Reflecting on reflection: students' evaluation of their moving and handling education.
This paper discusses the value of introducing the component of reflection into a nursing programme for the teaching and learning of moving and handling. Twenty-five students who had just completed a Common Foundation Programme, of a Diploma in Higher Education (Nursing) course, were asked to evaluate the usefulness of reflection for moving and handling. Their qualitative evaluations suggest that the process of reflection may be instrumental in enabling students to adopt a more questioning approach towards practice through the sharing of different beliefs and values, and that reflection may be instrumental in facilitating a change in practice. Some students chose to take action and change their unsafe moving and handling practice behaviour to a safer one and this was perceived to have personal health and safety benefits. The journey from a passive to a more assertive position was not always easy, however it was viewed to be empowering. This paper will draw on Freire's (1972) socio-political ideas that progressive education can facilitate a movement from a passive domesticating position towards an assertive liberating position.


Role of nitric oxide in ovarian follicular development and egg production in Japanese quail (Coturnix coturnix japonica).
Role of nitric oxide (NO) in regulating the reproductive functions at hypothalamo-hypophysealovarian axis in Japanese quail was studied. In first experiment, metabolites of NO, i.e. nitrite and nitrate (NO2 and NO3) were estimated together in hypothalamus, serum and ovarian follicles of good and poor layers. In the second experiment, different NO modulators such as L-arginine (L-Arg), sodium nitroprusside (SNP) and N(G)-nitro-L-arginine methyl ester, HCl (L-NAME) were administered to the birds. In the first experiment, significantly higher (P < 0.01) NO2 and NO3 levels in serum, hypothalamus and largest (F1) ovarian follicles were observed in good layers as compared to poor layers. Higher (P < 0.05) NO2 and NO3 concentration was observed in F1 follicles than smaller follicles (F2) only in good layers. The NO2 and NO3 concentration was significantly reduced (P < 0.05) in post ovulatory follicles (POFs) in comparison to F1 and F2 follicles. In the second experiment, the serum NO2 and NO3 concentrations were higher (P < 0.05) in the SNP, lower (P < 0.05) in the L-Name group and unchanged in the L-Arg treated group in comparison to control group. compared to control, L-Arg and SNP increased (P < 0.05) the hypothalamic NO2 and NO3 concentration where as L-NAME reduced (P < 0.05) these levels. The NO2 and NO3 concentration was increased (P < 0.05) as the follicle size increased and it was significantly reduced (P < 0.05) in POFs. The higher (P < 0.05) follicular NO2 and NO3 concentration was observed in L-Arg group in comparison to control group. Egg production was also found to be higher (P < 0.05) in L-Arg group whereas it was not different (P > 0.05) in SNP and L-NAME treated groups. The yolk weight and yolk to albumin ratio was reduced (P < 0.05) in L-NAME group in comparison to control group. It may be concluded from the present study that NO plays a key role in regulating follicular development, ovulatory mechanisms and egg production in Japanese quail.


Erysipelatoid Carcinoma.
Erysipelatoid Carcinoma (EC), also known as Inflammatory Metastatic Carcinoma, is a rare form of cutaneous metastasis, secondary to an internal malignancy, more often related to breast cancer. Clinically, the lesion has a well-marked, bound erythematous appearance, much like an infectious process, such as erysipelas and cellulitis, these being the most common differential diagnoses. It is characterized by an acute or subacute appearance with an erythematous plaque, sometimes hot and painful, being more often situated in the primary tumor vicinity, especially in the thorax wall in the region of a mastectomy due to breast cancer. Here we present the case of a 75-year-old patient with ductal infiltrated carcinoma for 3 years, who presented an acute erythematous and infiltrated plaque in the region of a previous mastectomy, with a final diagnosis of EC.


Activation of the CREB/c-Fos Pathway during Long-Term Synaptic Plasticity in the Cerebellum Granular Layer.
The induction of long-term potentiation and depression (LTP and LTD) is thought to trigger gene expression and protein synthesis, leading to consolidation of synaptic and neuronal changes. However, while LTP and LTD have been proposed to play important roles for sensori-motor learning in the cerebellum granular layer, their association with these mechanisms remained unclear. Here, we have investigated phosphorylation of the cAMP-responsive element binding protein (CREB) and activation of the immediate early gene c-Fos pathway following the induction of synaptic plasticity by theta-burst stimulation (TBS) in acute cerebellar slices. LTP and LTD were localized using voltage-sensitive dye imaging (VSDi). At two time points following TBS (15 min and 120 min), corresponding to the early and late phases of plasticity, slices were fixed and processed to evaluate CREB phosphorylation (P-CREB) and c-FOS protein levels, as well as Creb and c-Fos mRNA expression. High levels of P-CREB and Creb/c-Fos were detected before those of c-FOS, as expected if CREB phosphorylation triggered gene expression followed by protein synthesis. No differences between control slices and slices stimulated with TBS were observed in the presence of an N-methyl-D-aspartate receptor (NMDAR) antagonist. Interestingly, activation of the CREB/c-Fos system showed a relevant degree of colocalization with long-term synaptic plasticity. These results show that NMDAR-dependent plasticity at the cerebellum input stage bears about transcriptional and post-transcriptional processes potentially contributing to cerebellar learning and memory consolidation.


Human chorionic gonadotropin induces nestin expression in endothelial cells of the ovary via vascular endothelial growth factor signaling.
The intermediate filament protein nestin was originally found to be expressed in neuronal progenitor cells, but recent studies have shown that other cell types, including endocrine and vascular endothelial cells, express nestin. In the present study, we examined the expression and localization of nestin in the ovaries of developing, peripubertal, and adult rats. RT-PCR and Western blot analyses revealed that nestin mRNA and proteins were expressed in adult rat ovaries. Immunohistochemical analyses using adult rat ovaries showed that nestin was mainly localized to capillary endothelial cells of theca interna in follicles with more than two layers of granulosa cells and that its expression increased with follicle growth. Ontogenetically, ovarian nestin expression started at the peripubertal period when the first gonadotropin surge occurs. To test the possibility that gonadotropins induce nestin expression, prepubertal (postnatal d 21) rats were sc injected with equine chorionic gonadotropin (eCG) and/or human chorionic gonadotropin (hCG). A single injection of hCG, but not eCG, was sufficient to induce nestin expression in follicles, mainly in capillary endothelial cells of theca interna. Furthermore, pretreatment with an inhibitor of vascular endothelial growth factor receptor prevented the induction of the nestin expression by hCG. These findings demonstrate that the endogenous LH surge induces nestin expression in capillary endothelial cells of theca interna via the vascular endothelial growth factor signaling pathway. Nestin may be involved in angiogenesis in growing follicles, which is followed by follicle maturation and subsequent ovulation.


H8-BINOL chiral imidodiphosphoric acids catalyzed enantioselective synthesis of dihydroindolo-/-pyrrolo[1,2-a]quinoxalines.
The first enantioselective synthesis of 5,6-dihydroindolo[1,2-a]quinoxalines is achieved by using a newly developed H8-BINOL-type imidodiphosphoric acid catalyst with low catalyst loading through efficient Pictet-Spengler-type reactions of indolyl anilines with ketones. This methodology also generates phenyl-4,5-dihydropyrrolo[1,2-a]quinoxalines with high yields and excellent enantioselectivities. Moreover, this method was utilized to synthesize an HIV-1 inhibitor with high yield and good enantioselectivity through a one-step procedure.


The replication of human immunodeficiency virus type 1 in macrophages is enhanced after phagocytosis of apoptotic cells.
Clearance of apoptotic cells increases macrophage secretion of antiinflammatory mediators and might modulate viral replication in human immunodeficiency virus (HIV) type 1-infected macrophages. To study this, primary macrophages were infected with HIV-1 and exposed to apoptotic cells. It was found that phagocytosis of apoptotic cells potently enhanced HIV-1 growth. The peptide Arg-Gly-Asp-Ser, which binds to integrin receptors, inhibited the uptake of apoptotic cells and the subsequent enhancement of HIV-1 replication. Viral replication was preceded by increased secretion of transforming growth factor (TGF)-beta1 and partially reverted by anti-TGF-beta1 antibodies. Moreover, anti-TGF-beta1 antibodies inhibited HIV-1 replication in macrophages not exposed to apoptotic cells. A positive correlation was observed between TGF-beta1 production and HIV-1 growth, and the addition of TGF-beta1 amplified HIV-1 replication in macrophages from low TGF-beta1 producers. The findings suggest that TGF-beta1 favors HIV-1 replication in macrophages and that the clearance of apoptotic cells by HIV-1-infected macrophages contributes to persistent viremia in patients infected with HIV-1.


Hormonal influence on the secretory immune system of the eye: androgen control of secretory component production by the rat exorbital gland.
Androgens are known to regulate the level of secretory component (SC) in tears of male rats. The purpose of the present study was to explore the underlying mechanism of this hormone action by (i) identifying the ocular tissue(s) involved in SC production; and (ii) determining whether androgens increase SC production by this tissue. We also examined whether androgen administration influenced the concentration of SC in tears of female rats. Ocular tissues from adult Sprague-Dawley rats were cultured in the presence or absence of cycloheximide in the incubation medium. Secretory component in the culture media was measured by an RIA which detects primarily free SC. Analysis of media obtained after incubation of exorbital (lacrimal) glands, 'lid' tissues, globes, and Harderian glands revealed that only exorbital glands released substantial amounts of SC. This exorbital gland production of SC, which was significantly greater in tissues from male rats, as compared to those of female rats, was reduced by approximately 50% when cycloheximide was present in the culture medium. To determine whether SC production by exorbital glands was influenced by androgens, orchiectomized glands was influenced by androgens, orchiectomized rats were administered either saline or testosterone (2.0 mg/day for 4 days), and exorbital glands were cultured 24 hr after the last injection. Testosterone treatment in vivo induced a significant, cycloheximide-sensitive increase in SC production in vitro, compared to the glandular SC output of saline-injected controls. It is interesting that similar androgen treatment of ovariectomized females also resulted in elevated tear SC concentrations and enhanced output of SC by their exorbital glands in vitro. These findings indicate that the exorbital gland is primarily responsible for SC production in the rat eye and that androgens may modulate the synthesis of SC in this gland.


'They don't know much about us': educational reform impacts on students' learning in the clinical environment.
Placements are an integral component of the medical, nursing, and allied health curriculum. Literature on problem-based learning indicates that curriculum change can impact student experience. However, outside of the nursing literature, there is little research on the impact of education reform on students' experiences of placements. This paper reports on medical, midwifery and paramedic students' perception of the impact of education reform they experienced in the clinical setting. A qualitative study using a semi-structured schedule was conducted. Data was collected using focus groups (17), individual interviews (48) and written responses (2) from undergraduate students (103) and graduates (27) from a tertiary institution in Victoria, Australia. Recorded interviews were analysed, coded and categorised into themes. Whilst students indicated they were prepared for the impact of educational reform on their placement experience, they perceived that clinical educators responsible for teaching them were less prepared. Three themes were identified from the data: clinical educator's lack of familiarity with new curriculum, clinical educator's negative attitudes to curricular change and looking to the future. Our study advances the understanding of the implications of education reform during the clinical placement of medical, midwifery, and paramedic students. Whilst important lessons can be learned from the medical and nursing literature this study highlights that staff responsible for curriculum change need to action change management process to ensure that the clinical educators are able to deliver the revised program.


Effects of diabetes on myocardial infarct size and cardioprotection by preconditioning and postconditioning.
In spite of the current optimal therapy, the mortality of patients with ischemic heart disease (IHD) remains high, particularly in cases with diabetes mellitus (DM) as a co-morbidity. Myocardial infarct size is a major determinant of prognosis in IHD patients, and development of a novel strategy to limit infarction is of great clinical importance. Ischemic preconditioning (PC), postconditioning (PostC) and their mimetic agents have been shown to reduce infarct size in experiments using healthy animals. However, a variety of pharmacological agents have failed to demonstrate infarct size limitation in clinical trials. One of the possible reasons for the discrepancy between the results of animal experiments and clinical trials is that co-morbidities, including DM, modified myocardial responses to ischemia/reperfusion and to cardioprotective agents. Here we summarize observations of the effects of DM on myocardial infarct size and ischemic PC and PostC and discuss perspectives for protection of DM hearts.


Clinical application of glucagon-like Peptide 1 receptor agonists for the treatment of type 2 diabetes mellitus.
Glucagon-like peptide 1 (GLP-1) is secreted from enteroendocrine L-cells in response to oral nutrient intake and elicits glucose-stimulated insulin secretion while suppressing glucagon secretion. It also slows gastric emptying, which contributes to decreased postprandial glycemic excursions. In the 1990s, chronic subcutaneous infusion of GLP-1 was found to lower blood glucose levels in patients with type 2 diabetes. However, GLP-1's very short half-life, arising from cleavage by the enzyme dipeptidyl peptidase 4 (DPP-4) and glomerular filtration by the kidneys, presented challenges for clinical use. Hence, DPP-4 inhibitors were developed, as well as several GLP-1 analogs engineered to circumvent DPP-4-mediated breakdown and/or rapid renal elimination. Three categories of GLP-1 analogs, are being developed and/or are in clinical use: short-acting, long-acting, and prolonged-acting GLP-1 analogs. Each class has different plasma half-lives, molecular size, and homology to native GLP-1, and consequently different characteristic effects on glucose metabolism. In this article, we review current clinical data derived from each class of GLP-1 analogs, and consider the clinical effects reported for each category in recent head to head comparison studies. Given the relatively brief clinical history of these compounds, we also highlight several important efficacy and safety issues which will require further investigation.


Intermediate Levels of Bacillus subtilis CodY Activity Are Required for Derepression of the Branched-Chain Amino Acid Permease, BraB.
The global transcriptional regulator, CodY, binds strongly to the regulatory region of the braB gene, which encodes a Bacillus subtilis branched-chain amino acid (BCAA) permease. However, under conditions that maximize CodY activity, braB expression was similar in wild-type and codY null mutant cells. Nonetheless, expression from the braB promoter was significantly elevated in cells containing partially active mutant versions of CodY or in wild-type cells under growth conditions leading to intermediate levels of CodY activity. This novel pattern of regulation was shown to be due to two opposing mechanisms, negative and positive, by which CodY affects braB expression. A strong CodY-binding site located downstream of the transcription start point conferred negative regulation by direct interaction with CodY. Additionally, sequences upstream and downstream of the promoter were required for repression by a second pleiotropic B. subtilis regulator, ScoC, whose own expression is repressed by CodY. ScoC-mediated repression of braB in codY null mutants cells was as efficient as direct, CodY-mediated repression in wild-type cells under conditions of high CodY activity. However, under conditions of reduced CodY activity, CodY-mediated repression was relieved to a greater extent than ScoC-mediated repression was increased, leading to elevated braB expression. We conclude that restricting increased expression of braB to conditions of moderate nutrient limitation is the raison d'être of the feed-forward regulatory loop formed by CodY and ScoC at the braB promoter. The increase in BraB expression only at intermediate activities of CodY may facilitate the uptake of BCAA when they are not in excess but prevent unneeded BraB synthesis when other BCAA transporters are active.


THE ENDOCRINOLOGY OF AGING: A KEY TO LONGEVITY "GREAT EXPECTATIONS".
AMP = adenosine monophosphate CETP = cholesteryl ester transfer protein FOXO = Forkhead box O GH = growth hormone HDL = high-density lipoprotein IGF-1 = insulin-like growth factor 1 LDL = low-density lipoprotein miRNA = microRNA mTOR = mammalian target of rapamycin SIRT = sirtuin T4 = thyroxine TSH = thyroid-stimulating hormone "The Moving Finger writes; and, having writ, Moves on: nor all thy Piety nor Wit Shall lure it back to cancel half a Line, Nor all thy Tears wash out a Word of it." Omar Khayyam ( 1 ).


Antioxidant vitamins in the prevention of cardiovascular disease: a systematic review.
Do antioxidant vitamins, in regular food or as food supplements, protect against myocardial infarction and stroke? In this systematic literature review on the effects of antioxidant vitamins in the primary prevention of cardiovascular disorders, studies with ischaemic heart disease, stroke or combined cardiovascular events as end-points have been included. Studies on the effects of antioxidant vitamins on intermediary end-points (such as blood lipids and blood pressure) and as secondary prevention in patients with manifest cardiovascular disease are reviewed in a conventional manner. In observational studies (case-control or cohort design), people with high intake of antioxidant vitamins by regular diet or as food supplements generally have a lower risk of myocardial infarction and stroke than people who are low-consumers of antioxidant vitamins. The associations in observation studies have been shown for carotene, ascorbic acid as well as tocopherol. In randomized controlled trials, however, antioxidant vitamins as food supplements have no beneficial effects in the primary prevention of myocardial infarction and stroke. Serious adverse events have been reported. After an initial enthusiasm for antioxidants in the secondary prevention of cardiovascular disease, recent reports from of several large randomized trials have failed to show any beneficial effects. Thus, the apparent beneficial results of high intake of antioxidant vitamins reported in observational studies have not been confirmed in large randomized trials. The discrepancy between different types of studies is probably explained by the fact that supplement use is a component in a cluster of healthy behaviour. Antioxidant vitamins as food supplements cannot be recommended in the primary or secondary prevention against cardiovascular disease.


Absorption, distribution, and metabolic fate of 7-chloro-3,3a-dihydro-2-methyl-2H,9H-isoxazolo-(3,2-b)(1,3)-benzoxazin-9-one in rats, dogs, and humans.
The absorption and metabolic fate of 7-chloro-3,3a-dihydro-2-methyl-2H,9H-isoxazolo-(3,2-b)(1,3)-benzoxazin-9-one (I) was studied in rats, dogs, and humans. Orally administered I was readily absorbed by all species. In the rat, orally administered I was converted to its metabolite, 5-chlorosalicylic acid, by the intestinal wall. The half-lives of blood radioactivity, after the oral administration of I-9-14C, were about 18 and 12 hr in the rat and beagle hound, respectively. In human subjects, no intact I was detected in the bloodstream; however, the clearance of the metabolite, 5-chlorosalicylic acid, had a half-life of about 33 hr. Cleavage of the oxazine ring of I generated 5-chlorosalicylic acid, which was excreted both in the free form and conjugated with glycine and glucuronic acid. The isoxazole moiety was converted to beta-hydroxybutyric acid and its metabolites carbon dioxide and fumaric, citric, alpha-ketoglutaric, succinic, and malic acids. Binding of I to plasma proteins was extensive but was less than that of 5-chlorosalicylic acid.


[Editorial explanation for Expert consensus statement on Diemailing Kudiezi Injection in clinical practice].
Expert consensus statement on Diemailing Kudiezi Injection in clinical practice was approved on April 17,2019 by the Standardadization Office of the Chinese Association of Chinese Medicine. This project,which started in November 2017,has been developed and completed in accordance with the standard developing procedure. This paper will give a detailed introduction to the compilation process about the consensus. The aim is to enable readers to understand the background,purpose and basis of this consensus in a timely manner. Readers can learn about diffferent stages of develping process,including project management system,drafting,consulting,expert consensus,as well as current problems and shortcomings. Such an editorial explanation is just a dynamic follow-up of the whole consensus-making process. It also plays a good supervisory role in the whole consensus-making. It could be a guarantee for the quality of the consensus. There is no doubts that the editorial explanation is an important auxiliary document in the process of consensus-making. It is the extension and supplement of consensus content and a basis for fully understanding the technical content of this consensus. Therefore it is an indispensable document in the process of consensus-making.


Cinnamyl-alcohol dehydrogenase, a molecular marker specific for lignin synthesis: cDNA cloning and mRNA induction by fungal elicitor.
Cinnamyl-alcohol dehydrogenase (CAD; EC 22.214.171.124) catalyzes the final step in a branch of phenylpropanoid synthesis specific for production of lignin monomers. We have isolated a full-length cDNA clone encoding CAD, as a molecular marker specific for lignification, by immunoscreening a lambda gt11 library containing cDNAs complementary to mRNA from elicitor-treated cell cultures of bean (Phaseolus vulgaris L.). The clone comprises a single long open reading frame of 1767 base pairs, 31 base pairs of 5' leader, and 152 base pairs of 3' untranslated sequence. The deduced 65-kDa CAD polypeptide has several features that are strongly conserved in alcohol dehydrogenases. Addition of fungal elicitor to cell cultures stimulates CAD transcription, which leads to a remarkably rapid, but transient, accumulation of CAD mRNA, with no detectable lag and maximal levels after 1.5 hr. Southern blot analysis of bean genomic DNA indicates that elicitor-induced CAD is encoded by a single gene. The regulatory significance of the rapid activation of this CAD gene and the possible existence of a second, divergent CAD gene involved in lignification during xylogenesis are discussed.


Conservative approach in patients with pemphigus gingival vulgaris: a pilot study of five cases.
Objectives. The aim of this pilot study was to describe the clinical efficacy of a conservative oral hygiene protocol in patients affected by gingival pemphigus vulgaris (PV) applied in a case series. Methods. Subjects suffering from PV with gingival localisation and slightly responsive to conventional treatment with systemic corticosteroids and immunosuppressive drugs were selected among individuals treated in the Unit of Oral Medicine Section of the University of Turin. Five subjects received nonsurgical periodontal therapy, over a 7-day period, including oral hygiene instructions; patients were instructed about domiciliary oral hygiene maintenance and instructions were reinforced at each visit and personalised if necessary. Clinical outcome variables were recorded at baseline (before starting) and 16 weeks after intervention, including full mouth plaque score (FMPS), bleeding scores (FMBS), probing pocket depth (PPD), oral pemphigus clinical score (OPCS), and patient related outcomes (visual analogue score of pain). Results. Five patients were treated and, after finishing the proposed therapy protocol, a statistical significant reduction was observed for FMBS (P = 0.043) and OPCS (P = 0.038). Conclusions. Professional oral hygiene procedures with nonsurgical therapy are related to an improvement of gingival status and a decrease of gingival bleeding in patients affected by PV with specific gingival localization.


Composition and anti-oxidant, anti-cancer and anti-inflammatory activities of Artemisia herba-alba, Ruta chalpensis L. and Peganum harmala L.
In this study, biological activities of methanolic extracts from Artemisia herba-alba, Ruta chalpensis L. and Peganum harmala L. plants, collected in Centre of Tunisia, were investigated. Results showed an important phenolic composition of Artemisia herba-alba (123.95±4.3g GAE/kg of dry mass). The extract of this plant showed, using different antioxidant assays (DPPH, ABTS and AAPH/linoleic acid methods) and an IFN-γ/LPS induced RAW 264.7 murine macrophages' assay, the highest antioxidant (IC50 (DPPH assay) 20.64±0.84mg/L) and anti-inflammatory (72% inhibition at 150mg/L) activities, respectively. Excepting Peganum harmala L. extract, the two other extracts showed a high anticancer activity against several cell lines (human bladder carcinoma RT112, human laryngeal carcinoma Hep2 and human myelogenous leukemia K562), for A. herba-laba IC50=81.59±4.4, 59.05±3.66 and 90.96mg/L respectively, but not on normal peripheral blood mononuclear cells. All these biological activities are well correlated with the phenolic contents of these extracts. These findings demonstrate the remarkable potential of these plants as valuable source of antioxidants with exhibit original and interesting anti-inflammatory and anticancer capacities.


All-arthroscopic anatomic repair of an avulsed popliteus tendon in a multiple ligament-injured knee.
Multiple ligament-injured knees are a heterogeneous group of knee injuries that lack a clear consensus on optimal treatment. Current areas of controversy include optimal timing of surgery, ligamentous repair vs reconstruction, and combined vs staged procedures. In addition, multiple open, arthroscopic, and arthroscopic-assisted techniques exist for repair and reconstruction of the injured stabilizers of the knee.Many open posterolateral corner reconstruction techniques have been described, and this article represents the first description of an arthroscopic technique for repair of an avulsed popliteus tendon. This was performed with a standard anterolateral portal in addition to anterior and posterior superolateral portals. Nonabsorbable sutures were passed through the avulsed popliteus tendon in an outside-in technique using a suture shuttle. The nonabsorbable sutures were threaded though a tibial Beath pin, which was then passed through the prepared popliteus footprint and brought out medially. The final position of the popliteus was confirmed arthroscopically, and the sutures were tied medially over a screw post with a washer.Arthroscopic popliteus repair has many possible advantages. Because the popliteus tendon insertion is intracapsular, open repair necessitates a capsulotomy, with the potential for complications such as postoperative wound drainage, intra-articular sinus formation, infection, and stiffness. Arthroscopic repair may avoid these complications. The current case was performed in conjunction with an open but extracapsular posterolateral corner repair. Further experience with this technique is required to determine its safety and efficacy.


Diagnostic sensitivity/specificity of preattentive vision tests in glaucoma.
Damage to the nerve fiber layer or visual pathway might be expected to reduce the efficiency with which the visual system performs analysis of the ever-changing field of vision. The purpose of this article is to provide a further analysis of previously reported data (Loughman J, Davison P, Flitcroft I, Br J Ophthalmol 2007;91:1493-98.) to: (i) determine the sensitivity and specificity of a test of preattentive vision for glaucoma detection and (ii) provide a cutoff performance level that would serve to distinguish glaucoma in early cases. Three groups of observers (glaucoma, suspects, and normals) were examined, using computer-generated flicker, orientation, and vertical displacement targets to assess preattentive visual search (PAVS) efficiency. The task required rapid and accurate localization of a singularity embedded in a field of 119 homogenous distractors on either left or right hand side of a computer monitor. All subjects also completed a choice reaction time task. Receiver operating characteristic curve analysis demonstrates consistently high diagnostic sensitivity and specificity values (significantly above 90% for all tasks) using the raw PAVS data and also for a novel perceptual search index (which improves the diagnostic capacity of the test). Optimal performance cutoff values for each task were also computed. A test of PAVS efficiency demonstrates high sensitivity and specificity to early glaucoma. Analysis incorporating the perceptual search index confirms the high diagnostic capacity of the test.


Titanium clip prosthesis.
Prostheses for the reconstruction of a defective ossicular chain should be stable and firmly anchored to the ossicular remnants. This will prevent a defective connection from causing diminished sound transmission efficiency and will keep the prosthesis from tilting or even losing contact, which would result in a sound transmission block. Through temporal bone experimentation, we have consequently developed a very lightweight titanium prosthesis, which is fastened onto the stapes head with a clip mechanism. When temporal bone experiments using laser Doppler vibrometry confirmed that the prosthesis functioned well acoustically and when luxation experiments proved that it could be safely used without the risk of stapes dislocation, the prosthesis was used in a clinical application within an observational study. The University of Dresden Otorhinolaryngological Hospital as well as seven surgeons from five other hospitals participated in the study. The results of 133 operations showed that, in over 90% of the cases, the prosthesis could be implemented without problems and with good mechanical stability. The first acoustical results obtained during the first year from 49 patients showed a sound transmission improvement range from 12 dB to 14 dB. With the clip prosthesis, it seems possible to further improve defective middle ear function, which would allow the patient to regain social hearing after middle ear reconstruction. The reliability of the fastening is an innovation. Revision operations showed a stable prosthesis-stapes complex in the middle of a recurring cholesteatoma and the prosthesis could always be easily pulled from the stapedial suprastructure.


Neuroplasticity and psychiatry.
There is increasing concern that the course of psychiatric disorders may be affected by parameters such as the duration and intensity of symptoms of initial episodes of illness. As this indicates that abnormal function produces long-term changes within the brain, a review of the neuroscience literature regarding neuroplasticity is warranted. This article is a selective review, focusing in particular on results obtained from physiological experiments assessing plasticity within the mammalian neocortex. The possible relevance of results to psychiatry is discussed. While the most dramatic examples of neuroplasticity occur during a critical period of neural development, neuroplasticity can also occur in adult neocortex. Neuroplasticity appears to be activity-dependent: synaptic pathways that are intensively used may become strengthened, and conversely, there may be depression of transmission in infrequently used pathways. Results from neurophysiological experiments lend support to the clinical observation that the intensity and duration of a psychiatric disorder may adversely alter its long-term course. Rapid aggressive treatment may prevent this from occurring. While pharmacotherapy may reduce the duration and severity of symptoms, it may also have an independent, as yet unknown, effect on neuroplasticity.


Nonlinear dynamics of C-terminal tails in cellular microtubules.
The mechanical and electrical properties, and information processing capabilities of microtubules are the permanent subject of interest for carrying out experiments in vitro and in silico, as well as for theoretical attempts to elucidate the underlying processes. In this paper, we developed a new model of the mechano-electrical waves elicited in the rows of very flexible C-terminal tails which decorate the outer surface of each microtubule. The fact that C-terminal tails play very diverse roles in many cellular functions, such as recruitment of motor proteins and microtubule-associated proteins, motivated us to consider their collective dynamics as the source of localized waves aimed for communication between microtubule and associated proteins. Our approach is based on the ferroelectric liquid crystal model and it leads to the effective asymmetric double-well potential which brings about the conditions for the appearance of kink-waves conducted by intrinsic electric fields embedded in microtubules. These kinks can serve as the signals for control and regulation of intracellular traffic along microtubules performed by processive motions of motor proteins, primarly from kinesin and dynein families. On the other hand, they can be precursors for initiation of dynamical instability of microtubules by recruiting the proper proteins responsible for the depolymerization process.


Phenotypic variability in three carriers from a family with choroideremia and a frameshift mutation 1388delCCinsG in the REP-1 gene.
To perform genotype-phenotype correlations in a family with choroideremia. A three-generation family with two affected males and five carriers was the subject of the study. Molecular genetic analysis using single-strand conformation polymorphism analysis (SSCP) was conducted in all subjects, while electroretinography (ERG), multifocal ERG (mfERG), scanning laser ophthalmoscope microperimetry (SLO perimetry), fluorescein angiography, and Arden contrast color testing were performed in one male and three carriers. The findings in the affected male were typical for advanced choroideremia. The three carriers demonstrated a variable clinical phenotype including reduction of visual acuity and ERG and angiographic changes in one. Molecular genetic analysis revealed a functional null mutation (1388delCCinsG) in the REP-1 gene. A severe retinal pathology was found in the affected male, indicating that the 1388delCCinsG is a severe mutation. Varying phenotypes were present in the three carriers examined. The phenotype in carriers has been explained by random X-inactivation with varying expression of the inactivated and activated gene copy inside the same cell of both the retinal pigment epithelium and the rods. This thesis is in agreement with the clinical data obtained here.


Growing surfaces with anomalous diffusion: results for the fractal Kardar-Parisi-Zhang equation.
In this paper I study a model for a growing surface in the presence of anomalous diffusion, also known as the fractal Kardar-Parisi-Zhang equation (FKPZ). This equation includes a fractional Laplacian that accounts for the possibility that surface transport is caused by a hopping mechanism of a Levy flight. It is shown that for a specific choice of parameters of the FKPZ equation, the equation can be solved exactly in one dimension, so that all the critical exponents, which describe the surface that grows under FKPZ, can be derived for that case. Afterwards, the self-consistent expansion (SCE) is used to predict the critical exponents for the FKPZ model for any choice of the parameters and any spatial dimension. It is then verified that the results obtained using SCE recover the exact result in one dimension. At the end a simple picture for the behavior of the fractal KPZ equation is suggested and the upper critical dimension of this model is discussed.


Design, synthesis, biological evaluation and molecular docking study of novel pleuromutilin derivatives containing substituted benzoxazole as antibacterial agents.
A series of pleuromutilin analogs containing substituted benzoxazole were designed, synthesised, and assessed for their antibacterial activity both in vivo and in vitro. The MIC of the synthesised derivatives was initially assessed using the broth dilution method against four strains of Staphylococcus aureus (MRSA ATCC 43300, S. aureus ATCC 29213, clinical isolation of S. aureus AD3 and S. aureus 144). Most of the synthesised derivatives displayed prominent in vitro activity (MIC ≤ 0.5 µg/mL). Compounds 50 and 57 exhibited the most effective antibacterial effect against MRSA (MIC = 0.125 µg/mL). Furthermore, the time-kill curves showed that compounds 50 and 57 had a certain inhibitory effect against MRSA in vitro. The in vivo antibacterial activity of compound 50 was evaluated further using a murine thigh model infected with MRSA (-1.24 log10CFU/mL). Compound 50 exhibited superior antibacterial efficacy to tiamulin. It was also found that compound 50 did not display significant inhibitory effect on the proliferation of RAW 264.7 cells. Molecular docking study revealed that compound 50 can effectively bind to the active site of the 50S ribosome (the binding free energy -7.50 kcal/mol).


The susceptibility of hepatic collagen to homologous collagenase in human and experimental cirrhosis of the liver.
The susceptibility of hepatic collagen to homologous collagenase in human and experimental CCl4 cirrhosis of the liver has been explored in vitro by exposure of cryostat liver sections to the corresponding enzymes for different time periods. The morphology and extent of collagen degradation was studied by the Picrosirius red/polarizing microscopy technique. The results of various experiments indicate that collagen present in cryostat sections of both human and rat normal and cirrhotic livers is resistant to trypsin digestion for periods of exposure of up to 48 hours but that heating the sections to 60 C for 1 hour renders the collagen susceptible to degradation by trypsin. Incubation of cryostat liver sections with bacterial collagenase revealed progressive degradation of collagen with a uniform pattern of changes in the original color and diameter of the fibers. Exposure of liver sections to homologous collagenases gave rise to the same pattern of changes observed with bacterial collagenase, although less extensive when equal incubation periods were compared. Nevertheless, sufficiently prolonged incubation of liver sections with their homologous collagenases eventually showed degradation of all collagen present in all normal and cirrhotic liver sections. These observations suggest that in the presence of non rate-limiting concentrations of homologous collagenase, the susceptibility of hepatic collagen to the corresponding degrading enzyme is probably not responsible for the irreversibility of the disease.


Arterial ischemia in the deportalized liver following associating liver partition and portal vein ligation for staged hepatectomy.
Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a novel 2-stage technique intended to induce rapid growth of the future liver remnant (FLR). Initial reports of a 12% mortality rate have sparked debate regarding the safety of the procedure. A 64 years old male was planned for a right-sided hemi-hepatectomy due to colorectal cancer liver metastases. Intra-operatively it was decided to convert to an ALPPS due to unexpectedly small segments 2-4. Post-operative serum laboratory tests indicated an acute liver failure and radiological imaging showed no sign of arterial blood flow to the right hemi-liver. A computed tomography examination on post-operative day 3 revealed that the FLR had increased from 290 to 690 mL in 3 d (138% growth). In the following days serum values gradually improved and stage 2 was carried out on post-operative day 7. The rest of the hospital stay was uneventful and the patient made a full recovery. ALPPS is a fascinating advancement in liver surgery. Despite severe post-operative complications, in properly selected cases it provides successful outcomes that other modalities of treatment cannot offer.


Medicine Sellers for Prevention and Control of Sexually Transmitted Infections: Effect of a Quasi-Experimental Training Intervention in Bangladesh.
This study used a quasi-experimental pre-post design to test whether short training can improve medicine sellers' (MSs) practices and skills for prevention and control of sexually transmitted infections (STIs) in Bangladesh. The training included lectures, printed materials, and identification of referral sites. Difference-in-differences estimation was used to determine the effects of intervention on key primary and secondary outcomes. Advice given by the MSs in intervention group for partner treatment and condoms use increased significantly by 11% and 9%, respectively, after adjusting for baseline differences in education, religion, age, duration of training, and study site. Referral of clients to qualified service providers increased by 5% in the intervention group compared to the comparison group, but this change was not found to be statistically significant. Significantly higher proportion of MSs in the intervention group recognized the recommended medications as per the national syndromic management guidelines in Bangladesh for treatment of urethral discharge and genital ulcer symptoms. Short training intervention was found to be effective in improving MSs' practice of promoting condom use and partner treatment to the clients. We anticipate the need for broad based training programs of MSs to improve their skills for the prevention and control of STI/HIV in Bangladesh.


VOLUMETRIC SINGLE-LAYER INNER RETINAL ANALYSIS IN PATIENTS WITH HYDROXYCHLOROQUINE TOXICITY.
To compare retinal layer volumes using spectral-domain optical coherence tomography between eyes with hydroxychloroquine (HCQ) toxicity and control eyes. Using a previously validated algorithm, volumetric analysis from the macular cube scan of the ganglion cell layer, inner plexiform layer, inner nuclear layer, and outer retina (outer plexiform layer to retinal pigment epithelium) layers were compared in three sets of patients: patients with a clinical diagnosis of HCQ toxicity, age-matched patients taking HCQ but not manifesting overt toxicity, and age-matched control patients. There were 14 patients in each group. The ganglion cell layer (P = 0.01), inner plexiform layer (P = 0.004), inner nuclear layer (P < 0.001), and outer plexiform layer to retinal pigment epithelium (P < 0.001) volumes were significantly reduced in HCQ toxicity eyes relative to the HCQ exposure eyes. There were no significant inner and outer retinal volume differences between the HCQ exposure group and group with no HCQ use (P > 0.05 for all layers). Increasing disease severity correlated with increasing volume loss in the inner retina (2.27 mm in early disease vs. 1.78 mm in advanced retinopathy, P = 0.02). Hydroxychloroquine toxicity seems to result in both outer and inner retinal volumetric thinning compared with age-matched control patients and patients taking HCQ but not manifesting toxicity.


Positron emission tomography computed tomography features of monomorphic epitheliotropic intestinal T-cell lymphoma.
To define the positron emission tomography/computed tomography (PET/CT) features of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), a rare malignancy in European and North American populations and the most common form of primary intestinal T-cell lymphoma in Asian populations. 18F-fluorodeoxyglucose (FDG) PET/CT findings of a cohort of MEITL patients were retrospectively analyzed. Eight men and four women with MEITL investigated by PET/CT at diagnosis and relapse were retrospectively analyzed. On presentation, the primary involved sites were the small bowel (N = 8), large bowel (N = 2), stomach (N = 1) and small and large bowels (N = 1). The uninvolved small bowel did not show increased FDG-avidity to suggest enteropathy. On presentation, lymph nodes and other organs were involved in seven cases (58%). The primary lesions were hypermetabolic except in one case, where the colonic lesion was eumetabolic. At relapse, the stomach and large bowel might be involved even if the primary tumours arose from the small bowel, and multiple extra-intestinal metastases occurred. Interestingly, thoracic structures and the brain were frequently involved (50% and 25% respectively). These findings showed that in contrast to classical enteropathy-associated T-cell lymphoma, where the small bowel is the exclusive primary site (owing to its origin from coeliac disease) and distant metastases even during relapse are exceptional, MEITL might on presentation and during relapse involve any part of the gut, and metastasize to multiple extra-intestinal sites.


[Therapy of the symptoms of "dry skin"].
The symptom of dry skin is seen in some skin diseases, in old people and under various physical and chemical influences. The main pathogenetic factor is the dehydratation of the corneocytes. Therefore waterprotective and waterbinding creams are used. All water-in-oil-emulsions and ointment basics are waterprotective. So called moisturizers are added to the ointments to improve the waterbinding capacity. One natural moisturizer is urea, which for instance is contained in Basodexan ointment. There are new therapeutic ways since the introduction of the liposomes. Liposomes represent longlasting and precisely applicable deposits for moisturizer and other active extracts.


Placebo response in randomized controlled trials of antidepressants for pediatric major depressive disorder.
The authors examined characteristics and predictors of response to placebo in all available reports of short-term randomized controlled trials of antidepressants for pediatric major depressive disorder. Response, defined as a score <or=2 on the improvement item of the Clinical Global Impression scale, and potential predictors were extracted from 12 published and unpublished randomized controlled trials of second-generation antidepressants in participants 6-18 years of age with major depression. The single best predictor of the proportion of patients taking placebo who responded to treatment was the number of study sites. Baseline severity of illness also emerged as a significant inverse predictor of placebo response, although the strength of this relationship was diminished when number of sites was controlled for. After one large fluoxetine trial was excluded, younger participants showed a higher placebo response rate than older adolescents. Higher placebo response rates in more recent studies were explained by an increasing trend toward large multisite trials and by publication delays and failures to publish some negative trials. The recent shift toward large multisite trials of antidepressant medications for pediatric major depression may be contributing to an increasing incidence of response to placebo. Pharmacotherapy studies of pediatric depression that carefully recruit patients with at least moderately severe depression may be more informative and efficient than many trials conducted to date. Such studies should have sufficient power to determine whether age moderates medication and placebo response.


Improvement of the quality of lumazine synthase crystals by protein engineering.
Icosahedral macromolecules have a wide spectrum of potential nanotechnological applications, the success of which relies on the level of accuracy at which the molecular structure is known. Lumazine synthase from Bacillus subtilis forms a 150 A icosahedral capsid consisting of 60 subunits and crystallizes in space group P6(3)22 or C2. However, the quality of these crystals is poor and structural information is only available at 2.4 A resolution. As classical strategies for growing better diffracting crystals have so far failed, protein engineering has been employed in order to improve the overexpression and purification of the molecule as well as to obtain new crystal forms. Two cysteines were replaced to bypass misfolding problems and a charged surface residue was replaced to force different molecular packings. The mutant protein crystallizes in space group R3, with unit-cell parameters a = b = 313.02, c = 365.77 A, alpha = beta = 90.0, gamma = 120 degrees , and diffracts to 1.6 A resolution.


Initial response to a range of physical threats in an office environment.
The paper proposes that there are a number of low-probability, but not insignificant, physical threat scenarios relating to the office environment that warrant an initial response capability (in addition to fire evacuation drill). Explosive, contamination and intruder scenarios are included in the threats' scope. The term 'initial response' essentially refers to first actions relating to how and where to direct people to preserve life safety. Given the likelihood that an organisation would not have any emergency services support in the early stages of an incident, it follows that it is likely that the organisation would be 'on its own' to assess, decide and execute the initial response. Aside from any moral obligations, the paper proposes that there are potential legal obligations to compel an organisation to be so prepared. An important consideration explored is the feasibility of having an effective initial response capability. The relative simplicity and low cost of implementation and maintenance of a response is described. Lastly, the point is made that, aside from fire evacuation (which is a drill), all the other threat scenarios discussed require some decision making. It is not possible to be 100 per cent correct 100 per cent of the time. A decision support matrix is described with the objective of increasing the percentage chance of making the most appropriate decision most of the time. In particular, this is seen as an area for further discussion.


Neutral pyridyl-functionalized C,N-ortho-chelated aminoaryl platinum(II) corner building blocks for application in coordination reactions.
Two homoleptic pyridyl-functionalized C,N-ortho-chelating aminoaryl platinum(II) complexes, cis-[Pt(eta(2)-C,N)] (3a,b), were prepared via an unconventional method involving the initial synthesis of a bromide-functionalized C,N-chelating aminoaryl platinum(II) precursor complex 8, to which subsequently pyridyl groups were attached via a Suzuki-Miyaura C-C coupling reaction. The electron-donating properties of the pyridyl nitrogen atoms of the resulting complexes (3a,b) were used in complexation reactions with monocationic NCN-pincer (NCN = [C6H3(CH2NMe2)(2-)2,6]-) platinum(II) (11a) and palladium(II) (12a) nitrate complexes [M(NCN)(NO3)], thereby obtaining four trimetallic coordination complexes 16-19. The difference in the pyridine-metal coordination behavior between platinum and palladium was studied by varying the ratios of the reagents and by variable-temperature NMR experiments. IR and Raman analyses of 11a and 12a were performed to determine the coordination behavior of the nitrate counteranion, and it was found that both NO3- and H2O coordinate to the metal centers. The crystal structure determinations of free pyridyl complex 3a, [Pt(NCN)(NO3)] (11a), and [Pt(NCN)(NO3)].(H2O) (11b), as well as the crystal structure of trisplatinum coordination complex 16, are reported.


Design and fabrication of a metastable β-type titanium alloy with ultralow elastic modulus and high strength.
Titanium and its alloys have become the most attractive implant materials due to their high corrosion resistance, excellent biocompatibility and relatively low elastic modulus. However, the current Ti materials used for implant applications exhibit much higher Young's modulus (50 ~ 120 GPa) than human bone (~30 GPa). This large mismatch in the elastic modulus between implant and human bone can lead to so-called "stress shielding effect" and eventual implant failure. Therefore, the development of β-type Ti alloys with modulus comparable to that of human bone has become an ever more pressing subject in the area of advanced biomedical materials. In this study, an attempt was made to produce a bone-compatible metastable β-type Ti alloy. By alloying and thermo-mechanical treatment, a metastable β-type Ti-33Nb-4Sn (wt. %) alloy with ultralow Young's modulus (36 GPa, versus ~30 GPa for human bone) and high ultimate strength (853 MPa) was fabricated. We believe that this method can be applied to developing advanced metastable β-type titanium alloys for implant applications. Also, this approach can shed light on design and development of novel β-type titanium alloys with large elastic limit due to their high strength and low elastic modulus.


Specializing Nurses as An Indirect Education Program for Stoma Patients.
Education programs are beneficial for patients with different chronic conditions. Prior studies have examined direct education, where information is transferred directly to patients. In contrast, in this program, information is transferred directly to nurses who become specialists and transfer education individually to patients. Hence, this paper evaluates the impact of having specialist nurses for stoma patients at hospitals, as those nurses provide healthcare to patients but also inform and educate patients about their condition and needs. The analysis uses an observational study with ostomized patients in Spain at hospitals with and without specialist nurses, and measures health service utilization and health-related quality of life (HRQL), besides performing a cost analysis and a cost-effectiveness analysis at both types of hospitals. The results show that patients with access to specialist nurses self-manage better, present lower adverse events and a better evolution of HRQL, and significantly demand more consultations with specialist nurses and less to A&E, primary care or specialists, resulting in important savings for the health system. Consequently, specializing or hiring nurses to provide indirect education to stoma patients is cost-effective and highly beneficial for patients. This type of indirect education strategy might be considered for specific conditions with low incidence or difficulties in identifying target patients or delivering information directly to them.


Fused selenophene-thieno[3,2-b]thiophene-selenophene (ST)-based narrow-bandgap electron acceptor for efficient organic solar cells with small voltage loss.
A novel near-infrared-light-absorbing fused-ring electron acceptor, STIC, was developed for organic solar cells. STIC exhibited a narrow bandgap with an absorption edge reaching 940 nm, which was ascribed to the strong electron-rich selenophene-thieno[3,2-b]thiophene-selenophene (ST) unit and strong intramolecular charge transfer of STIC. Also, STIC-based devices showed low open-circuit voltage (Voc) loss values, attributed to the rigid ST core providing low reorganization energy. The device based on the PBDB-T:STIC blend exhibited a power conversion efficiency (PCE) of 9.68% with a high short-circuit current density (Jsc) of 19.96 mA cm-2 and a low Voc loss of 0.55 eV.


Death receptor activation-induced hepatocyte apoptosis and liver injury.
The TNFalpha receptor super-family consists of several members sharing a sequence homology in a unique function domain, the death domain, which is located in the intracellular portion of the receptor. These so-called death receptors, including Fas, TNF-R1 and TRAIL-R1/TRAIL-R2, are expressed on hepatocytes. When stimulated by their ligands, FasL, TNFalpha or TRAIL, respectively, the death receptors can activate multiple death domain-initiated apoptosis programs, including both extrinsic and intrinsic pathways. A cascade of caspases is activated, which cleave proteins important for the cell structure and function. Activation of the intrinsic pathway also leads to mitochondrial release of several apoptotic proteins and mitochondrial dysfunction, which kill the cell through both caspase-dependent and caspase-independent mechanisms. Death receptor-induced hepatocyte apoptosis contributes to the development of a number of liver diseases, including viral hepatitis, inflammatory hepatitis, Wilson's disease, alcoholic liver disease, endotoxiemia-induced liver failure and ischemia/reperfusion-induced liver damage. This article comprehensively reviews the mechanisms of induction and regulation of death receptor-initiated apoptosis in hepatocytes, examines how these molecular events affect our understanding of the pathogenesis of these diseases and further discusses the potential therapeutic application of the knowledge. We hope we can provide a cohesive and integrated perspective on the many aspects of these complicated processes.


Hip Arthroscopy in Patients Ages 50 Years or Older: Minimum 5-Year Outcomes, Survivorship, and Risk Factors for Conversion to Total Hip Replacement.
To report minimum 5-year outcomes and risk factors for conversion to total hip arthroplasty (THA) in patients ≥50 years old undergoing hip arthroscopy to treat labral tears and femoroacetabular impingement (FAI). Data were prospectively collected on patients who underwent hip arthroscopy to treat labral tears and FAI between February 2008 and January 2012. The inclusion criteria were ≥50 years old at surgery, arthroscopic treatment for both labral tears and FAI, and preoperative patient-reported outcome (PRO) scores for modified Harris Hip Score (mHHS), Nonarthritic Hip Score (NAHS), Hip Outcome Score-Sports Specific Subscale (HOS-SSS), and Visual Analog Scale (VAS). The exclusion criteria were Tönnis grade > 1 and previous hip conditions or surgeries. Of 103 eligible cases, 94 hips (91.3%) had minimum 5-year follow-up at a mean of 70.1 months (range, 60.0-95.1 months). All PROs and VASs demonstrated significant improvement at latest follow-up (P = .0001). Mean patient satisfaction was 8.4. All mean scores demonstrated durability from 2 years to latest follow-up, and NAHS (P = .009), HOS-SSS (P = .02), and VAS (P = .04) continued to significantly improve. Fifty-one (54.3%) of cases reached patient acceptable symptomatic state for mHHS, and 49 cases (52.1%) achieved minimal clinically important difference for this outcome measure. Four cases (4.3%) required secondary arthroscopy, and survivorship was 72.3%. Compared with survivors, the subgroup requiring THA demonstrated higher body mass indexes (P = .01), had larger alpha angles (P = .0200) and smaller lateral center-edge angles (P = .0200), and had higher proportions of Tönnis grade 1 (P = .0012), acetabular Outerbridge grade ≥ 2 (P = .0500), and femoral head Outerbridge grade ≥2 (P = .0001). Hip arthroscopy for the treatment of labral tears and FAI in patients ≥50 years old demonstrates statistically significant PRO improvements at minimum 5-year follow-up. However, due to potential for subsequent need for THA in a subset of this population, surgeons should use rigorous selection criteria and counsel patients appropriately. Level IV, case series.


Cross-talk between singlet oxygen- and hydrogen peroxide-dependent signaling of stress responses in Arabidopsis thaliana.
Upon a dark-to-light shift, the conditional fluorescent (flu) mutant of Arabidopsis releases singlet oxygen (1O2) within the plastid compartment. Distinct sets of nuclear genes are activated that are different from those induced by superoxide (O2*-)) and/or hydrogen peroxide (H2O2), suggesting that different types of reactive oxygen species activate distinct signaling pathways. It is not known whether the pathways operate separately or interact with each other. We have addressed this problem by modulating noninvasively the level of H2O2 in plastids by means of a transgenic line that overexpresses the thylakoid-bound ascorbate peroxidase (tAPX). The overexpression of the H2O2-specific scavenger reduced strongly the activation of nuclear genes in plants treated with the herbicide paraquat that in the light leads to the enhanced generation of O2*- and H2O2. In the flu mutant overexpressing tAPX, the intensity of 1O2-mediated cell death and growth inhibition was increased when compared with the flu parental line. Also, the expression of most of the nuclear genes that were rapidly activated after the release of 1O2 was significantly higher in flu plants overexpressing tAPX, whereas in wild-type plants, overexpression of tAPX did not lead to visible stress responses and had only a very minor impact on nuclear gene expression. The results suggest that H2O2 antagonizes the 1O2-mediated signaling of stress responses as seen in the flu mutant. This cross-talk between H2O2- and 1O2-dependent signaling pathways might contribute to the overall stability and robustness of wild-type plants exposed to adverse environmental stress conditions.


Age-Related Macular Degeneration Staging by Color Fundus Photography vs. Multimodal Imaging-Epidemiological Implications (The Coimbra Eye Study-Report 6).
Epidemiology of age-related macular degeneration (AMD) is based on staging systems relying on color fundus photography (CFP). We aim to compare AMD staging using CFP to multimodal imaging with optical coherence tomography (OCT), infra-red (IR), and fundus autofluorescence (FAF), in a large cohort from the Epidemiologic AMD Coimbra Eye Study. All imaging exams from the participants of this population-based study were classified by a central reading center. CFP images were graded according to the International Classification and Grading System for AMD and staged with Rotterdam classification. Afterward, CFP images were reviewed with OCT, IR, and FAF and stage update was performed if necessary. Early and late AMD prevalence was compared in a total of 1616 included subjects. In CFP-based grading, the prevalence was 14.11% for early AMD (n = 228) and 1.05% (n = 17) for late AMD, nine cases (0.56%) had neovascular AMD (nAMD) and eight (0.50%) geographic atrophy (GA). Using multimodal grading, the prevalence increased to 14.60% for early AMD (n = 236) and 1.61% (n = 26) for late AMD, with 14 cases (0.87%) of nAMD and 12 (0.74%) of GA. AMD staging was more accurate with the multimodal approach and this was especially relevant for late AMD. We propose that multimodal imaging should be adopted in the future to better estimate and compare epidemiological data in different populations.


Phospholamban involvement in the maintenance of basal calcium transport in cardiac sarcoplasmic reticulum.
Phosphorylation of cardiac sarcoplasmic reticulum membrane vesicles by exogenous c-AMP and c-AMP-dependent protein kinase stimulates calcium uptake and Ca2+-dependent ATP hydrolysis by 40-50% and results in the incorporation of 32P into a 22-KDa protein, phospholamban. Treatment of the membrane with DOC (0.0002% or 5 X 10(-6) M) solubilizes phospholamban from the membrane and induces a 90% inhibition of basal calcium uptake. This inhibition cannot be attributed to an alteration in vesicle integrity or membrane permeability. The (Ca2+ + Mg2+)-ATPase remains associated with the membrane fraction and exhibits optimal levels of Ca2+-stimulated ATP hydrolysis. Phosphorylation prior to DOC treatment allows retention of the phospholamban in the membrane, concomitant with maintenance of the calcium transport activity. The results presented suggest that phospholamban is involved in the maintenance of basal calcium transport function in cardiac sarcoplasmic reticulum and that its phosphorylation stimulates Ca2+ transport.


Comparison of sequential feeding and continuous feeding on the blood glucose of critically ill patients: a non-inferiority randomized controlled trial.
Glucose control is an important aspect in managing critically ill patients. The goal of this study was to compare the effects of sequential feeding (SF) and continuous feeding (CF) on the blood glucose of critically ill patients. A non-inferiority randomized controlled trial was adopted in this study. A total of 62 patients who were fed enteral nutritional suspension through gastric tubes were enrolled. After achieving 80% of the nutrition target calories (25 kcal·kg-1·day-1) through CF, the patients were then randomly assigned into SF and CF groups. In the SF group, the feeding/fasting time was reasonably determined according to the circadian rhythm of the human body as laid out in traditional Chinese medicine theory. The total daily dosage of the enteral nutritional suspension was equally distributed among three time periods of 7 to 9 o'clock, 11 to 13 o'clock, and 17 to 19 o'clock. The enteral nutritional suspension in each time period was pumped at a uniform rate within 2 h by an enteral feeding pump. In the CF group, patients received CF at a constant velocity by an enteral feeding pump throughout the study. Blood glucose values at five points (6:00/11:00/15:00/21:00/1:00) were monitored and recorded for seven consecutive days after randomization. Enteral feeding intolerance was also recorded. Non-inferiority testing was adopted in this study, the chi-square test or Fisher test was used for qualitative data, and the Mann-Whitney U test was used for quantitative data to determine differences between groups. In particular, a repeated measure one-way analysis of variance was used to identify whether changes in glucose value variables across the time points were different between the two groups. There were no significant demographic or physiological differences between the SF and CF groups (P > 0.050). The average glucose level in SF was not higher than that in CF (8.8 [7.3-10.3] vs. 10.7 [9.1-12.1] mmol/L, Z = -2.079, P for non-inferiority = 0.019). Hyperglycemia incidence of each patient was more common in the CF group than that in the SF group (38.4 [19.1-63.7]% vs. 11.8 [3.0-36.7]%, Z = -2.213, P = 0.027). Hypoglycemia was not found in either group. Moreover, there was no significant difference during the 7 days in the incidence of feeding intolerance (P > 0.050). In this non-inferiority study, the average blood glucose in SF was not inferior to that in CF. The feeding intolerance in SF was similar to that in CF. SF may be as safe as CF for critically ill patients. ClinicalTrials.gov, NCT03439618; https://clinicaltrials.gov/ct2/show/record/NCT03439618.


Dihydropyrimidine dehydrogenase-related enzymes predict efficacy and adverse reactions of UFT1+cisplatin neoadjuvant chemotherapy for gastric cancer.
Dihydropyrimidine dehydrogenase (DPD) and dihydropyrimidinase (DHP) are metabolic enzymes of fluoropyrimidine. UFT containing uracil (U) and Tegafur is the first reported DPD-inhibitory fluoropyrimidine. To clarify the significance of the enzyme activities, we examined the relationships between the effects and adverse reactions, and DPD and DHP activities in gastric cancer treated with UFT1+cisplatin neoadjuvant chemotherapy. Twenty-five gastric cancer patients were administered UFT at 370 mg/m(2)/day for 21 days and cisplatin at 15 mg/m(2)/day for 2 days. Dihydrouracil (DU) and U levels in the urine and DPD activities in the resected tumors were measured. Chemotherapeutic effects were classified histologically into non-responder and responder groups. The responder group accounted for 48% of the patients. All six patients with high DPD activities (> or = 0.08 nmol/min/ww) belonged to the non-responder group and 11 of 19 patients with low DPD activities (<0.08 nmol/min/ww) belonged to the responder group; the difference was significant (p=0.0435). Adverse reactions to UFT occurred in four patients, all of whom were among the six patients with abnormal DU/U values. The incidence of UFT adverse reactions was estimated at 67%. In conclusion, the measured levels of DPD-related enzyme activities appear to be significant for predicting the effects and adverse reactions to chemotherapy.


[Primary malignant fibrous histiocytoma of the breast, report of a case].
Although malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma of adult, it rarely arises in the breast tissue. Only seven cases have been previously reported in Japan. One case of the MFH of the mammary gland is presented in this paper. A 39 year old woman, who had received no radiation, was referred to our hospital due to a painful right breast lump. Excisional biopsy revealed yellowish white soft tumor with an obscured margin. Histological, tumor was composed of spindle shaped cells of a storiform pattern, which was diagnosed as MFH of the breast. Radical mastectomy (Br + Mj + Ax) was added to this patient. The tumor invaded to the fat tissue without metastasis to the axillary lymph nodes. We performed the post-operative adjuvant chemotherapy of Adriamycin. She made an uneventful recovery and is now free of disease eleven months postoperatively.


Demographic, socioeconomic and clinical correlates of self-management in multiple sclerosis.
Our aim was to identify demographic, clinical and socioeconomic predictors of self-management in multiple sclerosis (MS). The study was performed on a group of 283 patients with multiple sclerosis who completed Multiple Sclerosis Self-Management Scale - Revised (MSSM-R), Multiple Sclerosis Impact Scale (MSIS-29), Actually Received Support Scale (part of Berlin Social Support Scale), Expanded Disability Status Scale (EDSS) and Socioeconomic resources scale. Patients were recruited through cooperation with Multiple Sclerosis Rehabilitation Centre in Borne Sulinowo and Polish Society of Multiple Sclerosis. Demographic and illness-related problems were determined with self-report survey. The group consisted of 185 women and 98 men, with a mean age of 48 years. The level of disability and disease severity varied, mean time elapsed since MS diagnosis was 13 years. The final predictive model of self-management in MS was based on two main predictors: received support and available socioeconomic resources. Patients with MS who received adequate support from the closest relatives (R(2 )= 0.07, F(1, 279) = 21.84, p ≤ 0.01) and had larger available socioeconomic resources (R(2) = 0.11, F(2, 278) = 17.06, p ≤ 0.01), turned out to be the most effective in self-management. Moreover, a relationship between self-management in MS and gender as well as monthly income attributable to one family member was documented. We identified a group of MS patients who are at an increased risk of poor self-management and therefore require more attention from medical staff. This group includes patients with low level of received support, low socioeconomic resources and to a lesser degree men, and also persons receiving low monthly income. Implications for Rehabilitation Self-management of chronic illness is a key component of active participation in rehabilitation process. Low self-management in multiple sclerosis (MS) is considered to be one of the most important factors contributing to low rehabilitation efficacy, more severe long-term complications and increase in healthcare costs. Knowledge on predictors of self-management should be used in clinical practice when providing treatment, support, education and rehabilitation for patients with MS. Increasing support and improving social conditions are potentially important targets for interventions aimed at optimization of self-management, and thereby reduction of health care costs and improvement of health.


Efficacy of a novel hydrogel formulation in human volunteers.
In a two-period crossover study, 20 subjects without an ocular disease received single doses of either a novel timolol hydrogel (T-Gel 0.1%) or aqueous timolol 0.5% in one eye and placebo in the fellow eye. Diurnal variation curves of intraocular pressure of both eyes were obtained for a 24-hour period. Peak effects up to -30% of the baseline were observed. A statistically significant residual effect was still detectable 24 h after application. The timolol gel had the same efficacy in lowering intraocular pressure as the commercially available aqueous timolol solution with a five times higher strength. Equivalence of treatment effects was statistically proved.


Optical interband transitions in strained phosphorene.
In this paper, we have concentrated on the orbital and hybridization effects induced by applied triaxial strain on the interband optical conductivity (IOC) of phosphorene using a two-band Hamiltonian model, linear response theory and the Kubo formula. In particular, we study the dependence of the electronic band structure and of the IOC of a phosphorene single layer on the modulus and direction of the applied triaxial strain. The triaxial strain is included in a model through the introduction of strain-dependent hopping parameters using the Harrison rule. Among the various configurations for applying the triaxial strain, considerable findings are presented here in three classes: (i) uniform, (ii) in-plane uniform and (iii) non-uniform triaxial strain. The main consequence of applying triaxial strain is that of increasing and decreasing the band gap depending on the considered class of study, resulting in a blue shift and red shift of the interband optical transitions, respectively. Our results show that a pure blue shift independent of the strain modulus as well as strain sign (tensile or compressive) emerges when applying non-uniform triaxial strain. The overall feature of our outcomes is tailoring the edge-dependent optical responses of phosphorene in the presence of triaxial strain, which provides the required conditions of tuning the optical properties of phosphorene for future experimental research.


Clare-Bishop area in the cat: location and retinotopical projection.
Visual responses of single units in the cortex of the middle suprasylvian sulcus were evaluated in the pretrigeminal cat. Electrode penetrations which passed through the Clare-Bishop area were in 94 percent of the cases within the stereotaxic coordinates A2 and A8. Within the Clare-Bishop area 40 percent of the units were responsive to the visual stimuli employed whereas adjacent to it only 10-20 percent responded. Correlation between receptive field size and eccentricity was poor or absent. Most receptive field centers lay within the lower contralateral quadrant. Because of the large size of the receptive fields, their scatter and individual variability, it was not possible to depict a precise scheme of retinotopical projection.


Laboratory trials to infect insects and nematodes by some acaropathogenic Hirsutella strains (Mycota: Clavicipitaceous anamorphs).
Laboratory assays have been carried out to artificially infect insect larvae of the birch bark-beetle (Scolytus ratzeburgi Jans.-Coleoptera, Scolytidae) and codling moth Cydia pomonella L. -Lepidoptera, Tortricidae) as well as the potato cyst nematode-Globodera rostochiensis Wollenweber, sugar beet nematode-Heterodera schachtii Schmidt and root-knot nematode-Meloidogyne hapla Chif (Nematoda, Heteroderidae), by the phialoconidia of some fungal species of the genus Hirsutella. From among four species tested on insects only H. nodulosa Petch infected about 20% of S. ratzeburgi larvae, whereas H. kirchneri (Rostrup) Minter, Brady et Hall, H. minnesotensis Chen, Liu et Chen, and H. rostrata Bałazy et Wiśniewski did not affect insect larvae. Only single eggs of the root-knot nematode were infected by H. minnesotensis in the laboratory trials, whereas its larvae remained unaffected. No infection cases of the potato cyst nematode (G. rostochiensis) and sugar beet nematode eggs were obtained. Comparisons of DNA-ITS-region sequences of the investigated strains with GenBank data showed no differences between H. minnesotensis isolates from the nematodes Heterodera glycines Ichinohe and from tarsonemid mites (authors' isolate). A fragment of ITS 2 with the sequence characteristic only for H. minnesotensis was selected. Two cluster analyses indicated close similarity of this species to H. thompsonii as sister clades, but the latter appeared more heterogenous. Insect and mite pathogenic species H. nodulosa localizes close to specialized aphid pathogen H. aphidis, whereas the phytophagous mite pathogens H. kirchneri and H. gregis form a separate sister clade. Hirsutella rostrata does not show remarkable relations to the establishment of aforementioned groups. Interrelated considerations on the morphology, biology and DNA sequencing of investigated Hirsutella species state their identification more precisely and facilitate the establishment of systematic positions.


[Radiological diagnosis of mediastinal tumors (author's transl)].
In most cases mediastinal lesions can correctly be differentiated from tumor simulating conditions. Their effect on normal anatomical structures of the mediastinum can be revealed by different methods; but separating benign from malignant masses on the base of the radiological findings is not reliable enough.


The metastatic suppressor NDRG1 inhibits EMT, migration and invasion through interaction and promotion of caveolin-1 ubiquitylation in human colorectal cancer cells.
N-myc downstream-regulated gene 1 (NDRG1) has been reported to act as a key regulatory molecule in tumor progression-related signaling pathways, especially in tumor metastasis. However, the related mechanism has not been fully discovered yet. Herein we demonstrated that the novel molecule of cell migration and invasion, caveolin-1, has direct interaction with NDRG1 in human colorectal cancer (CRC) cells. Moreover, we discovered that NDRG1 reduces caveolin-1 protein expression through promoting its ubiquitylation and subsequent degradation via the proteasome in CRC cells. In addition, caveolin-1 mediates the suppressive function of NDRG1 in epithelial-mesenchymal transition, migration and invasion in vitro and metastasis in vivo. These results help to fulfill the potential mechanisms of NDRG1 in anti-metastatic treatment for human colorectal cancer.


Diagnosis and management of fetal cephalocele.
During a two-year period, nine cases of cephalocele were evaluated at the authors' perinatal ultrasound unit. There was one false positive and one false negative diagnosis. In five cases, multiple anomalies were present; three as part of the amnion rupture sequence. The obstetric management consisted of elective termination of pregnancy in five cases and cesarean section in four. The value of sonography in the diagnosis of cephalocele and associated syndromes and malformations is discussed. A plan of management and counseling based upon current understanding of prognosis is presented.


20(S)-25-methoxyl-dammarane-3β,12β,20-triol attenuates endoplasmic reticulum stress via ERK/MAPK signaling pathway.
Endoplasmic reticulum (ER) stress, together with unfolded protein response (UPR), can remove unfolded proteins and promote survival. However, severe and prolonged ER stress leads to cell death, tissue injury, and many serious diseases. Therefore, it is essential to identify drugs that can attenuate ER stress for ER-related disease treatment. A great deal of research shows that selenoprotein S (SelS) is a sensitive and ideal marker of ER stress. Here, we used a firefly luciferase reporter driven by SelS gene promoter to screen natural compounds that can attenuate ER stress. Then we identified compound 20(S)-25-methoxyl-dammarane-3β,12β,20-triol (25-OCH3-PPD) could inhibit the promoter activity of SelS, further results showed that 25-OCH3-PPD effectively inhibited tunicamycin (TM) induced up-regulation of SelS expression in both mRNA and protein levels. Moreover, 25-OCH3-PPD significantly inhibited glucose-regulated protein 78 (GRP78; the major ER stress marker) expression in TM-induced ER stress in HepG2 and HEK293T cells, suggesting that 25-OCH3-PPD could attenuate ER stress in these cells. Mechanism studies showed that 25-OCH3-PPD significantly activated ERK/MAPK signaling pathway, and the inhibition of ERK/MAPK by U0126 dramatically abolished the inhibitory effect of 25-OCH3-PPD on ER stress, suggesting that 25-OCH3-PPD attenuated ER stress at least partially through activation of ERK/MAPK signaling pathway. Taken together, our studies indicate that 25-OCH3-PPD is a novel small molecular compound reducing ER stress, and a potential drug for treating diseases associated with ER stress.


13-Hour progression of emphysematous hepatitis as depicted on repeat computerized tomography.
Emphysematous hepatitis is a rare, rapidly progressive and often fatal condition, which occurs predominantly in patients with uncontrolled diabetes mellitus. It results in the replacement of liver parenchyma by a collection of gas. Emphysematous infections of other abdominal and pelvic organs have long been established, but relatively little is known about the equivalent emphysematous infection of the liver with very few examples in the published literature. A review of the literature shows variability regarding timing of presentation and implicated organisms. To date, computerized tomography imaging has been purported to be diagnostic and vital to early management, as it clearly shows the characteristic appearance of air bubbles within the liver parenchyma. We report a case with inconclusive initial radiographic findings.


Risk factors for the presence of Aedes aegypti and Aedes albopictus in domestic water-holding containers in areas impacted by the Nam Theun 2 hydroelectric project, Laos.
We assessed risk factors for vectors of dengue and chikungunya viruses near a new hydroelectric project, Nam Theun 2, in Laos. Immature stages of Aedes aegypti were found only in sites within 40 km of the urban provincial capital, but Aedes albopictus was found throughout. Aedes aegypti pupae were most common in water storage jars (odds ratio [OR] = 4.72) and tires (OR = 2.99), and Ae. albopictus pupae were associated with tires in 2009 (OR = 10.87) and drums, tires, and jars in 2010 (drums OR = 3.05; tires OR = 3.45, jars OR = 6.59). Compared with water storage vessels, containers used for hygiene, cooking, and drinking were 80% less likely to harbor Ae. albopictus pupae in 2010 (OR = 0.20), and discarded waste was associated with a 3.64 increased odds of infestation. Vector control efforts should focus on source reduction of water storage containers, particularly concrete jars and tires.


Clear cell carcinoma arising in pleomorphic adenoma of the salivary gland.
Malignant change in pleomorphic adenoma of the salivary gland is not common. Clear cell carcinoma is an extremely rare form of malignant salivary gland tumor. A case of clear cell carcinoma of the submandibular gland arising in pleomorphic adenoma is reported.


[Liver transplantation in elderly patients].
Since the first liver transplantation (OLT) was performed by Starzl in 1963, this has become the standard therapy for end stage chronic liver disease and acute hepatic failure. It is also the therapy of choice in selected cases of hepatic malignancy. Due to the optimization of intra- and perioperative management, new immunosuppressant drugs and improved organ procurement, the clinical outcome in patient and graft survival has increased continuously. The shortage of donor organs has led to the development of new surgical techniques such as split- and living related transplantation. OLT should also be offered to elderly patients. Careful evaluation and patient selection results in good patient and graft survival after transplantation, which is comparable to that in with younger recipients.


Oxidative aromatization of 9,10-dihydroanthracenes using molecular oxygen promoted by activated carbon.
Substituted 9,10-dihydroanthracenes were oxidatively aromatized to the corresponding anthracenes effectively by using molecular oxygen as an oxidant and activated carbon (Darco KB, Aldrich, Inc.) as a promoter in xylene.


Transitions in an integrated model of renal replacement therapy in a regional health system.
The choice of renal replacement therapy (RRT) is an important decision that determines the quality of life and survival. Most patients change from one RRT modality to another to adapt RRT to clinical and psychosocial needs. This has been called «integrated model of RRT» that implies new questions about the best sequence of techniques. The study describes the impact of transitions between RRT modalities on survival using the Madrid Registry of Renal Patients (2008-2018). This study used the proportional hazards models and competitive risk models to perform an intention-to-treat (ITT), according to their 1st RRT modality and as-treated (AT) analysis, that consider also their 1st transition. A total of 8971 patients started RRT during this period in Madrid (6.6 Million population): 7207 (80.3%) on hemodialysis (HD), 1401 (15.6%) on peritoneal dialysis (PD) and 363 (4.2%) received a pre-emptive kidney transplantation (KT). Incident HD-patients were older (HD group 65.3 years (SD 15.3) vs PD group 58.1 years (SD 14.8) vs KTX group 52 years (SD 17.2); p < 0.001) and had more comorbidities. They presented higher mortality (HD group 40.9% vs PD group 22.8% vs KTX group 8.3%, p < 0.001) and less access to a transplant (HD group 30.4% vs PD group 51.6%; p < 0.001). Transitions between dialysis techniques define different groups of patients with different clinical outcomes. Those who change from HD to PD do it earlier (HD → PD: 0.7 years (SD 1.1) vs PD → HD: 1.5 years (SD 1.4) p < 0.001), are younger (HD → PD: 53.5 years (SD 16.7) vs PD → HD: 61.6 years (SD 14.6); p < 0.001), presented less mortality (HD → PD: 24.5% vs PD → HD: 32.0%; p < 0.001) and higher access to a transplant (HD → PD: 49.4% vs PD → HD: 31.7%; p < 0.001). Survival analysis by competitive risks is essential for integrated RRT models, especially in groups such as PD patients, where 51.6% of the patients were considered as lost follow-up (received a KTX after during the first 2.5 years on PD). In this analysis, survival of patients who change from one technique to another, is more similar to the destination modality than the origin one. Our data suggest that transitions between RRT-techniques describes different patients, who associate different risks, and could be analyzed in an integrated manner to define improvement actions. This approach should be incorporated into the analysis and reports of renal registries.


[Angiotensin II receptor blockers: current status and future prospects].
Angiotensin II receptor antagonists (AAIIs) are the most specific inhibitors of the renin-angiotensin-aldosterone system. There are two types of angiotensin II (Ang II) receptors, the AT(1) receptor, which is responsible for all the classical physiological properties of Ang II, and the AT(2) receptor, whose function in humans remains unclear. The different AAIIs used in clinical practice vary depending on their pharmacodynamic and pharmacokinetic properties, and, for some of them, depending on their metabolism in vivo into an active metabolite. AAIIs are relatively well tolerated, and, unlike angiotensin-converting enzyme inhibitors (ACEIs), do not induce cough. AAIIs are indicated in mild, moderate and severe essential hypertension, where their efficacy has been proven in many studies. The maximal antihypertensive effect is obtained in a few days or weeks, and is somewhat retarded when compared with ACEIs. Their effect is independent of age and sex, but does depend to a certain extent on ethnic origin, since Afro-American patients are less sensitive to AAIIs than Caucasians. In general, the antihypertensive and haemodynamic response to blockers of the renin-angiotensin system is potentiated in presence of a negative salt balance and attenuated in case of a positive salt balance. This means that AAII efficiency is improved by salt depletion induced by a salt-free diet or thiazide diuretics. AAIIs induce short-term improvement of haemodynamic parameters in cardiac insufficiency. Several ongoing clinical trials have been designed to compare their efficacy in cardiac insufficiency and myocardial infarction with those of reference treatments. Valsartan has been recently shown to improve morbimortality in patients with cardiac insufficiency and receiving a conventional treatment including an ACEI. It has been convincingly shown that blockade of the renin-aldosterone system by ACEIs decreases proteinuria and slows down the progression of renal insufficiency, especially in type 2 diabetic nephropathy. Recent trials have shown that AAIIs share the same properties as ACEIs in these indications. It appears that the beneficial effect of AAIIs and ACEIs is not entirely explained by the blood pressure lowering effect of these drugs. AAII administration increases renin release and Ang II production, which may overcome Ang II blockade. On this basis, the combination of an AAII and an ACEI has been proposed to achieve a maximal renin-angiotensin system blockade. Several experimental studies in animals and preliminary clinical studies all indicate that the combination of the two drugs may be more beneficial than either drug used alone in hypertension, cardiac insufficiency and post-myocardial infarction. Clinical trials are necessary to further document the putative advantages of such a combined therapy. The future of AAIIs depends on the following: progress made in the understanding of the molecular and cellular activities of angiotensin (angiotensin receptor signalling, receptor dimerisation, presence of other angiotensin receptor subtypes, role of AT(2) receptor, etc.);a comprehensive view of the role of the local renin system in various organs (local generation and effect of Ang II on cellular proliferation, fibrosis, inflammation, angiogenesis, etc.);predictability of the response to AAII treatment (genetic predisposition to AAII treatment, in conjunction with environmental factors); andresults of the ongoing clinical trials designed to assess the long-term effects of AAIIs in cardiovascular mortality and morbidity, in comparison with reference treatments.


Behavioral and Haemato-Biochemical Responses of Nguni and Boran Steers Post Relocation and Herd Regrouping in a Novel Environment.
Behavioural and blood-based physiological responses of Nguni (NG) and Boran (BR) steers, following relocation to a new environment and herd regrouping were examined. Ten steers of each genotype aged 9 months and reared under similar conditions were studied over 16 weeks: 1 for acclimatization and baseline measurements in original groups, 15 for post regrouping measurements. Each sampling week, direct visual observations and durations of aggressive and affiliative interactions were recorded between 0500-1900h for 3 conservative days. Blood samples were drawn fortnightly by jugular venipuncture for plasma cortisol, glucose, creatine kinase (CK) and haematological analysis. In weeks 1-5, BR had higher instances of head-butting (P=0.0311), mounts (P=0.0142) and threats (P=0.0241) compared to NG (P<0.0001, P=0.0412 and P=0.0241, respectively). However, these significantly declined from weeks 7-15 in both genotypes. Grooming increased consistently over the weeks in both genotypes (P=0.0214). Head-butting correlated with cortisol (r=-0.116), CK (r=-0.295) and neutrophil-to-lymphocyte ratio (r=-0.144). Grooming correlated (r=0.137) with white-blood-cell-count. Herd regrouping temporarily disrupted social behaviour, with BR showing more aggression towards NG steers. Nevertheless, the two genotypes established some stability within five weeks of social mixing.


Meningoencephalitis associated with Staphylococcus warneri in a dog.
A case of meningoencephalitis in a dog caused by Staphylococcus warneri is reported here. The history and clinical signs were suggestive of possible central nervous system infection. Analysis of cerebrospinal fluid documented a neutrophilic pleocytosis (890 cells/mul) and the presence of occasional intracellular cocci. Staphylococcus warneri was isolated from the microbiological culture of the cerebrospinal fluid. Treatment consisted of intravenous antibiotics, supportive care and anticonvulsants for the generalised seizures that developed after admission. Histological assessment confirmed the location and extension of bacterial meningoencephalitis. Thrombotic meningoencephalitis associated with Staphylococcus warneri infection has not, to the authors' knowledge, been previously reported in dogs.


Novel Insights into the Pathogenesis of Hirschsprung's-associated Enterocolitis.
To systematically summary the updated results about the pathogenesis of Hirschsprung's-associated enterocolitis (HAEC). Besides, we discussed the research key and direction based on these results. Our data cited in this review were obtained mainly from PubMed from 1975 to 2015, with keywords "Hirschsprung enterocolitis", "Hirschsprung's enterocolitis", "Hirschsprung's-associated enterocolitis", "Hirschsprung-associated enterocolitis", "HAEC", and "EC". Articles regarding the pathogenesis of HAEC were selected, and the articles mainly regarding the diagnosis, surgical approach, treatment, and follow-up were excluded. Several factors, mainly including mucus barrier, intestinal microbiota, and immune function, as well as some other factors such as genetic variations and surgical reasons, have been found to be related to the pathogenesis of HAEC. Changed quantity and barrier property of mucus, different composition of microbiota, and an abnormal immune state work together or separately trigger HAEC. The maintenance of intestinal homeostasis is due to a well cooperation of microbiota, mucus barrier, and immune system. If any part presents abnormal, intestinal homeostasis will be broken. Meanwhile, for patients with Hirschsprung's disease or HAEC, dysfunction of these parts has been found. Thus, the happening of HAEC may be mainly attributed to the disorders of intestinal microbiota, mucus barrier, and immune system.


Structural restoration of inactive recombinant fish growth hormones by chemical chaperonin and solvent restraint approaches.
Recombinant proteins may undergo conformational distortion, leading to aggregation and loss of function, when they are expressed in heterologous systems. The structural and functional restoration of such inactive proteins is highly desirable. We have over-expressed recombinant growth hormones from the fish ayu (Plecoglossus altivelis) and yellow grouper (Epinephelus awoara) by a pET expression system. Both recombinant proteins accumulate as insoluble form in Escherichia coli. We refolded these inactive proteins into the active form using a stepwise refolding process with a dilute denaturing agent as a steric blocker and chemical chaperonin. Optical characterization showed that stable folding intermediates with a helical conformation can be detected in the molten globule state. Moreover, the function of restored recombinant growth hormones was demonstrated by its ability to stimulate proliferation in zebrafish liver cells.


Involvement of Ataxin-3 (ATXN3) in the malignant progression of pancreatic cancer via deubiquitinating HDAC6.
Pancreatic cancer is a common digestive system cancer and one of the most lethal malignancies worldwide. Ataxin-3 (ATXN3) protein is a deubiquitinating enzyme implicated in the occurrence of diverse human cancers. The potential role of ATXN3 in pancreatic cancer still remains unclear. ATXN3 was screened from differentially-upregulated genes of GSE71989, GSE27890 and GSE40098 datasets. The mRNA and protein levels of ATXN3 was evaluated in pancreatic cancer samples and cell lines. Through the gain- and loss-of-function experiments, the effects of ATXN3 on cell proliferation, migration and invasion were evaluated using cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) staining, wound healing and Transwell assays. Subsequently, the interaction between ATXN3 and HDAC6 was confirmed using double immunofluorescence staining, co-immunoprecipitation (co-IP) and proximity ligation assay (PLA). The underlying mechanism of ATXN3 was determined by knockdown of HDAC6 in ATXN3-upregulated pancreatic cancer cells. The function of ATXN3 in vivo was verified through xenograft assay. High expression of ATXN3 was found in pancreatic cancer tissues. Increased ATXN3 expression dramatically promoted cell proliferation, migration, and invasion. The malignant phenotypes were suppressed in ATXN3-silenced pancreatic cancer cells. ATXN3 was proved to interact with HDAC6 and regulate its degradation through deubiquitination. Downregulation of HDAC6 inhibited ATXN3-induced development of pancreatic cancer cells through regulating the expression of PCNA, vimentin and E-cadherin. ATXN3 facilitated tumor growth of pancreatic cancer and increased HDAC6 expression in vivo. This study confirmed that ATXN3 facilitated malignant phenotypes of pancreatic cancer via reducing the ubiquitination of HDAC6.