MicroRNA 486-3p directly targets BIK and regulates apoptosis and invasion in colorectal cancer cells.
MicroRNAs influence almost every genetic pathway and are involved in colorectal cancer (CRC). However, the biological role of miR486-3p in CRC remains to be elucidated. In this study, miR486-3p expression in CRC cell lines and normal colonic epithelial cells was determined. After miR486-3p mimic, inhibitor, and BIK siRNA transfection, cell proliferation, apoptosis, and migration were examined. Furthermore, the target of miR486-3p was identified by luciferase-reporter assay and underlying molecular mechanisms studied. The results revealed that miR486-3p was significantly upregulated in CRC compared with normal colonic epithelial cells, whereas BIK expression was remarkably downregulated in CRC cells. MTT assays demonstrated that suppression of miR486-3p expression reduced CRC cell proliferation, whereas elevated miR486-3p or BIK silencing induced cell proliferation. Wound-healing assays and transwell experiments revealed that both upregulation of miR486-3p and down-regulation of BIK increased CRC cell migration and invasion ability. Moreover, bioinformatic target prediction identified BIK as a putative target of miR486-3p. Knockdown of miR486-3p was shown to upregulate BIK expression, whereas overexpression of miR486-3p suppressed the expression of BIK. Luciferase reporter assay results further confirmed this deduction. In conclusion, these findings suggest that miR486-3p is an oncogene in CRC. Gene therapy using miR486-3p inhibition may provide a new clue for CRC therapy.


Ileocolonic anastomotic ulcers: a case series and review of the literature.
Although gastric anastomotic ulcers have been well described, there are only a few reports in the literature, mostly in the pediatric population, of ulcers occurring at colonic anastomotic sites. Our aim was to determine the clinical profile of postoperative colonic anastomotic ulcers in adult patients undergoing colonoscopy at our institution. We performed a retrospective review of colonoscopies done at our institution between 1993 and 1997. Six patients with colonic anastomotic ulcers were identified; all had ileocolonic anastomoses. All patients presented with iron deficiency anemia with evidence of gastrointestinal (GI) blood loss and this was the indication for colonoscopy. The age at the time of ileocolonic anastomoses ranged from birth to 74 yr and age at the time of colonoscopy ranged from 24 to 76 yr. The interval between surgery and detection of anastomotic ulcer ranged from 15 months to 28 yr. Only two patients had a possible etiology: one with previous small bowel Crohn's disease, and the other with significant nonsteroidal antiinflammatory drugs (NSAID) use and evidence of small-bowel ulcers in the adjacent ileum as well. Three of the patients had previously undergone surgical resection and revision of the anastomosis without benefit; the ulcers recurred at the new anastomosis and continued to bleed. Ulcers can develop at sites of ileocolonic anastomoses. The commonest presentation is with iron deficiency anemia due to occult blood loss. The etiology of the ulcer, in most patients, remains speculative. The therapeutic approach to these ulcers is to discontinue all NSAIDs, treat underlying inflammatory bowel disease, if present, and supplement with oral iron. Surgery should be reserved for life-threatening bleeds or for anemia refractory to oral iron therapy.


Client self rated adult attachment patterns and the therapeutic alliance: a systematic review.
Attachment theory has been proposed as a suitable framework within which to understand and explore the therapeutic alliance. This review systematically explores research that has examined the relationship between clients' self reported attachment patterns and the therapeutic alliance. Methodological characteristics and study findings are reviewed and discussed with the aim of concluding whether assessing clients' attachment patterns would be beneficial to therapy. In spite of inconsistencies with regards to the measurement and conceptualisation of attachment and the alliance, the evidence suggests that clients who rate themselves as having a more secure attachment pattern are likely to rate the alliance as stronger. The implications of this for therapeutic practice are discussed.


The Cometary and Interstellar Dust Analyzer at comet 81P/Wild 2.
The CIDA (Cometary and Interstellar Dust Analyzer) instrument on the Stardust spacecraft is a time-of-flight mass spectrometer used to analyze ions formed when fast dust particles strike the instrument's target. In the spectra of 45 presumably interstellar particles, quinone derivates were identified as constituents in the organic component. The 29 spectra obtained during the flyby of Comet 81P/Wild 2 confirm the predominance of organic matter. In moving from interstellar to cometary dust, the organic material seems to lose most of its hydrogen and oxygen as water and carbon monoxide. These are now present in the comet as gas phases, whereas the dust is rich in nitrogen-containing species. No traces of amino acids were found. We detected sulfur ions in one spectrum, which suggests that sulfur species are important in cometary organics.


Achievement and maintenance of complete remission in a patient with acute myelogenous leukemia after weekly administration of interleukin-2.
Several groups have used high doses of interleukin-2 (IL-2), achieving a significant rate of responses in patients with acute myelogenous leukemia (AML). These results have mainly been observed in AML patients with limited disease (bone marrow blasts < 25%), but this therapy is associated with significant toxicity which is dose-related. In this report we describe a patient with AML in whom conventional chemotherapy had achieved partial remission. This patient received subcutaneously intermediate doses of IL-2 (12 x 10(6)/m2/week) and achieved complete remission which was maintained for eleven months. The side effects of IL-2 were mild. The results of this report document the antileukemic effect of IL-2 in AML with limited disease as well as the efficacy of subcutaneous maintenance treatment for prolonged periods.


Guided remote endarterectomy for superficial femoral artery occlusions: a technical note.
The aim of this paper was to describe a new modification of the remote endarterectomy for the treatment of long superficial femoral artery (SFA) occlusions and to present our preliminary results. Through a subinguinal incision and arteriotomy over the SFA origin, a hydrophilic guidewire was introduced into the subintimal plane of the SFA and advanced distally until reentry into the distal patent popliteal artery. The hydrophilic guidewire is exchanged for an Ablatz wire to provide support for the advancement of the single endarterectomy ring. The MollRing Cutter was introduced in the SFA after the removal of the single endarterectomy ring and it was advanced until the re-entry point. The atherosclerotic core was removed and a nitinol self-expanding stent was placed at the peripheral end of the endarterectomy. Arteriotomy was closed with a patch. Guided subintimally-assisted remote endarterectomy seems to be a successful and safe modification of the traditional technique in the treatment of SFA occlusion, in patients with critical limb ischemia.


Growth hormone treatment for growth hormone deficiency and idiopathic short stature: new guidelines shaped by the presence and absence of evidence.
The Pediatric Endocrine Society recently published new guidelines for the use of human growth hormone (hGH) and human insulin-like growth factor-I (hIGF-I) treatment for growth hormone deficiency, idiopathic short stature, and primary IGF-I deficiency in children and adolescents. This review places the new guidelines in historical contexts of the life cycle of hGH and the evolution of US health care, and highlights their future implications. The new hGH guidelines, the first to be created by the Grading of Recommendations Assessment, Development and Evaluation approach, are more conservative than their predecessors. They follow an extended period of hGH therapeutic expansion at a time when US health care is pivoting toward value-based practice. There are strong supporting evidence and general agreement regarding the restoration of hormonal normalcy in children with severe deficiency of growth hormone or hIGF-I. More complex are issues related to hGH treatment to increase growth rates and heights of otherwise healthy short children with either idiopathic short stature or 'partial' isolated idiopathic growth hormone deficiency. The guidelines-developing process revealed fundamental questions about hGH treatment that still need evidence-based answers. Unless and until such research is performed, a more restrained hGH-prescribing approach is appropriate.


[Forensic medical expertise of the injurious exposure].
The objective of the present study was to develop the standardized approach to the evaluation of the character of injurious exposure with a view to objective interpretation of the conditions of injury formation and the properties of the traumatic agent. The main attention was given to such parameters of the injurious exposure as loading conditions (mass, speed, direction) and the surface properties of the traumatic agent (area, shape, hardness). It is expected that the use of the proposed system for the evaluation of the injurious exposure in the practical work of forensic medical experts will enhance the reliability of their conclusions and help to avoid mistakes.


The effect of repeated preheating of dimethacrylate and silorane-based composite resins on marginal gap of class V restorations.
Background. One of the problems with composite resin restorations is gap formation at resin‒tooth interface. The present study evaluated the effect of preheating cycles of silorane- and dimethacrylate-based composite resins on gap formation at the gingival margins of Class V restorations. Methods. In this in vitro study, standard Class V cavities were prepared on the buccal surfaces of 48 bovine incisors. For restorative procedure, the samples were randomly divided into 2 groups based on the type of composite resin (group 1: di-methacrylate composite [Filtek Z250]; group 2: silorane composite [Filtek P90]) and each group was randomly divided into 2 subgroups based on the composite temperature (A: room temperature; B: after 40 preheating cycles up to 55°C). Marginal gaps were measured using a stereomicroscope at ×40 and analyzed with two-way ANOVA. Inter- and intra-group comparisons were analyzed with post-hoc Tukey tests. Significance level was defined at P < 0.05. Results. The maximum and minimum gaps were detected in groups 1-A and 2-B, respectively. The effects of composite resin type, preheating and interactive effect of these variables on gap formation were significant (P<0.001). Post-hoc Tukey tests showed greater gap in dimethacrylate compared to silorane composite resins (P< 0.001). In each group, gap values were greater in composite resins at room temperature compared to composite resins after 40 preheating cycles (P<0.001). Conclusion. Gap formation at the gingival margins of Class V cavities decreased due to preheating of both composite re-sins. Preheating of silorane-based composites can result in the best marginal adaptation.


Epidemiological surveillance of Serratia marcescens infections by bacteriocin typing.
During 10 months, 155 isolates of Serratia marcescens were cultured from 105 patients, of whom 49 were considered to have significant infection. The 155 isolates were typed by bacteriocin sensitivity, and 137 (88.4%) were assigned to 37 provisional bacteriocin groups; 18 isolates were nontypable. No major outbreaks of nosocomial infection were demonstrable; however, there were four chronologically separate minor episodes of cross-infection that involved two or three patients per room or unit, respectively.


Effects of N(omega)-nitro-L-arginine (L-NOARG) on blood flow and vasomotion in rat diaphragm microcirculation during hemorrhagic hypotension.
The role of N(omega)-nitro-L-arginine (L-NOARG), a nitric oxide (NO) synthase inhibitor, in the control of blood flow and vasomotion in rat diaphragm microcirculation during hemorrhagic hypotension was investigated by means of laser Doppler flowmetry (LDF). Fifty-six Sprague-Dawley rats were divided into seven groups. Ten minutes after one-stage hemorrhage to 40-60% of initial blood pressure, the rats received 15 min topical superfusion of saline (group 1, time control), 0.1 mM L-NOARG (group 2), 10 mM L-arginine (group 3), or vehicle (0.1% DMSO and 0.9 mN NaOH, group 4). For groups 5 and 6, L-NOARG or its vehicle was superfused for 15 min without hemorrhage. In group 7, the vasodilator responses to the endothelium-dependent vasorelaxant acetylcholine (ACH) and the endothelium-independent vasorelaxant sodium nitroprusside (SNP) were assessed at rest and after 25 min of hemorrhagic hypotension. The results showed no significant differences in blood flow, fundamental frequency, or relative amplitude of the rat diaphragm microcirculation before or after administration of the test agents among the first four groups during hemorrhagic hypotension or in groups 5 and 6 during sham operation without hypoperfusion. Hemorrhagic hypotension significantly decreased the vasodilator response to ACH (p = 0.003), but not to SNP. We conclude that NO did not play an important role in the regulation of blood flow or vasomotion in rat diaphragm microcirculation during acute hemorrhagic hypotension.


Reirradiation for patients with recurrence head and neck squamous cell carcinoma: a single-institution comparative study.
In the last decade, the number of publications that report on the use of external beam radiotherapy and high-dose-rate brachytherapy (HDR-BRT) in the treatment of recurrent head and neck cancer has increased, but no studies compare external beam radiotherapy and HDR-BRT. The aim of this study was to evaluate and to compare the efficacy and toxicity of the three-dimensional conformal radiotherapy (3D-CRT) and HDR-BRT in the treatment of recurrent head and neck cancer. A total of 64 patients with head and neck cancer recurrence were randomly assigned at a 1:1 ratio to receive either 3D-CRT (50Gy/25 fractions) in the control group or HDR-BRT (30Gy/12 fraction) in the experimental group. The overall survival rate of patients treated with HDR-BRT at 1 and 2-years was 74% and 67%, respectively, compare to 3D-CRT group - 51% and 32%, respectively (P=0.002). Local control at 1- and 2-years in patients who received HDR-BRT was 77% and 63% compare with 47% and 25%, respectively, for the patients who received the 3D-CRT (P<0.001). Most patients developed mild to moderate acute mucositis and dermatitis. In the 3D-CRT group, severe late toxicity was determined in 11 patients (35.5%), and in the HDR-BRT group, in 1 patient (3.1%) (P=0.001). There was no grade 5 toxicity. Following our results, we concluded that HDR-BRT is a more effective and safer treatment approach for head and neck cancer recurrences than 3D-CRT.


[Development, organization and evaluation of a public health surveillance system].
Health professionals who set health policies and manage prevention and disease control programs are committed to the goals of reducing disease and injury related morbidity and mortality and improving the public's health and quality of life. To determine what health policies are needed and what specific actions should be taken and which epidemiological investigations should be carried out in order to identify lack of coverage of public health programs, decision makers need continuous information in order to tackle upcoming technical questions and to identify the most serious existing and emerging health problems of today's society. Both, political decision makers and health professionals have to ask themselves how those health problems can be prevented and which are the most cost-effective prevention and control strategies for this purpose. Other important issues for the implementation of public health surveillance is the feasibility of available control strategies and their possible impact on different health outcomes. Alternative prevention and control activities have to be evaluated as how they meet the proposed objectives. Finally, remains the question, how scarce economic, material and human recourses should be allocated and targeted in order to achieve maximum impact for health goals. Only a sophisticated public health surveillance system can give answers to all those issues. Surveillance is defined as the ongoing systematic collection, analysis and interpretation of date on specific health events for use in planning, implementation and evaluation of public health programs. Timely dissemination of these data to persons who need to know is essential to effective prevention and control.(ABSTRACT TRUNCATED AT 250 WORDS)


Na+-stimulated ATPase of alkaliphilic halotolerant cyanobacterium Aphanothece halophytica translocates Na+ into proteoliposomes via Na+ uniport mechanism.
When cells are exposed to high salinity conditions, they develop a mechanism to extrude excess Na+ from cells to maintain the cytoplasmic Na+ concentration. Until now, the ATPase involved in Na+ transport in cyanobacteria has not been characterized. Here, the characterization of ATPase and its role in Na+ transport of alkaliphilic halotolerant Aphanothece halophytica were investigated to understand the survival mechanism of A. halophytica under high salinity conditions. The purified enzyme catalyzed the hydrolysis of ATP in the presence of Na+ but not K+, Li+ and Ca2+. The apparent Km values for Na+ and ATP were 2.0 and 1.2 mM, respectively. The enzyme is likely the F1F0-ATPase based on the usual subunit pattern and the protection against N,N'-dicyclohexylcarbodiimide inhibition of ATPase activity by Na+ in a pH-dependent manner. Proteoliposomes reconstituted with the purified enzyme could take up Na+ upon the addition of ATP. The apparent Km values for this uptake were 3.3 and 0.5 mM for Na+ and ATP, respectively. The mechanism of Na+ transport mediated by Na+-stimulated ATPase in A. halophytica was revealed. Using acridine orange as a probe, alkalization of the lumen of proteoliposomes reconstituted with Na+-stimulated ATPase was observed upon the addition of ATP with Na+ but not with K+, Li+ and Ca2+. The Na+- and ATP-dependent alkalization of the proteoliposome lumen was stimulated by carbonyl cyanide m - chlorophenylhydrazone (CCCP) but was inhibited by a permeant anion nitrate. The proteoliposomes showed both ATPase activity and ATP-dependent Na+ uptake activity. The uptake of Na+ was enhanced by CCCP and nitrate. On the other hand, both CCCP and nitrate were shown to dissipate the preformed electric potential generated by Na+-stimulated ATPase of the proteoliposomes. The data demonstrate that Na+-stimulated ATPase from A. halophytica, a likely member of F-type ATPase, functions as an electrogenic Na+ pump which transports only Na+ upon hydrolysis of ATP. A secondary event, Na+- and ATP-dependent H+ efflux from proteoliposomes, is driven by the electric potential generated by Na+-stimulated ATPase.


In Utero Tenofovir Exposure Is not Associated With Fetal Long Bone Growth.
Despite widespread use of tenofovir disoproxil fumarate (TDF) in pregnant and breastfeeding women, few data exist on fetal bone development after in utero TDF exposure. We evaluated fetal long bone growth in human immunodeficiency virus (HIV)-infected pregnant woman/fetus dyads in Cape Town, South Africa. Women were recruited from primary care antenatal services and underwent ultrasonography to determine femur (FLZ) and humerus (HLZ) length z scores. The duration of in utero TDF exposure was calculated in weeks. Linear regression models were applied to assess the associations between the duration of in utero TDF exposure and change in FLZ and HLZ. A total of 646 woman/fetus dyads contributed 1376 ultrasonographic scans to this analysis: 132 dyads with ≥25 weeks, 326 with 10-24 weeks, and 188 with <10 weeks of TDF exposure. Women receiving TDF for ≥25 weeks were older than those receiving TDF for 10-24 or <10 weeks (median age, 31 vs 28 and 28 years, respectively; P < .01), and had lower HIV RNA levels (median log10 HIV RNA level, 1.59 vs 4.08 and 3.83, respectively; P < .01). Throughout gestation, overall median FLZ and HLZ were 0.30 (interquartile range, -0.03 to 0.63) and 0.22 (-0.26 to 0.59) respectively. In multivariate analysis, there was no association between duration of in utero TDF exposure per 1-week increment and change in FLZ (ß = .00; P = .51) or change in HLZ (ß = .00; P = .40). Results were similar using mixed-effects models. Although longer follow-up is needed, these in utero data are reassuring and support the continued use of TDF in pregnancy.


IMPACT OF HEADLIGHT GLARE ON PEDESTRIAN DETECTION WITH UNILATERAL CATARACT.
Detecting pedestrians while driving at night is difficult, and is further impeded by oncoming headlight glare (HLG). Cataracts increase intraocular light scattering, making the task even more challenging. We used a within-subjects repeated measures design to determine the impact of HLG on driving with unilateral cataract. Pedestrian detection performance of six young normal vision (NV) subjects was measured with clear lens glasses and with simulated unilateral cataract (0.8 Bangerter foil) glasses. The subjects drove night-time scenarios in a driving simulator with and without custom simulated headlight glare. With simulated unilateral cataracts, pedestrian detection rates decreased and response times increased with oncoming HLG. We verified these effects with six patients who already underwent cataract surgery for one eye and were scheduled to get cataract surgery in the other eye. We measured their performance before and after the second cataract surgery. The results were similar to those obtained with the simulated unilateral cataract, confirming that a negative impact of HLG persists with untreated cataract in one eye.


A case of masquerading alloantibodies: the value of a multitechnique approach.
In an immunohematology reference laboratory, samples received for antibody identification react in many different ways requiring a variety of approaches. Sometimes, the clues from initial testing can lead to faulty assumptions and misdirection. Fortunately, a well-supplied reference laboratory will have access to a variety of techniques and reagents that, when used together, can reveal the true identity of the antibodies involved. We present a case of a patient sample with an apparent group AB, D+ blood type showing strong reactivity with all cells tested in the forward and reverse ABO, in the D testing as well as in a three-cell antibody screen. The initial assumption was that the plasma contained a cold autoantibody. Subsequent testing, including the use of gel column technology, ficin-treated cells, and antisera for phenotyping, showed the apparent cold autoantibody to bea red herring. Additional tube testing at immediate spin, 37°C,and indirect antiglobulin test (IAT) revealed the presence of four alloantibodies: anti-M and anti-E reacting at immediate spin, 37°C, and IAT plus anti-Fy(a) and anti-Jk(b) reacting at lAT.


[Direction of strategic use: a new classification of non-steroidal anti-inflammatory drugs based on reactivity with peroxidase].
The pharmaceutical effects of non-steroidal anti-inflammatory drugs (NSAIDs) occur through the inhibition of prostaglandin H synthase (PGHS). Prostaglandin H2 is produced from arachidonic acid via peroxidase and cyclooxygenase cycles in PGHS. NSAIDs exhibit different levels of reactivity in these reaction cycles. To prevent the development of side effect while maintaining the beneficial effects of drugs, a therapeutic strategy should be used. A new classification of NSAIDs has been proposed based on reactivity to peroxidase. Class 1 includes the majority of NSAIDs, which react with horseradish peroxidase (HRP) compounds I and II. Also, their drugs exhibit spectral changes induced by PGHS peroxidase and diminished ESR signals of the tyrosyl radical of metmyoglobin. They reduce compounds I and II of HRP and scavenge tyrosyl radicals. The branched chain mechanism by which the porphyrin radical is transferred to the tyrosine residue of the protein might be blocked by these NSAIDs. Class 2 includes salicylic acid derivatives that react only with the porphyrin radical and do not react with HRP compound II (oxoferryl species). Class 3 includes aspirin, nimesulide, tolmetin, and arylpropionic acid derivatives, including ibuprofen and the coxibs such as celecoxib and rofecoxib, which are not substrates for HRP or PGHS peroxidase. It seems that the selectivity of NSAIDs to PGHS1 and PGHS2 depends on their reactivity with cyclooxygenase rather than with the peroxidase of PGHS. The best drug for each inflammatory disease should therefore be selected for therapy.


Does regular antenatal exercise promote exclusive breastfeeding during the first 3 months of life? Secondary analyses of a randomized controlled trial.
Exclusive breastfeeding (EBF) and antenatal exercise are independently associated with positive short- and long-term health effects for women and their children. The aims of the study were to investigate whether antenatal exercise promotes EBF three months postpartum and further to explore factors associated with EBF at three months postpartum. This study was a follow-up of a Norwegian two-center randomized controlled trial to assess the effect of an antenatal exercise protocol. The recruited pregnant women were randomized to either a 12-week standardized antenatal exercise program with one weekly group training led by a physiotherapist and two weekly home training sessions or standard antenatal care. Women reported breastfeeding status in a questionnaire at three months postpartum. Of the 726 women, 88% were EBF at three months postpartum. There was no significant difference in EBF rates between the intervention group (87%) and the control group (89%). EBF was positively associated with maternal education (AOR=3.4; 95% CI: 1.7-6.7) and EBF at discharge from the hospital (AOR=22.2; 95% CI: 10-49). Admission to neonatal intensive care unit was identified as a significant barrier to EBF (AOR=0.2; 95% CI: 0.1-0.4). Significantly more women in the non-EBF group had sought professional help compared to women in the EBF group (p≤0.001). Regular physical exercise during pregnancy did not influence the exclusive breastfeeding rates at three months postpartum. Considering the health effects of exclusive breastfeeding and antenatal physical exercise, studies with follow-up periods beyond three months postpartum are warranted.


A phase II study of intensified chemotherapy alone as initial treatment for newly diagnosed anaplastic oligodendroglioma: an interim analysis.
Anaplastic oligodendrogliomas (AO) and anaplastic oligoastrocytomas (AOA) are currently treated with a combination of surgery, radiotherapy and chemotherapy. Myeloablative therapy with autologous peripheral blood progenitor cell rescue (APBPCR) is one strategy to exploit the chemosensitivity of these tumors while deferring cranial radiation in an effort to avoid radiation-related neurotoxicity. Twenty patients (16 AO, 4 AOA) with a median age of 46 years (range, 19-60) and KPS of 90 (range, 70-100) were treated with 4 cycles of procarbazine, Lomustine (CCNU) and vincristine (I-PCV) every six weeks. Responding patients were eligible for myeloablative therapy with busulfan and thiotepa followed by APBPCR. 1p and 19q chromosomes were analyzed prospectively but patients were enrolled without regard to deletion status. Fifteen patients (75%) had a response to I-PCV and 14 underwent transplant. Median disease-free and overall survival of the transplanted patients has not been reached but is at least 36 months. No patients required dose reduction or termination of I-PCV due to toxicity. Hepatic veno-occlusive disease (VOD) was a complication of transplant in three patients and resulted in one death. Patients with and without deletions of 1p and 19q had durable responses. This regimen conferred durable responses in more than one-half of patients, allowing deferral of radiotherapy for three years or longer. The major limitation of this approach is the acute toxicity associated with both the induction and consolidation regimens; temozolomide has replaced I-PCV for the current trial and the incidence and severity of VOD is being followed closely.


IL-1 serves as a secondary signal for IL-9 expression.
IL-9 is produced in vitro by activated CD4+ T cell lines of the Th2 subtype and by naive CD4+ T cells. Here we show that T cell lines stimulated with Con A in the presence of accessory cells (AC) such as irradiated spleen cells or bone marrow-derived macrophages produced substantially more IL-9 than T cells stimulated with Con A alone. These data suggest that AC influence the production of IL-9 through accessory signals that result in an at least 10-fold increase of IL-9 secretion by the respective T cells. Addition of IL-1 to T cells activated by Con A, PHA, or anti-CD3 antibodies revealed that this monokine was responsible for the potentiation of IL-9 production. This finding was confirmed by applying anti-IL-1 antibodies. The production of other lymphokines, namely, IL-3, IL-4, and IL-6, by activated T cells was not or only marginally enhanced in the presence of AC or IL-1, thus indicating that the synthesis of IL-9 is regulated differently from that of other Th2-derived lymphokines. Furthermore, it was demonstrated by Northern blot analysis that IL-1 increases IL-9 expression at the pretranslational level. Because IL-1 alone failed to induce the production of IL-9 by T cells, this monokine acts as a costimulator in combination with a T cell receptor-mediated signal.


Head Exposure to Cold during Whole-Body Cryostimulation: Influence on Thermal Response and Autonomic Modulation.
Recent research on whole-body cryotherapy has hypothesized a major responsibility of head cooling in the physiological changes classically reported after a cryostimulation session. The aim of this experiment was to verify this hypothesis by studying the influence of exposing the head to cold during whole-body cryostimulation sessions, on the thermal response and the autonomic nervous system (ANS). Over five consecutive days, two groups of 10 participants performed one whole-body cryostimulation session daily, in one of two different systems; one exposing the whole-body to cold (whole-body cryostimulation, WBC), and the other exposing the whole-body except the head (partial-body cryostimulation, PBC).10 participants constituted a control group (CON) not receiving any cryostimulation. In order to isolate the head-cooling effect on recorded variables, it was ensured that the WBC and PBC systems induced the same decrease in skin temperature for all body regions (mean decrease over the 5 exposures: -8.6°C ± 1.3°C and -8.3 ± 0.7°C for WBC and PBC, respectively), which persisted up to 20-min after the sessions (P20). The WBC sessions caused an almost certain decrease in tympanic temperature from Pre to P20 (-0.28 ± 0.11°C), while it only decreased at P20 (-0.14 ± 0.05°C) after PBC sessions. Heart rate almost certainly decreased after PBC (-8.6%) and WBC (-12.3%) sessions. Resting vagal-related heart rate variability indices (the root-mean square difference of successive normal R-R intervals, RMSSD, and high frequency band, HF) were very likely to almost certainly increased after PBC (RMSSD:+49.1%, HF: +123.3%) and WBC (RMSSD: +38.8%, HF:+70.3%). Plasma norepinephrine concentration was likely increased in similar proportions after PBC and WBC, but only after the first session. Both cryostimulation techniques stimulated the ANS with a predominance of parasympathetic tone activation from the first to the fifth session and in slightly greater proportion with WBC than PBC. The main result of this study indicates that the head exposure to cold during whole-body cryostimulation may not be the main factor responsible for the effects of cryostimulation on the ANS.


Pushing the limit of BGO-based dual-ended Cherenkov PET detectors through photon transit time correction.

The high production cost of commonly used lutetium-based fast scintillators and the development of silicon photomultipliers technology have made bismuth germanate (BGO) a promising candidate for time-of-flight positron emission tomography (TOF PET) detectors owing to its generation of prompt Cherenkov photons. However, using BGO as a hybrid scintillator is disadvantageous owing to its low photon statistics and distribution that does not conform well to a single Gaussian. To mitigate this, a proposal was made to increase the likelihood of detecting the first Cherenkov photons by positioning two photosensors in opposition at the entrance and exit faces of the scintillator and subsequently selectively picking an earlier timestamp. Nonetheless, the timing variation arising from the photon transit time remains affected by the entire length of the crystal, thereby presenting a possibility for further enhancement.
Approach: In this study, we aimed to improve the timing performance of the dual-ended BGO Cherenkov TOF PET detector by capitalizing on the synergistic advantages of applying depth-of-interaction (DOI) information and crystal surface finishes or reflector properties. A dual-ended BGO detector was implemented using a 3 × 3 × 15 mm3 BGO crystal. Coincidence events were acquired against a 3 × 3 × 3 mm3 LYSO:Ce:Mg reference detector. The timing performance of the dual-ended BGO detectors was analyzed using conventionally proposed timestamp methods before and after DOI correction.
Results:
Through a DOI-based correction of photon transit time spread, we demonstrated a further improvement in the timing resolution of the BGO-based Cherenkov TOF PET detector utilizing a dual-ended detector configuration and adaptive arrival time pickoff. We achieved further improvements in timing resolution by correcting the offset spread induced by the fluctuation of timing signal rise time in the dual-ended detector.
Significance: Although polishing the crystal surface was still favorable in terms of full-width-half-maximum (FWHM) value, incorporating DOI information from the unpolished crystal to compensate for photon travel time facilitated additional enhancement in the overall timing performance, thereby surpassing that achieved with the polished crystal.&#xD.


Denticare on thirty Manila dentists.
A limited study on the willingness of 30 Chapter members to join Denticare and on reasonable membership fees and fees for services was also conducted. It appeared that these Chapter members were interested in Denticare and ready to pay for membership fees. The schedule of standardized fees based on 70th percentile estimates, likewise appeared reasonable and could be acceptable to both providers and recipients of the services.


[On the formation of open skull fractures inflicted by cutting objects].
The objective of the present work was to study the properties of thrusting weapons, the conditions of their action, and the influence on the formation of cranial vault fractures. The lacerated wounds were simulated using an ordinary axe, native skull and isolated cranial vaults, specially designed multilayer polymeric models of bone and other tissues. This approach made it possible to obtain the objective characteristics of a thrusting blow as a medium-speed thrust (7- 20 m/s) with the impact mass commensurate with or exceeding the weight of the affected object. In indispensable condition for such thrust consists of the counteraction of the forces on a hard substrate. The traumatic agent must have the partially limited and maximally convex contact 1 surface (blade) harder than that of the affected object. Moreover, the character of a lacerated fracture strongly depends on the strin-stress properties of the skull.


Dietary intake of carotenoids and risk of type 2 diabetes.
Carotenoids may reduce diabetes risk, due to their antioxidant properties. However, the association between dietary carotenoids intake and type 2 diabetes risk is still unclear. Therefore, the objective of this study was to examine whether higher dietary carotenoid intakes associate with reduced type 2 diabetes risk. Data from 37,846 participants of the European Prospective Investigation into Cancer and Nutrition- Netherlands study were analyzed. Dietary intakes of β-carotene, α-carotene, β-cryptoxanthin, lycopene, lutein & zeaxanthin and the sum of these carotenoids were assessed using a validated food frequency questionnaire. Incident type 2 diabetes was mainly self-reported, and verified against general practitioner information. Mean ±SD total carotenoid intake was 10 ± 4 mg/day. During a mean ±SD follow-up of 10 ± 2 years, 915 incident cases of type 2 diabetes were ascertained. After adjustment for age, sex, diabetes risk factors, dietary intake, waist circumference and BMI, higher β-carotene intakes associated inversely with diabetes risk [Hazard Ratio quartile 4 versus quartile 1 (HR(Q4)): 0.78 (95%CI:0.64,0.95), P-linear trend 0.01]. For α-carotene, a borderline significant reduced risk was observed, with a HR(Q4) of 0.85 (95%CI:0.70,1.03), and P-linear trend 0.05. β-cryptoxanthin, lycopene, lutein & zeaxanthin, and the sum of all carotenoids did not associate with diabetes risk. This study shows that diets high in β-carotene and α-carotene are associated with reduced type 2 diabetes in generally healthy men and women.


A high-resolution nitrate vulnerability assessment of sandy aquifers (DRASTIC-N).
Groundwater protection against agricultural diffuse nitrate pollution is of paramount importance for safeguarding groundwater-dependent aquatic ecosystems and protecting human health by securing clean groundwater for drinking water production. Nitrate vulnerability assessment of aquifers is the core of a scientifically sound strategy for management and protection of groundwater by authorities. A multitude of methods exists for assessing intrinsic aquifer vulnerability. The objective of this paper is to develop a nitrate-specific groundwater vulnerability assessment method based on the globally recognized DRASTIC method, which was developed by the US Environmental Protection Agency in the 1980s. We propose a new method "DRASTIC-N″ for assessing aquifer nitrate vulnerability, which for the first time expands the seven original geological and hydrogeological parameters with a geochemical parameter for redox condition. The development of DRASTIC-N is based on the longstanding Danish practice of performing detailed groundwater mapping based on dense sampling of geophysical, geological, and geochemical data. DRASTIC-N is compared to the widely used and documented Danish nitrate vulnerability assessment method SCANVA in a study area where the primary aquifer used for drinking water production is composed of heterogeneous sandy glacial deposits. Both SCANVA and DRASTIC-N result in vulnerability maps, which show similar patterns of nitrate vulnerability with a fair overall agreement of 71%. DRASTIC-N provides a framework for systematic and transparent application, which can facilitate stakeholder involvement and help authorities in groundwater protection and decision-making with regards to nitrate pollution. DRASTIC-N is suitable for nitrate vulnerability assessments of glacially deposited sandy aquifers, an abundant and important water resource worldwide, potentially threatened by nitrate pollution from anthropogenic activities.


Intravenous thrombolysis with alteplase in the treatment of acute cerebral infarction.
To compare the efficacy and safety of intravenous thrombolysis with alteplase and intravenous thrombolysis with urokinase for patients with acute cerebral infarction. This prospective study included 140 patients with acute cerebral infarction who were admitted to our hospital between June 2018 and June 2019. They were randomly divided into two groups. The control group (70 cases) was treated with urokinase intravenous thrombolysis, and the observation group (70 cases) was given alteplase intravenous thrombolytic therapy. The treatment efficacy and safety of the two groups were compared. The total effective rate of the observation group was 95.7%, and that of the control group was 78.6%, i.e., the total effective rate of the observation group was significantly superior to the that of the control group (P < 0.05). After treatment, the observation group had significantly lower National Institutes of Health Stroke Scale (NIHSS) score and significantly higher mini-mental state examination (MMSE) score than the control group; the difference was statistically significant (P<0.05). After treatment, the levels of inflammatory factors of both groups significantly decreased compared to before treatment, and the decrease in the observation group was larger than that in the control group (P<0.05). The levels of serum homocysteine (Hcy) and monocyte chemoattractant protein-1 (MCP-1) in the observation group were significantly lower than those in the control group after treatment, and the differences were statistically significant (P<0.05). The incidence of hemorrhagic adverse reaction in the observation group was lower than that in the control group (P<0.05). In the treatment of acute cerebral infarction, ccompared with urokinase, alteplase can further relieve cognitive impairment and promote the recovery of nerve function through inhibiting levels of inflammatory factors and levels of serum Hcy and MCP-1.


Effects of anti-hypertensive drugs on esophageal body contraction.
To clarify the effects of anti-hypertensive drugs on esophageal contraction and determine their possible relationship with gastro-esophageal reflux disease. Thirteen healthy male volunteers were enrolled. Esophageal body peristaltic contractions and lower esophageal sphincter (LES) pressure were measured using high resolution manometry. All subjects were randomly examined on four separate occasions following administrations of nifedipine, losartan, and atenolol, as well as without any drug administration. Peristaltic contractions by the esophageal body were separated into three segments by two troughs. The peak peristaltic pressures in the mid and lower segments of the esophageal body under atenolol administration were significantly higher than those without medication in a supine position. On the other hand, peristaltic pressures under nifedipine administration were lower than those observed without drug administration. Losartan did not change esophageal body peristalsis. Atenolol elevated LES pressure and slowed peristaltic wave transition, while the effects of nifedipine were the opposite. Among the anti-hypertensive drugs tested, atenolol enhanced esophageal motor activity, which was in contrast to nifedipine.


Integrin-dependent response to laminin-511 regulates breast tumor cell invasion and metastasis.
The basement membrane protein, laminin (LM)-511, is a potent adhesive and migratory substrate for metastatic breast tumor cells in vitro. Its expression correlates with tumor grade and metastatic potential in vivo. These observations suggest that responsiveness to autocrine or paracrine-derived LM-511 may be an important property regulating breast cancer metastasis in vivo. To address this, we compared the metastatic potential of 4T1 mammary carcinoma cells to that of 4T1 variants isolated by repeated chemotactic migration toward LM-511 in vitro (4T1LMF4) followed by serial injection into the mammary gland and recovery of spontaneous metastases from bone (4T1BM2). Variant subpopulations exhibited a distinct morphology on LM-511 and increased expression of β1 and β4 integrins compared to parental 4T1 cells. Importantly, mice inoculated with 4T1LMF4 and 4T1BM2 variants showed a 2.5- to 4-fold increase in the incidence of spontaneous metastasis to bone compared to 4T1 tumor-bearing mice. Functionally, 4T1BM2 variants were more adherent and more invasive toward LM-511 than parental 4T1 cells. Treatment of 4T1BM2 cells with lebein-1, a disintegrin with selectivity toward LM-type integrin receptors, potently inhibited their migration and invasion toward LM-511. Similarly, α3β1 integrin-dependent migration and invasion of human MDA-MB-231 breast carcinoma cells toward LM-511 were significantly inhibited by lebein-1. Taken together, these results provide strong evidence that LM-511 contributes to the metastasis of breast tumors and suggest that targeting integrin-LM-511 interactions with lebein-1 or other inhibitors of LM-511 receptors may have therapeutic potential for patients with advanced breast cancer.


Control of viscous fingering patterns in a radial Hele-Shaw cell.
We study numerically and experimentally the dynamics and control of viscous fingering patterns in a circular Hele-Shaw cell. The nonlocality and nonlinearity of the system, especially interactions among developing fingers, make the emergent pattern difficult to predict and control. By controlling the injection rate of the less viscous fluid, we can precisely suppress the evolving interfacial instabilities. There exist denumerable attractive, self-similarly evolving symmetric, universal shapes. Experiments confirm the feasibility of the control strategy, which is summarized in a morphology diagram.


Relationship of airway symptoms from chemicals to capsaicin cough sensitivity in atopic subjects.
It is well known that some patients with allergy complain of airway symptoms from chemicals (ASCs) and strong odours. However, the importance of such information for the treatment of allergic disease is not known. Such symptoms in non-allergic patients have previously been shown to be related to increased sensory nerve reactivity, which is expressed as increased cough sensitivity to inhaled capsaicin. The aim of this study was to examine ASC in atopic patients and relate it to cough reaction to capsaicin inhalation. Fifty-seven consecutively chosen, skin prick-positive patients with symptoms of the upper and/or lower airways completed a questionnaire concerning ASC. The patients were then divided into two groups, those with and those without such symptoms. Both groups were provoked with inhaled capsaicin in three increments and compared with 73 healthy control subjects. Out of 57 atopic patients, 34 reported ASC agents and 23 did not. The patients with ASC were older (P<0.01) and coughed significantly more on capsaicin provocation (P<0.001), but did not differ from them with respect to the allergic disease or its treatment or to smoking habits. Patients with atopy but without ASC did not differ from healthy controls with regard to sensitivity to capsaicin inhalation. The scored degree of ASC was directly related to the number of coughs during the capsaicin provocation. ASC in atopic patients are related to increased airway sensory nerve reactivity. There is still no explanation for this in certain patients with atopy, but age may be a confounding factor.


Angiography in the management of massive lower gastrointestinal tract hemorrhage.
Initial stabilization of blood volume and immediate resuscitative measures should be used for lower gastrointestinal tract bleeding. Upper gastrointestinal tract lesions should be excluded with nasogastric intubation and upper endoscopy if the history or nasogastric aspirate suggests an upper gastrointestinal tract source. Proctosigmoidoscopy should be done to exclude mucosal disease, hemorrhoidal bleeding or local carcinoma. If all of these are negative and the patient is bleeding massively, we recommend arteriography with catheterization of the superior mesenteric, inferior mesenteric and celiac arteries. These procedures should be carried out within less than four hours. If a bleeding site is demonstrated, the use of local infusion of vasopressin for permanent control should be considered only in the poor risk patient in whom the operative risk is prohibitive. Massive hemorrhage from the lower gastrointestinal tract in an elderly population is usually due to diverticular bleeding and not to angiodysplasia. The bleeding site was more common in the right than in the left colon. Angiography has been proved to be an important diagnostic procedure to localize the site of the bleeding and has been invaluable in the surgical management of these patients.


Universal sensor array for highly selective system identification using two-dimensional nanoparticles.
A typical lock-and-key sensing strategy, relying only on the most dominant interactions between the probe and target, could be too limiting. In reality, the information received upon sensing is much richer. Non-specific events due to various intermolecular forces contribute to the overall received information with different degrees, and when analyzed, could provide a much more powerful detection opportunity. Here, we have assembled a highly selective universal sensor array using water-soluble two-dimensional nanoparticles (nGO, MoS2 and WS2) and fluorescent DNA molecules. The array is composed of 12 fluorescently silent non-specific nanoreceptors (2D-nps) and used for the identification of three radically different systems; five proteins, three types of live breast cancer cells and a structure-switching event of a macromolecule. The data matrices for each system were processed using Partial Least Squares (PLS) discriminant analysis. In all of the systems, the sensor array was able to identify each object or event as separate clusters with 95% confidence and without any overlap. Out of 15 unknown entities with unknown protein concentrations tested, 14 of them were predicted successfully with correct concentration. 8 breast cancer cell samples out of 9 unknown entities from three cell types were predicted correctly. During the assembly of each nanoprobe, the intrinsic non-covalent interactions between unmodified 2D nanoparticles and ssDNAs were exploited. The unmodified 2D materials offer remarkable simplicity in the layout and the use of ssDNAs as probes provides limitless possibilities because the natural interaction of a ssDNA and 2D surface can be fine-tuned with the nucleobase composition, oligonucleotide length and type of 2D nanomaterial. Therefore, the approach described here can be advanced and fine-tuned indefinitely for meeting a particular sensing criterion. Though we have only studied three distinct elements, this approach is universal enough to be applied to a wide-range of systems.


Electrophysiological evidence for context reinstatement effects on object recognition memory.
Reinstating the context present at encoding during the test phase generally enhances recognition memory compared with changing the context when specific item-context associations are established during encoding. However, it remains unclear whether context reinstatement improves the performance in differentiating between old and similar items in recognition memory tests and what underlying cognitive processes are involved. Using the context reinstatement paradigm together with event-related potentials (ERP), we examined the context-dependent effects of background scenes on recognition discrimination among similar objects. Participants were instructed to associate intentionally specific objects with background scenes during the encoding phase and subsequently complete an object recognition memory task, during which old and similar new objects were presented superimposed over the studied old or similar new background scenes. Electroencephalogram was recorded to measure the electrophysiological manifestations of cognitive processes associated with episodic retrieval. Behavioral results revealed enhanced performance in differentiating old from similar objects in the old context, as opposed to the similar context condition. Importantly, ERP results indicated a more pronounced recollection-related parietal object old/new effect in the old context compared to the similar context condition. This suggests that the ability to distinguish between old and similar objects in recognition memory is primarily driven by recollection rather than familiarity, particularly when the encoding context is reinstated during the test phase. Our findings are in line with the account that the impact of context reinstatement on object recognition memory is attributable to the enhanced recollection of specific item-context associations during retrieval and provides evidence for the specificity of episodic associative representations.


Antagonism between Gdf6a and retinoic acid pathways controls timing of retinal neurogenesis and growth of the eye in zebrafish.
Maintaining neurogenesis in growing tissues requires a tight balance between progenitor cell proliferation and differentiation. In the zebrafish retina, neuronal differentiation proceeds in two stages with embryonic retinal progenitor cells (RPCs) of the central retina accounting for the first rounds of differentiation, and stem cells from the ciliary marginal zone (CMZ) being responsible for late neurogenesis and growth of the eye. In this study, we analyse two mutants with small eyes that display defects during both early and late phases of retinal neurogenesis. These mutants carry lesions in gdf6a, a gene encoding a BMP family member previously implicated in dorsoventral patterning of the eye. We show that gdf6a mutant eyes exhibit expanded retinoic acid (RA) signalling and demonstrate that exogenous activation of this pathway in wild-type eyes inhibits retinal growth, generating small eyes with a reduced CMZ and fewer proliferating progenitors, similar to gdf6a mutants. We provide evidence that RA regulates the timing of RPC differentiation by promoting cell cycle exit. Furthermore, reducing RA signalling in gdf6a mutants re-establishes appropriate timing of embryonic retinal neurogenesis and restores putative stem and progenitor cell populations in the CMZ. Together, our results support a model in which dorsally expressed gdf6a limits RA pathway activity to control the transition from proliferation to differentiation in the growing eye.


Augmented Reality for Human-Robot Collaboration and Cooperation in Industrial Applications: A Systematic Literature Review.
With the continuously growing usage of collaborative robots in industry, the need for achieving a seamless human-robot interaction has also increased, considering that it is a key factor towards reaching a more flexible, effective, and efficient production line. As a prominent and prospective tool to support the human operator to understand and interact with robots, Augmented Reality (AR) has been employed in numerous human-robot collaborative and cooperative industrial applications. Therefore, this systematic literature review critically appraises 32 papers' published between 2016 and 2021 to identify the main employed AR technologies, outline the current state of the art of augmented reality for human-robot collaboration and cooperation, and point out future developments for this research field. Results suggest that this is still an expanding research field, especially with the advent of recent advancements regarding head-mounted displays (HMDs). Moreover, projector-based and HMDs developed approaches are showing promising positive influences over operator-related aspects such as performance, task awareness, and safety feeling, even though HMDs need further maturation in ergonomic aspects. Further research should focus on large-scale assessment of the proposed solutions in industrial environments, involving the solution's target audience, and on establishing standards and guidelines for developing AR assistance systems.


Comparison of specimens for detection of porcine reproductive and respiratory syndrome virus infection in boar studs.
Porcine reproductive and respiratory syndrome virus (PRRSV)-contaminated semen from boars is a route of transmission to females, and early detection of PRRSV infection in boars is a key component in sow farm biosecurity. The purpose of this study was to determine the optimum diagnostic specimen(s) for the detection of acute PRRSV infection in boars. Individually housed boars (n = 15) were trained for semen and oral fluid collection and then vaccinated with a commercial PRRSV modified live virus vaccine. Starting on the day of vaccination and for 14 days thereafter, oral fluid specimens were collected daily from all boars. The 15 boars were subdivided into three groups of 5, and serum, blood swabs and 'frothy saliva' were collected at the time of semen collection on a 3-day rotation. Frothy saliva, derived from the submandibular salivary gland, is produced by aroused boars. Semen was centrifuged, and semen supernatant and cell fractions were tested separately. All samples were randomly ordered and then tested by PRRSV real-time quantitative reverse-transcription polymerase chain reaction assay (rRT-PCR) and PRRSV antibody ELISA. In this study, a comparison of serum, blood swab, and oral fluid rRT-PCR results found no statistically significant differences in the onset of detection or proportion of positives, but serum was numerically superior to oral fluids for early detection. Serum and oral fluid provided identical rRT-PCR results at ≥ 5 day post-vaccination. Likewise, the onset of detection of PRRSV antibody in serum, oral fluid and frothy saliva was statistically equivalent, with serum results again showing a numerical advantage. These results showed that the highest assurance of providing PRRSV-negative semen to sow farms should be based on rRT-PCR testing of serum collected at the time of semen collection. This approach can be augmented with oral fluid sampling from a random selection of uncollected boars to provide for statistically valid surveillance of the boar stud.


Dependence of centriole formation on protein synthesis.
Centriole formation was studied after inhibition of protein synthesis for various portions of the cell cycle. Synchronous populations of mitotic L929 (mouse) cells were plated into petri dishes and the course of procentriole formation was monitored by electron microscope analysis. The frequency with which procentrioles were seen in association with mature centrioles normally increased steadily in the interval from 4 to 12 h after mitosis. The formation of procentrioles was abruptly inhibited by the addition of cycloheximide at any time from mitosis until 12 h postmitosis (S phase). This suggested that the formation of procentrioles was dependent upon protein synthesis immediately before their appearance. Prophase-accociated elongation of procentrioles appeared to occur normally in cells treated with cycloheximide for up to 4 h before prophase, though the mitotic index in treated cultures decreased somewhat. Thus, protein synthesis did not appear to be essential for procentriolar elongation to the mature length.


Chromosomal mapping, differential origin and evolution of the S100 gene family.
S100 proteins are calcium-binding proteins, which exist only in vertebrates and which constitute a large protein family. The origin and evolution of the S100 family in vertebrate lineages remain a challenge. Here, we examined the synteny conservation of mammalian S100A genes by analysing the sequence of available vertebrate S100 genes in databases. Five S100A gene members, unknown previously, were identified by chromosome mapping analysis. Mammalian S100A genes are duplicated and clustered on a single chromosome while two S100A gene clusters are found on separate chromosomes in teleost fish, suggesting that S100A genes existed in fish before the fish-specific genome duplication took place. During speciation, tandem gene duplication events within the cluster of S100A genes of a given chromosome have probably led to the multiple members of the S100A gene family. These duplicated genes have been retained in the genome either by neofunctionalisation and/or subfunctionalisation or have evolved into non-coding sequences. However in vertebrate genomes, other S100 genes are also present i.e. S100P, S100B, S100G and S100Z, which exist as single copy genes distributed on different chromosomes, suggesting that they could have evolved from an ancestor different to that of the S100A genes.


An update on the safety and efficacy of decitabine in the treatment of myelodysplastic syndromes.
Myelodysplastic syndromes (MDS) are clonal bone marrow malignancies characterized by peripheral cytopenias and dysplastic changes in the bone marrow with various clinical features. Patients with MDS, in particular those with intermediate-2 (Int-2) and high-risk disease, have a poor prognosis. The mainstay of treatment includes cytoxic chemotherapy and supportive care. Over the last decade, promising results from studies focusing on hypomethylating agents, such as decitabine (5-aza-deoxycytidine) and 5-azacitidine, have led to the expansion of the therapeutic arsenal for MDS. This review presents the current data available on the clinical efficacy and safety profile for decitabine as a treatment for MDS. Although not fully understood, decitabine's antitumor activity may involve its ability to induce hypomethylation and reactivation of genes responsible for cellular differentiation, stimulate an immune response, induce DNA damage/apoptotic response pathways, and/or augment stem cell renewal. Future studies that use epigenetic therapies that combine hypomethylating agents with histone deacetylase inhibitors (HDACi) and head-to-head comparison studies of decitabine and 5-azacitidine will provide valuable pre-clinical and clinical data, enhancing our understanding of these drugs.


Mapping electrical properties heterogeneity of tumor using boundary informed electrical properties tomography (BIEPT) at 7T.
To develop and evaluate a boundary informed electrical properties tomography (BIEPT) technique for high-resolution imaging of tumor electrical properties (EPs) heterogeneity on a rodent tumor xenograft model. Tumor EP distributions were inferred from a reference area external to the tumor, as well as internal EP spatial variations derived from a plurality of relative transmit B1 measurements at 7T. Edge sparsity constraint was enforced to enhance numerical stability. Phantom experiments were performed to determine the imaging accuracy and sensitivity for structures of various EP values, as well as geometrical sizes down to 1.5 mm. Numerical simulation of a realistic rodent model was used to quantify the algorithm performance in the presence of noise. Eleven athymic rats with human breast cancer xenograft were imaged in vivo, and representative pathological samples were acquired for comparison. Reconstructed EPs of the phantoms correspond well to the ground truth acquired from dielectric probe measurements, with the smallest structure reliably detectable being 3 mm. EPs heterogeneity inside a tumor is successfully retrieved in both simulated and experimental cases. In vivo tumor imaging results demonstrate similar local features and spatial patterns to anatomical MRI and pathological slides. The imaged conductivity of necrotic tissue is higher than that of viable tissues, which agrees with our expectation. BIEPT enables robust detection of tumor EPs heterogeneity with high accuracy and sensitivity to small structures. The retrieved quantitative EPs reflect tumor pathological features (e.g., necrosis). These results provide strong rationale to further expand BIEPT studies toward pathological conditions where EPs may yield valuable, non-invasive biomarkers.


High light-directing micrometer-sized parabolic mirror arrays.
Excellent light-directing abilities are demonstrated by well-designed three-dimensional micrometer-sized parabolic mirrors that are fabricated by direct laser writing and subsequent surface coating of titanium and silver. The full-width at half-maximum of the measured light divergence for the mirrors with different geometries is much less than 20 μm, even when the height is up to 130 μm. These results are beneficial for developing highly collimating light-emitting diodes. The simulation for the mirrors reveals that the electric field intensity distribution is highly confined toward the central axis of the mirrors, which is consistent with the experimental results.


[Should metabolic acidosis be alkalinized?].
At present, the administration of bicarbonate for metabolic acidosis has become controversial with regard to the indications and the modalities of treatment. Scientific evidence of the therapeutic value of bicarbonate is still lacking. In the opposite, there is a strong evidence of its adverse effects, such a paradoxical acidosis, sodium load and over all a worsening of haemodynamic status. Other therapeutic measures are limited. They include the administration of Carbicarb which does not increase the CO2 content, haemodialysis with bicarbonate and/or hyperventilation. As for every therapeutic action, the treatment must rely on an interpretation of the pathophysiological mechanism, resulting in the definition of therapeutic goals. The amendment of acidosis is not always a therapeutic priority. In ketoacidosis for instance, the depth of acidosis is mainly related to the degree of dehydration, the treatment of which results in a normalization of pH.


[Inhibitory regulation of glutamate receptors in the frog motoneuron].
The interaction of exogenously applied excitatory (glutamate and their agonists NMDA, AMPA, kainate) and inhibitory (glycine and GABA) amino acid effects was studied intracellularly in the motoneurones of the isolated frog spinal cord. During simultaneous glycine or GABA bath applications GLU-, AMPA-, KA- and NMDA-evoked responses were, respectively, decreased up to 45.8 +/- 2.9% (n = 12) and 67.8 +/- 3.9% (n = 16), 13.9 +/- 4.3% (n = 9) and 32.1 +/- 8.3% (n = 12), 36.8 +/- 8.2% (n = 7) and 48.0 +/- 11.8% (n = 6), 7.7 +/- 3.5% (n = 9) and 18.1 +/- 3.8% (n = 14) from the control. Sequential applications of EAA after glycine or GABA as well as the applications of EAA-agonist and glycine (GABA) mixture demonstrated similar results. The decrease of EAA-responses by glycine and GABA was abolished by selective GlyR antagonist strychnine (1 microM) and the selective GABAR antagonist SR95531 (gabazine, 20 MM), respectively. The data revealed differences in inhibitory effect of glycine and GABA on the excitation responses mediated by different types of glutamate receptors in the frog motoneurones: the predominant inhibitory effect of glycine and GABA on NMDA-responses and weak inhibitory effect on KA- and GLU-responses. Inhibitory effect of glycine was twice as much as that of GABA at the same concentration.


Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass.
Left ventricular mass (LVM) and cardiac gene expression are complex traits regulated by factors both intrinsic and extrinsic to the heart. To dissect the major determinants of LVM, we combined expression quantitative trait locus1 and quantitative trait transcript (QTT) analyses of the cardiac transcriptome in the rat. Using these methods and in vitro functional assays, we identified osteoglycin (Ogn) as a major candidate regulator of rat LVM, with increased Ogn protein expression associated with elevated LVM. We also applied genome-wide QTT analysis to the human heart and observed that, out of 22,000 transcripts, OGN transcript abundance had the highest correlation with LVM. We further confirmed a role for Ogn in the in vivo regulation of LVM in Ogn knockout mice. Taken together, these data implicate Ogn as a key regulator of LVM in rats, mice and humans, and suggest that Ogn modifies the hypertrophic response to extrinsic factors such as hypertension and aortic stenosis.


Marketing analysis of a positive technology app for the self-management of psychological stress.
The INTERSTRESS project developed a completely new concept in the treatment of psychological stress: Interreality, a concept that combines cognitive behavioral therapy with a hybrid, closed-loop empowering experience bridging real and virtual worlds. This model provides the opportunity for individual citizens to become active participants in their own health and well-being. This article contains the results of the Marketing Trial and analysis of the opinions of individual consumers/end users of the INTERSTRESS product. The specific objective of this study was to evaluate the feasibility, efficacy and user acceptance of a novel mobile-based relaxation training tool in combination with biofeedback exercises and wearable biosensors. Relaxation was aided through immersion in a mobile virtual scenario (a virtual island) featuring pre-recorded audio narratives guiding a series of relaxation exercises. During biofeedback exercises, a wearable biosensor system provided data which directly modified the virtual reality experience in real-time. Thirty-six participants evaluated the product and overall feedback from users was positive, with some variation seen based on participant gender. A larger market study is now underway to understand if there are cultural variations in acceptability of the device.


Association Between Genomic Metrics and Immune Infiltration in Triple-Negative Breast Cancer.
Why some triple-negative breast cancers (TNBCs) have high and others have low immune cell infiltration is unknown. Understanding how immune surveillance shapes the cancer genome could help in the selection of patients and the development of more effective immunotherapy strategies. To examine the association between genomic metrics and the extent of immune infiltration in TNBCs. This study, performed from June 1, 2015, through January 31, 2017, used DNA and RNA sequencing data and messenger RNA expression results from The Cancer Genome Atlas (TCGA) breast cancer data set (n = 1215) to calculate previously described immune metagene expression values and histologic lymphocyte counts to quantify immune infiltration and assign prognostic categories to TNBCs. It used the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) data set as an independent validation cohort. The study compared clonal heterogeneity, somatic total mutational load, neoantigen load, and somatic copy number alteration levels between immune-rich TNBC cohorts with good prognosis and immune-poor TNBC cohorts with poor prognosis. The study also compared the distribution of mutations in 119 canonical cancer genes. Correlation between immune prognostic category and genomic metrics of the cancer. This study of 193 TNBC samples with patient survival information found an inverse association between clonal heterogeneity and immune metagene expression (ρ = −0.395, P = 2 × 10−8). The study also found an inverse association between immune metagene expression and somatic copy number alteration levels (ρ = −0.484, P = 2 × 10−10). Lymphocyte-rich TNBCs with good prognosis had significantly lower mutation and neoantigen counts than did lymphocyte-poor TNBCs with poor prognosis. The robustness of the study results was confirmed by using various immune metagenes in the same TCGA data set and in the independent METABRIC data set. This study suggests that immune-rich TNBCs may be under an immune surveillance that continuously eliminates many immunogenic clones, resulting in lower clonal heterogeneity. These cancers may also represent the subset of TNBCs that could derive benefit from immune checkpoint inhibitor therapy to tilt the balance in favor of the immune system.


Nonvenereal sclerosing lymphangitis of the penis.
Sclerosing lymphangitis of the penis with a purplish, cord-like structure, singular or multiple around the coronal sulcus, appears 24 to 48 hours after sexual relations. There is edema of the glans penis and coronal area, which is doughy and plastic. The condition is self-limited.


Non-suicidal self-injury among adolescents: diagnostic correlates and relation to suicide attempts.
Non-suicidal self-injury (NSSI) is a prevalent behavioral problem, yet many fundamental aspects of NSSI remain unknown. This case series study reports on the diagnostic correlates of adolescents with a recent history of NSSI and examines the relation between NSSI and suicide attempts. Data are from clinical interviews with 89 adolescents admitted to an adolescent psychiatric inpatient unit who engaged in NSSI in the previous 12 months. Results revealed that 87.6% of adolescents engaging in NSSI met criteria for a DSM-IV Axis I diagnosis (M=3.0, S.D.=2.2, range=0 to 8 diagnoses), including externalizing (62.9%), internalizing (51.7%), and substance use (59.6%) disorders. Most adolescents assessed also met criteria for an Axis II personality disorder (67.3%). Overall, 70% of adolescents engaging in NSSI reported a lifetime suicide attempt and 55% reported multiple attempts. Characteristics of NSSI associated with making suicide attempts included a longer history of NSSI, use of a greater number of methods, and absence of physical pain during NSSI. These findings demonstrate the diagnostic heterogeneity of adolescents engaging in NSSI, highlight the significant overlap between NSSI and suicide attempts, and provide a point of departure for future research aimed at elucidating the relations between non-suicidal and suicidal self-injury.


Dyspareunia: a symptom of female sexual dysfunction.
Dyspareunia is one of the most common sexual symptoms that carries wide-ranging potential foor emotional and physical pain. Informed therapeutic intervention can be useful in helping a person with sexual problems. Organic causes underlying dyspareunia are usually temporary and easily correctable. They are rare as a cause of a continuing problem, compared to issues of intrapersonal and interpersonal conflict. One of the keys to achieving a satisfying relationship on an adult-to-adult basis requires that each partner assume responsibility for his/her own sexual pleasure. The woman who withdraws into the assumption that she has an organic problem in the absence of abnormal findings, or that her partner or therapist must find a solution, abdicates responsibility for her own sexual pleasure. Although few of us will be therapists in the sense that the role is generally understood, indentifying and responding to sexual concerns of patients is part of the professional's commitment. Ultimately, our goal is the same for any problem of human development-- to facilitate the realization of the potentialities of the person.


Use of alkaline phosphatase staining to differentiate canine osteosarcoma from other vimentin-positive tumors.
Aspiration of lytic bone lesions is an excellent diagnostic test in the initial evaluation of primary bone neoplasia. However, cytologically, it can be difficult to differentiate osteosarcoma (OSA) from other bone neoplasms, including fibrosarcoma, chondrosarcoma, synovial cell sarcoma, and plasma cell myeloma. The purpose of this study is to determine the sensitivity and specificity of alkaline phosphatase (ALP) staining to differentiate OSA from other tumors that express vimentin by immunocytochemistry or immunohistochemistry. ALP is a hydrolytic enzyme present in multiple tissues including liver, kidney, intestine, placenta, and bone. Hypothetically, neoplasms actively producing bone should be specifically positive for ALP staining. Unstained, cytologic specimens were incubated for 8-10 minutes with nitroblue tetrazolium chloride/5-bromo-4-chloro-3-indolyl phosphate toluidine salt-phosphatase substrate. A positive reaction stains the membrane of the cells gray to black. Samples were counterstained with a Romanowsky's stain to determine whether the sample was of representative cellularity. A total of 61 vimentin-positive neoplasms have been evaluated and confirmed histopathologically. Tumors that expressed vimentin and were positive for ALP included 33 OSAs, one multi-lobular tumor of bone, one amelanotic melanoma, and one chondrosarcoma. Tumors that expressed vimentin and were negative for ALP included chondrosarcomas (three of four), multiple fibrosarcomas, and multiple synovial cell sarcomas. The sensitivity is 100%, and the specificity is 89%. In conclusion, ALP appears to be a highly sensitive and fairly specific marker in the diagnosis of OSA.


[Stimulation of nucleic acid biosynthesis by phosphopentoses].
Phosphopentose stimulation of nucleic acids biosynthesis for 3h after subcutaneous phosphopentose administration in doses of 18 and 27 mg per rat has been stated. Injections of phosphopentoses (ribose-5-phosphate, xylulose-6-phosphate, ribulose-5-phosphate in the ratio of 1.0:0.3:0.3) were followed by a two-fold increase in the rate of [2-14C] orothic acid incorporation into cytoplasmic RNA of the rat liver. It is supposed that rapidly exchanging types of RNA contribute most of all to the effect of the label incorporation increase and the stimulation mechanism is associated with a rise of phosphoribosyl pyrophosphate accessibility as a substrate and an allosteric regulator of key enzymes of the synthesis of purine and pyrimidine nucleotides.


Postbiotics for NOD2 require nonhematopoietic RIPK2 to improve blood glucose and metabolic inflammation in mice.
Defining the host receptors and metabolic consequences of bacterial components can help explain how the microbiome influences metabolic diseases. Bacterial peptidoglycans that activate nucleotide-binding oligomerization domain-containing (NOD)1 worsen glucose control, whereas NOD2 activation improves glycemia. Receptor-interacting serine/threonine-protein kinase 2 (RIPK2) is required for innate immunity instigated by NOD1 and NOD2. The role of RIPK2 in the divergent effects of NOD1 versus NOD2 on blood glucose was unknown. We found that whole body deletion of RIPK2 negated all effects of NOD1 or NOD2 activation on blood glucose during an acute, low level endotoxin challenge in mice. It was known that NOD1 in hematopoietic cells participates in insulin resistance and metabolic inflammation in obese mice. It was unknown if RIPK2 in hematopoietic cells is required for the glucose-lowering and anti-inflammatory effects of NOD2 activation. We hypothesized that RIPK2 in nonhematopoietic cells dictated the glycemic effects of NOD2 activation. We found that whole body deletion of RIPK2 prevented the glucose-lowering effects of repeated NOD2 activation that were evident during a glucose tolerance test (GTT) in high-fat diet (HFD)-fed wild-type (WT) mice. NOD2 activation lowered glucose during a GTT and lowered adipose tissue inflammation in mice with RIPK2 deleted in hematopoietic cells. We conclude that RIPK2 in nonhematopoietic cells mediates the glucose lowering and anti-inflammatory effects of NOD2-activating postbiotics. We propose a model where lipopolysaccharides and NOD1 ligands synergize in hematopoietic cells to promote insulin resistance but NOD2 activation in nonhematopoietic cells promotes RIPK2-dependent immune tolerance and lowering of inflammation and insulin resistance.


Colonisation of basal cell carcinoma and actinic keratosis by malignant melanoma in situ in a patient with xeroderma pigmentosum variant.
Although malignant melanoma (MM) and both basal cell carcinoma (BCC) and actinic keratosis (AK) are sun-induced lesions, the coexistence of these entities at the same anatomical site (collision tumour) is exceedingly rare. We report the case of a 54-year-old woman with a known history of xeroderma pigmentosum variant (XPV) who presented with 2 separate skin lesions over the middle and upper right forearm, respectively. The clinical impression was that of BCCs or squamous cell lesions. On histological examination, both specimens showed features of melanoma in situ (MIS). In the first lesion, MIS merged with and colonised a superficial and focally invasive BCC. In the second lesion, MIS merged with an AK. No separate invasive nests of malignant melanoma were seen in either specimen. The atypical melanocytes were highlighted by Melan-A and HMB-45 immunostaining, whereas the epithelial cells in both the BCC and AK stained with the pancytokeratin MNF-116. The patient had a previous history of multiple MMs and non-melanomatous skin cancers and finally developed widespread metastatic malignant melanoma, which proved fatal. The rare and interesting phenomenon of collision tumours may pose diagnostic difficulties. To our knowledge, this is the first reported simultaneous presentation of cytologically malignant collision tumours in a patient with XPV.


Better postpartal performance in dairy cows supplemented with rumen-protected methionine compared with choline during the peripartal period.
The onset of lactation in dairy cows is characterized by high output of methylated compounds in milk when sources of methyl group are in short supply. Methionine and choline (CHOL) are key methyl donors and their availability during this time may be limiting for milk production, hepatic lipid metabolism, and immune function. Supplementing rumen-protected Met and CHOL may improve overall performance and health of transition cows. The objective of this study was to evaluate the effect of supplemental rumen-protected Met and CHOL on performance and health of transition cows. Eighty-one multiparous Holstein cows were used in a randomized, complete, unbalanced block design with 2×2 factorial arrangement of Met (Smartamine M, Adisseo NA, Alpharetta, GA) and CHOL (ReaShure, Balchem Inc., New Hampton, NY) inclusion (with or without). Treatments (20 to 21 cows each) were control (CON), CON+Met (SMA), CON+CHOL (REA), and CON+Met+CHOL (MIX). From -50 to -21d before expected calving, all cows received the same diet (1.40Mcal of NEL/kg of DM) with no Met or CHOL. From -21d to calving, cows received the same close-up diet (1.52Mcal of NEL/kg of DM) and were assigned randomly to treatments (CON, SMA, REA, or MIX) supplied as top dresses. From calving to 30 DIM, cows were fed the same postpartal diet (1.71Mcal of NEL/kg of DM) and continued to receive the same treatments through 30 DIM. The Met supplementation was adjusted daily at 0.08% DM of diet and REA was supplemented at 60g/d. Incidence of clinical ketosis and retained placenta tended to be lower in Met-supplemented cows. Supplementation of Met (SMA, MIX) led to greater DMI compared with other treatments (CON, REA) in both close-up (14.3 vs. 13.2kg/d, SEM 0.3) and first 30d postpartum (19.2 vs. 17.2kg/d, SEM 0.6). Cows supplemented with Met (SMA, MIX) had greater yields of milk (44.2 vs. 40.4kg/d, SEM 1.2), ECM (44.6 vs. 40.5kg/d, SEM 1.0), and FCM (44.6 vs. 40.8kg/d, SEM 1.0) compared with other (CON, REA) treatments. Milk fat content did not differ in response to Met or CHOL. However, milk protein content was greater in Met-supplemented (3.32% vs. 3.14%, SEM 0.04%) but not CHOL-supplemented (3.27 vs. 3.19%, SEM 0.04%) cows. Supplemental CHOL led to greater blood glucose and insulin concentrations with lower glucose:insulin ratio. No Met or CHOL effects were detected for blood fatty acids or BHB, but a Met × time effect was observed for fatty acids due to higher concentrations on d 20. Results from the present study indicate that peripartal supplementation of rumen-protected Met but not CHOL has positive effects on cow performance.


Identification of a major microfibril-associated glycoprotein-1-binding domain in fibrillin-2.
Using yeast two-hybrid, ligand blotting, and solid phase binding assays, we have shown that microfibril-associated glycoprotein-1 (MAGP-1) interacts with the 8-cysteine motif of fibrillin-2 encoded by exon 24. Binding to this sequence was demonstrated for full-length MAGP-1 as well as for the MAGP-1 matrix-binding domain encoded by exons 7 and 8. The matrix-binding domain, but not the full-length protein, also bound to regions of fibrillin-2 defined by exons 16 and 17, exon 20, and exons 23 and 24. Interestingly, no binding was detected to sequences near the N or C terminus where MAGP-1 and MAGP-2, respectively, were shown to interact with fibrillin-1. The localization of MAGP-1 binding to the 8-Cys domain encoded by exon 24 suggests that the bead structure of microfibrils consists of exon 24 and portions of the central region of fibrillin-2. Exon 24 in fibrillin lies in the region of the molecule where mutations produce the most severe phenotypes associated with Marfan syndrome (fibrillin-1) and congenital contractural arachnodactyly (fibrillin-2). It is possible that these mutations alter the ability of fibrillin to bind MAGP-1, which may contribute to the severity of the disease.


Control of Drosophila tracheal branching by the novel homeodomain gene unplugged, a regulatory target for genes of the bithorax complex.
We have identified a novel Drosophila homeodomain gene, unplugged (unp), whose function is required for formation of the tracheal branches that penetrate the CNS. In unp mutant embryos the segmentally repeated ganglionic branches stall and fail to penetrate the CNS and the segment-specific cerebral branch and associated cerebral anastomosis fail to form. Expression of unp in the founder cells for the cerebral branch within the first tracheal metamere is repressed in posterior segments by Ubx and other bithorax complex genes. This pattern of expression and homeotic gene regulation is reproduced by an unusual 2.6 kb cis-regulatory sequence located downstream of the unp transcription unit. Since the unp protein is localized to the nucleus of tracheal precursor cells as they migrate and extend, unp protein appears to play a regulatory role in neural branching of the tracheae, and the segment-specific aspects of these neural branching patterns appear to be generated by homeotic regulation of unp expression.


Advancements and challenges in generating accurate animal models of gestational diabetes mellitus.
The maintenance of glucose homeostasis during pregnancy is critical to the health and well-being of both the mother and the developing fetus. Strikingly, approximately 7% of human pregnancies are characterized by insufficient insulin production or signaling, resulting in gestational diabetes mellitus (GDM). In addition to the acute health concerns of hyperglycemia, women diagnosed with GDM during pregnancy have an increased incidence of complications during pregnancy as well as an increased risk of developing type 2 diabetes (T2D) later in life. Furthermore, children born to mothers diagnosed with GDM have increased incidence of perinatal complications, including hypoglycemia, respiratory distress syndrome, and macrosomia, as well as an increased risk of being obese or developing T2D as adults. No single environmental or genetic factor is solely responsible for the disease; instead, a variety of risk factors, including weight, ethnicity, genetics, and family history, contribute to the likelihood of developing GDM, making the generation of animal models that fully recapitulate the disease difficult. Here, we discuss and critique the various animal models that have been generated to better understand the etiology of diabetes during pregnancy and its physiological impacts on both the mother and the fetus. Strategies utilized are diverse in nature and include the use of surgical manipulation, pharmacological treatment, nutritional manipulation, and genetic approaches in a variety of animal models. Continued development of animal models of GDM is essential for understanding the consequences of this disease as well as providing insights into potential treatments and preventative measures.


[Clinical aspects and treatment of calf muscle cramps during pregnancy].
Of 8204 gravidae, 486 (5,9%) complained at least once of muscle cramps during pregnancy. Muscle cramps were noticed most often in the second half of pregnancy. Gravidae with muscle cramps were on the average older and of higher parity; there was no relationship between muscle cramps and complications during pregnancy or unfavorable fetal outcome. In an uncontrolled therapeutic trial 21 women with muscle cramps received 1,8 g monomagnesium-aspartate twice daily per mouth for 4 weeks. 21 women with muscle cramps had no therapy. 4 weeks after the initiation of magnesium therapy 19/21 women were free of symptoms, compared to only 7/21 patients in the control group. Muscle cramps during pregnancy do not have to be considered a risk factor; they can be significantly improved by the administration of oral magnesium.


Temporal fluctuations of Y-chromosomal variation in Bos taurus.
Phylogeography has recently become more abundant in studies of demographic history of both wild and domestic species. A single nucleotide polymorphism (SNP) in the intron of the Y-chromosomal gene UTY19 displays a north-south gradient in modern cattle. Support for this geographical distribution of haplogroups has previously also been seen in ancient cattle from Germany. However, when analysing 38 historic remains of domestic bulls and three aurochs from northern Europe for this SNP we found no such association. Instead, we noted extensive amounts of temporal variation that can be attributed to transportation of cattle and late breed formation.


Psychiatric brain banking: three perspectives on current trends and future directions.
Postmortem human brain tissue is critical for advancing neurobiological studies of psychiatric illness, particularly for identifying brain-specific transcripts and isoforms. State-of-the-art methods and recommendations for maintaining psychiatric brain banks are discussed in three disparate collections, the National Institute of Mental Health Brain Tissue Collection, the Harvard Brain Tissue Resource Center, and the Mount Sinai School of Medicine Alzheimer's Disease and Schizophrenia Brain Bank. While the National Institute of Mental Health Brain Tissue Collection obtains donations from medical examiners and focuses on clinical diagnosis, toxicology, and building life span control cohorts, the Harvard Brain Tissue Resource Center is designed as a repository to collect large-volume, high-quality brain tissue from community-based donors across a nationwide network, placing emphasis on the accessibility of tissue and related data to research groups worldwide. The Mount Sinai School of Medicine Alzheimer's Disease and Schizophrenia Brain Bank has shown that prospective recruitment is a successful approach to tissue donation, placing particular emphasis on clinical diagnosis through antemortem contact with donors, as well as stereological tissue sampling methods for neuroanatomical studies and frozen tissue sampling approaches that enable multiple assessments (e.g., RNA, DNA, protein, enzyme activity, binding) of the same tissue block. Promising scientific approaches for elucidating the molecular and cellular pathways in brain that may contribute to schizophrenia are briefly discussed. Despite different perspectives from three established brain collections, there is consensus that varied networking strategies, rigorous tissue and clinical characterization, sample and data accessibility, and overall adaptability are integral to the success of psychiatric brain banking.


Validation of the stages of change with mild, moderate, and strenuous physical activity behavior, intentions, and self-efficacy.
The stages of change construct of the Transtheoretical Model (TTM) has been proposed for examining exercise adoption. Studies investigating the construct validity of the stages of change for exercise have used physical activity of moderate or higher intensity as operationalization criterion. Since it has been shown that physical activity of lower intensity also provides health benefits, we investigated whether the stages of change appropriately address lower intensity physical activity. Data with respect to the stages of change as well as behavior, intention and self-efficacy associated with mild, moderate, and strenuous exercise were collected in a sample of 467 males and females aged 20 - 85. Results show that the stages of change can be distinguished by moderate and strenuous but are not consistent with mild exercise. Implications for future research utilizing the stage of change conceptualization are discussed and development of new stage assessment instruments for mild exercise is recommended.


Detection of testicular ultrasonographic lesions in severe male infertility.
We retrospectively assessed the number and histology of testicular lesions diagnosed clinically and by ultrasonography in a population of infertile men. From October 2000 to January 2003, 560 infertile men underwent physical examination, hormonal assessment (follicle-stimulating hormone, luteinizing hormone, testosterone) and scrotal ultrasonography. Eight men were diagnosed with focal testicular ultrasonographic lesions. In 4 cases there was a palpable lesion and in the other 4 cases the lesion was not palpable, diagnosed by ultrasonography (1 was cryptorchid). Only cases of lesions with clear-cut ultrasonographic edges and no history of recent genital infections were considered for explorative surgery through the groin. Microcalcifications were reported if present. The testicle was only preserved when frozen section examination revealed a benign lesion and the margins were negative. Gynecomastia was not present in any patient. No microcalcifications were observed. Follicle-stimulating hormone was high in all patients (range 19.8 to 66.0 mUI/ml, mean 34.4). Luteinizing hormone levels were variable (range 1.32 to 28 mUI/ml, mean 12.3). Testosterone was normal in all cases (range 2.82 to 6.25 ng/ml, mean 4.2). Ultrasonographic features of the lesions were hypoechoic area (6 patients) and mixed hyper-hypoechoic area (2 patients). Histological outcomes of Leydig cell tumor (in 3 patients), focal Leydig cell hyperplasia (1 patient), fibrosis (1 patient), diffuse Leydig cell hyperplasia (1 patient), classic seminoma (1 patient) and embryonal carcinoma (in 1 patient) were observed. Of 560 infertile patients 8 (1.4%) showed focal testicular lesions, 2 (0.4%) were diagnosed with germ cell tumors and 3 (0.5%) with interstitial cell neoplasms. The malignant tumors were both palpable and in 2 of 3 cases Leydig cell tumors were diagnosed only with ultrasonography.


Recent Trends and Effectiveness of Antiretroviral Regimens Among Men Who Have Sex With Men Living With HIV in the United States: The Multicenter AIDS Cohort Study (MACS) 2008-2017.
We evaluated trends and population effectiveness (tolerability, HIV suppression) of current combination antiretroviral therapy (cART) regimens mindful of treatment guidelines. Trend analyses included 18 017 person-visits (1457 men) on cART during 2008-2017 in the Multicenter AIDS Cohort Study. Effectiveness analyses of current regimens used 3598 person-visit-pairs (745 men) on cART in 2014-2017. Inverse-probability-of-treatment-and-censoring weighted Poisson regression with robust variances was used to evaluate the association between regimens and switching, adherence and HIV RNA <20 copies/mL. Integrase strand transfer inhibitor (INSTI)-based regimen usage has increased since 2008. Almost 90% of cART initiators started with INSTI-cART in 2016-2017; cART adherence was stable around 90% and 83%-85% suppressed virus (<20 cp/mL). Commonly used regimens in 2014-2017 contained disoproxil fumarate/emtricitabine (TDF/FTC) backbone with efavirenz (EFV, n = 1161 person-visits), elvitegravir/cobicistat (EVG/c, n = 551), rilpivirine (RPV, n = 492), darunavir/ritonavir (DRV/r, n = 351), or atazanavir (ATV)/r (n = 333). Others were dolutegravir/abacavir/lamivudine (DTG/ABC/3TC, n = 401) and EVG/c/tenofovir alafenamide/FTC (EVG/c/TAF/FTC, n = 309). Compared to EFV/TDF/FTC users, ATV/r+TDF/FTC users switched more (rate ratio [RR] = 1.80, 95% confidence interval (CI), 1.17-2.76), while those on DTG/ABC/3TC (RR [95% CI] = 0.16 [0.08-0.31]) or EVG/c/TAF/FTC (RR [95% CI] = 0.12 [0.06-0.27]) switched less. The rate of suppressed HIV RNA was 15% (95% CI, 2%-26%) lower among younger EVG/c/TDF/FTC users and 18% (95% CI, 3%-34%) higher in older DRV/r+TDF/FTC users; adherence did not differ by regimen. Consistent with guidelines, recent cART initiators started with INSTI-cART, which was associated with less switching early after initiation. Factors beyond those studied here, such as need for salvage therapy, unique personal characteristics, drug interactions, and cost may influence treatment decisions.


Effects of dietary fibre and protein on urea transport across the cecal mucosa of piglets.
In ruminants, gastrointestinal recycling of urea is acutely enhanced by fibre-rich diets that lead to high ruminal concentration of short chain fatty acids (SCFA), while high ammonia has inhibitory effects. This study attempted to clarify if urea flux to the porcine cecum is similarly regulated. Thirty-two weaned piglets were fed diets containing protein (P) of poor prececal digestibility and fibre (F) at high (H) or low levels (L) in a 2 × 2 factorial design. After slaughter, cecal content was analyzed and the cecal mucosa incubated in Ussing chambers to measure the effect of pH, SCFA and NH4 (+) on the flux rates of urea, short-circuit current (I sc) and tissue conductance (G t). NH4 (+) significantly enhanced I sc (from 0.5 ± 0.2 to 1.2 ± 0.1 μEq cm(-2) h(-1)). No acute effects of SCFA or ammonia on urea flux were observed. Tissue conductance was significantly lower in the high dietary fibre groups irrespective of the protein content. Only the HP-LF group emerged as different from all others in terms of urea flux (74 ± 6 versus 53 ± 3 nmol cm(-2) h(-1)), associated with higher cecal ammonia concentration and reduced fecal consistency. The data suggest that as in the rumen, uptake of ammonia by the cecum may involve electrogenic transport of the ionic form (NH4 (+)). In contrast to findings in the rumen, neither a high fibre diet nor acute addition of SCFA enhanced urea transport across the pig cecum. Instead, a HP-LF diet had stimulatory effects. A potential role for urea recycling in stabilizing luminal pH is discussed.