bluuebunny/crossref_metadata_2025 huggingface dataset:
Nocebo Hyperalgesia can be Induced by the Observation of a Model Showing Natural Pain Expressions
Authors: Vögtle Elisabeth , Kröner-Herwig Birgit , Barke Antonia
Published: June 2019

Objectives:

Nocebo hyperalgesia is an increase in pain through the expectation of such an increase as a consequence of a sham treatment. Nocebo hyperalgesia can be induced by observation of a model demonstrating increased pain via verbal pain ratings. The aim of the present study was to investigate whether observing natural pain behavior, such as facial pain expressions, can also induce nocebo responses.

Materials and Methods:

Eighty female participants (age: 22.4 y±4.8) underwent a pressure-pain procedure (algometer) on both hands and rated their pain on a numerical rating scale. All participants received ointment on one of their hands, but no explanation was given for this. Before their own participation, the participants watched a video in which a woman underwent the same procedure and who either modeled increased pressure pain upon ointment application (nocebo condition) or showed a neutral facial expression throughout (control condition).

Results:

A 2×2 analysis of variance with condition (nocebo; control) as a between-subjects factor and ointment application (with; without) as a within-subject factor revealed a main effect for ointment and a condition×ointment interaction. In the nocebo condition, pain ratings were higher with ointment than without.

Discussion:

For the first time, it was shown that watching a model demonstrating pain through facial expressions induced nocebo hyperalgesia. As we mostly express pain through natural pain behavior rather than through pain ratings, this paradigm extends our knowledge of observational learning about pain and may have implications for contexts in which persons watch others undergo painful procedures.
Toxicologic and Inhibitory Receptor Actions of the Etomidate Analog ABP-700 and Its Metabolite CPM-Acid
Authors: Valk Beatrijs I. , McGrath Megan , Lehoux Dario , Zerler Brad , Marota John J. A. , Raines Douglas E.
Published: June 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

The etomidate analog ABP-700 produces involuntary muscle movements that could be manifestations of seizures. To define the relationship (if any) between involuntary muscle movements and seizures, electroencephalographic studies were performed in Beagle dogs receiving supra-therapeutic (~10× clinical) ABP-700 doses. γ-aminobutyric acid type A (GABAA) and glycine receptor studies were undertaken to test receptor inhibition as the potential mechanism for ABP-700 seizures.

Methods

ABP-700 was administered to 14 dogs (6 mg/kg bolus followed by a 2-h infusion at 1 mg · kg-1 · min-1, 1.5 mg · kg-1 · min-1, or 2.3 mg · kg-1 · min-1). Involuntary muscle movements were documented, electroencephalograph was recorded, and plasma ABP-700 and CPM-acid concentrations were measured during and after ABP-700 administration. The concentration-dependent modulatory actions of ABP-700 and CPM-acid were defined in oocyte-expressed α1β3γ2L GABAA and α1β glycine receptors (n = 5 oocytes/concentration) using electrophysiologic techniques.

Results

ABP-700 produced both involuntary muscle movements (14 of 14 dogs) and seizures (5 of 14 dogs). However, these phenomena were temporally and electroencephalographically distinct. Mean peak plasma concentrations were (from lowest to highest dosed groups) 35 μM, 45 μM, and 102 μM (ABP-700) and 282 μM, 478 μM, and 1,110 μM (CPM-acid). ABP-700 and CPM-acid concentration–GABAA receptor response curves defined using 6 μM γ-aminobutyric acid exhibited potentiation at low and/or intermediate concentrations and inhibition at high ones. The half-maximal inhibitory concentrations of ABP-700 and CPM-acid defined using 1 mM γ-aminobutyric acid were 770 μM (95% CI, 590 to 1,010 μM) and 1,450 μM (95% CI, 1,340 to 1,560 μM), respectively. CPM-acid similarly inhibited glycine receptors activated by 1 mM glycine with a half-maximal inhibitory concentration of 1,290 μM (95% CI, 1,240 to 1,330 μM).

Conclusions

High dose ABP-700 infusions produce involuntary muscle movements and seizures in Beagle dogs via distinct mechanisms. CPM-acid inhibits both GABAA and glycine receptors at the high (~100× clinical) plasma concentrations achieved during the dog studies, providing a plausible mechanism for the seizures.
Point of Care Ultrasound to Identify Diaphragmatic Dysfunction after Thoracic Surgery
Authors: Spadaro S. , Grasso S. , Dres M. , Fogagnolo A. , Dalla Corte F. , Tamburini N. , Maniscalco P. , Cavallesco G. , Alvisi V. , Stripoli T. , De Camillis E. , Ragazzi R. , Volta C. A.
Published: June 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Postoperative diaphragmatic dysfunction after thoracic surgery is underestimated due to the lack of reproducible bedside diagnostic methods. We used point of care ultrasound to assess diaphragmatic function bedside in patients undergoing video-assisted thoracoscopic or thoracotomic lung resection. Our main hypothesis was that the thoracoscopic approach may be associated with lower incidence of postoperative diaphragm dysfunction as compared to thoracotomy. Furthermore, we assessed the association between postoperative diaphragmatic dysfunction and postoperative pulmonary complications.

Methods

This was a prospective observational cohort study. Two cohorts of patients were evaluated: those undergoing video-assisted thoracoscopic surgery versus those undergoing thoracotomy. Diaphragmatic dysfunction was defined as a diaphragmatic excursion less than 10 mm. The ultrasound evaluations were carried out before (preoperative) and after (i.e., 2 h and 24 h postoperatively) surgery. The occurrence of postoperative pulmonary complications was assessed up to 7 days after surgery.

Results

Among the 75 patients enrolled, the incidence of postoperative diaphragmatic dysfunction at 24 h was higher in the thoracotomy group as compared to video-assisted thoracoscopic surgery group (29 of 35, 83% vs. 22 of 40, 55%, respectively; odds ratio = 3.95 [95% CI, 1.5 to 10.3]; P = 0.005). Patients with diaphragmatic dysfunction on the first day after surgery had higher percentage of postoperative pulmonary complications (odds ratio = 5.5 [95% CI, 1.9 to 16.3]; P = 0.001). Radiologically assessed atelectasis was 46% (16 of 35) in the thoracotomy group versus 13% (5 of 40) in the video-assisted thoracoscopic surgery group (P = 0.040). Univariate logistic regression analysis indicated postoperative diaphragmatic dysfunction as a risk factor for postoperative pulmonary complications (odds ratio = 5.5 [95% CI, 1.9 to 16.3]; P = 0.002).

Conclusions

Point of care ultrasound can be used to evaluate postoperative diaphragmatic function. On the first postoperative day, diaphragmatic dysfunction was less common after video-assisted than after the thoracotomic surgery and is associated with postoperative pulmonary complications.
The Utility of Leukocyte Esterase Strip Test in the Diagnosis of Pediatric Septic Arthritis
Authors: Mortazavi Seyed Mohammad Javad , Kalantar Hadi , Baghdadi Soroush , Nabian Mohammad H. , Haj Zargarbashi Ramin , Riahi Ahmad , Moharrami Alireza , Zahraei Bakhsh Fatemeh , Baghdadi Taghi
Published: June 2019

Background:

Most tests used to diagnose pediatric septic arthritis are either not accurate or do not produce rapid results. A leukocyte esterase (LE) strip test has previously been validated for the diagnosis of adult native and periprosthetic joint infections. The purpose of this prospective study was to: (1) evaluate the performance characteristics of the LE strip test in the diagnosis of pediatric septic arthritis and (2) determine the false positive rate of LE strip test on the aseptic synovial fluid (SF).

Methods:

Between May 2016 and November 2018, SF was obtained from children who were hospitalized at our tertiary referral center on the basis of suspicion of septic arthritis. All patients underwent arthrocentesis, and the aspirate was tested with LE strip test, leukocyte count, and culture. Twenty-five patients satisfied the inclusion criteria. For the second part of the study, SF from 25 children undergoing surgery for developmental dysplasia of the hip was collected and tested with LE strip test, leukocyte count, and culture.

Results:

In the first part of this study, 19 joints were classified as septic and 6 as aseptic. Considering a positive LE strip test (“++” and “+++” readings) indicative of septic arthritis yielded a sensitivity of 100%, specificity of 83%, positive predictive value of 95%, and negative predictive value of 100%. In the second part, all 25 patients with an aseptic SF had a negative test result (“−” and “+” readings).

Conclusions:

The LE strip test seems to be a valuable additional tool in the diagnosis of pediatric septic arthritis. The LE strip test has the advantages of being inexpensive and simple, providing real-time results and having a perfect negative predictive value to rule out the diagnosis of septic arthritis.

Level of Evidence:

Level II—diagnostic.
All-Cause 30-Day Mortality After Surgical Treatment for Head and Neck Squamous Cell Carcinoma in the United States
Authors: Bukatko Aleksandr R. , Patel Parth B. , Kakarla Vindhya , Simpson Matthew C. , Adjei Boakye Eric , Patel Shivam H. , Stamatakis Katherine A. , Varvares Mark A. , Osazuwa-Peters Nosayaba
Published: June 2019

Objectives:

Thirty-day (30-day) mortality, a common posttreatment quality metric, is yet to be described following surgery for head and neck squamous cell carcinoma (HNSCC). This study aimed to measure 30-day postoperative mortality in HNSCC and describe clinical/nonclinical factors associated with 30-day mortality.

Methods:

In this retrospective cohort study, the National Cancer Database (2004 to 2013) was queried for eligible cases of HNSCC (n=91,858). Adult patients were included who were treated surgically with curative intent for the primary HNSCC, not missing first treatment, survival, and follow-up information. The outcome of interest was all-cause mortality within 30 days of definitive surgery. Clinical and nonclinical factors associated with all-cause 30-day postoperative mortality were estimated using a fully adjusted, multivariable logistic regression, which accounted for time-varying nature of adjuvant therapy.

Results:

A total of 775 patients died within 30 days of definitive surgery for HNSCC (30-day mortality rate of 0.84%). Thirty-day mortality rate was however up to 2.33% (95% confidence interval [CI], 1.91%-2.75%) depending on comorbidity. In the fully adjusted model, increasing severity of comorbidity was associated with greater odds of 30-day mortality (Charlson-Deyo comorbidity scores of 1: adjusted odds ratio [aOR], 1.43; 95% CI, 1.21-1.69, and of 2+ aOR, 2.55; 95% CI, 2.07-3.14). Odds of 30-day mortality were greater among Medicaid patients (aOR, 1.77; 95% CI, 1.30-2.41), and in patients in neighborhoods with little education (≥ 29% missing high school diploma: aOR, 1.35; 95% CI, 1.02-1.78).

Conclusions:

Patients with higher 30-day mortality were those with a greater burden of comorbidities, with little education, and covered by Medicaid.
Sleep Difficulties in Infancy Are Associated with Symptoms of Inattention and Hyperactivity at the Age of 5 Years: A Longitudinal Study
Authors: Huhdanpää Hanna , Morales-Muñoz Isabel , Aronen Eeva T. , Pölkki Pirjo , Saarenpää-Heikkilä Outi , Paunio Tiina , Kylliäinen Anneli , Paavonen E. Juulia
Published: June 2019

Objective:

Sleep difficulties are associated with cognitive and behavioral problems in childhood. However, it is still unclear whether early sleep difficulties are related to later development. We studied whether parent-reported sleep duration, night awakenings, and parent-reported sleep problems in early childhood are associated with symptoms of inattention and hyperactivity at the age of 5 years.

Method:

Our study is based on the Child-Sleep birth cohort initially comprising 1673 families, of which 713 were retained at the age of 5 years. We used the Brief Infant Sleep Questionnaire and the Infant Sleep Questionnaire, which were filled out by the parents when their child was 3, 8, and 24 months and 5 years old. Symptoms of inattention and hyperactivity at the age of 5 years were assessed using the Strengths and Difficulties Questionnaire and the Five-to-Fifteen questionnaire.

Results:

Sleep duration at the age of 3, 8, and 24 months was associated with inattentiveness at 5 years of age. Moreover, parent-reported sleep problems at the age of 24 months were related to both inattentive and hyperactive symptoms at the age of 5 years. Finally, at the age of 5 years, parent-reported sleep problems and night awakenings were associated with concurrent symptoms of inattention and hyperactivity.

Conclusion:

Our findings suggest that certain sleep characteristics related to sleep quality and quantity in early childhood are associated with inattentiveness and hyperactivity at the age of 5 years. Interestingly, sleep duration in early childhood is consistently related to inattention at the age of 5 years.
Maternal Self-Efficacy Is Protective for Child (but Not Mother) Body Mass Index Among Mexican-Origin Children with Negative Temperament
Authors: Rajan Sonali , Jahromi Laudan , Bravo Diamond , Umaña-Taylor Adriana , Updegraff Kimberly
Published: June 2019

Objective:

Childhood obesity persists as a serious public health concern, particularly among Mexican-origin youth. Teen mothers are also at heightened obesity risk. Multiple factors may exacerbate this risk, including stressors associated with parenting. Indeed, difficult child temperaments pose unique parenting challenges, which may also be linked to physical health outcomes in mothers. The purpose of this study was to examine whether the interaction between negative child temperament and parenting self-efficacy is related to the body mass index (BMI) of young children and their adolescent mothers while controlling for important contextual factors. We also examined which pathways differed for girls versus boys.

Methods:

Data were from a longitudinal study spanning 5 years that included 204 Mexican-origin young mothers and their children (with data collected at birth, age 4 years, and age 5 years). A multigroup structural equation modeling framework was used.

Results:

The rate of early childhood obesity was low in comparison with national averages, whereas the rate of adolescent mother obesity was notably higher than the national average. Negative child temperament was associated with higher child BMI among those adolescent mothers with low parenting self-efficacy. Among the children with a negative temperament, their mothers' high parenting self-efficacy may have served as a protective factor against unhealthy child BMI. This significant interaction held for both boys and girls.

Conclusion:

Research evaluating the potential effectiveness of interventions that promote parenting self-efficacy during early childhood as a means to reduce the rate of obesity among children of adolescent mothers should be conducted.
Baseline Mental Health and Psychosocial Functioning of Transgender Adolescents Seeking Gender-Affirming Hormone Therapy
Authors: Kuper Laura E. , Mathews Stacy , Lau May
Published: June 2019

Objective:

Research suggests that adolescents seeking gender-affirming hormone therapy experience elevated rates of depression, anxiety, and difficulties with peer relationships. Less is known regarding more specific aspects of mental health and psychosocial functioning. Furthermore, few studies have explored variations in mental health and psychosocial functioning by age, gender, degree of physical dysphoria, and informant type (adolescent, mother, and father).

Method:

Participants are adolescents (n = 149) and parents/guardians (n = 247) who presented to a multidisciplinary gender clinic in Dallas, TX for an initial assessment before initiation of gender-affirming hormone therapy. Adolescents completed the Youth Self-Report (YSR) and the Body Image Scale (a measure of physical dysphoria), and parents/guardians completed the Child Behavior Checklist (CBCL).

Results:

Approximately half of participants reported clinically significant difficulties with internalizing symptoms and psychosocial functioning (particularly engagement in activities), with approximately one-third indicating significant difficulties with depression, anxiety, obsessive compulsive, and posttraumatic stress symptoms. Parents reported fewer symptoms than adolescents across several subscales, but differences were generally small. By contrast, gender differences were found across all internalizing subscales and were generally large. Age and body dissatisfaction were not independently associated with broadband measures but, in combination with gender, were strongly associated with variance in YSR and CBCL reports of internalizing symptoms.

Conclusion:

Elevated rates of depression, anxiety, and competency difficulties were broadly consistent with the previous literature and demonstrate the need for investment in the clinical training and infrastructure to provide comprehensive care to this population. Differences in mental health and psychosocial functioning by gender and clinic location appear to be less straightforward.
Determination of estradiol and progesterone content in capsules and creams from compounding pharmacies
Authors: Stanczyk Frank Z. , Niu Chunying , Azen Colleen , Mirkin Sebastian , Amadio Julia M.
Published: June 2019

Objectives:

To analytically characterize the doses of estradiol and progesterone found in compounded combined forms of oral capsule and transdermal cream formulations, and determine the consistency of the hormone formulations within a batch.

Methods:

Prescriptions for combined estradiol/progesterone capsules (0.5 and 100 mg, respectively) and creams (0.5 and 100 mg/g, respectively) were sent to 15 custom-compounding pharmacies. Estradiol and progesterone levels were measured by radioimmunoassays. Hormone levels were measured in 2 capsules and 2 creams from each pharmacy; 10 capsules from 3 pharmacies; and top/middle/bottom layer of cream containers to assess consistency. The magnitude and sources of variation for the measurements were examined by analysis of variance models.

Results:

Thirteen pharmacies filled the prescriptions. Measured estradiol levels were 0.365 to 0.551 mg for capsules and 0.433 to 0.55 mg/g for creams, and progesterone levels were 90.8 to 135 mg for capsules and 93 to 118 mg/g for creams. Greater variations in estradiol levels were observed between pharmacies for estradiol in capsules than in creams; however, measured estradiol levels within pharmacies were more consistent in the capsules than the creams. Similar results were obtained for progesterone levels.

Conclusion:

The variations in estradiol and progesterone levels observed in compounded hormone therapy formulations justify concerns regarding risks as a result of variability, which have been outlined by The North American Menopause Society, the American College of Obstetricians and Gynecologists, and the US Food and Drug Administration (FDA) in their statements regarding compounded hormone use. These data support the need for an US FDA-approved bioidentical hormone therapy.

Video Summary: Supplemental Digital Content 1, http://links.lww.com/MENO/A425.
Childhood abuse and vasomotor symptoms among midlife women
Authors: Carson Mary Y. , Thurston Rebecca C.
Published: June 2019

Objective:

Childhood maltreatment is related to adverse health outcomes. However, the relation of childhood maltreatment to the menopause transition—a universal transition for women often accompanied by troubling symptoms such as vasomotor symptoms—is relatively underexplored. This study tested whether childhood abuse and neglect are associated with menopausal vasomotor symptoms, utilizing both physiologic and prospective self-report measures of vasomotor symptoms.

Methods:

In all, 295 nonsmoking perimenopausal and postmenopausal women aged 40 to 60 years with and without vasomotor symptoms completed psychosocial measures, including the Child Trauma Questionnaire, ambulatory physiologic (sternal skin conductance) and self-report measurement of vasomotor symptoms during wake and sleep, and actigraphy measurement of sleep. Relationships between childhood abuse/neglect and vasomotor symptoms during wake and sleep were tested in linear regression models controlling for demographics, body mass index, and menopause stage.

Results:

44% of the sample reported abuse or neglect during childhood. Among women reporting vasomotor symptoms, childhood sexual or physical abuse was associated with more frequent physiologically-recorded vasomotor symptoms during sleep (sexual abuse: b [SE] = 1.45 [0.52], P = 0.006; physical abuse: b [SE] = 0.97 [0.47], P = 0.03) in multivariable models. Among these women, women with a physical or sexual abuse history had approximately 1.5 to 2-fold the number of sleep vasomotor symptoms than women without this history.

Conclusions:

Childhood abuse is associated with more frequent physiologically-detected vasomotor symptoms during sleep.
CLINICAL FEATURES OF PATCHY CHORIORETINAL ATROPHY IN PATHOLOGIC MYOPIA
Authors: Du Ran , Fang Yuxin , Jonas Jost B. , Yokoi Tae , Takahashi Hiroyuki , Uramoto Kengo , Kamoi Koju , Yoshida Takeshi , Ohno-Matsui Kyoko
Published: June 2019

Purpose:

To reveal clinical features of patchy atrophy in pathologic myopia and investigate the status of the Bruch membrane and retinal pigment epithelium by swept-source optical coherence tomography.

Methods:

This study reviewed highly myopic patients who visited the high myopia clinic between January 2015 and February 2018. Wide-field photographs and wide-field fundus autofluorescence fundus images were used as the primary method for identifying PAs, and swept-source optical coherence tomography images were used for investigating the retinochoroid status of PAs.

Results:

Four hundred fifty-six PAs were detected in 137 eyes (118 patients). Patchy atrophys were located most often in the macular area (28.3%), followed by the inferior (25.9%), temporal (18.9%), nasal (14.5%), and superior (12.5%) region. All 210, PAs which had been fully or partially scanned by swept-source optical coherence tomography, showed a retinal pigment epithelium defect, and 174 (82.9%) PAs showed a Bruch membrane defect on the available scans. In 101 (82.8%) of 122 PAs with clearly detectable borders of the retinal pigment epithelium and Bruch membrane defect, the Bruch membrane defects were smaller than the retinal pigment epithelium defects. A dome-shape inward bulging of the sclera was observed in 10 PAs.

Conclusion:

These morphological findings may provide a basis for exploring the biomechanical etiology of the PAs as part of the development of pathologic myopia.
Factors influencing nurse practitioners' decisions to join nurse practitioner associations
Authors: Rowley Tom , Balk Julie , Guo Jia-Wen , Wallace Andrea S.
Published: June 2019

Background and purpose:

The benefits of professional association membership to individual health care providers are well established. However, not all nurse practitioners (NPs) are members of professional associations. Research is available on factors that influence registered nurses' decisions to join professional associations, but little is known regarding factors influencing the decisions of NPs. The purpose of this study was to identify factors affecting NPs' decisions to join NP associations.

Methods:

A cross-sectional survey of NPs (N = 537) was conducted electronically in accordance with the Checklist for Reporting Results of Internet E-Surveys guidelines. The Professional Association Membership Questionnaire was used to develop the survey. Three hundred twenty-eight respondents (61.1%) had a current membership in a professional association and 209 (38.9%) were nonmembers. Although both members and nonmembers expressed a desire for professional programs, improvement in the profession, and personal development, current members scored significantly higher in each of these factors (p < .001 to p = .015).

Conclusion:

The results suggest that factors influencing NPs' decisions to join professional associations include the desire for professional programs, improvement of the profession, and personal development.

Implications for practice:

Professional associations seeking to improve health outcomes by creating more competent, safe NPs and keeping the public's trust should consider focusing on efforts that foster education, professional networking and new ideas, and self-improvement.
Eltrombopag
Authors: Shobha Vineeta , Sanil Sandra , Roongta Rashmi
Published: June 2019

Background

Eltrombopag, a thrombopoietin receptor agonist, is effective in chronic immune thrombocytopenia (ITP). The data in lupus ITP are sparse. This study aimed to assess the efficacy and safety of eltrombopag in lupus ITP.

Methods

This is a single-center study conducted between 2012 and 2017 of 12 subjects with systemic lupus erythematosus–associated ITP. Patients with inadequate or suboptimal response to steroids and other immunosuppressants treated with eltrombopag were included in the study. Time taken for response to therapy (defined as platelets >1 lakh), dose, duration of treatment, and adverse effects of the drug were noted.

Results

A total of 12 subjects were included in the study. The median platelet count at initiation of eltrombopag was 19,000 per μL. The time taken for response to therapy was 8 days. The median platelet count at 1-month follow-up was 241,000 per μL. All patients were concurrently treated with steroids and other immunosuppressants. Sustained benefit after stopping eltrombopag was noted in all patients. No adverse events including thrombotic complication were noted.

Conclusions

Eltrombopag is a new drug in our arsenal for treatment of ITP in lupus. It is a rapidly effective, safe, and orally administered medication. It indirectly contributes to reduction in the dose of steroids and immunosuppressants, thereby minimizing their cumulative adverse effects. It is a promising and safe option for the treatment of lupus-associated thrombocytopenia, but this needs further confirmation from multicenter, multiethnic, randomized controlled trials.
Diagnostic Performance of Doppler Ultrasonography for the Detection of Fetal Anemia
Authors: Lyu Chun-ju , Xu Cui , Yu Jie , Xia Li-ping
Published: June 2019

This study evaluates the diagnostic performance of Doppler ultrasound in diagnosing fetal anemia. Data were taken from relevant study reports published in peer-reviewed journals identified after a literature search in electronic databases. Random effects meta-analyses were performed by pooling the effect sizes of diagnostic indices (sensitivity, specificity, positive/negative predictive values, and false-positive rate) or correlation coefficients reported by individual studies. As a result, 31 studies (1848 pregnancies; gestation age, 28.25 weeks [95% confidence interval {CI}, 26.87–29.63]) were included in the meta-analysis. Anemia was found in 63.7% (95% CI, 49.7–77.7) fetuses, and severe anemia was found in 36.7% (95% CI, 26.9–46.4) fetuses. Sensitivity and specificity of Doppler ultrasound for detecting fetal anemia in alloimmunized fetuses at middle cerebral artery peak systolic velocity cutoff of 1.5 multiple of median for gestation age were 83.42% (95% CI, 71.75–95.09) and 80.30% (95% CI, 73.58–87.02), respectively. Positive predictive value, negative predictive value, and false-positive rate were 76.35% (95% CI, 65.98–86.72), 80.0% (95% CI, 76.63–83.37), and 10.4% (95% CI, 5.9–14.9), respectively. Correlation coefficient between hematological anemia and Doppler ultrasound–measured blood flow velocity was −0.706 (95% CI, −0.765 to −0.635; P ˂ 0.00001). In conclusion, Doppler ultrasound–measured middle cerebral artery peak systolic velocity at 1.5 multiple of median provides good diagnostic strength for the detection of alloimmunized fetal anemia. A strong correlation between Doppler velocimetric measures and hematological anemia is also observed.
Stable or seral? Fire-driven alternative states in aspen forests of western North America
Authors: Morris Jesse L. , DeRose R. Justin , Brussel Thomas , Brewer Simon , Brunelle Andrea , Long James N.
Published: June 2019

As important centres for biological diversity, aspen forests are essential to the function and aesthetics of montane ecosystems in western North America. Aspen stands are maintained by a nuanced relationship with wildfire, although in recent decades aspen mortality has increased. The need to understand the baseline environmental conditions that favour aspen is clear; however, long-term fire history reconstructions are rare due to the scarcity of natural archives in dry montane settings. Here, we analyse a high-resolution lake sediment record from southwestern, Utah, USA to quantify the compositional and burning conditions that promote stable (or seral) aspen forests. Our results show that aspen presence is negatively correlated with subalpine fir and that severe fires tend to promote persistent and diverse aspen ecosystems over centennial timescales. This information improves our understanding of aspen disturbance ecology and identifies the circumstances where critical transitions in montane forests may occur.
Sibling relatedness rather than father absence predicts earlier age at menarche in ELSPAC cohort
Authors: Lenárt Peter , Zlámal Filip , Kukla Lubomír , Jarkovský Jiří , Bienertová-Vašků Julie
Published: June 2019

Many studies during the past 50 years have found an association between father absence and earlier menarche. In connection with these findings, several evolutionary theories assume that father absence is a causal factor accelerating reproductive development. However, a recent study analysing data from the Avon Longitudinal Study of Parents and Children (ALSPAC) found that father absence does not predict age at menarche when adjusted for sibling relatedness. In this study, we have replicated these results in the Czech section of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC), which used the same questionnaires as ALSPAC to study a geographically distinct population. Our results support the conclusion that sibling relatedness rather than father absence predicts age at menarche. Furthermore, our results show that age at menarche in 1990s UK and Czech cohorts is very similar despite socioeconomic differences between the two countries.
Physiological determinants of the internesting interval in sea turtles: a novel ‘water-limitation’ hypothesis
Authors: Price Edwin R. , Sotherland Paul R. , Wallace Bryan P. , Spotila James R. , Dzialowski Edward M.
Published: June 2019

The internesting interval separates successive clutches of sea turtle eggs, and its duration varies both among and within species. Here, we review the potential physiological limits to this interval, and develop the hypothesis that desalination capacity limits the internesting interval owing to the requirement for water deposition in eggs. Sea turtles deposit 1–4 kg of water per clutch in egg albumen; for most species, this represents about 2% of adult body mass. We calculate how quickly turtles can recover this water by estimating maximal salt excretion rates, metabolic water production and urinary losses. From this water balance perspective, the ‘water-limitation’ hypothesis is plausible for green turtles but not for leatherbacks. Some plasma biochemistry studies indicate dehydration in sea turtles during the nesting season, although this is not a universal finding and these data have rarely been collected during the internesting interval itself. There is mixed support for a trade-off between clutch size and the length of the interval. We conclude that the ‘water-limitation’ hypothesis is plausible for most sea turtle species, but requires direct experimentation.
Behaviour, morphology and microhabitat use: what drives individual niche variation?
Authors: Costa-Pereira Raul , Pruitt Jonathan
Published: June 2019

Generalist populations are often composed of individuals each specialized on only a subset of the resources exploited by the entire population. However, the traits underlying such niche variation remain underexplored. Classically, ecologists have focused on understanding why populations vary in their degree of intraspecific niche variation, with less attention paid to how individual-level traits lead to intraspecific differences in niches. We investigated how differences in behaviour, morphology and microhabitat affect niche variation between and within individuals in two species of spider
Anelosimus studiosus
and
Theridion murarium
. Our results convey that behaviour (i.e. individual aggressiveness) was a key driver of intraspecific trophic variation in both species. More aggressive individuals capture more prey, but particularly more Coleoptera, Hymenoptera and Diptera. These findings suggest that behavioural traits play a critical role in determining individuals' diet and that behaviour can be a powerful force in driving intraspecific niche variation.
From the South Seas to Soho Square: Joseph Banks's Library, collection and Kingdom of natural history
Authors: Rose Edwin D.
Published: June 2019

The library and herbarium of Joseph Banks was one of the most prominent natural history collections of late eighteenth-century Britain. The examination of the working practices used in Banks's library, which was based at 32 Soho Square from 1777, reveals the activities of the numerous individuals who worked for Banks and on his collections from the early 1770s until 1820. Banks's librarians and their assistants used a range of paper technologies to classify and catalogue the vast numbers of new botanical species being discovered at this time. These practices of managing information changed as the decades progressed, reflecting the changes to systems of classification and the different research projects of Banks and his natural history staff. Banks's great wealth and powerful position as President of the Royal Society gave him the means to build and use this rigorously organized collection and library to influence a range of other private and institutional collections for almost 50 years.
Assessing the impact, genomics and evolution of type II secretion across a large, medically important genus: the Legionella type II secretion paradigm
Authors: White Richard C. , Cianciotto Nicholas P.
Published: June 2019

The type II secretion system (T2SS) plays a major role in promoting bacterial survival in the environment and in human hosts. One of the best characterized T2SS is that of

Legionella pneumophila

, the agent of Legionnaires’ disease. Secreting at least 25 proteins, including degradative enzymes, eukaryotic-like proteins and novel effectors, this T2SS contributes to the ability of

L. pneumophila

to grow at low temperatures, infect amoebal and macrophage hosts, damage lung tissue, evade the immune system, and undergo sliding motility. The genes encoding the T2SS are conserved across the genus

Legionella

, which includes 62 species and >30 pathogens in addition to

L. pneumophila

. The vast majority of effectors associated with

L. pneumophila

are shared by a large number of

Legionella

species, hinting at a critical role for them in the ecology of

Legionella

as a whole. However, no other species has the same repertoire as

L. pneumophila

, with, as a general rule, phylogenetically more closely related species sharing similar sets of effectors. T2SS effectors that are involved in infection of a eukaryotic host(s) are more prevalent throughout

Legionella

, indicating that they are under stronger selective pressure. The

Legionella

T2SS apparatus is closest to that of

Aquicella

(another parasite of amoebae), and a significant number of

L. pneumophila

effectors have their closest homologues in

Aquicella

. Thus, the T2SS of

L. pneumophila

probably originated within the order

Legionellales

, with some of its effectors having arisen within that

Aquicella

-like progenitor, while other effectors derived from the amoebal host, mimiviruses, fungi and less closely related bacteria.
Endemic fluoroquinolone-resistant Salmonella
enterica serovar Kentucky ST198 in northern India
Authors: Mahindroo Jaspreet , Thanh Duy Pham , Nguyen To Nguyen Thi , Mohan Balvinder , Thakur Siddhartha , Baker Stephen , Taneja Neelam
Published: June 2019

Salmonella

e
nterica serovar Kentucky is an emergent human pathogen. Human infection with ciprofloxacin-resistant
S. enterica
Kentucky ST198 has been reported in Europe and North America as a consequence of travel to Asia/the Middle East. This is, to the best of our knowledge, the first study reporting the identification of this epidemic clone in India and South Asia.
Enterococcus faecium genome dynamics during long-term asymptomatic patient gut colonization
Authors: Bayjanov Jumamurat R. , Baan Jery , Rogers Malbert R. C. , Troelstra Annet , Willems Rob J. L. , van Schaik Willem
Published: June 2019

Enterococcus faecium

is a gut commensal of humans and animals. In addition, it has recently emerged as an important nosocomial pathogen through the acquisition of genetic elements that confer resistance to antibiotics and virulence. We performed a whole-genome sequencing-based study on 96 multidrug-resistant

E. faecium

strains that asymptomatically colonized five patients with the aim of describing the genome dynamics of this species. The patients were hospitalized on multiple occasions and isolates were collected over periods ranging from 15 months to 6.5 years. Ninety-five of the sequenced isolates belonged to

E. faecium

clade A1, which was previously determined to be responsible for the vast majority of clinical infections. The clade A1 strains clustered into six clonal groups of highly similar isolates, three of which consisted entirely of isolates from a single patient. We also found evidence of concurrent colonization of patients by multiple distinct lineages and transfer of strains between patients during hospitalization. We estimated the evolutionary rate of two clonal groups that each colonized single patients at 12.6 and 25.2 single-nucleotide polymorphisms (SNPs)/genome/year. A detailed analysis of the accessory genome of one of the clonal groups revealed considerable variation due to gene gain and loss events, including the chromosomal acquisition of a 37 kbp prophage and the loss of an element containing carbohydrate metabolism-related genes. We determined the presence and location of 12 different insertion sequence (IS) elements, with ISEfa5 showing a unique pattern of location in 24 of the 25 isolates, suggesting widespread ISEfa5 excision and insertion into the genome during gut colonization. Our findings show that the

E. faecium

genome is highly dynamic during asymptomatic colonization of the human gut. We observed considerable genomic flexibility due to frequent horizontal gene transfer and recombination, which can contribute to the generation of genetic diversity within the species and, ultimately, can contribute to its success as a nosocomial pathogen.
VIEW-MOD: A Versatile Illumination Engine With a Modular Optical Design for Fluorescence Microscopy
Authors: Liu Bei , Hobson Chad M. , Pimenta Frederico M. , Nelsen Evan , Hsiao Joe , O’Brien Timothy , Falvo Michael R. , Hahn Klaus M. , Superfine Richard
Published: June 2019

We developed VIEW-MOD (Versatile Illumination Engine With a Modular Optical Design): a compact, multi-modality microscope, which accommodates multiple illumination schemes including variable angle total internal reflection, point scanning and vertical/horizontal light sheet. This system allows combining and flexibly switching between different illuminations and imaging modes by employing three electrically tunable lenses and two fast-steering mirrors. This versatile optics design provides control of 6 degrees of freedom of the illumination source (3 translation, 2 tilt, and beam shape) plus the axial position of the imaging plane. We also developed standalone software with an easy-to-use GUI to calibrate and control the microscope. We demonstrate the applications of this system and software in biosensor imaging, optogenetics and fast 3D volume imaging. This system is ready to fit into complex imaging circumstances requiring precise control of illumination and detection paths, and has a broad scope of usability for a myriad of biological applications.
Identification of two independentCOL5A1variants in dogs with Ehlers Danlos syndrome
Authors: Bauer Anina , Bateman John F. , Lamande Shireen R. , Hanssen Eric G , Kirejczyk Shannon G.M. , Yee Mark , Ramiche Ali , Jagannathan Vidyha , Welle Monika , Leeb Tosso , Bateman Fiona L
Published: June 2019

BACKGROUND

The Ehlers Danlos syndromes (EDS) are a heterogeneous group of heritable disorders affecting connective tissues. The mutations causing the various forms of EDS in humans are well characterized, but the genetic mutations causing EDS-like clinical pathology in dogs are not known, thus hampering accurate clinical diagnosis.

RESULTS

Clinical analysis of two independent cases of skin hyperextensibility and fragility, one with pronounced joint hypermobility was suggestive of EDS. Whole genome sequencing revealedde novomutations ofCOL5A1in both cases, confirming the diagnosis of the classical form of EDS. The heterozygousCOL5A1p.Gly1013ValfsTer260 mutation characterized in case 1 introduced a premature termination codon and would be expected to result in α1(V) mRNA nonsense-mediated mRNA decay and collagen V haploinsufficiency. While mRNA was not available from this dog, biochemical analysis of the dermis suggested reduced collagen V in the dermis and ultrastructural analysis demonstrated variability in collagen fibril diameter and the presence of collagen aggregates, termed ‘collagen cauliflowers’, consistent withCOL5A1mutations underlying classical EDS. In the second case DNA sequencing demonstrated a p.Gly1571Arg missense variant in theCOL5A1gene. While samples were not available for further analysis, such a glycine substitution would be expected to destabilize the strict molecular structure of the collagen V triple helix and thus affect protein stability and/or integration of the mutant collagen into the collagen V/collagen I heterotypic dermal fibrils.

CONCLUSIONS

This is the first report of genetic variants in theCOL5A1gene causing the clinical presentation of EDS in dogs. These data provide further evidence of the important role of collagen V in dermal collagen fibrillogenesis. Importantly from the clinical perspective we show the utility of DNA sequencing, combined with the established clinical criteria, in the accurate diagnosis of EDS in dogs.
A subset of broadly responsive Type III taste cells contribute to the detection of bitter, sweet and umami stimuli
Authors: Banik Debarghya Dutta , Benfey Eric D. , Martin Laura E. , Kay Kristen E. , Loney Gregory C. , Nelson Amy R. , Ahart Zachary C. , Kemp Barrett T. , Kemp Bailey R. , Torregrossa Ann-Marie , Medler Kathryn F.
Published: June 2019

Taste receptor cells use multiple signaling pathways to detect chemicals in potential food items. These cells are functionally grouped into different types: Type I cells act as support cells and have glial-like properties; Type II cells detect bitter, sweet, and umami taste stimuli; and Type III cells detect sour and salty stimuli. We have identified a new population of taste cells that are broadly tuned to multiple taste stimuli including bitter, sweet, sour and umami. The goal of this study was to characterize these broadly responsive (BR) taste cells. We used an IP3R3-KO mouse (does not release calcium (Ca2+) from Type II cells when stimulated with bitter, sweet or umami stimuli) to characterize the BR cells without any potentially confounding input from Type II cells. Using live cell Ca2+ imaging in isolated taste cells from the IP3R3-KO mouse, we found that BR cells are a subset of Type III cells that respond to sour stimuli but also use a PLCβ3 signaling pathway to respond to bitter, sweet and umami stimuli. Unlike Type II cells, individual BR cells are broadly tuned and respond to multiple stimuli across different taste modalities. Live cell imaging in a PLCβ3-KO mouse confirmed that BR cells use a PLCβ3 signaling pathway to generate Ca2+ signals to bitter, sweet and umami stimuli. Analysis of c-Fos activity in the nucleus of the solitary tract (NTS) and short term behavioral assays revealed that BR cells make significant contributions to taste.
The oncogenic Kaposi’s sarcoma-associated herpesvirus encodes a mimic of the tumor suppressive miR-15/16 miRNA family
Authors: Morrison Kylee , Manzano Mark , Chung Kevin , Schipma Matthew J. , Bartom Elizabeth T. , Gottwein Eva
Published: June 2019

Many tumor viruses encode oncogenes of cellular origin. Here, we report the first instance of an oncoviral mimic of a cellular tumor suppressor. The Kaposi’s sarcoma-associated herpesvirus (KSHV) miRNA miR-K6-5p shares sequence similarity to the tumor suppressive cellular miR-15/16 miRNA family. We show that miR-K6-5p inhibits cell cycle progression, a hallmark function of miR-16. miR-K6-5p regulates conserved miR-15/16 targets, including many cell cycle regulators. Inhibition of miR-K6-5p in KSHV-transformed B cells conferred a significant growth advantage. Altogether, our data show that KSHV encodes a functional mimic of the miR-15/16 miRNA family. While it is exceedingly well established that oncogenic viruses encode oncogenes of cellular origin, this is the first example of an oncogenic virus that encodes a viral mimic of a cellular tumor suppressor. Encoding a tumor suppressive miRNA could help KSHV balance viral oncogene expression and thereby avoid severe pathogenesis in the healthy host.
Guiding T lymphopoiesis from pluripotent stem cells by defined transcription factors
Authors: Guo Rongqun , Hu Fangxiao , Weng Qitong , Lv Cui , Wu Hongling , Liu Lijuan , Li Zongcheng , Zeng Yang , Bai Zhijie , Zhang Mengyun , Liu Yuting , Liu Xiaofei , Xia Chengxiang , Wang Tongjie , Zhou Peiqing , Wang Kaitao , Dong Yong , Luo Yuxuan , Zhang Xiangzhong , Guan Yuxian , Geng Yang , Du Juan , Li Yangqiu , Lan Yu , Chen Jiekai , Liu Bing , Wang Jinyong
Published: June 2019

Achievement of immunocompetent and therapeutic T lymphopoiesis from pluripotent stem cells is a central aim in T cell regenerative medicine. To date, preferentially regenerating T lymphopoiesis in vivo from pluripotent stem cells (PSC) remains a practical challenge. Here we documented that synergistic and transient expression of Runx1 and Hoxa9 restricted in the time window of endothelial to hematopoietic transition and hematopoietic maturation stages induced in vitro from PSC (iR9-PSC) preferentially generated engraftable hematopoietic progenitors capable of homing to thymus and developing into mature T (iT) cells in primary and secondary immunodeficient recipients. Single-cell transcriptome and functional analyses illustrated the cellular trajectory of T lineage induction from PSC, unveiling the T-lineage specification determined at as early as hemogenic endothelial cell stage and identifying the bona fide pre-thymic progenitors. The iT cells distributed normally in central and peripheral lymphoid organs and exhibited abundant TCRαβ repertoire. The regenerative T lymphopoiesis rescued the immune-surveillance ability in immunodeficient mice. Furthermore, gene-edited iR9-PSC produced tumor-specific-T cells in vivo that effectively eradicated tumor cells. This study provides insight into universal generation of functional and therapeutic T lymphopoiesis from the unlimited and editable PSC source.