bluuebunny/crossref_metadata_2025_split huggingface dataset:
Invasive cervical cancer audit: a relative increase in interval cancers while coverage increased and incidence declined
Authors: Herbert A , Anshu  , Gregory M , Gupta SS , Singh N 
Published: April 2009

Objective  To examine screening histories of women with invasive cervical cancer in a 12‐year period during the introduction of organised screening to assess its effectiveness.Study Design  Screening histories were classified into six categories: no cytology record (1), previous cytology more than 5 years before diagnosis (2) and previous cytology within 5 years of diagnosis (3–6). Categories 3–6 were described as interval cancers and comprised previous negative cytology (3), previous repeats for low‐grade cytology (4), previous recommendations for investigation (5) and previous treatment (6).Setting  Southampton and South West Hampshire (SSWH).Population  Women resident in SSWH registered with invasive cervical carcinoma between 1985 and 1996.Methods  Data were held for analysis on an anonymous spreadsheet.Main outcome measures  Association of screening history categories with 3‐year time period, age group, type and stage of cancer and route to diagnosis; incidence per 100 000 women aged 25–64 years screened and not screened within 5 years in 1991–93 and 1994–96.Results  Interval cancers increased as a proportion of all cancers from 31.5% in 1985–87 to 48.6% in 1994–96 (P= 0.002) and showed a peak in 1991–93. Their incidence decreased from 20.1 to 10.9 per 100 000 eligible women aged 25–64 years screened within 5 years (P= 0.008) between 1991–93 and 1994–96, while incidence in women not screened within 5 years was unchanged (44.2 and 40.4). Factors other than previous negative smears were recorded in 50.9% of interval cancers. Interval cancers were more likely to be low stage, screen detected and were diagnosed in younger women (P < 0.00001).Conclusions  Interval cancers should be assessed as a proportion of eligible women screened within the same period of time and not as a proportion of all cancers. This audit demonstrates the importance of accurate cytology, appropriate follow up, prompt investigation and effective treatment of high‐grade precancerous lesions.
The effect of physical activity on pelvic organ prolapse
Authors: Ali‐Ross NS , Smith ARB , Hosker G 
Published: April 2009

Objective  The objective of this study was to determine whether pelvic organ prolapse increases after physical activity.Design  Prospective observational study.Setting  St Mary’s Hospital, Manchester, UK.Sample  Women undergoing surgery for pelvic organ prolapse.Methods  Fifty‐four women were recruited to the study. Symptoms and POPQ findings were assessed after a period of prescribed activity and overnight bedrest.Main outcome measures  Primary outcome was an increase in Pelvic Organ Prolapse Quantification (POPQ) measurements with activity. Secondary outcomes were association of symptoms or quality‐of‐life scores (Pelvic Floor Distress Inventory [PFDI] and Pelvic Floor Impact Questionnaire [PFIQ]) with an increase in POPQ measurements.Results  There was a significant increase in POPQ stage and five vaginal parameters (Aa, Ba, C, Ap and Bp) with physical activity (P < 0.001). Reported symptoms, higher PFDI and PFIQ scores and higher individual symptom bother scores were not more common in the women with greater pelvic organ descent (measured by the POPQ system) following physical activity.Conclusions  Greater pelvic organ prolapse was found on POPQ examination following physical activity, but this was not associated with worsening of symptoms and greater impairment of quality of life.
Long‐term mortality in women treated for cervical intraepithelial neoplasia
Authors: Jakobsson M , Gissler M , Paavonen J , Tapper A‐M 
Published: April 2009

Objective  The objective of this study was to study whether women surgically treated for cervical intraepithelial neoplasia (CIN) have increased mortality later in life. We also wanted to study whether pregnancy beyond 22 weeks post‐treatment affects the risk.Design  Register‐based retrospective cohort study from Finland.Setting  National data of the Hospital Discharge Register and the Cause‐of‐Death Register during 1986–2003.Population  A total of 25 827 women who had surgical treatment for CIN during 1986–2003.Methods  We calculated standardised mortality ratios (SMRs) by dividing the numbers of observed deaths (until 31 December 2006) by the numbers of expected deaths.Main outcome measures  SMRs for different causes‐of‐death groups.Results  The overall mortality increased by 17% after treatment for CIN, including increased risk of dying from all diseases and medical conditions (SMR 1.13, 95% CI 1.01–1.26), cancers (SMR 1.09, 95% CI 0.91–1.27) and injury deaths (SMR 1.31, 95% CI 1.03–1.58). As expected, the mortality from cervical cancer was high (SMR 7.69, 95% CI 4.23–11.15). Women who had delivered post‐treatment tended to have decreased overall mortality (SMR 0.78, 95% CI 0.52–1.04) and decreased disease mortality (SMR 0.63, 95% CI 0.37–0.90). However, the mortality rate was significantly increased for women who had subsequent preterm delivery (SMR 2.51, 95% CI 1.24–3.78). In this subgroup, there was a tendency of increased mortality from diseases of the circulatory system, alcohol‐related causes and injury deaths.Conclusions  Mortality rate was increased after surgical treatment for CIN. However, women who had delivered post‐treatment had decreased overall disease mortality rate. Subsequent preterm delivery may be a risk marker for increased long‐term mortality.
A 2‐year study on cytomegalovirus infection during pregnancy in a French hospital
Authors: Picone O , Vauloup‐Fellous C , Cordier A‐G , Parent Du Châtelet I , Senat M‐V , Frydman R , Grangeot‐Keros L 
Published: April 2009

Objectives To evaluate the proportion of pregnant women agreeing to cytomegalovirus (CMV) serologic screening. To collect data on CMV infection during pregnancy.Design Prospective study.Setting During two years, all pregnant women were informed on CMV infection. If the patient agreed, serological testing was performed around 12 weeks of gestation (WG) and, if negative, redone around 36 WG.Population Four thousand two hundred and eighty‐seven pregnant women followed from 12 weeks to delivery.Methods If the first CMV serologic test was negative, detailed hygiene information was given to the parents. Diagnosis of primary infection was based on the detection of CMV‐G, CMV‐M and low CMV‐G avidity index. When maternal infection was confirmed, diagnosis of CMV congenital infection was done in the newborns by urine culture within the three days following birth. Crude infection‐rate data consisted of the number of CMV infection cases and person‐time units for both exposed to hygiene CMV information (12 to 36 WG) and unexposed pregnant women (first 12 WG).Main outcome measures Rate of CMV seropositive and seronegative women. Rate of women agreeing for screening. Rate of primary infection. Rate of seroconversion. Number of CMV‐infected newborns.Results Among the 4287 women followed, 3792 were either seronegative or with an unknown immune status. 96.7% out of them agreed for screening. 53.2% were initially CMV‐specific IgG negative. Primary infection was detected in nine women between 0 and 12 WG (0.46%) and seroconversion was diagnosed in five women between 12 and 36 WG (0.26%) (midP = 0.02, 95% CI [1.07–13.6]).Conclusions If clear information on CMV infection during pregnancy is given, patients frequently agree to screening. The rate of seroconversion after information, observed in this study, is low after counselling.
Cost‐effectiveness analysis of alternative first‐trimester pregnancy termination strategies in Mexico City
Authors: Hu D , Grossman D , Levin C , Blanchard K , Goldie SJ 
Published: April 2009

Objective To assess the comparative health and economic outcomes associated with three alternative first‐trimester abortion techniques in Mexico City and to examine the policy implications of increasing access to safe abortion modalities within a restrictive setting.Design Cost‐effectiveness analysis.Setting Mexico City.Population Reproductive‐aged women with unintended pregnancy seeking first‐trimester abortion.Methods Synthesising the best available data, a computer‐based model simulates induced abortion and its potential complications and is used to assess the cost‐effectiveness of alternative safe modalities for first‐trimester pregnancy termination: (1) hospital‐based dilatation and curettage (D&C), (2) hospital‐based manual vacuum aspiration (MVA), (3) clinic‐based MVA and (4) medical abortion using vaginal misoprostol.Main outcome measures Number of complications, lifetime costs, life expectancy, quality‐adjusted life expectancy.Results In comparison to the magnitude of health gains associated with all safe abortion modalities, the relative differences between strategies were more pronounced in terms of their economic costs. Assuming all options were equally available, clinic‐based MVA was the least costly and most effective. Medical abortion with misoprostol provided comparable benefits to D&C, but cost substantially less. Enhanced access to safe abortion was always more influential than shifting between safe abortion modalities.Conclusions This study demonstrates that the provision of safe abortion is cost‐effective and will result in reduced complications, decreased mortality and substantial cost savings compared with unsafe abortion. In Mexico City, shifting from a practice of hospital‐based D&C to clinic‐based MVA and enhancing access to medical abortion will have the best chance to minimise abortion‐related morbidity and mortality.
World Health Organisation multicentre randomised trial of supplementation with vitamins C and E among pregnant women at high risk for pre‐eclampsia in populations of low nutritional status from developing countries
Authors: Villar J , Purwar M , Merialdi M , Zavaleta N , thi Nhu Ngoc N , Anthony J , De Greeff A , Poston L , Shennan A ,   on behalf of the WHO Vitamin C and Vitamin E trial group
Published: April 2009

Objective  To determine if vitamin C and E supplementation in high‐risk pregnant women with low nutritional status reduces pre‐eclampsia.Design  Multicentred, randomised, controlled, double‐blinded trial.Setting  Antenatal care clinics and Hospitals in four countries.Population  Pregnant women between 14 and 22 weeks’ gestation.Method  Randomised women received 1000 mg vitamin C and 400 iu of vitamin E or placebo daily until delivery.Main outcome measures  Pre‐eclampsia, low birthweight, small for gestational age and perinatal death.Results  Six hundred and eighty‐seven women were randomised to the vitamin group and 678 to the placebo group. Groups had similar gestational ages (18.1; SD 2.4 weeks), socio‐economic, clinical and demographical characteristics and blood pressure at trial entry. Risk factors for eligibility were similar, except for multiple pregnancies: placebo group (14.7%), vitamins group (11.8%). Previous pre‐eclampsia, or its complications, was the most common risk factor at entry (vitamins 41.6%, placebo 41.3%). Treatment compliance was 87% in the two groups and loss to follow‐up was low (vitamins 2.0%, placebo 1.3%). Supplementation was not associated with a reduction of pre‐eclampsia (RR: 1.0; 95% CI: 0.9–1.3), eclampsia (RR: 1.5; 95% CI: 0.3–8.9), gestational hypertension (RR: 1.2; 95% CI: 0.9–1.7), nor any other maternal outcome. Low birthweight (RR: 0.9; 95% CI: 0.8–1.1), small for gestational age (RR: 0.9; 95% CI: 0.8–1.1) and perinatal deaths (RR: 0.8; 95% CI: 0.6–1.2) were also unaffected.Conclusion  Vitamins C and E at the doses used did not prevent pre‐eclampsia in these high‐risk women.
Muscarinic toxins: tools for the study of the pharmacological and functional properties of muscarinic receptors
Authors: Servent Denis , Fruchart‐Gaillard Carole 
Published: April 2009

AbstractMuscarinic receptors mediate metabotropic actions of acetylcholine in the CNS and PNS and autocrine functions of acetylcholine in non‐neuronal systems. Because of the lack of highly selective muscarinic ligands, the precise location, functional role, and roles in various diseases of the five muscarinic receptor subtypes remain unclear. Muscarinic toxins isolated from the venom ofDendroaspissnakes have a natural high affinity and selectivity, associated with roles as competitive antagonists, allosteric modulators, and potential agonists. These toxins may therefore be invaluable tools for studying muscarinic receptors. We review data on the structural and pharmacological characterization of the muscarinic toxins, focusing on recent structure–function studies on toxin–receptor interactions. We discuss the potential benefits of using these toxins for investigating muscarinic functionin vivo.
p53/CEP‐1 increases or decreases lifespan, depending on level of mitochondrial bioenergetic stress
Authors: Ventura Natascia , Rea Shane L. , Schiavi Alfonso , Torgovnick Alessandro , Testi Roberto , Johnson Thomas E. 
Published: April 2009

SummaryMitochondrial pathologies underlie a number of life‐shortening diseases in humans. In the nematode Caenorhabditis elegans, severely reduced expression of mitochondrial proteins involved in electron transport chain‐mediated energy production also leads to pathological phenotypes, including arrested development and/or shorter life; in sharp contrast, mild suppression of these same proteins extends lifespan. In this study, we show that the C. elegans p53 ortholog cep‐1 mediates these opposite effects. We found that cep‐1 is required to extend longevity in response to mild suppression of several bioenergetically relevant mitochondrial proteins, including frataxin – the protein defective in patients with Friedreich’s Ataxia. Importantly, we show that cep‐1 also mediates both the developmental arrest and life shortening induced by severe mitochondrial stress. These findings support an evolutionarily conserved function for p53 in modulating organismal responses to mitochondrial dysfunction and suggest that metabolic checkpoint responses may play a role in longevity control and in human mitochondrial‐associated diseases.
Diminished contraction‐induced intracellular signaling towards mitochondrial biogenesis in aged skeletal muscle
Authors: Ljubicic Vladimir , Hood David A. 
Published: April 2009

SummaryThe intent of this study was to determine whether aging affects signaling pathways involved in mitochondrial biogenesis in response to a single bout of contractile activity. Acute stimulation (1 Hz, 5 min) of the tibialis anterior (TA) resulted in a greater rate of fatigue in old (36 month), compared to young (6 month) F344XBN rats, which was associated with reduced ATP synthesis and a lower mitochondrial volume. To investigate fiber type‐specific signaling, the TA was sectioned into red (RTA) and white (WTA) portions, possessing two‐ to 2.5‐fold differences in mitochondrial content. The expression and contraction‐mediated phosphorylation of p38, MKK3/6, CaMKII and AMPKα were assessed. Kinase protein expression tended to be higher in fiber sections with lower mitochondrial content, such as the WTA, relative to the RTA muscle, and this was exaggerated in tissues from senescent, compared to young animals. At rest, kinase activation was generally similar between young and old animals, despite the age‐related variations in mitochondrial volume. In response to contractile activity, age did not influence the signaling of these kinases in the high‐oxidative RTA muscle. However, in the low‐oxidative WTA muscle, contraction‐induced kinase activation was attenuated in old animals, despite the greater metabolic stress imposed by contractile activity in this muscle. Thus, the reduction of contraction‐evoked kinase phosphorylation in muscle from old animals is fiber type‐specific, and depends on factors which are, in part, independent of the metabolic milieu within the contracting fibers. These findings imply that the downstream consequences of kinase signaling are reduced in aging muscle.
Once daily dose gentamicin in neonates — is our dosing correct?
Authors: Serane Tiroumourougane V , Zengeya Stanley , Penford Gemma , Cooke Jane , Khanna Gitika , McGregor‐Colman Elle 
Published: April 2009

AbstractAim: The aim of this paper is to study the safety and efficacy (measured by therapeutic level) of once daily gentamicin in neonates ≥32 weeks of gestation and ≤7 days of age.Setting: Level II neonatal intensive care unit.Subjects: Neonates ≥32 weeks of gestation and ≤7 days of age treated with gentamicin for presumed sepsis.Methods: Gentamicin was administered by intravenous injection at 4 mg/kg/day once daily. Peak and trough gentamicin levels were measured at the third dose.Results: In neonates with gestational age between 32 and 36 weeks, 14 out of 65 (22%) had trough serum concentration >2 mg/L. Only 39 (60%) had peak and trough levels within the therapeutic range. All babies who had audiometric evaluation (62 out of 65) had normal hearing. Out of the 65 babies, 60 had paired serum creatinine levels estimated and none had evidence of renal dysfunction. Among term neonates, only 2 out of 50 had the trough serum concentration of >2 mg/L. In 38 (76%) of the 50 neonates, the trough serum gentamicin concentration was <2.0 mg/L and the peak level was <10 mg/L. Forty‐eight babies had audiometric evaluation which was normal.Conclusion: A dose of 4 mg/kg/day produces serum gentamicin levels outside the therapeutic range in two‐fifths of neonates between 32 and 36 ± 6 weeks. A single dose of 4 mg/kg/day of gentamicin is appropriate for term babies and probably excessive for 32–36 weeks’ neonates.
Nutrient limitation along eutrophic rivers? Roles of N, P and K input in a species‐rich floodplain hay meadow
Authors: Loeb Roos , Kuijpers Lisa , Peters Roy C.J.H. , Lamers Leon P.M. , Roelofs Jan G.M. 
Published: April 2009

AbstractQuestion: Is the growth of biodiverse floodplain plant communities along nutrient‐rich lowland rivers still limited by nutrients?Location: Floodplains of the river Overijsselse Vecht, the Netherlands.Methods: Soil characteristics and potential nutrient limitation of the vegetation types were studied in two hay meadows, both belonging to the Fritillario‐Alopecuretum, in the floodplain of the eutrophic river Overijsselse Vecht (the Netherlands). The meadows had different fertilization histories: one was a species‐rich hay meadow managed as a nature reserve, the other a newly created nature reserve that had been used as an agricultural pasture before. Sods collected from both locations were transferred to a glasshouse, fertilized weekly with NP, NK, PK, NPK or control solutions and harvested three times a year during two successive growing seasons.Results: Biomass production of sods from both locations of this floodplain still appeared to be limited by N. Interestingly, the sods from the existing nature reserve were also limited by K, but only in the second year. Fertilization caused a shift in the relative abundance of the different plant families. Tissue nutrient concentrations were increased by fertilization with the nutrient in question, but decreased if biomass production was stimulated.Conclusions: Even in eutrophic river areas, the nutrient concentrations of the surface water may still determine the development of potentially biodiverse floodplain vegetation.Nomenclature: Van der Meijden (2005)
Effects of climate on occurrence and size of large fires in a northern hardwood landscape: historical trends, forecasts, and implications for climate change in Témiscamingue, Québec
Authors: Drever C. Ronnie , Bergeron Yves , Drever Mark C. , Flannigan Mike , Logan Travis , Messier Christian 
Published: April 2009

AbstractQuestions:What climate variables best explain fire occurrence and area burned in the Great Lakes‐St Lawrence forest of Canada? How will climate change influence these climate variables and thereby affect the occurrence of fire and area burned in a deciduous forest landscape in Témiscamingue, Québec, Canada?Location:West central Québec and the Great Lakes‐St Lawrence forest of Canada.Methods:We first used an information‐theoretic framework to evaluate the relative role of different weather variables in explaining occurrence and area burned of large fires (>200 ha, 1959‐1999) across the Great Lakes‐St Lawrence forest region. Second, we examined how these weather variables varied historically in Témiscamingue and, third, how they may change between the present and 2100 according to different scenarios of climate change based on two Global Circulation Models.Results:Mean monthly temperature maxima during the fire season (Apr‐Oct) and weighted sequences of dry spells best explained fire occurrence and area burned. Between 1910 and 2004, mean monthly temperature maxima in Témiscamingue showed no apparent temporal trend, while dry spell sequences decreased in frequency and length. All future scenarios show an increase in mean monthly temperature maxima, and one model scenario forecasts an increase in dry spell sequences, resulting in a slight increase in forecasted annual area burned.Conclusion:Despite the forecasted increase in fire activity, effects of climate change on fire will not likely affect forest structure and composition as much as natural succession or harvesting and other disturbances, principally because of the large relative difference in area affected by these processes.
Crystal structures of the regulatory subunit of Thr‐sensitive aspartate kinase from Thermus thermophilus
Authors: Yoshida Ayako , Tomita Takeo , Kono Hidetoshi , Fushinobu Shinya , Kuzuyama Tomohisa , Nishiyama Makoto 
Published: April 2009

Crystal structures of the regulatory subunit of Thr‐sensitive aspartate kinase (AK; EC 2.7.2.4) from Thermus thermophilus (TtAKβ) were determined at 2.15 Å in the Thr‐bound form (TtAKβ‐Thr) and at 2.98 Å in the Thr‐free form (TtAKβ‐free). Although both forms are crystallized as dimers, the contact surface area of the dimer interface in TtAKβ‐free (3200 Å2) is smaller than that of TtAKβ‐Thr (3890 Å2). Sedimentation equilibrium analyzed by ultracentrifugation revealed that TtAKβ is present in equilibrium between a monomer and dimer, and that Thr binding shifts the equilibrium to dimer formation. In the absence of Thr, an outward shift of β‐strands near the Thr‐binding site (site 1) and a concomitant loss of the electron density of the loop region between β3 and β4 near the Thr‐binding site are observed. The mechanism of regulation by Thr is discussed on the basis of the crystal structures. TtAKβ has higher thermostability than the regulatory subunit of Corynebacterium glutamicum AK, with a difference in denaturation temperature (Tm) of 40 °C. Comparison of the crystal structures of TtAKβ and the regulatory subunit of C. glutamicum AK showed that the well‐packed hydrophobic core and high Pro content in loops contribute to the high thermostability of TtAKβ.