bluuebunny/crossref_metadata_2025_split huggingface dataset:
High rates of midazolam injection and associated harms in Bangkok, Thailand
Authors: Hayashi Kanna , Suwannawong Paisan , Ti Lianping , Kaplan Karyn , Wood Evan , Kerr Thomas 
Published: December 2012

AbstractAimsTo identify the prevalence and correlates of midazolam injection among injecting drug users in Thailand.DesignSerial cross‐sectional mixed‐methods study.SettingBangkok, Thailand.Participants  A total of 435 adults who had injected drug(s) in the past 6 months were recruited through peer outreach and word of mouth in Bangkok in 2011.MeasurementsMultivariable logistic regression was used to analyze self‐reported data collected through an interviewer‐administered survey in July–October 2011 (n = 435). Additionally, qualitative data were collected in June–July 2009 (n = 10) and analyzed to explore the health problems attributable to midazolam injection.FindingsAmong 435 survey participants, the prevalence of daily midazolam injection in the past 6 months was 37.0% (95% confidence interval: 32–42). While 75.8% of the daily midazolam injectors identified heroin as their drug of choice, 91.8% of these individuals reported substituting heroin with midazolam when heroin was unavailable. In multivariable analyses, daily midazolam injection was associated with femoral vein injection [adjusted odds ratio (AOR) = 4.48], polydrug use (AOR = 4.94), daily heroin injection (AOR = 3.25), binge use (AOR = 1.75) and perceived increase in policing pressure (AOR = 1.95) (all P < 0.05). Qualitative accounts indicated severe health problems associated with midazolam injection, including nerve and vascular injuries.ConclusionMidazolam misuse is increasing among injecting drug users in Bangkok and appears to be used primarily as a substitute for heroin. Midazolam injection was associated independently with various risk factors for injection‐related complications. Given the many deleterious effects of midazolam injection, novel interventions for midazolam injectors are needed urgently.
Endoglin in Amniotic Fluid as a Risk Factor for the Subsequent Development of Bronchopulmonary Dysplasia
Authors: Kim Sun K. , Romero Roberto , Savasan Zeynep A. , Xu Yi , Dong Zhong , Lee Deug‐Chan , Yeo Lami , Hassan Sonia S. , Chaiworapongsa Tinnakorn 
Published: December 2012

ObjectiveCross‐talk between inflammation and angiogenesis pathways has been recently reported. The objectives of this study were to: (i) examine whether amniotic fluid (AF) concentrations of soluble endoglin (sEng), a protein with anti‐angiogenic properties, change during pregnancy, parturition, or intra‐amniotic infection and/or inflammation (IAI); (ii) determine whether an increase in sEng in the AF of patients with preterm labor (PTL) and preterm prelabor rupture of membranes (PROM) is associated with adverse neonatal outcomes; and (iii) investigate potential sources of sEng in AF.Study designA cross‐sectional study was conducted to include patients in the following groups: (i) mid‐trimester (n = 20); (ii) PTL with term delivery (n = 95); (iii) PTL leading to preterm delivery with (n = 40) and without IAI (n = 46); (iv) preterm PROM with (n = 37) and without IAI (n = 37); (v) term in labor (n = 48) and not in labor (n = 44). AF concentrations of sEng were determined by enzyme‐linked immunosorbent assay. Chorioamniotic membranes, umbilical cord blood, and AF macrophages were examined for the expression of endoglin.Results(i) Patients with IAI had a higher median AF concentration of sEng than those without IAI (P = 0.02 for PTL and 0.06 for preterm PROM); (ii) AF concentrations of sEng in the 3rd and 4th quartiles were associated with IAI (OR 2.5 and 7.9, respectively); (iii) an AF sEng concentration ≥779.5 pg/mL was associated with bronchopulmonary dysplasia (BPD) (OR 7.9); (iv) endoglin was co‐localized with CD14+ macrophages in AF pellets of patients with IAI by immunofluorescence and flow cytometry; and (v) the concentration of sEng in the supernatant was significantly increased after the treatment of macrophages with endotoxin or TNF‐α.ConclusionsSoluble endoglin participates in the host response against IAI. Activated macrophages may be a source of sEng concentrations in the AF of patients with IAI. An increase of sEng in the AF is associated with BPD and adverse neonatal outcomes.
In vivo Multiphoton Microscopy Technique to Reveal the Physiology of the Mouse Uterus
Authors: Zenclussen Ana C. , Olivieri David N. , Dustin Michael L. , Tadokoro Carlos E. 
Published: December 2012

ProblemPregnancy is a challenge to the maternal immune system as it allows the growing of a semiallogeneic fetus within the uterus. Such tolerance suggests a set of complex cellular distributions and interactions inside the organ. Until now, direct observation of such processes was absent because proper intravital imaging techniques were not available.MethodWe developed a new two‐photon microscope stage together with a set of surgical procedures to provide direct observation of immune cell within the mouse uterus.ResultsUsing our technique, we observed an accumulation of dendritic cells (DCs) in the uterus during the estrus phase of the estrus cycle. Some of the observed DC clusters were located near the lumen of the uterus or small blood vessels, each situated on the antimesometrium side.ConclusionWhile two‐photon microscopy has become a widely used technology for intravital imaging, new advances in the development of staging and experimental protocols can still push the limits of this technique for exploring new biology. As proof of this, we demonstrated that with specially designed staging and surgical protocols, we observed the formation of DC clusters in the uterus; structures that may play a role in the complex immunology of the uterus–fetal interface.
Cesarean section en caul and asphyxia in preterm infants
Authors: Jin Zhen , Wang Xiaoyan , Xu Qiwei , Wang Pingting , Ai Wanting 
Published: December 2012

AbstractWe reviewed the outcome for 211 women undergoing a planned en caul (within intact membranes) cesarean section and for 836 control women with conventional lower segment section, in the period 2001–2010 at a university‐affiliated hospital in China, where the former technique has been practiced. Of the intended en caul sections there were 141 successful deliveries (66.8%), and 70 that failed and were converted to conventional lower segment cesarean section. Maternal blood loss was similar for both operation types, but the rate of asphyxia was significantly lower among preterm infants delivered by the en caul method than in the control cases. Multivariate logistic regression revealed that the volume of amniotic fluid, a low Bishop score and high birthweight were associated with failed en caul deliveries. Cesarean section en caul can be a safer option than lower segment section when preterm delivery is required.
Responsiveness of emergency obstetric care systems in low‐ and middle‐income countries: a critical review of the “third delay”
Authors: Cavallaro Francesca L. , Marchant Tanya J. 
Published: December 2012

AbstractWe reviewed the evidence on the duration, causes and effects of delays in providing emergency obstetric care to women attending health facilities (the third delay) in low‐ and middle‐income countries. We performed a critical literature review using terms related to obstetric care, birth outcome, delays and developing countries. A manual search of reference lists of key articles was also performed. 69 studies met the inclusion criteria. Most studies reported long delays in providing care, and the mean waiting time for women admitted with complications was as much as 24 h before treatment. The three most cited barriers to providing timely care were shortage of treatment materials, surgery facilities and qualified staff. Existing evidence is insufficient to estimate the effect of delays on birth outcomes. Delays in providing emergency obstetric care seem common in resource‐constrained settings but further research is necessary to determine the effect of the third delay on birth outcomes.
The impact of previous birth experiences on maternal fear of childbirth
Authors: Størksen Hege Therese , Garthus‐Niegel Susan , Vangen Siri , Eberhard‐Gran Malin 
Published: December 2012

AbstractObjectivesThis study aimed to assess the relation between fear of childbirth and previous birth experiences.DesignA prospective study of pregnant women.SettingAkershus University Hospital, Norway.PopulationParous women (n = 1357) scheduled to give birth at Akershus University Hospital in Norway during 2009–2011.MethodsData were collected using two self‐completed questionnaires at pregnancy weeks 17 and 32. Fear of childbirth was assessed by the Wijma Delivery Expectancy Questionnaire. Previous overall birth experience was measured using a numeric rating scale, and previous obstetric complications were assessed using an index of seven obstetric complications: emergency cesarean section, instrumental vaginal delivery, extensive blood loss, retained placenta, serious maternal infection during labor, thrombosis, and anal sphincter tears.Main outcome measureFear of childbirth.ResultsThe odds ratio of fear of childbirth was 4.8 (95% confidence interval (CI) 2.8–8.3) for a previous negative overall birth experience, 1.9 (95% CI 1.2–3.1) for one obstetric complication and 2.6 (95% CI 1.2–5.5) for two or more complications. The estimates were adjusted for mental health, labor pain, time since last delivery, age, and education. Almost 80% of women who experienced obstetric complications neither considered the birth a negative overall experience nor developed a fear of childbirth.ConclusionsThe association between a previous subjectively negative birth experience and fear of childbirth was high and was greater than the association between previous obstetric complications and fear of childbirth.
Response to laboratory selection with cyromazine and susceptibility to alternative insecticides in sheep blowfly larvae from the New South Wales Monaro
Authors: Levot GW 
Published: December 2012

ObjectiveTo determine the significance of cyromazine resistance in blowfly larvae from a region where resistance has been previously confirmed and to measure susceptibility of the cyromazine‐resistant blowflies to ivermectin and spinosad.MethodsBlowfly larvae from five properties located within 5 km of where cyromazine‐resistant Lucilia cuprina were detected in 2011 were tested for resistance to cyromazine. The original cyromazine‐resistant ‘Nimmitabel’ strain was reared for 13 generations on homogenised liver containing cyromazine at a concentration lethal to susceptible larvae. Larval development bioassays in which batches of neonate larvae were transferred onto homogenised bovine liver containing cyromazine or dicyclanil were used to determine whether the level of resistance had increased. The sensitivities of the ‘Nimmitabel’ strain to ivermectin and spinosad were also measured.ResultsCyromazine‐resistant larvae were identified in samples from four of the five properties near to the site of the original resistance detection. The ‘Nimmitabel’ strain responded to laboratory selection by becoming more resistant to cyromazine (8×) and to dicyclanil (3×). No larvae died after feeding on homogenate containing cyromazine at a concentration lethal to susceptible larvae. There was no cross‐resistance to ivermectin or spinosad in the ‘Nimmitabel’ strain.ConclusionThe modest increases in resistance to cyromazine and dicyclanil following laboratory selection suggest that unless the situation worsens considerably, it is unlikely that this resistance will have a significant effect on flystrike protection provided by these insecticides if applied as directed on product labels. Moreover, cyromazine‐resistant larvae remained susceptible to ivermectin and spinosad.
A single intra‐articular injection with IL‐4 plus IL‐10 ameliorates blood‐induced cartilage degeneration in haemophilic mice
Authors: van Meegeren Monique E. R. , Roosendaal Goris , Coeleveld Katja , Nieuwenhuizen Laurens , Mastbergen Simon C. , Lafeber Floris P. J. G. 
Published: December 2012

SummaryThe combination of interleukin (IL)‐4 and IL‐10 protects against blood‐induced cartilage damage in vitro. It has been hypothesized that the combination of these cytokines is effective if applied early in the process of cartilage damage. The present study investigated whether a single intra‐articular injection of IL‐4 plus IL‐10 immediately after a joint bleed limits cartilage damage in an in vivo haemophilia mouse model of blood‐induced joint damage. Factor VIII knockout mice with severe haemophilia A were punctured once with a needle below the patella to induce a joint haemorrhage. Subsequently IL‐4 plus IL‐10 (n = 24) or vehicle (n = 24) was injected intra‐articularly. After 35 days, the time needed for development of detectable joint degeneration, knee joints were examined for cartilage damage by macroscopic and microscopic evaluation. A single intra‐articular injection of IL‐4 plus IL‐10 ameliorated progression of cartilage degeneration caused by a single joint bleed to a certain extent. No effect on inflammation was observed at this time point. A single intra‐articular injection of IL‐4 plus Il‐10 directly after a single joint bleed limits progression of cartilage degeneration over time. Improved bioavailability (half‐life) of both cytokines might improve their protective ability in the development of cartilage degeneration, and probably also inflammation.
Repeated short‐term use of eltrombopag in patients with chronic immune thrombocytopenia (ITP)
Authors: Bussel James B. , Saleh Mansoor N. , Vasey Sandra Y. , Mayer Bhabita , Arning Michael , Stone Nicole L. 
Published: December 2012

SummaryEltrombopag is a thrombopoietin‐receptor agonist that stimulates platelet production and increases platelet counts in patients with chronic immune thrombocytopenia (ITP). This open‐label, single‐arm study evaluated consistency of response and safety following repeated intermittent dosing of eltrombopag 50 mg daily over 3 cycles (1 cycle = up to 6 weeks on therapy followed by up to 4 weeks off therapy). The primary endpoint was proportion of patients with a response (platelet count ≥50 × 109/l and ≥2× baseline) in Cycle 1 who subsequently responded in Cycle 2 or 3. Fifty‐two of 65 evaluable patients (80%) responded in Cycle 1; these responding patients comprised the primary analysis population. Of these, 45/52 (87%) responded in Cycle 2 or 3 [95% confidence interval (CI), 74–94%] and 34/48 (71%; 95% CI, 56–83%) responded in both Cycles 2 and 3. Time to response was consistent, with >50% of responders responding by Day 8 in each cycle. Bleeding rates relative to baseline decreased by approximately 50% during each treatment cycle. The frequency or severity of adverse events, most commonly headache, did not increase over successive cycles. If a chronic ITP patient not requiring consistent therapy responds to short‐term eltrombopag, then subsequent courses of eltrombopag, as needed, are likely to be safe and effective.
Gliotoxin is a potent NOTCH2 transactivation inhibitor and efficiently induces apoptosis in chronic lymphocytic leukaemia (CLL) cells
Authors: Hubmann Rainer , Hilgarth Martin , Schnabl Susanne , Ponath Elena , Reiter Marlies , Demirtas Dita , Sieghart Wolfgang , Valent Peter , Zielinski Christoph , Jäger Ulrich , Shehata Medhat 
Published: December 2012

SummaryChronic lymphocytic leukaemia (CLL) cells express constitutively activated NOTCH2 in a protein kinase C (PKC)– dependent manner. The transcriptional activity of NOTCH2 correlates not only with the expression of its target gene FCER2 (CD23) but is also functionally linked with CLL cell viability. In the majority of CLL cases, DNA‐bound NOTCH2 complexes are less sensitive to the γ‐secretase inhibitor (GSI) DAPT. Therefore, we searched for compounds that interfere with NOTCH2 signalling at the transcription factor level. Using electrophoretic mobility shift assays (EMSA), we identified the Aspergillum‐derived secondary metabolite gliotoxin as a potent NOTCH2 transactivation inhibitor. Gliotoxin completely blocked the formation of DNA‐bound NOTCH2 complexes in CLL cells independent of their sensitivity to DAPT. The inhibition of NOTCH2 signalling by gliotoxin was associated with down regulation of CD23 (FCER) expression and induction of apoptosis. Short time exposure of CLL cells indicated that the early apoptotic effect of gliotoxin is independent of proteasome regulated nuclear factor κB activity, and is associated with up regulation of NOTCH3 and NR4A1 expression. Gliotoxin could overcome the supportive effect of primary bone marrow stromal cells in an ex vivo CLL microenvironment model. In conclusion, we identified gliotoxin as a potent NOTCH2 inhibitor with a promising therapeutic potential in CLL.
BCR‐ABL1 transcript at 3 months predicts long‐term outcomes following second generation tyrosine kinase inhibitor therapy in the patients with chronic myeloid leukaemia in chronic phase who failed Imatinib
Authors: Kim Dennis D. , Lee Honggi , Kamel‐Reid Suzanne , Lipton Jeffrey H. 
Published: December 2012

SummaryThe BCR‐ABL1 transcript level at 3 months can predict long‐term outcomes following frontline therapy with Imatinib or Dasatinib in chronic myeloid leukaemia (CML) patients. However, data is lacking for second‐generation tyrosine kinase inhibitor (2GTKI) therapy after Imatinib failure. A total of 112 patients with CML in chronic phase receiving 2GTKI after Imatinib failure were reviewed. Treatment outcomes including complete cytogenetic (CCyR), major molecular (MMR) and molecular response 4·5 (4·5 log reduction of BCR‐ABL1 transcript level, MR4·5), treatment failure, progression‐free and overall survival (OS) were compared according to BCR‐ABL1 transcript levels at 3 or 6 months, divided into <1%IS, 1–10%IS and ≥10%IS. BCR‐ABL1 transcript level at 3 months showed better correlation with OS (P < 0·001) than that at 6 months (P = 0·147). Better OS was also observed in the patients achieving <1%IS (100%) and 1–10%IS (100%) than those with ≥10%IS at 3 months (70·6%, P < 0·001). Those with <1%IS showed the best CCyR, MMR and MR4·5 rates; 1–10%IS, intermediate; and ≥10%IS, the lowest CCyR, MMR and MR4·5 rates. The group with <1%IS at 3 months maintained significantly lower BCR‐ABL1 transcript level compared to other two groups. In conclusion, the BCR‐ABL1 transcript level at 3 months is the most relevant surrogate for outcomes following 2GTKI therapy after Imatinib failure.
The contribution of the endogenous TRPV1 ligands 9‐HODE and 13‐HODE to nociceptive processing and their role in peripheral inflammatory pain mechanisms
Authors: Alsalem Mohammad , Wong Amy , Millns Paul , Arya Pallavi Huma , Chan Michael Siang Liang , Bennett Andrew , Barrett David A , Chapman Victoria , Kendall David A 
Published: December 2012

Background and PurposeThe transient receptor potential vanilloid type 1 (TRPV1) plays a fundamental role in the detection of heat and inflammatory pain responses. Here we investigated the contribution of two potential endogenous ligands [9‐ and 13‐ hydroxyoctadecadienoic acid (HODE)] to TRPV1‐mediated noxious responses and inflammatory pain responses.Experimental Approach9‐ and 13‐HODE, and their precursor, linoleic acid, were measured in dorsal root ganglion (DRG) neurons and in the hindpaws of control and carrageenan‐inflamed rats by liquid chromatography/tandem electrospray mass spectrometry. Calcium imaging studies of DRG neurons were employed to determine the role of TRPV1 in mediating linoleic acid, 9‐HODE‐ and 13‐HODE‐evoked responses, and the contribution of 15‐lipoxygenase to the generation of the HODEs. Behavioural studies investigated the contribution of 9‐ and 13‐HODE and 15‐lipoxygenase to inflammatory pain behaviour.Key Results9‐HODE (35 ± 7 pmol g−1) and 13‐HODE (32 ± 6 pmol g−1) were detected in hindpaw tissue, but were below the limits of detection in DRGs. Following exposure to linoleic acid, 9‐ and 13‐HODE were detected in DRGs and TRPV1 antagonist‐sensitive calcium responses evoked, which were blocked by the 15‐lipoxygenase inhibitor PD146176 and an anti‐13‐HODE antibody. Levels of linoleic acid were significantly increased in the carrageenan‐inflamed hindpaw (P < 0.05), whereas levels of 9‐ and 13‐HODE were, however, decreased. Intraplantar co‐administration of anti‐9‐ and 13‐HODE antibodies and treatment with PD146176 significantly (P < 0.01) attenuated carrageenan‐induced hyperalgesia.Conclusions and ImplicationsThis study demonstrates that, although 9‐ and 13‐HODE can activate TRPV1 in DRG cell bodies, the evidence for a role of these lipids as endogenous peripheral TRPV1 ligands in a model of inflammatory pain is at best equivocal.
The sensory dorsal organs of crustaceans
Authors: Lerosey‐Aubril Rudy , Meyer Roland 
Published: December 2012

ABSTRACTThe cuticle of crustaceans bears numerous organs, of which the functions of many are unknown. One of these, the sensory dorsal organ (SDO), is present in a wide diversity of taxa. Here we critically review the variability, ultrastructure, distribution, and possible function of this enigmatic cuticular organ. Previous data are complemented by new observations on larvae and adults of various malacostracans. The SDO is composed of four sensors arranged as the corners of a square, the centre of which is occupied by a gland. Pores or pegs surrounding this central complex may also form part of the organ. The arrangement and the external aspect of the five main elements varies greatly, but this apparently has little impact on their ultrastructural organisation. The sensors and the gland are associated with a particularly thin cuticle. Each sensor contains four outer dendritic segments and the central gland is made of a single large cell. It is not yet known what this large cell secretes. The SDO is innervated from the tritocerebrum and therefore belongs to the third cephalic segment. A similar organ, here called the posterior SDO, has been repeatedly observed more posteriorly on the carapace. It resembles the SDO but has a greater number of sensors (usually six, but up to ten) apparently associated with only two outer dendritic segments. The SDO and the posterior SDO are known in the Eumalacostraca, the Hoplocarida, and the Phyllocarida. Some branchiopods also possess a ‘dorsal organ’ resembling both the SDO and the ion‐transporting organ more typical of this group. This may indicate a common origin for these two functionally distinct groups of organs. New observations on the posterior SDO support the hypothesis that the SDO and the posterior SDO are homologous to the lattice organ complexes of thecostracans. However, the relationship between the SDO and the dorsal cephalic hump of calanoid copepods remains unclear. No correlation can be demonstrated between the presence of a SDO and a particular ecological or biological trait. In fossils, the most convincing examples of SDO‐like organs are found in some Late Cambrian arthropods from the Alum Shale of southern Sweden. They suggest that related organs might have been present in non‐crustacean Cambrian arthropods. The distribution of the SDO and posterior SDO in extant and fossil crustaceans strongly suggests that these organs originated early in the history of the group, and are crucial to the functioning of these organisms. However, except for knowing that the sensors are chemoreceptors and that in a given organ a functional relationship probably exists between them and the gland, little is known about this function. The description of a SDO in freshwater carideans, which can be easily reared in a laboratory, opens the way for behavioural and physiological experiments to be undertaken that could prove crucial for the determination of this function.