietary addition of 0.4% Met increased versican mRNA levels. In conclusion, the addition of Met to LP could improves wool production performance and feed efficiency and reduce nitrogen emissions in Angora rabbits. Met can promote hair follicle development, which may be associated with IGF1, KAP, and the versican signaling.


Intolerance of uncertainty moderates the relationship between high personal standards but not evaluative concerns perfectionism and eating disorder symptoms cross-sectionally and prospectively.
Two dimensions of perfectionism related to eating disorder (ED) symptoms are evaluative concerns and high standards. Evaluative concerns are consistently linked with ED symptoms, whereas there are conflicting results regarding high standards and ED symptoms. High standards are unrelated to ED symptoms in some studies and are linked to higher ED symptoms in others. Intolerance of uncertainty (IU) may influence the relation between high standards and ED symptoms; individuals elevated in both IU and high standards may find it distressing to be uncertain about future situations for fear of not living up to high expectations and use ED behaviors to cope with such uncertainty. In the current study (N = 216), we explored whether IU moderates the relationships between high standards and evaluative concerns and ED symptoms, both cross-sectionally and prospectively across two weeks. IU significantly moderated high standards and ED symptoms both cross-sectionally and across time while accounting for baseline ED symptoms, but did not moderate the relationship between evaluative concerns and ED symptoms. Higher standards were associated with greater ED symptoms in individuals higher, but not lower in IU. These findings suggest high standards may only contribute to ED symptoms when individuals are also high in IU.


Primary structural determinants essential for potent inhibition of cAMP-dependent protein kinase by inhibitory peptides corresponding to the active portion of the heat-stable inhibitor protein.
PKI-(5-24)-amide is a 20-residue peptide with the sequence, Thr5-Thr-Tyr-Ala-Asp-Phe-Ile-Ala-Ser-Gly-Arg-Thr-Gly-Arg-Arg-Asn-A la-Ile-His- Asp24-NH2, that corresponds to the active portion of the heat-stable inhibitor protein of cAMP-dependent protein kinase (Cheng, H.-C., Kemp, B. E., Pearson, R. B., Smith, A. J., Misconi, L., Van Patten, S. M., and Walsh, D. A. (1986) J. Biol. Chem. 261, 989-992). Amino acid residues in PKI-(5-24)-amide responsible for the potent inhibition (Ki = 2.3 nM) of the catalytic subunit of protein kinase were further investigated using deletion and substitution analogs of the synthetic peptide. Residues 5, 23, and 24 were not required for activity since the 17-residue PKI-(6-22)-amide retained full potency. Sequential removal of the first seven amino acids from the NH2 terminus of PKI-(5-24)-amide caused a progressive 50-fold loss of inhibitory potency. In contrast, substitution of either Thr6, Asp9, or Ile11 with alanine, or Ala8 by leucine, in PKI-(5-22)-amide produced less than 3-fold decreases in potency. Of the 2 aromatic residues in PKI-(5-22)-amide, the individual substitution of Phe10 and Tyr7 by alanine caused, respectively, 90- and 5-fold decreases in inhibitory potency, demonstrating important roles for each. This NH2-terminal portion of the peptide is believed to contain a significant portion of alpha-helix. Many recognition or structural determinants are also essential in the COOH-terminal portion of PKI-(5-22)-amide. In addition to the basic subsite provided by the three arginines, several other of the residues are critical for full inhibitory potency. Substitution of Ile22 by glycine in either PKI-(5-22)-amide or PKI-(14-22)-amide lowered the inhibitory potency by 150- and 50-fold, respectively. Separate replacement of Gly17 or Asn20, in either PKI-(5-22)-amide or PKI-(14-22)-amide, caused 7-15-fold decreases in potency. Substitution of both Gly17 and Asn20 together (in PKI-(14-22)-amide) produced a synergistic loss of inhibitory activity. [Leu13,Ile14]PKI-(5-22)-amide, a doubly substituted analog exhibited a 42-fold increase in Ki value. We conclude that Ser13 and/or Gly14, Gly17, Asn20, and Ile22 each contribute important features to the binding of these inhibitory peptides to the protein kinase, either by providing recognition determinants, inducing structure, and/or allowing essential peptide backbone flexibility.(ABSTRACT TRUNCATED AT 400 WORDS)


The actin cytoskeleton: a key regulator of apoptosis and ageing?
Evidence from many organisms has shown that the accumulation of reactive oxygen species (ROS) has a detrimental effect on cell well-being. High levels of ROS have been linked to programmed cell death pathways and to ageing. Recent reports have implicated changes to the dynamics of the actin cytoskeleton in the release of ROS from mitochondria and subsequent cell death.


Radar reflector guided axillary surgery in node positive breast cancer patients.
In patients with non-palpable breast cancer, the availability of wireless localization techniques facilitates removal of the target lesion. One such technique uses a radar reflector for localization (RRL). This study evaluates the feasibility and effectiveness of RRL to guide excision of axillary lymph nodes in patients with node-positive breast cancer. Our Breast Cancer Database was queried for patients diagnosed with breast cancer, between 5/2017 and 10/2021, who underwent preoperative placement of a radar reflector into a biopsy proven axillary lymph node. Clinicopathologic data were reported using descriptive statistics. Twenty patients underwent preoperative placement of a radar reflector into the axilla. Intraoperatively, the clip and radar reflector were successfully removed in all patients. Among the 10 patients treated with NAC, 5 patients achieved an axillary pathologic complete response (pCR) and were spared a complete axillary lymph node dissection (cALND). Among the entire cohort, RRL resulted in a 53% reduction in the number of lymph nodes removed. Wireless localization of axillary lymph nodes is safe and feasible. The technique ensures excision of biopsy proven positive axillary lymph nodes and enables a targeted approach to assessing the axilla, both in the setting of NAC and upfront surgery.


Electric-field-modulated exchange coupling within and between magnetic clusters on metal surfaces: Mn dimers on Cu(1 1 1).
The effects of external electric fields (EFs) on the magnetic state and substrate-mediated magnetic coupling between Mn dimers on Cu(1 1 1) have been studied using a first-principles theoretical method. The calculations show that a change in the ground-state magnetic order, from antiferromagnetic (AF) to ferromagnetic (FM), can be induced within an isolated Mn2 on Cu(1 1 1) by applying a moderately strong EF of about 1 V Å(-1). The magnetic exchange coupling between pairs of dimers displays Ruderman-Kittel-Kasuya-Yosida-like oscillations as a function of the interdimer distance, which depend significantly on the magnetic order within the dimers (FM or AF) and on their relative orientation on the surface. Moreover, it is observed that applying EFs allows modulation of the exchange coupling within and between the clusters as a function of the intercluster distance. At short distances, AF order within the dimers is favoured even in the presence of EFs, while for large distances the EF can induce a FM order. EFs pointing outwards and inwards with respect to the surface favour parallel and antiparallel magnetic alignment between the dimers, resspectively. The dependence of the substrate-mediated interaction on the magnetic state of Mn2 is qualitatively interpreted in terms of the differences in the scattering of spin-polarized surface electrons.


Impact of Awareness of Breast Density on Perceived Risk, Worry, and Intentions for Future Breast Cancer Screening among Korean Women.
This study sought to examine perceived risk and concerns for breast cancer according to awareness of breast density and states thereof among Korea women and to identify the impact of such awareness on screening intentions. This study was based on the 2017 Korean National Cancer Screening Survey of a nationally representative and randomly selected sample of Koreans. Ordinal logistic regression was conducted to examine associations for awareness of and knowledge on breast density in relation to psychological factors. Multivariate logistic regression analyses were conducted to investigate significant factors associated with intentions to undergo breast cancer screening. Among a total of 1,609 women aged 40-69 years, 62.0% were unaware of their breast density, and only 29.7% had good breast density knowledge. Awareness of one's breast density and knowledge about breast density were positively associated with perceptions of absolute and comparative risk and cancer worry. Women aware of their breast density (adjusted odds ratio [aOR], 1.35 for women aware of having a non-dense breast; aOR, 4.17 for women aware of having a dense breast) and women with a good level of breast density knowledge (aOR, 1.65) were more likely to undergo future breast cancer screening. Breast density awareness and knowledge showed positive associations with psychological factors and breast cancer screening intentions. However, the majority of Korean women were not aware of their breast density status and demonstrated poor knowledge about breast density. These results demonstrate a need for better health communication concerning breast density.


Haemodynamic response to nitrous oxide during high-dose fentanyl pancuronium anaesthesia.
Ten patients subjected to coronary by-pass surgery were studied to determine the haemodynamic effects of replacing Fio2 1.0 normoventilation with nitrous oxide in oxygen (Fio2 0.3) after induction of anaesthesia with fentanyl (50 micrograms/kg), flunitrazepam and pancuronium. In all patients the application of N2O decreased systemic arterial pressures by an average of 10% (P less than 0.001), but left pulmonary arterial pressures and systemic vascular resistance unchanged. The slight bradycardia induced was associated with moderate depression of the cardiac index and the left ventricular stroke work index (P less than 0.001) at the time when the rate-pressure product was decreased by 20% (P less than 0.001). The cardiac depression produced by N2O was most prominent in patients with left ventricular wall hypokinesia and an ejection fraction below 55%, in whom the cardiac work index was diminished by 29%. The replacement of oxygen with nitrous oxide in oxygen during high-dose fentanyl-pancuronium anaesthesia seems not to be associated with sympathetic stimulation, and the myocardial depressant effect of N2O should be weighed against the possible reduction in myocardial oxygen consumption with special care in patients with compromised myocardial function.


Long-term survival of a patient with pulmonary metastatic urothelial carcinoma following metastasectomy.
Cisplatin-based systemic chemotherapy is the gold standard for the treatment of patients with metastatic urothelial carcinoma (UC), which is a chemosensitive cancer. However, long-term survival has been deemed disappointing. We describe here a case of UC with solitary pulmonary metastasis who had successfully achieved long-term disease-free survival by combination of cisplatin-based chemotherapy and pulmonary metastasectomy. From the finding of this article, we propose that adjuvant chemotherapy may be considered as a viable option after metastasectomy in low volume pulmonary metastatic UC patients.


Telomeres and race: what can we learn about human biology from health differentials?
The advent of molecular technology that can be applied across large population samples has added--rather than reduced--complexity in the analysis of the intertwined effects of social history and heritable factors on health outcomes. The report by Hunt et al. in this issue of Aging Cell provides an example of the promises and dilemmas associated with this increased complexity.


First report of Brevundimonas aurantiaca human infection: infective endocarditis on aortic bioprostheses and supracoronary aortic graft acquired by water dispenser of domestic refrigerator.
Infective endocarditis (IE) is a feared life-threatening complication that requires a multidisciplinary approach. Although a variety of microorganisms have caused IE, Brevundimonas aurantiaca human infection has never been reported previously. To our knowledge, this is the first reported case of endocarditis and human infection due to B. aurantiaca.


Prognostic factors of quality of life after transoral laser microsurgery for laryngeal cancer.
We aimed to evaluate factors influencing quality of life (QOL) after transoral laser microsurgery (TLM) of laryngeal cancer. Four hundred and one consecutive disease-free patients were evaluated 1 year after treatment using the University of Washington-QOL v4, the SF-12 (short form of SF-36), and a questionnaire about self-rated health status. The importance of age, gender, tumor location, tumor size, tumor stage, neck dissection and adjuvant treatment were evaluated. One year after TLM patients had a good QOL, with only 6 % of patients reporting a worsening in their health status. Radiation therapy (p = 0.000) and neck dissection (p = 0.000) were negative factors for disease-specific QOL, whereas age ≥ 70 (p = 0.01) was a positive independent factor for mental score of SF-12. Speech was negatively influenced by tumor size (p = 0.001) as was swallowing by age (p = 0.001) and postoperative radiation (p = 0.000). Patients treated with TLM present a good QOL 1 year after surgery. Radiation and neck dissection negatively impact QOL. Elderly patients cope better with their disabilities.


Biologic failure of a ligament advanced reinforcement system artificial ligament in anterior cruciate ligament reconstruction: a report of serious knee synovitis.
A ligament advanced reinforcement system (LARS) artificial ligament has been proposed for use in anterior cruciate ligament reconstruction in some cases, and an emerging body of reports has shown its success in the short term. However, there are great concerns about the potential risks of complications, which might prevent its extensive use. We report a rare case of serious synovitis 3 years postoperatively in a 26-year-old man who underwent LARS artificial ligament reconstruction. During revision arthroscopy, we observed a large amount of synovial hyperplasia in the knee joint, containing a large amount of hemosiderin deposition. In addition, the femoral tunnel was placed too anteriorly, and the ligament was ruptured near the tibial tunnel. Histologically, there was thick fibrous scar tissue around the graft, and poorly organized fibrous scar tissue infiltrated into the graft fibers, which could cause loss of structural integrity of the ligament and eventual graft failure. Collectively, our findings might arouse further in-depth research on the development of artificial ligament.


Percutaneous cholecystostomy: techniques and applications.
Acute cholecystitis (AC) is a critical condition requiring immediate medical attention and treatment and is one of the most frequently encountered acute abdomen emergencies in surgical practice, requiring hospitalization. Laparoscopic cholecystectomy is considered the favored treatment for patients with AC who are fit for surgery. However, in high-risk patients considered poor surgical candidates, percutaneous cholecystostomy (PC) has been suggested and employed as a safe and reliable alternative option. PC is a minimally invasive, nonsurgical, image-guided intervention that drains and decompresses the gallbladder, thereby preventing its perforation and sepsis. It can act as a bridge to surgery, but it may also serve as a definitive treatment for some patients. The goal of this review is to familiarize physicians with PC and, more importantly, its applications and techniques, pre- and post-procedural considerations, and adverse events.


Psychophysiologic treatment of chronic tinnitus: a randomized clinical trial.
Tinnitus seems to be associated with psychophysiological over-activation (e.g., of head and shoulder muscles). Therefore we aimed to develop and evaluate a new intervention program including a psychophysiological approach. Forty-three tinnitus sufferers were randomized to 2 groups, one receiving a psychophysiologically oriented intervention lasting 7 intervention sessions (plus 2 assessment sessions), whereas the other group waited for a comparable time period. Afterward, patients on the waiting list also received the intervention. Physiological variables were muscle activity of head and shoulders and electrodermal activity. Psychological assessments took place at pretreatment, post-treatment, and 6 months later. Follow-up data were available from 95% of participants. Major outcome variables were self-rating scales (e.g., tinnitus annoyance assessed by the Tinnitus Questionnaire), and diary data (self-control, daily time of perceiving the tinnitus). On most tinnitus specific variables, patients in the treatment group improved significantly more than patients on the waiting list. Main effect sizes for tinnitus-specific variables were up to 0.89. Muscle reactivity of head muscles at the beginning predicted significant treatment effects. Compared with meta-analytical reviews of psychological interventions for tinnitus sufferers, the presented treatment is brief and in the upper range of effectiveness.


Melorheostosis: report of a new case with linear scleroderma.
Melorheostosis is a very rare bone disease of unknown etiology characterised by linear hyperostosis and associated with fibrosis of soft tissues and the skin. This uncommon sclerosing bone dysplasia was first described by Leri and Joanny in 1922, and since then, until 1993, approximately 300 cases were reported in the literature. Linear scleroderma is a localised proliferation of connective tissue and has rarely been associated with melorheostosis. In this paper, we present a new case of melorheostosis with linear scleroderma which, to the best of our knowledge, is the first case reported in Turkey.


Setting ambiguity in C2/c with dibromidotetrakis(1H-pyrazole-kappaN2)manganese(II) as an example. Addendum.
In the paper by Ruth et al. [Acta Cryst. (2007), C63, m566-m569], remarks regarding the results of Bolotina et al. [J. Appl. Cryst. (2003), 36, 1334-1341] are withdrawn.


Acute glucosamine-induced insulin resistance in muscle in vivo is associated with impaired capillary recruitment.
Glucose toxicity and glucosamine-induced insulin resistance have been attributed to products of glucosamine metabolism. In addition, endothelial cell nitric oxide synthase is inhibited by glucosamine. Since insulin has endothelial nitric-oxide-dependent vasodilatory effects in muscle, we hypothesise that glucosamine-induced insulin resistance in muscle in vivo is associated with impaired vascular responses including capillary recruitment. Glucosamine (6.48 mg kg(-1) min(-1) for 3 h) was infused with or without insulin (10 mU kg(-1) min(-1)) into anaesthetised rats under euglycaemic conditions. Glucosamine infusion alone increased blood glucosamine (1.9+/-0.1 mmol/l) and glucose (5.4+/-0.2 to 7.7+/-0.3 mmol/l) (p<0.05) but not insulin. Glucosamine induced both hepatic and muscle insulin resistance as evident from measures of glucose appearance and disposal as well as hind-leg glucose uptake, which was inhibited by approx. 50% (p<0.05). Insulin-mediated increases in femoral arterial blood flow and capillary recruitment were completely blocked by glucosamine. Glucosamine mediates a major impairment of insulin action in muscle vasculature associated with the insulin resistance of muscle. Further studies will be required to assess whether the impaired capillary recruitment contributes to insulin resistance.


Frontiers in functional dyspepsia.
Functional dyspepsia (FD) refers to unexplained pain or discomfort in the upper abdomen and is commonly seen in gastroenterology practice. The underlying pathophysiologic mechanisms associated with FD are unclear, although traditionally, delayed gastric emptying, visceral hypersensitivity to acid or mechanical distention, and impaired gastric accommodation have been implicated as putative physiologic disturbances. It also remains uncertain whether FD and irritable bowel syndrome are different presentations of the same disorder. Recent data on pathophysiologic mechanisms of FD have focused on postprandial motor disturbances (accelerated gastric emptying, antral-fundic incoordination, and abnormal phasic contractions), alterations of neurohormonal mechanisms in response to a meal, and previous acute infection. Pharmacologic therapies for FD may be guided by these novel mechanisms, as current available therapeutic options are limited. Novel prokinetics and gastric accommodation modulators, visceral analgesics, and agents targeting the neurohormonal response to food ingestion are the next therapeutic frontiers in FD. This review summarizes traditional knowledge and more recent advances in the pathophysiology of FD and potential therapeutic opportunities.


Multiple familial pilomatricomas: an unusual case.
Although solitary pilomatricomas are relatively common, multiple pilomatricomas occur rarely, in 2-3.5% of reported cases. The majority of cases of familial multiple pilomatricomas occur in association with myotonic dystrophy. The occurrence of multiple familial pilomatricomas in patients who are otherwise well is extremely rare. We describe a 29-year-old man with multiple pilomatricomas whose father and brother also had similar lesions. There is no history of myotonic dystrophy.


An improved mathematical prediction of the time evolution of the Covid-19 pandemic in Italy, with a Monte Carlo simulation and error analyses.
We present an improved mathematical analysis of the time evolution of the Covid-19 pandemic in Italy and a statistical error analyses of its evolution, including a Monte Carlo simulation with a very large number of runs to evaluate the uncertainties in its evolution. A previous analysis was based on the assumption that the number of nasopharyngeal swabs would be constant. However, the number of daily swabs is now more than five times what it was when we did our previous analysis. Therefore, here we consider the time evolution of the ratio of the new daily cases to number of swabs, which is more representative of the evolution of the pandemic when the number of swabs is increasing or changing in time. We consider a number of possible distributions representing the evolution of the pandemic in Italy, and we test their prediction capability over a period of up to 6 weeks. The results show that a distribution of the type of Planck black body radiation law provides very good forecasting. The use of different distributions provides an independent possible estimate of the uncertainty. We then consider five possible trajectories for the number of daily swabs and we estimate the potential dates of a substantial reduction in the number of new daily cases. We then estimate the spread in a substantial reduction, below a certain threshold, of the daily cases per swab among the Italian regions. We finally perform a Monte Carlo simulation with 25,000 runs to evaluate a random uncertainty in the prediction of the date of a substantial reduction in the number of diagnosed daily cases per swab.


Age-related macular degeneration eyes presenting with cuticular drusen and reticular pseudodrusen.
This study aimed to describe the clinical characteristics of age-related macular degeneration (AMD) eyes with both cuticular drusen (CD) and reticular pseudodrusen (RPD). Clinical records of patients diagnosed with CD or RPD with multimodal imaging was reviewed for patients diagnosed with both CD and RPD. The distribution patterns of CD (macular and diffuse type) and RPD (localized, intermediate, and diffuse type), presence of soft drusen, large drusen (> 200 µm), variant subretinal drusenoid deposits, and macular complications were investigated. Of the 220 eyes of 110 patients diagnosed with CD and 926 eyes of 463 patients diagnosed with RPD, 13 eyes of seven patients met the diagnostic criteria for both CD and RPD. The mean age at initial presentation was 71.4 ± 8.8 years and six patients were female. The mean subfoveal choroidal thickness was 143.8 ± 25.1 µm. The distribution of CD was of the macular type in all eyes. Distribution of RPD was localized in 11 eyes (84.6%) and intermediate in two eyes (15.4%). Soft drusen, large drusen, and variant subretinal drusenoid deposits were present in 13 (100%), 12 (92.3%) and, seven (53.8%) eyes, respectively. Macular neovascularization was observed in two eyes (15.4%). CD and RPD can coexist in eyes with AMD. Multimodal imaging should be used for AMD eyes with features suggestive of CD and RPD, considering the high likelihood of developing late AMD.


Identification of epithelial-mesenchymal transition-related circRNA-miRNA-mRNA ceRNA regulatory network in breast cancer.
Circular RNAs (circRNAs) have attracted lots of attention in tumorigenesis and progression. However, circRNAs as crucial regulators in epithelial-mesenchymal transition have not been systematically identified in breast cancer. The purpose of our research was to investigate the circRNA network associated with epithelial-mesenchymal transition in breast cancer. Expression profiling data of circRNAs were identified by circRNA microarray in transfected ZEB1 and control breast cancer cells. The differentially expressed circRNAs, miRNAs, and mRNAs were determined via fold change filtering. The competing endogenous RNAs (ceRNAs) network was established on the foundation of the relationship between circular RNAs, miRNAs and mRNAs. The CytoHubba was used to determine the hub genes from the protein-protein interaction (PPI) regulatory network. The GEPIA database was used to observe the expression of the hub genes mRNA between breast cancer tissues and normal tissues. The HPA database was applied to investigate the expression of six hub genes at the protein level. Morever, we further used Kaplan-Meier plotter to perform survival analysis of these hub genes. The top three up-regulated differential expressed circRNAs were identified by circRNA microarray. Following the Real-time PCR validation of the three circRNAs, two circRNAs (hsa_circRNA_002082 and hsa_circRNA_400031) were selected for further analysis. After the predicted target miRNA, ten circRNA-miRNA interactions including two circRNAs and ten miRNAs were determined. Furthermore, the Venn diagram was used to intersect the predicted target genes and the differentially expressed genes, and screened 174 overlapped genes. Subsequently, we constructed a PPI network, and selecting six hub genes, containing KIF4A, CENPF, OIP5, ZWINT, DEPDC1, BUB1B. The mRNA expression levels of the six hub genes were obviously up-regulated in breast cancer. The protein expression levels of KIF4A, CENPF, OIP5, and DEPDC1 were significantly increased in breast cancer tissues. Moreover, the survival analysis results revealed that high expression of the six hub genes were obviously correlated with poor prognosis of breast cancer patients. Our study constructed and analyzed a circRNA-associated ceRNA regulatory network and discovered that hsa_circRNA_002082 and hsa_circRNA_400031 may mechanism as ceRNAs to serve key roles in breast cancer epithelial-mesenchymal transition.


Where does the new regime of medical specialty certification go?
The certification system of medical specialty is going to be changed to a new regime after the proposal of reorganization conducted by the Government in 2013. This review focuses on the issue of program-based accreditation of the training institution which is the core of the new regime. In particular, the strategy for surgical subspecialty such as thoracic surgery is discussed.


Stringent control in the archaeal genus Sulfolobus.
Six Archaea belonging to the phylum Euryarchaeota were previously analyzed with respect to stringent control. Only one of the strains studied was shown to possess Bacteria-like stringent control over stable RNA accumulation; ppGpp and pppGpp production was totally lacking in all Archaea analyzed. To broaden our knowledge of stringent control in the Archaea, we examined here the accumulation of stable RNA and the production of ppGpp and pppGpp under amino acid starvation in three species of the genus Sulfolobus belonging to the Crenarchaeota, an archaeal phylum distant from the Euryarchaeota. In these species the accumulation of sRNA was arrested when aminoacylation of tRNA was inhibited by pseudomonic acid. Furthermore, stringent control of stable RNA accumulation was relaxed by some protein synthesis inhibitors that do not interfere with aminoacylation of tRNA, a feature typical of bacterial stringent control. Neither ppGpp nor pppGpp could be detected during growth or under amino acid starvation, and the intracellular GTP levels did not decrease in the course of the stringent response. These results show that: (1) stringency is widespread in wild-type thermoacidophilic archaea; (2) in the crenarchaeal species analyzed here SC depends on the deaminoacylation of tRNA; (3) in the strains analyzed ppGpp is not produced during normal growth nor during the stringent reaction; it is therefore not an effector either of SC over sRNA synthesis or of growth control. (p)ppGpp appears to be completely absent from the Archaea and thus constitutes an additional feature that distinguishes the Bacteria from the Archaea.


Sexual Trauma, Cognitive Appraisals, and Sexual Intrusive Thoughts and Their Subtypes: A Moderated Mediation Analysis.
The relationships between sexual trauma, cognitive appraisals, and subtypes of sexual intrusive thoughts have not been adequately examined in the context of obsessive-compulsive concerns. We employed variations of a moderated mediation model to test these relationships, situating sexual trauma as the predictor, sexual intrusive thoughts as the outcome, cognitive appraisals of these thoughts as the mediator, and subtypes of sexual intrusive thoughts as the moderator of the predictor-mediator link. Based on the continuum perspective, 180 individuals (159 females, 21 males) with or without a history of sexual trauma were recruited to complete measures assessing their most distressing sexual intrusion, cognitive appraisals, and severity of sexual intrusive thoughts. The results indicated that individuals with a history of sexual trauma reported more intrusions with sexual harm content, greater distress with sexual intrusions, more dysfunctional appraisals, and more severe sexual intrusions. The trauma-sexual intrusions link was also separately mediated by responsibility and importance/control appraisals (and when combined), with medium-to-large effect sizes, although this model was not moderated by whether intrusions contained sexual harm content or not. These findings shed light on the posttraumatic effects of sexual violence on sexual intrusions, their appraisals, and level of distress and functional impairment associated with sexual intrusive thoughts, with key clinical and research implications.


Unusual Presentation of Osteoid Osteoma of the Cervical Spine with Dysphagia: A Case Report.
It is uncommon for bony cervical spine lesions to cause dysphagia. Middle-aged female presented in the outpatient clinic with complaints of dysphagia of insidious onset. Patient's medical history, clinical manifestation and imaging studies guided the diagnosis of spinal osteoid osteoma. The presentation and surgical management are discussed in this report. The online version contains supplementary material available at 10.1007/s12070-023-03835-w.


Synthesis and evaluation of N-acetylneuraminic acid-based affinity matrices for the purification of sialic acid-recognizing proteins.
The synthesis of 2-S-(2-aminoethyl) 5-acetamido-3,5-dideoxy-2-thio-D-galacto-2-nonulopyranosidonic acid (1) has been successfully achieved from the precursors methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2-S-acetyl-3,5-dideoxy-2-thio-D-glyce ro-alpha-D-galacto-2-nonulopyranosonate (2) and 2-bromo-N-(tert-butoxycarbonyl)-ethylamine (5). Compounds 1 and 2 were coupled, via amino and thioglycosidic linkages, respectively, to epoxy-activated Sepharose 6B. The resultant affinity adsorbents have proved efficient in purifying the sialic acid-recognizing enzyme Vibrio cholerae sialidase, in a one-step process with yields in the order of 60%.


Long non-coding RNA SPRY4-IT1 promotes proliferation and metastasis in nasopharyngeal carcinoma cell.
Long non-coding RNA SPRY4 intronic transcript 1 (Lnc RNA SPRY4-IT1) was aberrant-expressed in various kinds of cancer. Increasing evidence demonstrated that lnc RNAs involved in tumorigenesis and metastasis. In this study, we aimed to explore the biological role of SPRY4-IT1 on the phenotype of nasopharyngeal carcinoma (NPC) in vitro and in vivo. The expression level of SPRY4-IT1 in NPC cell lines were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) and colony formation assay were used to detect cell proliferation. Wound-healing assay, transwell assay and animal experiment were performed to evaluate the ability of cell migration and metastasis. Cell cycle distribution and apoptosis were determined by flow cytometry. Western blotting and immunofluorescence were employed to identify protein expression. SPRY4-IT1 was significantly up-regulated in several NPC cell lines (6-10B, CNE-2, and HONE-1) compared with human immortalized nasopharyngeal epithelial cell (NP69). Silencing of SPRY4-IT1 inhibited proliferation, migration, and metastasis, and induced significant G2/M phase arrest and apoptosis. Western blotting showed that the expression levels of cell cycle-related proteins (cyclin B1, cdc2 and p-cdc2) were down-regulated and apoptosis-associated proteins (PARP, cleaved PARP and cleaved caspase-3) were up-regulated after knockdown of SPRY4-IT1. The expression level of E-cadherin was increased and the expression of Vimentin, Snail and Twist1 were decreased after the SPRY4-IT1 knockdown. lncRNA SPRY4-IT1 played a significant role in NPC proliferation, migration and metastasis, suggesting that SPRY4-IT1 might be a potential therapeutic target for the treatment of NPC.


Correlation of 19F-NMR spectra of halothane in rat tumor and non-tumor tissues with membrane alterations.
The membrane environments in normal and tumor rat tissue and the effect of hyperthermia thereon are studied with 19F-NMR spectroscopy of the general anesthetic halothane. Normal and tumor cell types are clearly differentiated by the halothane resonance. A hydrophobic environment prominent in tumor tissue is more sensitive to heat treatment than the corresponding environments of normal cells. Studies of extracted lipids suggest that this may be due in part to the considerable difference in lipid temperature response which exists between normal and kidney tumor cells.


[Insertional Achilles tendinopathy : Differentiated diagnostics and therapy].
Achilles tendinopathy at the calcaneal insertion is classified into insertional tendinopathy, retrocalcaneal and superficial bursitis. The aim of this study was to present the current evidence on conservative and surgical treatment of insertional tendinopathy of the Achilles tendon. Conservative first-line therapy includes reduction of activity levels, administration of non-steroidal anti-inflammatory drugs (NSAID), adaptation of footwear, heel wedges and orthoses or immobilization. In addition, further conservative therapy options are also available. Eccentric stretching exercises should be integral components of physiotherapy and can achieve a 40% reduction in pain. Extracorporeal shock wave therapy has been shown to reduce pain by 60% with a patient satisfaction of 80%. Due to the limited evidence, injections with platelet-rich plasma (PRP), dextrose (prolotherapy) or polidocanol (sclerotherapy) cannot currently be recommended. Operative therapy is indicated after 6 months of unsuccessful conservative therapy. Open debridement allows all pathologies to be addressed, including osseous abnormalities and intratendinous necrosis. The success rate of over 70% is contrasted by complication rates of up to 40%. The Achilles tendon should be reattached, if detached by >50%. No valid data are available for the transfer of the tendon of the flexor hallucis longus (FHL) muscle but it is frequently applied in cases of more than 50% debridement of the diameter of the Achilles tendon. Lengthening of the gastrocnemius muscle cannot be recommended because insufficient data are available. Tendoscopy is a promising treatment option for isolated retrocalcaneal bursitis and has shown similar success rates to open debridement with significantly lower complication rates.


Are Primary Health Care Features Associated with Reduced Late Neonatal Mortality in Brazil? An Ecological Study.
To analyze the effect and efficiency of the characteristics of PHC facilities' structures and the work process of PHC teams on late neonatal mortality (LNM). This ecological time-series study adopted 3.764 Brazilian municipalities as analysis units. The independent variables were sorted into three hierarchical levels and four blocks. The distal level consisted of economic and demographic variables; the intermediate level comprised health coverage and demand for services; and the proximal level included structure and work process. The dependent variable was LNM. A linear mixed-effects regression analysis with a hierarchical approach was performed, estimating the crude (β) and adjusted (alpha = 5%) regression coefficients. Data involution analysis and municipalities were the decision-making unit according to their strata. LNM was directly associated with the number of live births and unemployment rate. LNM was inversely associated with the year, per capita income, the community health worker's strategy coverage, vaginal delivery, household visits, and available vaccines. In the 2002-2014 period, the number of municipalities efficient in reducing LNM dropped from 38 to 27. In 2014, a more significant investment occurred in the number of vaginal deliveries in almost all strata to make inefficient municipalities efficient. The deaths of children aged 7-28 days are affected by the characteristics of the PHC structure and work process.


Effect of Grape Marc Added Diet on Live Weight Gain, Blood Parameters, Nitrogen Excretion, and Behaviour of Sheep.
A 39-day field experiment was conducted to assess the effect of grape marc (GM) feeding on sheep productivity, health, and environmental sustainability. Forty merino sheep were divided into two dietary groups, each having five replications (n = 4 sheep/replication). Experimental diet consisted of: (i) control: 55% lucerne hay + 40% wheat grain + 5% faba bean; (ii) GM treatment: control diet with 20% replaced by GM on a dry matter (DM) basis. The GM treatment contained 2-10% higher phytochemical contents than the control. The DMI from the GM treatment was 15% higher than the control (p < 0.001). No difference was found in sheep live weight gain, behaviour, and quality between groups (p > 0.05). No difference was found in total faecal production, faecal organic matter, and nitrogen contents (p > 0.05) and parasitic egg count. The GM treatment led to higher nitrogen intake (23.1 vs. 27.2 g/d) and faecal nitrogen excretion (6.3 vs. 8.7 g/d) compared to the control. Urinary creatinine, allantoin, and purine derivatives were lower in the GM treatment than control (p < 0.05). However, both groups had similar purine derivatives/DMI (i.e., indicator of rumen microbial protein synthesis efficiency; p > 0.05). Overall, the results showed that GM can replace 20% of the control ration to maintain sheep productivity, health, and environmental sustainability.


Perceived benefits of the hepatitis C peer educators: a qualitative investigation.
Although opioid-dependent patients are disproportionately impacted by hepatitis C (HCV), many do not receive treatment. In addition to HCV treatment-access barriers, substance-using patients may be reluctant to pursue treatment because of wariness of the medical system, lack of knowledge, or stigma related to HCV treatment. Implementation of a formal peer education program is one model of reducing provider- and patient-level barriers to HCV treatment, by enhancing mutual trust and reducing stigma. We used thematic qualitative analysis to explore how 30 HCV patients and peer educators perceived a HCV peer program within an established methadone maintenance program in the USA. Participants unanimously described the program as beneficial. Participants described the peer educators' normalization and dispelling of myths and fears around HCV treatment, and their exemplification of HCV treatment success, and reductions in perceived stigma. Peer educators described personal benefits. These findings indicate that HCV peer educators can enhance HCV treatment initiation and engagement within opioid substitution programs.


Contribution of iron status at birth to infant iron status at 9 months: data from a prospective maternal-infant birth cohort in China.
The contribution of iron status at birth to iron status in infancy is not known. We used a physiologic framework to evaluate how iron status at birth related to iron status at 9 months, taking iron needs and sources into account. In a longitudinal birth cohort in China, iron status measures in cord blood and venous blood in infancy (9 months) and clinical data were prospectively collected in 545 healthy term maternal-infant dyads. We used structural equation modeling (SEM) to create a 9-month iron composite and to assess direct and indirect contributions of multiple influences on 9-month iron status. Logistic regression was used to calculate odds ratios for iron deficiency (ID), iron deficiency anemia (IDA), and anemia. Approximately 15% (78/523) of infants were born with cord SF <75 µg/l, suggesting fetal-neonatal ID. At 9 months, 34.8% (186/535) and 19.6% (105/535) of infants had ID and IDA, respectively. The following factors were independently associated with poorer 9-month iron status: higher cord zinc protoporphyrin/heme (ZPP/H) (adjusted estimate -0.18, P < 0.001) and serum transferrin receptor (sTfR) (-0.11, P = 0.004), lower cord hemoglobin (Hb) (0.13, P = 0.004), lower birth weight (0.15, P < 0.001), male sex (0.10, P = 0.013), older age at testing (-0.26, P < 0.001), higher 9-month weight (-0.12, P = 0.006) and breastfeeding (0.38, P < 0.001). Breastfeeding at 9 months showed the strongest association, adjusting for all other factors. Compared to formula-fed infants, the odds of IDA were 19.1 (95% CI: 6.92, 52.49, P < 0.001) and 3.6 (95% CI: 1.04, 12.50, P = 0.043) times higher in breastfed and mixed-fed infants, respectively. Indicators of iron status at birth, postnatal iron needs, and iron sources independently related to iron status at 9 months. Sex was an additional factor. Public health policies to identify and protect infants at increased risk of ID should be prioritized.


Risk factors of asymptomatic restenosis in patients with first anterior ST elevation myocardial infarction treated by primary percutaneous coronary intervention.
The issue of predicting coronary artery restenosis, especially silent, in patients following primary percutaneous coronary intervention (PCI) has been extensively studied, however, risk factors have not been fully defined. To asses the frequency of silent restenosis and its predictors in patients with anterior ST elevation myocardial infarction (STEMI) treated with primary PCI and implantation of bare metal stents (BMS). We recruited a cohort of 114 patients with first anterior STEMI treated with primary PCI within 12 hours of the onset of symptoms, and with the left anterior descending coronary artery occlusion (TIMI 0) and successful flow restoration (TIMI 3). A 12-lead ECG was performed before and 60 minutes after PCI. Troponin I and CK-MB were measured on admission and after six, 12 and 24 hours. Transthoracic echocardiography (TTE) was performed at discharge. Resting TTE and coronary angiography were performed after a six month follow-up in asymptomatic patients. The frequency of silent restenosis in our study group was 23.9%. The best multivariate models in logistic regression of restenosis prediction were: lower end-systolic volume of the left ventricle assessed two days after infarction longer lesion and smaller reference diameter of the stented vessel. Silent restenosis in patients with first anterior STEMI treated by primary PCI with the use of BMS is still frequent. The best ways to identify patients with silent restenosis at six month follow-up, apart from the lower end systolic volume in the echocardiographic study, are longer narrowing in the infarct-related artery and lower reference diameter of the treated vessel.


Post-ictal Generalized EEG Suppression is reduced by Enhancing Dorsal Raphe Serotonergic Neurotransmission.
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. A proposed risk marker for SUDEP is the duration of post-ictal generalized EEG suppression (PGES). The mechanisms underlying PGES are unknown. Serotonin (5-HT) has been implicated in SUDEP pathophysiology. Seizures suppress activity of 5-HT neurons in the dorsal raphe nucleus (DRN). We hypothesized that suppression of DRN 5-HT neuron activity contributes to PGES and increasing 5-HT neurotransmission or stimulating the DRN before a seizure would decrease PGES duration. Adult C57BL/6J and Pet1-Cre mice received EEG/EMG electrodes, a bipolar stimulating/recording electrode in the right basolateral amygdala, and either a microdialysis guide cannula or an injection of adeno-associated virus (AAV) allowing expression of channelrhodopsin2 plus an optic fiber into the DRN. Systemic application of the selective 5-HT reuptake inhibitor citalopram (20 mg/kg) decreased PGES duration from seizures induced during wake (n = 23) and non-rapid eye movement (NREM) sleep (n = 13) whereas fluoxetine (10 mg/kg) pretreatment decreased PGES duration following seizures induced from wake (n = 11), but not NREM sleep (n = 9). Focal chemical (n = 6) or optogenetic (n = 8) stimulation of the DRN reduced PGES duration following seizures in kindled mice induced during wake. During PGES, animals exhibited immobility and suppression of EEG activity that was reduced by citalopram pretreatment. These results suggest 5-HT and the DRN may regulate PGES.


Audiological Diagnosis in a Case of Retrocochlear Pathology Post Traumatic Brain Injury: A Case Report.
This case report is a follow up of a patient with traumatic brain injury (TBI) post road traffic accident; hearing loss, speech understanding difficulty and tinnitus being the main complaints. CT scan showed brainstem contusion. The diagnosis of retro-cochlear pathology was arrived at after using a test battery approach.