bluuebunny/crossref_metadata_2025 huggingface dataset:
Variability in Wound Care Recommendations Following Dermatologic Procedures
Authors: Nguyen Julie K. , Huang Alisen , Siegel Daniel M. , Jagdeo Jared
Published: April 2019

BACKGROUND

Dermatologists routinely perform office-based surgical procedures that result in cutaneous wounds. Wound care instructions are an important resource for postoperative patients. As there is no consensus on the ideal wound care regimen after dermatologic procedures, recommendations may vary.

OBJECTIVE

To evaluate the current recommendations for wound care following dermatologic procedures.

METHODS

The authors conducted a cross-sectional assessment of dermatology wound care handouts available online. The handouts were evaluated based on predefined parameters: topical agent recommendations for wound healing, caution against topical antibiotic use, and discussion of scarring, infection, bleeding, analgesia, and lifestyle considerations.

RESULTS

A total of 169 handouts were evaluated. The majority (84%) recommended the application of petrolatum-based products, specifically Vaseline (75%) and Aquaphor (43%). Nearly half (43%) recommended the use of topical antibiotics, whereas 24% advised patients to avoid antibiotic ointments. Handouts variably addressed scarring (36%), infection (72%), bleeding (69%), pain (66%), and lifestyle modifications (64%).

CONCLUSION

The instructions provided in dermatology patient handouts are highly variable, with various topical agents being recommended for wound healing. Topical antibiotics are not indicated for prophylaxis in clean dermatologic procedures but are still widely used. Greater efforts should be made to ensure that patients receive consistent and evidence-based wound care guidance.
A Systematic Review Examining the Exercise Parameters Required to Induce the Repeated Bout Effect: Implications for Acute Care Physical Therapists
Authors: VanWye William R. , Goldberg Melissa D. , Green Anna E. , Harrold Timothy J. , Dick Sonya C.
Published: April 2019

Background:

Acute care physical therapists regularly use therapeutic exercise to target body structures and functions as a supplement to or even replacing activity-based interventions. Interestingly, little is known regarding the mechanism of action explaining how exercise enables future activity and participation. One potential mechanism of action is the repeated bout effect (RBE), which is the phenomenon that a single bout of exercise provides protective adaptations for future exercise/physical activity.

Purpose:

To perform a systematic review examining the exercise parameters required to induce the RBE and explore how the results apply to acute care physical therapists.

Data Sources:

Academic Search Complete, CINAHL, MasterFILE Premier, MEDLINE, PsycINFO, and SPORTDiscus.

Study Selection:

The search included articles appearing before January 1, 2017. The following were the inclusion criteria: human subjects, randomized controlled trial design, published in English, treatment and control group engaged in exercise, lower extremity exercise intervention, and pre- and postintervention creatine kinase blood marker measurement.

Data Extraction and Quality Assessment:

Three reviewers extracted data and then assessed the methodological quality of the included articles.

Results:

Of the 1780 potential studies, seven were included. The RBE can be induced with exercise that includes an eccentric component, as well as with maximal voluntary isometric contractions at elongated muscle lengths. Concentric-only exercise does not induce the RBE and could instead blunt it. Stretching does not induce the RBE; however, it does not blunt it.

Conclusion:

The RBE enhances a person's tolerance for future exercise/physical activity. Consequently, the use of exercise to induce the RBE would be advantageous during initial and subsequent acute care physical therapist interventions. Future research is needed to specifically address the precise dose needed to induce the RBE in middle-aged and older adults, those with acute and chronic diseases, and women of all ages.
A Long-Term, Open-Label Study to Evaluate the Safety and Tolerability of Brexpiprazole as Adjunctive Therapy in Adults With Major Depressive Disorder
Authors: Hobart Mary , Zhang Peter , Skuban Aleksandar , Brewer Claudette , Hefting Nanco , Sanchez Raymond , McQuade Robert D.
Published: April 2019

Background

Long-term treatment is recommended in major depressive disorder (MDD) to prevent relapse and to restore functioning. The aim of this study (Orion; NCT01360866) was to assess the long-term safety, tolerability, and efficacy of open-label treatment with adjunctive brexpiprazole in adult patients with MDD.

Methods

Patients rolled over into this 52-week study (amended to 26 weeks) from 3 randomized, double-blind, placebo-controlled studies. Patients received brexpiprazole 0.5 to 3 mg/d (flexible dose) adjunct to their current antidepressant treatment. The primary outcome variable was the frequency and severity of treatment-emergent adverse events (TEAEs). Efficacy was assessed as a secondary objective using clinical rating scales.

Results

A total of 2944 patients were enrolled (1547 for 52 weeks, 1397 for 26 weeks), of whom 1895 (64.4%) completed the study. The TEAEs with incidence of 5% or greater were weight increase (17.7%), somnolence (8.0%), headache (7.2%), akathisia (6.7%), increased appetite (6.3%), insomnia (6.3%), fatigue (6.1%), viral upper respiratory tract infection (5.4%), and anxiety (5.2%). Most TEAEs were mild or moderate in severity. The mean increase in body weight was 2.7 kg to week 26 and 3.2 kg to week 52; 25.8% of patients had a weight increase of 7% or greater at any postbaseline visit. There were no clinically relevant findings related to extrapyramidal symptoms, prolactin, lipids, or glucose. Patients’ symptoms and functioning showed continual improvement.

Conclusions

Adjunctive treatment with open-label brexpiprazole 0.5 to 3 mg/d was generally well tolerated for up to 52 weeks in patients with MDD and was associated with continued improvement in efficacy measures and functional outcomes.
Acceptability of Women Self-Sampling versus Clinician-Collected Samples for HPV DNA Testing: A Systematic Review
Authors: Morgan Karen , Azzani Meram , Khaing Si Lay , Wong Yut-Lin , Su Tin Tin
Published: April 2019

Objectives

Female self-sampling for human papillomavirus (HPV) DNA testing is an alternative screening method that can potentially increase cervical cancer screening coverage. This review addresses the acceptability of HPV DNA testing using self-sampling compared with conventional clinician-collected sampling. Barriers to and others factors associated with acceptability of either method were also examined.

Methods

The following electronic resources were searched: Medline @EBSCOHOST(Medline), Embase, PubMed, and CINAHL databases. Manual searches were also conducted. The main outcome of interest was the acceptability of HPV DNA testing by self-sampling in comparison with clinician-collected sampling.

Results

In total, 23 articles were included in this systematic review. The majority (19 studies) were quantitative intervention studies and 4 studies were qualitative observational studies. Eleven studies reported a preference for self-sampling by women compared with clinician-collected sampling (64.7%–93%). The remaining studies found that women preferred clinician-collected sampling because mainly of respondents' lack of confidence in their ability to complete self-sampling correctly. In most articles reviewed, the studied associated factors, such as demographic factors (age, marital status, and ethnicity), socioeconomic factors (income, education level), reproductive factors (condom use, number of children, current use of contraception, and number of partners), and habits (smoking status) were not found to be significantly associated with preference.

Conclusions

Both methods of sampling were found to be acceptable to women. Self-sampling is cost-effective and could increase the screening coverage among underscreened populations. However, more information about the quality, reliability, and accuracy of self-sampling is needed to increase women's confidence about using to this method.
Asthma severity, nature or nurture: genetic determinants
Authors: Raby Benjamin A.
Published: April 2019

Purpose of review

This article reviews the progress in the search for the genetic determinants of severe asthma.

Recent findings

Twin studies estimate that approximately 25% of the phenotypic variability in asthma severity is determined by genetic factors, with the remainder determined by nongenetic factors including environmental and psychosocial factors, behavioral traits, and comorbidities. Most genetic association studies of asthma severity performed to date are underpowered and not designed to clearly distinguish asthma severity variants from asthma susceptibility variants. However, the most recent genome-wide asthma severity association study, conducted in more than 57 000 individuals, demonstrated significant associations for 25 loci, including three not previously associated with asthma: GATA3, MUC5AC, and KIAA1109. Of these, the MUC5AC association was restricted to cohorts that included moderate-to-severe (but not mild) asthma. Additional insights from rare monogenic disorders that can present as severe asthma include recognition that loss-of-function variants in the filaggrin gene known to cause ichthyosis vulgaris are consistently associated with more severe asthma outcomes. Other notable loci of interest include RAD50-IL13 on chromosome 5q and the ORMDL3-GSDMB locus on chromosome 17q21.

Severe asthma is a polygenic trait. Future research should explore the role of rare genetic variation and gene-by-environment interaction.
Prevention of allergy with diverse and healthy microbiota: an update
Authors: Chernikova Diana , Yuan Irene , Shaker Marcus
Published: April 2019

Purpose of review

Microbiota consist of symbiotic microscopic neighbors that interact on and within our bodies in diverse and incompletely understood ways throughout our lifetime. Though various associations with allergic disease have been described, clear effective therapeutic interventions to prevent allergy have been elusive.

Recent findings

The human microbiome is influenced by multiple factors, including: mode of infant delivery (vaginal vs. cesarean section), breastfeeding, diet, presence of siblings and pets, exposure to antibiotics and other medications (particularly antacids), lifestyle, and developmental context. Microbial species promoting atopic responses and tolerance have been described. Specific microbiota likely act through distinct metabolic pathways to promote the health of their human hosts, optimally directing the developing immune system away from pro-allergic, Th2-dominated responses to more T-regulatory-influenced behaviors.

Evidence suggests that specific healthy infant microbiome signatures may influence development of some components of the allergic march of childhood by decreasing atopic dermatitis, asthma, and food allergy. Further understanding of factors that influence healthy microbiota may lead to specific strategies tailored for early intervention and disease prevention.
Role of Initiating Supportive Care Preceding Veno-occlusive Disease Diagnosis Following Allogeneic Hematopoietic Stem Cell Transplantation in Children
Authors: Rayner Patricia , Spruit Jessica L. , Chu Roland , Yankelevich Maxim , Henry Meret , Ravindranath Yaddanapudi , Savaşan Süreyya
Published: April 2019

Severe veno-occlusive disease (VOD) following hematopoietic stem cell transplantation has a high mortality rate. The clinical course of VOD, role of preemptive and aggressive supportive care, and outcomes were investigated in a retrospective study from 2007 to 2014. Defibrotide was not available in all but one case with VOD at our center during the study. Forty-nine allogeneic transplants with intravenous busulfan-based or total body irradiation-based myeloablative conditioning were included. The median after hematopoietic stem cell transplantation day for suspicion of developing VOD (pre-VOD phase) was 6 due to weight gain, hepatomegaly, and/or mild increase in total bilirubin without fulfilling the modified Seattle criteria in 22 cases (45%). Despite fluid restriction, aggressive diuresis, and fresh frozen plasma infusions, 16 patients (33%) developed VOD by +10 days. Five cases (31%) had severe, 9 (56%) moderate, and 2 (13%) mild VOD. Eight cases (50%) required transfer to intensive care. One patient was given defibrotide, which was later discontinued due to concerns of adverse effects. Day +100 survival was 100% with complete resolution of VOD. Preemptive and aggressive supportive care could help achieve favorable outcomes in VOD and may have ameliorated the severity. This approach may be combined with other measures in the prevention/treatment of VOD.
State Legislation to Prevent Diversion of Opioids in Hospice Programs
Authors: Kneuss Tiffany G. , Protus Bridget McCrate , Lovell Amanda G. , Kullgren Justin G.
Published: April 2019

The problem of opioid diversion and its contribution to the opioid epidemic are well known nationally, existing even within hospice care. Proper disposal of opioids may be a critical factor in reducing diversion. In 2014, Ohio implemented legislation requiring a hospice employee to destroy or witness disposal of all unused opioids within a patient’s plan of care. The purpose of this study was to determine the impact of Ohio Revised Code 3712.062 on hospice programs’ policies and procedures to prevent opioid diversion in the home. Directors of Ohio-licensed hospices were surveyed to assess the percentage of programs with a written policy in place for disposal of opioids and to calculate a compliance score based on responses to survey questions assessing compliance with legislation components. Fifty-two surveys were completed (39.4%). All survey respondents reported having a written policy in place. A 95.5% average compliance score was calculated, with the largest disparity occurring with timing of opioid disposal. While Ohio Revised Code 3712.062 requires opioid disposal at the time of patient’s death or when no longer needed by the patient, only 84% of respondents report disposing opioids upon discontinuation. Overall, a high compliance rate was seen among hospice programs indicating such regulation is manageable to meet.
Severe Calcific Chronic Constrictive Pericarditis as an Unexpected Cause of Death
Authors: Boussaid Marwa , Mesrati Mohamed Amin , Mahjoub Yosra , Limem Hiba , Ben Abdeljalil Nouha , Zakhama Abdelfatteh , Aissaoui Abir
Published: April 2019

Chronic calcific constrictive pericarditis is a rare condition. It can cause severe morbidity and even mortality. The diagnosis may be difficult to establish due to its variable clinical signs. We report an autopsy case of a 54-year-old male with a past medical history of well treated hypertension, diabetes and dyspnea present of 2 weeks, who was discovered dead in his bed. The postmortem examination showed a large band of calcification of the pericardium with obliteration of the pericardial space. Both pericardium and epicardium were thickened with bread-and-butter appearance. Microscopic examination showed thickened pericadium which is formed by a fibrous paucicellular tissue containing extensive basophilic calcifications.
Non-Neoplastic and Benign Tumoral Lesions of the Thymic Gland: A Review and Update
Authors: Hamza Ameer , Weissferdt Annikka
Published: April 2019

The thymus is a dynamic organ that undergoes changes throughout life and can demonstrate a myriad of pathologic alterations. A number of benign entities of the thymus prove to be diagnostic dilemmas owing to their resemblance and association with true thymic tumors. These are usually discovered incidentally on routine imaging and most patients are either asymptomatic or present with signs and symptoms of compression of adjacent organs. The radiologic appearance of these lesions varies from simple cysts to complex masses that are suspicious for malignancy. The diagnosis is usually made purely on morphologic grounds, however, immunohistochemical stains can help rule out possible differential diagnoses. Surgical removal is usually curative in these lesions and recurrences are rare. The prognosis is excellent, however, some of these lesions may be associated with myasthenia gravis and/or thymomas. In this review, we describe non-neoplastic lesions and benign tumoral lesions of the thymus, with emphasis on the clinical, radiologic, and pathologic features. The differential diagnosis of each entity is also discussed.
Pregnancy and Neonatal Outcomes Following Prenatal Exposure to Dolutegravir
Authors: Vannappagari Vani , Thorne Claire ,   for APR and EPPICC
Published: April 2019

Background:

Birth outcome data with dolutegravir exposure during pregnancy, particularly in the first trimester, are needed.

Setting:

Data were prospectively collected from the Antiretroviral Pregnancy Registry and European Pregnancy and Paediatric HIV Cohort Collaboration.

Methods:

We reviewed 2 large, independent antiretroviral pregnancy registries to assess birth outcomes associated with maternal dolutegravir treatment during pregnancy.

Results:

Of 265 pregnancies reported to the Antiretroviral Pregnancy Registry, initial exposure to dolutegravir occurred at conception or first trimester in 173 pregnancies and during the second or third trimester in 92 pregnancies. There were 246 (92.8%) live births resulting in 255 neonates (9 twins), 6 (2.3%) induced abortions, 11 (4.2%) spontaneous abortions, and 2 (0.8%) stillbirths. Birth defects occurred in 7 (2.7%) of 255 live-born neonates, 5 (3.1%) of 162 (includes 6 twins) with conception/first-trimester exposure. Of 101 pregnancies reported to the European Pregnancy and Paediatric HIV Cohort Collaboration, outcomes were available for 84 pregnancies (16 continuing to term and 1 lost to follow-up). There were 81 live births (80 with known initial dolutegravir exposure at conception or first, second, and third trimesters in 42, 21, and 17 live births, respectively), 1 stillbirth (second-trimester exposure), 1 induced abortion (first-trimester exposure), and 1 spontaneous abortion (first-trimester exposure), respectively. Birth defects occurred in 4 live births (4.9%; 95% confidence interval: 1.4 to 12.2), 3 of 42 (7.1%) with exposure at conception or first trimester.

Conclusions:

Our findings are reassuring regarding dolutegravir treatment of HIV infection during pregnancy but remain inconclusive because of small sample sizes.
Impact of HIV-Status Disclosure on HIV Viral Load in Pregnant and Postpartum Women on Antiretroviral Therapy
Authors: Brittain Kirsty , Mellins Claude A. , Remien Robert H. , Phillips Tamsin K. , Zerbe Allison , Abrams Elaine J. , Myer Landon
Published: April 2019

Background:

HIV-status disclosure is widely encouraged by counseling services, in part because it is thought to improve antiretroviral therapy (ART) adherence and thus HIV viral suppression. However, few longitudinal studies have examined the impact of disclosure on HIV viral load (VL) during pregnancy and postpartum.

Methods:

We explored these associations among 1187 women living with HIV, enrolled between March 2013 and June 2014 in Cape Town, South Africa.

Results:

Among women who tested HIV-positive before pregnancy, we observed no association between disclosure and VL at entry into antenatal care among those already on ART, nor at delivery and 12 months postpartum among those initiating ART. Among women who tested HIV-positive during pregnancy and initiated ART subsequently, disclosure to a male partner was associated with a reduced risk of VL ≥50 copies/mL at delivery (adjusted risk ratio: 0.56; 95% confidence interval: 0.31 to 1.01). After stratification by relationship status, this association was only observed among women who were married and/or cohabiting. In addition, disclosure to ≥1 family/community member was associated with a reduced risk of VL ≥50 copies/mL at 12 months postpartum (adjusted risk ratio: 0.69; 95% confidence interval: 0.48 to 0.97) among newly-diagnosed women.

Conclusions:

These findings suggest that the impact of disclosure on VL is modified by 3 factors: (1) timing of HIV diagnosis (before vs. during the pregnancy); (2) relationship to the person(s) to whom women disclose; and (3) in the case of disclosure to a male partner, relationship status. Counseling about disclosure may be most effective if tailored to individual women's circumstances.
225Ac Prostate-Specific Membrane Antigen Posttherapy α Imaging
Authors: Usmani Sharjeel , Rasheed Rashid , Al kandari Fareeda , Marafi Fahad , Naqvi Syed Ali Raza
Published: April 2019

225Ac-based PSMA-targeted therapy has emerged as promising agent for the treatment of metastatic castration-resistant prostate cancer. Posttherapy image is used for tracer localization and dosimetry. Prior 2 photopeaks of 440 and 218 KeV were reported for posttherapy imaging. Our study of gamma ray spectrum, phantom, and clinical images show that imaging with 3 major photopeaks of 78, 218, and 440 KeV gives better quality images, high count statistics, and higher number of lesion delineations. It is therefore suggested that posttherapy imaging may be carried out using 3 major abundant photopeaks.
An Anatomic Study of the Keyhole Supra-Tentorium to Infra-Tentorium Endoscope Approach
Authors: Ye Pin , Sun Tao , Li Zongfang , Yang Zhihong , Li Guoping , Chen Shaochun
Published: April 2019

To provide anatomic basis for the retrosigmoid supra-tentorium to infra-tentorium keyhole approach and to explore the feasibility, 60 skulls were observed and measured to demonstrate the position relations among related bony landmarks, 12 cadaveric heads were dissected and measured for localization of the keyhole and the incision through tentorium. For giving the angle and depth for endoscopic approach, 40 adult volunteers were performed head MRI scan and the pictures were measured and analyzed. The surface projection of sigmoid and transverse sinus can be positioned by mastoidale, external occipital protuberance, and anterior end of parietomastoid suture (AEPMS) on body. There is a safe trigone of cerebellar tentorium (STCT) among inner edge of upper curve of sigmoid sinus, entrance of tentorial sinus/vein and midpoint of posterior edge of temporal arcuate eminence. 15 mm superior to the midpoint between asterion and AEPMS can be recognized as the central point of the keyhole. Magnetic resonance imaging pictures show there is potential subarachnoid space for endoscopic approach from the indicated keyhole to pontocerebellar trigone. This study demonstrated endoscopy can arrive at pontocerebellar trigone through the STCT and the keyhole supra-tentorium to infra-tentorium endoscope approach is feasible in anatomy and will contribute to excise lesions involving both supra- and infra-tentorial structures.
Type III Intraosseous Meningioma Invading Superior Sagittal Sinus and Skull Periosteum
Authors: Su Jiahao , Ba Yueyang , Liang Sitao , Liu Huijiao
Published: April 2019

Type III intraosseous meningioma is a very rare type of meningioma with extracranial extension. Herein, the author reported a case of type IIIC intraosseous meningioma with invasion of the superior sagittal sinus and skull periosteum. A 67-year-old woman was admitted to our hospital due to a mass on the left frontoparietal region for 4 years. Magnetic resonance imaging showed a skull tumor with invasion of the superior sagittal sinus. After partial resection of the tumor, pathological and immunohistochemical staining revealed that the epithelial meningioma derived from skull involved the skull periosteum. There was no enlargement of residual parasagittal tumor after 1 year of follow-up. The intraosseous meningioma in the present case was a rare benign tumor with good prognosis after surgery.
A Patient With a Protuberant Fibro-Osseous Lesion of the Temporal Bone
Authors: Maroun Christopher A. , Khalifeh Ibrahim , Faddoul Daniel S. , Zaytoun George , Moukarbel Roger V.
Published: April 2019

Protuberant fibro-osseous lesion of the temporal bone, otherwise known as “Bullough's lesion”, is a rare, benign exophytic fibro-osseous tumor. In this brief report, we present a case of a 61-year-old woman with a history of a right-sided skull mass that had been increasing in size for approximately 6 years before presentation. Clinical, radiological and histological features are examined and discussed. We achieved excellent results with surgical resection, with no evidence of recurrence.
Rapid phenotypic evolution in multidrug-resistant Klebsiella pneumoniae hospital outbreak strains
Authors: van Dorp Lucy , Wang Qi , Shaw Liam P. , Acman Mislav , Brynildsrud Ola B. , Eldholm Vegard , Wang Ruobing , Gao Hua , Yin Yuyao , Chen Hongbin , Ding Chuling , Farrer Rhys A. , Didelot Xavier , Balloux Francois , Wang Hui
Published: April 2019

Carbapenem-resistant

Klebsiella pneumoniae

(CRKP) increasingly cause high-mortality outbreaks in hospital settings globally. Following a patient fatality at a hospital in Beijing due to a bla
KPC-2-positive CRKP infection, close monitoring was put in place over the course of 14 months to characterize all bla
KPC-2-positive CRKP in circulation in the hospital. Whole genome sequences were generated for 100 isolates from bla
KPC-2-positive isolates from infected patients, carriers and the hospital environment. Phylogenetic analyses identified a closely related cluster of 82 sequence type 11 (ST11) isolates circulating in the hospital for at least a year prior to admission of the index patient. The majority of inferred transmissions for these isolates involved patients in intensive care units. Whilst the 82 ST11 isolates collected during the surveillance effort all had closely related chromosomes, we observed extensive diversity in their antimicrobial resistance (AMR) phenotypes. We were able to reconstruct the major genomic changes underpinning this variation in AMR profiles, including multiple gains and losses of entire plasmids and recombination events between plasmids, including transposition of bla
KPC-2. We also identified specific cases where variation in plasmid copy number correlated with the level of phenotypic resistance to drugs, suggesting that the number of resistance elements carried by a strain may play a role in determining the level of AMR. Our findings highlight the epidemiological value of whole genome sequencing for investigating multi-drug-resistant hospital infections and illustrate that standard typing schemes cannot capture the extraordinarily fast genome evolution of CRKP isolates.
Transcriptional maintenance of cortical somatostatin interneuron subtype identity during migration
Authors: Munguba Hermany , Nikouei Kasra , Hochgerner Hannah , Oberst Polina , Kouznetsova Alexandra , Ryge Jesper , Batista-Brito Renata , Munoz-Manchado Ana Belén , Close Jennie , Linnarsson Sten , Hjerling-Leffler Jens
Published: April 2019

Recent work suggests that cortical interneuron diversity arises from genetic mechanisms guided by the interplay of intrinsic developmental patterning and local extrinsic cues. Individual genetic programs underlying subtype identity are at least partly established in postmitotic neural precursors, prior to their tangential migration and integration in the cortical circuitry. Nevertheless, it is unclear how distinct interneuron identities are maintained during their migration and maturation. Sox6 is a transcription factor with an established role in MGE-derived interneuron maturation and positional identity. To determine its role in maintaining somatostatin (Sst)-expressing interneurons’ subtype identity, we conditionally removed Sox6 in migrating Sst interneurons and assessed the effects on their mature identity using single-cell RNA-sequencing (scRNAseq), in situ hybridization and electrophysiology. Sox6 removal prior to migration in Sst-expressing neurons reduced subtype diversity without affecting overall number of neurons. Seven out of nine Sst-expressing molecular subtypes were absent in the mature primary somatosensory cortex of Sox6-cKO mice, including the Chodl-Nos1-expressing type which has been shown to be specified at, or shortly after, cell cycle exit. The remaining Sst-expressing subtypes in the Sox6-cKO cortex comprised three molecular subtypes, Crh-C1ql3 and Hpse-Cbln4, and a third subtype that seemed to be a molecular hybrid of these subtypes. Moreover, Sox6-cKO cells still expressed genes enriched within the entire class of Sst-expressing neurons, such as Sst, Lhx6, Satb1, Elfn1 and Mafb. Removal of Sox6 at P7, after cells have reached their final destination and begin integration into the network, did not disrupt Chodl-Nos1 marker expression. Our findings suggest that expression of Sox6 during the migratory phase of cortical interneurons is necessary for maintenance of Sst+ subtype identity, indicating that subtype maintenance during migration requires active transcriptional programs.
Flat Electrode Contacts for Peripheral Nerve Stimulation
Authors: Bucksot Jesse E , Wells Andrew J , Rahebi Kimiya C , Sivaji Vishnoukumaar , Romero-Ortega Mario , Kilgard Michael P , Rennaker Robert L , Hays Seth A
Published: April 2019

The majority of available systems for nerve stimulation use circumferential stimulation electrodes inside an insulating cuff, which produce largely uniform current density within the nerve. Flat stimulation electrodes that contact only one side of the nerve may provide advantages including simpler implantation, ease of production, and more resistance to mechanical failure. However, it is possible that the flat configuration will yield inefficient fiber recruitment due to a less uniform current distribution within the nerve. Here we tested the hypothesis that flat electrodes will require higher current amplitude to achieve effective stimulation than circumferential designs. Computational modeling and in vivo experiments were performed to evaluate fiber recruitment in different nerves and different species using a variety of electrode designs. Initial results demonstrated similar fiber recruitment in the rat vagus and sciatic nerves with a standard circumferential cuff electrode and a cuff electrode modified to approximate a flat configuration. Follow up experiments comparing true flat electrodes to circumferential electrodes on the rabbit sciatic nerve confirmed that fiber recruitment was equivalent between the two designs. These findings demonstrate that flat electrodes represent a viable design for nerve stimulation that may provide advantages over the current circumferential designs for applications in which the goal is uniform activation of the nerve.
Parsimonious scenario for the emergence of viroid-like repliconsde novo
Authors: Catalán Pablo , Elena Santiago F. , Cuesta José A. , Manrubia Susanna
Published: April 2019

Viroids are small, non-coding, circular RNA molecules that infect plants. Different hypotheses for their evolutionary origin have been put forward, such as an early emergence in a precellular RNA World or severalde novoindependent evolutionary origins in plants. Here we discuss the plausibility ofde novoemergence of viroid-like replicons by giving theoretical support to the likelihood of different steps along a parsimonious evolutionary pathway. While Avsunviroidae-like structures are relatively easy to obtain through evolution of a population of random RNA sequences of fixed length, rod-like structures typical of Pospiviroidae are difficult to fix. Using different quantitative approaches, we evaluate the likelihood that RNA sequences fold into a rod-like structure and bear specific sequence motifs facilitating interactions with other molecules,e.g.RNA polymerases, RNases and ligases. By means of numerical simulations, we show that circular RNA replicons analogous to Pospiviroidae emerge if evolution is seeded with minimal circular RNAs that grow through the gradual addition of nucleotides. Further, these rod-like replicons often maintain their structure if independent functional modules are acquired that impose selective constraints. The evolutionary scenario we propose here is consistent with the structural and biochemical properties of viroids described to date.
The origins of anterograde interference in visuomotor adaptation
Authors: Lerner Gonzalo , Albert Scott , Caffaro Pedro A. , Villalta Jorge I. , Jacobacci Florencia , Shadmehr Reza , Della-Maggiore Valeria
Published: April 2019

Anterograde interference refers to the negative impact of prior learning on the propensity for future learning. Previous work has shown that subsequent adaptation to two perturbations of opposing sign,AandB, impairs performance inB. Here, we aimed to unveil the mechanism at the basis of anterograde interference by tracking its impact as a function of time through a 24h period. We found that the memory ofAbiased performance inBfor all time intervals. Conversely, learning from error was hindered up to 1h following acquisition ofA, with release from interference occurring at 6h. These findings suggest that poor performance induced by prior learning is driven by two distinct mechanisms: a long-lasting bias that acts as a prior and hinders the initial level of performance, and a short-lasting learning impairment that originates from a reduction in error-sensitivity. Our work provides insight into the timeline of memory stabilization in visuomotor adaptation.
Functional diversity plays a role in driving β-diversity: Or does it?
Authors: Murray-Stoker David
Published: April 2019

Patrick and Brown (2018) suggest that functional diversity of the species pool has an important role in generating β-diversity. Using a combination of path analysis and model selection, they ostensibly provide support for this hypothesis; however, they neglected to put theory and modeling into proper ecological and statistical context. Here, I present a re-analysis of their data. I conclude that the drivers of β-diversity are variable, with functional diversity typically having a reduced, if any, role compared to consistently stronger roles played by γ-diversity or environmental variation on structuring β-diversity.
The complex genetic architecture of recombination and structural variation in wheat uncovered using a large 8-founder MAGIC population
Authors: Shah Rohan , Huang B Emma , Whan Alex , Newberry Marcus , Verbyla Klara , Morell Matthew K , Cavanagh Colin R
Published: April 2019

Background

Identifying the genetic architecture of complex traits requires access to populations with sufficient genetic diversity and recombination. Multi-parent Advanced Generation InterCross (MAGIC) populations are a powerful resource due to their balanced population structure, allelic diversity and enhanced recombination. However, implementing a MAGIC population in complex polyploids such as wheat is not trivial, as wheat harbours many introgressions, inversions and other genetic factors that interfere with linkage mapping.

Results

By utilising a comprehensive crossing strategy, additional rounds of mixing and novel genotype calling approaches, we developed a bread wheat eight parent MAGIC population made up of more than 3000 fully genotyped recombinant inbred lines derived from 2151 distinct crosses, and achieved a dense genetic map covering the complete genome. Further rounds of inter-crossing led to increased recombination in inbred lines, as expected. The comprehensive and novel approaches taken in the development and analysis of this population provide a platform for genetic discovery in bread wheat. We identify previously unreported structural variation highlighted by segregation distortion, along with the identification of epistatic allelic interactions between specific founders. We demonstrate the ability to conduct high resolution QTL mapping using the number of recombination events as a trait, and identify several significant QTLs explaining greater than 50% of the variance.

Conclusions

We report on a novel and effective resource for genomic and trait exploration in hexaploid wheat, that can be used to detect small genetic effects and epistatic interactions due to the high level of recombination and large number of lines. The interactions and genetic effects identified provide a basis for ongoing research to understand the basis of allelic frequencies across the genome, particularly where economically important loci are involved.
Ferrous-glutathione coupling mediates ferroptosis and frailty inCaenorhabditis elegans
Authors: Jenkins Nicole L. , James Simon A. , Salim Agus , Sumardy Fransisca , Speed Terence P. , Conrad Marcus , Richardson Des R. , Bush Ashley I. , McColl Gawain
Published: April 2019

All eukaryotes require iron. Replication, detoxification, and a cancer-protective form of regulated cell death termedferroptosis1, all depend on iron metabolism. Ferrous iron accumulates over adult lifetime in theCaenorhabditis elegansmodel of ageing2. Here we show that glutathione depletion is coupled to ferrous iron elevation in these animals, and that both occur in late life to prime cells for ferroptosis. We demonstrate that blocking ferroptosis, either by inhibition of lipid peroxidation or by limiting iron retention, mitigates age-related cell death and markedly increases lifespan and healthspan inC. elegans. Temporal scaling of lifespan is not evident when ferroptosis is inhibited, consistent with this cell death process acting at specific life phases to induce organismal frailty, rather than contributing to a constant ageing rate. Because excess age-related iron elevation in somatic tissue, particularly in brain3–5, is thought to contribute to degenerative disease6, 7, our data indicate that post-developmental interventions to limit ferroptosis may promote healthy ageing.
Ambient temperature effects on stress-induced hyperthermia in Svalbard ptarmigan
Authors: Nord Andreas , Folkow Lars P.
Published: April 2019

Stress-induced hyperthermia (SIH) is commonly observed during handling in homeotherms. However, in birds, handling in cold environments typically elicits hypothermia. It is unclear whether this indicates that SIH is differently regulated in this taxon or if it is due to size, because body temperatures changes during handling in low temperature have only been measured in small birds ≤ 0.03 kg (that are more likely to suffer high heat loss when handled). We have, therefore, studied thermal responses to handling stress in the intermediate-sized (0.5-1.0 kg) Svalbard ptarmigan (Lagopus muta hyperborea) in 0°C and −20°C, in winter and spring. Handling caused elevated core body temperature, and peripheral vasoconstriction that reduced back skin temperature. Core temperature increased less and back skin temperature decreased more in −20°C than in 0°C, probably because of higher heat loss rate at the lower temperature. Responses were qualitatively consistent between seasons, despite higher body condition/insulation in winter and dramatic seasonal changes in photoperiod, possibly affecting stress responsiveness. Our study supports the notion that SIH is a general thermoregulatory reaction to acute stressors in endotherms, but also suggests that body size and thermal environment should be taken into account when evaluating this response in birds.
Limiting-stress-elimination hypothesis: approach to increase savanna cowpea productivity by stress reduction
Authors: Atta-Boateng Acheampong , Berlyn Graeme P.
Published: April 2019

We propose and test the Limiting-Stress-Elimination Hypothesis (LSEH), as a decision axiom to guide in determining the optimal intervention strategy towards yield allocation in a savanna legume. We considered osmotic stress and soil nitrogen (N) limitation, which both characterize Guinea savanna agro-ecozone. We hypothesized that biomass allocation will increase when the limiting stress is eliminated at least until the next limiting stress impacts yield. We assessed responses ofVigna unguiculata(L.) Walp (cowpea) to osmotic stress treatments (non-hormonal biostimulant and exogenous metabolite) and N input by leaf level physiology, N-fixing capacity and biomass. The relative increase in biomass (%), and pod yields reveal that osmotic stress (45%) more than nitrogen (13%) is limiting to cowpea growth under Guinea savanna conditions, although N fertilization increased nodulation and maximized PSII quantum yield. In the Sprengel-Liebig’s decrement from the maximum concept, the decrement from the maximum for each stressor must be minimized in order to produce the absolute maximum production. However, this may not be economically feasible in many situations. Conversely, LSEH demonstrates that significant productivity is attainable by eliminating a relatively more limiting stress, osmotic stress, regardless of the limitation and natural demand for the relatively less limiting N in leguminous cowpea in the savanna.
Behavioural analysis of single-cell aneural ciliate,Stentor roeselii, using machine learning approaches
Authors: Trịnh Kiều Mi , Wayland Matthew T. , Prabakaran Sudhakaran
Published: April 2019

There is still a significant gap between our understanding of neural circuits and the behaviours they compute – i.e. the computations performed by these neural networks (Carandini 2012). Learning, behaviour, and memory formation, what used to only be associated with animals with neural systems, have been observed in many unicellular aneural species, namely Physarum, Paramecium, and Stentor (Tang & Marshall 2018). As these are fully functioning organisms, yet being unicellular, there is a much better chance to elucidate the detailed mechanisms underlying these learning processes in these organisms without the complications of highly interconnected neural circuits. An intriguing learning behaviour observed inStentor roeselii(Jennings 1902) when stimulated with carmine has left scientists puzzled for more than a century. So far, none of the existing learning paradigm can fully encapsulate this particular series of five characteristic avoidant reactions. Although we were able to observe all responses described in literature and in a previous study (Dexter et al. 2019, manuscript in preparation), they do not conform to any particular learning model. We then investigated whether models based on machine learning approaches, including decision tree, random forest, and feed-forward neural networks could infer and predict the behavior ofS. roeselii. Our results showed that an artificial neural network with multiple ‘computational’ neurons is inefficient at modelling the single-celled ciliate’s avoidant reactions. This has highlighted the complexity of behaviours in aneural organisms. Additionally, this report will also discuss the significance of elucidating molecular details underlying learning and decision-making processes in these unicellular organisms, which could offer valuable insights that are applicable to higher animals.
Antagonistic and auxin-dependent phosphoregulation of columella PIN proteins controls lateral root gravitropic setpoint angle in Arabidopsis
Authors: Roychoudhry Suruchi , Sageman-Furnas Katelyn , Wolverton Chris , Goodman Heather L. , Grones Peter , Mullen Jack , Hangarter Roger , Friml Jiří , Kepinski Stefan
Published: April 2019

Lateral roots of many species are maintained at non-vertical angles with respect to gravity. These gravitropic setpoint angles (GSAs) are intriguing because their maintenance requires that roots are able to effect gravitropic response both with and against the gravity vector. Here we have used the Arabidopsis lateral root in order to investigate the molecular basis of the maintenance of non-vertical GSAs. We show that gravitropism in the lateral root is angle-dependent and that both upward and downward graviresponse requires auxin transport and the generation of auxin asymmetries consistent with the Cholodny-Went model. We show that the symmetry in auxin distribution in lateral roots growing at GSA can be traced back to a net, balanced polarization of PIN3 and PIN7 auxin transporters in the columella cells. Further, upward and downward graviresponse in lateral roots correlates with corresponding changes in PIN3 and PIN7 polar localisation. Finally, we show that auxin, in addition to driving tropic growth in the lateral root, acts within the columella to regulate GSA via the PIN phosphatase subunit RCN1 in a PIN3-dependent and PIN7-independent manner. Together, these findings provide a molecular framework for understanding gravity-dependent nonvertical growth in Arabidopsis lateral roots.
Opposing contributions of GABAergic and glutamatergic ventral pallidal neurons to motivational behaviours
Authors: Stephenson-Jones Marcus , Bravo-Rivera Christian , Ahrens Sandra , Furlan Alessandro , Fernandes-Henriques Carolina , Li Bo
Published: April 2019

The ventral pallidum (VP) is critical for invigorating reward seeking and is also involved in punishment avoidance, but how it contributes to such opposing behavioural actions remains unclear. Here we show that GABAergic and glutamatergic VP neurons selectively control behaviour in opposing motivational contexts. In vivo recording combined with optogenetics in mice revealed that these two populations oppositely encode positive and negative motivational value, are differentially modulated by animal’s internal state and determine the behavioural response during motivational conflict. Furthermore, GABAergic VP neurons are essential for movements towards reward in a positive motivational context, but suppress movements in an aversive context. In contrast, glutamatergic VP neurons are essential for movements to avoid a threat but suppress movements in an appetitive context. Our results indicate that GABAergic and glutamatergic VP neurons encode the drive for approach and avoidance, respectively, with the balance between their activities determining the type of motivational behaviour.
Coordinating Receptor Expression and Wiring Specificity in Olfactory Receptor Neurons
Authors: Li Hongjie , Li Tongchao , Horns Felix , Li Jiefu , Xie Qijing , Xu Chuanyun , Wu Bing , Kebschull Justus M. , Vacek David , Xie Anthony , Luginbuhl David J. , Quake Stephen R. , Luo Liqun
Published: April 2019

The ultimate function of a neuron is determined by both its physiology and connectivity, but the transcriptional regulatory mechanisms that coordinate these two features are not well understood1–4. TheDrosophilaOlfactory receptor neurons (ORNs) provide an excellent system to investigate this question. As in mammals5, eachDrosophilaORN class is defined by the expression of a single olfactory receptor or a unique combination thereof, which determines their odor responses, and by the single glomerulus to which their axons target, which determines how sensory signals are represented in the brain6–10. In mammals, the coordination of olfactory receptor expression and wiring specificity is accomplished in part by olfactory receptors themselves regulating ORN wiring specificity11–13. However,Drosophilaolfactory receptors do not instruct axon targeting6, 14, raising the question as to how receptor expression and wiring specificity are coordinated. Using single-cell RNA-sequencing and genetic analysis, we identified 33 transcriptomic clusters for fly ORNs. We unambiguously mapped 17 to glomerular classes, demonstrating that transcriptomic clusters correspond well with anatomically and physiologically defined ORN classes. We found that each ORN expresses ~150 transcription factors (TFs), and identified a master TF that regulates both olfactory receptor expression and wiring specificity. A second TF plays distinct roles, regulating only receptor expression in one class and only wiring in another. Thus, fly ORNs utilize diverse transcriptional strategies to coordinate physiology and connectivity.