bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutrition transition among adolescents of a south-Mediterranean country: dietary patterns, association with socio-economic factors, overweight and blood pressure. A cross-sectional study in Tunisia
Authors: Aounallah-Skhiri Hajer , Traissac Pierre , El Ati Jalila , Eymard-Duvernay Sabrina , Landais Edwige , Achour Noureddine , Delpeuch Francis , Romdhane Habiba Ben , Maire Bernard
Published: April 2011

Background

The increase in the burden of chronic diseases linked to the nutrition transition and associated dietary and lifestyle changes is of growing concern in south and east Mediterranean countries and adolescents are at the forefront of these changes. This study assessed dietary intake and association with socio-economic factors and health outcomes among adolescents in Tunisia.

Methods

Cross-sectional survey (year 2005); 1019 subjects 15-19 y. from a clustered random sample. Dietary intake was assessed by a validated semi-quantitative frequency questionnaire (134 items) as was physical activity; the Diet Quality Index International measured diet quality; dietary patterns were derived by multiple correspondence analysis from intakes of 43 food groups. Body Mass Index (BMI) ≥85thand 95thpercentile defined overweight and obesity. Waist Circumference (WC) assessed abdominal fat. High blood pressure was systolic (SBP) or diastolic blood pressure (DBP) ≥90thof the international reference for 15-17 y., and SBP/DBP ≥120/80 mm Hg for 18-19 y.

Results

Energy intake levels were quite high, especially for females. The macro-nutrient structure was close to recommendations but only 38% had a satisfactory diet quality. A main traditional to modern dietary gradient, linked to urbanisation and increased economic level, featured an increasing consumption of white bread, dairy products, sugars, added fats and fruits and decreasing consumption of oils, grains, legumes and vegetables; regarding nutrients this modern diet score featured a decreasing relationship with total fat and an increase of calcium intake, but with an increase of energy, sugars and saturated fat, while vitamin C, potassium and fibre decreased. Adjusted for age, energy and physical activity, this modern pattern was associated with increased overweight in males (2ndvs. 1sttertile: Prevalence Odds-Ratio (POR) = 4.0[1.7-9.3], 3rdvs. 1st: POR = 3.3[1.3-8.7]) and a higher WC. Adjusting also for BMI and WC, among females, it was associated with decreased prevalence of high blood pressure (2ndvs. 1sttertile: POR = 0.5[0.3-0.8], 3rdvs. 1sttertile: POR = 0.4[0.2-0.8]).

Conclusion

The dietary intake contrasts among Tunisian adolescents, linked to socio-economic differentials are characteristic of a nutrition transition situation. The observed gradient of modernisation of dietary intake features associations with several nutrients involving a higher risk of chronic diseases but might have not only negative characteristics regarding health outcomes.
Comparison of morphological changes in efferent lymph nodes after implantation of resorbable and non-resorbable implants in rabbits
Authors: Bondarenko Alexandr , Hewicker-Trautwein Marion , Erdmann Nina , Angrisani Nina , Reifenrath Janin , Meyer-Lindenberg Andrea
Published: April 2011

Background

Magnesium alloys as biodegradable implant materials received much interest in recent years. It is known that products of implant degradation can induce several types of immune response. Hence, the aim of this study was to examine the morphological changes of efferent lymph nodes after implantation of different resorbable magnesium alloys (MgCa0.8, LAE442) in comparison to commercially available resorbable (PLA) and non-resorbable (titanium) implant materials as well as control groups without implant material.

Methods

The different implant materials were inserted intramedullary into the rabbit tibia. After postoperative observation periods of three and six months, popliteal lymph nodes were examined histologically and immunhistologically and compared to lymph nodes of sham operated animals and animals without surgery. Haematoxylin and eosin staining was performed for cell differentiation. Mouse anti-CD79α and rat anti-CD3 monoclonal primary antibodies were used for B- and T-lymphocyte detection, mouse anti-CD68 primary antibodies for macrophage detection. Evaluation of all sections was performed applying a semi quantitative score.

Results

The histological evaluation demonstrated low and moderate levels of morphological changes for both magnesium alloys (LAE442 and MgCa0.8). Higher than moderate values were reached for titanium in sinus histiocytosis and histiocytic apoptosis (3 months) and for PLA in histiocytic apoptosis (3 and 6 months). The immune response to all investigated implants had a non-specific character and predominantly was a foreign-body reaction. LAE442 provoked the lowest changes which might be due to a lower degradation rate in comparison to MgCa0.8. Therewith it is a promising candidate for implants with low immunogenic potential.

Conclusion

Both examined magnesium alloys did not cause significantly increased morphological changes in efferent lymph nodes in comparison to the widely used implant materials titanium and PLA. LAE442 induced even lower immunological reactions. Therewith MgCa0.8 and especially LAE442 are appropriate candidates for biomedical use.
Review of Zero-D and 1-D Models of Blood Flow in the Cardiovascular System
Authors: Shi Yubing , Lawford Patricia , Hose Rodney
Published: April 2011

Background

Zero-dimensional (lumped parameter) and one dimensional models, based on simplified representations of the components of the cardiovascular system, can contribute strongly to our understanding of circulatory physiology. Zero-D models provide a concise way to evaluate the haemodynamic interactions among the cardiovascular organs, whilst one-D (distributed parameter) models add the facility to represent efficiently the effects of pulse wave transmission in the arterial network at greatly reduced computational expense compared to higher dimensional computational fluid dynamics studies. There is extensive literature on both types of models.

Method and Results

The purpose of this review article is to summarise published 0D and 1D models of the cardiovascular system, to explore their limitations and range of application, and to provide an indication of the physiological phenomena that can be included in these representations. The review on 0D models collects together in one place a description of the range of models that have been used to describe the various characteristics of cardiovascular response, together with the factors that influence it. Such models generally feature the major components of the system, such as the heart, the heart valves and the vasculature. The models are categorised in terms of the features of the system that they are able to represent, their complexity and range of application: representations of effects including pressure-dependent vessel properties, interaction between the heart chambers, neuro-regulation and auto-regulation are explored. The examination on 1D models covers various methods for the assembly, discretisation and solution of the governing equations, in conjunction with a report of the definition and treatment of boundary conditions. Increasingly, 0D and 1D models are used in multi-scale models, in which their primary role is to provide boundary conditions for sophisticate, and often patient-specific, 2D and 3D models, and this application is also addressed. As an example of 0D cardiovascular modelling, a small selection of simple models have been represented in the CellML mark-up language and uploaded to the CellML model repository http://models.cellml.org/. They are freely available to the research and education communities.

Conclusion

Each published cardiovascular model has merit for particular applications. This review categorises 0D and 1D models, highlights their advantages and disadvantages, and thus provides guidance on the selection of models to assist various cardiovascular modelling studies. It also identifies directions for further development, as well as current challenges in the wider use of these models including service to represent boundary conditions for local 3D models and translation to clinical application.
Placentation in Sigmodontinae: a rodent taxon native to South America
Authors: Favaron Phelipe O , Carter Anthony M , Ambrósio Carlos E , Morini Adriana C , Mess Andrea M , de Oliveira Moacir F , Miglino Maria A
Published: April 2011

Background

Sigmodontinae, known as "New World rats and mice," is a large subfamily of Cricetidae for which we herein provide the first comprehensive investigation of the placenta.

Methods

Placentas of various gestational ages ranging from early pregnancy to near term were obtained for five genera, i.e. Necromys, Euryoryzomys, Cerradomys, Hylaeamys, and Oligoryzomys. They were investigated by means of histology, immunohistochemistry, a proliferation marker, DBA-lectin staining and transmission electron microscopy.

Results

The chorioallantoic placenta was organized in a labyrinthine zone, spongy zone and decidua and an inverted yolk sac persisted until term. The chorioallantoic placenta was hemotrichorial. The interhemal barrier comprised fetal capillary endothelium and three layers of trophoblast, an outermost, cellular layer and two syncytial ones, with interspersed trophoblast giant cells (TGC). In addition, accumulations of TGC occurred below Reichert's membrane. The junctional zone contained syncytial trophoblast, proliferative cellular trophoblast, glycogen cells and TGC that were situated near to the maternal blood channels. In three of the genera, TGC were also accumulated in distinct areas at the placental periphery. PAS-positive glycogen cells derived from the junctional zone invaded the decidua. Abundant maternal uNK cells with positive response to PAS, vimentin and DBA-lectin were found in the decidua. The visceral yolk sac was completely inverted and villous.

Conclusion

The general aspect of the fetal membranes in Sigmodontinae resembled that found in other cricetid rodents. Compared to murid rodents there were larger numbers of giant cells and in some genera these were seen to congregate at the periphery of the placental disk. Glycogen cells were found to invade the decidua but we did not identify trophoblast in the walls of the deeper decidual arteries. In contrast these vessels were surrounded by large numbers of uNK cells. This survey of wild-trapped specimens from five genera is a useful starting point for the study of placentation in an important subfamily of South American rodents. We note, however, that some of these rodents can be captive bred and recommend that future studies focus on the study of time dated pregnancies.
Overweight worsens apoptosis, neuroinflammation and blood-brain barrier damage after hypoxic ischemia in neonatal brain through JNK hyperactivation
Authors: Tu Yi-Fang , Tsai Yau-Sheng , Wang Lan-Wan , Wu Hsin-Chieh , Huang Chao-Ching , Ho Chien-Jung
Published: April 2011

Background

Apoptosis, neuroinflammation and blood-brain barrier (BBB) damage affect the susceptibility of the developing brain to hypoxic-ischemic (HI) insults. c-Jun N-terminal kinase (JNK) is an important mediator of insulin resistance in obesity. We hypothesized that neonatal overweight aggravates HI brain damage through JNK hyperactivation-mediated upregulation of neuronal apoptosis, neuroinflammation and BBB leakage in rat pups.

Methods

Overweight (OF) pups were established by reducing the litter size to 6, and control (NF) pups by keeping the litter size at 12 from postnatal (P) day 1 before HI on P7. Immunohistochemistry and immunoblotting were used to determine the TUNEL-(+) cells and BBB damage, cleaved caspase-3 and poly (ADP-ribose) polymerase (PARP), and phospho-JNK and phospho-BimEL levels. Immunofluorescence was performed to determine the cellular distribution of phospho-JNK.

Results

Compared with NF pups, OF pups had a significantly heavier body-weight and greater fat deposition on P7. Compared with the NF-HI group, the OF-HI group showed significant increases of TUNEL-(+) cells, cleaved levels of caspase-3 and PARP, and ED1-(+) activated microglia and BBB damage in the cortex 24 hours post-HI. Immunofluorescence of the OF-HI pups showed that activated-caspase 3 expression was found mainly in NeuN-(+) neurons and RECA1-(+) vascular endothelial cells 24 hours post-HI. The OF-HI group also had prolonged escape latency in the Morris water maze test and greater brain-volume loss compared with the NF-HI group when assessed at adulthood. Phospho-JNK and phospho-BimEL levels were higher in OF-HI pups than in NF-HI pups immediately post-HI. JNK activation in OF-HI pups was mainly expressed in neurons, microglia and vascular endothelial cells. Inhibiting JNK activity by AS601245 caused more attenuation of cleaved caspase-3 and PARP, a greater reduction of microglial activation and BBB damage post-HI, and significantly reduced brain damage in OF-HI than in NF-HI pups.

Conclusions

Neonatal overweight increased HI-induced neuronal apoptosis, microglial activation and BBB damage, and aggravated HI brain damage in rat pups through JNK hyperactivation.
Improving the prediction of yeast protein function using weighted protein-protein interactions
Authors: Ahmed Khaled S , Saloma Nahed H , Kadah Yasser M
Published: April 2011

Background

Bioinformatics can be used to predict protein function, leading to an understanding of cellular activities, and equally-weighted protein-protein interactions (PPI) are normally used to predict such protein functions. The present study provides a weighting strategy for PPI to improve the prediction of protein functions. The weights are dependent on the local and global network topologies and the number of experimental verification methods. The proposed methods were applied to the yeast proteome and integrated with the neighbour counting method to predict the functions of unknown proteins.

Results

A new technique to weight interactions in the yeast proteome is presented. The weights are related to the network topology (local and global) and the number of identified methods, and the results revealed improvement in the sensitivity and specificity of prediction in terms of cellular role and cellular locations. This method (new weights) was compared with a method that utilises interactions with the same weight and it was shown to be superior.

Conclusions

A new method for weighting the interactions in protein-protein interaction networks is presented. Experimental results concerning yeast proteins demonstrated that weighting interactions integrated with the neighbor counting method improved the sensitivity and specificity of prediction in terms of two functional categories: cellular role and cell locations.
Sequence characteristics of T4-like bacteriophage IME08 genome termini revealed by high throughput sequencing
Authors: Jiang Xiaofang , Jiang Huanhuan , Li Cun , Wang Sheng , Mi Zhiqiang , An Xiaoping , Chen Jiankui , Tong Yigang
Published: April 2011

Background

T4 phage is a model species that has contributed broadly to our understanding of molecular biology. T4 DNA replication and packaging share various mechanisms with human double-stranded DNA viruses such as herpes virus. The literature indicates that T4-like phage genomes have permuted terminal sequences, and are generated by a DNA terminase in a sequence-independent manner;

Methods

genomic DNA of T4-like bacteriophage IME08 was subjected to high throughput sequencing, and the read sequences with extraordinarily high occurrences were analyzed;

Results

we demonstrate that both the 5' and 3' termini of the IME08 genome starts with base G or A. The presence of a consensus sequence TTGGA|G around the breakpoint of the high frequency read sequences suggests that the terminase cuts the branched pre-genome in a sequence-preferred manner. Our analysis also shows that terminal cleavage is asymmetric, with one end cut at a consensus sequence, and the other end generated randomly. The sequence-preferred cleavage may produce sticky-ends, but with each end being packaged with different efficiencies;

Conclusions

this study illustrates how high throughput sequencing can be used to probe replication and packaging mechanisms in bacteriophages and/or viruses.
Molecular detection of multiple viral targets in untreated urban sewage from Greece
Authors: Kokkinos Petros A , Ziros Panos G , Mpalasopoulou Αggeliki , Galanis Alexis , Vantarakis Apostolos
Published: April 2011

Background

Urban sewage virological analysis may produce important information about the strains that cause clinical and subclinical infections in the population, thus supporting epidemiological studies.

Methods

In the present study, a twenty one-month survey (November 2007 to July 2009) was conducted in order to evaluate the presence of human adenoviruses (hAdV), hepatitis A viruses (HAV), hepatitis E viruses (HEV), Noroviruses (NoV), and human Polyomaviruses (hPyV) in untreated sewage samples collected from the inlet of Patras' municipal biological wastewater treatment plant, located in southwestern Greece. Nucleic acid amplification techniques were applied for viral nucleic acid detection. Positive samples were confirmed by sequencing and comparative phylogenetic analysis was performed on the isolated viral strains.

Results

In total, viruses were detected in 87.5% (42/48) of sewage samples. AdVs, PyVs, HAV, and NoVs were detected in 45.8% (22/48), 68.8% (33/48), 8.3% (4/48), and 6.3% (3/48) of the samples collected from the plant's inlet, while HEV was not detected at all. Adenovirus types 8 (Ad8), 40 (Ad40) and 41 (Ad41) were recognized, while JC and BK polyomaviruses were recorded. Noroviruses were identified as GII.4. HAV was typed as genotype IA.

Conclusions

Our study demonstrates the advantages of environmental surveillance as a tool to elucidate the molecular epidemiology of community circulating viruses. We underline the need of environmental surveillance programs in countries such as Greece with inadequate and problematic epidemiological surveillance system and no environmental surveillance system currently in action.
Multimodal Assessment of Painful Peripheral Neuropathy Induced by Chronic Oxaliplatin-Based Chemotherapy in Mice
Authors: Renn Cynthia L , Carozzi Valentina A , Rhee Peter , Gallop Danisha , Dorsey Susan G , Cavaletti Guido
Published: April 2011

Background:

A major clinical issue affecting 10-40% of cancer patients treated with oxaliplatin is severe peripheral neuropathy with symptoms including cold sensitivity and neuropathic pain. Rat models have been used to describe the pathological features of oxaliplatin-induced peripheral neuropathy; however, they are inadequate for parallel studies of oxaliplatin's antineoplastic activity and neurotoxicity because most cancer models are developed in mice. Thus, we characterized the effects of chronic, bi-weekly administration of oxaliplatin in BALB/c mice. We first studied oxaliplatin's effects on the peripheral nervous system by measuring caudal and digital nerve conduction velocities (NCV) followed by ultrastructural and morphometric analyses of dorsal root ganglia (DRG) and sciatic nerves. To further characterize the model, we examined nocifensive behavior and central nervous system excitability by in vivo electrophysiological recording of spinal dorsal horn (SDH) wide dynamic range neurons in oxaliplatin-treated mice

Results:

We found significantly decreased NCV and action potential amplitude after oxaliplatin treatment along with neuronal atrophy and multinucleolated DRG neurons that have eccentric nucleoli. Oxaliplatin also induced significant mechanical allodynia and cold hyperalgesia, starting from the first week of treatment, and a significant increase in the activity of wide dynamic range neurons in the SDH.

Conclusions:

Our findings demonstrate that chronic treatment with oxaliplatin produces neurotoxic changes in BALB/c mice, confirming that this model is a suitable tool to conduct further mechanistic studies of oxaliplatin-related antineoplastic activity, peripheral neurotoxicity and pain. Further, this model can be used for the preclinical discovery of new neuroprotective and analgesic compounds.
Value of diffusion weighted MR imaging as an early surrogate parameter for evaluation of tumor response to high-dose-rate brachytherapy of colorectal liver metastases
Authors: Wybranski Christian , Zeile Martin , Löwenthal David , Fischbach Frank , Pech Maciej , Röhl Friedrich-Wilhelm , Gademann Günther , Ricke Jens , Dudeck Oliver
Published: April 2011

Background

To assess the value of diffusion weighted imaging (DWI) as an early surrogate parameter for treatment response of colorectal liver metastases to image-guided single-fraction 192Ir-high-dose-rate brachytherapy (HDR-BT).

Methods

Thirty patients with a total of 43 metastases underwent CT- or MRI-guided HDR-BT. In 13 of these patients a total of 15 additional lesions were identified, which were not treated at the initial session and served for comparison. Magnetic resonance imaging (MRI) including breathhold echoplanar DWI sequences was performed prior to therapy (baseline MRI), 2 days after HDR-BT (early MRI) as well as after 3 months (follow-up MRI). Tumor volume (TV) and intratumoral apparent diffusion coefficient (ADC) were measured independently by two radiologists. Statistical analysis was performed using univariate comparison, ANOVA and paired t test as well as Pearson's correlation.

Results

At early MRI no changes of TV and ADC were found for non-treated colorectal liver metastases. In contrast, mean TV of liver lesions treated with HDR-BT increased by 8.8% (p = 0.054) while mean tumor ADC decreased significantly by 11.4% (p < 0.001). At follow-up MRI mean TV of non-treated metastases increased by 50.8% (p = 0.027) without significant change of mean ADC values. In contrast, mean TV of treated lesions decreased by 47.0% (p = 0.026) while the mean ADC increased inversely by 28.6% compared to baseline values (p < 0.001; Pearson's correlation coefficient of r = -0.257; p < 0.001).

Conclusions

DWI is a promising imaging biomarker for early prediction of tumor response in patients with colorectal liver metastases treated with HDR-BT, yet the optimal interval between therapy and early follow-up needs to be elucidated.
Longitudinal evaluation the pulmonary function of the pre and postoperative periods in the coronary artery bypass graft surgery of patients treated with a physiotherapy protocol
Authors: Moreno Adalgiza M , Castro Renata RT , Sorares Pedro PS , Anna Mauricio Sant' , Cravo Sergio LD , Nóbrega Antônio CL
Published: April 2011

Background

The treatment of coronary artery disease (CAD) seeks to reduce or prevent its complications and decrease morbidity and mortality. For certain subgroups of patients, coronary artery bypass graft surgery (CABG) may accomplish these goals. The objective of this study was to assess the pulmonary function in the CABG postoperative period of patients treated with a physiotherapy protocol.

Methods

Forty-two volunteers with an average age of 63 ± 2 years were included and separated into three groups: healthy volunteers (n = 09), patients with CAD (n = 9) and patients who underwent CABG (n = 20). Patients from the CABG group received preoperative and postoperative evaluations on days 3, 6, 15 and 30. Patients from the CAD group had evaluations on days 1 and 30 of the study, and the healthy volunteers were evaluated on day 1. Pulmonary function was evaluated by measuring forced vital capacity (FVC), maximum expiratory pressure (MEP) and Maximum inspiratory pressure (MIP).

Results

After CABG, there was a significant decrease in pulmonary function (p < 0.05), which was the worst on postoperative day 3 and returned to the preoperative baseline on postoperative day 30.

Conclusion

Pulmonary function decreased after CABG. Pulmonary function was the worst on postoperative day 3 and began to improve on postoperative day 15. Pulmonary function returned to the preoperative baseline on postoperative day 30.
A mutation in the dynein heavy chain gene compensates for energy deficit of mutant SOD1 mice and increases potentially neuroprotective IGF-1
Authors: Fergani Anissa , Eschbach Judith , Oudart Hugues , Larmet Yves , Schwalenstocker Birgit , Ludolph Albert C , Loeffler Jean-Philippe , Dupuis Luc
Published: April 2011

Background

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons. ALS patients, as well as animal models such as mice overexpressing mutant SOD1s, are characterized by increased energy expenditure. In mice, this hypermetabolism leads to energy deficit and precipitates motor neuron degeneration. Recent studies have shown that mutations in the gene encoding the dynein heavy chain protein are able to extend lifespan of mutant SOD1 mice. It remains unknown whether the protection offered by these dynein mutations relies on a compensation of energy metabolism defects.

Results

SOD1(G93A) mice were crossbred with mice harboring the dynein mutant Cramping allele (Cra/+ mice). Dynein mutation increased adipose stores in compound transgenic mice through increasing carbohydrate oxidation and sparing lipids. Metabolic changes that occurred in double transgenic mice were accompanied by the normalization of the expression of key mRNAs in the white adipose tissue and liver. Furthermore, Dynein Cra mutation rescued decreased post-prandial plasma triglycerides and decreased non esterified fatty acids upon fasting. In SOD1(G93A) mice, the dynein Cra mutation led to increased expression of IGF-1 in the liver, increased systemic IGF-1 and, most importantly, to increased spinal IGF-1 levels that are potentially neuroprotective.

Conclusions

These findings suggest that the protection against SOD1(G93A) offered by the Cramping mutation in the dynein gene is, at least partially, mediated by a reversal in energy deficit and increased IGF-1 availability to motor neurons.
Improving prehospital trauma management for skiers and snowboarders - need for on-slope triage?
Authors: Hasler Rebecca M , Schmucker Uli , Evangelopoulos Dimitrios S , Hirschberg Ron E , Zimmermann Heinz , Exadaktylos Aristomenis K
Published: April 2011

Background

Injuries from skiing and snowboarding became a major challenge for emergency care providers in Switzerland. In the alpine setting, early assessment of injury and health status is essential for the initiation of adequate means of care and transport. Nevertheless, validated standardized protocols for on-slope triage are missing. This article can assist in understanding the characteristics of injured winter sportsmen and exigencies for future on-slope triage protocols.

Methods

Six-year review of trauma cases in a tertiary trauma centre. Consecutive inclusion of all injured skiers and snowboarders aged >15 (total sample) years with predefined, severe injury to the head, spine, chest, pelvis or abdomen (study sample) presenting at or being transferred to the study hospital. Descriptive analysis of age, gender and injury pattern.

Results

Amongst 729 subjects (total sample) injured from skiing or snowboarding, 401 (55%, 54% of skiers and 58% of snowboarders) suffered from isolated limb injury. Amongst the remaining 328 subjects (study sample), the majority (78%) presented with monotrauma. In the study sample, injury to the head (52%) and spine (43%) was more frequent than injury to the chest (21%), pelvis (8%), and abdomen (5%). The three most frequent injury combinations were head/spine (10% of study sample), head/thorax (9%), and spine/thorax (6%). Fisher's exact test demonstrated an association for injury combinations of head/thorax (p < 0.001), head/abdomen (p = 0.019), and thorax/abdomen (p < 0.001).

Conclusion

The data presented and the findings from previous investigations indicate the need for development of dedicated on-slope triage protocols. Future research must address the validity and practicality of diagnostic on-slope tests for rapid decision making by both professional and lay first responders. Thus, large-scale and detailed injury surveillance is the future research priority.
An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models
Authors: Donatello Simona , Hudson Lance , Cottell David C , Blanco Alfonso , Aurrekoetxea Igor , Shelly Martin J , Dervan Peter A , Kell Malcolm R , Stokes Maurice , Hill Arnold DK , Hopkins Ann M
Published: April 2011

Background

Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression.

Methods

Primary cultures were established from human breast tumour and adjacent non-tumour tissue. Putative progenitor cell populations were isolated based on co-expression or concomitant absence of the epithelial and myoepithelial markers EPCAM and CALLA respectively.

Results

Significant reductions in cellular senescence were observed in tumour versus non-tumour cultures, accompanied by a stepwise increase in proliferation:senescence ratios. A novel correlation between tumour aggressiveness and an imbalance of putative progenitor subpopulations was also observed. Specifically, an increased double-negative (DN) to double-positive (DP) ratio distinguished aggressive tumours of high grade, estrogen receptor-negativity or HER2-positivity. The DN:DP ratio was also higher in malignant MDA-MB-231 cells relative to non-tumourogenic MCF-10A cells. Ultrastructural analysis of the DN subpopulation in an invasive tumour culture revealed enrichment in lipofuscin bodies, markers of ageing or senescent cells.

Conclusions

Our results suggest that an imbalance in tumour progenitor subpopulations imbalances the functional relationship between proliferation and senescence, creating a microenvironment favouring tumour progression.
MUC4 stabilizes HER2 expression and maintains the cancer stem cell population in ovarian cancer cells
Authors: Ponnusamy Moorthy P , Seshacharyulu Parthasarathy , Vaz ArokiaPriyanka , Dey Parama , Batra Surinder K
Published: April 2011

Background

Recent evidence has suggested that the capability of cancer to grow, propagate and relapse after therapy is dependent on a small subset of the cell population within the tumor, called cancer stem cells. Therefore, this subpopulation of cells needs to be targeted with different approaches by identification of unique stem-cell specific target antigens. One of the well known tumor antigens is the epithelial cell mucin MUC4, which is aberrantly expressed in ovarian cancer as compared to the normal ovary and plays a pivotal role in the aggressiveness and metastasis of ovarian cancer cells. In the present study, we aimed to analyze the cancer stem cell population in MUC4 overexpressed ovarian cancer cells.

Methods

MUC4 was ectopically overexpressed in SKOV3 ovarian cancer cells. Western blot analysis was performed for MUC4, HER2, CD133, ALDH1 and Shh expression in MUC4 overexpressed cells. Confocal analysis of MUC4, HER2 and CD133 was also done in the MUC4 overexpressed cells. CD133 and Hoechst33342 dye staining was used to analyze the cancer stem cell population via FACS method in SKOV3-MUC4 cells.

Results

MUC4 overexpressed SKOV3 cells showed an increased expression of HER2 compared to control cells. MUC4 overexpression leads to increased (0.1%) side population (SP) and CD133-positive cancer stem cells compared to the control cells. Interestingly, the tumor sphere type circular colony formation was observed only in the MUC4 overexpressed ovarian cancer cells. Furthermore, the cancer stem cell marker CD133 was expressed along with MUC4 in the isolated circular colonies as analyzed by both confocal and western blot analysis. HER2 and cancer stem cell specific marker ALDH1 along with Shh, a self-renewal marker, showed increased expression in the isolated circular colonies compared to MUC4-transfected cells.

Conclusion

These studies demonstrate that MUC4 overexpression leads to an enriched ovarian cancer stem cell population either directly or indirectly through HER2. In future, this study would be helpful for MUC4-directed therapy for the ovarian cancer stem cell population.
Clinical relevance of findings in trials of antipsychotics: systematic review
Authors: Lepping Peter , Sambhi Rajvinder S. , Whittington Richard , Lane Steven , Poole Rob
Published: April 2011

Background

There is concern over the methods used to evaluate antipsychotic drugs.

Aims

To assess the clinical relevance of findings in the literature.

Method

A systematic review identified studies of antipsychotics that used the Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Syndrome Scale (PANSS). A published method of translating these into Clinical Global Impression – Change scale (CGI–C) scores was used to measure clinical relevance.

Results

In total 98 data-sets were included in the BPRS analysis and 202 data-sets in the PANSS analysis. When aggregated scores were translated into notional CGI–C scores, most drugs reached ‘minimal improvement’ on the BPRS, but few reached that level for PANSS. This was true of both first- and second-generation drugs, including clozapine. Amisulpride and olanzapine had better than average CGI–C scores.

Conclusions

Our findings show improvements of limited clinical relevance. The CGI–C scores were better for the BPRS than for the PANSS.
Disease-modifying properties of long-term lithium treatment for
amnestic mild cognitive impairment: randomised controlled
trial
Authors: Forlenza Orestes V. , Diniz Breno S. , Radanovic Márcia , Santos Franklin S. , Talib Leda L. , Gattaz Wagner F.
Published: April 2011

Background

Two recent clinical studies support the feasibility of trials to evaluate
the disease-modifying properties of lithium in Alzheimer's disease,
although no benefits were obtained from short-term treatment.

Aims

To evaluate the effect of long-term lithium treatment on cognitive and
biological outcomes in people with amnestic mild cognitive impairment
(aMCI).

Method

Forty-five participants with aMCI were randomised to receive lithium
(0.25–0.5 mmol/l) (n = 24) or placebo
(n = 21) in a 12-month, double-blind trial. Primary
outcome measures were the modification of cognitive and functional test
scores, and concentrations of cerebrospinal fluid (CSF) biomarkers
(amyloid-beta peptide (Aβ42), total tau (T-tau),
phosphorylated-tau) (P-tau). Trial registration: NCT01055392.

Results

Lithium treatment was associated with a significant decrease in CSF
concentrations of P-tau (P = 0.03) and better
perform-ance on the cognitive subscale of the Alzheimer's Disease
Assessment Scale and in attention tasks. Overall tolerability of lithium
was good and the adherence rate was 91%.

Conclusions

The present data support the notion that lithium has disease-modifying
properties with potential clinical implications in the prevention of
Alzheimer's disease.
Impact of screening for risk of suicide: randomised controlled
trial
Authors: Crawford Mike J. , Thana Lavanya , Methuen Caroline , Ghosh Pradip , Stanley Sian V. , Ross Juliette , Gordon Fabiana , Blair Grant , Bajaj Priya
Published: April 2011

Background

Concerns have been expressed about the impact that screening for risk of
suicide may have on a person's mental health.

Aims

To examine whether screening for suicidal ideation among people who
attend primary care services and have signs of depression increases the
short-term incidence of feeling that life is not worth living.

Method

In a multicentre, single-blind, randomised controlled trial, 443 patients
in four general practices were randomised to screening for suicidal
ideation or control questions on health and lifestyle (trial
registration: ISRCTN84692657). The primary outcome was thinking that life
is not worth living measured 10–14 days after randomisation. Secondary
outcome measures comprised other aspects of suicidal ideation and
behaviour.

Results

A total of 443 participants were randomised to early (n
= 230) or delayed screening (n = 213). Their mean age
was 48.5 years (s.d. = 18.4, range 16–92) and 137 (30.9%) were male. The
adjusted odds of experiencing thoughts that life was not worth living at
follow-up among those randomised to early compared with delayed screening
was 0.88 (95% CI 0.66–1.18). Differences in secondary outcomes between
the two groups were not seen. Among those randomised to early screening,
37 people (22.3%) reported thinking about taking their life at baseline
and 24 (14.6%) that they had this thought 2 weeks later.

Conclusions

Screening for suicidal ideation in primary care among people who have
signs of depression does not appear to induce feelings that life is not
worth living.
Annual high-dose vitamin D3and mental well-being: randomised controlled trial
Authors: Sanders Kerrie M. , Stuart Amanda L. , Williamson Elizabeth J. , Jacka Felice N. , Dodd Seetal , Nicholson Geoff , Berk Michael
Published: April 2011

Background

Epidemiological evidence supports a relationship between vitamin D and mental well-being, although evidence from large-scale placebo-controlled intervention trials is lacking.

Aims

To examine if vitamin D supplementation has a beneficial effect on mood in community-dwelling older women; if a single annual large dose of vitamin D has a role in the prevention of depressive symptoms; and if there is an association between serum 25-hydroxyvitamin D levels and mental health.

Method

A double-blind, randomised, placebo-controlled trial of women aged 70 or older (the Vital D Study: ISRCTN83409867 and ACTR12605000658617). Participants were randomly assigned to receive 500 000 IU vitamin D3(cholecalciferol) orally or placebo every autumn/winter for 3–5 consecutive years. The tools utilised at various time points were the General Health Questionnaire, the 12-item Short Form Health Survey, the Patient Global Impression–Improvement scale and the WHO Well-Being Index. Serum 25-hydroxyvitamin D levels were measured in a subset of 102 participants.

Results

In this non-clinical population, no significant differences between the vitamin D and placebo groups were detected in any of the measured outcomes of mental health. Serum 25-hydroxyvitamin D levels in the vitamin D group were 41% higher than the placebo group 12 months following their annual dose. Despite this difference, scores from the questionnaires did not differ. Furthermore, there was no interaction between those on antidepressant/anxiety medication at baseline and the treatment groups.

Conclusions

The lack of improvement in indices of mental well-being in the vitamin D group does not support the hypothesis that an annual high dose of vitamin D3is a practical intervention to prevent depressive symptoms in older community-dwelling women.
Lithium in drinking water and suicide mortality
Authors: Kapusta Nestor D. , Mossaheb Nilufar , Etzersdorfer Elmar , Hlavin Gerald , Thau Kenneth , Willeit Matthäus , Praschak-Rieder Nicole , Sonneck Gernot , Leithner-Dziubas Katharina
Published: April 2011

Background

There is some evidence that natural levels of lithium in drinking water may have a protective effect on suicide mortality.

Aims

To evaluate the association between local lithium levels in drinking water and suicide mortality at district level in Austria.

Method

A nationwide sample of 6460 lithium measurements was examined for association with suicide rates per 100 000 population and suicide standardised mortality ratios across all 99 Austrian districts. Multivariate regression models were adjusted for well-known socioeconomic factors known to influence suicide mortality in Austria (population density, per capita income, proportion of Roman Catholics, as well as the availability of mental health service providers). Sensitivity analyses and weighted least squares regression were used to challenge the robustness of the results.

Results

The overall suicide rate (R2= 0.15, β =–0.39,t=–4.14,P= 0.000073) as well as the suicide mortality ratio (R2= 0.17, β =–0.41,t=–4.38,P= 0.000030) were inversely associated with lithium levels in drinking water and remained significant after sensitivity analyses and adjustment for socioeconomic factors.

Conclusions

In replicating and extending previous results, this study provides strong evidence that geographic regions with higher natural lithium concentrations in drinking water are associated with lower suicide mortality rates.
Tardive dyskinesia: psychiatrists' knowledge and practice
Authors: Joseph Chennattucherry John , Currie Alan , Piracha Imran
Published: April 2011

Aims and method

We surveyed 180 experienced psychiatrists on their training and practice in diagnosing and managing tardive dyskinesia in the current atypical antipsychotic era.

Results

About two-thirds of psychiatrists (n = 124, 69%) responded to the survey. A significant minority had no training in tardive dyskinesia, yet almost everyone recognised the need for formal training in this area. We noted a discrepancy between what respondents believed should be their ideal practice and their reported actual clinical practice. As many as 58% considered that tardive dyskinesia could be a reason for patients to pursue litigation. Many had concerns about prescribing antipsychotics for unlicensed indications, especially for incapacitous patients.

Clinical implications

It is important to recognise current practice and gaps in training, not only to enhance training and patient care but also to mitigate against the risk of litigation.
Teaching, learning and assessing evidence-based psychiatry
Authors: Carney Stuart , Warner James , Ahmad Sheraz , Rands Gianetta , Suleman Sajid ,   On behalf of the MRCPsych Critical Review Paper Panel
Published: April 2011

This paper sets out the rationale, process for development and the content of the new evidence-based practice syllabus, which is examined as part of the Membership of the Royal College of Psychiatrists' Paper 3. The syllabus was developed by the Critical Review Paper Panel of the Royal College of Psychiatrists. Suggestions for learning and teaching evidence-based practice are also put forward.
Fibromyalgia: psychiatrists should now be picking up the baton
Authors: Neal Leigh A.
Published: April 2011

Recent functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) scan studies have demonstrated the importance of the modulation of pain perception by the emotional regions of the brain in fibromyalgia. In the absence of any other objective biological abnormality, is it time to review the respective roles of primary care, psychiatry and rheumatology in the classification, diagnosis and management of fibromyalgia?
Usefulness of reader feedback on the Royal College of Psychiatrists' public information leaflets
Authors: Briscoe Martin , Briscoe Simon , Timms Philip , Ramsay Ros
Published: April 2011

Aims and method

To describe the process for reader feedback on the Royal College of Psychiatrists' online public information leaflets, to report the findings of a retrospective analysis of feedback received over a 14-month period, and to discuss the value of feedback, particularly in relation to the Information Standard quality mark introduced by the Department of Health.

Results

We received 38 700 completed feedback forms during the period under analysis. We derived scores from the feedback forms, which enabled us to identify those that should be prioritised for review. Written comments from readers highlighted specific areas of the leaflets that required further work.

Clinical implications

The development of our public mental health information can be guided using feedback from our readers.
Scottish place of safety legislation: local audit of Section 297 Mental Health (Care and Treatment) (Scotland) Act 2003
Authors: Macaskill Amy M. , Brodie Barbara A. , Keil Brian
Published: April 2011

Aims and method

Following recommendations made by our 2004–2005 audit, we carried out a re-audit of the local Section 297 protocol in 2007–2008. Our aim was to establish the quality of documented information provided by the police; adherence to the protocol; completion rates of documentation; and rates of notification to the Mental Welfare Commission for Scotland, in keeping with the standards set in the Code of Practice of the Mental Health (Care and Treatment) (Scotland) Act 2003.

Results

We reliably traced 84 POS1 forms completed in accordance with the protocol. The audit identified a rate of 74–89% notification to the Mental Welfare Commission for Scotland. By comparison, there is a surprisingly wide variation in notification rates across Scotland. Good-quality information was given by the police, despite receiving no additional training.

Clinical implications

This audit highlights a serious lack of information about place-of-safety legislation in Scotland. For patients in the catchment area, the joint protocol and use of standard documentation has significantly standardised patient care. Other health boards and police forces should consider this as they implement legislation.
The myth of mental illness: 50 years later
Authors: Szasz Thomas
Published: April 2011

Fifty years ago I noted that modern psychiatry rests on a basic conceptual error – the systematic misinterpretation of unwanted behaviours as the diagnoses of mental illnesses pointing to underlying neurological diseases susceptible to pharmacological treatments. I proposed instead that we view persons called ‘mental patients' as active players in real life dramas, not passive victims of pathophysiological processes outside their control. In this essay, I briefly review the recent history of this culturally validated medicalisation of (mis)behaviours and its social consequences.
Glucose Regulates Cyclin D2 Expression in Quiescent and Replicating Pancreatic β-Cells Through Glycolysis and Calcium Channels
Authors: Salpeter Seth J. , Klochendler Agnes , Weinberg-Corem Noa , Porat Shay , Granot Zvi , Shapiro A. M. James , Magnuson Mark A. , Eden Amir , Grimsby Joseph , Glaser Benjamin , Dor Yuval
Published: April 2011

Understanding the molecular triggers of pancreatic β-cell proliferation may facilitate the development of regenerative therapies for diabetes. Genetic studies have demonstrated an important role for cyclin D2 in β-cell proliferation and mass homeostasis, but its specific function in β-cell division and mechanism of regulation remain unclear. Here, we report that cyclin D2 is present at high levels in the nucleus of quiescent β-cells in vivo. The major regulator of cyclin D2 expression is glucose, acting via glycolysis and calcium channels in the β-cell to control cyclin D2 mRNA levels. Furthermore, cyclin D2 mRNA is down-regulated during S-G2-M phases of each β-cell division, via a mechanism that is also affected by glucose metabolism. Thus, glucose metabolism maintains high levels of nuclear cyclin D2 in quiescent β-cells and modulates the down-regulation of cyclin D2 in replicating β-cells. These data challenge the standard model for regulation of cyclin D2 during the cell division cycle and suggest cyclin D2 as a molecular link between glucose levels and β-cell replication.