bluuebunny/crossref_metadata_2025 huggingface dataset:
Preliminary study of contrast-enhanced ultrasound in combination with blue dye vs. indocyanine green fluorescence, in combination with blue dye for sentinel lymph node biopsy in breast cancer
Authors: Zhou Yidong , Li Yan , Mao Feng , Zhang Jing , Zhu Qingli , Shen Songjie , Lin Yan , Zhang Xiaohui , Liu He , Xiao Mengsu , Jiang Yuxin , Sun Qiang
Published: October 2019

Background

This preliminary study aimed to examine the feasibility of sentinel lymph node biopsy (SLNB) using contrast-enhanced ultrasound (CEUS) vs. indocyanine green fluorescence (ICG), combined with blue dye in patients with breast cancer.

Methods

This was a retrospective study of consecutive female patients with invasive stage I-III (based on pre-operative physical examination and imaging) primary breast cancer at the Peking Union Medical College Hospital between 01/2013 and 01/2015 who underwent preoperative SLNB by ICG + blue dye or CEUS + blue dye. The numbers of detected SLNs, detection rates, and recurrence-free survival (RFS) rates were compared between the two groups.

Results

A total of 443 patients were included. The detection rates of SLNs in the CEUS + blue dye and ICG + blue dye groups were 98.4 and 98.1%, respectively (P = 0.814). The average numbers of SLNs detected per patient showed no significant difference between the two groups (3.06 ± 1.33 and 3.12 ± 1.31 in the CEUS + blue dye and ICG + blue dye groups, respectively; P = 0.659). After a median follow-up of 46 months, five patients in the CEUS + blue dye group and 15 in the ICG + blue dye group had recurrence. RFS rates showed no significant difference (P = 0.55).

Conclusion

This preliminary study suggests that CEUS + blue dye and ICG + blue dye are both feasible for SLN detection in breast cancer.
High-level expression of protein tyrosine phosphatase non-receptor 12 is a strong and independent predictor of poor prognosis in prostate cancer
Authors: Weidemann Sören A. , Sauer Charlotte , Luebke Andreas M. , Möller-Koop Christina , Steurer Stefan , Hube-Magg Claudia , Büscheck Franziska , Höflmayer Doris , Tsourlakis Maria Christina , Clauditz Till S. , Simon Ronald , Sauter Guido , Göbel Cosima , Lebok Patrick , Dum David , Fraune Christoph , Kind Simon , Minner Sarah , Izbicki Jakob , Schlomm Thorsten , Huland Hartwig , Heinzer Hans , Burandt Eike , Haese Alexander , Graefen Markus , Heumann Asmus
Published: October 2019

Background

Protein tyrosine phosphatase non-receptor 12 (PTPN12) is ubiquitously tyrosine phosphatase with tumor suppressive properties.

Methods

PTPN12 expression was analyzed by immunohistochemistry on a tissue microarray with 13,660 clinical prostate cancer specimens.

Results

PTPN12 staining was typically absent or weak in normal prostatic epithelium but seen in the majority of cancers, where staining was considered weak in 26.5%, moderate in 39.9%, and strong in 4.7%. High PTPN12 staining was associated with high pT category, high classical and quantitative Gleason grade, lymph node metastasis, positive surgical margin, high Ki67 labeling index and early prostate specific antigen recurrence (p < 0.0001 each). PTPN12 staining was seen in 86.4% of TMPRSS2:ERG fusion positive but in only 58.4% of ERG negative cancers. Subset analyses discovered that all associations with unfavorable phenotype and prognosis were markedly stronger in ERG positive than in ERG negative cancers but still retained in the latter group. Multivariate analyses revealed an independent prognostic impact of high PTPN12 expression in all cancers and in the ERG negative subgroup and to a lesser extent also in ERG positive cancers. Comparison with 12 previously analyzed chromosomal deletions revealed that high PTPN12 expression was significantly associated with 10 of 12 deletions in ERG negative and with 7 of 12 deletions in ERG positive cancers (p < 0.05 each) indicating that PTPN12 overexpression parallels increased genomic instability in prostate cancer.

Conclusions

These data identify PTPN12 as an independent prognostic marker in prostate cancer. PTPN12 analysis, either alone or in combination with other biomarkers might be of clinical utility in assessing prostate cancer aggressiveness.
Initial and delayed thyroid-stimulating hormone elevation in extremely low-birth-weight infants
Authors: Yoon Shin Ae , Chang Yun Sil , Ahn So Yoon , In Sung Se , Park Won Soon
Published: October 2019

Background

To determine the incidence, etiology, and outcomes of thyroid-stimulating hormone (TSH) elevation in extremely low-birth-weight infants (ELBWIs).

Methods

Newborn thyroid screening data of 584 ELBWIs (birth weight, < 1000 g; gestational age, ≥ 23 weeks) were retrospectively analyzed to identify initial (≤ 2 postnatal weeks) and delayed (> 2 weeks) TSH elevations. Growth and neurodevelopmental outcomes at 2 years’ corrected age (CA) were assessed according to levothyroxine replacement.

Results

Initial and delayed TSH elevations were detected at CAs of 27 and 30 weeks, respectively, with incidence rates of 0.9 and 7.2%, respectively. All infants with initial TSH elevations had perinatal asphyxia, and 95% of those with delayed TSH elevation were exposed to various stressors, including respiratory support, drugs, and surgery within 2 weeks before diagnosis of TSH elevation. Free thyroxine (T4) levels were simultaneously reduced in 80 and 57% of infants with initial and delayed TSH elevations, respectively. Both initial and delayed TSH elevations were transient, regardless of levothyroxine replacement. Infants receiving levothyroxine replacement therapy had significantly higher TSH elevations, significantly lower free T4 levels, and significantly reduced mortality, compared to untreated infants. However, levothyroxine replacement had no significant effect on long-term growth and neurodevelopmental outcomes.

Conclusions

The timing of insult superimposition on hypothalamic–pituitary–thyroid axis maturation is a major determinant of initial or delayed TSH elevation in ELBWIs. Levothyroxine replacement did not affect growth or neurodevelopmental outcomes in this population.
Are volunteering and caregiving associated with suicide risk? A Census-based longitudinal study
Authors: Rosato Michael , Tseliou Foteini , Wright David M. , Maguire Aideen , O’Reilly Dermot
Published: October 2019

Background

Opposing risks have been identified between different prosocial activities, with volunteering having been linked to better mental health while caregiving has been associated with higher prevalence and incidence of depression. This study explored suicide risk of people engaged in prosocial activities of caregiving and/or volunteering.

Methods

A Census-based record linkage study of 1,018,000 people aged 25–74 years (130,816 caregivers; 110,467 volunteers; and 42,099 engaged in both) was undertaken. Caregiving (light: 1–19; intense: ≥20 h/week), volunteering and mental health status were derived from 2011 Census records. Suicide risk (45 months follow-up) was assessed using Cox models adjusted for baseline mental health.

Results

Intense caregiving was associated with worse mental health (ORadj = 1.15: 95%CI = 1.12, 1.18) and volunteering with better mental health (OR = 0.87: 95%CI = 0.84, 0.89). For those engaged in both activities, likelihood of poor mental health was determined by caregiving level. There were 528 suicides during follow-up, with those engaged in both activities having the lowest risk of suicide (HR = 0.34: 95%CI = 0.14, 0.84). Engaging in either volunteering or caregiving was associated with lower suicide risk for those with good mental health at baseline (HR = 0.66: 95%CI = 0.49, 0.88) but not for their peers with baseline poor mental health (HR = 1.02: 95%CI = 0.69, 1.51).

Conclusions

Although an increased risk of poor mental health was identified amongst caregivers, there was no evidence of an increased risk of suicide.
Can an insole for obese individuals maintain the arch of the foot against repeated hyper loading?
Authors: Saito Yuki , Chikenji Takako S. , Takata Yuichi , Kamiya Tomoaki , Uchiyama Eiichi
Published: October 2019

Background

Insoles are often applied as preventive therapy of flatfoot deformity, but the therapeutic effects on obese individuals are still controversial. We aimed to investigate the effect of insole use on time-dependent changes in the foot arch during a repeated-loading simulation designed to represent 20,000 contiguous steps in individuals with a BMI value in the range of 30–40 kg/m2.

Methods

Eighteen cadaveric feet were randomly divided into the following three groups: normal, obese, and insole. Ten thousand cyclic loadings of 500 N (normal group) or 1000 N (obese and insole groups) were applied to the feet. We measured time-dependent change in arch height and calculated the bony arch index (BAI), arch flexibility, and energy absorption.

Results

The normal group maintained more than 0.21 BAI, which is the diagnostic criterion for a normal arch, throughout the 10,000 cycles; however, BAI was less than 0.21 at 1000 cycles in the obese group (mean, 0.203; 95% confidence interval [CI] 0.196–0.209) and at 6000 cycles in the insole group (mean, 0.200; 95% CI, 0.191–0.209). Although there was a significant time-dependent decrease in flexibility and energy absorption in both the obese and insole groups (P < 0.001), the difference between 1 and 10,000 cycles were significantly smaller in the insole group than in the obese group (P = 0.024).

Conclusions

Use of insoles for obese individuals may help to slow time-dependent foot structural changes. However, the effect was not enough to maintain the foot structure against repeated hyper loadings.
Hypomagnesemia is associated with new-onset diabetes mellitus following heart transplantation
Authors: Peled Yael , Ram Eilon , Lavee Jacob , Tenenbaum Alexander , Fisman Enrique Z. , Freimark Dov , Klempfner Robert , Sternik Leonid , Shechter Michael
Published: October 2019

Background

Diabetes mellitus (DM) is a major cause of morbidity and mortality following heart transplantation (HT), with 21% and 35% of survivors being affected within 1 and 5 years following HT, respectively. Magnesium deficiency is common among HT patients treated with calcineurin inhibitors and is a known risk factor for DM in non-HT patients. We therefore investigated the association between serum Mg (s-Mg) levels and new-onset diabetes after transplantation (NODAT).

Methods

Between 2002 and 2017, 102 non-DM HT patients were assessed. In accordance with the mean value of all s-Mg levels recorded during the first year post-HT, patients were divided into high s-Mg (≥ 1.8 mg/dL) and low s-Mg (< 1.8 mg/dL) groups. The endpoint was NODAT, defined according to the diagnostic criteria of the American Diabetes Association.

Results

Baseline clinical and demographic characteristics for the high (n = 45) and low s-Mg (n = 57) groups were similar. Kaplan–Meier survival analysis showed that 15-year freedom from NODAT was significantly higher among patients with high vs low s-Mg (85% vs 46% log-rank test, p < 0.001). Consistently, multivariate analysis adjusted for age, gender, immunosuppression therapies, BMI and mean creatinine values in the first year post-HT, showed that low s-Mg was independently associated with a significant > 8-fold increased risk for NODAT (95% CI 2.15–32.63, p = 0.003). Stroke rate was significantly higher in patients with low s-Mg levels vs high s-Mg (14% vs 0, p = 0.025), as well as long term mortality (HR 2.6, 95% CI 1.02–6.77, p = 0.05).

Conclusions

Low s-Mg level post-HT is an independent risk factor for NODAT in HT patients. The implications of interventions, focusing on preventing or correcting low s-Mg, for the risk of NODAT and for clinical outcomes should be evaluated.
Suboptimal concordance in testing and retesting results of triple-negative breast carcinoma cases among laboratories: one institution experience
Authors: De Jesus Jose , Rosa Marilin
Published: October 2019

Background

Triple-negative breast carcinoma (TNBC) patients do not benefit from hormone- or human epidermal growth factor receptor 2- (HER2-) targeted therapies. Accurate testing is pivotal for these patients.

Methods

TNBC cases that were retested at our institution during a 3-year period were evaluated for concordance rates in estrogen (ER) and progesterone (PR) receptor and HER2 results.

Results

We found 19 (22%) discrepancies (13 major/6 minor) among 86 cases. Minor discrepancies were in HER2 changes by immunohistochemistry, and all cases were demonstrated to be negative by and dual in situ hybridization. All major discrepancies were in ER/PR expression changes. In only 2 cases the treatment changed based on repeated results and/or patient history.

Conclusions

Discrepancies in prognostic/predictive testing continue to be frequent despite rigorous regulations. However, since for the majority of patients in our setting, the treatment plan did not change, reflex retesting for TNBC has been deemed unnecessary in our institution.
Elevated triglyceride-to-HDL cholesterol ratio is an indicator for insulin resistance in middle-aged and elderly Taiwanese population: a cross-sectional study
Authors: Yeh Wei-Chung , Tsao Yu-Chung , Li Wen-Cheng , Tzeng I-Shiang , Chen Liang-Sien , Chen Jau-Yuan
Published: October 2019

Background

Previous studies have reported that the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio could be a simple clinical indicator of insulin resistance (IR), but the results indicated that there were heterogeneities between different ethnicities. We aimed to investigate the association between TG/HDL-C and IR (as measured by homeostasis model assessment of IR [HOMA-IR]), and establish a clinical prediction rule for IR in middle-aged and elderly Taiwanese.

Methods

A total of 398 subjects were recruited, and each subject completed a questionnaire that included personal and medical history data, and underwent anthropometric measurement and blood sampling. IR was defined as HOMA-IR index value ≥2.0. Chi-squared test, independent two-sample t-test, Pearson’s correlation coefficient, and multiple logistic regression were used to evaluate the association between IR and TG/HDL-C ratio. A receiver operating characteristic (ROC) analysis was conducted to evaluate the ability of the developed clinical prediction rule to correctly discriminate between subjects of IR positive and IR negative groups.

Results

A significant association between IR and TG/HDL-C ratio was identified with a Pearson’s correlation coefficient of 0.35 (p-value< 0.001). In multiple logistic regression, high BMI (OR = 1.23; 95% C.I. = 1.13–1.33), hypertension (OR = 1.90; 95% C.I. = 1.12–3.21), diabetes mellitus (OR = 5.44; 95% C.I. = 2.93–10.08) and high TG/HDL ratio (OR = 1.45; 95% C.I. = 1.23–1.72) were significantly associated with the risk of elevated HOMA-IR.

The area under ROC curves for TG/HDL-C ratio was 0.729 and the optimal threshold value was 2.197 where the corresponding of sensitivity and specificity were 72.4 and 65.1%.

Conclusions

Our findings showed that the elevated TG/HDL-C ratio was significantly associated with IR and could be used as an indicator of IR among the middle-aged and elderly population in Taiwan. It is clinically available, thus eliminating any additional costs. Future research is warranted to investigate the use of TG/HDL-C ratio combined with other risk factors for predicting IR under diverse ethnic backgrounds.
Perspectives on the HIV continuum of care among adult opioid users in New York City: a qualitative study
Authors: Tofighi Babak , Sindhu Selena S. , Chemi Chemi , Lewis Crystal Fuller , Dickson Victoria Vaughan , Lee Joshua D.
Published: October 2019

Background

Engagement in the HIV care continuum combined with office-based opioid treatment remains a cornerstone in addressing the intertwined epidemics of opioid use disorder (OUD) and HIV/AIDS. Factors influencing patient engagement with OUD and HIV care are complex and require further study.

Methods

In this qualitative study, in-depth interviews were conducted among 23 adult patients who use drugs (PWUD) in an inpatient detoxification program in New York City. The semi-structured interview guide elicited participant experiences with various phases of the HIV care continuum, including factors influencing access to HIV care, interactions with HIV and primary care providers, preferences around integrated care approaches for OUD and HIV, and barriers experienced beyond clinical settings which affected access to HIV care (e.g., insurance issues, transportation, cost, retrieving prescriptions from their pharmacy). Data collection and thematic analysis took place concurrently using an iterative process-based established qualitative research method.

Results

Respondents elicited high acceptability for integrated or co-located care for HIV and OUD in primary care. Factors influencing engagement in HIV care included (1) access to rapid point-of-care HIV testing and counseling services, (2) insurance coverage and costs related to HIV testing and receipt of antiretroviral therapy (ART), (3) primary care providers offering HIV care and buprenorphine, (4) illicit ART sales to pharmacies, (5) disruption in supplies of ART following admissions to inpatient detoxification or residential treatment programs, (6) in-person and telephone contact with peer support networks and clinic staff, (7) stigma, and (8) access to administrative support in primary care to facilitate reengagement with care following relapse, behavioral health services, transportation vouchers, and relocation from subsidized housing exposing patients to actively using peers.

Conclusion

These findings suggest expanding clinical and administrative support in primary care for PWUDs with patient navigators, case managers, mobile health interventions, and peer support networks to promote linkage and retention in care.
Frequency of Screening and SBT Technique Trial - North American Weaning Collaboration (FAST-NAWC): a protocol for a multicenter, factorial randomized trial
Authors: Burns K. E. A. , Rizvi Leena , Cook Deborah J. , Seely Andrew J. E. , Rochwerg Bram , Lamontagne Francois , Devlin John W. , Dodek Peter , Mayette Michael , Tanios Maged , Gouskos Audrey , Kay Phyllis , Mitchell Susan , Kiedrowski Kenneth C. , Hill Nicholas S. ,   For the Canadian Critical Care Trials Group
Published: October 2019

Rationale

In critically ill patients receiving invasive mechanical ventilation (MV), research supports the use of daily screening to identify patients who are ready to undergo a spontaneous breathing trial (SBT) followed by conduct of an SBT. However, once daily (OD) screening is poorly aligned with the continuous care provided in most intensive care units (ICUs) and the best SBT technique for clinicians to use remains controversial.

Objectives

To identify the optimal screening frequency and SBT technique to wean critically ill adults in the ICU.

Methods

We aim to conduct a multicenter, factorial design randomized controlled trial with concealed allocation, comparing the effect of both screening frequency (once versus at least twice daily [ALTD]) and SBT technique (Pressure Support [PS] + Positive End-Expiratory Pressure [PEEP] vs T-piece) on the time to successful extubation (primary outcome) in 760 critically ill adults who are invasively ventilated for at least 24 h in 20 North American ICUs. In the OD arm, respiratory therapists (RTs) will screen study patients between 06:00 and 08:00 h. In the ALTD arm, patients will be screened at least twice daily between 06:00 and 08:00 h and between 13:00 and 15:00 h with additional screens permitted at the clinician’s discretion. When the SBT screen is passed, an SBT will be conducted using the assigned technique (PS + PEEP or T-piece). We will follow patients until successful extubation, death, ICU discharge, or until day 60 after randomization. We will contact patients or their surrogates six months after randomization to assess health-related quality of life and functional status.

Relevance

The around-the-clock availability of RTs in North American ICUs presents an important opportunity to identify the optimal SBT screening frequency and SBT technique to minimize patients’ exposure to invasive ventilation and ventilator-related complications.

Trial registration

Clinical Trials.gov, NCT02399267. Registered on Nov 21, 2016 first registered.
Effect of lacosamide in peripheral neuropathic pain: study protocol for a randomized, placebo-controlled, phenotype-stratified trial
Authors: Carmland Malin E. , Kreutzfeldt Melissa , Holbech Jakob V. , Andersen Niels T. , Jensen Troels S. , Bach Flemming W. , Sindrup Søren H. , Finnerup Nanna B.
Published: October 2019

Background

Neuropathic pain is a common pain condition that has a major negative impact on health-related quality of life. However, despite decades of research, it remains difficult to treat neuropathic pain. Lacosamide is a sodium-channel blocker that is efficacious in animal models of neuropathic pain. In humans, its effect in neuropathic pain is inconclusive, based on inconsistent results and very large placebo responses. Previous trials have not used patient stratification or looked for predictors for response.

Methods

This study will be conducted as a multicenter, randomized, double-blind, placebo-controlled, parallel, phase 2, proof-of-concept, phenotype-stratified study. The study will enroll 108 patients with peripheral neuropathic pain who will be randomized to a 12-week treatment with lacosamide or placebo up to 400 mg/day in a 2:1 ratio. The primary objective is to compare the change in the mean value of the patients’ daily ratings of average pain intensity from baseline to the last week of treatment in patients with and without the irritable nociceptor phenotype in the per-protocol population. A supportive objective is to compare the effect of lacosamide with that of placebo in the two phenotypes. Secondary and tertiary outcomes include the Patient Global Impression of Change, pain relief, presence of 30% and 50% pain reduction, sleep disturbance, depression, and anxiety.

Discussion

We will examine the concept of individualized therapy based on phenotyping, and expect that this study will provide important information on the usefulness of lacosamide in the treatment of peripheral neuropathic pain.

Trial registration

ClinicalTrials.gov, NCT03777956. Registered on 18 December 2018.
Contributions of vitamin D in the management of depressive symptoms and cardiovascular risk factors: study protocol for a randomized, double-blind, placebo-controlled clinical trial
Authors: Porto Catarina Magalhães , de Paula Santana da Silva Tatiana , Sougey Everton Botelho
Published: October 2019

Background

Depression is a major cause of chronic disability throughout the world and an important cardiovascular risk factor, increasing the relative risk of coronary artery disease as well as rates of cardiovascular morbidity and mortality. Concomitant to the high prevalence of depression, there has been a reduction in exposure to sunlight with the increase in urbanization and the use of sun protectors, which has led to a reduction in serum levels of 25-hydroxyvitamin D. Therefore, this paper describes a protocol for a clinical trial with the aim of evaluating the effects of vitamin D supplementation on depression and cardiovascular risk factors to contribute evidence regarding the potential influence of supplementation on mood regulation.

Methods

This protocol study was guided by the Standard Protocol Items: Recommendations for Interventional Trials. A randomized, placebo-controlled, double-blind clinical trial will be conducted involving 224 adults (age range 18–60 years) with depression who are taking antidepressants and have no history of vitamin D supplementation, psychiatric comorbidities, chronic kidney disease, hypercalcemia, or neoplasm. The participants will be recruited from the psychiatric outpatient clinics of two universities in northeast Brazil. Eligible participants who provide written consent will be randomly designated to either the intervention group (n = 112; vitamin D supplementation 50,000 IU per week for 6 months) or the control group (n = 112; placebo taken weekly for 6 months). Measures for monitoring depressive symptoms, clinical examinations, and laboratory tests for evaluating cardiovascular risk factors and serum vitamin D levels will be performed before and after the intervention period.

Discussion

To the best of our knowledge, this will be the first clinical trial with the aim of testing the effectiveness of vitamin D supplementation on the reduction of cardiovascular risk and as an adjuvant to depression therapy for a prolonged period (6 months). The findings will contribute to the understanding of the therapeutic effects of vitamin D supplementation in the management of depression and can help guide public policies directed toward vitamin supplementation for the reduction of cardiovascular risk.

Trial registration

Brazilian Clinical Trials Registry, RBR-6yj8sj/Universal Trial Number (UTN) U1111-1217-9237. Registered on 23 July 2018.
Vector competence is strongly affected by a small deletion or point mutations in bluetongue virus
Authors: van Gennip René G. P. , Drolet Barbara S. , Rozo Lopez Paula , Roost Ashley J. C. , Boonstra Jan , van Rijn Piet A.
Published: October 2019

Background

Transmission of vector-borne virus by insects is a complex mechanism consisting of many different processes; viremia in the host, uptake, infection and dissemination in the vector, and delivery of virus during blood-feeding leading to infection of the susceptible host. Bluetongue virus (BTV) is the prototype vector-borne orbivirus (family Reoviridae). BTV serotypes 1–24 (typical BTVs) are transmitted by competent biting Culicoides midges and replicate in mammalian (BSR) and midge (KC) cells. Previously, we showed that genome segment 10 (S10) encoding NS3/NS3a protein is required for virus propagation in midges. BTV serotypes 25–27 (atypical BTVs) do not replicate in KC cells. Several distinct BTV26 genome segments cause this so-called ‘differential virus replication’ in vitro.

Methods

Virus strains were generated using reverse genetics and their growth was examined in vitro. The midge feeding model has been developed to study infection, replication and disseminations of virus in vivo. A laboratory colony of C. sonorensis, a known competent BTV vector, was fed or injected with BTV variants and propagation in the midge was examined using PCR testing. Crossing of the midgut infection barrier was examined by separate testing of midge heads and bodies.

Results

A 100 nl blood meal containing ±105.3 TCID50/ml of BTV11 which corresponds to ±20 TCID50 infected 50% of fully engorged midges, and is named one Midge Alimentary Infective Dose (MAID50). BTV11 with a small in-frame deletion in S10 infected blood-fed midge midguts but virus release from the midgut into the haemolymph was blocked. BTV11 with S1[VP1] of BTV26 could be adapted to virus growth in KC cells, and contained mutations subdivided into ‘corrections’ of the chimeric genome constellation and mutations associated with adaptation to KC cells. In particular one amino acid mutation in outer shell protein VP2 overcomes differential virus replication in vitro and in vivo.

Conclusion

Small changes in NS3/NS3a or in the outer shell protein VP2 strongly affect virus propagation in midges and thus vector competence. Therefore, spread of disease by competent Culicoides midges can strongly differ for very closely related viruses.
Investigation of insulin-like growth factors/insulin-like growth factor binding proteins regulation in metabolic syndrome patients
Authors: Pouriamehr Somayeh , Barmaki Haleh , Rastegary Mozhdeh , Lotfi Farzaneh , Nabi Afjadi Mohsen
Published: October 2019

Objective

The insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are thought to play a significant role in metabolic pathways and glucose metabolism. Unregulated levels of IGFs/IGFBPs have been associated with the development of glucose intolerance and metabolic syndrome X (MSx). We hypothesized that change of IGFs/IGFBPs levels could increase the risk of MSx; thus, this study aimed to evaluate the serostatus of IGFs/IGFBPs in individuals with MSx.

Results

After adjustment for metabolic parameters, MSx patients had a lower level of IGF-1, IGFBP-1, and IGFBP-2 compared with subjects in the control group. Further analysis revealed a positive correlation between serum levels of IGF-1 and IGF-2 (p < 0.05), as well as serum IGFBP-3 and IGF-2 (p < 0.05). Also, the statistical analysis showed a negative association of serum IGF-1 with plasma glucose and total cholesterol levels (p < 0.05). Besides, a negative relationship was found between serum concentrations of IGF-1/IGF-2 and the risk of developing MSx. These data indicated that some components of IGFs/IGFBPs are linked with the pathogenesis of MSx. In conclusion, these inverse associations showed a possible linkage between the IGF/IGFBP signaling pathway and the development of MSx. It seems the decreased concentrations of IGFs edmay be regarded as a potential biomarker for early diagnosis or even prognosis of MSx but need more systematic studies to confirmed it.
Transcatheter occlusion of giant congenital coronary cameral fistulae: a case series
Authors: Nkya Deogratias A. , Sinyangwe Greenwood , Takawira Farirai Fani
Published: October 2019

Background

A coronary cameral fistula is a rare connection between a coronary artery and a cardiac chamber or vein bypassing the cardiac capillary bed system. Most of these fistulae are congenital and solitary, although they can be acquired and multiple.

Cases presentation

Case 1: A 10-year-old black South African boy presented with a long-standing history of fatigue; he had a heart murmur, and a bounding pulse and wide pulse pressure. An echocardiogram demonstrated a large coronary cameral fistula involving his left coronary artery and his left ventricle. This was also confirmed on ascending aortogram. Surgical ligation was done and his symptoms improved afterward, but a small residual fistula remained. Case 2: A 7-year-old black South African boy had decreased effort tolerance and a heart murmur on the mid-sternal border. He had cardiomegaly on chest roentgenogram and a dilated left coronary artery origin on echocardiogram. An ascending aortogram confirmed a large left coronary cameral fistula draining to the left ventricle. Case 3: A 28-year-old black South African woman with decreased effort tolerance and chest pain on exertion had a continuous murmur over the lower sternal border. Echocardiography demonstrated a dilated right coronary artery with a fistulous connection to her right ventricle. An ascending aortogram demonstrated a tortuous coronary cameral fistula arising from her right coronary artery to her right ventricle. All three patients were successfully treated percutaneously using the Amplatzer vascular plug type II device.

Conclusion

The availability of numerous vascular closure devices has made transcatheter occlusion the treatment of choice for the majority of coronary cameral fistulae, rather than the traditional surgical ligation.
Changes in dynamic arterial elastance induced by volume expansion and vasopressor in the operating room: a prospective bicentre study
Authors: de Courson Hugues , Boyer Philippe , Grobost Romain , Lanchon Romain , Sesay Musa , Nouette-Gaulain Karine , Futier Emmanuel , Biais Matthieu
Published: October 2019

Background

Dynamic arterial elastance (Eadyn), defined as the ratio between pulse pressure variations and stroke volume variations, has been proposed to assess functional arterial load. We evaluated the evolution of Eadyn during volume expansion and the effects of neosynephrine infusion in hypotensive and preload-responsive patients.

Methods

In this prospective bicentre study, we included 56 mechanically ventilated patients in the operating room. Each patient had volume expansion and neosynephrine infusion. Stroke volume and stroke volume variations were obtained using esophageal Doppler, and pulse pressure variations were measured through the arterial line. Pressure response to volume expansion was defined as an increase in mean arterial pressure (MAP) ≥ 10%.

Results

Twenty-one patients were pressure responders to volume expansion. Volume expansion induced a decrease in Eadyn (from 0.69 [0.58–0.85] to 0.59 [0.42–0.77]) related to a decrease in pulse pressure variations more pronounced than the decrease in stroke volume variations. Baseline and changes in Eadyn after volume expansion were related to age, history of arterial hypertension, net arterial compliance and effective arterial elastance. Eadyn value before volume expansion > 0.65 predicted a MAP increase ≥ 10% with a sensitivity of 76% (95% CI 53–92%) and a specificity of 60% (95% CI 42–76%). Neosynephrine infusion induced a decrease in Eadyn (from 0.67 [0.48–0.80] to 0.54 [0.37–0.68]) related to a decrease in pulse pressure variations more pronounced than the decrease in stroke volume variations. Baseline and changes in Eadyn after neosynephrine infusion were only related to heart rate.

Conclusion

Eadyn is a potential sensitive marker of arterial tone changes following vasopressor infusion.
Investigating Undergraduate Biology Students’ Science Identity Production
Authors: Le Paul T. , Doughty Leanne , Thompson Amreen Nasim , Hartley Laurel M.
Published: October 2019

Identity production is a complex process in which a person determines who he or she is via internal dialogue and sociocultural participation. Understanding identity production is important in biology education, because students’ identities impact classroom experiences and their willingness to persist in the discipline. Thus, we suggest that educators foster spaces where students can engage in producing science identities that incorporate positive perceptions of who they are and what they have experienced. We used Holland’s theory of identity and Urrieta’s definitions of conceptual identity production (CIP) and procedural identity production (PIP) to explore the process of students’ science identity production. We interviewed 26 students from five sections of a general biology course for majors at one higher education institution. The interview protocol included items about students’ identities, influential experiences, perceptions of science, and perceptions of their classroom communities. From the interviews, we developed hierarchical coding schemes that focused on characterizing students’ CIP and PIP. Here, we describe how students’ socially constructed identities (race, gender, etc.) and their experiences may have impacted the production of their science identities. We found that authoring (i.e., making meaning of) experiences and recognition by others as a community member influenced students’ science identity production.
Controlled Multifactorial Coagulopathy: Effects of Dilution, Hypothermia, and Acidosis on Thrombin Generation In Vitro
Authors: Mitrophanov Alexander Y. , Szlam Fania , Sniecinski Roman M. , Levy Jerrold H. , Reifman Jaques
Published: October 2019

BACKGROUND:

Coagulopathy and hemostatic abnormalities remain a challenge in patients following trauma and major surgery. Coagulopathy in this setting has a multifactorial nature due to tissue injury, hemodilution, hypothermia, and acidosis, the severity of which may vary. In this study, we combined computational kinetic modeling and in vitro experimentation to investigate the effects of multifactorial coagulopathy on thrombin, the central enzyme in the coagulation system.

METHODS:

We measured thrombin generation in platelet-poor plasma from 10 healthy volunteers using the calibrated automated thrombogram assay (CAT). We considered 3 temperature levels (31°C, 34°C, and 37°C), 3 pH levels (6.9, 7.1, and 7.4), and 3 degrees of dilution with normal saline (no dilution, 3-fold dilution, and 5-fold dilution). We measured thrombin-generation time courses for all possible combinations of these conditions. For each combination, we analyzed 2 scenarios: without and with (15 nM) supplementation of thrombomodulin, a key natural regulator of thrombin generation. For each measured thrombin time course, we recorded 5 quantitative parameters and analyzed them using multivariable regression. Moreover, for multiple combinations of coagulopathic conditions, we performed routine coagulation tests: prothrombin time (PT) and activated partial thromboplastin time (aPTT). We compared the experimental results with simulations using a newly developed version of our computational kinetic model of blood coagulation.

RESULTS:

Regression analysis allowed us to identify trends in our data (P < 10−5). In both model simulations and experiments, dilution progressively reduced the peak of thrombin generation. However, we did not experimentally detect the model-predicted delay in the onset of thrombin generation. In accord with the model predictions, hypothermia delayed the onset of thrombin generation; it also increased the thrombin peak time (up to 1.30-fold). Moreover, as predicted by the kinetic model, the experiments showed that hypothermia increased the area under the thrombin curve (up to 1.97-fold); it also increased the height of the thrombin peak (up to 1.48-fold). Progressive acidosis reduced the velocity index by up to 24%; acidosis-induced changes in other thrombin generation parameters were much smaller or none. Acidosis increased PT by 14% but did not influence aPTT. In contrast, dilution markedly prolonged both PT and aPTT. In our experiments, thrombomodulin affected thrombin-generation parameters mainly in undiluted plasma.

CONCLUSIONS:

Dilution with normal saline reduced the amount of generated thrombin, whereas hypothermia increased it and delayed the time of thrombin accumulation. In contrast, acidosis in vitro had little effect on thrombin generation.
P-cadherin-induced decorin secretion is required for collagen fiber alignment and directional collective cell migration
Authors: Le Borgne-Rochet Maïlys , Angevin Lucie , Bazellières Elsa , Ordas Laura , Comunale Franck , Denisov Evgeny V. , Tashireva Lubov A. , Perelmuter Vladimir M. , Bièche Ivan , Vacher Sophie , Plutoni Cédric , Seveno Martial , Bodin Stéphane , Gauthier-Rouvière Cécile
Published: October 2019

Directional collective cell migration (DCCM) is crucial for morphogenesis and cancer metastasis. P-cadherin (also known as CDH3), which is a cell–cell adhesion protein expressed in carcinoma and aggressive sarcoma cells and associated with poor prognosis, is a major DCCM regulator. However, it is unclear how P-cadherin-mediated mechanical coupling between migrating cells influences force transmission to the extracellular matrix (ECM). Here, we found that decorin, a small proteoglycan that binds to and organizes collagen fibers, is specifically expressed and secreted upon P-cadherin, but not E- and R-cadherin (also known as CDH1 and CDH4, respectively) expression. Through cell biological and biophysical approaches, we demonstrated that decorin is required for P-cadherin-mediated DCCM and collagen fiber orientation in the migration direction in 2D and 3D matrices. Moreover, P-cadherin, through decorin-mediated collagen fiber reorientation, promotes the activation of β1 integrin and of the β-Pix (ARHGEF7)/CDC42 axis, which increases traction forces, allowing DCCM. Our results identify a novel P-cadherin-mediated mechanism to promote DCCM through ECM remodeling and ECM-guided cell migration.
Surpassing the subitizing threshold: appetitive–aversive conditioning improves discrimination of numerosities in honeybees
Authors: Howard Scarlett R. , Avarguès-Weber Aurore , Garcia Jair E. , Greentree Andrew D. , Dyer Adrian G.
Published: October 2019

Animals including humans, fish and honeybees have demonstrated a quantity discrimination threshold at four objects, often known as subitizing elements. Discrimination between numerosities at or above the subitizing range is considered a complex capacity. In the current study, we trained and tested two groups of bees on their ability to differentiate between quantities (4 versus 5 through to 4 versus 8) when trained with different conditioning procedures. Bees trained with appetitive (reward) differential conditioning demonstrated no significant learning of this task, and limited discrimination above the subitizing range. In contrast, bees trained using appetitive–aversive (reward–aversion) differential conditioning demonstrated significant learning and subsequent discrimination of all tested comparisons from 4 versus 5 to 4 versus 8. Our results show conditioning procedure is vital to performance on numerically challenging tasks, and may inform future research on numerical abilities in other animals.
Head, Heart, or Hands: How Do Employees Respond to a Radical Global Language Change over Time?
Authors: Reiche B. Sebastian , Neeley Tsedal B.
Published: October 2019

To understand how recipients respond to radical change over time across cognitive, affective, and behavioral dimensions, we conducted a longitudinal study of a mandated language change at a Chilean subsidiary of a large U.S. multinational organization. The engineering-focused subsidiary aiming to facilitate cross-border interactions embedded language-acquisition experts to transition all employees from Spanish to English full time. We gathered survey data and objective fluency scores from the language change recipients at five points over a period of two years. Using variable- and person-centered exploratory analyses, our results suggest that recipients’ negative affective responses to the language change precede their cognitive responses or self-efficacy, predicting their current language learning. Further, we find that recipients’ cognitive and affective responses over time differentially influence two future behavioral outcomes: intention to leave the organization and willingness to adopt the change. Although cognitive rather than affective responses over time drive recipients’ intentions to leave, affective responses influence recipients’ willingness to adopt English. Finally, we show that change recipients followed three trajectories of cognitive responses and two trajectories of affective responses over time. We discuss theoretical and practical implications to the literature on organizational change, emotions, and language in global organizations.
A VIOLÊNCIA ESCOLAR NA FORMAÇÃO DOCENTE
Authors: Longo Monique Marques
Published: October 2019

Conceitos como violência escolar, homicídios, conflitos interpessoais, bullying, agressões físicas e verbais têm sido veiculados cada vez mais não apenas no ambiente escolar mas nas mídias em geral. A temática faz urgir a inserção de propostas de combate ao problema tanto nas agendas políticas como na formação docente. Mas como esses temas têm sido abordados nos cursos de licenciatura ante a iminência da problemática na escola? O presente artigo objetiva responder a questão a partir de uma pesquisa empírica realizada em seis cursos de licenciatura de três universidades cariocas, duas públicas e uma privada. São apresentadas análises de conteúdos dos seis currículos analisados e informações construídas a partir de dezenoves entrevistas com alunos e professores inseridos nesses cursos. Constatou-se a superficialidade e insuficiência da temática nos cursos de formação docente assim como a eficácia de uma experiência realizada por uma disciplina constituinte de um dos cursos analisados.
PALEOCENE SEISMIC FACIES IN THE CONTINENTAL MARGIN OF URUGUAY (SOUTH AMERICA)
Authors: Soto Matías , Viera Belén , Morales Ethel , Conti Bruno , Hernández-Molina Francisco Javier
Published: October 2019

In this contribution seismic facies of the Paleocene sequence are characterized in offshore basins of Uruguay through the study of a 2D seismic database. Seven seismic horizons were identified, limiting six sedimentary intervals with different characteristics. Hence, the complexity of the Paleocene sequence is greater than suggested by other studies. Seismic facies located in the basis of the sequence can be interpreted as sandy deposits related to the action of both turbidity and bottom currents. The identification of these deposits agrees with the expected Cretaceous source rocks, in addition to the importance of the overlying Paleocene shales as a regional seal. The results of this work open interesting exploratory perspectives in the continental margin of Uruguay. FACIES SÍSMICAS DO PALEOCENE NA MARGEM CONTINENTAL DO URUGUAI (AMÉRICA DO SUL) ResumoNesta contribuição, as fácies sísmicas da sequência do Paleoceno são caracterizadas em bacias offshore do Uruguai através do estudo de uma base de dados sísmica 2D. Foram identificados sete horizontes sísmicos, limitando seis intervalos sedimentares com diferentes características. Neste estudo verifica-se que a complexidade da seqüência do Paleoceno é maior do que a sugerida por outros estudos. A fácies sísmicas localizadas na base da sequência podem ser interpretadas como sendo depósitos arenosos resultantes da ação de correntes de turbidez e de fundo. Estes depósitos correspondem a rochas-fonte cretáceas, estando cobertas regionalmente por importantes rochas selantes correspondentes a folhelhos do Paleoceno. Os resultados deste trabalho abrem interessantes perspectivas exploratórias na margem continental do Uruguai.Palavras-chave: Paleoceno. Facies Sísmicas. Margem Continental do Uruguai.
Are you handling genital oedema confidently?
Authors: Noble-Jones Rhian , Thomas Melanie J. , Davies Lara , Morgan Karen
Published: October 2019

Men, women or children can suffer from oedema (swelling) of the genitalia. When differential diagnosis has excluded acute trauma or pathology and swelling remains, the condition may be diagnosed as genital lymphoedema, a chronic condition that increases the relative risk of cellulitis. Diagnosis of genital oedema is often delayed due to problems with patient and health professional behaviour, in terms of embarrassment, lack of confidence or lack of knowledge. Awareness of this condition and knowledge on how to manage it will go a long way in helping both patients and clinicians overcome the challenges of addressing genital oedema. This article describes the authors' experiences in managing genital oedema. It also briefly discusses a new international project that seeks to identify the knowledge and training that health professionals need to manage this condition more confidently.
Interface pressures with compression systems: relevance to clinical practice
Authors: Muldoon Jeanette
Published: October 2019

Interface pressures with compression depend on many factors relating to the science of measurement and intrinsic, patient-related factors, including limb size and tissue texture. While it is important for manufacturers of compression devices to measure pressures, it may not always be relevant to clinical practice where application methods and oedematous limbs may affect final pressures. Accurate performance of any compression system relies on the use of the right technology for the right condition and patient lifestyle. Correct application following training and in accordance with instructions for use may be adapted according to individual patient comfort and needs, including mobility, tissue texture and the stage of management. In order to provide treatment regimens that are safe, effective and well tolerated by patients, as well as being easy to apply and demonstrate sound economic practice, science needs to meet clinical practice. Patient reporting is an important for successful treatment, matching clinical effectiveness with patient acceptance during reassessment and monitoring.