bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNAs in development and disease
Authors: Erson AE , Petty EM
Published: January 2009

Since the discovery of microRNAs (miRNAs) inCaenorhabditiselegans, mounting evidence illustrates the important regulatory roles for miRNAs in various developmental, differentiation, cell proliferation, and apoptosis pathways of diverse organisms. We are just beginning to elucidate novel aspects of RNA mediated gene regulation and to understand how heavily various molecular pathways rely on miRNAs for their normal function. miRNAs are small non‐protein‐coding transcripts that regulate gene expression post‐transcriptionally by targeting messenger RNAs (mRNAs). While individual miRNAs have been specifically linked to critical developmental pathways, the deregulated expression of many miRNAs also has been shown to have functional significance for multiple human diseases, such as cancer. We continue to discover novel functional roles for miRNAs at a rapid pace. Here, we summarize some of the key recent findings on miRNAs, their mode of action, and their roles in both normal development and in human pathology. A better understanding of how miRNAs operate during the normal life of a cell as well as in the pathogenesis of disease when deregulated will provide new avenues for diagnostic, prognostic, and therapeutic applications.
STXBP1: the second synaptic vesicle release gene involved in epilepsy
Authors: Kumar RA
Published: January 2009

De novo mutations in the gene encoding STXBP1 (MUNC18‐1) cause early infantile epileptic encephalopathy Saitsu et al. (2008) Nature Genetics 40: 782–788
Williams–Beuren syndrome: novel risk alleles in transmitting parents
Authors: Babatz TD , Kumar RA
Published: January 2009

Copy number variation at the 7q11.23 segmental duplications is a susceptibility factor for the Williams–Beuren syndrome deletion Cuscó et al. (2008) Genome Research 18 (5): 683–694. Epub 21 February 2008
Common vs rare variants and a case for neurodevelopment in schizophrenia
Authors: Babatz TD , Kumar RA
Published: January 2009

Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia Walsh et al. (2008) Science 320 (5875): 539–543. Epub 27 March 2008
PTPN11analysis for the prenatal diagnosis of Noonan syndrome in fetuses with abnormal ultrasound findings
Authors: Lee KA , Williams B , Roza K , Ferguson H , David K , Eddleman K , Stone J , Edelmann L , Richard G , Gelb BD , Kornreich R
Published: January 2009

Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, congenital heart defects and distinctive facies. The disorder is genetically heterogeneous with approximately 50% of patients havingPTPN11mutations. Prenatally, the diagnosis of NS has been suspected following certain ultrasound findings, such as cystic hygroma, increased nuchal translucency (NT) and hydrops fetalis. Studies of fetuses with cystic hygroma have suggested an NS prevalence of 1–3%. A retrospective review was performed to assess the utility ofPTPN11testing based on prenatal sonographic findings (n= 134). The most commonly reported indications for testing were increased NT and cystic hygroma. Analysis showed heterozygous missense mutations in 12 fetuses, corresponding to a positive test rate of 9%.PTPN11mutations were identified in 16% and 2% of fetuses with cystic hygroma and increased NT, respectively. Among fetuses with isolated cystic hygroma,PTPN11mutation prevalence was 11%. The mutations observed in the three fetuses with hydrops fetalis had previously been reported as somatic cancer mutations. PrenatalPTPN11testing has diagnostic and possible prognostic properties that can aid in risk assessment and genetic counseling. As NS is genetically heterogeneous, negativePTPN11testing cannot exclude the diagnosis and further study is warranted regarding the other NS genes.
Psychosocial outcome following genetic risk counselling for familial colorectal cancer. A comparison of affected patients and family members
Authors: Keller M , Jost R , Haunstetter CM , Sattel H , Schroeter C , Bertsch U , Cremer F , Kienle P , Tariverdian M , Kloor M , Gebert J , Brechtel A
Published: January 2009

Few studies have reported prospective data on psychosocial outcomes after genetic counselling in families with suspected hereditary non‐polyposis colorectal cancer (HNPCC). This prospective study examines the impact of multidisciplinary risk counselling on the psychosocial outcome of 139 affected cancer patients and 233 family members without cancer at risk for HNPCC. Participants completed questionnaires specific to HNPCC before and 8 weeks after attending the familial cancer clinic. Affected patients’ levels of distress were closely related to their health status and exceeded that of unaffected individuals, as did worry regarding their relatives’ risk. A significant reduction in general anxiety (Hospital Anxiety and Depression Scale), distress specific to familial CRC (Impact of Events Scale) and general cancer worry (Distress Hereditary Disorder) was demonstrated after counselling in both affected patients and unaffected individuals. Reduction in distress was more pronounced in affected patients given a high risk of HNPCC compared with those at intermediate risk. Among unaffected individuals, distress declined regardless of what clinical risk they were assigned. Their perceptions of risk and cancer‐related threat declined, while confidence in effective surveillance increased. These results suggest the beneficial effects of multidisciplinary counselling even when high‐risk information is conveyed. A patient’s previous cancer experience is likely to contribute to clinically relevant distress (15% of those patients), indicating the need for appropriate counselling.
The rate of germline mutations and large deletions of SMAD4 and BMPR1A in juvenile polyposis
Authors: Calva‐Cerqueira D , Chinnathambi S , Pechman B , Bair J , Larsen‐Haidle J , Howe JR
Published: January 2009

Juvenile polyposis (JPS) is an autosomal dominant syndrome that predisposes individuals to develop gastrointestinal polyps and cancer. Germline point mutations in SMAD4 and BMPR1A have been identified as causing JPS in approximately 40–60% of patients, but few studies have looked at the rate of large deletions. In this study, we determined the overall prevalence of genetic changes of SMAD4 and BMPR1A by sequencing and by screening for larger deletions. DNA was extracted from 102 JPS probands, and each exon and intron–exon boundary of SMAD4 and BMPR1A were sequenced. Coding and non‐coding exons of SMAD4 and BMPR1A were screened for deletions with multiplex ligation‐dependent probe amplification (MLPA). By sequencing, 20 probands had point mutations of SMAD4 and 22 of BMPR1A. By MLPA, one proband had deletion of most of SMAD4, one of both BMPR1A and PTEN, one of the 5′ end of BMPR1A, and another of the 5′ end of SMAD4. The overall prevalence of SMAD4 and BMPR1A point mutations and deletions in JPS was 45% in the largest series of patients to date. Large deletions are less frequent in JPS patients, but represent other heritable causes of JPS, which should be screened for in pre‐symptomatic genetic testing.
Refining the phenotype of α‐1a Tubulin (TUBA1A) mutation in patients with classical lissencephaly
Authors: Morris‐Rosendahl DJ , Najm J , Lachmeijer AMA , Sztriha L , Martins M , Kuechler A , Haug V , Zeschnigk C , Martin P , Santos M , Vasconcelos C , Omran H , Kraus U , Van der Knaap MS , Schuierer G , Kutsche K , Uyanik G
Published: January 2009

Mutations in the α‐1a Tubulin (TUBA1A) gene have recently been found to cause cortical malformations resemblant of classical lissencephaly but with a specific combination of features. To date, TUBA1A mutations have been described in five patients and three foetuses. Our aims were to establish how common TUBA1A mutations are in patients with lissencephaly and to contribute to defining the phenotype associated with TUBA1A mutation. We performed mutation analysis in the TUBA1A gene in 46 patients with classical lissencephaly. In 44 of the patients, mutations in the LIS1 and/or DCX genes had previously been excluded; in 2 patients, mutation analysis was only performed in TUBA1A based on magnetic resonance imaging (MRI) findings. We identified three new mutations and one recurrent mutation in five patients with variable patterns of lissencephaly on brain MRI. Four of the five patients had congenital microcephaly, and all had dysgenesis of the corpus callosum and cerebellar hypoplasia, and variable cortical malformations, including subtle subcortical band heterotopia and absence or hypoplasia of the anterior limb of the internal capsule. We estimate the frequency of mutation in TUBA1A gene in patients with classical lissencephaly to be approximately 4%, and although not as common as mutations in the LIS1 or DCX genes, mutation analysis in TUBA1A should be included in the molecular genetic diagnosis of classical lissencephaly, particularly in patients with the combination of features highlighted in this paper.
Mitochondrial haplogroup is associated with the phenotype of familial amyloidosis with polyneuropathy in Swedish and French patients
Authors: Olsson M , Hellman U , Planté‐Bordeneuve V , Jonasson J , Lång K , Suhr OB
Published: January 2009

Familial amyloidotic polyneuropathy (FAP) is a monogenic disease caused by mutations in the transthyretin (TTR) gene. The phenotype of the most common TTR mutation, V30M, varies within and between populations. Oxidative stress and protein misfolding are cellular processes involved in the development of FAP. Because the mitochondria are important for both these processes, we investigated if mitochondrial haplogroups are related to age at onset of the disease in Swedish and French FAP patients. Mitochondrial haplogroup analysis was performed on 25 early‐onset (below 40 years) and 29 late‐onset (above 51 years) Swedish FAP patients. DNA from 249 Swedish individuals served as controls. In addition, 6 early‐onset and 17 late‐onset French FAP patients were examined with 25 French controls. The haplogroup distribution among late‐onset Swedish and French cases was similar to that found in the general populations, whereas among early‐onset cases a different haplogroup distribution was seen. The relatively rare haplogroup K was significantly more common among early‐onset cases. Our findings substantiate the suggestion that a genetic component, still to be found, affecting mitochondrial function has an impact on the amyloid generating process in transthyretin amyloidosis.
Multiple granular cell tumors are an associated feature of LEOPARD syndrome caused by mutation in PTPN11
Authors: Schrader KA , Nelson TN , De Luca A , Huntsman DG , McGillivray BC
Published: January 2009

We report a patient with a clinical and molecular diagnosis of LEOPARD syndrome (LS) associated with multiple granular cell tumors (MGCT). Bidirectional sequencing of exons 7, 12, and 13 of the PTPN11 gene revealed the T468M missense mutation in exon 12. This mutation has been previously reported in patients with LS. To our knowledge, this is the first report of MGCT associated with molecularly characterized LS and provides the first molecular evidence linking granular cell tumors (GCT) to the Ras/mitogen‐activated protein (MAP) kinase pathway. We propose that MGCT can be associated with LS. Analysis of GCT from this case tested negatively for loss of heterozygosity (LOH) at the PTPN11 and NF1 loci and did not show deletions of the PTEN gene. The absence of LOH of PTPN11 supports published functional data that T468M is a dominant‐negative mutation.
Biochemical markers associated with executive function in adolescents with early and continuously treated phenylketonuria
Authors: Sharman R , Sullivan K , Young R , McGill J
Published: January 2009

Debate continues as to why executive function (EF) continues to show impairments in children with early and continuously treated phenylketonuria (ECT‐PKU). Using a mixed model, we measured EF in 10 adolescent children with ECT‐PKU and 6 sibling controls, and examined associations between EF and (1) phenylalanine (phe) and (2) the phenylalanine : tyrosine ratio (phe : tyr). Measurements were taken on two occasions anticipated to yield variation in concurrent biochemistry resulting from changes in dietary compliance (i.e. holiday vs non‐holiday period). A repeated measures anova using the Behaviour Rating Inventory of Executive Function yielded the following results: no significant interactions; two significant group effects of substantially impaired working memory and initiation skills in children with ECT‐PKU compared with controls, irrespective of occasion and two significant time effects, suggestive of slightly poorer non‐holiday planning and organization scores in both groups. Further analyses revealed that phe levels were not significantly different on these occasions, suggesting that holiday dietary compliance may be better than expected. Correlations between EF and biochemistry in children with PKU showed that participant’s lifetime phe : tyr ratio was positively and significantly associated with EF impairment, more so than phe‐only measures.
The impact of familial environment on depression scores after genetic testing for cancer susceptibility
Authors: Ashida S , Hadley DW , Vaughn BK , Kuhn NR , Jenkins JF , Koehly LM
Published: January 2009

The associations between characteristics of family relationships and family trends in cancer worry and the psychological adjustment of recipients of genetic testing for cancer susceptibility were investigated. Data provided by 178 individuals from 24 families with Lynch syndrome who participated in a cohort study investigating psychological and behavioral outcomes of genetic testing were used. Responses from multiple family members were aggregated to construct family trends representing norms and departure from norms in cancer worry. Lower perceived family cohesion at baseline and decrease in this variable at 6 months after receipt of test results were associated with higher depression scores at 12 months. More variability in cancer worry among family members at baseline was also associated with higher depression scores at 12 months. Increase in family conflict was associated with decrease in depression scores among individuals from families with higher levels of cancer worry on average and less variability among the members. Family relationships and family trends in levels of cancer worry may play important roles in the psychological adjustment of genetic test recipients. The findings highlight the complexity of familial environment surrounding individuals that undergo genetic testing and suggest the benefits of considering these factors when providing genetic services.
Molecular and clinical consequences of novel mutations in the arylsulfatase A gene
Authors: Ługowska A , Wlodarski P , Płoski R , Mierzewska H , Dudzińska M , Matheisel A , Świętochowska H , Tylki‐Szymańska A
Published: January 2009

Metachromatic leukodystrophy (MLD), a severe neurodegenerative metabolic disorder, is caused by deficient activity of arylsulfatase A (ARSA; EC 3.1.6.8), which leads to a progressive demyelinating process in central and peripheral nervous systems. In this study, a DNA sequence analysis was performed on six Polish patients with different types of MLD. Six novel mutations were identified: one nonsense (p.R114X), three missense (p.G122C, p.G293C, p.C493F) and two frameshift mutations (g.445_446dupG and g.2590_2591dupC). Substitutions p.G293C and p.C493F and duplication g.445_446dupG caused a severe reduction of enzyme activity in transient transfection experiments on mammalian cells (less than 1% of wild‐type (WT) ARSA activity). Duplication 2590_2591dupC preserved low‐residual ARSA activity (10% of WT ARSA). In summary, the novel MLD‐causing mutations in the exons 2, 5 and even in 8 of the ARSA gene described here can be classified as severe type 0, leading in homozygosity to the late infantile form MLD. Growth retardation, delayed motor development, gait disturbances, tonic–clonic seizures and non‐epileptic muscle spasms were the first onset symptoms in patients with late infantile form of MLD. In individual with juvenile type MLD gait disturbances evidenced the onset of the disease, while in a patient with late juvenile MLD, difficulties at school were displayed.
Radiotherapy for childhood cancer and risk for congenital malformations in offspring: a population‐based cohort study
Authors: Winther JF , Boice JD , Frederiksen K , Bautz A , Mulvihill JJ , Stovall M , Olsen JH
Published: January 2009

Offspring of childhood cancer survivors may be at risk of genetic disease due to the mutagenic cancer treatments received by their parents. Congenital malformations were evaluated in a population‐based cohort study of 1715 offspring of 3963 childhood cancer survivors and 6009 offspring of 5657 survivors’ siblings. The Danish Central Population Register, Cancer Registry and Hospital Register were used to identify study subjects and congenital malformations. Gonadal and uterine radiation doses were characterized based on standard radiation‐treatment regimens. The prevalence of congenital malformations at birth in offspring of survivors (44 cases, 2.6%) was slightly higher but not statistically different from that of offspring of siblings (140 cases, 2.3%) [prevalence proportion ratio (PPR), 1.1; 95% confidence interval, 0.8–1.5] or of the general population (observed‐to‐expected ratio, 1.2; 0.9–1.6). Including malformations diagnosed later in life did not change the ratios appreciably. The risk for malformations was slightly higher in the offspring of irradiated parents than in that of non‐irradiated parents (PPR 1.2 vs 1.0) but was unrelated to gonadal dose. This study provides evidence that cancer therapy of children does not increase the risk for malformations in their offspring. Continued monitoring of genetic risks among their offspring, however, is warranted.
Estrogen receptor status in CHEK2‐positive breast cancers: implications for chemoprevention
Authors: Cybulski C , Huzarski T , Byrski T , Gronwald J , Dębniak T , Jakubowska A , Górski B , Wokołorczyk D , Masojć B , Narod SA , Lubiński J
Published: January 2009

To investigate the relationship between CHEK2 mutation status and estrogen receptor (ER) status in unselected cases of early‐onset breast cancer from Poland, we screened 4441 women diagnosed with breast cancer younger than 51 years and 7217 controls for three inherited mutations in CHEK2 (1100delC, IVS2+1G>A, del5395). ER status was compared between CHEK2‐positive and CHEK2‐negative breast cancer cases. A truncating mutation in CHEK2 was seen in 140 of 4441 cases and in 70 of 7217 controls [odds ratio (OR) = 3.3; 95% CI = 2.5–4.4; p < 0.0001]. ER status was available for 92 of 140 mutation carriers and for 3001 of 4301 non‐carriers with breast cancer. The OR was higher for ER‐positive cancers (OR = 3.9; 95% CI = 2.7–5.4; p < 0.0001) than for ER‐negative cancers (OR = 2.1; 95% CI = 1.3–3.3; p = 0.002). Sixty‐six of the 92 breast cancers in carriers of CHEK2 truncating mutations were ER positive compared with 1742 of the 3001 breast cancers in non‐carriers (72% vs 58%; p = 0.01). Women with a CHEK2 mutation face a fourfold increase in the risk of ER‐positive breast cancer and might be candidates for tamoxifen chemoprevention.
Clinical and Molecular diagnosis of the skeletal dysplasias associated with mutations in the gene encoding Fibroblast Growth Factor Receptor 3 (FGFR3) in Portugal
Authors: Almeida MR , Campos‐Xavier AB , Medeira A , Cordeiro I , Sousa AB , Lima M , Soares G , Rocha M , Saraiva J , Ramos L , Sousa S , Marcelino JP , Correia A , Santos HG
Published: January 2009

Mutations in the gene that encodes Fibroblast Growth Factor Receptor 3 (FGFR3) are associated with Achondroplasia (MIM 100800), Hypochondroplasia (MIM 146000), Muenke Syndrome (MIM 602849), Thanatophoric Dysplasia (MIM 187600, MIM 187601) and Lacrimo‐Auriculo‐Dento‐Digital Syndrome (MIM 149730).Here we report a clinical and molecular study in a large cohort of 125 Portuguese patients with these skeletal disorders. The identification of the P250R mutation allowed the confirmation of the Muenke Syndrome in 9 out of the 52 cases referred. Two known mutations were found in the Thanatophoric Dysplasia referred cases. No mutations were identified in the LADD syndrome patient. In Achondroplasia and Hypochondroplasia, genetic heterogeneity was present amongst the 70 clinically diagnosed patients with 5 different mutations identified. As in other studies, complex phenotypic heterogeneity amongst patients carrying the same gene defect was observed. In several cases, the new amino acids encoded, as a consequence of mutations, were related to the severity of patients’ phenotype. The presence of 10 misdiagnosed cases emphasizes the importance of performing mutation analysis of the hotspot regions responsible for both dysplasias (Ach and Hch). For patients with an unquestionable clinical diagnosis, lacking the most common mutations, a complete screening of FGFR3 is necessary.
Genetic analysis of first‐trimester miscarriages with a combination of cytogenetic karyotyping, microsatellite genotyping and arrayCGH
Authors: Zhang Y‐X , Zhang Y‐P , Gu Y , Guan F‐J , Li S‐L , Xie J‐S , Shen Y , Wu B‐L , Ju W , Jenkins EC , Brown WT , Zhong N
Published: January 2009

Miscarriage is the spontaneous loss of an embryo or fetus before the 20th week of pregnancy. Most miscarriages occur before the end of the first trimester (<13 weeks). Although many risk factors relate to this occurrence, genetic factors play the most important role. Chromosomal abnormalities, including both numerical and structural anomalies, underlie the majority of miscarriages. In this study, we employed a comprehensive approach using cytogenetic karyotyping, polymerase chain reaction (PCR)‐based genotyping, and microarray‐based comparative genomic hybridization (arrayCGH) in combination to analyze chromosomal profiles of 115 first‐trimester miscarriages of Chinese women. Seventy cases (61%) were found to have chromosomal anomalies, of which 90% were numerical and 10% were structural. Cytogenetic karyotyping identified 78.6% (55/70), PCR assays 2.9% (2 triploids), and arrayCGH 18.6% (13/70) of the anomalies. In this study, a microdeletion of 108 kb and four microduplications sizing from 300 to 1460 kb were observed. An advantage of using this combination approach is that microsatellite genotyping and arrayCGH can be accomplished in spite of culture failure and maternal cell contamination. In addition, arrayCGH can detect submicroscopic chromosomal anomalies and gene dosage alterations.
Cilia get serious: Meckel–Gruber and Bardet–Biedl syndromes represent a spectrum of allelic disorders
Authors: Brunham LR
Published: January 2009

Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet‐Biedl syndrome Leitch et al. (2008) Nature Genetics 40: 443–448
Cystic kidney diseases and planar cell polarity signaling
Authors: Bacallao RL , McNeill H
Published: January 2009

Renal cystic diseases are a major clinical concern as they are the most common genetic cause of end‐stage renal disease. While many of the genes causing cystic disease have been identified in recent years, knowing the molecular nature of the mutations has not clarified the mechanisms underlying cyst formation. Recent research in model organisms has suggested that cyst formation may be because of defective planar cell polarity (PCP) and/or ciliary defects. In this review, we first outline the clinical features of renal cystic diseases and then discuss current research linking our understanding of cystic kidney disease to PCP and cilia.
Comparison of intrathecal magnesium, fentanyl, or placebo combined with bupivacaine 0.5% for parturients undergoing elective cesarean delivery
Authors: UNLUGENC H. , OZALEVLI M. , GUNDUZ M. , GUNASTI S. , URUNSAK I. F. , GULER T. , ISIK G.
Published: January 2009

Background: Intrathecal (i.t.) administration of magnesium has been reported to potentiate opioid antinociception in rats and humans. In this prospective, randomized, double‐blind, study, we investigated the sensory, motor, and analgesic block characteristics of i.t. magnesium 50 mg compared with fentanyl 25 μg and saline when added to 0.5% bupivacaine (10 mg).

Methods: Ninety ASA I or II adult patients undergoing cesarean section were randomly allocated to receive 1.0 ml of 0.9% sodium chloride in group S, 50 mg of magnesium sulfate (1.0 ml) 5% in group M, or 25 μg of fentanyl (1.0 ml) in group F following 10 mg of bupivacaine 0.5% i.t. We recorded the following: onset and duration of sensory and motor block, maximal sensory block height, the time to reach the maximal dermatomal level of sensory block, and the duration of spinal anesthesia.

Results: Magnesium did not shorten the onset time of sensory and motor blockade or prolong the duration of spinal anesthesia. The duration of sensory (P<0.032) and motor (P<0.002) blockade was significantly shorter in M and S groups than in the F group. The time to reach the maximal dermatomal level of sensory block was significantly shorter in the F group than in the S and M groups (P<0.002).

Conclusion: In patients undergoing cesarean section with spinal anesthesia, the addition of magnesium sulfate (50 mg) i.t. to 10 mg of spinal bupivacaine (0.5%) did not shorten the onset time of sensory and motor blockade or prolong the duration of spinal anesthesia, as seen with fentanyl.
Depth of anaesthesia monitoring in obese patients: a randomized study of propofol–remifentanil
Authors: MEYHOFF C. S. , HENNEBERG S. W. , JØRGENSEN B. G. , GÄTKE M. R. , RASMUSSEN L. S.
Published: January 2009

Background: In obese patients, depth of anaesthesia monitoring could be useful in titrating intravenous anaesthetics. We hypothesized that depth of anaesthesia monitoring would reduce recovery time and use of anaesthetics in obese patients receiving propofol and remifentanil.

Methods: We investigated 38 patients with a body mass index ≥30 kg/m2 scheduled for an abdominal hysterectomy. Patients were randomized to either titration of propofol and remifentanil according to a cerebral state monitor (CSM group) or according to usual clinical criteria (control group). The primary end point was time to eye opening and this was assessed by a blinded observer.

Results: Time to eye opening was 11.8 min in the CSM group vs. 13.4 min in the control group (P=0.58). The average infusion rate for propofol was a median of 516 vs. 617 mg/h (P=0.24) and for remifentanil 2393 vs. 2708 μg/h (P=0.04). During surgery, when the cerebral state index was continuously between 40 and 60, the corresponding optimal propofol infusion rate was 10 mg/kg/h based on ideal body weight.

Conclusion: No significant reduction in time to eye opening could be demonstrated when a CSM was used to titrate propofol and remifentanil in obese patients undergoing a hysterectomy. A significant reduction in remifentanil consumption was found.
Preliminary Studies on Cryopreservation of Common Tench (Tinca tinca) Embryos (Work in Progress)
Authors: El‐Battawy KA , Linhart O
Published: January 2009

Contents

Vitrification could provide a promising tool for the cryopreservation of fish embryos. However, to achieve cryopreservation using vitrification, chilling sensitivity and cryoprotectants toxicity were determined using tench embryos at four developmental stages (11, 17, 23 and 29 h). Embryos treated with alcalase (2 ml/998 ml, 2 min at 22°C) were exposed to chilling with/without warming. Other embryos were exposed to methanol and glycerol at the concentration of 10% and 20% for periods of 20 min. At last, embryos were incubated at special incubator cages where hatching rates were counted. Regarding chilling sensitivity and exposure to chilling followed by warming, the hatching rates of embryos decreased significantly (p < 0.001) after exposure to 0°C at all developmental stages except the 29‐h stage compared with the controls. The embryo stage most sensitive to chilling was 11‐h stage. The 29‐h stage exhibited the least sensitivity to low temperature while 17‐h and 23‐h stages were intermediate in their sensitivity to chilling. The toxicity of methanol increased significantly (p < 0.001) with developmental stage for 11, 17 and 23‐h stages. The highest hatching rates of tench embryos were obtained with 29‐h embryos using various concentrations of methanol. The hatching rates of tench embryos exposed to glycerol concentrations were approximately similar to those embryos exposed to methanol concentrations except for 11‐h embryos that showed no hatching. Unfortunately, we could not obtain living embryos in any of the conditions examined after vitrification. In conclusion, it was quite difficult to vitrify the tench embryos during this study using various vitrifying solutions and the method reported by Chen & Tian (2005) and further studies are needed to achieve successful cryopreservation.
Cortisol Profiles in Sows Submitted to an Intermittent Suckling Regime Compared with that of Abruptly Weaned Sows
Authors: Kluivers‐Poodt M , Gerritsen R , Van Nes A , Langendijk P
Published: January 2009

Contents

The aim of this study was to monitor changes in cortisol levels in sows around the time of separation from their piglets, in two different intermittent suckling regimes, compared with that in conventionally weaned sows. Sows were either weaned at 21 days of lactation (CONT) or subjected to an intermittent suckling regime (IS) from 14 days of lactation onwards. Sows in the IS regimes were separated from their piglets for 12 h every day, either from 08:00 to 20:00 hours (IS12) or from 08:00 to 14:00 hours and 20:00 to 02:00 hours (IS6). Separation caused a transient increase in cortisol levels on the first (CONT and IS12) and second (IS12) day of separation, compared with a gradual decline from early morning when the sows were still continuously suckling. In IS6 sows, in contrast, the transient rise in cortisol levels after separation at 08:00 hours was observed on the first 3 days and also on day 7 of the IS regime. Cortisol parameters were correlated with peri‐ovulatory characteristics like onset of oestrus, onset of the LH surge and time of ovulation. Onset of the LH surge was delayed in IS6 sows. In conclusion, increase in cortisol levels as a consequence of separation of sows and piglets, is an acute, incidental phenomenon in IS12 and CONT sows, but shows a repeated acute elevation in IS6 sows, possibly placing IS6 sows at a higher risk of influencing peri‐ovulatory processes and developing cystic follicles.
Effects of Matrix Filtration of Low‐Quality Boar Semen Doses on Sperm Quality
Authors: Bussalleu E , Pinart E , Rivera MM , Briz M , Sancho S , Yeste M , Casas I , Fàbrega A , Rigau T , Rodriguez‐Gil JE , Bonet S
Published: January 2009

Contents

The aim of this work was to develop a method to enhance the sperm parameters of ejaculates with low sperm quality from Piétrain boars. Seminal doses were filtered through columns of DEAE Sephadex (length 2.5 ± 0.5 cm), CM Sephadex (length 5 ± 0.5 cm), glass wool (length 2 ± 0.5 cm) or glass bead (length 10 ± 0.5 cm), with an exit flow rate of 1 ml/40 s in all cases. For each male, 10 ml of the sperm cell‐rich fraction diluted at 1 : 6 were filtered. Sperm quality was assessed before and after filtration. Sperm morphology, sperm motility and sperm concentration were determined using the computer program sca® 2002 Production, and sperm viability was evaluated by fluorescence multistaining. Osmotic resistance test and hyperosmotic resistance test were used to determine the osmotic resistance of spermatozoa, whereas l‐lactate production estimated the metabolic activity. Results showed a decrease of sperm concentration and osmotic resistance of spermatozoa after filtration in the four matrixes. However, an increase in the frequency of viable spermatozoa with intact acrosome after filtration in glass bead columns and an increase of morphologically normal spermatozoa after filtration in Sephadex CM‐50, glass wool and glass bead columns were observed. Despite the decrease in the frequency of progressive motile spermatozoa, l‐lactate production and mitochondrial sheath integrity maintained constant after filtration. Our findings indicate that column filtration is an effective method to enhance the sperm quality by selecting viable and morphologically normal spermatozoa without altering DNA, plasma membrane, mitochondrial sheath integrity or inducing premature acrosome reaction.
Diabetes mellitus and geriatric syndromes
Authors: Araki Atsushi , Ito Hideki
Published: January 2009

Diabetes mellitus is associated with an increased prevalence and incidence of geriatric syndrome: functional disabilities, depression, fall, urinary incontinence, malnutrition and cognitive impairment. Geriatric syndrome not only leads to frailty, loss of independence and low quality of life, but also becomes a major obstacle in the treatment and care of diabetic people. The risk factors or contributing factors of geriatric symptoms are micro‐ and macrovascular complications, age‐rated comorbid disease and aging per se. Comprehensive geriatric assessment of geriatric syndrome, including basic activities of daily living, instrumental activities of daily living, gait and balance, visual acuity, the Mini‐Mental State Examination, depression scores, history and risk of fall, urination and nutrition, should be performed as part of the care of elderly diabetic patients, in particular old‐old patients. Because geriatric syndromes are multifactorial and share risk factors, diabetic people with any geriatric symptoms should be treated with a common concentric strategy, such as supervised exercise therapy including muscle‐strengthening training, psychological support, social support for adherence, and good glycemic control with avoidance of hypoglycemia.
Assessment of rolling walkers used by older adults in senior‐living communities
Authors: Liu Hao (Howe)
Published: January 2009

Aim:  Rolling walkers (RW) are among the most common ambulatory devices used in senior‐living communities. However, many observational studies have associated RW use with an increased risk of falling. Studies on how older RW users obtain and use their RW are lacking. Therefore, this study's purpose was to provide information about RW use that can aid clinical professionals in understanding how to educate RW users.

Methods:  Data was gathered from 158 RW users (≥65 years old) who had used their RW for an approximate mean of 24 months. Assessment utilized questionnaires, inspections and demonstrations.

Results:  Almost 80% of all participants obtained an RW without consultation with a medical professional (61% through their own means; 19% through medical professionals without receiving instruction or demonstration). The most common misuse was incorrect RW height (55%). Maintenance problems were observed in approximately 17% of the RW. All users admitted that their walkers had not been rechecked by medical professionals since they had obtained them. Forward‐leaning posture was apparent in participants during static standing (40%) and during ambulation (50%). Forward‐leaning posture during ambulation seemed to be more problematic in causing falls.

Conclusion:  Lack to consult a medical professional when obtaining an RW, incorrect RW height, poor RW maintenance and forward‐leaning posture were problems commonly identified. This knowledge could assist medical professionals in implementing strategies to address these problems.
Present status and perspectives regarding the therapeutic strategy for acute myeloid leukemia, non‐Hodgkin's lymphoma and multiple myeloma in the elderly
Authors: Ohta Masatsugu
Published: January 2009

The incidence of cancers increases with advancing age. To improve the quality of life of elderly patients with hematological malignancies, appropriate therapeutic approaches have to be provided under adequate informed consent and with evaluation of the prognostic factors that predict the therapeutic outcome of each disease. Even in elderly patients, combination chemotherapies are effective for obtaining a good outcome for selected populations judged by factors such as performance status, pre‐existing comorbid conditions or disease features; however, non‐intensive treatment or supportive care might also be considered for patient groups with a poor prognosis. Therefore, the clinical parameters of the relevance for treatment decisions in the elderly are herein addressed. During cancer treatment, attention must be paid to the presence of age‐related organ dysfunction, drug resistance, drug‐induced side‐effects such as end organ‐targeted toxicity, or neutropenia due to myelosuppression by cytotoxic drugs. Current therapeutic approaches are therefore expected to have good compliance and better outcome in elderly patients by the introduction of several molecularly targeted therapies, novel nucleoside analogs or non‐myeloablative stem cell transplantation.
Full‐term pregnancies after multiple hepatobiliary operations for choledochal cyst: A case report
Authors: Hasiakos Dimitris , Papakonstantinou Katerina , Vaggos George , Vitoratos Nikolaos , Papadias Konstantinos
Published: January 2009

Choledochal cysts are rare congenital cystic dilatations of the biliary tree. Choledochal cysts in pregnancy are a rare entity and represent a diagnostic and therapeutic challenge. The authors present a case of two full‐term pregnancies in a woman who underwent multiple hepatobiliary operations for a choledochal cyst. The patient had two major problems: a type IVa choledochal cyst with atrophy of the left side of the liver and a congenitally dilated pancreatic duct in the head of the gland. She underwent a drainage surgical procedure using a Roux loop of jejunum and a revision surgery in which complete excision of the cyst and hepaticojejunostomy was performed. The surgical management was completed by a left lateral hepatic segmentectomy. During her first pregnancy, she experienced an episode of cholangitis, most probably due to the remaining congenitally dilated pancreatic duct. In succeeding years, the patient presented with recurrent pancreatitis and finally she underwent a Whipple operation. After that, the patient had a second pregnancy without any complications from the biliary tract system. Although choledochal cysts rarely occur in pregnancy, clinicians should be aware of this condition, as delayed or inappropriate therapy may be catastrophic for both the mother and the fetus.
New frontiers of assisted reproductive technology (Chien Tien Hsu Memorial Lecture 2007)
Authors: Ho P. C.
Published: January 2009

Many significant advances have been made in assisted reproductive technology since the birth of the first baby conceived with in vitro fertilization and embryo transfer. The development of recombinant gonadotropins and gonadotropin releasing hormone antagonists helps to simplify the ovarian stimulation. Excessive ovarian stimulation should be avoided because of the risks of ovarian hyperstimulation syndrome and reduction in endometrial receptivity. Maturation of oocytes in vitro has been developed in some centers. It is still uncertain whether techniques such as assisted hatching, blastocyst transfer and pre‐implantation aneuploidy screening can improve the live birth rates in assisted reproduction. The introduction of pre‐implantation genetic diagnosis for selection of human lymphocyte antigens (HLA) compatible embryos for treatment of siblings has raised ethical concerns. There is a higher risk of obstetric complications and congenital abnormalities even in singleton pregnancies achieved with assisted reproduction. Because of the risks of multiple pregnancies, elective single embryo transfer is increasingly used in good‐prognosis patients. With a good freezing program, the cumulative pregnancy rate (including the pregnancies from subsequent replacement of frozen‐thawed embryos) is not adversely affected. Improvement in cryopreservation techniques has made it possible to cryopreserve slices of ovarian tissue or oocytes, thus helping women who have to receive sterilizing forms of anti‐cancer treatment to preserve their fertility. It is important that the development of the new techniques should be based on good scientific evidence. Ethical, legal and social implications should also be considered before the introduction of new techniques.
An unsupervised classification method of uterine electromyography signals: Classification for detection of preterm deliveries
Authors: Diab M. O. , Marque C. , Khalil M.
Published: January 2009

Aim: This article proposes an unsupervised classification method that can be applied to the electromyography signal of uterine contractions for the detection of preterm birth.

Methods: The frequency content of the electromyography changes from one woman to another, and during pregnancy, so wavelet decomposition is first used to extract the parameters of each contraction, and an unsupervised statistical classification method based on Fisher's test is used to classify the events. A principal component analysis projection is then used as evidence of the groups resulting from this classification. Another method of classification based on a competitive neural network is also applied on the same signals. Both methods are compared.

Results: Results show that uterine contractions may be classified into independent groups according to their frequency content and according to term (either at recording or at delivery).
The strength of annealed, heat‐strengthened and fully tempered float glass
Authors: VEER F. A. , LOUTER P. C. , BOS F. P.
Published: January 2009

In the last two decades architectural glass has made an enormous leap from a secondary material to a material that combines structural and cladding roles. The structural role is a new and problematic one. In contrast to most other engineering materials the strength of glass is not a material parameter but a parameter dependent on processing quality and damage to the glass surface. There is also no real agreement on how strong glass is. There is a concept Euronorm for structural glass that has values for the characteristic strength for annealed, heat‐strengthened, fully tempered and chemically toughened glass. There is however no real agreement on the validity of these values for design of glass beams or columns. To provide an independent set of values a statistically significant series of four‐point bending tests on glass were conducted using both lying and standing positions resulting in a set of values for the characteristic strength.
Stress‐intensity factors for circular hollow section V‐joints with a rack‐plate chord
Authors: QIAN XUDONG
Published: January 2009

This study investigates the fatigue crack‐driving force, measured by the linear‐elastic stress‐intensity factors (SIFs), for a surface crack at the root of the welds in a thick‐walled, circular hollow section (CHS) V‐shape joint, typically installed in modern offshore jack‐up platforms. The primary (chord) member of the V‐joint consists of two half CHSs welded to both sides of a thick rack plate, while the secondary (brace) member adopts thick‐walled CHSs. The surface‐breaking crack considered in this study locates at the interface between the rack plate and the weld metal joining the half CHS, and represents an initial flaw introduced by lack of penetration in the welding procedure. The finite‐element model incorporates a very detailed, local crack‐front mesh in a global continuous mesh through a mesh‐tying procedure, which ensures displacement continuity between the independent master surface and the dependent slave surface. A simple plate model verifies the mesh‐tying procedure in computing the linear‐elastic stress‐intensity factors for two remote loading conditions. The computation of the stress‐intensity factors employs a linear‐elastic interaction integral approach. The comparison of the computed SIF values with a previous experimental measurement for a CHS T‐joint verifies the accuracy and feasibility of the interaction integral approach in computing SIF values for surface cracks in welded tubular connections. Subsequent numerical analysis on the gapped V‐joints examines the mixed‐mode SIF values for different loading conditions and includes an array of practical joint geometric parameters and crack sizes. The nondimensional mode I stress‐intensity factors generally increases with the following variations in the joint geometric parameters: an increase in the chord radius to the wall thickness ratio (γ=d0/2t0), an increase in the brace diameter to the chord diameter ratio (β=d1/d0), a decrease in the crack depth ratio (a/t) or an increase in the crack length c. The current study identifies a practical group of V‐joints that requires detailed treatment in the fatigue assessment procedure. These V‐joints adopt a large β ratio and demonstrate high mode‐mixity angles [ψ= tan−1(KII/KI)] with correspondingly high mode I and mode II stress‐intensity factors.
Carrying photosynthesis genes increases ecological fitness of cyanophage in silico
Authors: Hellweger Ferdi L.
Published: January 2009

Several viruses infecting marine cyanobacteria carry photosynthesis genes (e.g. psbA, hli) that are expressed, yield proteins (D1, HLIP) and help maintain the cell's photosynthesis apparatus during the latent period. This increases energy and speeds up virus production, allowing for a reduced latent period (a fitness benefit), but it also increases the DNA size, which slows down new virus production and reduces burst size (a fitness cost). How do these genes affect the net ecological fitness of the virus? Here, this question is explored using a combined systems biology and systems ecology (‘systems bioecology’) approach. A novel agent‐based model simulates individual cyanobacteria cells and virus particles, each with their own genes, transcripts, proteins and other properties. The effect of D1 and HLIP proteins is explicitly considered using a mechanistic photosynthesis component. The model is calibrated to the available database for Prochlorococcus ecotype MED4 and podovirus P‐SSP7. Laboratory‐ and field‐scale in silico survival, competition and evolution (gene packaging error) experiments with wild type and genetically engineered viruses are performed to develop vertical survival and fitness profiles, and to determine the optimal gene content. The results suggest that photosynthesis genes are nonessential, increase fitness in a manner correlated with irradiance, and that the wild type has an optimal gene content.