bluuebunny/crossref_metadata_2025 huggingface dataset:
Total testosterone may not decline with ageing in Korean men aged 40 years or older
Authors: Kim Young‐Sang , Hong Doohee , Lee Duck‐Joo , Joo Nam‐Seok , Kim Kwang‐Min
Published: February 2012

Objective

It is generally believed that gonadal function in men declines with ageing. However, observations on ageing‐related decrease in total testosterone (TT) are not consistent. The aim of this study is to examine the ageing‐related changes of testosterone and to investigate the influence of the ageing‐related factors on TT.

Design

Changes of TT with ageing were observed in longitudinal design in a single health promotion centre.

Subjects

A total of 220 Korean men aged ≥40 years were included between 2002 and 2011. TT assay was repeated for all subjects, with an interval of ≥3 years.

Measurements

Information of medical history and lifestyle habits was collected. Anthropometry and blood pressure were measured. TT, glucose, creatinine, highly sensitive C‐reactive protein, liver enzymes and lipid profiles were tested.

Results

Mean TT level did not decline significantly with ageing during median 4·3 years follow‐up (18·1 vs 17·8 nm, P = 0·439). Longitudinal change of TT was approximately + 0·8% per year. TT was negatively correlated with body mass index (BMI), waist circumference and glucose. With mixed effects model, diabetes (P = 0·038) and BMI (P = 0·007) affected TT level, but age and follow‐up interval did not.

Conclusions

TT did not change significantly in 220 Korean men for a median 4·3 years follow‐up. TT was not influenced by the age and follow‐up interval. BMI and diabetes mellitus affected TT decline.
More for less: a study of environmental flows during drought in two Australian rivers
Authors: WHITE HAYLEY L. , NICHOLS SUSAN J. , ROBINSON WAYNE A. , NORRIS RICHARD H.
Published: February 2012

1. In rivers affected by drought, flow regulation can further reduce flow and intensify its effects. We measured ecological responses to environmental flows, during a prolonged drought in a regulated river (Cotter River), compared with a drought affected, unregulated river (Goodradigbee River) in south‐eastern Australia.

2. Environmental flows in the regulated Cotter River were reduced from a monthly average base flow of 15 MLd−1 to only 5 MLd−1, which was implemented as two test flow regimes. Initially, flows were delivered in cycles of 14 days at 3 MLd−1 followed by 3 days at 14 MLd−1 and then another 14 days at 3 MLd−1 to make up the monthly average of 5 MLd−1. This flow regime continued for 6 months, after which a preliminary ecological assessment indicated deterioration in river condition. Consequently, the flow regime was altered to a cycle of 2 MLd−1 for 28 days followed by 20 MLd−1 for either 3 or 4 days. This new flow regime continued for another 5 months.

3. The ecological outcomes of the test flow regimes were assessed in terms of (i) the provision of available habitat (wetted channel) for aquatic biota; (ii) the accumulation of periphyton; and (iii) the structure and richness of macroinvertebrate assemblages.

4. Flow of 20 MLd−1 covered most of the streambed in the Cotter River, thus providing more wetted area and connectivity between habitats than flows of 2, 3 or 14 MLd−1. Depth and velocity were always less in the Cotter River than in the unregulated Goodradigbee River. Periphyton decreased in the Cotter River during the 2/20 MLd−1 flow regime, which combined the lowest and greatest test flow volumes, while periphyton did not change significantly in the unregulated river.

5. The reduced flow in the Cotter River resulted in fewer macroinvertebrates than expected (13) compared with unregulated Goodradigbee sites (19), although the magnitude of the differences did not depend on the test flow releases. Macroinvertebrates in the Cotter River became numerically dominated by Diptera and Oligochaeta, while Ephemeroptera, Plecoptera and Trichoptera decreased in abundance.

6. In the Cotter River, the monthly average flow of 5 MLd−1 (exceeded 97% of the time pre‐regulation) was insufficient to maintain the macroinvertebrate assemblages in reference condition, regardless of release patterns. However, short‐term ecological objectives were achieved, such as reduced periphyton accumulation and increased habitat availability, and the environmental flows maintained the river’s ability to recover (resilience) when higher flows returned.
A laboratory study of the effects of shelter availability and invasive crayfish on the growth of native stream fish
Authors: MATSUZAKI SHIN‐ICHIRO S. , SAKAMOTO MASAKI , KAWABE KIYOSHI , TAKAMURA NORIKO
Published: February 2012

1. The alteration of stream habitats by urbanisation reduces the availability of shelter. Reduced shelter availability may increase both predation risks and metabolic costs, negatively affecting the growth performance of stream fish. Although urbanised streams often allow the establishment of invasive species, the additive or interactive effects of shelter availability and invasive species are rarely explored. The invasive red swamp crayfish (Procambarus clarkii) is a strong shelter competitor and predator in streams.

2. We conducted a stream‐channel experiment to investigate how shelter availability and this invasive crayfish species affect the growth performance (measured as the loss in body mass under starved conditions) of two native benthic species, Japanese crucian carp (Carassius auratus complex) and an endangered cobitid fish (Lefua echigonia).

3. We found that both the absence of shelter and the presence of crayfish increased body mass loss in the crucian carp. However, the growth performance of the crucian carp was improved by the presence of shelter except in the presence of crayfish, in which case the shelter available did not ameliorate the negative effect of the crayfish on growth performance (i.e. an interactive effect). This result suggests that crayfish may affect the growth performance of the crucian carp through chemical cues as well as through shelter occupancy.

4. In contrast, shelter availability is the primary factor affecting the body mass loss of the cobitid fish. However, the growth performance of these fish was unaffected by the presence of crayfish. The change in the growth performance of the cobitid fish in response to the absence of shelter was greater than that of the crucian carp. This finding suggests that the cobitid fish may be more vulnerable than the crucian carp to a reduction in shelter availability.

5. Our study demonstrates that reduced shelter availability and/or crayfish invasion can have significant, indirect negative effects on the growth performance of native fish, but whether those effects are interactive might vary depending on the species. Our findings have clear implications for stream restoration and habitat assessment.
Ontogenetic constraints and diet shifts in Perch (Perca fluviatilis): mechanisms and consequences for intra‐cohort cannibalism
Authors: BYSTRÖM PÄR , HUSS MAGNUS , PERSSON LENNART
Published: February 2012

1. In many populations, sufficient size variation to allow for cannibalism may develop not only among age cohorts but also within them. Here, we used data on resource dynamics, consumer body size distribution and gape size limitation to unravel mechanisms promoting cannibalism within cohorts of young‐of‐the‐year (YOY) perch (Perca fluviatilis).

2. Perch are strongly gape limited when feeding on large zooplankton during early ontogeny. As a consequence, only initially large fish were able to shift to feeding on abundant large invertebrates, necessary to sustain fast growth.

3. We suggest that a combination of high initial size variation and exclusive access to resources for individuals with an initial size advantage is a prerequisite for the development of a size distribution sufficient for intra‐cohort cannibalism to occur.

4. During the time when cannibalism was observed, growth of the largest individuals in YOY perch cohorts was faster than that of smaller individuals. However, the energy gain from cannibalism did not increase growth rate enough to reach a size necessary to feed on more abundant size classes of victims, and therefore, the effect of cannibalism on overall cohort density was minor.

5. In addition to a high energy gain from cannibalism allowing for fast growth, strong resource limitation and slow growth rates of small individuals (i.e. potential victims) are a prerequisite not only for the development of intra‐cohort cannibalism but also for its persistence.
Suitability of infrared microspectroscopic imaging for histopathology of the uterine cervix
Authors: Einenkel Jens , Braumann Ulf‐Dietrich , Steller Wolfram , Binder Hans , Horn Lars‐Christian
Published: February 2012

Einenkel J, Braumann U‐D, Steller W, Binder H & Horn L‐C  (2012) Histopathology 60, 1084–1098

Suitability of infrared microspectroscopic imaging for histopathology of the uterine cervix

Aims:  Infrared microspectroscopy (IR‐MSP) has been proposed for automated histological tissue differentiation of unstained specimens based on chemical analysis of cell and extracellular constituents. This study aimed to determine the accuracy of IR‐MSP‐based histopathology of cervical carcinoma sections with complex tissue architecture under practically relevant testing conditions.

Methods and results:  In total, 46 regions of interest, covering an area of almost 50 mm2 on sections derived from paraffin‐embedded tissue of radical hysterectomy specimens, were analysed by IR‐MSP (nominal resolution ∼4.2 μm). More than 2.8 million pixel spectra that were processed using fuzzy c‐means clustering followed by hierarchical cluster analysis permitted image segmentation regarding different biochemical properties. Linear image registration was applied to compare these segmentation results with manual labelling on haematoxylin and eosin‐stained references (resolution ∼0.7 μm). For recognition of nine tissue types, sensitivities were 42–91% and specificities were 79–100%, mostly being affected by peritumoral inflammatory responses. Algorithmic variation of the outline of dysplasia and carcinoma revealed a spatial preference of false values in tissue transition areas.

Conclusions:  This imaging technique has potential as a new method for tissue characterization; however, the recognition accuracy does not justify a pathologist‐independent tissue analysis, and the application is only possible in combination with concomitant conventional histopathology.
The epidemiology, pathogenesis and histopathology of fatty liver disease
Authors: Levene Adam P , Goldin Robert D
Published: February 2012

Levene A P & Goldin R D  (2012) Histopathology 61, 141–152

The epidemiology, pathogenesis and histopathology of fatty liver disease

Fatty liver disease includes non‐alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD), each of which is increasing in prevalence. Each represents a histological spectrum that extends from isolated steatosis to steatohepatitis and cirrhosis. NAFLD is associated with obesity, diabetes, and insulin resistance, and is considered to be the liver manifestation of the metabolic syndrome. The pathogenesis of NAFLD and ALD involves cytokines, adipokines, oxidative stress, and apoptosis. Histopathology is the gold standard for assessing the severity of liver damage in NAFLD and ALD. We have reviewed the literature, and described and compared the epidemiology, natural disease history, pathogenesis and histopathology of NAFLD and ALD.
Angiogenin up‐regulation correlates with adverse clinicopathological and biological factors, increased microvascular density and poor patient outcome in neuroblastomas
Authors: Dungwa Josiah V , Uparkar Urmila , May Margaret T , Ramani Pramila
Published: February 2012

Dungwa J V, Uparkar U, May M T & Ramani P  (2012) Histopathology 60, 911–923

Angiogenin up‐regulation correlates with adverse clinicopathological and biological factors, increased microvascular density and poor patient outcome in neuroblastomas

Aims:  As new biomarkers are urgently needed to identify children with high‐risk neuroblastoma (NB), we studied the contribution of angiogenin (ANG) to angiogenesis and its association with clinicopathological and biological features and patient outcome in NB.

Methods and results:  Ninety NBs and 12 ganglioneuromas (GNs) were immunostained for ANG and CD31. ANG expression in NB tumoral cells (ANG scores) and vessels [ANG microvascular density (MVD)] and total MVD (CD31 MVD) were determined. The ANG score was significantly greater in NBs than in GNs (P = 0.015) and in NBs from children with stage 4 tumours, high‐risk disease, unfavourable pathology (P < 0.001 for each), MYCN amplification (P = 0.003), and 1p deletion (P = 0.002). ANG scores correlated with ANG MVD and CD31 MVD (P < 0.001 for each). Total ANG and CD31 protein levels, measured with a sensitive enzyme‐linked immunosorbent assay, were highly correlated (P = 0.003). High ANG scores were associated with decreased overall and event‐free survival (log‐rank test, P = 0.025 and P = 0.018, respectively). High ANG MVD was associated with decreased overall and event‐free survival (log‐rank test, P = 0.009 and P = 0.026, respectively). High CD31 MVD was associated with decreased event‐free survival (P = 0.045).

Conclusions:  The strong correlation of ANG up‐regulation with total MVD and adverse clinicopathological and biological factors indicates that ANG supports growth and progression in NB.
Does insulin‐like growth factor 1 receptor (IGF‐1R) targeting provide new treatment options for chordomas? A retrospective clinical and immunohistochemical study
Authors: Scheipl Susanne , Froehlich Elke V , Leithner Andreas , Beham Alfred , Quehenberger Franz , Mokry Michael , Stammberger Heinz , Varga Peter P , Lazáry Aron , Windhager Reinhard , Gattenloehner Stefan , Liegl Bernadette
Published: February 2012

Scheipl S, Froehlich E V, Leithner A, Beham A, Quehenberger F, Mokry M, Stammberger H, Varga P P, Lazáry A, Windhager R, Gattenloehner S & Liegl B  (2012) Histopathology 60, 999–1003

Does insulin‐like growth factor 1 receptor (IGF‐1R) targeting provide new treatment options for chordomas? A retrospective clinical and immunohistochemical study

Aims:  The overall prognosis of chordoma is poor, and current treatment options are limited. The insulin‐like growth factor 1 receptor (IGF‐1R) pathway is important for cell signalling, and attractive for selective inhibition. We investigated the expression of IGF‐1R and its ligands, IGF‐1 and IGF‐2, in a series of 50 chordomas, in order to assess whether IGF‐1R‐signalling could be a potential target for specific inhibition in chordomas.

Methods and results:  Fifty chordomas (34 primary tumours, 16 recurrences) from 44 patients were evaluated immunohistochemically for the expression of IGF‐1R, IGF‐1 and IGF‐2. Thirty‐eight chordomas (76%) expressed IGF‐1R, 46 (92%) expressed IGF‐1 and 25 (50%) expressed IGF‐2. Semi‐quantitative analyses revealed a moderate to strong staining intensity in ≥50% of tumour cells for IGF‐1R, IGF‐1 and IGF‐2 in 18 (36%), 32 (64%) and eight (16%) chordomas, respectively. Tumour volume correlated significantly with IGF‐1R‐staining intensity in primary chordomas (P = 0.042).

Conclusions:  IGF‐1R and IGF‐1 are expressed in the majority of chordomas. IGF‐1 expression is much stronger than IGF‐2 expression. Patients whose chordomas show a moderate to strong staining intensity in ≥50% of tumour cells for IGF‐1R (36%) might benefit most from IGF‐1R targeting, particularly if they suffer from large and surgically non‐resectable chordomas.
Quantifying hepatic steatosis – more than meets the eye
Authors: Levene Adam P , Kudo Hiromi , Armstrong Matthew J , Thursz Mark R , Gedroyc Wladyslaw M , Anstee Quentin M , Goldin Robert D
Published: February 2012

Levene A P, Kudo H, Armstrong M J, Thursz M R, Gedroyc W M, Anstee Q M & Goldin R D  (2012) Histopathology 60, 971–981

Quantifying hepatic steatosis – more than meets the eye

Aims:  The non‐alcoholic fatty liver disease (NAFLD) activity score (NAS) is the histological tool used to assess disease severity based on steatosis, inflammation and hepatocyte ballooning. As steatosis contributes up to three of a potential eight points to NAS, it is important to quantify steatosis accurately. We sought to determine the optimum histological technique for identifying fat in tissue.

Methods and results:  Using tissue from a mouse model of NAFLD, with validation in human liver biopsies, the percentage steatosis and fat droplet size were assessed in haematoxylin and eosin (H&E)‐ and Oil Red‐O (ORO)‐stained sections by light microscopy and digital image analysis (DIA). Results were compared to biochemical tissue triglyceride content and MRI assessment of hepatic lipid content. H&E steatosis assessment correlated poorly with tissue triglyceride concentration. However, ORO DIA exhibited much higher sensitivity and specificity for steatosis and correlated very well with triglyceride concentration in mouse and human liver (R = 0.706, P = 0.001 and R = 0.894, P =0.041, respectively). MRI‐based assessment of steatosis was inaccurate.

Conclusions:  ORO DIA is the most accurate method for detecting and quantifying steatosis. Although H&E‐based NAS remains clinically valid in both clinical research and experimental situations, ORO DIA is a more robust technique to assess liver steatosis accurately for NAS scoring.
A biometric study of C‐shaped root canal systems in mandibular second molars using cone‐beam computed tomography
Authors: Seo D.‐G. , Gu Y. , Yi Y.‐A. , Lee S.‐J. , Jeong J.‐S. , Lee Y. , Chang S.‐W. , Lee J.‐K. , Park W. , Kim K.‐D. , Kum K.‐Y.
Published: February 2012

Seo D‐G, Gu Y, Yi Y‐A, Lee S‐J, Jeong J‐S, Lee Y, Chang S‐W, Lee J‐K, Park W, Kim K‐D, Kum K‐Y. A biometric study of C‐shaped root canal systems in mandibular second molars using cone‐beam computed tomography. International Endodontic Journal, 45, 807–814, 2012.

Aim  To investigate the configuration of C‐shaped canals in mandibular second molars, canal wall thickness and the orientation of the thinnest area at 1‐mm intervals from the canal orifice to the apex by using cone‐beam computed tomographic (CBCT) images.

Methodology  Three‐dimensional CBCT images of 92 Korean mandibular second molars having C‐shaped root canals were analysed to determine their configuration using a modification of Melton’s classification, as well as the thinnest walls and their location. Associations between configuration type and distance from the canal orifice to the apex, as well as associations between the directional orientation of the thinnest root wall and distance from the canal orifice to the apex, were assessed by Fisher’s exact test. Because serial measurements of minimum wall thicknesses were correlated with individual teeth, a mixed‐effects analysis was applied.

Results  The most common configuration types were Melton’s type I in the coronal region and Melton’s type III in the apical region. Mean thicknesses of the thinnest root canal walls were 1.39 ± 0.38, 0.85 ± 0.25 and 0.77 ± 0.20 mm in the coronal, middle and apical regions, respectively. The thicker the root canal walls at the orifice region, the greater the decrease in thickness towards the apical region (P < 0.05), with the linguo‐central root area being the thinnest. The pattern of decreasing thickness from the orifice to the apex formed a nonlinear cubic curve.

Conclusions  The most prevalent configuration types were Melton’s type I (coronal region) and type III (apical region). The linguo‐central root area was the thinnest in C‐shaped root canals of Korean mandibular second molars. These anatomical variations should be considered during surgical or nonsurgical endodontic procedures.
High prevalence of micropenis in 2710 male newborns from an intensive‐use pesticide area of Northeastern Brazil
Authors: Gaspari L. , Sampaio D. R. , Paris F. , Audran F. , Orsini M. , Neto J. B. , Sultan C.
Published: February 2012

Exposure to endocrine‐disrupting chemicals (EDCs) has been suggested to contribute to the increasing trends of external genital malformation in male newborns. In Northeastern Brazil, the poor sanitary conditions found in the favelas encourage the widespread use of pesticides. This 2‐year study of a total birth cohort of full‐term male newborns in the regional hospitals of Campina Grande (Paraíba, Brazil) sought to (1) accurately establish for the first time the incidences of neonatal male genital malformations, (2) investigate the endocrine and genetic aetiologies of these malformations, and (3) evaluate their associations with possible prenatal exposure to EDCs. A total of 2710 male newborns were explored for cryptorchidism, hypospadias and micropenis. Cases were referred to the Pediatric Endocrine Clinic for endocrine and genetic investigations, and all parents were interviewed about their environmental/occupational exposure to EDCs before/during pregnancy by paediatric endocrinologists using a detailed questionnaire. We observed 56 cases of genital malformation (2.07%), including 23 cryptorchidism (0.85%), 15 hypospadias (0.55%), and 18 micropenis (0.66%). All cases exhibited normal/subnormal testosterone production and none presented androgen receptor or 5α‐reductase gene mutation. More than 92% of these newborns presented foetal contamination by EDCs, as their mothers reported daily domestic use of pesticides (i.e., DDT) and other EDCs. Most of these undervirilized male newborns presented additional EDC contamination, as 80.36% of the mothers and 58.63% of the fathers reported paid or unpaid work that entailed the use of pesticides and other EDCs before/during pregnancy for the mothers and around the time of fertilization for the fathers. The high rate of micropenis in our population associated with an elevated percentage of parental environmental/occupational exposure to EDCs before/during pregnancy indicates that foetal contamination may be a risk factor for the development of male external genital malformation.
Obesogens, stem cells and the developmental programming of obesity
Authors: Janesick A. , Blumberg B.
Published: February 2012

Obesogens are chemicals that directly or indirectly lead to increased fat accumulation and obesity. Obesogens have the potential to disrupt multiple metabolic signalling pathways in the developing organism that can result in permanent changes in adult physiology. Prenatal or perinatal exposure to obesogenic endocrine disrupting chemicals has been shown to predispose an organism to store more fat from the beginning of its life. For example, excess oestrogen or cortisol exposure in the womb or during early life resulted in an increased susceptibility to obesity and metabolic syndrome later in life. This review focuses on the effects of environmental chemicals, such as the model obesogen, tributyltin (TBT), on the development of obesity. We discuss evidence linking the obesogenic effects of TBT with its ability to activate the peroxisome proliferator‐activated receptor gamma and stimulate adipogenesis. We also discuss how TBT and other environmental obesogens may lead to epigenetic changes that predispose exposed individuals to subsequent weight gain and obesity. This suggests that humans, who have been exposed to obesogenic chemicals during sensitive windows of development, might be pre‐programmed to store increased amounts of fat, resulting in a lifelong struggle to maintain a healthy weight and exacerbating the deleterious effects of poor diet and inadequate exercise.
Estimating partial observability and nonlinear climate effects on stochastic community dynamics of migratory waterfowl
Authors: Almaraz Pablo , Green Andy J. , Aguilera Eduardo , Rendón Miguel A. , Bustamante Javier
Published: February 2012

1. Understanding the impact of environmental variability on migrating species requires the estimation of sequential abiotic effects in different geographic areas across the life cycle. For instance, waterfowl (ducks, geese and swans) usually breed widely dispersed throughout their breeding range and gather in large numbers in their wintering headquarters, but there is a lack of knowledge on the effects of the sequential environmental conditions experienced by migrating birds on the long‐term community dynamics at their wintering sites.

2. Here, we analyse multidecadal time‐series data of 10 waterfowl species wintering in the Guadalquivir Marshes (SW Spain), the single most important wintering site for waterfowl breeding in Europe. We use a multivariate state‐space approach to estimate the effects of biotic interactions, local environmental forcing during winter and large‐scale climate during breeding and migration on wintering multispecies abundance fluctuations, while accounting for partial observability (observation error and missing data) in both population and environmental data.

3. The joint effect of local weather and large‐scale climate explained 31·6% of variance at the community level, while the variability explained by interspecific interactions was negligible (<5%). In general, abiotic conditions during winter prevailed over conditions experienced during breeding and migration. Across species, a pervasive and coherent nonlinear signal of environmental variability on population dynamics suggests weaker forcing at extreme values of abiotic variables.

4. Modelling missing observations through data augmentation increased the estimated magnitude of environmental forcing by an average 30·1% and reduced the impact of stochasticity by 39·3% when accounting for observation error. Interestingly however, the impact of environmental forcing on community dynamics was underestimated by an average 15·3% and environmental stochasticity overestimated by 14·1% when ignoring both observation error and data augmentation.

5. These results provide a salient example of sequential multiscale environmental forcing in a major migratory bird community, which suggests a demographic link between the breeding and wintering grounds operating through nonlinear environmental effects. Remarkably, this study highlights that modelling observation error in the environmental covariates of an ecological model can be proportionally more important than modelling this source of variance in the population data.
Case study of cognitive behavioural therapy awareness educational programme using blended learning, UK
Authors: EL ANSARI W. , DUNNE J.
Published: February 2012

Accessible summary

This paper highlighted some opportunities as well as challenges in relation to cognitive behavioural therapy, and examined a cognitive behavioural therapy awareness educational programme delivered by a blended learning approach at the University of Gloucestershire, UK.

The challenges associated with initiation and running of such educational programmes included the time commitments for busy practitioners to complete the award, learners' motivation and engagement with the course, and some challenges associated with e‐leaning.

The paper concludes with suggestions for the way forward for such educational programmes.

This paper examined the opportunities as well as challenges in relation to the use of cognitive behavioural therapy (CBT). The opportunities include the increased range of mental health conditions and other disorders where CBT (in isolation or with other interventions) could be effective to address them, as well as policies around workforce education and training that support the expansion of psychological therapies, particularly CBT services. The challenges include the urgent need of heightened awareness among the wider platform of health and social care workers about CBT principles, structure, framework, methods of delivery, wider applications, evaluation and appropriate referral of clients, and stepped model of care. In response to such needs, the paper described CBT awareness educational award at the University of Gloucestershire, UK: the Certificate of Professional Studies in Awareness of Cognitive and Behavioural Therapies Practice delivered at Level III and M level. The challenges associated with the initiation and running of such educational programmes are highlighted, as well as suggestions for the way forward considering the learners', employers' and educational providers' perspectives.
Individualized, transdiagnostic approaches to complex presentations: a case study
Authors: BINNIE J.
Published: February 2012

Accessible summary

Basing psychological treatment on diagnosis can work but not always.

People are complicated and so are their problems.

Being responsive and adapting treatment plans is important.

Cognitive behavioural therapy is an evidence‐based approach to helping people resolve their mental distress. Cognitive behavioural therapy practitioners are often encouraged to adapt their interventions according to the person's diagnosis. However, this approach can be too simplistic. This paper aimed to reflect on working with complex clinical presentations and to explore how transdiagnostic approaches can be effectively integrated into standard cognitive behavioural interventions. To achieve these aims, a case study of cognitive behavioural therapy assessment and treatment was presented. The interventions used are described in detail. The move away from a diagnostic‐led intervention to a transdiagnostic perspective based on the individualized formulation is described. Reflections on the process are discussed and the overall approach used is evaluated with recommendations made to enhance future clinical practice.
Fish migrate underground: the example of Delminichthys adspersus (Cyprinidae)
Authors: PALANDAČIĆ ANJA , MATSCHINER MICHAEL , ZUPANČIČ PRIMOŽ , SNOJ ALEŠ
Published: February 2012

Complex aquatic systems of karst harbour a rich but little‐investigated biodiversity. In Croatia and Bosnia–Herzegovina karst, temporal springs are inhabited by a group of minnow‐like fishes that retreat to the associated ground water during dry seasons and spend several months underground. The most abundant species in this group is Delminichthys adspersus (Heckel 1843), which also has the most fragmented distribution range. To determine the population composition and dispersal patterns, and to detect potential underground migration, a large genetic data set comprising 544 specimens of D. adspersus covering most of its distribution area was analysed. Analysis of mitochondrial cytochrome b sequences (∼1000 bp) and eight microsatellite loci showed that D. adspersus comprises at least three subpopulations with gene flow occurring among them. Coalescent‐based analysis revealed a complex migration pattern, with several unidirectional dispersal paths, including between temporal springs that share no surface connection. The results of this study suggest the existence of recurrent underground migration of fish in a karst environment and demonstrate the complexity of its hydrological network. The findings are relevant to conservation strategies for endemic karst organisms and karst ecosystems as a whole.
Targeting of Cameleons to various subcellular compartments reveals a strict cytoplasmic/mitochondrial Ca2+ handling relationship in plant cells
Authors: Loro Giovanna , Drago Ilaria , Pozzan Tullio , Schiavo Fiorella Lo , Zottini Michela , Costa Alex
Published: February 2012

Here we describe use of a mitochondrial targeted Cameleon to produce stably transformed Arabidopsis plants that enable analyses of mitochondrial Ca2+ dynamics in planta and allow monitoring of the intra‐mitochondrial Ca2+ concentration in response to physiological or environmental stimuli. Transgenic plants co‐expressing nuclear and mitochondrial targeted Cameleons were also generated and analyzed. Here we show that mitochondrial Ca2+ accumulation is strictly related to the intensity of the cytoplasmic Ca2+ increase, demonstrating a tight association between mitochondrial and cytoplasmic Ca2+ dynamics. However, under all experimental conditions, mitochondrial Ca2+ dynamics were substantially different from those monitored in the cytoplasm, demonstrating that mitochondria do not passively sense cytosolic Ca2+, but actively modulate the intra‐mitochondrial level of the cation. In particular, our analyses show that the kinetics of Ca2+ release from mitochondria are much slower than in the cytoplasm and nucleus. The mechanisms and functional implications of these differences are discussed.
A heat‐activated calcium‐permeable channel – Arabidopsis cyclic nucleotide‐gated ion channel 6 – is involved in heat shock responses
Authors: Gao Fei , Han Xiaowei , Wu Jianhai , Zheng Shuzhi , Shang Zhonglin , Sun Daye , Zhou Rengang , Li Bing
Published: February 2012

An increased concentration of cytosolic calcium ions (Ca2+) is an early response by plant cells to heat shock. However, the molecular mechanism underlying the heat‐induced initial Ca2+ response in plants is unclear. In this study, we identified and characterized a heat‐activated Ca2+‐permeable channel in the plasma membrane of Arabidopsis thaliana root protoplasts using reverse genetic analysis and the whole‐cell patch‐clamp technique. The results indicated that A. thaliana cyclic nucleotide‐gated ion channel 6 (CNGC6) mediates heat‐induced Ca2+ influx and facilitates expression of heat shock protein (HSP) genes and the acquisition of thermotolerance. GUS and GFP reporter assays showed that CNGC6 expression is ubiquitous in A. thaliana, and the protein is localized to the plasma membrane of cells. Furthermore, it was found that the level of cytosolic cAMP was increased by a mild heat shock, that CNGC6 was activated by cytosolic cAMP, and that exogenous cAMP promoted the expression of HSP genes. The results reveal the role of cAMP in transduction of heat shock signals in plants. The correlation of an increased level of cytosolic cAMP in a heat‐shocked plant with activation of the Ca2+ channels and downstream expression of HSP genes sheds some light on how plants transduce a heat stimulus into a signal cascade that leads to a heat shock response.
The bHLH protein ROX acts in concert with RAX1 and LAS to modulate axillary meristem formation in Arabidopsis
Authors: Yang Fang , Wang Quan , Schmitz Gregor , Müller Dörte , Theres Klaus
Published: February 2012

During post‐embryonic shoot development, new meristems are initiated in the axils of leaves. They produce secondary axes of growth that determine morphological plasticity and reproductive efficiency in higher plants. In this study, we describe the role of the bHLH‐protein‐encoding Arabidopsis gene REGULATOR OF AXILLARY MERISTEM FORMATION (ROX), which is the ortholog of the branching regulators LAX PANICLE1 (LAX1) in rice and barren stalk1 (ba1) in maize. rox mutants display compromised axillary bud formation during vegetative shoot development, and combination of rox mutants with mutations in RAX1 and LAS, two key regulators of axillary meristem initiation, enhances their branching defects. In contrast to lax1 and ba1, flower development is unaffected in rox mutants. Over‐expression of ROX leads to formation of accessory side shoots. ROX mRNA accumulates at the adaxial boundary of leaf and flower primordia. However, in the vegetative phase, axillary meristems initiate after ROX expression has terminated, suggesting an indirect role for ROX in meristem formation. During vegetative development, ROX expression is dependent on RAX1 and LAS activity, and all three genes act in concert to modulate axillary meristem formation.
The impact of photoperiod insensitive Ppd‐1a mutations on the photoperiod pathway across the three genomes of hexaploid wheat (Triticum aestivum)
Authors: Shaw Lindsay M. , Turner Adrian S. , Laurie David A.
Published: February 2012

Flowering time is a trait that has been extensively altered during wheat domestication, enabling it to be highly productive in diverse environments and providing a rich source of variation for studying adaptation mechanisms. Hexaploid wheat is ancestrally a long‐day plant, but many environments require varieties with photoperiod insensitivity (PI) that can flower in short days. PI results from mutations in the Ppd‐1 gene on the A, B or D genomes, with individual mutations conferring different degrees of earliness. The basis of this is poorly understood. Using a common genetic background, the effects of A, B and D genome PI mutations on genes of the circadian clock and photoperiod pathway were studied using genome‐specific expression assays. Ppd‐1 PI mutations did not affect the clock or immediate clock outputs, but affected TaCO1 and TaFT1, with a reduction in TaCO1 expression as TaFT1 expression increased. Therefore, although Ppd‐1 is related to PRR genes of the Arabidopsis circadian clock, Ppd‐1 affects flowering by an alternative route, most likely by upregulating TaFT1 with a feedback effect that reduces TaCO1 expression. Individual genes in the circadian clock and photoperiod pathway were predominantly expressed from one genome, and there was no genome specificity in Ppd‐1 action. Lines combining PI mutations on two or three genomes had enhanced earliness with higher levels, but not earlier induction, of TaFT1, showing that there is a direct quantitative relationship between Ppd‐1 mutations, TaFT1 expression and flowering.
Phylloquinone (vitamin K1) biosynthesis in plants: two peroxisomal thioesterases of lactobacillales origin hydrolyze 1,4‐dihydroxy‐2‐naphthoyl‐coa
Authors: Widhalm Joshua R. , Ducluzeau Anne‐Lise , Buller Nicole E. , Elowsky Christian G. , Olsen Laura J. , Basset Gilles J. C.
Published: February 2012

It is not known how plants cleave the thioester bond of 1,4‐dihydroxy‐2‐naphthoyl‐CoA (DHNA‐CoA), a necessary step to form the naphthoquinone ring of phylloquinone (vitamin K1). In fact, only recently has the hydrolysis of DHNA‐CoA been demonstrated to be enzyme driven in vivo, and the cognate thioesterase characterized in the cyanobacterium Synechocystis. With a few exceptions in certain prokaryotic (Sorangium and Opitutus) and eukaryotic (Cyanidium, Cyanidioschyzon and Paulinella) organisms, orthologs of DHNA‐CoA thioesterase are missing outside of the cyanobacterial lineage. In this study, genomic approaches and functional complementation experiments identified two Arabidopsis genes encoding functional DHNA‐CoA thioesterases. The deduced plant proteins display low percentages of identity with cyanobacterial DHNA‐CoA thioesterases, and do not even share the same catalytic motif. GFP‐fusion experiments demonstrated that the Arabidopsis proteins are targeted to peroxisomes, and subcellular fractionations of Arabidopsis leaves confirmed that DHNA‐CoA thioesterase activity occurs in this organelle. In vitro assays with various aromatic and aliphatic acyl‐CoA thioester substrates showed that the recombinant Arabidopsis enzymes preferentially hydrolyze DHNA‐CoA. Cognate T‐DNA knock‐down lines display reduced DHNA‐CoA thioesterase activity and phylloquinone content, establishing in vivo evidence that the Arabidopsis enzymes are involved in phylloquinone biosynthesis. Extraordinarily, structure‐based phylogenies coupled to comparative genomics demonstrate that plant DHNA‐CoA thioesterases originate from a horizontal gene transfer with a bacterial species of the Lactobacillales order.
Direct to consumer genetic testing: a systematic review of position statements, policies and recommendations
Authors: Skirton H , Goldsmith L , Jackson L , O'Connor A
Published: February 2012

Skirton H, Goldsmith L, Jackson L, O’Connor A. Direct to consumer genetic testing: a systematic review of position statements, policies and recommendations.

In healthcare settings, genetic tests to determine whether an individual had inherited a genetic mutation are ordered by a health professional, and the results are interpreted and conveyed to the patient by that person. However, direct to consumer genetic testing (DTCGT) has enabled individuals to purchase genetic tests and receive results without the intervention of a health professional. To inform a set of guidelines for consumers and health professionals, we undertook a systematic review of position statements, policies and recommendations on the use of DTCGT. We performed a search of seven databases and the Internet for relevant documents. The search terms were ‘direct to consumer’ and ‘genetic test', and documents in English published from 2002 to 2011 were included. The search retrieved 314 items, of which 14 were eligible for review. Five themes were derived from thematic analysis: motivation for use, potential benefits, potential harms, recommendations to guide consumers and need for research. The authors of these documents described more potential harms than benefits, but, although some stated that direct to consumer testing should be actively discouraged, others supported consumer rights to make autonomous choices. Further research into the impact of direct to consumer testing on health services and consumers is required to inform policies.
Associations between atopic markers in asthma and intestinal helminth infections in Cuban schoolchildren
Authors: Vereecken Kim , Kanobana Kirezi , Wördemann Meike , Junco Diaz Raquel , Menocal Heredia Lenina , Ruiz Espinosa Aniran , Nuñez Fidel Angel , Rojas Rivero Lazara , Bonet Gorbea Mariano , Polman Katja
Published: February 2012

To cite this article: Vereecken K, Kanobana K, Wördemann M, Junco Diaz R, Menocal Heredia L, Ruiz Espinosa A, Nuñez FA, Rojas Rivero L, Bonet Gorbea M, Polman K. Associations between atopic markers in asthma and intestinal helminth infections in Cuban schoolchildren. Pediatric Allergy Immunology 2012: 23: 332–338.

Total serum IgE (tIgE), allergen‐specific IgE (sIgE), and skin prick test (SPT) are commonly used markers for atopy and atopic disease. The association between these measures and their relationship to clinical symptoms differs in affluent and non‐affluent countries. We investigated the role of intestinal helminth infections in observed variations in atopic markers and asthma, and possible diagnostic and epidemiological consequences. A cross‐sectional study was conducted in Cuban schoolchildren (n = 1285; 4–14 yrs). Atopy was determined by SPT, sIgE, and tIgE; asthma by International Study of Asthma and Allergies in Childhood questionnaire; and intestinal helminth infections by stool examination. Percentages of tIgE, sIgE, and SPT positives were 88.9%, 25.5%, and 16.5%, respectively. Asthma was found in 20.8%, and helminth infections in 20.9% of the children. All three atopic markers were significantly associated with each other and with asthma. Median tIgE levels were higher in helminth‐infected than in uninfected children, irrespective of their status of atopy/asthma. Discordant results between SPT and sIgE were observed in 22.6% of the children. Among SPT positives, 41% were sIgE negative. The proportion of SPT negatives among sIgE positives was 74% in helminth‐infected and 58.4% in uninfected children (p < 0.05). Helminth infections affected tIgE levels, reconfirming the limited value of tIgE for diagnosis of atopy and asthma in tropical areas. Higher frequencies of sIgE than positive SPTs were observed, especially in helminth‐infected children. This corresponds with current hypothesis on the role of helminths in atopy. However, the observed proportion of sIgE negatives among children with positive SPT suggests that other mechanisms may also be involved.
The stationary distribution of a continuously varying strategy in a class‐structured population under mutation–selection–drift balance
Authors: LEHMANN L.
Published: February 2012

Many traits and/or strategies expressed by organisms are quantitative phenotypes. Because populations are of finite size and genomes are subject to mutations, these continuously varying phenotypes are under the joint pressure of mutation, natural selection and random genetic drift. This article derives the stationary distribution for such a phenotype under a mutation–selection–drift balance in a class‐structured population allowing for demographically varying class sizes and/or changing environmental conditions. The salient feature of the stationary distribution is that it can be entirely characterized in terms of the average size of the gene pool and Hamilton's inclusive fitness effect. The exploration of the phenotypic space varies exponentially with the cumulative inclusive fitness effect over state space, which determines an adaptive landscape. The peaks of the landscapes are those phenotypes that are candidate evolutionary stable strategies and can be determined by standard phenotypic selection gradient methods (e.g. evolutionary game theory, kin selection theory, adaptive dynamics). The curvature of the stationary distribution provides a measure of the stability by convergence of candidate evolutionary stable strategies, and it is evaluated explicitly for two biological scenarios: first, a coordination game, which illustrates that, for a multipeaked adaptive landscape, stochastically stable strategies can be singled out by letting the size of the gene pool grow large; second, a sex‐allocation game for diploids and haplo‐diploids, which suggests that the equilibrium sex ratio follows a Beta distribution with parameters depending on the features of the genetic system.
Intestinal glucose absorption in calves as affected by different carbohydrate sources
Authors: Klinger S. , Noci B. , Müller K. , Breves G.
Published: February 2012

From numerous recent studies, it has been demonstrated that the development of the forestomach system in ruminants and thus microbial carbohydrate fermentation do not exclude the potential of the small intestines for enzymatic carbohydrate digestion and subsequent monosaccharide absorption. However, the role of regulatory nutritional factors is still under discussion. Therefore, we investigated the kinetic parameters of intestinal Na+‐dependent glucose absorption and SGLT1 expression using isolated brush border membrane vesicles (BBMV) from the jejunum of 10‐week‐old calves kept on either hay, concentrate or corn silage‐based diets in addition to milk replacer. While the maximal transport capacity was significantly higher for concentrate and corn silage‐fed animals, SGLT1 protein expression was highest in BBMV isolated from hay‐fed animals. This observation differs from the prevalent conception that induction of Na+‐dependent glucose uptake via SGLT1 is based on an increased number of transporters at the brush border membrane.
The Effect of Glycerol Concentrations on the Post‐thaw In Vitro Characteristics of Cryopreserved Sex‐sorted Boar Spermatozoa
Authors: Parrilla I , del Olmo D , Caballero I , Tarantini T , Cuello C , Gil MA , Roca J , Martinez EA , Vazquez JM
Published: February 2012

Contents

The objective of this study was to optimize protocols for the cryopreservation of sex‐sorted boar spermatozoa. In the experiment 1, we evaluated the effects of a standard boar sperm cryopreservation procedure (3% final glycerol concentration) on the in vitro characteristics of sex‐sorted sperm frozen at low sperm concentrations (20 × 106 sperm/ml; S20 group). Non‐sorted spermatozoa frozen at 1000 × 106 (C1000 group) and 20 × 106 (C20 group) sperm/ml were used as the freezing control groups. In experiment 2, the effects of different final glycerol concentrations (0.16%, 0.5%, 1.0%, 2.0% and 3.0%) on post‐thaw quality of the S20 and C20 groups were evaluated. In both experiments, the samples were evaluated prior to freezing (5°C) and at 30, 90 and 150 min after thawing. Experiment 1 indicated that freezing sperm at low concentrations decreased (p < 0.05) the total motility (TM) and progressive motility (PM) at 90 and 150 min after thawing regardless of whether the sperm were sorted or not. However, the sperm membrane integrity was not affected at any evaluation step. Inexperiment 2, significant effects on the TM and PM because of increased glycerol concentrations in the S20 and C20 groups were observed only at 90 and 150 min after thawing. The samples frozen in 3% glycerol showed lower (p < 0.05) TM and PM values when compared to those frozen in the presence of 0.5% and 1% glycerol. In both experiments, non‐sorted control samples displayed higher percentages of spermatozoa with damaged DNA than sorted spermatozoa. In conclusion, the optimization of cryopreservation conditions by decreasing the glycerol concentrations can improve post‐thaw motility of sex‐sorted spermatozoa frozen at low concentrations.