bluuebunny/crossref_metadata_2025 huggingface dataset:
Activating SRC/MAPK signaling via 5-HT1A receptor contributes to the effect of vilazodone on improving thrombocytopenia
Authors: Zhou Ling , Ni Chengyang , Liao Ruixue , Tang Xiaoqin , Yi Taian , Ran Mei , Huang Miao , Liao Rui , Zhou Xiaogang , Qin Dalian , Wang Long , Huang Feihong , Xie Xiang , Wan Ying , Luo Jiesi , Wang Yiwei , Wu Jianming
Published: February 2024

Thrombocytopenia caused by long-term radiotherapy and chemotherapy exists in cancer treatment. Previous research demonstrates that 5-Hydroxtrayptamine (5-HT) and its receptors induces the formation of megakaryocytes (MKs) and platelets. However, the relationships between 5-HT1A receptor (5-HTR1A) and MKs is unclear so far. We screened and investigated the mechanism of vilazodone as a 5-HTR1A partial agonist in promoting MK differentiation and evaluated its therapeutic effect in thrombocytopenia. We employed a drug screening model based on machine learning (ML) to screen the megakaryocytopoiesis activity of VLZ. The effects of Vilazodone (VLZ) on megakaryocytopoiesis were verified in HEL and Meg-01 cells. Tg (itga2b: eGFP) zebrafish was performed to analyze the alterations in thrombopoiesis. Moreover, we established a thrombocytopenia mice model to investigate VLZ administration accelerates platelet recovery and function. We carried out network pharmacology, Western blotting and immunofluorescence to demonstrate the potential targets and pathway of VLZ. VLZ has been predicted to have a potential biological action. Meanwhile, VLZ administration promotes MK differentiation and thrombopoiesis in cells and zebrafish models. Progressive experiments showed that VLZ has a potential therapeutic effect on radiation-induced thrombocytopenia
in vivo
. The network pharmacology and associated mechanism study indicated that SRC and MAPK signaling are both involved in the processes of megakaryopoiesis facilitated by VLZ. Furthermore, the expression of 5-HTR1A during megakaryocyte differentiation is closely related to the activation of SRC and MAPK. Our findings demonstrated that the expression of 5-HTR1A on MK, VLZ could bind to the 5-HTR1A receptor and further regulate the SRC/MAPK signaling pathway to facilitate megakaryocyte differentiation and platelet production, which provides new insights into the alternative therapeutic options for thrombocytopenia.
رقص روزن داران
Authors: هولم ویلادز , لوسلبن لیزا کاترین , زیمرمن هایکه جین , کلریچی مونیکا , پانیری جولیانا , آب نیکی محمد , همتی نژاد فرشته
Published: February 2024

تمرکز: آشنایی با روزن داران از طریق تمرین و ارائه آهنگ رقص ورزن داران (The Foraminifera Boogie). دانش آموزان و معلمان همچنین می توانند تصمیم بگیرند که همراه با موسیقی متن ضبط شده ساز بنوازند.

 

اهداف آموزشی: در این فعالیت، دانش آموزان گوش دادن به یکدیگر و موسیقی را تمرین خواهند کرد. آنها شعر را یاد می گیرند و از صدای خود برای خواندن آهنگ استفاده می کنند. این را می توان با نواختن آلات موسیقی واقعی یا استفاده از سازهایی که خود دانش آموزان ساخته اند ترکیب کرد (به عنوان مثال به فعالیت "سمفونی تراوش سرد" مراجعه کنید). این فعالیت موسیقی را با داستان علمی روزنه داران گرد هم می آورد.

 

کلمات کلیدی: اقیانوس، محققان، موجودات کمتر شناخته شده در اقیانوس منجمد شمالی، زندگی مشترک انسان ها و دیگر موجودات زنده، زمان سیاره ای.
Fine-scale mapping of chromosome 9q22.33 identifies candidate causal variant in ovarian cancer
Authors: Xing Tongyu , Zhao Yanrui , Wang Lili , Geng Wei , Liu Wei , Zhou Jingjing , Huang Caiyun , Wang Wei , Chu Xinlei , Liu Ben , Chen Kexin , Zheng Hong , Li Lian
Published: February 2024

Ovarian cancer is a complex polygenic disease in which genetic factors play a significant role in disease etiology. A genome-wide association study (GWAS) identified a novel variant on chromosome 9q22.33 as a susceptibility locus for epithelial ovarian cancer (EOC) in the Han Chinese population. However, the underlying mechanism of this genomic region remained unknown. In this study, we conducted a fine-mapping analysis of 130 kb regions, including 1,039 variants in 200 healthy women. Ten variants were selected to evaluate the association with EOC risk in 1,099 EOC cases and 1,591 controls. We identified two variants that were significantly associated with ovarian cancer risk (rs7027650, P = 1.91 × 10−7; rs1889268, P = 3.71 × 10−2). Expression quantitative trait locus (eQTL) analysis found that rs7027650 was significantly correlated with COL15A1 gene expression (P = 0.009). The Luciferase reporter gene assay confirmed that rs7027650 could interact with the promoter region of COL15A1, reducing its activity. An electrophoretic mobility shift assay (EMSA) showed the allele-specific binding capacity of rs7027650. These findings revealed that rs7027650 could be a potential causal variant at 9q22.33 region and may regulate the expression level of COL15A1. This study offered insight into the molecular mechanism behind a potential causal variant that affects the risk of ovarian cancer.
Galectin-3 promotes fibrosis in ovarian endometriosis
Authors: Yang Guimin , Deng Yupeng , Cao Guangming , Liu Chongdong
Published: February 2024

Objective

This study aimed to investigate the potential role of galectin-3 (Gal-3) in the pathogenesis of fibrotic alterations in ovarian endometriosis (OVE).

Methods

In this study, we collected the ectopic endometrial tissues and eutopic endometrial tissues from 31 OVE patients treated by laparoscopy, and the eutopic endometrial tissues from 23 non-OVE patients with leiomyoma or other benign diseases were used as control. Hematoxylin and eosin (H&E) and Masson’s trichrome staining were utilized for histopathological assessment. The primary normal endometrial stromal cells (NESC), ectopic endometrial stromal cells (ECSC), and eutopic endometrial stromal cells (EUSC) were isolated. Gal-3 overexpression plasmids (Gal-OE) and short hairpin RNA targeting Gal-3 (Gal-3-shRNA) were transfected into the immortalized human endometriotic cell line 12Z, respectively. RT-qPCR, Western blot analysis, and immunohistochemistry were used to detect the mRNA and protein expression levels of Gal-3, type I collagen (COL-1), connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA), respectively.

Results

H&E and Masson staining showed that ovarian ectopic endometrium exhibited glandular hyperplasia, high columnar glandular epithelium, apical plasma secretion, more subnuclear vacuoles, and obvious fibrosis, compared with normal endometrium. The mRNA and protein levels of Gal-3 , CTGF, α-SMA, and COL-1 were all upregulated in the ectopic endometrial tissues of OVE patients compared to the eutopic endometrial tissues from OVE patients and non-OVE patients. Moreover, ECSC expressed higher levels of Gal-3, CTGF, α-SMA, and COL-1 than EUSC and NESC. Follow-up investigations demonstrated that the Gal-3 overexpression substantially increased fibrosis-related markers including CTGF, α-SMA, and COL-1 within the 12Z cell line. Conversely, Gal-3 knockdown showed the opposite effects.

Conclusion

Gal-3 promotes fibrosis in OVE, positioning it as a prospective therapeutic target for mitigating fibrosis in endometriosis.
Monodisperse copper‐ and silver‐nanocolloids suitable for heat‐conductive fluids
Authors: Bönnemann H. , Botha S. S. , Bladergroen B. , Linkov V. M.
Published: March 2005

Copper colloid was prepared via reductive stabilization. The suspension of the trioctylaluminum‐stabilized copper colloid was peptized using Korantin SH and cashew nut shell liquid (CNSL). Fluids with particle sizes <10 nm were obtained with Korantin and 7–15 nm in the case of CNSL. However, the copper colloid is air sensitive. A very straightforward one‐step method leads to air‐stable silver nanofluids. Thermal decomposition of silver lactate in the presence of Korantin SH and mineral oil as the medium gave a silver nanofluid. Silver particle formation and air stability were monitored using UV–VIS spectroscopy. The presence of monodispersed spherical silver nanoparticles was confirmed. Transmission electron microscopy showed a two‐dimensional assembly of the silver particles with a size distribution of 9.5 ± 0.7 nm. FTIR has revealed information about the interaction between the surfactant and the silver surface. Copyright © 2005 John Wiley & Sons, Ltd.
The effect of phenyltin chlorides on osmotically induced erythrocyte haemolysis
Authors: Miszta Adam , Gabrielska Janina , Przestalski Stanisław , Langner Marek
Published: March 2005

The toxicity of many amphiphilic compounds may result from their effect on the lipid phase of biological membranes. Upon incorporation such compounds may change the properties of membranes in general and in particular alter the organization of membrane lipids. These changes should affect, among other things, the mechanical properties of membranes. We selected two amphiphilic compounds, diphenyltin dichloride (Ph2SnCl2) and triphenyltin chloride (Ph3SnCl), which are known to be located at different regions of the lipid bilayer and to be toxic. As a model biological membrane the erythrocyte plasma membrane was used. Analysis of the haemolysis kinetics showed differences between the effect of the compound studied on mechanical properties at so‐called non‐lytic concentrations. Diphenyltin dichloride showed a limited effect on erythrocyte haemolysis, whereas triphenyltin chloride affected all the parameters measured (extent of initial haemolysis, extent of final haemolysis and membrane mechanical strength). We correlated these effects with the location of the investigated compounds in liposomes. The presented data show that triphenyltin chloride reduces the erythrocyte plasma membrane mechanical strength and increases the extent of haemolysis under osmotic stress conditions. Copyright © 2005 John Wiley & Sons, Ltd.
Enhancement of attraction and trap catches of the old‐house borer, Hylotrupes bajulus (Coleoptera: Cerambycidae), by combination of male sex pheromone and monoterpenes
Authors: Reddy Gadi VP , Fettköther Regina , Noldt Uwe , Dettner Konrad
Published: March 2005

Monoterpenoid compounds extracted from wood of Scots pine, Pinus sylvestris L, synergized the attraction of the old‐house borer, Hylotrupes bajulus (L), to the male pheromone (3R)‐3‐hydroxy‐2‐hexanone ((3R)‐ketol) + 1‐butanol. Glasshouse experiments using ground traps baited with extracts derived from Scots pine wood or the monoterpenes (+)‐α‐pinene, (−)‐verbenone, (−)‐trans‐pinocarveol and (+)‐terpinen‐4‐ol attracted significantly more H bajulus females, but caught fewer of them, than the synthetic pheromone mixture alone. Traps baited with higher concentrations of the monoterpene mixture attracted fewer females than those baited with lower dosages, whilst very high concentrations of the mixture (6–10 vials) caught no insects. However, a combination of (3R)‐ketol + 1‐butanol or (±)‐3‐ketol + 1‐butanol with monoterpenes resulted in the capture of significantly more females than either the sex pheromone or the monoterpene mixture alone. Traps baited with a blend of the male's sex pheromone or the monoterpenes attracted significantly more, but caught fewer, males than females. Here again, a combination of the above blends enhanced the attraction of males significantly when compared with the attractancy of either of the compounds/mixtures used alone. Copyright © 2005 Society of Chemical Industry
Semiquantitative histomorphometric analysis of myocardium following partial left ventriculectomy: 1‐year follow‐up
Authors: Vasiljević Jovan D. , Otašević Petar , Popović Zoran B. , Nešković Aleksandar N. , Vidaković Radoslav , Popović Zoran V. , Radovančević Branislav , Frazier O. Howard , Gradinac Siniša
Published: March 2005

Background:

Although partial left ventriculectomy (PLV) may have beneficial clinical effects in patients with dilated cardiomyopathy (DCM), there are no reports on effects of PLV on myocardial histology. The objective of this study was to assess histological properties of the LV myocardium 1 year following PLV as compared to histology at the time of the operation.

Methods:

The study group consisted of 15 consecutive PLV survivors, predominantly male (13/15), aged 45±12 years. Surgical specimens and endomyocardial biopsies, taken 12 months postoperatively, were processed routinely and stained with Masson‐trichrome. The following morphometric parameters were assessed semiquantitavely: (1) degree of hypertrophy and attenuation; (2) nuclear evidence of hypertrophy; (3) myofibrillar volume fraction; (4) degree of degenerative vacuolar changes; and (5) fibrosis volume fraction.

Results

Both New York Heart Association (NYHA) functional class and ejection fraction (EF) improved 12 months following surgery as compared to preoperative values (2.40±0.69 vs. 3.33±0.49, p<0.001, and 33.21±12.05% vs. 20.21±9.07%, p<0.001, respectively). Morphometric analysis demonstrated postoperative decrease in the degree of attenuation as compared to preoperative values (1.40±0.51 vs. 2.47±0.64, p<0.01), as well as a decrease in fibrosis volume fraction (2.07±0.80 vs. 2.67±0.49, p<0.001) and nuclear hypertrophy (1.27±0.46 vs. 1.67±0.62, p<0.05). On the other hand, postoperative increase in myofibrillar volume fraction (1.87±0.61 vs. 1.40±0.61, p<0.01) was noted.

Conclusion

One year postoperatively, PLV has favourable effects on myocardial morphology that parallels improvement in the patient's functional status and LV systolic function.
Cyclooxygenase inhibition causes marked impairment of renal function in elderly subjects treated with diuretics and ACE‐inhibitors
Authors: Juhlin Tord , Björkman Sven , Höglund Peter
Published: March 2005

Background:

Treatment with angiotensin‐converting enzyme (ACE)‐inhibitors is known to cause an initial reduction in glomerular filtration rate (GFR) in patients with congestive heart failure. The long‐term beneficial effects of ACE‐inhibitors in these patients can be counteracted by cyclooxygenase‐inhibitors.

Aims:

To quantify the negative renal effects of the cyclooxygenase‐inhibitor diclofenac in elderly healthy subjects and to assess how treatment with an ACE‐inhibitor, after activation of the renin–angiotensin system, influences these renal effects.

Methods:

Fourteen elderly, healthy subjects received oral diclofenac and placebo in a double‐blind cross‐over fashion. The study was divided in two parts; in part one, subjects received no pre‐treatment and in part two, the subjects were given pre‐treatment with bendroflumethiazide and enalapril in order to activate the renin–angiotensin system.

Results:

Diclofenac induced significant (p<0.05) decreases in GFR, urine flow, excretion rates of sodium and potassium, electrolyte clearance, osmolality clearance and free water clearance both with and without renin–angiotensin system activation. Least square means (95% CI) of all observations during the first 6 h after dosing showed that diclofenac caused a reduction in GFR from 71 (64–78) to 59 (52–66) ml/min. After pre‐treatment, diclofenac further reduced GFR from 60 (52–67) to 48 (40–55) ml/min. After diclofenac administration, urine flow fell from 7.4 (6.4–8.3) to 5.1 (4.2–6.1) ml/min, after pre‐treatment, diclofenac gave a further reduction from 4.1 (3.1–5.1) to 2.2 (1.3–3.2) ml/min. More than half of the reductions were caused by the pre‐treatment.

Conclusion:

Renal function in elderly, healthy subjects is impaired after acute intake of diclofenac. This impairment is observed both with and without activation of the renin–angiotensin system and ACE‐inhibitor treatment but is more pronounced after pre‐treatment.
Shock properties of H2O ice
Authors: Stewart Sarah T. , Ahrens Thomas J.
Published: March 2005

To understand the mechanics and thermodynamics of impacts on, and collisions between, icy planetary bodies, we measured the dynamic strength and shock states in H2O ice. Here, we expand upon previous analyses and present a complete description of the phases, temperature, entropy, and sound velocity along the ice shock Hugoniot. Derived from shock wave measurements centered at initial temperatures (T0) of 100 K and 263 K, the Hugoniot is composed of five regions: (1) elastic shocks in ice Ih, (2) ice Ih deformation shocks, and shock transformation to (3) ice VI, (4) ice VII, and (5) liquid water. In each region, data obtained at different initial temperatures are described by a single US − Δup shock equation of state. The dynamic strength of ice Ih is strongly dependent on initial temperature, and the Hugoniot Elastic Limit varies from 0.05 to 0.62 GPa, as a function of temperature and peak shock stress. We present new bulk sound velocity measurements and release profiles from shock pressures between 0.4 and 1.2 GPa. We report revised values for the shock pressures required to induce incipient melting (0.6 ± 0.05, 1.6 ± 0.3 GPa) and complete melting (2.5 ± 0.1, 4.1 ± 0.3 GPa) upon isentropic release from the shock state (for T0 = 263, 100 K). On account of the >40% density increase upon transformation from ice Ih to ices VI and VII, the critical shock pressures required for melting are factors of 2 to 10 lower than earlier predicted. Consequently, hypervelocity impact cratering on planetary surfaces and mutual collisions between porous cometesimals will result in abundant shock‐induced melting throughout the solar system.
Glacial water mass geometry and the distribution of δ13C of ΣCO2 in the western Atlantic Ocean
Authors: Curry W. B. , Oppo D. W.
Published: March 2005

Oxygen and carbon isotopic data were produced on the benthic foraminiferal taxa Cibicidoides and Planulina from 25 new piston cores, gravity cores, and multicores from the Brazil margin. The cores span water depths from about 400 to 3000 m and intersect the major water masses in this region. These new data fill a critical gap in the South Atlantic Ocean and provide the motivation for updating the classic glacial western Atlantic δ13C transect of Duplessy et al. (1988). The distribution of δ13C of ΣCO2 requires the presence of three distinct water masses in the glacial Atlantic Ocean: a shallow (∼1000 m), southern source water mass with an end‐member δ13C value of about 0.3–0.5‰ VPDB, a middepth (∼1500 m), northern source water mass with an end‐member value of about 1.5‰, and a deep (>2000 m), southern source water with an end‐member value of less than −0.2‰, and perhaps as low as the −0.9‰ values observed in the South Atlantic sector of the Southern Ocean (Ninnemann and Charles, 2002). The origins of the water masses are supported by the meridional gradients in benthic foraminiferal δ18O. A revised glacial section of deep water δ13C documents the positions and gradients among these end‐member intermediate and deep water masses. The large property gradients in the presence of strong vertical mixing can only be maintained by a vigorous overturning circulation.
Chemical kinetics simulation for atmospheric pressure air plasmas in a streamer regime
Authors: Barni R. , Esena P. , Riccardi C.
Published: March 2005

We present a theoretical analysis of air discharges at high pressure which operates in a streamer regime. The aim is to provide a simplified framework to study the chemical kinetics in the discharge gas phase. We have tried to model the characteristics of actually existing devices, such as dc and ac discharges in sharp point-plane, point to point, or coaxial cylinder configuration, dielectric barrier discharges. Within such scheme it is possible to perform numerical simulations in order to predict the evolution of the gas-phase chemical composition. As a first application we have chosen to simulate the chemical kinetics induced in a single isolated streamer and the results of this approach are examined within this paper. In particular, we have studied the detailed temporal evolution of the discharge gas phase using reference values for the simulation free parameters. The interplay between different time scale processes is shown. The effect due to charged as well as metastable species on chemical kinetics has been discussed too. Then we have studied the dependence of chemical species density on discharge parameters such as the electron temperature, the electron density, the transverse radius of the streamer, and the streamer formation time. Many results can be proven relevant for a better understanding of the operating conditions during technological sensible processing based on atmospheric pressure plasma.
A simple neural network model of the hippocampus suggesting its pathfinding role in episodic memory retrieval
Authors: Samsonovich Alexei V. , Ascoli Giorgio A.
Published: March 2005

The goal of this work is to extend the theoretical understanding of the
relationship between hippocampal spatial and memory functions to the level of
neurophysiological mechanisms underlying spatial navigation and episodic
memory retrieval. The proposed unifying theory describes both phenomena within
a unique framework, as based on one and the same pathfinding function of the
hippocampus. We propose a mechanism of reconstruction of the context of
experience involving a search for a nearly shortest path in the space of
remembered contexts. To analyze this concept in detail, we define a simple
connectionist model consistent with available rodent and human
neurophysiological data. Numerical study of the model begins with the spatial
domain as a simple analogy for more complex phenomena. It is demonstrated how
a nearly shortest path is quickly found in a familiar environment. We prove
numerically that associative learning during sharp waves can account for the
necessary properties of hippocampal place cells. Computational study of the
model is extended to other cognitive paradigms, with the main focus on
episodic memory retrieval. We show that the ability to find a correct path may
be vital for successful retrieval. The model robustly exhibits the pathfinding
capacity within a wide range of several factors, including its memory load (up
to 30,000 abstract contexts), the number of episodes that become associated
with potential target contexts, and the level of dynamical noise. We offer
several testable critical predictions in both spatial and memory domains to
validate the theory. Our results suggest that (1) the pathfinding function of
the hippocampus, in addition to its associative and memory indexing functions,
may be vital for retrieval of certain episodic memories, and (2) the
hippocampal spatial navigation function could be a precursor of its memory
function.
Activation of group II metabotropic glutamate receptors induces depotentiation in amygdala slices and reduces fear-potentiated startle in rats
Authors: Lin Chia-Ho , Lee Chia-Ching , Huang Ya-Chun , Wang Su-Jane , Gean Po-Wu
Published: March 2005

There is a close correlation between long-term potentiation (LTP) in the
synapses of lateral amygdala (LA) and fear conditioning in animals. We predict
that reversal of LTP (depotentiation) in this area of the brain may ameliorate
conditioned fear. Activation of group II metabotropic glutamate receptors
(mGluR II) with DCG-IV induces depotentiation in the LA. The induction of
depotentiation is independent of NMDA receptors, L-type Ca++
channels, and calcineurin activity, but requires presynaptic activity and
extracellular Ca++.
(2S,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)glycine
(DCG-IV) depotentiation is accompanied by a decrease in the frequency but not
the amplitude of miniature excitatory post-synaptic currents (mEPSCs) and
could be mimicked by endogenously released glutamate. DCG-IV inhibited the
release of glutamate evoked by 4-AP but not that evoked by ionomycin,
suggesting that the effect of DCG-IV is not mediated by an action downstream
of Ca++ entry. Intra-amygdala infusion of mGluR II agonist blocks
the consolidation of fear memory measured with fear-potentiated startle. Taken
together, the present results characterize the properties of DCG-IV
depotentiation and reveal a close parallel between depotentiation in the
amygdala slice and the reduction of conditioned fear in animals.
ON THE ERROR IN THE MONTE CARLO PRICING OF SOME FAMILIAR EUROPEAN PATH‐DEPENDENT OPTIONS
Authors: Hörfelt Per
Published: March 2005

This paper studies the relative error in the crude Monte Carlo pricing of some familiar European path‐dependent multiasset options. For the crude Monte Carlo method it is well known that the convergence rate O(n−1/2), where n is the number of simulations, is independent of the dimension of the integral. This paper also shows that for a large class of pricing problems in the multiasset Black‐Scholes market the constant in O(n−1/2) is independent of the dimension. To be more specific, the constant is only dependent on the highest volatility among the underlying assets, time to maturity, and degree of confidence interval.
Conflicting demands on wetland ecosystem services: nutrient retention, biodiversity or both?
Authors: HANSSON LARS‐ANDERS , BRÖNMARK CHRISTER , ANDERS NILSSON P , ÅBJÖRNSSON KAJSA
Published: March 2005

1. Wetland ecosystems may, besides having considerable economical value, increase landscape biodiversity and function as traps for nutrients from land to freshwater‐ and marine systems. As a result of these features, wetlands are nowadays often protected and restored, and many countries have even initiated wetland construction programmes.

2. In the present study, we aim at increasing the knowledge on how to improve the design of a wetland with respect to both biodiversity and nutrient retention, by analysing physical, chemical and biological features of a large set of constructed wetlands.

3. Our results show that a combination of the wetland features, namely shallow depth, large surface area and high shoreline complexity are likely to provide a high biodiversity of birds, benthic invertebrates and macrophytes and to have high nitrogen retention, whereas a small, deep wetland is likely to be more efficient in phosphorus retention, but less valuable in terms of biodiversity.

4. Hence, among the features used to design new wetlands, area, depth and shoreline complexity have fundamental, and sometimes conflicting, effects on nutrient retention and biodiversity. This means that there are, within limits, possibilities to direct the ecosystem function of a specific wetland in desired directions.
Aspects of the relationship between doctors and depressed patients that enhance satisfaction with primary care
Authors: NOLAN P. , BADGER F.
Published: March 2005

Depression will be the second most common threat to health by the end of the next decade. The incidence of depression in primary care is already high. This has serious implications for the types of services available, the range of personnel who deliver them and the extent to which patients are helped by the treatments provided. Research reveals that approximately two‐thirds of patients with depression are treated with medication, although it is not known how effective medication is in the long term. It would appear that the relationship between the patient and prescriber is a highly significant factor in determining whether or not patients adhere to treatment regimens and to what extent they improve. This study used a qualitative approach to identify how patients treated with medication for their depression perceived the relationship with their prescribing clinician, what kinds of information and advice they received and what they wanted. Several aspects of the helpful relationship are identified, such as the characteristics and behaviour of the clinician, as well as the way in which information is imparted. The frequency of monitoring consultations and patients’ perceptions of their importance were also examined. The issue of stigma, particularly self‐stigma and what can be done to prevent it, is discussed. The paper concludes with suggestions for improving the quality of primary care for patients’ prescribed medication for depression, and especially for making maximum use of the initial consultation. The main implication for mental health nurses is that central to all interventions for depression is the primacy of the relationship, without which, clients’ belief in treatment is diminished.
Culture shift: carer empowerment and cooperative inquiry
Authors: LLOYD M. , CARSON A.
Published: March 2005

Government policy has directed local services to address the needs of carers as a way of maintaining care in the community. This study was initiated to enable carers to develop an information pack based upon their identified needs. Cooperative inquiry was the method used to ensure full participation of the carers. Group meetings were already in existence through a charity organization who provides a carers support network. The first author participated in a number of carers group meetings. Cooperative inquiry was used to clarify a number of themes identified and reflective cycles ensured that those themes remained relevant. It was found that carers did want to be involved in their relative's care, not as passive recipients but as collaborative care providers. To do this they need to be fully informed of the processes of care provision. Carers need information that is relevant, easily accessible and obtainable in varying degrees of comprehension. This study suggests that a culture shift within mental health nursing is necessary if professionals are to recognize that a perceived lack of support may lead to a breakdown in relationships between the carer, the person being cared for and the professionals.
Effect of postpartum iron supplementation on red cell and iron parameters in non‐anaemic iron‐deficient women: a randomised placebo‐controlled study
Authors: Krafft A. , Perewusnyk G. , Hänseler E. , Quack K. , Huch R. , Breymann C.
Published: March 2005

Objective  To investigate the effect of oral iron on postpartum red cell and iron parameters in non‐anaemic women with iron deficiency.

Design  Randomised study of supplementation with oral iron sulphate 80 mg daily or placebo for 12 weeks starting 24−48 hours after delivery, with visits antepartum and 1, 4, 6 and 12 weeks postpartum.

Setting  Swiss university hospital obstetric unit.

Participants  Fifty‐two women with antenatal iron deficiency (serum ferritin <15 μg/L) and no antenatal or postnatal anaemia (haemoglobin >11 g/dL up to 48 hours before delivery, and >10 g/dL postpartum), divided into two groups comparable in antenatal iron status.

Methods  Supplementation was started 24–48 hours after delivery (visit 1:V1). Additional tablets were issued one week after V1 (V2), four weeks after V1 (V3) and six weeks after V1 (V4). The last visit took place 12 weeks after visit 1 and 6 weeks after visit 4 (V5). Patients were required to return blisters and boxes whether they were used and unused at each visit and compliance was assessed by counting the tablets. Blood samples for haematology and iron status testing were taken before delivery and at each visit.

Main outcome measures  Iron status (serum ferritin, hypochromic red cells, iron, transferrin saturation, soluble transferrin receptor concentration); erythropoiesis (standard parameters, including reticulocyte indices); and inflammatory response (serum neopterin, C‐reactive protein, white cell count) in five‐datapoint profiles.

Results  Increased ferritin (P= 0.0004) and transferrin saturation (P= 0.03), decreased soluble transferrin receptors (P= 0.02); increased haemoglobin (P= 0.02) and decreased hypochromic red cells (P= 0.04) compared with placebo at 12 weeks, with no differences in other red cell or reticulocyte parameters. There was a positive correlation between C‐reactive protein and postpartum ferritin. No correlation was observed in the puerperium between C‐reactive protein and hypochromic red cells or soluble transferrin receptors.

Conclusions  Haemoglobin levels and iron stores in women with term gestational iron deficiency benefit significantly from iron supplementation compared with placebo, even in an industrialised population.
Exercise‐induced arterial hypoxemia is not different during cycling and running in triathletes
Authors: Laursen Paul B. , Rhodes Edward C. , Langill Robert H. , Taunton Jack E. , McKenzie Donald C.
Published: March 2005

This study examined the effect of running and cycling on exercise‐induced arterial hypoxemia (EIAH) in individuals well trained in each modality. Thirteen male triathletes (x̄±SD: age=36±5 years, mass=69±8 kg, body fat=12±1%) performed progressive exercise to exhaustion during cycle ergometry and treadmill running. Gas exchange was determined, while oxyhemoglobin saturation (SaO2) was measured with an ear oximeter. At maximal exercise, the respiratory exchange ratio (1.15±0.06 vs. 1.10±0.05) and the ventilatory equivalent for oxygen uptake (37.6±3.8 vs. 34.2±2.7) were greater during cycling vs. running (P<0.05). However, there were no differences at maximal exercise in oxygen uptake (64.4±3.2 vs. 67.0±4.6 mL kg−1 min−1), SaO2 (93.4±2.8% vs. 92.6±2.2%), or the ventilatory equivalent for carbon dioxide (V̇E/V̇CO2; 33.1±3.1 vs. 31.0±3.1), during cycling vs. running, respectively. During submaximal exercise, the V̇E/V̇CO2 was less for cycling (26.0±1.0) compared with running (29.1±0.4; P<0.05), but this had no apparent effect on the SaO2 response. In conclusion, EIAH was not significantly different during cycling and running in athletes who were well trained in both exercise modalities.
Stress and life dissatisfaction are inversely associated with jogging and other types of physical activity in leisure time—The Copenhagen City Heart Study
Authors: Schnohr P. , Kristensen T.S. , Prescott E. , Scharling H.
Published: March 2005

The associations between physical activity in leisure time with special focus on jogging and the level of mental stress and life dissatisfaction were studied in 12 028 randomly selected men and women aged 20–79 years. The associations were similar in men and women; thus, results are given for pooled data. The odds ratios (ORs) are presented as adjusted for sex, age, body mass index, smoking, alcohol consumption, education and income. With increasing physical activity in leisure time, there was a decrease in high level of stress, between sedentary persons and joggers, OR=0.30 (95% confidence interval (CI) from 0.16 to 0.56). With increasing physical activity there was also a decrease in life dissatisfaction, between sedentary persons and joggers, OR=0.30 (95% CI from 0.18 to 0.52). Although there was a dose–response effect between physical activity and psychosocial well‐being the most pronounced difference with regard to the level of stress and dissatisfaction was seen between the group with low and the group with moderate physical activity, e.g., 2–4 h of walking per week.

In conclusion, we recommend that increased well‐being should be a key argument in future campaigns for increased leisure‐time physical activity.
Glucose clearance is higher in arm than leg muscle in type 2 diabetes
Authors: Olsen David B. , Sacchetti Massimo , Dela Flemming , Ploug Thorkil , Saltin Bengt
Published: March 2005

Insulin‐mediated glucose clearance (GC) is diminished in type 2 diabetes. Skeletal muscle has been estimated to account for essentially all of the impairment. Such estimations were based on leg muscle and extrapolated to whole body muscle mass. However, skeletal muscle is not a uniform tissue and insulin resistance may not be evenly distributed. We measured basal and insulin‐mediated (1 pmol min−1 kg−1) GC simultaneously in the arm and leg in type 2 diabetes patients (TYPE 2) and controls (CON) (n= 6 for both). During the clamp arterio‐venous glucose extraction was higher in CON versus TYPE 2 in the arm (6.9 ± 1.0 versus 4.7 ± 0.8%; mean ±s.e.m.; P= 0.029), but not in the leg (4.2 ± 0.8 versus 3.1 ± 0.6%). Blood flow was not different between CON and TYPE 2 but was higher (P < 0.05) in arm versus leg (CON: 74 ± 8 versus 56 ± 5; TYPE 2: 87 ± 9 versus 43 ± 6 ml min−1 kg−1 muscle, respectively). At basal, CON had 84% higher arm GC (P= 0.012) and 87% higher leg GC (P= 0.016) compared with TYPE 2. During clamp, the difference between CON and TYPE 2 in arm GC was diminished to 54% but maintained at 80% in the leg. In conclusion, this study shows that glucose clearance is higher in arm than leg muscles, regardless of insulin resistance, which may indicate better preserved insulin sensitivity in arm than leg muscle in type 2 diabetes.
A pH‐sensitive potassium conductance (TASK) and its function in the murine gastrointestinal tract
Authors: Yun Cho Sang , Beckett Elizabeth A. , Baker Salah A. , Han Insoo , Park Kyu Joo , Monaghan Kevin , Ward Sean M. , Sanders Kenton M. , Koh Sang Don
Published: March 2005

The excitability of smooth muscles is regulated, in part, by background K+ conductances that determine resting membrane potential. However, the K+ conductances so far described in gastrointestinal (GI) muscles are not sufficient to explain the negative resting potentials of these cells. Here we describe expression of two‐pore K+ channels of the TASK family in murine small and large intestinal muscles. TASK‐2, cloned from murine intestinal muscles, resulted in a pH‐sensitive, time‐dependent, non‐inactivating K+ conductance with slow activation kinetics. A similar conductance was found in native intestinal myocytes using whole‐cell patch‐clamp conditions. The pH‐sensitive current was blocked by local anaesthetics. Lidocaine, bupivacaine and acidic pH depolarized circular muscle cells in intact muscles and decreased amplitude and frequency of slow waves. The effects of lidocaine were not blocked by tetraethylammonium chloride, 4‐aminopyridine, glibenclamide, apamin or MK‐499. However, depolarization by acidic pH was abolished by pre‐treatment with lidocaine, suggesting that lidocaine‐sensitive K+ channels were responsible for pH‐sensitive changes in membrane potential. The kinetics of activation, sensitivity to pH, and pharmacology of the conductance in intestinal myocytes and the expression of TASK‐1 and TASK‐2 in these cells suggest that the pH‐sensitive background conductance is encoded by TASK genes. This conductance appears to contribute significantly to resting potential and may regulate excitability of GI muscles.
Evolution of Oxygen Secretion in Fishes and the Emergence of a Complex Physiological System
Authors: Berenbrink Michael , Koldkjær Pia , Kepp Oliver , Cossins Andrew R.
Published: March 2005

We have reconstructed the events that led to the evolution of a key physiological innovation underpinning the large adaptive radiation of fishes, namely their unique ability to secrete molecular oxygen (O
2
). We show that O
2
secretion into the swimbladder evolved some 100 million years after another O
2
-secreting system in the eye. We unravel the likely sequence in which the functional components of both systems evolved. These components include ocular and swimbladder countercurrent exchangers, the Bohr and Root effects, the buffering power and surface histidine content of hemoglobins, and red blood cell Na
+
/H
+
exchange activity. Our synthesis reveals the dynamics of gains and losses of these multiple traits over time, accounting for part of the huge diversity of form and function in living fishes.
Response of XIAP, ARC, and FLIP apoptotic suppressors to 8 wk of treadmill running in rat heart and skeletal muscle
Authors: Siu Parco M. , Bryner Randall W. , Murlasits Zsolt , Alway Stephen E.
Published: March 2005

Although it has been demonstrated that exercise training has an antiapoptotic effect on postmitotic myocytes, the mechanisms responsible for this effect are still largely unclear. Because the antiapoptotic effect of exercise training in postmitotic myocytes could be possibly mediated by the upregulation of apoptotic suppressors, this study examined the effect of endurance training on endogenous apoptotic suppressors including X-chromosome-linked inhibitor of apoptosis protein (XIAP), apoptosis repressor with caspases recruitment domain protein (ARC), and FADD-like inhibitor protein (FLIP) in skeletal and cardiac muscles. Eight adult Sprague-Dawley rats were trained 5 days weekly for 8 wk on treadmill, and eight sedentary rats served as controls. Soleus and ventricle muscles were dissected 2 days after the last training session. The mRNA content of XIAP, ARC, and FLIP was estimated by RT-PCR with ribosomal 18S RNA used as an internal control. The protein expression of XIAP, ARC, FLIPS, and FLIPαwas assessed by Western immunoblot. After training, mRNA content of ARC and FLIP was not different between the control and trained animals, whereas XIAP mRNA content was elevated by 22 and 14% in the trained soleus and cardiac muscles, respectively, relative to the control samples. No difference was found in the protein content of FLIPSand FLIPαbetween control and trained muscles, whereas XIAP and ARC protein content was increased by 18 and 38%, respectively, in the soleus muscle of trained animals. Furthermore, negative relationships were found between XIAP and apoptotic DNA fragmentation as well as ARC and caspase-3 activity. These findings are consistent with the hypothesis that the modulation of apoptotic suppressors is involved in training-induced attenuation of apoptosis in skeletal and cardiac muscles.
Mutation Analysis of Autosomal Dominant Polycystic Kidney Disease Genes in Han Chinese
Authors: Zhang Shuzhong , Mei Changlin , Zhang Dianyong , Dai Bing , Tang Bing , Sun Tianmei , Zhao Haidan , Zhou Yukun , Li Lin , Wu Yumei , Wang Wenjing , Shen Xuefei , Song Ji
Published: March 2005

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in two genes, PKD1 and PKD2. The complexity of these genes, particularly PKD1, has complicated genetic screening, though recent advances have provided new opportunities for amplifying these genes. In the Han Chinese population, no complete mutational analysis has previously been conducted across the entire span of PKD1 and PKD2. Here, we used single-strand conformation polymorphism (SSCP) analysis to screen the entire coding sequence of PKD1 and PKD2 in 85 healthy controls and 72 Han Chinese from 24 ADPKD pedigrees. In addition to 11 normal variants, we identified 17 mutations (12 in PKD1 and 5 in PKD2), 15 of which were novel ones (11 for PKD1 and 4 for PKD2). We did not identify any seeming mutational hot spots in PKD1 and PKD2. Notably, we found several disease-associated C–T or G–A mutations that led to charge or hydrophobicity changes in the corresponding amino acids. This suggests that the mutations cause conformational alterations in the PKD1 and PKD2 protein products that may impact the normal protein functions. Our study is the first report of screenable mutations in the full-length PKD1 and PKD2 genes of the Han Chinese, and also offers a benchmark for comparisons between Caucasian and Han ADPKD pedigrees and patients.
Combining Affymetrix microarray results
Authors: Stevens John R , Doerge RW
Published: March 2005

Background

As the use of microarray technology becomes more prevalent it is not unusual to find several laboratories employing the same microarray technology to identify genes related to the same condition in the same species. Although the experimental specifics are similar, typically a different list of statistically significant genes result from each data analysis.

Results

We propose a statistically-based meta-analytic approach to microarray analysis for the purpose of systematically combining results from the different laboratories. This approach provides a more precise view of genes that are significantly related to the condition of interest while simultaneously allowing for differences between laboratories. Of particular interest is the widely used Affymetrix oligonucleotide array, the results of which are naturally suited to a meta-analysis. A simulation model based on the Affymetrix platform is developed to examine the adaptive nature of the meta-analytic approach and to illustrate the usefulness of such an approach in combining microarray results across laboratories. The approach is then applied to real data involving a mouse model for multiple sclerosis.

Conclusion

The quantitative estimates from the meta-analysis model tend to be closer to the "true" degree of differential expression than any single lab. Meta-analytic methods can systematically combine Affymetrix results from different laboratories to gain a clearer understanding of genes' relationships to specific conditions of interest.
Towards precise classification of cancers based on robust gene functional expression profiles
Authors: Guo Zheng , Zhang Tianwen , Li Xia , Wang Qi , Xu Jianzhen , Yu Hui , Zhu Jing , Wang Haiyun , Wang Chenguang , Topol Eric J , Wang Qing , Rao Shaoqi
Published: March 2005

Background

Development of robust and efficient methods for analyzing and interpreting high dimension gene expression profiles continues to be a focus in computational biology. The accumulated experiment evidence supports the assumption that genes express and perform their functions in modular fashions in cells. Therefore, there is an open space for development of the timely and relevant computational algorithms that use robust functional expression profiles towards precise classification of complex human diseases at the modular level.

Results

Inspired by the insight that genes act as a module to carry out a highly integrated cellular function, we thus define a low dimension functional expression profile for data reduction. After annotating each individual gene to functional categories defined in a proper gene function classification system such as Gene Ontology applied in this study, we identify those functional categories enriched with differentially expressed genes. For each functional category or functional module, we compute a summary measure (s) for the raw expression values of the annotated genes to capture the overall activity level of the module. In this way, we can treat the gene expressions within a functional module as an integrative data point to replace the multiple values of individual genes. We compare the classification performance of decision trees based on functional expression profiles with the conventional gene expression profiles using four publicly available datasets, which indicates that precise classification of tumour types and improved interpretation can be achieved with the reduced functional expression profiles.

Conclusion

This modular approach is demonstrated to be a powerful alternative approach to analyzing high dimension microarray data and is robust to high measurement noise and intrinsic biological variance inherent in microarray data. Furthermore, efficient integration with current biological knowledge has facilitated the interpretation of the underlying molecular mechanisms for complex human diseases at the modular level.