[The belly-board technic for the sparing of the small intestine. Studies on positioning accuracy taking into consideration conformational irradiation technics].
The immobilization error of patients positioned on the open table-top device in prone position as well as the movement of the small bowel out of the pelvis by this positioning technique was determined. The positioning error is of special importance for the 3-dimensional treatment planning for conformational radiotherapy. The positioning error was determined by superpositioning 106 portal films with the corresponding simulator films from 21 patients with carcinoma of the rectum who-received 3D-planned conformational radiotherapy (3-field technique with irregular blocks). The movement of the small bowel out of the pelvis was studied by comparing simulator films after barium swallow in supine and open table-top position as well with 3D-treatment plans of the same patient in both positions in 3 cases. The positioning error along the medio-lateral, dorso-ventral and cranio-caudal axis was 1.4/0.6/1.8 mm and the standard deviation 4.4/6.8/6.3 mm, respectively. In comparison to the supine position more rotation errors in the sagittal view were observed (37% and 9% respectively) with a median of 5.1 degrees. Six out of 22 patients showed no adhesions of the small bowel and a complete movement out of the treatment field was achieved. 14 out of 16 Patients with adhesions revealed a partial movement of the small bowel out of the treatment field. Comparing 3D-treatment plans in both positions again demonstrated a marked reduction of the irradiated small bowel volume with the use of the open table-top device. The open table-top device positioning technique is a simple and cheap positioning support to reduce small bowel obstructions by radiation therapy of pelvic and retroperitoneal tumors. For the radiation treatment planning the data suggest a safety margin to compensate positioning errors of approximately 1.5 cm referring to the 95% confidence interval.


The origin of the naked grains of maize.
The most critical step in maize (Zea mays ssp. mays) domestication was the liberation of the kernel from the hardened, protective casing that envelops the kernel in the maize progenitor, teosinte. This evolutionary step exposed the kernel on the surface of the ear, such that it could readily be used by humans as a food source. Here we show that this key event in maize domestication is controlled by a single gene (teosinte glume architecture or tga1), belonging to the SBP-domain family of transcriptional regulators. The factor controlling the phenotypic difference between maize and teosinte maps to a 1-kilobase region, within which maize and teosinte show only seven fixed differences in their DNA sequences. One of these differences encodes a non-conservative amino acid substitution and may affect protein function, and the other six differences potentially affect gene regulation. Molecular evolution analyses show that this region was the target of selection during maize domestication. Our results demonstrate that modest genetic changes in single genes can induce dramatic changes in phenotype during domestication and evolution.


Copy number alterations in prostate tumors and disease aggressiveness.
Detecting genomic alterations that result in more aggressive prostate cancer may improve clinical treatment and our understanding of the biology underlying this common but complex disease. To this end, we undertook a genome-wide copy number alterations (CNAs) study of clinicopathological characteristics of 62 prostate tumors using the Illumina 1M single nucleotide polymorphism array. The highest overall frequencies of CNAs were on chromosomes 8q (gains), 8p (loss and copy-neutral), and 6q (copy-loss). Combined loss and copy-neutral events were associated with increasing disease grade (P = 0.03), stage (P = 0.01), and diagnostic prostate specific antigen (PSA) (P = 0.01). Further evaluation of CNAs using gene ontology identified pathways involved with disease aggressiveness. The "regulation of apoptosis" pathway was associated with stage of disease (P = 0.004), while the "reproductive cellular process" pathway was associated with diagnostic PSA (P = 0.00038). Specific genes within these pathways exhibited strong associations with clinical characteristics; for example, in the apoptosis pathway BNIP3L was associated with increasing prostate tumor stage (P = 0.007). These findings confirm known regions of CNAs in prostate cancer and localize additional regions and possible genes (e.g., BNIP3L, WWOX, and GATM) that may help to clarify the genetic basis of prostate cancer aggressiveness.


Synthesis of Pectin and Eggshell Biowaste-Mediated Nano-hydroxyapatite (nHAp), Their Physicochemical Characterizations, and Use as Antibacterial Material.
The current study reports the synthesis of sustainable nano-hydroxyapatite (nHAp) using a wet chemical precipitation approach. The materials used in the green synthesis of nHAp were obtained from environmental biowastes such as HAp from eggshells and pectin from banana peels. The physicochemical characterization of obtained nHAp was carried out using different techniques. For instance, X-ray diffractometer (XRD) and FTIR spectroscopy were used to study the crystallinity and synthesis of nHAp respectively. In addition, the morphology and elemental composition of nHAP were studied using FESEM equipped with EDX. HRTEM showed the internal structure of nHAP and calculated its grain size which was 64 nm. Furthermore, the prepared nHAp was explored for its antibacterial and antibiofilm activity which has received less attention previously. The obtained results showed the potential of pectin-bound nHAp as an antibacterial agent for various biomedical and healthcare applications.


Evidence-based practice? An evolution is necessary for bovine practitioners, teachers, and researchers.
We suggest a definition of evidence-based veterinary medicine that takes into account its objectives and practicality. We view it as an information tool that does not replace experience but helps to improve background knowledge and solve clinical foreground questions. It could be defined as the use of accurate, informative, and clear summarized information (abstracts) of high-level research studies that is obtained quickly via free-access databases available via the Internet and that is provided by a proactive veterinary scientific community in search of transparency, accountability, and evidence.


Resolution and contrast enhancement of subtractive second harmonic generation microscopy with a circularly polarized vortex beam.
We extend the subtractive imaging method to label-free second harmonic generation (SHG) microscopy to enhance the spatial resolution and contrast. This method is based on the intensity difference between two images obtained with circularly polarized Gaussian and doughnut-shaped beams, respectively. By characterizing the intensity and polarization distributions of the two focused beams, we verify the feasibility of the subtractive imaging method in polarization dependent SHG microscopy. The resolution and contrast enhancement in different biological samples is demonstrated. This work will open a new avenue for the applications of SHG microscopy in biomedical research.


An evaluation of dilute acid and ammonia fiber explosion pretreatment for cellulosic ethanol production.
The challenge associated with cellulosic ethanol production is maximizing sugar yield at low cost. Current research is being focused to develop a pretreatment method to overcome biomass recalcitrance in an efficient way. This review is focused on two major pretreatments: dilute acid (DA) and ammonia fiber explosion (AFEX) pretreatment of corn stover and how these pretreatment cause morphological and chemical changes to corn stover in order to overcome the biomass recalcitrance. This review highlights the key differences of these two pretreatments based on compositional analysis, cellulose and its crystallinity, morphological changes, structural changes to lignin, enzymatic reactivity and enzyme adsorption onto pretreated solids and finally cellulosic ethanol production from the hydrolysate of DA and AFEX treated corn stover. Each stage of the process, AFEX pretreated corn stover was superior to DA treated corn stover.


Comparison of outcomes in non-head injured trauma patients using pre-injury warfarin or direct oral anticoagulant therapy.
Patients on prehospital anticoagulation with warfarin or direct oral anticoagulants (DOACs) represent a vulnerable subset of the trauma population. While protocolized warfarin reversal is widely available and easily implemented, prehospital anticoagulation with DOAC is cost prohibitive with only a few reversal options. This study aims to compare hospital outcomes of non-head injured trauma patients taking pre-injury DOAC versus warfarin. A retrospective cohort study at a level 1 trauma center was performed. All adult trauma patients with pre-injury anticoagulation admitted between January 2015 and December 2018, were stratified into DOAC-using and warfarin-using groups. Patients were excluded if they had traumatic brain injury (TBI). Univariate and multivariable analyses were performed. Outcomes measures included in-hospital mortality, blood transfusion requirements, ICU length of stay (LOS), hospital LOS and discharge disposition. 374 non-TBI trauma patients on anticoagulation were identified, of which 134 were on DOACs and 240 on warfarin. Patients on DOACs had a higher ISS (9 [IQR, 9-10] vs. 9 [IQR, 5-9]; p<0.001), and lower admission INR values (1.2 [IQR, 1.1-1.3] vs 2.4 [IQR, 1.8-2.7]; p<0.001) than warfarin users. Use of reversal agents was higher in warfarin users (p<0.001). Relative to warfarin, DOAC users did not differ significantly with respect to hospital mortality (OR 0.47, 95% CI [0.13-1.73]). Multivariable analysis (not possible for mortality) did not show significant difference for RBC transfusion requirements (OR 0.92 [0.51-1.67]), ICU LOS (OR 1.08 [0.53-2.19]), hospital LOS (OR 1.10 [0.70-1.74]) or discharge disposition (OR 0.56 [0.29-1.11]) between the groups. Despite lower reversal rates and higher ISS, non-TBI trauma patients with pre-injury DOAC use had similar outcomes as patients on pre-injury warfarin. There may be equipoise to have larger, prospective studies evaluating the comparative safety of DOACs and warfarin in the population prone to low energy fall type injuries.


The retinofugal pathways in a primitive actinopterygian, the chondrostean Acipenser güldenstädti. An experimental study using degeneration, radioautographic and HRP methods.
Experimental study of the retinofugal pathways in Acipenser güldenstädti was carried out on 109 specimens using 3 experimental tracing methods: Fink-Heimer (after retinal ablation), radioautography (after intraocular injection of tritiated markers) and HRP (after intraocular injection of HRP or iontophoretic deposit of HRP on the optic nerve). The optic fiber was found to partially decussate at the chiasm and to project to 5 contralateral regions: (1) hypothalamus (area optica hypothalami); (2) thalamus (area optica dorsalis thalami, area optica mediale thalami, nucleus thalamicus tractus optici marginalis, nucleus laminaris ventralis); (3) pretectum (nucleus pretectalis ventralis, nucleus commissurae posterioris, nucleus intercalaris lateralis); (4) optic tectum (superficial layers); and (5) mesencephalic tegmentum (area optica accessoria). The ipsilateral component was well developed and innervated the same regions mentioned above. A few contralateral optic fibers crossed again in the posterior commissure and terminated within ipsilateral visual pretectal structures. Although the architecture of the visual centers was less elaborated in this paleopterygian than in neopterygians (holosteans, teleosteans), we observed that the general organization of the retinal contralateral projections in this fish was comparable to that of more advanced actinopterygians. Our results indicate that this pattern was probably set at a very early date, perhaps as soon as the emergence of the chondrostean grade at the beginning of the Devonian.


BLT1 and BLT2: the leukotriene B(4) receptors.
Two receptors for leukotriene B(4) (LTB(4)) have been molecularly identified: BLT1 and BLT2. Both receptors are G protein-coupled seven transmembrane domain receptors, whose genes are located in very close proximity to each other in the human and mouse genomes. The two receptors differ in their affinity and specificity for LTB(4): BLT1 is a high-affinity receptor specific for LTB(4), whereas BLT2 is a low-affinity receptor that also binds other eicosanoids. The two receptors also differ in their pattern of expression with BLT1 being expressed primarily in leukocytes, whereas BLT2 is expressed more ubiquitously. By mediating the activities of LTB(4), these receptors participate both in host immune responses and in the pathogenesis of inflammatory diseases. Reduced disease severity in animal inflammatory models seen with LTB(4) receptor antagonists and in mice with targeted deletion of BLT1 have revealed important roles for LTB(4) and its receptors in regulating pathologic inflammation.


A new one-stage surgical technique for postlaryngectomy speech.
A new one-stage surgical technique for the postlaryngectomy speech applied to the 17 patients and its results are described herein. The essential part of this technique consists of the construction of a tracheo-esophageal shunt using only the remainder of the trachea obtained at the time of laryngectomy to reestablish an air communication between the trachea and the gullet. Fourteen patients of the 17 patients thus operated upon developed conversational abilities equivalent to the normal subject, except that they use a finger during the speech for the occlusion of the tracheal opening. This technique can be applied to almost all candidates for total laryngectomy with or without neck dissection. The initial speech was developed in 25 days after operation in average. The inflow of the salivas and/or fluids into trachea is not problematic in these patients. It has been well known that an air communication reestablished between the natural air way and the gullet could reproduce a vocal function after total laryngectomy [5]. Despite very few surgical techniques for this purpose have been described and applied clinically, although a tremendous effort has been made for the complete removal of the malignancy and the avoidance of recurrence up to the present [1--4, 6]. A new surgical method for achieving a tracheo-esophageal shunt for the postoperative vocal function is described herein.


Effect of intravenous coadministration of human stroma cell lines on engraftment of long-term repopulating clonal myelodysplastic syndrome cells in immunodeficient mice.
Engraftment of clonal hematopoietic precursor cells from patients with myelodysplastic syndrome (MDS) in immunodeficient mice has been difficult to achieve by intravenous (i.v.) injection. We used i.v. coadministration of the human marrow stroma cell line HS27a with CD34+ MDS cells in Nod.cg-Prkdc(scid) Il2rg(tm1wjll) (NSG) mice to provide signals that would facilitate engraftment. Hematopoietic cells from 24 MDS patients were transplanted. Cells from all patients were engrafted, and engraftment was documented in 44 of 46 evaluable mice (95%). Immunohistochemistry revealed human HS27a stroma colocalizing with human hematopoietic cells in mouse spleens. Human CD34+ precursors harvested from marrow and spleen of primary murine recipients, when combined with HS27a cells, were also engrafted successfully in secondary NSG recipients, showing persistence of the original clonal characteristics. This observation supports the concept that clonal markers were present in long-term repopulating cells. We suggest that HS27a stroma cells 'traveled' in direct contact with hematopoietic precursors and enabled their propagation. An essential signal for engraftment appears to be CD146, which is prominently expressed on HS27a cells. This xenotransplantation model will allow to further dissect signals that control engraftment of MDS cells and should be amenable to in vivo treatment studies.


Predicting in vitro tissue culture growth for cytogenetic evaluation of stillborn fetuses.
A prospective study was undertaken of 131 perinatal deaths to determine whether gestational age, body weight, maceration degree and autopsy interval influenced successful in vitro tissue culture for cytogenetic evaluation. Perinatal populations were categorized as neonatal death (NND), fresh stillbirth (FSB), or graded as macerated stillbirth (MAC-0, MAC-1, MAC-2, MAC-3). Metaphase production by at least 15 cells separated 'growth' from 'no growth' categories after sampling liver, kidney and spleen. Body weight and degree of maceration were predictive of successful 'growth', while gestational age and autopsy interval were not. Body weight was significant in separating 'growth' from 'no growth' in NND (P = 0.05), FSB, MAC-0 and MAC-1 (P = 0.01). Growth probabilities were 0.78 (NND), 0.57 (FSB), 0.49 (MAC-0), 0.38 (MAC-1) and zero for MAC-2 and MAC-3. We conclude that (a) tissues from MAC-2 and MAC-3 fetuses do not grow and thus need not be sampled at autopsy, (b) maceration degree and body weight can be used to predict the growth probability in the other categories, (c) tissue samples can be taken during daylight hours, since autopsy interval does not influence successful growth provided the fetus is refrigerated at 4 degrees C, (d) all of the above conclusions have cost-efficiency implications for cytogenetic laboratories.


[The effect of sodium thiosulfate on nonspecific body resistance and on the immune reactions in acute acrylonitrile poisoning].
Experiments on noninbred Wistar mice and rats showed that acute acrylonitrile (0.5 LD50) intoxication leads to decrease of nonspecific resistance of the organism and humoral and cellular immunity responses. The antidote sodium thiosulfate increases suppression of the responses under study.


Relationships between young drivers' personality characteristics, risk perceptions, and driving behaviour.
Research has shown that inexperienced drivers underestimate the risks associated with a range of driving situations. In addition, personality factors are an important influence on both risk perceptions and driving behaviour. The study investigated the strength of relationship between personality factors, risk perceptions, and driving behaviour among young, mainly inexperienced drivers. One-hundred and fifty-nine students aged between 17 and 20 completed an online questionnaire assessing five facets of personality, four components of risk perceptions, and one measure of driving behaviour. Using structural equation modeling as a means of assessing the overall fit of each model, 39% of the variance in young drivers' speeding was accounted for by Excitement-Seeking, Altruism, their Aversion to Risk Taking, and their own likelihood of having an accident, with Altruism and Aversion to Risk Taking both showing moderate negative relationships. Road safety interventions should examine whether they strengthen young drivers' appreciation of the impact of their actions on others through positive reinforcement of altruistic norms.


Initial clinical cases of the use of a NF-kappaB decoy at the site of coronary stenting for the prevention of restenosis.
Nuclear factor-kappaB (NF-kappaB) plays a pivotal role in restenosis after percutaneous coronary intervention (PCI) and the aim of the present clinical trials was to evaluate the effectiveness of a NF-kappaB decoy for preventing restenosis. The initial case was a patient suffering from effort angina who had stenoses in the proximal and middle portions of the right coronary artery. The patient received 2 stents; the NF-kappaB decoy was delivered to the distal site, but not the proximal site. Six months after the PCI, the NF-kappaB decoy had suppressed restenosis in comparison with the no-decoy transfection site. The second case was a patient who underwent single-stent insertion and decoy transfection at the same site, and minimal intimal thickening was observed at 6 month after PCI. No systemic adverse effects were observed in either case. These results indicate the clinical usefulness and safety of NF-kappaB decoy transfection after PCI, but further evaluations are necessary to confirm its clinical effectiveness.


Different O-glycosylation of respiratory mucin glycopeptides from a patient with cystic fibrosis.
The O-linked oligosaccharides from three fractions of highly glycosylated mucin glycopeptides obtained from sputum of a patient with cystic fibrosis were characterized and compared regarding size, composition, sequence and when possible linkage positions. Neutral and sialic acid-containing glycans were permethylated and analyzed by high-temperature GC-MS and MALDI-MS, showing more than 60 different oligosaccharides with a size of up to 15 monosaccharide units. Some of the observed oligosaccharides are novel for respiratory secretions, one being a trifucosylated heptasaccharide with the proposed structure: Fuc-Gal-4(Fuc-3)GlcNAc-(Fuc-)Gal-3GalNAcol. The glycosylation of two of the glycopeptide fractions was similar with regard to the neutral and sialylated oligosaccharides despite their different origins from the sol or gel phase. Analysis of the sulfated oligosaccharides by FAB-MS/MS indicated that the gel fraction contained C-6 linked sulfate groups while the two sol fractions also contained C-3 linked sulfate. The results suggest the presence of different glycosylated mucin domains, probably originating from different mucin glycoforms and/or apoproteins in the airway of cystic fibrosis patients.


Ventriculocoronary connections in hypoplastic right heart syndrome: autopsy serial section study of six cases.
Myocardial sinusoids communicating with the coronary systems occur in pulmonary atresia with intact ventricular septum. To test the hypothesis that the extent of ventriculocoronary connections correlates with the degree of right ventricular outflow obstruction as evidenced by clinical, angiographic and gross anatomic findings, a serial section study of six human autopsy hearts representing a spectrum of hypoplastic right heart was undertaken. Slides were evaluated for the presence and extent of ventriculocoronary connections, associated developmental abnormalities and secondary changes in the ventricular walls. Whereas extensive blind-ended deep sinusoids were a feature of all five cases with unrelieved obstruction, ventriculocoronary connections were identified in three. Changes that suggested ongoing remodeling provide new evidence for the postnatal temporal evolution of these anomalous communications. The regional distribution of myofiber disarray in hypoplastic right heart supports the concept that vascularization parallels myocardial organization in the developing human heart.


Lymph node targeted multi-epitope subunit vaccine promotes effective immunity to EBV in HLA-expressing mice.
The recent emergence of a causal link between Epstein-Barr virus (EBV) and multiple sclerosis has generated considerable interest in the development of an effective vaccine against EBV. Here we describe a vaccine formulation based on a lymph node targeting Amphiphile vaccine adjuvant, Amphiphile-CpG, admixed with EBV gp350 glycoprotein and an engineered EBV polyepitope protein that includes 20 CD8+ T cell epitopes from EBV latent and lytic antigens. Potent gp350-specific IgG responses are induced in mice with titers >100,000 in Amphiphile-CpG vaccinated mice. Immunization including Amphiphile-CpG also induces high frequencies of polyfunctional gp350-specific CD4+ T cells and EBV-specific CD8+ T cells that are 2-fold greater than soluble CpG and are maintained for >7 months post immunization. This combination of broad humoral and cellular immunity against multiple viral determinants is likely to provide better protection against primary infection and control of latently infected B cells leading to protection against the development of EBV-associated diseases.


Characterization of a newly discovered T-cell receptor beta-chain heterodimer expressed on a CD8+ bone marrow subpopulation that promotes allogeneic stem cell engraftment.
The facilitating cell is a rare CD8+ bone marrow subpopulation that can enhance allogeneic hematopoietic stem cell engraftment across complete major histocompatibility complex barriers without inducing acute graft-versus-host disease. Here we describe a CD3epsilon-associated complex on the facilitating cell surface that consists of the T-cell receptor beta-chain disulfide-linked to a previously unknown 33-kilodalton glycoprotein. Provisionally called FCp33, this glycoprotein does not represent any of the known protein chains or surrogates associated with CD3-T-cell receptor beta. Expression of this CD3-T-cell receptor beta-FCp33 complex directly correlates with the facilitating cell's functional ability to enhance allogeneic stem cell engraftment in vivo.


Distribution of micro-essential (Fe, Cu, Zn) and toxic (Hg) metals in tissues of two nutritionally distinct hydrothermal shrimps.
Hydrothermal ecosystems of the Mid Atlantic Ridge (MAR) are dominated by shrimps and mussels that are naturally exposed to elevated levels of heavy metals providing unique in situ laboratories for ecotoxicological investigations. This study reports on the tissue compartmentalization of both micro-essential (Fe, Zn, Cu) and toxic metals (Hg) in two nutritionally distinct cariddean vent shrimps: Rimicaris exoculata and Mirocaris fortunata, in order to shed light on organism-biota interactions at hydrothermal vents. High metal concentrations in shrimps confirmed extreme exposure levels at both geochemically different hydrothermal vents (Rainbow and Lucky Strike). However, Hg concentrations were below those reported in species for human consumption that may either suggest low bioavailability of the metal, or its effective detoxification/depuration by the hydrothermal shrimp that needs to be confirmed by post-capture toxicological investigations. Distribution of metals in different tissues had very similar patterns in both shrimp species, the target organs being gill and pylorus. Tissue levels correlated well with end-member fluid composition with regard to element ratios, i.e. Fe/Zn and Fe/Cu ratios in end-member fluids reported for Rainbow and L. Strike were conserved in the gills of M. fortunata. Moreover, R. exoculata that lives closer to venting exits as compared to M. fortunata, had similar or often less metals accumulated in selected organs, possibly owing to its higher degree of adaptation to hydrothermal conditions. Despite of high concentrations in tissues micro essential metals only represented a small fraction (14-36%) of the whole body burden indicating preponderance of minerals on the surface and/or in the gut, and thus points to improper use of whole body concentration in metal bioavailability interpretations at hydrothermal vents.


The Perception of Emotions in Spoken Language in Undergraduates with High Functioning Autism Spectrum Disorder: A Preserved Social Skill.
Identifying emotions in speech is based on the interaction of lexical content and prosody. This may be disrupted in individuals with High-Functioning Autism Spectrum Disorder (HF-ASD). Undergraduates with HF-ASD (n = 20) and matched typically developed peers (n = 20) were tested using the (Hebrew) Test for Rating of Emotions in Speech. Participants rated the degree to which a target-emotion is present in spoken sentences, in which the emotional-lexical and -prosodic content appear in different combinations from trial to trial. No group differences were found in measures of emotion-identification, selective-attention (focusing on one target-channel) and integration. These preserved abilities can partially explain the high levels of independence and self-control characterizing students with HF-ASD. Support programs may rely on such skills to improve social interactions.


Survival Rate of Ultrawide Diameter Implants Placed into Molar Postextraction Sockets and in Function for Up to 144 Months.
Innovations in macroimplant design, specifically ultrawide implants 7.0 mm or greater in diameter, have allowed immediate molar replacement. This is a retrospective study assessing the survival rates of ultrawide diameter implants (7.0, 8.0, 9.0 mm) immediately placed into molar extraction sockets. Implants were followed up to 144 months postplacement. A retrospective study was conducted of all patients treated in a private surgical practice between January 1, 2008 and December 31, 2020, who received ultrawide dental implants (7.0, 8,0, 9.0 mm.) placed immediately into molar extraction sockets. Wide diameter healing abutments were placed on all implants at the time of surgery. Abutments and crown restorations were fabricated after at least 4 months of unloaded healing. Patient age, sex, implant location and implant diameters were examined for survival. Insertion torque values at the time of placement and time in function were also evaluated. Biometric statistics were computed with p-values (<0.05. Descriptive and bivariate statistics were computed; p-values were set at 0.05. Five hundred forty-four patients (225 males; 319 females) average age 62.5 years (range 27 to 95) had 563 implants placed. Five hundred thirty-five of five hundred sixty-three (535/563) implants survived; 28 failed [clinical survival rate (CSR) 95.03%]. Number and time in function were: 0 to 12 years 100%; 0 to 9 years 85%; 0 to 6 years 69%; 0 to 3 years 35% or 10 to 12 years 16%; 7 to 9 years 16%; 4 to 6 years 34%; 0 to 3 years 35%. No significant differences were found between sex and implant failures (p = 0.22). Maxillary (266/285; 93.3%) and mandibular (269/278; 96.8%) implant CSRs were not significantly different. Three implant diameters were used: 7.0 mm (206/563) [36.6%]; 8.0 mm (267/563) [47.4%]; 9.0 mm (90/563) [15.9%]. Clinical survival rates were: 7.0 mm (201/206) [97.6%]; 8.0 mm (252/267) [94.4%]; 9.0 mm (82/90) [91.1%]. Mean age for patients with failed implants did not show any significant differences (p = 0.1398). Fifteen of the 28 failed implants failed within 120 days of surgical placement (prior to definitive restoration; [53.6%]; 4 implants failed between 4 and 12 months [14.3%]; 9 implants failed at least 1-year postloading [32.1%]. The results of this long-term retrospective study regarding ultrawide diameter implants suggested that these implants were viable treatment options for immediate molar replacement following tooth extraction in either jaw with an unloaded healing protocol. High clinical survival rates were reported over a 144-month (12-year) timeframe.


Effects of A23187 in cultures containing only rat Schwann cells and sensory neurons.
Serum from approximately 40% of patients with the acute Guillain-Barré syndrome (GBS) selectively destroys myelin and myelin-related Schwann cells in cultures containing only rat dorsal root ganglion neurons and Schwann cells. To determine if the effects of GBS serum on myelin and myelin-related Schwann cells could be mediated through elevations in the intracellular concentration of calcium ions, we compared the effects of cytotoxic serum to A23187, a divalent cation ionophore. Both myelin- and nonmyelin-related Schwann cells were killed along with neurons in the presence of A23187 and extracellular calcium ions. Myelin sheaths also underwent vesicular disruption. The ultrastructural appearance of myelin and myelin-related Schwann cell lysis caused by A23187 were essentially identical to damage produced by GBS serum. These observations suggest that GBS serum factors might damage myelin and myelin-related Schwann cells in culture by an increase in myelin-related Schwann cell permeability to extracellular calcium ions. In contrast, A23187 causes necrosis of Schwann cells and neurons as well as myelin lysis by a nonselective increase in membrane permeability to extracellular calcium ions.


Anti-MDA5 antibody-positive clinically amyopathic dermatomyositis with diffuse alveolar damage diagnosed by transbronchial lung cryobiopsy: A case report.
Diffuse alveolar damage (DAD) is known to be a pathological hallmark of acute respiratory distress syndrome or acute interstitial pneumonia, and to have a poor prognosis. We report a case of anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive clinically amyopathic dermatomyositis (CADM) with rapidly progressive interstitial lung disease (RP-ILD), in which DAD was confirmed by transbronchial lung cryobiopsy at an early stage without respiratory failure. Although this patient initially did not show respiratory failure, his respiratory condition gradually worsened despite intensive immunosuppression therapy and he died 3 months later. Therefore, the early pathological findings of DAD did not match the clinical picture, which showed no respiratory failure. However, these findings were consistent with the subsequent course and poor outcome. Histological DAD, even in the absence of respiratory failure, may indicate a subsequent poor prognosis and explain the refractory course of RP-ILD with anti-MDA5 antibody-positive CADM.


Experience of the implementation and outcomes of universal testing for Lynch syndrome in the United Kingdom.
Colorectal cancer (CRC) is diagnosed in approximately 45 000 people annually in the UK, and it is estimated that Lynch syndrome (LS) accounts for 3.1% of these cases. In February 2017, National Institute for Health and Care Excellence (NICE guideline DG27 recommended universal testing of new cases of CRC for mismatch repair (MMR) status. The aim of this study was to implement universal testing for LS in CRC patients in a secondary care setting. We prospectively collected data on consecutive newly diagnosed CRC patients at our centre from November 2016 to August 2018, including evidence of MMR status determined by immunohistochemistry. We recorded clinicopathological data including age at diagnosis, stage, tumour site, reported histological findings and MMR tumour status. Statistical analysis was performed using the chi-square test and the two-tailed t-test for binary and continuous variables, respectively. A cohort of 203 consecutive patients were diagnosed with CRC during this period. Universal MMR testing was performed for the 198 CRC patients in whom a diagnosis of adenocarcinoma was confirmed, with colonoscopic biopsy used as the source material in 68.6% of cases. Twenty-three CRCs (11.6%) were MMR deficient (dMMR). Most dMMR CRCs (21/23) were early stage tumours (Dukes A or B, P = 0.002). In 39 Dukes B CRCs in patients under 70 years of age, the result of MMR testing influenced decision-making about personalized treatment with 5-fluorouracil based chemotherapy. Our results demonstrate that universal testing of all new cases of CRC for features suggestive of LS is feasible and effective in the UK. Our data also indicate the importance of genetic testing and personalized oncological care.


Designing Complex Radial Heterostructures of Te/Bi2Te3and Te/Bi2-xPbxTe3Nanowires: Fundamental Mechanistic Insights into Nanowire Growth and Evolution.
Metal Telluride/Te heterostructure nanowires are important thermoelectric materials and it is important to be able to tune these materials according to the requirement of the application. In order to do so, a good understanding of the reaction mechanism and critical observation of the evolution of the nanowire heterostructure during the course of reaction is essential. Here, single crystalline, anisotropic Te core/ Bi2Te3 shell nanowires have been synthesized by a facile template-based wet chemical synthesis method. The formation and evolution mechanism of the heterostructure has been elucidated by several control reactions, detailed transmission electron microscopy (TEM) and composition analysis using energy dispersive spectroscopy (EDS) in scanning transmission electron microscopy (STEM) mode of the products of the reactions. Fundamental understanding of the formation mechanism and time-dependent evolution of the core-shell structure in the nanowire have led to successful designing of higher order heterostructures involving Te/Bi2-xPbxTe3. Through this study, interesting insights into the crystal structure evolution, crystal growth and miscibility of PbTe and Bi2Te3 into each other is obtained.


Comparative analysis of data reduction techniques for questionnaire validation using self-reported driver behaviors.
Exploratory data reduction techniques, such as Factor Analysis (FA) and Principal Component Analysis (PCA), are widely used in questionnaire validation with ordinal data, such as Likert Scale data, even though both techniques are indicated to metric measures. In this context, this study presents an e-survey, conducted to obtain self-reported behaviors between Brazilian drivers (N = 1,354, 55.2% of males) and Portuguese drivers (N = 348, 46.6% of males) based on 20 items from the Driver Behavior Questionnaire (DBQ) on a five-point Likert Scale. This paper aimed to examine DBQ validation using FA and PCA compared to Categorical Principal Component Analysis (CATPCA) which is more indicative to use with Likert Scale data. The results from all techniques confirmed the most replicated factor structure of DBQ, distinguishing behaviors as errors, ordinary violations, and aggressive violation. However, after Varimax rotation, CATPCA explained 11% more variance compared to FA and 2% more than PCA. We identified cross-loadings among the component of the techniques. An item changed its dimension in the CATPCA results but did not change the structural interpretability. Individual scores from dimension 1 of CATPCA were significantly different from FA and PCA. Individual scores from factor 1 of CATPCA were significantly different from FA and PCA. Practical applications: The CATPCA seems to be more advantageous in order to represent the original data and considering data constrains. In addition to finding an interpretable factorial structure, the representation of the original data is regarded as relevant since the factor scores could be used for crash prediction in future analyses.


Identification of the airborne aggregation pheromone of the common bed bug, Cimex lectularius.
Adults and juveniles of the common bed bug, Cimex lectularius L. (Hemiptera: Cimicidae), return to and aggregate in harborages after foraging for hosts. We tested the hypothesis that the aggregation is mediated, in part, by an airborne aggregation pheromone. Volatiles from experimental C. lectularius harborages were captured on Porapak Q, fractionated by liquid chromatography, and bioassayed in dual-choice, still-air olfactometer experiments. Of 14 compounds with >100 pg abundance in gas chromatography-mass spectrometry analyses of two bioactive fractions, 10 compounds [nonanal, decanal, (E)-2-hexenal, (E)-2-octenal, (2E,4E)-octadienal, benzaldehyde, (+)- and (-)-limonene, sulcatone, benzyl alcohol] proved to be essential components of the C. lectularius airborne aggregation pheromone.


Ultrastructural localization of adenosine triphosphatase activity in lymphocytes activated in vitro by phytohaemagglutinin.
The ultrastructural localization of Ca2+, Mg2+-activated ATPase was studied in phytohaemagglutinin activated lymphocytes and in normal unstimulated lymphocytes. Cells, fixed in paraformaldehyde--glutaraldehyde, were incubated in a medium containing 3 mM ATP, 5 mM CaCl2 and 2.4 mM Pb(NO3)2 in 0.1 M tris buffer at pH 8.5, the optimum pH for histochemical demonstration of this enzyme. Reaction product was localized in the endoplasmic reticulum, nuclear membrane, Golgi apparatus and mitochondria and on the membrane surrounding large electron-dense bodies. Cytoplasmic vesicles and the plasma membrane were negative. Activity in unstimulated lymphocytes showed a similar localization but the amount of endoplasmic reticulum was much less than in activated lymphocytes. The pH of the medium was critical for the localization of the enzyme. At pH 7.5, the cytoplasmic reaction was almost completely inhibited but a dense precipitate was present on the outer surface of the plasma membrane. The reaction was stimulated by either Ca2+ or Mg2+ and was greatly decreased in the absence of these cations or in the presence of p-chloromercuribenzoate or N-ethylmaleimide. Oligomycin inhibited selectively the reaction in mitochondria but not the reaction at other sites. While the reaction in mitochondria showed complete substrate specificity, a mild reaction was obtained at the other sites with uridine diphosphate or sodium beta-glycophosphate as substrate. ATP was, however, the preferential substrate.


Rat alpha 1-cysteine proteinase inhibitor. An acute phase reactant identical with alpha 1 acute phase globulin.
alpha 1-Cysteine proteinase inhibitor was isolated from normal and acute phase rat serum. The procedure, which includes successive fractionations on AcA 34, Cibacron blue Sepharose, DEAE-Sephacel, and hydroxyapatite, but avoids the use of an affinity chromatography step on a cysteine proteinase gel, led to the preparation of two electrophoretically distinct components. These resolved to a single band of apparent Mr = 68,000 when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A slightly higher Mr was estimated from gel filtration studies, possibly related to the rather high carbohydrate content (15.25% of the dry weight). The purified protein exhibited strong inhibiting capacity towards papain with a Ki of 5 X 10(-11) M. As shown by immunochemical quantitation as well as functional activity, a 6-10-fold increase in the alpha 1-cysteine cysteine proteinase inhibitor content was recorded in inflammatory serum, thus demonstrating the protein to be a typical acute phase reactant. Its partial physicochemical characterization (Mr, isoelectric point, extinction coefficient, amino acid and carbohydrate compositions) shows large similarities with alpha 1 acute phase globulin whose biological function remains unknown, and which is present at the same concentration (about 0.5 g/liter) in normal serum. Identity between the two molecules has been further demonstrated by double immunodiffusion analysis since a continuous precipitating line was observed when purified alpha 1-cysteine proteinase inhibitor was reacted against anti-alpha 1 acute phase globulin and anti-alpha 1-cysteine cysteine proteinase inhibitor antibodies.


POLθ prevents MRE11-NBS1-CtIP-dependent fork breakage in the absence of BRCA2/RAD51 by filling lagging-strand gaps.
POLθ promotes repair of DNA double-strand breaks (DSBs) resulting from collapsed forks in homologous recombination (HR) defective tumors. Inactivation of POLθ results in synthetic lethality with the loss of HR genes BRCA1/2, which induces under-replicated DNA accumulation. However, it is unclear whether POLθ-dependent DNA replication prevents HR-deficiency-associated lethality. Here, we isolated Xenopus laevis POLθ and showed that it processes stalled Okazaki fragments, directly visualized by electron microscopy, thereby suppressing ssDNA gaps accumulating on lagging strands in the absence of RAD51 and preventing fork reversal. Inhibition of POLθ DNA polymerase activity leaves fork gaps unprotected, enabling their cleavage by the MRE11-NBS1-CtIP endonuclease, which produces broken forks with asymmetric single-ended DSBs, hampering BRCA2-defective cell survival. These results reveal a POLθ-dependent genome protection function preventing stalled forks rupture and highlight possible resistance mechanisms to POLθ inhibitors.


Long-term clinical results of selective laser trabeculoplasty in the treatment of primary open angle glaucoma.
To investigate the long-term efficacy of selective laser trabeculoplasty (SLT) in primary open-angle glaucoma, the authors performed a non-randomized, prospective, non-comparative clinical case series. Fifty-two eyes of 52 patients (19 male, 33 female) with primary open angle glaucoma were treated with SLT. Patients were treated with the Coherent Selecta 7000 (Coherent, Palo Alto, CA, USA) frequency-doubled q-switched Nd:YAG laser (532 nm). A total of approximately 50 non-overlapping spots were placed over 180 degrees of the trabecular meshwork at energy levels ranging from 0.6 to 1.4 mJ per pulse. After surgery, patients were maintained with the drug regimen identical to that before treatment. After 1 year the average reduction in intraocular pressure (IOP) from the baseline was 24.3% (6.0 mmHg), after 2 years 27.8% (6.12 mmHg), after 3 years 24.5% (5.53 mmHg), and after 4 years 29.3% (6.33 mmHg). A Kaplan-Meier survival analysis revealed a 1-year success rate of 60%, a 2-year success rate of 53%, a 3-year success rate of 44%, and a 4-year success rate of 44%. Despite a declining success rate, SLT is an effective method to lower IOP over an extended period of time.


Parents' perceptions of research with newborns.
To examine beliefs and attitudes of parents about research with babies. Survey of 72 parents of newborn babies in the neonatal intensive care unit (NICU), and 159 parents of normal newborns using instrument designed for the study. The instrument included questions with graded responses and five research scenarios with varied risks and benefits. Statistical analysis included chi(2) analysis and Fisher's exact test. Parents showed generally favorable attitudes toward research with babies. There were few differences between the two groups of parents, but there was a trend toward more trust in doctors by "NICU parents." Couples with newborns in NICU were significantly more likely to enroll their newborn in a study involving moderate risk and possible major direct benefit. Almost a third of the sample in both groups was willing to enroll their newborn in a study with moderate risk and no direct benefit. Parents believe research is necessary and want to be asked for consent, but many feel they have limited knowledge and would depend on their physician's advice. The fact, that some might enroll their newborn in a study involving a risky procedure that would not benefit the newborn, supports the notion of vulnerability and emphasizes the fact that physicians must be alert to the possibility of coercion and undue influence.


[Conventional techniques of visual field examination Part 2: confrontation visual field testing -- kinetic perimetry].
Evaluation of visual field findings is an essential ophthalmological task. Applying psychophysical principles enables noninvasive (topo-)diagnosis in cases of unexplained visual loss or suspected lesions of the visual pathway. Furthermore, any kind of expert opinion or ability test critically depends on adequate visual field findings. Repeated examinations allow functional follow-up of a disease and assessment of therapeutic efficiency. This paper explicitly focuses on conventional strategies since these are widespread, easily accessible, standardized, and well established in everyday practice over years. Standardized white-on-white perimetry with moving targets (kinetic perimetry) is the major topic of this paper (part 2) in addition to "rough"/preliminary confrontation visual field testing. This review series is aimed at imparting basic concepts in perimetry and psychophysics to ophthalmologists and also addresses interested physicians from other disciplines.


Immunohistochemical identification and localization of pancreatic polypeptide cells in the pancreas and gastrointestinal tract of the human fetus and adult man.
Pancreatic polypeptide (PP)-containing cells were detected by using anti-bovine PP (BPP) serum in the pancreas and gastrointestinal tract of human fetuses, premature infants and in the pancreas, antrum and jejunum of adult man obtained by biopsy from patients with normal gastroduodenal endoscopy. The localization was established by studying the distribution of PP cells in comparison to the distribution of glucagon-, somatostatin- and insulin cells. The first PP cells are seen in the pancreas at 10 weeks of gestation. They are located preferentially in the lower part of the head of the pancreas. The specificity of immunocytological reaction was ascertained by the inhibition of the reaction by bovine pancreatic polypeptide, glucagon and insulin did not modify the immunocytological reaction.


Use of vaccinia virus to express biopharmaceutical products.
Recent technological advancements have fostered the continued development of vaccinia virus as an efficient eukaryotic cloning and expression vector system. Genetically engineered vaccinia virus strains have been constructed for use (i) as recombinant vaccines for the prophylaxis of infectious disease, (ii) in producing significant quantities of biologically active polypeptide factors or enzymes, and (iii) as basic research tools with which to investigate primary structure-function relationships between proteins and their catalytic activities. This review examines the basic vaccinia vector system, its advantages and limitations, and current areas of research. As a specific example of the power and utility of this approach, attention is focused on the application of this technology to the field of neurobiology, specifically the use of recombinant vaccinia to study the expression, processing, and transport of cellular neuropeptides.


Toward a nonhuman model of contingency management: effects of reinforcing abstinence from nicotine self-administration in rats with an alternative nondrug reinforcer.
Reinforcing abstinence from drug use with alternative nondrug reinforcers (e.g., contingency management) is one of the most effective interventions for drug abuse. While nonhuman studies have also shown that access to alternative nondrug reinforcers reduces drug self-administration, this effect has not been examined in nicotine self-administration models. Moreover, abstinence contingencies per se under free-operant conditions have not been examined. The objective of this experiment was to begin development of a model of contingency management interventions by employing a differential-reinforcement-of-alternative-behavior (DRA) schedule of alternative nondrug reinforcement in rats self-administering nicotine. Two groups of rats were trained to self-administer nicotine under a multiple schedule of nicotine and sucrose delivery. The DRA-group was then exposed to an interlocking FR3 nicotine DRA t-sec sucrose schedule. Under this schedule, nicotine continued to be available under the FR schedule while a sucrose pellet was made available contingent upon every pause in self-administration responding (DRA interval) of 40, 80, or 160 s. The FT-group was exposed to noncontingent delivery of sucrose under fixed time (FT) schedules at an average rate equal to that obtained under the DRA schedule in the DRA-group. The DRA schedule significantly reduced NSA by 73, 69, and 59% at the DRA 40, 80, and 160 s intervals, respectively, compared to baseline, while noncontingent sucrose had no significant effect. The effect of the DRA schedule was apparent throughout the NSA sessions. The present assay approximates the abstinence contingencies arranged in contingency management interventions for drug abuse and provides a preliminary nonhuman model of such interventions.


The interaction between mitochondrial haplogroups (M7a/D) and physical activity on adiponectin in a Japanese population.
Mitochondrial haplogroups F, A, and M7a are associated with increased risks of lifestyle diseases, while haplogroups N9 and D are associated with decreased risks of lifestyle diseases or with longevity. The current study determined the existence of interactions between 5 selected haplogroups and physical activity (PA) on total and high-molecular-weight (HMW) adiponectin in 3,994 men and 6,014 women. The interactions between haplogroups (M7a/D) and PA on adiponectin were significant in men (total and HMW: P-interaction = 0.041 and 0.011). The positive association of PA with adiponectin in men carrying haplogroup M7a is attenuated in comparison to men carrying haplogroup D.


Management of High-Grade Coronary Artery Disease and Concomitant Glanzmann Thrombasthenia.
In the present case report, we describe the management of severe coronary artery disease in a patient with Glanzmann thrombasthenia. To the best of our knowledge, there are no established guidelines for revascularization in this setting, and we pose novel discussion points regarding the nuanced care of this patient. (Level of Difficulty: Intermediate.).


Endotoxemia associated with cardiopulmonary bypass.
Endotoxin (lipopolysaccharide) concentrations were determined in the systemic venous blood in nine patients undergoing cardiopulmonary bypass. Lipopolysaccharide concentrations were low and stable until institution of cardiopulmonary bypass (preanesthetic concentration 0.128 +/- 0.032 ng/ml [mean +/- standard error of the mean]; prebypass level 0.136 +/- 0.03 ng/ml). After the start of bypass, the plasma concentration of lipopolysaccharide rose progressively with time to a mean value of 0.347 +/- 0.044 ng/ml (p less than 0.01), which was 0.227 ng/ml above baseline. Upon release of the aortic clamp, an additional rise in lipopolysaccharide concentration occurred after to 5 to 15 minutes to a mean value of 0.428 +/- 0.06 ng/ml (p less than 0.001) above baseline. The concentration then decayed to the baseline level 45 to 75 minutes after termination of bypass. The peak lipopolysaccharide concentration above the baseline positively correlated with both the length of bypass (r = 0.839, p less than 0.005) and the duration of aortic cross-clamping (y = 0.0030X + 0.173 r = 0.85, p less than 0.001) when flow was nonpulsatile. The peak occurred during the period of myocardial and pulmonary reperfusion. This rise in endotoxin concentration may be one of the factors responsible for the prolonged postoperative recovery seen in some patients.


Choline acetyltransferase. The absence of multiple forms and purification from mouse brain.
No multiple forms of choline acetyltransferase were found in extracts of human, mouse, rabbit, guinea pig, cat, and rat brain. A single form of this enzyme only was also demonstrated in bovine nervous tissue, including brain, dorsal and ventral roots, spinal cord, and femoral nerve. The difference from other published findings is believed to be due to ammonium sulfate fractionation, which was not used in the present study. In addition, multiple forms of the enzyme were obtained by others using isoelectric focusing, whereas this study employed gel filtration. Choline acetyltransferase was highly purified form mouse brain using a procedure similar to that used for the enzyme from bovine brain. The steps involved: (1) making an acetone-chloroform powder from whole mouse brains, (2) extracting the powder and chromatographing the soluble fraction with organomercurial Sepharose, (3) passing the enzyme solution through a column of DEAE-cellulose, (4) eluting from hydroxyapatite, and (5) removing contaminants by subunit exchange chromatography. The final preparation was essentially homogeneous as revealed by polyacrylamide gel electrophoresis.


A Review on the Clinical Diagnosis of Multiple System Atrophy.
Multiple system atrophy (MSA) is a rare, adult-onset, progressive neurodegenerative disorder with major diagnostic challenges. Aiming for a better diagnostic accuracy particularly at early disease stages, novel Movement Disorder Society criteria for the diagnosis of MSA (MDS MSA criteria) have been recently developed. They introduce a neuropathologically established MSA category and three levels of clinical diagnostic certainty including clinically established MSA, clinically probable MSA, and the research category of possible prodromal MSA. The diagnosis of clinically established and clinically probable MSA is based on the presence of cardiovascular or urological autonomic failure, parkinsonism (poorly L-Dopa-responsive for the diagnosis of clinically established MSA), and cerebellar syndrome. These core clinical features need to be associated with supportive motor and non-motor features (MSA red flags) and absence of any exclusion criteria. Characteristic brain MRI markers are required for a diagnosis of clinically established MSA. A research category of possible prodromal MSA is devised to capture patients manifesting with autonomic failure or REM sleep behavior disorder and only mild motor signs at the earliest disease stage. There is a number of promising laboratory markers for MSA that may help increase the overall clinical diagnostic accuracy. In this review, we will discuss the core and supportive clinical features for a diagnosis of MSA in light of the new MDS MSA criteria, which laboratory tools may assist in the clinical diagnosis and which major differential diagnostic challenges should be borne in mind.


Academic resilience in UK pharmacy education - a pilot study applying love and break up letters methodology.
Academic resilience is seen as a positive attribute that supports academic attainment and protects against attrition and burnout. Studies have reported that UK pharmacy students have lower academic resilience and wellbeing than the general UK student population but the reasons for this have not been established. This study pilots the use of a novel methodology, love and break-up letter methodology (LBM), to explore these issues focusing on the lived experience of pharmacy students. Final year undergraduate pharmacy study were purposely recruited to the study. Employing LBM, each participant was invited to write reflective love and break-up letters to their academic resilience in higher education during a focus group. Letters and transcripts of subsequent focus group discussion on the feelings and ideas expressed in the letters were thematically analysed. Three meta-themes were identified within the data; the curriculum as gas lighting; the curriculum as abusive; and the curriculum as controlling. Students described how the curriculum diminishes academic resilience by working against their sense of agency and self-esteem. A constant threat of failure emerged as defining the student lived experience; students felt controlled by a curriculum with negative impacts on wellbeing and perseverance. This is the first study to use LBM to explore academic resilience in UK pharmacy students. The results provide evidence that some students view the pharmacy curriculum as a source of relentless adversity that is responsible for promoting a hidden negative connection between students and their education. Further study is required to determine if the results can be generalised across the UK pharmacy student body to explain why UK pharmacy students have lower academic resilience than other UK university students and the steps needed to improve academic resilience in UK pharmacy students.


Studies on the synthesis of naphthoquinoids.
Four derivatives of 6-oxo-3,4,4a,5-tetrahydro-3-hydroxy-2,2-dimethylnaphtho-1,2-pyran (1), known as bactericidal, bacteriostatic, fungicidal, fungistatic agents, were synthesized to investigate the effect of substituents on the aromatic ring.


Biological effects of long-duration, high-field (4 T) MRI on growth and development in the mouse.
The effects of long-duration, high-field magnetic resonance imaging (MRI) on fetal growth and postnatal development in mice were studied. Seven experimental groups of pregnant ICR mice were exposed for 9 hours on day 9 and/or day 12 post coitus (pc) to magnetic fields (4 T static, 5 T/sec switched gradient, and 0.2 W/kg radiofrequency at 170 MHz) associated with MRI conditions. Two experimental groups (sham and exposure groups) were exposed to a combination of ultrasound (day 9 pc, 3.25 MHz, focused) and MRI-associated fields (day 12 pc). No statistically significant changes in fetal growth were observed in the animals exposed to only MRI or ultrasound fields. However, in the combined ultrasound and MRI-exposed group, the fetal weight and crown-rump length were reduced compared with the sham and cage controls. These results suggest that MRI and ultrasound exposure well in excess of current clinical conditions can exert biological effects if applied at sensitive stages of fetal development.


Noradrenergic Locus Coeruleus pathways in pain modulation.
The noradrenergic system is crucial for several activities in the body, including the modulation of pain. As the major producer of noradrenaline (NA) in the central nervous system (CNS), the Locus Coeruleus (LC) is a nucleus that has been studied in several pain conditions, mostly due to its strategic location. Indeed, apart from a well-known descending LC-spinal pathway that is important for pain control, an ascending pathway passing through this nucleus may be responsible for the noradrenergic inputs to higher centers of the pain processing, such as the limbic system and frontal cortices. Thus, the noradrenergic system appears to modulate different components of the pain experience and accordingly, its manipulation has distinct behavioral outcomes. The main goal of this review is to bring together the data available regarding the noradrenergic system in relation to pain, particularly focusing on the ascending and descending LC projections in different conditions. How such findings influence our understanding of these conditions is also discussed.


[Detection of the critical period of pituitary-adrenal system development during postembryonic chicken ontogenesis].
Studies have been made on postembryonic development of the hypophyseal-adrenal system in domestic hens. Most significant functional rearrangements were observed at the 3rd week of life, when corticosteroid content of the blood plasma decreased threefold. Birds subjected to a series of cold stresses at this time, exhibited more rapid sexual maturation, more rapid reaction of the adrenals to exogenous corticotropin and higher resistance to unfavourable factors. Stress expositions in other days of the first month of life also resulted in trace phenomena, although these were less evident. It is suggested that the 3rd week after hatching is a critical period in the development of ihe hypophyseal-adrenal system in hens.


Influence of an antiestrogenic drug (tamoxifen) on Müllerian duct agenesia induced by various steroidal sex hormones in the female chick embryo.
The caudal deficiencies of the Müllerian ducts (MDs) induced in chick embryos after early treatment with testosterone propionate (TP), 17 beta-estradiol benzoate (EB), or dihydrotestosterone (DHT) are the consequence of agenesia, i.e., a stop in duct development occurring during the sexually indifferent stage. The present work shows that EB and DHT act on the MDs in binding cellular estrogen receptors. Indeed, the antiestrogenic drug, tamoxifen, which competes with estrogens at the receptor site level, significantly decreases the percentage and extent of these MD caudal deficiencies. The results also show that such receptors are already present at a time when MDs begin to grow from 4.5 to 5 days of embryonic life onward. On the other hand, tamoxifen does not significantly modify agenesia induced by TP.


Monitoring agricultural rodenticide use and secondary exposure of raptors in Scotland.
Despite the documented risk of secondary poisoning to non-target species by anticoagulant rodenticides there is no statutory post-approval monitoring of their use in the UK. This paper presents results from two Scottish monitoring schemes for the period 2000-2010; recording rodenticide use on arable farms and the presence of residues in raptor carcasses. More than three quarters of arable farms used anticoagulant rodenticides; predominately the second generation compounds difenacoum and bromadiolone. There was widespread exposure to anticoagulant rodenticides in liver tissues of the raptor species tested and the residues encountered generally reflected agricultural use patterns. As found in other studies, Red Kites (Milvus milvus) appeared to be particularly vulnerable to rodenticide exposure, 70 % of those sampled (n = 114) contained residues and 10 % died as a result of rodenticide ingestion. More unexpectedly, sparrowhawks (Accipiter nisus), which prey almost exclusively on birds, had similar exposure rates to species which prey on rodents. Although, with the exception of kites, confirmed mortality from rodenticides was low, the widespread exposure recorded is concerning. Particularly when coupled with a lack of data about the sub-lethal effects of these compounds. This raises questions regarding whether statutory monitoring of use is needed; both to address whether there are deficiencies in compliance with approval conditions or whether the recommended risk management procedures are themselves adequate to protect non-target wildlife.


The Impact of Right Atrial Size to Predict Success of Direct Current Cardioversion in Patients With Persistent Atrial Fibrillation.
The prognostic implication of right atrial (RA) and left atrial (LA) size for an immediate success of direct current cardioversion (DCCV) in atrial fibrillation (AF) remains unclear. This study aimed to compare RA and LA size for the prediction of DCCV success. Between 2012 and 2018, 734 consecutive outpatients were screened for our prospective registry. Each eligible patient received a medical history, blood analysis, and transthoracic echocardiography with a focus on indexed RA (iRA) area and LA volume (iLAV) prior to DCCV with up to three biphasic shocks (200-300-360 J) or additional administration of amiodarone or flecainide to restore sinus rhythm. We enrolled 589 patients, and DCCV was in 89% (n=523) successful. Mean age was 68 ± 10 years, and 40% (n=234) had New York heart association class >II. A prevalence of the male sex (64%, n=376) and of persistent AF (86%, n=505) was observed. Although DCCV success was associated with female sex (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.06-3.65), with absence of coronary heart disease and normal left ventricular function (OR, 2.24; 95% CI, 1.26-4.25), with short AF duration (OR, 1.93; 95% CI, 1.05-4.04) in univariable regression, only iRA area remained a stable and independent predictor of DCCV success (OR, 0.27; 95% CI, 0.12-0.69; area under the curve 0.71), but not iLAV size (OR, 1.16; 95% CI, 1.05-1.56) in multivariable analysis. iRA area is superior to iLAV for the prediction of immediate DCCV success in AF.


Challenges and Opportunities in Electrocatalytic CO2 Reduction to Chemicals and Fuels.
The global temperature increase must be limited to below 1.5 °C to alleviate the worst effects of climate change. Electrocatalytic CO2 reduction (ECO2 R) to generate chemicals and feedstocks is considered one of the most promising technologies to cut CO2 emission at an industrial level. However, despite decades of studies, advances at the laboratory scale have not yet led to high industrial deployment rates. This Review discusses practical challenges in the industrial chain that hamper the scaling-up deployment of the ECO2 R technology. Faradaic efficiencies (FEs) of about 100 % and current densities above 200 mA cm-2 have been achieved for the ECO2 R to CO/HCOOH, and the stability of the electrolysis system has been prolonged to 2000 h. For ECO2 R to C2 H4 , the maximum FE is over 80 %, and the highest current density has reached the A cm-2 level. Thus, it is believed that ECO2 R may have reached the stage for scale-up. We aim to provide insights that can accelerate the development of the ECO2 R technology.


The Symptom Experience of HIV/HCV-Coinfected Adults.
Hepatitis C virus (HCV) infection has emerged as a major problem for adults with HIV infection. This report describes the symptom experience of HIV/HCV-coinfected adults at entry into a longitudinal mixed-method study. In-depth qualitative interviews and a standardized quantitative symptom measure were used to capture the symptom experiences of 39 (46% women) HIV/HCV-coinfected patients. Four major themes emerged from the qualitative interviews: (a) difficulty differentiating between HIV and HCV-related symptoms, (b) commonly cited HCV-related symptoms, (c) ways to control or manage HCV-related symptoms, and (d) lack of symptoms or tests to monitor HCV disease. Participants reported an average of 10 different symptoms and a mean symptom experience score of 18.33 (range = 2-47). Results show the significant symptom burden experienced by HIV/HCV-coinfected adults. However, results suggest that the prevalence of symptoms for HIV/HCV-coinfected patients may not be greater than those experienced by patients with HIV infection alone.


PAD4 Deficiency Improves Bleomycin-induced Neutrophil Extracellular Traps and Fibrosis in Mouse Lung.
Excessive release of neutrophil extracellular traps (NETs) has been implicated in several organ fibrosis, including pulmonary fibrosis. NETs constitute a phenomenon in which decorated nuclear chromatin with cytosolic proteins is released into the extracellular space. PAD4 (peptidylarginine deiminase 4) plays an important role in the formation of NETs. However, the role of NETs in the pathogenesis of pulmonary fibrosis remains undefined. Here, we identified NETs in the alveolar and interstitial lung space of mice undergoing bleomycin (BLM)-induced lung fibrosis, which was suppressed by a pan-PAD inhibitor, Cl-amidine. In vitro, BLM directly induced NETs in blood neutrophils, which was also inhibited by Cl-amidine. Furthermore, Padi4 gene knockout (PAD4-KO) in mice led to the alleviation of BLM-induced NETs and pulmonary fibrosis and to the expression of inflammatory and fibrotic genes. PAD4 deficiency prevented decreases in alveolar epithelial and pulmonary vascular endothelial cell numbers and increases in ACTA2-positive mesenchymal cells and S100A4-positive fibroblasts in the lung. Hematopoietic cell grafts from PAD4-KO mice, not wild-type mice, resolved BLM-induced lung fibrosis and fibrotic gene expression in wild-type and PAD4-KO mice, suggesting that expression of PAD4 in hematopoietic cells may be involved in the development of lung fibrosis. These data suggest that PAD4 deficiency could ameliorate BLM-induced formation of NETs and lung fibrosis, suggesting that this pathway could serve as a therapeutic target for pulmonary fibrosis treatment.


Molecular genetic analysis of surveillance biopsy samples from Barrett's mucosa--significance of sampling.
Our aim was to determine the spectrum and accumulation of mutations in surveillance biopsies from Barrett's mucosa of individual patients during follow-up. We performed loss of heterozygosity (LOH) analysis of six recently described tumor suppressor genes relevant for the carcinogenesis of Barrett's adenocarcinoma from laser-microdissected, paraffin-embedded biopsy samples of Barrett's mucosa without or with low-grade dysplastic change. 118 biopsy samples from 26 patients were taken during surveillance programs in time intervals ranging between 6 and 51 months. We found no significant increase in LOH events at least in a 51-month interval. In two patients, Barrett's adenocarcinoma was diagnosed 6 months after the first diagnosis of Barrett's mucosa. Six of 26 patients did not show LOH. The remaining patients exhibited a striking variation of LOH patterns and accumulations in biopsy samples during follow-up. From our microsatellite marker panel, we were not able to define a single surrogate marker that could serve as a potential biomarker, indicating an increased risk of progression to Barrett's adenocarcinoma. However, LOH combinations, especially APC/p16(INK4) or APC/p53, deserve attention as putative biomarkers in future studies. Our results raise important questions regarding the biological dynamics of mutations in Barrett's mucosa in addition to the influence of sampling, especially with regard to the number of biopsies taken from Barrett's mucosa.


Thymic Stromal Lymphopoietin Induction Is Mediated by the Major Whey Proteins α-Lactalbumin and β-Lactoglobulin through the NF-κB Pathway in Immune Cells.
α-Lactalbumin and β-lactoglobulin are two major whey proteins that specifically bind immunoglobulin E and are suspected as major allergens causing cow's milk allergy (CMA). Recent studies have shown that thymic stromal lymphopoietin is a critical factor linking at the interface of the body and environment to the T-helper 2 response. However, it is not known whether thymic stromal lymphopoietin expression is changed by α-lactalbumin and β-lactoglobulin in immune cells. Using RT-PCR and ELISA, the present study was conducted to examine if intravenous injection of α-lactalbumin and β-lactoglobulin increased pro-inflammatory cytokines, T-helper 2 cytokines, and thymic stromal lymphopoietin expression in several immune cells, including macrophages, mast cells, and keratinocytes. Results showed that α-lactalbumin and β-lactoglobulin induced thymic stromal lymphopoietin, interleukin-6, and tumor necrosis factor-α expression. It was concluded that the allergenicity of α-lactalbumin and β-lactoglobulin may be attributed to thymic stromal lymphopoietin induction, T-helper 2 cytokines, and pro-inflammatory cytokines.


[Characterization of the adaptive response to the action of gamma-rays, induced by low doses of 14C in Chinese hamster fibroblasts].
It has been studied the correlation of the mitotic activity of the chromosome aberrations and apoptosis, in the V-79 cells pre-exposure to an adapting dose of ionizing radiation from 14C-thymidine prior to an acute challenge dose of gamma-rays. In spite of that the incubation of the cells with isotope increased of the yield of the chromosome aberrations, but the cells became more resistant to following gamma-irradiation. Increasing the adaptive dose of the 14C on degree didn't influence on the present of the adaptive response. However, using concentrations of the 14C damaged metaphase/anaphase transition and cells blocked in this check-point by apoptotic death. The results suggest, that the cellular selection has been involved in 14C-induced adaptive response, estimated by level of asymmetric chromosome aberrations in V-79 cells.


Seroprevalence rates of HPyV6, HPyV7, TSPyV, HPyV9, MWPyV and KIPyV polyomaviruses among the healthy blood donors.
Human polyomaviruses HPyV6, HPyV7, TSPyV, HPyV9, MWPyV, and KIPyV have been discovered between 2007 and 2012. TSPyV causes a rare skin disease trichodysplasia spinulosa in immunocompromised patients, the role of remaining polyomaviruses in human pathology is not clear. In this study, we assessed the occurrence of serum antibodies against above polyomaviruses in healthy blood donors. Serum samples were examined by enzyme-linked immunoassay (ELISA), using virus-like particles (VLPs) based on the major VP1 capsid proteins of these viruses. Overall, serum antibodies against HPyV6, HPyV7, TSPyV, HPyV9, MWPyV, and KIPyV were found in 88.2%, 65.7%, 63.2%, 31.6%, 84.4%, and 58%, respectively, of this population. The seroprevalence generally increased with age, the highest rise we observed for HPyV9 and KIPyV specific antibodies. The levels of anti-HPyV antibodies remained stable across the age-groups, except for TSPyV and HPyV9, where we saw change with age. ELISAs based on VLP and GST-VP1 gave comparable seroprevalence for HPyV6 antibodies (88.2% vs.85.3%) but not for HPyV7 antibodies (65.7% vs. 77.2%), suggesting some degree of crossreactivity between HPyV6 and HPyV7 VP1 proteins. In conclusion, these results provide evidence that human polyomaviruses HPyV6, HPyV7, TSPyV, HPyV9, MwPyV, and KIPyV circulate widely in the Czech population and their seroprevalence is comparable to other countries.


Immediate effects of 'Ujjayi Pranayama' on aerodynamic, acoustic and self perception parameters of voice in teachers.
Voice plays a major role in communication, and it reveals the speaker's physical and emotional health, personality, and identity. Professional voice users are dependent on their voice for their livelihood. A minimal change or deviation in their voice can interfere with their career. Since respiration is the source for voice production, good lung capacity and the inspiratory-expiratory ratio are very important in maintaining a good voice quality. Ujjayi Pranayama, an effective breathing technique is targeted in this study. To investigate the immediate effects of Ujjayi pranayama on acoustic, aerodynamic and self-perception parameters of voice in teachers. Twenty normophonic female teachers performed this breathing technique taught by yoga professional. Parameters of aerodynamic, acoustic, and self-perception were analyzed at pre and post-practice. Significant differences in the acoustic variables including intensity and jitter were observed. Aerodynamic parameters have shown significant improvements in the variables including Maximum phonation Duration (MPD), Estimated Subglottal Pressure (ESGP), Laryngeal Conductance (LAC), Laryngeal Resistance (LAR) and Sound Pressure Level (SPL). Among the study participants, 80% have rated the Ujjayi pranayama as useful in prepping their voice for the vocal loading tasks. In view of the better objective evidence and significant improvements in the study variables including the participant's self-perception, authors suggest that Ujjayi pranayama can also be used in voice rehabilitation as a vocal warm-up exercise.


Histochemical analysis of extracellular matrix material in embryonic mouse lens morphogenesis.
Extracellular matrix material (ECM) present during mouse lens morphogenesis was studied histologically by the periodic acid-Schiff, Alcian blue 8GX, pH 2.5, high iron diamine, and Van Gieson methods, and enzymatically with bovine testicular hyaluronidase, Streptomyces hyaluronidase, malt diastase, and collagenase. The basal lamina of the optic vesicle prior to lens placode formation was found to be higher in glycosaminoglycan (GAG) content than was the ectodermal basal lamina. Upon apposition of the optic vesicle and presumptive lens ectoderm, the ECM plus basal laminae appeared as the equivalent of adding both optic vesicle-associated and ectodermal-associated basal lamina. The proposal is made that the initial triggering mechanism of lens morphogenesis consists of a cross-linking and polymerization of optic vesicle-associated GAG to ectodermal-associated glycoproteins resulting in a firm attachment between the structures. Basal lamina associated with the presumptive pigmented retina and also the more ventral part of the interface matrix were found to change from predominantly GAG in early stages to collagen deposits in more advanced stages, temporally coinciding with the appearance of differentiative markers in each structure. This pattern of GAG turnover and replacement by collagen during the course of development is also seen in mouse salivary gland morphogenesis (M. R. Bernfield, S. D. Banerjee, and R. H. Cohn (1972). J. Cell Biol. 52, 674-686.).


Portrayal of body weight on children's television sitcoms: a content analysis.
Television programs portray characters with idealized body types that for most viewers are unattainable. These body types have become a common source of comparison for many young viewers who evaluate their own self-worth and bodies based on the models they see on television. This study examines body weight, both in terms of frequency and portrayals, focusing on how preadolescent and adolescent characters' bodies are presented on the sitcoms from three children's television networks. The results indicate that while children's situation comedies have relatively few overweight characters, this small percentage closely parallels national figures. Male and female characters do not differ in their distribution across weight categories. However, when character ethnicity is factored, significant shifts occur. Surprisingly, no differences were observed in the portrayal of physical and mental attributes among weight categories except in social popularity where overweight characters were not as embedded in social networks. Compared to other relevant studies, this research provides some evidence that the treatment and portrayal of overweight characters in children-targeted sitcoms is more positive, equitable, and less stereotypical than in other programming venues and that children are experiencing body type diversity in these fictional portrayals. Nonetheless, above average weight characters still suffer some social marginality and ethnic misrepresentation.


Metabolic Features of Tumor Dormancy: Possible Therapeutic Strategies.
Tumor relapse represents one of the main obstacles to cancer treatment. Many patients experience cancer relapse even decades from the primary tumor eradication, developing more aggressive and metastatic disease. This phenomenon is associated with the emergence of dormant cancer cells, characterized by cell cycle arrest and largely insensitive to conventional anti-cancer therapies. These rare and elusive cells may regain proliferative abilities upon the induction of cell-intrinsic and extrinsic factors, thus fueling tumor re-growth and metastasis formation. The molecular mechanisms underlying the maintenance of resistant dormant cells and their awakening are intriguing but, currently, still largely unknown. However, increasing evidence recently underlined a strong dependency of cell cycle progression to metabolic adaptations of cancer cells. Even if dormant cells are frequently characterized by a general metabolic slowdown and an increased ability to cope with oxidative stress, different factors, such as extracellular matrix composition, stromal cells influence, and nutrient availability, may dictate specific changes in dormant cells, finally resulting in tumor relapse. The main topic of this review is deciphering the role of the metabolic pathways involved in tumor cells dormancy to provide new strategies for selectively targeting these cells to prevent fatal recurrence and maximize therapeutic benefit.


Invasive stratified mucin-producing carcinoma (ISMC) of uterine cervix: description of pathological findings and prognosis factors in a series of 15 Chinese patients.
Invasive stratified mucin-producing carcinoma (ISMC), an invasive form of stratified mucin-producing intraepithelial lesion (SMILE), is a newly named human papillomavirus (HPV) associated mucous adenocarcinoma of cervix. We aim to provide more clinical and pathological data for this uncommon disease. Fifteen cases diagnosed as ISMC in our hospital were included, and their clinical and pathological data were retrospectively analyzed. The patients' median age was 43 years (range, 30-54 years). The most prevalent symptom was abnormal vaginal bleeding. HPV test indicated high-risk HPV in all of our 15 cases. In addition, we observed several other architectural patterns of ISMC, including nest, gland-forming or lumen-forming, papillary with extravasated pools of mucin and solid. Immunohistochemically, all of our ISMC cases showed block-like expression of P16 and diffuse positive expression of CK8 and CK18, while P63, P40 and CK5/6 were spotted positive, or completely negative. Most importantly, ISMC has a relatively high lymph node metastasis rate of 33%. ISMC is a special type of HPV-associated adenocarcinoma, displaying a wide morphologic spectrum combined with a unique immunohistochemical profile. Clinically, ISMC may have a higher rate of lymph node metastasis, which suggests more attention to postoperative follow-up.


Spatial control over cell attachment by partial solvent entrapment of poly lysine in microfluidic channels.
We demonstrate spatial control over cell attachment on biodegradable surfaces by flowing cell adhesive poly (D-lysine) (PDL) in a trifluoroethanol (TFE)-water mixture through microfluidic channels placed on a biodegradable poly (lactic acid)-poly (ethylene glycol) (PLA-PEG) substrate. The partial solvent mixture swells the PLA-PEG within the confines of the microfluidic channels allowing PDL to diffuse on to the surface gel layer. When excess water is flowed through the channels substituting the TFE-water mixture, the swollen PLA surface collapses, entrapping PDL polymer. Results using preosteoblast human palatal mesenchymal cells (HEPM) indicate that this new procedure can be used for facile attachment of cells in localized regions. The PEG component of the PLA-PEG copolymer prevents cells from binding to the nonpatterned regions.


miR-141-3p affects β-catenin signaling and apoptosis by targeting Ubtd2 in rats with anorectal malformations.
Anorectal malformations (ARMs) are the most common gastrointestinal malformations. miR-141-3p was obtained from whole-transcriptome sequencing, and Ub domain-containing protein 2 (Ubtd2) was predicted as the target gene. An ARM rat model was induced using ethylenethiourea. Fluorescence in situ hybridization and immunofluorescence were used to detect the spatiotemporal expression of miR-141-3p and Ubtd2, respectively. A dual-luciferase reporter assay confirmed their targeting relationship, and cell proliferation and apoptosis were investigated after transfection in the intestinal epithelium (IEC-6). Additionally, western blotting and co-immunoprecipitation were used to examine the protein levels and the endogenous binding relationship. miR-141-3p was downregulated in the ARM group, whereas Ubtd2 increased and colocalized with TUNEL-positive cells. After miR-141-3p inhibition, protein expression of USP5 and β-catenin was affected via Ubtd2, and USP5 could bind to both Ubtd2 and β-catenin. Flow cytometry analysis and caspase 3/7 staining demonstrated that downregulated miR-141-3p promoted cell apoptosis through Ubtd2. In summary, targeting Ubtd2 decreased in miR-141-3p and promoted apoptosis of intestinal epithelium and regulated β-catenin expression. This may cause aberrant apoptosis during hindgut development and mediate the imbalance of β-catenin signaling in the cloaca, further affecting the occurrence of ARMs.


Modelling idiopathic intracranial hypertension in rats: contributions of high fat diet and testosterone to intracranial pressure and cerebrospinal fluid production.
Idiopathic intracranial hypertension (IIH) is a condition characterized by increased intracranial pressure (ICP), impaired vision, and headache. Most cases of IIH occur in obese women of childbearing age, though age, BMI, and female sex do not encompass all aspects of IIH pathophysiology. Systemic metabolic dysregulation has been identified in IIH with a profile of androgen excess. However, the mechanistic coupling between obesity/hormonal perturbations and cerebrospinal fluid dynamics remains unresolved. Female Wistar rats were either fed a high fat diet (HFD) for 21 weeks or exposed to adjuvant testosterone treatment for 28 days to recapitulate IIH causal drivers. Cerebrospinal fluid (CSF) and blood testosterone levels were determined with mass spectrometry, ICP and CSF dynamics with in vivo experimentation, and the choroid plexus function revealed with transcriptomics and ex vivo isotope-based flux assays. HFD-fed rats presented with increased ICP (65%), which was accompanied by increased CSF outflow resistance (50%) without altered CSF secretion rate or choroid plexus gene expression. Chronic adjuvant testosterone treatment of lean rats caused elevated ICP (55%) and CSF secretion rate (85%), in association with increased activity of the choroid plexus Na+,K+,2Cl- cotransporter, NKCC1. HFD-induced ICP elevation in experimental rats occurred with decreased CSF drainage capacity. Adjuvant testosterone, mimicking the androgen excess observed in female IIH patients, elevated the CSF secretion rate and thus ICP. Obesity-induced androgen dysregulation may thus contribute to the disease mechanism of IIH.


Effect on the postprandial glycaemic level of the addition of water to a meal ingested by healthy subjects and type 2 (non-insulin-dependent) diabetic patients.
The effects on postprandial glycaemic reactions of adding a glass of water to a meal were studied in 7 healthy male subjects and 20 Type 2 (non-insulin-dependent) diabetic patients for a period of up to 3 h. The subjects were served a meal of potatoes and meat, with or without 300 ml of water, in random order on two mornings after a 12-h fast. The diabetic patients were considered as well-controlled or not well-controlled according to HbA1c and blood glucose fasting values. Water addition increased the peak blood glucose (p less than 0.02) and serum insulin (p less than 0.02) levels in healthy subjects, and the blood glucose concentration in well-controlled diabetic patients (p less than 0.02). The addition of water also increased the overall blood glucose response, calculated as the positive incremental area, in healthy subjects by 68 +/- 25% (p less than 0.02) and in well-controlled diabetic patients by 40 +/- 14% (p less than 0.01). In poorly-controlled diabetic patients, however, the addition of water did not display significant effects, probably due to the varying fasting glycaemia in these patients. Thus, altering the physical property of a meal by dilution with water can affect the physiological responses; the results are considered to be relevant for the on-going discussion concerning the use of physiological responses to foods as a basis for diet instructions to diabetic patients.


Age-related differences in dynamic balance control during stair descent and effect of varying step geometry.
The incidence of stairway falls and related injuries remains persistently high; however, the risk of stair injuries could be reduced through improved stairway design. The current study investigated dynamic balance control during stair descent and the effects of varying the step geometry. Data were collected from 20 healthy young and 20 older adults as they descended three staircases (riser heights of 7, 7.5 and 8 inches (178, 190 and 203 mm, respectively)). At each riser height, the tread run length was varied between 8 and 14 inches (203 mm and 356 mm) in one-inch (25 mm) increments. Kinematic data provided measures of segmental and whole-body dynamic control. Results demonstrated that older adults had greater lateral tilt of the upper body than young adults, but actually had larger margins of stability than the young in the antero-posterior direction as a result of their slower cadence. Nonetheless, for both age groups, the longer run lengths were found to provide the largest margins of stability. In addition, increase in run length and decrease in riser height tended to reduce forward upper body tilt. These results help to explain the underlying biomechanical factors associated with increased risk of falls and the relationship with step geometry. Considering the importance of stair ambulation in maintaining independence and activity in the community, this study highlights the definite need for safer stair design standards to minimize the risk of falls and increase stair safety across the lifespan.


Lateralized contribution of prefrontal cortex in controlling task-irrelevant information during verbal and spatial working memory tasks: rTMS evidence.
The functional organization of working memory (WM) in the human prefrontal cortex remains unclear. The present study used repetitive transcranial magnetic stimulation (rTMS) to clarify the role of the dorsolateral prefrontal cortex (dlPFC) both in the types of information (verbal vs. spatial), and the types of processes (maintenance vs. manipulation). Subjects performed three independent experiments (1-back and 2-back tasks) while rTMS was applied over dlPFC for 500 ms in the last period of the delay. In two experiments (1 and 2) physically identical stimuli (letters shown at different locations on a screen) under different domain conditions (letters or locations) were employed. Under these conditions, we discovered a double dissociation only in the 2-back task: during the letter condition, when applied to the right dlPFC, rTMS significantly delayed task performance, whereas, the same result was present during the location condition, but only when rTMS was applied to the left dlPFC. The other 2-back task (experiment 3), in which we had eliminated the task-irrelevant information (i.e. we used stimuli that varied only in one domain), did not show significant results. We propose that the functional dichotomy of the hemispheres may be due to mechanisms of cognitive control on interference, which resolve conflict through the inhibition of task-irrelevant information only during high WM load. In conclusion, these findings confirm the role of dlPFC in implementing top-down attentional control, and provide evidence for the theoretical suggestion that working memory serves to control selective attention in the normal human brain.


Light-Independent Biological Conversion of CO2.
Sevcan Erşan is a postdoctoral researcher at UCLA. Previously, she conducted postdoctoral research at the University of Hohenheim in Germany. She received her PhD in biotechnology from Yeditepe University, Turkey, and her bachelor's and master's degrees in food engineering from Istanbul Technical University, Turkey. She is experienced in waste utilization, bioprocessing technologies, and biological activities associated with phytochemicals. Her current research focuses on natural product chemistry and sustainable biotechnology. Junyoung Park is an assistant professor of Chemical and Biomolecular Engineering and co-director of the Metabolomics Center at UCLA. His research group focuses on systems-level analysis of metabolic networks to elucidate regulatory mechanisms and engineer metabolism. He aims to apply this knowledge to solving energy and environmental problems and curing human diseases such as cancer and diabetes. Before moving to Los Angeles, he conducted postdoctoral research at MIT. He received his bachelor's degrees in mathematics and bioengineering from UC San Diego and a master's and PhD in chemical engineering from Princeton University.


Mapping study of brain dopamine- and epinephrine-sensitive sites which cause feeding suppression in the rat.
Central injections of dopamine (DA) or epinephrine (EPI) have been found to suppress feeding behavior in hungry rats. In the present study, 24 different brain areas, in 299 animals, were examined to localize the precise region of catecholamine (CA) sensitivity. Essentially all sites outside the hypothalamus, as well as in the medial portion of the hypothalamus, were relatively or totally unresponsive to DA or EPI. The area of greatest sensitivity for both agonists (where they yielded a 50--70% suppression of feeding) was found to be the perifornical region of the lateral hypothalamus, extending from the caudal aspect of the paraventricular nucleus to the caudal aspect of the ventromedial nucleus. Dorsal, lateral, or ventrolateral movement of the injection site away from the fornix and into the zona incerta or the lateral hypothalamic medial forebrain bundle area caused a dramatic reduction in the effectiveness of the CA. These findings are consistent with histochemical studies, which have shown the fornix to be surrounded by CA varicosities, and pharmacological studies, which have shown the perifornical region to be most sensitive to the anorexic effect of centrally injected amphetamine, which releases endogenous CA. It is suggested that the perifornical hypothalamus plays a role in the process of inhibiting food consumption in response to increased dopaminergic and adrenergic activity.


Efficacy and toxicity of peritumoral delivery of nanoconjugated cisplatin in an in vivo murine model of head and neck squamous cell carcinoma.
Treatment of locally advanced head and neck squamous cell carcinoma (HNSCC) uses a multidisciplinary approach often limited by the toxicity and drug resistance of platinum agents. To test whether a nanocarrier-conjugated cisplatin boosting locoregional drug delivery improves tumor efficacy while decreasing systemic toxicity over systemic cisplatin in a murine model of locally advanced HNSCC. A randomized, controlled, in vivo study compared standard cisplatin with nanocarrier (hyaluronan [HA])-conjugated cisplatin (HA-cisplatin) each at 50% of the maximum tolerated doses in a murine model of locally advanced HNSCC (10 mice/arm, each injected with 1 × 106 MDA-1986 HNSCC cells, with phosphate-buffered saline and HA-only control arms). Mice were treated for 3 weeks and observed for 3 additional weeks. Academic medical center. Forty female Nu/Nu mice. Randomization and treatment arms were initiated once tumor volumes reached 30 mm3. Injection with MDA-1986 HNSCC cells followed by 3 weeks of treatment with cisplatin, HA-cisplatin, phosphate-buffered saline, or HA only. Animal weights and tumor volumes were measured 3 times each week (modified RECIST [Response Evaluation Criteria in Solid Tumors]). At necropsy, animal kidneys were examined for nephrotoxic effects and cochleae were examined for ototoxic effects. The mice treated with HA-cisplatin showed superior tumor efficacy (1 with complete clinical response, 3 with partial response, 1 with stable disease, and 5 with progressive disease) compared with standard cisplatin (no animals with complete clinical response, 1 with partial response, 1 with stable disease, and 8 with progressive disease), which was statistically significant (P = .003). All control animals developed progressive disease. Weight loss and body score were surrogate measures of treatment toxicity. The HA-cisplatin group had the least weight loss (mean [SD], 10.8% [4.7%]) compared with the cisplatin group (13.6% [5.6%]; P = .25). Body score dropped to 2 or less in all cisplatin-treated mice but not in any HA-cisplatin-treated mice, which also lacked any histologic signs of nephrotoxic or ototoxic effects. Nanoconjugated HA-cisplatin significantly improves tumor efficacy with lower toxicity compared with standard cisplatin in locally advanced HNSCC in vivo, justifying additional translational studies.