bluuebunny/crossref_metadata_2025 huggingface dataset:
Diversity and Characterization of Oomycetes Associated with Corn Seedlings in Michigan
Authors: Rojas J. A. , Witte A. , Noel Z. A. , Jacobs J. L. , Chilvers M. I.
Published: May 2019

Corn is a staple feed and biofuel crop with a value close to $3.7 billion dollars for Michigan’s economy. Knowledge about distribution and abundance of seedling pathogens in Michigan corn fields is limited. Here we used a combination of culture-based and next-generation sequencing of soil samples to determine the extent of species associated with diseased corn seedlings and those present in soil. Over 2 years, symptomatic seedlings and associated soil samples were collected from 11 Michigan fields. A total of 170 oomycete cultures were obtained from seedlings using a semiselective medium (CMA-PARPB) and identified using the internal transcribed spacer region. Thirty-three species were isolated, with Pythium inflatum (25%; clade B) and P. sylvaticum (12%; clade F) being the most abundant species. For the amplicon-based approach, the cytochrome oxidase subunit I marker (COI) mitochondrial region was amplified from soil samples and sequenced using Illumina MiSeq. The dominant Pythium clades present in the soil were F, I, D, and B and accounted for at least 75% of the abundance in all locations. Pythium clades F, I, and D were recovered with similar trends with the culture and amplicon approach; however, clade B was highly abundant in plant isolation, but not in soil. The 20 most abundant species were characterized for pathogenicity and fungicide sensitivity. P. irregulare and P. ultimum var. ultimum were the most virulent at both 15 and 20°C. Isolates were tested for their sensitivity to mefenoxam and ethaboxam. Most isolates were sensitive to both chemistries, but P. rostratifingens and P. aff. torulosum were less sensitive to ethaboxam and P. ultimum var. ultimum less sensitive to mefenoxam. The survey and isolate characterization provides a better understanding of seedling and root rot disease of corn and opportunities to improve management of this disease complex.
Partnered Educational Governance: Rethinking Student Agency in Undergraduate Medical Education
Authors: Bilodeau Philippe Antoine , Liu Xin Mei , Cummings Beth-Ann
Published: May 2019

Historically, students have been “consumers” of undergraduate medical education (UME) rather than stakeholders in its design and implementation. Student input has been retrospective, and although UME leaders have been open to feedback, matters most important to students have often been overlooked, leaving students feeling largely unheard. Student representation has also lacked structure and unity of feedback.

A vision for effective student representation drove the creation of a partnered educational governance (PEG) model at McGill University in Montreal, Quebec, Canada, where sharing of expertise between student representatives and UME leadership has improved the UME program and the educational experience of students.

The PEG model is grounded in the literature on student government, the student-as-partner framework, and theories of accountability. As part of the model, the student Medical Education Committee, an organized structure for discussion and reporting to student constituents, was established. This structure allows student representatives, entrusted by their peers and faculty, to proactively provide input to UME committees in the development of policies and curricula. The partnership between students and faculty facilitates a shared understanding of educational challenges and potential solutions.

Within the first year, meaningful changes associated with the PEG model included increased student engagement in key program decisions, such as the redesign of a research course and an update to the absences and leaves policy. The PEG model enables unified student representation that is accountable and representative—and has a significant impact on outcomes—while maintaining the UME program’s ownership of and responsibility for the curriculum and policies.
Qualitative Research Methods in Medical Education
Authors: Sawatsky Adam P. , Ratelle John T. , Beckman Thomas J.
Published: May 2019

Qualitative research was originally developed within the social sciences. Medical education is a field that comprises multiple disciplines, including the social sciences, and utilizes qualitative research to gain a broader understanding of key phenomena within the field. Many clinician educators are unfamiliar with qualitative research. This article provides a primer for clinician educators who want to appraise or conduct qualitative research in medical education. This article discusses a definition and the philosophical underpinnings for qualitative research. Using the Standards for Reporting Qualitative Research as a guide, this article provides a step-wise approach for conducting and evaluating qualitative research in medical education. This review will enable the reader to understand when to utilize qualitative research in medical education and how to interpret reports using qualitative approaches.
The Effect of Hearing-Protection Devices on Auditory Situational Awareness and Listening Effort
Authors: Smalt Christopher J. , Calamia Paul T. , Dumas Andrew P. , Perricone Joseph P. , Patel Tejash , Bobrow Johanna , Collins Paula P. , Markey Michelle L. , Quatieri Thomas F.
Published: May 2019

Objectives:

Hearing-protection devices (HPDs) are made available, and often are required, for industrial use as well as military training exercises and operational duties. However, these devices often are disliked, and consequently not worn, in part because they compromise situational awareness through reduced sound detection and localization performance as well as degraded speech intelligibility. In this study, we carried out a series of tests, involving normal-hearing subjects and multiple background-noise conditions, designed to evaluate the performance of four HPDs in terms of their modifications of auditory-detection thresholds, sound-localization accuracy, and speech intelligibility. In addition, we assessed their impact on listening effort to understand how the additional effort required to perceive and process auditory signals while wearing an HPD reduces available cognitive resources for other tasks.

Design:

Thirteen normal-hearing subjects participated in a protocol, which included auditory tasks designed to measure detection and localization performance, speech intelligibility, and cognitive load. Each participant repeated the battery of tests with unoccluded ears and four hearing protectors, two active (electronic) and two passive. The tasks were performed both in quiet and in background noise.

Results:

Our findings indicate that, in variable degrees, all of the tested HPDs induce performance degradation on most of the conducted tasks as compared to the open ear. Of particular note in this study is the finding of increased cognitive load or listening effort, as measured by visual reaction time, for some hearing protectors during a dual-task, which added working-memory demands to the speech-intelligibility task.

Conclusions:

These results indicate that situational awareness can vary greatly across the spectrum of HPDs, and that listening effort is another aspect of performance that should be considered in future studies. The increased listening effort induced by hearing protectors may lead to earlier cognitive fatigue in noisy environments. Further study is required to characterize how auditory performance is limited by the combination of hearing impairment and the use of HPDs, and how the effects of such limitations can be linked to safe and effective use of hearing protection to maximize job performance.
New insights into human prolactin pathophysiology: genomics and beyond
Authors: Chang Sydney , Copperman Alan B.
Published: May 2019

Purpose of review

To briefly summarize what is known regarding hyperprolactinemia and prolactin-secreting tumors, and review recent findings.

Recent findings

Prolactin was previously thought to inhibit secretion of gonadotropin-releasing hormone (GnRH) by directly inhibiting the firing of GnRH neurons, resulting in hypogonadotropic hypogonadism and infertility. However, kisspeptin has recently been implicated as the mediator of hyperprolactinemia-induced infertility, by acting upstream of the GnRH neurons as an integrator of endocrine signals.

Macroprolactin is generally considered to be inactive and clinically insignificant, but new studies have suggested that patients with macroprolactinemia may have reproductive manifestations as well as sexual dysfunction.

Several mutations and polymorphisms in the prolactin receptor have been described, which could describe a genetic cause for prolactinomas and characterize cases of isolated familial hyperprolactinemia.

Kisspeptin and tyrosine kinase inhibitors have emerged as potential new therapeutic targets for the treatment of hyperprolactinemia and dopamine-resistant prolactinomas.

Molecular studies are shedding light on the pathophysiology of hyperprolactinemia and the effects of excess prolactin production on the reproductive system. Similarly, genetic studies have begun to reveal how differences in prolactin receptor function may account for some of the previously ‘idiopathic’ cases of hyperprolactinemia and bring to light new causes of prolactinomas. Further elucidation of the transcriptional pathways affected by these genetic changes may help to create new therapeutic targets.
Informed consent in gynecologic surgery
Authors: Overcarsh Patricia , Arvizo Cynthia , Harvey Lara
Published: May 2019

Purpose of review

Informed consent is frequently used interchangeably with obtaining a signature on a form. This oversimplification shifts the value from the process of informed consent to the documentation. This review focuses on the recommended components of the consent process, barriers encountered, factors influencing patient satisfaction, attempts to improve the consent practice, and considerations in special populations.

Recent findings

The process of informed consent is key to promoting shared decision-making and patient autonomy. Several barriers exist to providing optimal consent including time constraints as well as educational, cultural, and language barriers. Innovative approaches such as audiovisual aids show promise in overcoming barriers and improving the consent process.

Patients seek expertise and knowledge to aid in making decisions that align with their care goals. Providers have an obligation to provide individualized and accessible counseling. Ongoing research is needed to optimize this process.
Central Corneal Thickness in Childhood Cataract
Authors: Thau Avrey , Dawodu Oseluese , Mireskandari Kamiar , Ali Asim , Tehrani Nasrin , DeBenedictis Caroline , Bhoiwala Devang , Aultman William , Alnabi Waleed A. , Leiby Benjamin E. , Levin Alex V.
Published: May 2019

Purpose:

We explored elevated central corneal thickness (CCT) in children with cataracts as possibly reflecting preexisting corneal malformation related to specific cataract morphology.

Methods:

All children consecutively seen during the study periods who had cataracts and corneal pachymetry as part of their routine care were enrolled at academic centers in large cities of Canada and the United States. Study data collected included age, sex, CCT, and cataract morphology. Differences among cataract morphology groups with respect to mean CCT measurements were evaluated and compared with a historical control thickness of 558 μm.

Results:

A total of 96 children were enrolled in this study. The average subject age was 5.1 years, and 55 children (57%) were female. The mean CCT value for all subjects was 566.1 μm. There was little evidence to conclude that the cataract morphology groups differed from each other (P = 0.65) or from controls with respect to CCT.

Conclusions:

In children, CCT is likely independent of cataract morphology. This implies that factors other than preoperative malformation are more likely related to elevated CCT observed in children with aphakia and pseudophakia.
Shoulder Pain and the Weight-bearing Shoulder in the Wheelchair Athlete
Authors: Soo Hoo Jennifer
Published: May 2019

Shoulder pain is one of the most common complaints amongst wheelchair athletes. There are many debated potential risk factors for shoulder pain in this population including inherent anatomy, increased loading forces, overuse, age, wheelchair use duration, trunk control, and sport played. Proper identification of etiology of shoulder pain with a thorough history and physical examination is important for management purposes. Treatment can be challenging as complete rest from exacerbating activities is often difficult as upper extremity use is necessary for everyday life activities such as mobility and transfers. Addition of shoulder maintenance strengthening program focusing on strengthening adductors, external rotators, and scapular retractors is important to keep shoulder muscles well-balanced to prevent injury.
Extracorporeal Membrane Oxygenation Mortality in High-Risk Populations: An Analysis of the Pediatric Health Information System Database
Authors: Coleman Ryan D. , Goldman Jordana , Moffett Brady , Guffey Danielle , Loftis Laura , Thomas James , Shekerdemian Lara S
Published: May 2019

The number of children receiving extracorporeal membrane oxygenation (ECMO) has increased substantially, and includes a growing population of children with complex underlying conditions who previously may not have been considered ECMO candidates. However, it remains unclear to what extent the underlying disease impacts the risk of death in these patients, particularly related to malignancy, bone marrow transplantation, complex congenital heart disease (CHD), or chromosomal abnormalities. A retrospective study was performed using the Pediatric Health Information System database of all children placed on ECMO more than a 10 year period between 2004 and 2013. Patients with diagnoses of bone marrow transplant, leukemia, lymphoma, neutropenia, immune system abnormalities, genetic abnormalities, neoplastic disorders, and complex CHD were selected as “high risk” and their outcomes were compared with overall outcomes. Extracorporeal membrane oxygenation was used in 9,194 children. Two thousand two hundred (24%) were identified as high risk. Bone marrow transplant (81% mortality; odds ratio [OR] 3.49), leukemia (66% mortality; OR 1.88), and neutropenia (58% mortality; OR 1.62) were associated with higher odds of mortality. Complex CHD (52% mortality) and genetic syndromes (48%) were not associated with higher mortality. These findings are pertinent for clinicians and families when considering ECMO candidacy in these children.
Progress in research on gold nanoparticles in cancer management
Authors: Peng Jingwen , Liang Xiaoqiu
Published: May 2019

Introduction:

The rapid advancement of nanotechnology in recent years has fuelled burgeoning interest in the field of nanoparticle research, particularly its application in cancer management. At present, there seems to be heightened interest in the application of gold nanoparticles (AuNPs) to the management of cancer, encompassing diagnosis, monitoring, and treatment. AuNPs could be used as drug delivery agents that target cancer cells or in gene therapy. These efforts are undertaken in the hope of revolutionizing current methods and strategies for cancer treatment. This review will focus on the current applications of AuNPs in cancer management.

Objectives, data sources, study appraisal and synthesis methods, results:

objectives, data sources, study eligibility criteria, participants, and interventions, study appraisal and synthesis methods, results are not required, as the study will be a literature review. Just introduction, ethics and dissemination, and conclusion are applicable.

Ethics and dissemination:

Ethical approval and informed consent are not required, as the study is a literature review and does not involve direct contact with patients or alterations to patient care.

Conclusion:

AuNPs have many properties that are of great value for the diagnosis and treatment of tumors. AuNPs are small in size and can penetrate widely and deposit on the tumor site, bind to many proteins and drugs, target delivery drugs, and have good biocompatibility. The application of AuNPs in the diagnosis and treatment of tumors is very considerable. In the near future, AuNPs will certainly play an important role in the treatment of tumors.
Acupuncture for patients with premature ovarian insufficiency
Authors: Huang Li , Chen Yu , Luo Mei , Tang Yancai , Wei Shaobin
Published: May 2019

Background:

Premature ovarian insufficiency (POI) is a difficult-to-treat gynecological disorder with complex etiologies. Although acupuncture has gained increased popularity for the management of POI, evidence regarding its efficacy is lacking. This systematic review protocol aims to describe a meta-analysis to assess the effectiveness and safety of acupuncture for patients with POI.

Methods:

The following 10 databases will be searched from the publishment to July 2019: PubMed, Embase, the Web of Science, the Cochrane Central Register of Controlled Trials, 4 Chinese databases (China National Knowledge Infrastructure, Wanfang Digital Periodicals, Chinese Biomedical Literature Database, Chinese Scientific Journal Database database), 1 Korean medical database (KoreaMed), 1 Japanese medical database (National Institute of Informatics). The primary outcomes will be the resumption of menstruation and the serum FSH levels, and the secondary outcomes include the serum Estradiol levels, anti-Mullerian hormone levels, antral follicle count, follicular growth, endometrial thickness, and adverse events. We will use RevMan V.5.3 to conduct the meta-analysis, if possible. If it is not allowed, a descriptive analysis or a subgroup analysis will be conducted. Risk ratio for dichotomous data and mean differences or standardized mean differences for continuous data will be calculated with 95% confidence intervals using a random effects model or a fixed effects model.

Results:

This study will provide the latest analysis of the currently available evidence for the efficacy of acupuncture in treating POI.

PROSPERO registration number:

CRD42019125996.
Spleen stiffness and volume help to predict posthepatectomy liver failure in patients with hepatocellular carcinoma
Authors: Peng Wei , Zhang Xiao-Yun , Li Chuan , Wen Tian-Fu , Yan Lv-Nan , Yang Jia-Yin
Published: May 2019

Posthepatectomy liver failure (PHLF) is the main cause of perioperative death, and liver cirrhosis is one of the most important risk factors for PHLF. Spleen stiffness (SS) is a novel ultrasonic indicator for liver cirrhosis and portal hypertension, however, it is not clear that whether it has a significant influence on PHLF. Future remnant liver volume (FRLV) is a significant factor for liver regeneration after hepatectomy, spleen volume (SV) could also predict the degree of liver cirrhosis, and recent literatures reported that SV to FRLV ratio (SV/FRLV) could predict small for size syndrome (SFSS) in liver transplantation, however, the relationship between SV/FRLV and PHLF in patients receiving hepatectomy is not known. Systemic inflammatory response (SIR) plays a significant role in the pathogenesis and progression of liver cirrhosis, however, it is not very clear about the exact relationship between SIR and PHLF.

We prospectively collected the medical data of consecutive patients diagnosed with hepatocellular carcinoma (HCC) who underwent hepatectomy from August 2015 to February 2016. Preoperative measurements of SS, liver stiffness (LS), SV, FRLV, and SIR were performed on all patients. A univariate analysis was performed to find the risk factors of PHLF and a multivariate analysis was used to identify independent risk factors. The predictive efficiency of the risk factors was evaluated by receiver operating characteristic (ROC) curve.

Twenty three (23) (14.6%) patients developed PHLF. Univariate analysis found several variables significantly related to PHLF, they were as follows: tumor diameter (P = .01), cirrhosis (P = .001), neutrophil to lymphocyte ratio (NLR) (P = .018), LS (P = .001), SS (P = .001), SV/FRLV (P < .001), operation duration (P = .003), transfusion (P = .009), hepatic inflow occlusion (HIO) (P = .001). Finally, SV/FRLV (P < .001, hazard ratio (HR) = 26.356, 95% confidence interval (CI) 1.627–425.21), SS (P = .009, HR = 1.077, 95%CI 1.017–1.141), and HIO time (P = .002, HR = 1.043, 95%CI 1.014–1.072) were determined as the independent risk factors of PHLF by multivariate analysis.

SS and SV/FRLV help to predict the development of PHLF in patients with hepatocellular carcinoma.
Efficacy of dexmedetomidine for treatment of patients with sepsis
Authors: Zhang Wen-Qing , Xu Po , Zhan Xiao-Hong , Zheng Peng , Yang Wei
Published: May 2019

Background:

This meta-analysis aimed to evaluate the effect of dexmedetomidine on prognosis in patients with sepsis.

Methods:

Computer-related electronic databases were searched, including PubMed, Embase, Web of Science, the Cochrane Library, and the China National Knowledge Infrastructure, from the date of database construction to January 2019. Stata 12.0 was used to perform a meta-analysis of short-term mortality [intensive care unit (ICU) mortality or 28-day mortality], ICU length of stay, and mechanical ventilation. Mortality was expressed using risk ratio (RR) and 95% confidence interval (CI). ICU length of stay and mechanical ventilation were expressed as weighted mean difference (WMD) and 95% CIs.

Results:

We finally included 8 randomized controlled trials in this meta-analysis. Compared with the control group, the dexmedetomidine group had a lower occurrence of 28-day mortality (RR, 0.49; 95% CI, 0.35 to 0.69; P = .000) and ICU mortality (RR, 0.44; 95% CI, 0.23 to 0.84; P = .013). However, there was no statistically significant difference for the length of hospital stay (WMD, −0.05; 95% CI, −0.59 to 0.48; P = .840) and mechanical ventilation time (WMD, 1.05; 95% CI, −0.27 to 2.37; P = .392) between dexmedetomidine group and control group.

Conclusions:

In patients with sepsis, dexmedetomidine can reduce the short-term mortality of patients, but could not shorten the ICU length of stay and mechanical ventilation time. More clinical randomized controlled trials are needed to verify the efficacy and safety of dexmedetomidine on the length of hospital stay and mechanical ventilation time.
Efficacy and safety of Soshiho-tang in patients with atopic dermatitis and gastrointestinal disorders
Authors: Kang Su-Jin , Jo Eun-Heui , Yang Geum-Jin , Shim Yu-Hwa , Hong Ji-Eun , Park Min-Cheol
Published: May 2019

Background:

Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease that affects the quality of life in patients with AD. Since there is limitation of conventional treatment of AD, complementary treatment is required to treat AD symptoms more effectively and safely Soshiho-tang (SSHT) is a traditional herbal medicine that exhibits anti-inflammatory and anti-ulcer effects and improves the immune function. In this clinical trial, we will evaluate the efficacy and safety of SSHT in patients with AD and gastrointestinal disorders in comparison with placebo.

Methods/design:

This study is a single-center, randomized, double-blind, placebo-controlled, and investigator-initiated clinical trial. A total of 60 patients aged 3 to 18 years with AD and gastrointestinal disorders and who received a diagnosis of AD by Hanifin & Rajka criteria with a Scoring Atopic Dermatitis (SCORAD) index between 15 and 49 will be enrolled. Participants will be randomly assigned to the SSHT or placebo group in a ratio of 1:1. Additionally, they will have a visit schedule comprising 4 visits including a screening visit during 8 to 10 weeks. The participants will be administered SSHT or placebo 3 times a day for 4 weeks. The primary outcome will be measured by a change of the SCORAD index. The secondary outcome measures include the following: survey questionnaires for the perception of gastrointestinal disorders, amount and frequency of ointment usage for AD, dermatology quality of life index, itchiness and sleep disability score in visual analog scale, percutaneous water loss, skin surface temperature, Hamilton anxiety rating scale, and children's depression inventory.

Discussion:

In our knowledge, this will be the first clinical trial to assess the efficacy and safety of SSHT in patients with AD and gastrointestinal disorders. The findings of this study will provide new treatment options for patients with AD and gastrointestinal disorders.

Trial registration:

Korean National Clinical Trial Registry, Clinical Research Information Service. (KCT0003713) https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=13489<ype=&rtype=
Molecular Classification of Breast Cancer
Authors: Tsang Julia Y.S. , Tse Gary M.
Published: May 2019

Cancer classification aims to provide an accurate diagnosis of the disease and prediction of tumor behavior to facilitate oncologic decision making. Traditional breast cancer classification, mainly based on clinicopathologic features and assessment of routine biomarkers, may not capture the varied clinical courses of individual breast cancers. The underlying biology in cancer development and progression is complicated. Recent findings from high-throughput technologies added important information with regard to the underlying genetic alterations and the biological events in breast cancer. The information provides insights into new treatment strategies and patient stratifications that impact on the management of breast cancer patients. This review provides an overview of recent data on high throughput analysis of breast cancers, and it analyzes the relationship of these findings with traditional breast cancer classification and their clinical potentials.
Microvascular and Systemic Impact of Resuscitation with PEGylated Carboxyhemoglobin-Based Oxygen Carrier or Hetastarch in a Rat Model of Transient Hemorrhagic Shock
Authors: Nugent William H. , Sheppard Forest R. , Dubick Michael A. , Cestero Ramon F. , Darlington Daniel N. , Jubin Ronald , Abuchowski Abe , Song Bjorn K.
Published: May 2019

Background:

Hemorrhage is the leading cause of preventable, traumatic death. Currently, prehospital resuscitation fluids provide preload but not oxygen-carrying capacity—a critical blood function that mitigates microvascular ischemia and tissue hypoxia during hemorrhagic shock. Solutions containing polymerized hemoglobin have been associated with vasoactive and hypertensive events. A novel hemoglobin-based oxygen carrier, modified with PEGylation and CO moieties (PEG-COHb), may overcome these limitations.

Objectives:

To evaluate the systemic and microcirculatory effects of PEG-COHb as compared with the 6% hetastarch in a rat model of hemorrhagic shock.

Methods:

Male Sprague Dawley rats (N = 20) were subjected to severe, controlled, hemorrhagic shock. Animals were randomized to 20% estimated blood-volume resuscitation with either 6% hetastarch or PEG-COHb. Continuous, invasive, cardiovascular measurements, and arterial blood gases were measured. Microcirculatory measurements of interstitial oxygenation (PISFO2) and vasoactivity helped model oxygen delivery in the spinotrapezius muscle using intravital and phosphorescence quenching microscopy.

Results:

Hemorrhage reduced mean arterial pressure (MAP), arteriolar diameter, and PISFO2, and increased lactate 10-fold in both groups. Resuscitation with both PEG-COHb and hetastarch improved cardiovascular parameters. However, PEG-COHb treatment resulted in higher MAP (P < 0.001), improved PISFO2 (14 [PEG-COHb] vs. 5 [hetastarch] mmHg; P < 0.0001), lower lactate post-resuscitation (P < 0.01), and extended survival from 90 to 142 min (P < 0.001) as compared with the hetastarch group.

Conclusions:

PEG-COHb improved MAP PISFO2, lactate, and survival time as compared with 6% hetastarch resuscitation. Importantly, hypertension and vasoactivity were not detected in response to PEG-COHb resuscitation supporting further investigation of this resuscitation strategy.
Compliance With Pelvic Floor Physical Therapy in Patients Diagnosed With High-Tone Pelvic Floor Disorders
Authors: Woodburn Katherine L. , Tran Misha C. , Casas-Puig Viviana , Ninivaggio Cara S. , Ferrando Cecile A.
Published: May 2019

Objective

The primary objective of this study was to describe patient compliance with pelvic floor physical therapy (PFPT) for high-tone pelvic floor disorders (HTPFD) and to compare patients who are compliant with prescribed therapy to those who are not. The secondary objective is to describe second-line treatments offered for HTPFD for returning patients.

Methods

This is a retrospective cohort study of women with a HTPFD who were prescribed PFPT at a tertiary care referral center. Patients were excluded if they had a primary diagnosis of urinary incontinence, had undergone prior PFPT, or if PFPT was part of preoperative planning. Noncompliance with PFPT was defined as not being formally discharged from therapy by the treating therapist.

Results

Data on PFPT compliance were available for 662 patients (87.3%). A total of 128 patients (19.4%) were fully compliant. Noncompliant patients were more likely to smoke and to have mental health disease compared with compliant patients (18% vs 8.7%, P = 0.01, and 50.4% vs 37.5%, P = 0.009, respectively). A total of 285 patients (43.1%) returned to their prescribing provider. Noncompliant patients were less likely to return to their provider: 63.4% versus 29.7%, P = <0.0001. Of the patients who returned, 183 (64.2%) were offered second-line treatment.

Conclusions

Only 1 in 5 patients referred to PFPT for management of a high-tone pelvic floor disorder is compliant with the recommended therapy. Patients who are noncompliant are less likely to return to their prescribing provider, and less than half of referred patients return. Sixty percent of patients who return are offered second-line treatment.
Reliability of Symptoms and Dipstick for Postoperative Catheter-Associated Urinary Tract Infections
Authors: Holthaus Emily A. , Ferrando Cecile A. , Jelovsek J. Eric , Barber Matthew D.
Published: May 2019

Objective

The aim of the study was to determine the diagnostic reliability of patient symptoms and urine dipstick results, including blood, leukocyte esterase, and nitrite, in diagnosing postoperative catheter-associated urinary tract infections (CAUTIs) after gynecologic surgery.

Methods

A prospective cohort study of patients undergoing gynecologic surgeries who required short-term (>24 hours) postoperative catheterization was conducted. Patients completed a questionnaire regarding symptoms. Urine dipstick analysis was completed on catheterized urine samples and urine was sent for culture for all patients. Positive likelihood ratios (LRs) were used to examine diagnostic reliability of patient symptoms and urine dipstick results in diagnosing postoperative CAUTIs.

Results

Fifty-seven patients with postoperative short-term indwelling catheterization were recruited, 25 (44%) of whom had CAUTIs diagnosed by urine culture at recruitment and 32 (56%) of whom did not have CAUTIs. Urine dipstick parameters were found to successfully diagnose CAUTIs, with positive LRs of 1.44 (95% confidence interval [CI], 1.04–1.99), 6.77 (95% CI, 2.23–20.52), and 9.47 (95% CI, 1.23–72.69) for blood, leukocyte esterase, and nitrite, respectively. The combination of leukocyte esterase and nitrite yielded a positive LR of 9.48 (95% CI, 2.62–34.25). Individual symptoms, alone or in combination, did not successfully diagnose positive urine culture (positive LRs <1.8).

Conclusions

Urine dipstick parameters are reliable diagnostic tests for diagnosing postoperative CAUTIs after gynecologic surgery, particularly when in combination. Patient symptoms have little diagnostic value for positive urine cultures in catheterized patients after gynecologic surgery.
Cryptosporidium
Authors: Chalmers Rachel M. , Davies Angharad P. , Tyler Kevin
Published: May 2019

The protozoan Cryptosporidium is notorious for its resistance to chlorine disinfection, a mainstay of water treatment. Human infections, mainly of the small intestine, arise from consumption of faecally contaminated food or water, environmental exposure, and person-to-person or animal-to-person spread. Acute gastrointestinal symptoms can be prolonged but are usually self-limiting. Problems arise with immune-deficient, including malnourished, people including chronic diarrhoea, hepato-biliary tree and extra-gastrointestinal site infection, and few options for treatment or prevention exist. Although genomics has enabled refined classification, identification of chemotherapeutic targets and vaccine candidates, and putative factors for host adaption and pathogenesis, their confirmation has been hampered by a lack of biological tools.
Rapid evolution and biogeographic spread in a colorectal cancer
Authors: Alves Joao M , Prado-Lopez Sonia , Cameselle-Teijeiro Jose Manuel , Posada David
Published: May 2019

How and when tumoral clones start spreading to surrounding and distant tissues is currently unclear. Here, we leveraged a model-based evolutionary framework to investigate the demographic and biogeographic history of a colorectal cancer. Our analyses strongly support an early monoclonal metastatic colonization, followed by a rapid population expansion at both primary and secondary sites. Moreover, we infer a hematogenous metastatic spread seemingly under positive selection, plus the return of some tumoral cells from the liver back to the colon lymph nodes. This study illustrates how sophisticated techniques typical of organismal evolution can provide a detailed picture of the complex tumoral dynamics over time and space.
Early life stress alters transcriptomic patterning across reward circuitry in male and female mice
Authors: Peña Catherine Jensen , Smith Milo , Ramakrishnan Aarthi , Cates Hannah M. , Bagot Rosemary C. , Kronman Hope G. , Patel Bhakti , Chang Austin B. , Purushothaman Immanuel , Dudley Joel , Morishita Hirofumi , Shen Li , Nestler Eric J.
Published: May 2019

Abuse, neglect, and other forms of early life stress (ELS) significantly increase risk for psychiatric disorders including depression. In this study, we show that ELS in a postnatal sensitive period increases sensitivity to adult stress in female mice, consistent with our earlier findings in male mice. We used RNA-sequencing in the ventral tegmental area, nucleus accumbens, and prefrontal cortex of male and female mice to show that adult stress is distinctly represented in the brain’s transcriptome depending on ELS history. We identify: 1) biological pathways disrupted after ELS and associated with increased behavioral stress sensitivity, 2) putative transcriptional regulators of the effect of ELS on adult stress response, and 3) subsets of primed genes specifically associated with latent behavioral changes. We also provide transcriptomic evidence that ELS increases sensitivity to future stress through enhancement of known programs of cortical plasticity.
Flexible and accurate decoding of neural populations through stochastic comodulation
Authors: Haimerl Caroline , Savin Cristina , Simoncelli Eero P.
Published: May 2019

Sensory-guided behavior requires reliable encoding of information (from stimuli to neural responses) and flexible decoding (from neural responses to behavior). In typical decision tasks, a small subset of cells within a large population encode task-relevant stimulus information and need to be identified by later processing stages for relevant information to be transmitted. A statistically optimal decoder (e.g., maximum likelihood) can utilize task-relevant cells for any given task configuration, but relies on complete knowledge of the relationship between the task and the stimulus-response and noise properties of the encoding population. The brain could learn an optimal decoder for a task through supervised learning (i.e., regression), but this typically requires many training trials, and thus lacks the flexibility of humans or animals, that can rapidly adjust to changes in task parameters or structure. Here, we propose a novel decoding solution based on functionally targeted stochastic modulation. Population recordings during different discrimination tasks have revealed that a substantial portion of trial-to-trial variability in cell responses can be explained by stochastic modulatory signals that are shared, and that seem to preferentially target task-informative neurons (Rabinowitz et al., 2015). The variability introduced by these modulators corrupts the encoded stimulus signal, but we propose that it also serves as a label for the informative neurons, allowing the decoder to solve the identification problem. We show in simulations of a modulated Poisson spiking model that a linear decoder with readout weights proportional to the estimated neuron-specific strength of modulation achieves performance close to an optimal decoder.
Dopaminergic learning and arousal circuits mediate opposing effects on alcohol consumption in Drosophila
Authors: Ojelade Shamsideen A. , Butts Andrew R. , Merrill Collin B. , Champaloux Eve Privman , Aso Yoshinori , Wolin Danielle , Cofresi Roberto U. , Gonzales Rueben A. , Rubin Gerald M. , Venton B. Jill , Rodan Aylin R. , Rothenfluh Adrian
Published: May 2019

The response to drugs of abuse is a combination of aversive and reinforcing reactions. While much is known about the role of dopamine in mammalian drug reinforcement, we know little about the brain circuits mediating drug aversion. Here we show that two distinct dopaminergic circuits mediate reinforcing and acute aversive responses to alcohol consumption in Drosophila. Protocerebral anterior medial dopamine neurons projecting to the mushroom bodies are required for flies to acquire alcohol preference. Conversely, a bilateral pair of dopamine neurons projecting to the dorsal fan-shaped body (dFSB) mediates acute alcohol avoidance. Alcohol consumption can be reduced by decreasing the activity of the appetitive reinforcement-circuit to the mushroom bodies, or by increasing activity in the dopamine neurons projecting to the dFSB. Thus, distinct dopaminergic pathways can be targeted to reduce the intake of harmful drugs.
Mitochondrial Morphology Regulates Organellar Ca2+Uptake and Changes Cellular Ca2+Homeostasis
Authors: Kowaltowski Alicia J. , Menezes‐Filho Sergio L. , Assali Essam , Gonçalves Isabela G. , Abreu Phablo , Miller Nathanael , Nolasco Patricia , Laurindo Francisco R. M. , Bruni‐Cardoso Alexandre , Shirihai Orian
Published: May 2019

Changes in mitochondrial size and shape have been implicated in several physiological processes, but their role in mitochondrial Ca2+uptake regulation and overall cellular Ca2+homeostasis is largely unknown. Here we show that modulating mitochondrial dynamics towards increased fusion through expression of a dominant negative form of the fission protein DRP1 (DRP1‐DN) markedly increased both mitochondrial Ca2+retention capacity and Ca2+uptake rates in permeabilized C2C12 cells. Similar results were seen using the pharmacological fusion‐promoting M1 molecule. Conversely, promoting a fission phenotype through the knockdown of the fusion protein mitofusin 2 (MFN2) strongly reduced mitochondrial Ca2+uptake speed and capacity in these cells. These changes were not dependent on modifications in inner membrane potentials or the mitochondrial permeability transition. Implications of mitochondrial morphology modulation on cellular calcium homeostasis were measured in intact cells; mitochondrial fission promoted lower basal cellular calcium levels and lower endoplasmic reticulum (ER) calcium stores, as measured by depletion with thapsigargin. Indeed, mitochondrial fission was associated with ER stress. Additionally, the calcium‐replenishing process of store‐operated calcium entry (SOCE) was impaired in MFN2 knockdown cells, while DRP1‐DN‐promoted fusion resulted in faster cytosolic Ca2+increase rates. Overall, our results show a novel role for mitochondrial morphology in the regulation of mitochondrial Ca2+uptake, which impacts on cellular Ca2+homeostasis.
Regularized selection indices for breeding value prediction using hyper-spectral image data
Authors: Lopez-Cruz Marco , Olson Eric , Rovere Gabriel , Crossa Jose , Dreisigacker Susanne , Mondal Suchismita , Singh Ravi , de los Campos Gustavo
Published: May 2019

High-throughput phenotyping (HTP) technologies can produce data on thousands of phenotypes per unit being monitored. These data can be used to breed for economically and environmentally relevant traits (e.g., drought tolerance); however, incorporating high-dimensional phenotypes in genetic analyses and in breeding schemes poses important statistical and computational challenges. To address this problem, we developed regularized selection indices; the methodology integrates techniques commonly used in high-dimensional phenotypic regressions (including penalization and rank-reduction approaches) into the selection index (SI) framework. Using extensive data from CIMMYT’s (International Maize and Wheat Improvement Center) wheat breeding program we show that regularized SIs derived from hyper-spectral data offer consistently higher accuracy for grain yield than those achieved by canonical SIs, and by vegetation indices commonly used to predict agronomic traits. Regularized SIs offer an effective approach to leverage HTP data that is routinely generated in agriculture; the methodology can also be used to conduct genetic studies using high-dimensional phenotypes that are often collected in humans and model organisms including body images and whole-genome gene expression profiles.
Significant control of Zika infection in macaques depends on the elapsing time after dengue exposure
Authors: Serrano-Collazo Crisanta , Pérez-Guzmán Erick X. , Pantoja Petraleigh , Hassert Mariah A. , Rodríguez Idia V. , Giavedoni Luis , Hodara Vida , Parodi Laura , Cruz Lorna , Arana Teresa , Martínez Melween I. , White Laura , Brien James D , de Silva Aravinda , Pinto Amelia K. , Sariol Carlos A.
Published: May 2019

Prior exposure to a single serotype of dengue virus (DENV) predisposes individuals to severe disease upon secondary heterologous DENV infection. Here we show that the length of time between DENV/Zika (ZIKV) infections has a qualitative impact on controlling ZIKV replication. We identified limited but significant differences in the magnitude of the early humoral immune response associated with a period of twelve months but not three months of DENV convalescence. However, their role limiting ZIKV replication is not conclusive. There was no evidence of in vivo antibody-dependent amplification of ZIKV by DENV immunity in any group. We are also showing that the significant differences among groups may be linked to a pre-existing polyfunctional CD4+ T cells response (increased IFN-g and Cd107a before ZIKV infection) and to an early and continuous expansion of the CD4+ effector memory cells early on after ZIKV infection. Those significant differences were associated with a period of 12 months after DENV infection that were not observed in a span of 3-months. These results suggest that there is a window of optimal cross-protection between ZIKV and DENV with significant consequences. These results have pivotal implications while interpreting ZIKV pathogenesis in flavivirus-experimented populations, diagnostic results interpretation and vaccine designs among others.

Author Summary

Since its introduction in the Americas region ZIKV virus has been associated to severe birth defects. One of the questions that remains open is the role of previous dengue or any other flavivirus immunity in the pathogenesis of ZIKV and more important, if the time elapse between DENV and ZIKV play a role enhancing ZIKV pathogenesis as it is the case for subsequent DENV infections. On this work, using NHP as a model we compared the effect of a period of 12 months vs. a period of 3 months of DENV immunity in the outcome of ZIKV infection. We found that previous DENV infection, at any of the tested period of time do not induce ZIKV enhancement. More relevant are showing that when the two infection occurs at least one year apart the preexisting DENV immunity is better at controlling ZIKV replication and that the role of the neutralizing antibodies is very limited. On the contrary our results suggest that early after ZIKV infection the cellular immune response, may plays a predominant role. Our findings have critical relevance to understand the dynamic interaction between these two flavivirus, their pathogenies, diagnosis and vaccine design.
Changes in lipid composition and ultrastructure associated with functional maturation of the cuticle during adult maize leaf development
Authors: Bourgault Richard , Matschi Susanne , Vasquez Miguel , Qiao Pengfei , Sonntag Annika , Charlebois Caleb , Mohammadi Marc , Scanlon Michael J. , Smith Laurie G. , Molina Isabel
Published: May 2019

Although extensive prior work has characterized cuticle composition, function, ultrastructure and development in many plant species, much remains to be learned about how these features are interrelated. Moreover, very little is known about the adult maize leaf cuticle in spite of its significance for agronomically important traits in this major crop. We analyzed cuticle composition, ultrastructure, and permeability along the developmental gradient of partially expanded adult maize leaves to probe the relationships between these features. The water barrier property is acquired at the cessation of cell expansion. Wax types and chain lengths accumulate asynchronously along the developmental gradient, while overall wax load does not vary. Cutin begins to accumulate prior to establishment of the water barrier and continues thereafter. Ultrastructurally, pavement cell cuticles consist of an epicuticular layer, a thin cuticle proper that acquires an inner, osmiophilic layer during development, and no cuticular layer. Cuticular waxes of the adult maize leaf are dominated by alkanes and wax esters localized mainly in the epicuticular layer. Establishment of the water barrier coincides with a switch from alkanes to esters as the major wax type, and the emergence of an osmiophilic (likely cutin-rich) layer of the cuticle proper.

Higlight statement

Chemical, ultrastructural and functional analysis of cuticle development in partially expanded adult maize leaves revealed important roles for wax esters and an osmiophilic, likely cutin-rich, layer in protection from dehydration.
Multiplexed dissection of a model human transcription factor binding site architecture
Authors: Davis Jessica E. , Insigne Kimberly D. , Jones Eric M. , Hastings Quinn B , Kosuri Sriram
Published: May 2019

In eukaryotes, transcription factors orchestrate gene expression by binding to TF-Binding Sites (TFBSs) and localizing transcriptional co-regulators and RNA Polymerase II to cis-regulatory elements. The strength and regulation of transcription can be modulated by a variety of factors including TFBS composition, TFBS affinity and number, distance between TFBSs, distance of TFBSs to transcription start sites, and epigenetic modifications. We still lack a basic comprehension of how such variables shaping cis-regulatory architecture culminate in quantitative transcriptional responses. Here we explored how such factors determine the transcriptional activity of a model transcription factor, the c-AMP Response Element (CRE) binding protein. We measured expression driven by 4,602 synthetic regulatory elements in a massively parallel reporter assay (MPRA) exploring the impact of CRE number, affinity, distance to the promoter, and spacing between multiple CREs. We found the number and affinity of CREs within regulatory elements largely determines overall expression, and this relationship is shaped by the proximity of each CRE to the downstream promoter. In addition, while we observed expression periodicity as the CRE distance to the promoter varied, the spacing between multiple CREs altered this periodicity. Finally, we compare library expression between an episomal MPRA and a new, genomically-integrated MPRA in which a single synthetic regulatory element is present per cell at a defined locus. We observe that these largely recapitulate each other although weaker, non-canonical CREs exhibited greater activity in the genomic context.