bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibiotic-induced gut metabolome and microbiome alterations increase the susceptibility to Candida albicans colonization in the gastrointestinal tract
Authors: Gutierrez Daniel , Weinstock Anthony , Antharam Vijay C , Gu Haiwei , Jasbi Paniz , Shi Xiaojian , Dirks Blake , Krajmalnik-Brown Rosa , Maldonado Juan , Guinan Jack , Thangamani Shankar
Published: November 2019

Antibiotic-induced alterations in the gut ecosystem increases the susceptibility to Candida albicans, yet the mechanisms involved remains poorly understood. Here we show that mice treated with the broad-spectrum antibiotic cefoperazone promoted the growth, morphogenesis and gastrointestinal (GI) colonization of C. albicans. Using metabolomics, we revealed that the cecal metabolic environment of the mice treated with cefoperazone showed a significant alteration in intestinal metabolites. Levels of carbohydrates, sugar alcohols and primary bile acids increased, whereas carboxylic acids and secondary bile acids decreased in antibiotic treated mice susceptible to C. albicans. Furthermore, using in-vitro assays, we confirmed that carbohydrates, sugar alcohols and primary bile acids promote, whereas carboxylic acids and secondary bile acids inhibit the growth and morphogenesis of C. albicans. In addition, in this study we report changes in the levels of gut metabolites correlated with shifts in the gut microbiota. Taken together, our in-vivo and in-vitro results indicate that cefoperazone-induced metabolome and microbiome alterations favor the growth and morphogenesis of C. albicans, and potentially play an important role in the GI colonization of C. albicans.
Endophytic bacterial communities of oilseed rape associate with genotype-specific resistance against Verticillium longisporum
Authors: Glaeser Stefanie P , Gabur Iulian , Haghighi Hossein , Bartz Jens-Ole , Kämpfer Peter , Snowdon Rod , Obermeier Christian
Published: November 2019

Associations of endophytic bacterial community composition of oilseed rape (Brassica napus L.) with quantitative resistance against the soil-borne fungal pathogen Verticillium longisporum was assessed by 16S rRNA gene amplicon sequencing in roots and hypocotyls of four plant lines with contrasting genetic composition in regard to quantitative resistance reactions. The plant compartment was found to be the dominating driving factor for the specificity of bacterial communities in healthy plants. Furthermore, V. longisporum infection triggered a stabilization of phylogenetic group abundance in replicated samples suggesting a host genotype-specific selection. Genotype-specific associations with bacterial phylogenetic group abundance were identified by comparison of plant genotype groups (resistant versus susceptible) and treatment groups (healthy versus V. longisporum-infected) allowing dissection into constitutive and induced directional association patterns. Relative abundance of Flavobacteria, Pseudomonas, Rhizobium and Cellvibrio was associated with resistance/susceptibility. Relative abundance of Flavobacteria and Cellvibrio was increased in resistant genotypes according to their known ecological functions. In contrast, a higher relative abundance of Pseudomonas and Rhizobium, which are known to harbor many species with antagonistic properties to fungal pathogens, was found to be associated with susceptibility, indicating that these groups do not play a major role in genetically controlled resistance of oilseed rape against V. longisporum.
The interplay between fishery yield and top predator culling in a multispecies fishery context
Authors: da S Costa Michel Iskin , Anjos Lucas Dos
Published: November 2019

In food webs, fishery can play the role of top predator, competing thus with other top predators for valuable food resources. In this view, it has been claimed in fisheries management that culling of top predators can be a means to improve fishery yield. To investigate this hypothesis, we use theoretical population models to assess in a multispecies context how fishery yield from target species harvest responds to top predator cull. Defying crisp summary, the four analysed food web models show that this response may be either positive or negative or both, indicating that in terms of multispecies fishery management the harvest yield may not accrue as a consequence of predator removal. In addition, this multitude of behaviours points also to the fact that the response of fishery yield to top predator cull may be difficult to assess.
Solving the ‘Gig-saw’? Collective Rights and Platform Work
Authors: Doherty Michael , Franca Valentina
Published: November 2019

There are few topics in contemporary labour law scholarship that have generated more literature than work in the so-called ‘platform economy’. To date, much work has focussed on the question of defining the personal scope of the employment relationship and on the problems of using existing classifications of employment status in the context of work organised via platforms. This article seeks to address the much less-discussed issue of how collective bargaining may function in the ‘platform economy’, and the role of collective labour law actors, most notably the social partners. The article argues that, rather than focussing on individual employment status and litigation, it is by developing a regulatory framework supportive of, and that involves key stakeholders in, strong sectoral collective bargaining that work in the ‘platform economy’ can be adequately regulated to the benefit of workers, business and the State.
Treatment of a Full-Thickness Burn Injury With NovoSorb Biodegradable Temporizing Matrix and RECELL Autologous Skin Cell Suspension: A Case Series
Authors: Larson Kenneth W , Austin Cindy L , Thompson Simon J
Published: November 2019

Dermal substitutes coupled with split thickness skin graft are the primary method of treating most severe full-thickness burns particularly when there is a lack of healthy donor skin. Although dermal replacements optimize functional and aesthetic outcomes in patients, the risk of infection and the amount of time required to process most dermal substitutes delay treatment potentially compromising graft take and the overall healing process. The purpose of this case series is to describe the treatment course of patients with severe burn injuries using a novel synthetic Biodegradable Temporizing Matrix (NovoSorb BTM) in conjunction with RECELL Autologous Cell Harvesting Device, a new methodology allowing for a timely point-of-care preparation of an autologous skin cell suspension in combination with a 3:1 split-thickness skin graft. To the best of our knowledge, this is the first reported case series to describe the treatment algorithm and clinical outcomes of deep full-thickness burns utilizing BTM in conjunction with RECELL ASCS.
Why Are Queens Broodless? Failed Nest Initiation Not Linked to Parasites, Mating Status, or Ovary Development in Two Bumble Bee Species of Pyrobombus (Hymenoptera: Apidae: Bombus)
Authors: Mullins Jessica L , Strange James P , Tripodi Amber D
Published: November 2019

Bumble bees (Bombus [Hymenoptera: Apidae]) are important pollinators for agricultural crops, which has led to their commercial domestication. Despite their importance, little is known about the reproductive biology of bumble bees native to North America. The Hunt bumble bee (Bombus huntii Greene [Hymenoptera: Apidae]) and the Vosnesensky bumble bee (Bombus vosnesenskii Radoszkowski [Hymenoptera: Apidae] are native candidates for commercial production in western North America due to their efficacy in providing commercial pollination services. Availability of pollinators native to the region in which services would be provided would minimize the likelihood of introducing exotic species and spreading novel disease. Some parasites are known to affect bumble bee reproduction, but little is known about their prevalence in North America or how they affect queen success. Only 38% of wild-caught B. huntii and 51% wild-caught B. vosnesenskii queens collected between 2015 and 2017 initiated nests in the laboratory. Our objective was to identify causal factors leading to a queen’s inability to oviposit. To address this, we dissected each broodless queen and diagnosed diseases, assessed mating status, and characterized ovary development. Nematodes, arthropods, and microorganisms were detected in both species. Overall, 20% of queens were infected by parasites, with higher rates in B. vosnesenskii. Over 95% of both species were mated, and over 88% had developed ovaries. This suggests that parasitism and mating status were not primary causes of broodlessness. Although some failure to nest can be attributed to assessed factors, additional research is needed to fully understand the challenges presented by captive rearing.
The Practitioner’s Bookshelf: New Books on Undocumented Storytellers in the United States and on the Crime of Aggression in International Law
Authors: Valente Rubia R , Phillips Brian
Published: November 2019

In this instalment of ‘The Practitioner’s Bookshelf’—a new feature of the JHRP Review section containing brief reviews of recent publications of particular interest to human rights practitioners—Rubia R. Valente (Baruch College, City University of New York) discusses an analysis of narratives from the immigrant rights movement in the USA and Brian Phillips (Reviews Editor, JHRP) assesses a study of the crime of aggression in international law.
Molecular dynamics study of ACBP denaturation in alkyl sulfates demonstrates possible pathways of unfolding through fused surfactant clusters
Authors: Poghosyan Armen H , Schafer Nicholas P , Lyngsø Jeppe , Shahinyan Aram A , Pedersen Jan Skov , Otzen Daniel E
Published: November 2019

Anionic surfactants denature proteins at low millimolar concentrations, yet little is known about the underlying molecular mechanisms. Here, we undertake 1-μs-long atomistic molecular dynamics simulations of the denaturation of acyl coenzyme A binding protein (ACBP) and compare our results with previously published and new experimental data. Since increasing surfactant chain length is known to lead to more rapid denaturation, we studied denaturation using both the medium-length alkyl chain surfactant sodium dodecyl sulfate (SDS) and the long alkyl chain surfactant sodium hexadecyl sulfate (SHS). In silico denaturation on the microsecond timescale was not achieved using preformed surfactant micelles but required ACBP to be exposed to monomeric surfactant molecules. Micellar self-assembly occurred together with protein denaturation. To validate our analyses, we calculated small-angle X-ray scattering spectra of snapshots from the simulations. These agreed well with experimental equilibrium spectra recorded on ACBP-SDS mixtures with similar compositions. Protein denaturation occurs through the binding of partial micelles to multiple preferred binding sites followed by the accretion of surfactant monomers until these partial micelles merge to form a mature micelle and the protein chain is left disordered on the surface of the micelle. While the two surfactants attack in a similar fashion, SHS’s longer alkyl chain leads to a more efficient denaturation through the formation of larger clusters that attack ACBP, a more rapid drop in native contacts, a greater expansion in size, as well as a more thorough rearrangement of hydrogen bonds and disruption of helices.
Holographic chaos, pole-skipping, and regularity
Authors: Natsuume Makoto , Okamura Takashi
Published: November 2019

We investigate the “pole-skipping” phenomenon in holographic chaos. According to pole-skipping, the energy-density Green’s function is not unique at a special point in the complex momentum plane. This arises because the bulk field equation has two regular near-horizon solutions at the special point. We study the regularity of the two solutions more carefully using curvature invariants. In the upper-half $\omega$-plane, one solution, which is normally interpreted as the outgoing mode, is in general singular at the future horizon and produces a curvature singularity. However, at the special point, both solutions are indeed regular. Moreover, the incoming mode cannot be uniquely defined at the special point due to these solutions.
Holographic complexity for disentangled states
Authors: Numasawa Tokiro
Published: November 2019

We consider the maximal volume and the action, which are conjectured to be gravity duals of the complexity, in the black hole geometries with end-of-the-world branes. These geometries are duals of boundary states in conformal field theories which have small real space entanglement. When we raise the black hole temperature while keeping the cutoff radius, black hole horizons or end-of-the-world branes come in contact with the cutoff surface. In this limit, holographic entanglement entropy reduces to zero. We study the behavior of the volume and the action, and find that the volume reduces to zero in this limit. The behavior of the action depends on their regularization. We study the implication of these results to the reference state of the holographic complexity both in the complexity = volume or the complexity = action conjectures.
Trehalose Synthesis Contributes to Osmotic Stress Tolerance and Virulence of the Bacterial Wilt PathogenRalstonia solanacearum
Authors: MacIntyre April M. , Barth John X. , Pellitteri Hahn Molly C. , Scarlett Cameron O. , Genin Stéphane , Allen Caitilyn
Published: November 2019

The xylem-dwelling plant pathogen Ralstonia solanacearum changes the chemical composition of host xylem sap during bacterial wilt disease. The disaccharide trehalose, implicated in stress tolerance across all kingdoms of life, is enriched in sap from R. solanacearum–infected tomato plants. Trehalose in xylem sap could be synthesized by the bacterium, the plant, or both. To investigate the source and role of trehalose metabolism during wilt disease, we evaluated the effects of deleting the three trehalose synthesis pathways in the pathogen: TreYZ, TreS, and OtsAB, as well as its sole trehalase, TreA. A quadruple treY/treS/otsA/treA mutant produced 30-fold less intracellular trehalose than the wild-type strain missing the trehalase enzyme. This trehalose-nonproducing mutant had reduced tolerance to osmotic stress, which the bacterium likely experiences in plant xylem vessels. Following naturalistic soil-soak inoculation of tomato plants, this triple mutant did not cause disease as well as wild-type R. solanacearum. Further, the wild-type strain out-competed the trehalose-nonproducing mutant by over 600-fold when tomato plants were coinoculated with both strains, showing that trehalose biosynthesis helps R. solanacearum overcome environmental stresses during infection. An otsA (trehalose-6-phosphate synthase) single mutant behaved similarly to ΔtreY/treS/otsA in all experimental settings, suggesting that the OtsAB pathway is the dominant trehalose synthesis pathway in R. solanacearum.
Translocator protein mediates olfactory repulsion
Authors: Ma Zongyuan , Guo Xiaojiao , Liu Jipeng
Published: November 2019

Translocator protein (TSPO, 18kDa), which was previously known as a peripheral‐type benzodiazepine receptor, is associated with psychiatric disorders and acts as a neuroimaging biomarker. However, its function and mechanism in modulating behaviors are less well‐known. Herein, we found that TSPO in migratory locusts shows conserved protein traits and is expressed at high levels in the brains. The expression levels of tspo mRNA and protein were higher in brains of solitary locusts than those in gregarious locusts, whereas the mRNA and protein expression levels remained stable during crowding and isolation, suggesting that the expression level of TSPO is potentially associated with behavioral phenotype of solitary locusts. Moreover, tspo RNAi knockdown in the brains of solitary locusts decreased their olfactory repulsion. After RNAi knockdown of tyramine receptor (TyR) in the brains of solitary locusts, RNA‐seq analysis identified that a functional class of receptors, which included tspo, was downregulated significantly. Moreover, tspo mRNA and protein expression levels were downregulated and upregulated after TyR RNAi knockdown and activation, respectively. tspo RNAi knockdown in the brains of solitary locusts induced the attractive response and inhibited the function of tyramine (TA)‐TyR in inducing olfactory repulsion. In gregarious locusts, tspo RNAi knockdown inhibited the function of TA‐TyR inducing olfactory repulsion. This study confirms that TSPO acts as a crucial effector protein in TA‐TyR signaling to modulate olfactory repulsion. Furthermore, this study provides a novel mechanism by which TSPO functionally connects a G‐protein‐coupled receptor and a mitochondria membrane protein in modulating olfactory repulsion.
Exploring nurse vs. NP disaster response competencies
Authors: Adelman Deborah S. , Fant Catherine , Wood Laura , Zak Concetta
Published: November 2019

This second installment of the Disaster Response Series covers the nurse competencies for disaster response outlined by the International Council of Nurses and the World Health Organization and explores how NP disaster response competencies from the National Organization of Nurse Practitioner Faculties align with nurse competencies.
APRN transition to practice
Authors: Urbanowicz Janet
Published: November 2019

Leaving the comfort zone of being an experienced RN for a new career as an inexperienced advanced practice registered nurse (APRN) is one of the greatest difficulties of the APRN transition to practice. Although this challenge is frequently discussed in the literature, progress in creating transition programs has been slow. To date, very few formal APRN residency or fellowship transition programs exist. Practicing APRNs can advocate for a formal transition program in their organizations.
From pregnancy to renal disease
Authors: Mitchell-Brown Fay , Pubols Jessica
Published: November 2019

Preeclampsia is a hypertensive disorder of pregnancy defined as new-onset hypertension that develops during pregnancy and resolves after delivery. Using a case history as an illustration, this article discusses hypertensive disorders of pregnancy with a focus on preeclampsia and its renal implications.
The Birth, Death, and Renaissance (?) of Dissection: A Critique of Anatomy Teaching With—or Without—the Human Body
Authors: Marom Assaf
Published: November 2019

A riveting debate regarding the fate of dissection, the classical method of anatomy, is sweeping through medical academia, as imaging tools gain a greater foothold in anatomy teaching programs. This Perspective does not aim to grapple with the question of “how should anatomy be taught” but rather to explain why the transformation of anatomical education is taking place by situating these developments in the broader philosophical context of modern medicine, offered by Michel Foucault’sThe Birth of the Clinic: An Archaeology of Medical Perception. Emphasizing the body’s crucial role in the epistemological change in medical practice in the early 19th century, Foucault coined the term “medical gaze” to denote the doctor’s observation of the patient’s body in search of signs of disease. Within this new systematic perception of disease, which brought about the anatomo-clinical method, the clinical gaze thus embraced the study of the body via dissection. The author contends that the introduction of medical imaging into the diagnostic process has resulted in a shift in the focus of the clinical gaze from the body to its medical image and that this process is mirrored in anatomy by its discarding of the cadaver. Given the fundamental differences between the phenomenology of the body and its medical image, the author suggests that when using medical images in medical schools and teaching hospitals, one teaches, at the very least, a new kind of anatomy. Foucault’s analysis of the paintingThe Treachery of Imagesby Réne Magritte lends some support to the ideas presented here.
Can Better Selection Tools Help Us Achieve Our Diversity Goals in Postgraduate Medical Education? Comparing Use of USMLE Step 1 Scores and Situational Judgment Tests at 7 Surgical Residencies
Authors: Gardner Aimee K. , Cavanaugh Katelyn J. , Willis Ross E. , Dunkin Brian J.
Published: November 2019

Purpose

Use of the United States Medical Licensing Examination (USMLE) for residency selection has been criticized for its inability to predict clinical performance and potential bias against underrepresented minorities (URMs). This study explored the impact of altering traditional USMLE cutoffs and adopting more evidence-based applicant screening tools on inclusion of URMs in the surgical residency selection process.

Method

Multimethod job analyses were conducted at 7 U.S. general surgical residency programs during the 2018–2019 application cycle to gather validity evidence for developing selection assessments. Unique situational judgment tests (SJTs) and scoring algorithms were created to assess applicant competencies and fit. Programs lowered their traditional USMLE Step 1 cutoffs and invited candidates to take their unique SJT. URM status (woman, racial/ethnic minority) of candidates who would have been considered for interview using traditional USMLE Step 1 cutoffs was compared with the candidate pool considered based on SJT performance.

Results

A total of 2,742 general surgery applicants were invited to take an online SJT by at least 1 of the 7 programs. Approximately 35% of applicants who were invited to take the SJT would not have met traditional USMLE Step 1 cutoffs. Comparison of USMLE-driven versus SJT-driven assessment results demonstrated statistically different percentages of URMs recommended, and including the SJT allowed an average of 8% more URMs offered an interview invitation (P < .01).

Conclusions

Reliance on USMLE Step 1 as a primary screening tool precludes URMs from being considered for residency positions at higher rate than non-URMs. Developing screening tools to measure a wider array of candidate competencies can help create a more equitable surgical workforce.
Maternal and Neonatal Hair Cortisol Levels and Psychological Stress Are Associated With Onset of Secretory Activation of Human Milk Production
Authors: Caparros-Gonzalez Rafael A. , Romero-Gonzalez Borja , Gonzalez-Perez Raquel , Lara-Cinisomo Sandraluz , Martin-Tortosa Pablo L. , Oliver-Roig Antonio , Peralta-Ramirez Maria Isabel
Published: November 2019

Background:

Several factors can influence the production of mothers' own milk.

Purpose:

To assess the influence of maternal psychological stress, maternal cortisol levels, and neonatal hair cortisol levels on timing of secretory activation.

Methods:

A prospective study was conducted at 2 public health centers in Andalusia, Spain. Participants were 60 pregnant women and their 60 neonates. Hair cortisol levels and psychological stress (pregnancy-specific stress [Prenatal Distress Questionnaire, PDQ] and perceived stress [Perceived Stress Scale, PSS]) were evaluated during the third trimester and the postpartum period. This study was part of the GESTASTRESS cohort study on the effects of stress during pregnancy.

Results:

Higher PDQ and PSS scores (P < .05) in the third trimester were associated with later onset of secretory activation. Higher postpartum maternal hair cortisol levels were associated with a delayed secretory activation of mother's own milk (P < .05).

Implications for Research:

Future studies should look at the influence of psychological stress and cortisol levels on hormones involved in mother's own milk production.

Implications for Practice:

Neonatal nurses and other healthcare providers should be familiar with levels of neonates' exposure to maternal prenatal stress prior to birth.
Outcome analysis following arthroscopic augmentation with autologous hamstring graft in partial tear of the anterior cruciate ligament with preservation of an intact bundle: A case series
Authors: Joshi Narendra , Singh Kamaldeep , Modi Lalit K. , Dhukia Rakesh K. , Meena Bharatlal , Gora Rajendra K.
Published: November 2019

Background:

The anatomic approach to anterior cruciate ligament (ACL) reconstruction has shifted management focus of the commonly encountered partial tear from resection and complete reconstruction to augmentation (i.e. selective bundle reconstruction with preservation of intact remnant bundle). The purpose of this study was to prospectively evaluate functional outcome after augmentation of partial ACL tears.

Methods:

Thirty-four patients with a partial ACL tear in whom a conservative trial failed were treated with either anteromedial or posteromedial single-bundle reconstruction, using an isolated semitendinosus graft and conserving the remnant bundle. Outcomes were evaluated clinically using the 2000 International Knee Documentation Committee [IKDC] knee examination forms, and manual laxity tests. Subjective evaluation was done using the 2000 IKDC subjective knee evaluation, Lysholm knee score, and 2000 IKDC functional score. Patient activity level was determined using the Tegner activity score. IKDC knee grades were assigned based on final evaluation on the 2000 IKDC knee examination forms.

Results:

At final follow-up 2000 IKDC knee examination grades significantly improved, with 21 in group B (61.8%) and 12 in group A (35.3%), while preoperatively most were classified as group C (76.5%). Similarly, IKDC subjective and Lysholm scores were significantly better after follow-up. The difference between mean Tegner activity level preinjury (6.029±0.9040) and at follow-up (5.67±1.006) was not significant.

Conclusions:

Selective bundle reconstruction with preservation of remnants restores knee stability and function. The results are encouraging, with excellent improvement in functional scores.

Level of Evidence:

Level IV.
Posterior Sternoclavicular Dislocation: Do We Need “Cardiothoracic Backup”? Insights From a National Sample
Authors: Leonard Dana A. , Segovia Nicole A. , Kaur Japsimran , Lucas Justin , Bishop Julius , Vorhies John S.
Published: November 2019

Objectives:

To describe the incidence of and risk factors for vascular injury associated with P-SCD.

Methods:

We used data from the HCUP-NIS from 2015 to 2016 and defined a cohort of patients with sternoclavicular dislocation (SCD) using ICD-10-CM diagnosis codes. We further isolated a subset with P-SCD. We describe the incidence of thoracic vascular injury, demographics, and injury severity score in this cohort.

Results:

Of an estimated 550 patients who had SCD, 140 (25%) were identified as having a P-SCD. No vascular injuries occurred in the P-SCD cohort. Among all patients with SCD, <2% of patients had a vascular injury, all of whom had an injury severity score ≥15, independent of the vascular injury itself. Among patients with an isolated P-SCD injury (55), overall length of stay was 1.8 days and total charges averaged $29,724.45. There was no mortality among patients with isolated P-SCD.

Conclusions:

Here, we report no vascular injuries in the largest known series of P-SCD. Among all patients with SCD, vascular injury was rare, occurring only in severely polytraumatized patients. The recommendation for routine involvement of cardiothoracic surgeons in all cases of P-SCD should be re-examined.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
A Medical School Dean's Guide to Orienting Educational Leaders on Roles, Responsibilities, and Resources
Authors: Christner Jennifer G. , Smith Jamie S. , Appelbaum Nital P.
Published: November 2019

Continuing professional development of physicians often revolves around clinical activities. Accordingly, there is a lack of intentional development and support of medical education leaders despite such individuals having critical influence over key organizational functions. Unequivocally, educational leaders have complex and dynamic jobs that require clear delineation of roles, responsibilities, and resources available to successfully train the next generation of health professionals. Although there is guidance on how to longitudinally onboard medical education leaders, there is little information on how to effectively orient such leaders on the functional nature of their jobs. Baylor College of Medicine’s medical school dean developed and delivered a 2-day orientation program to educational leaders to clarify roles, responsibilities, and resources. Postevaluation surveys aimed to identify key session content that would be frequently used by educational leaders to oversee key aspects of medical education. The purpose of this article is to outline the structure and content of an orientation program designed for medical education leaders, and share postevaluation data to identify which sessions were most used in practice. Other deans are encouraged to take ownership over the professional development of their educational leaders and delivering similar programming.
Induced sarcoid-like reactions in patients with metastatic melanoma treated with dabrafenib and trametinib: a monocentric retrospective study
Authors: Huynh Sandra , Lheure Coralie , Franck Nathalie , Goldman-Lévy Gabrielle , Aractingi Selim , Dupin Nicolas , Kramkimel Nora , Guégan Sarah
Published: November 2019

Combined BRAF and MEK inhibition is one of the first-line treatment strategies for patients with advanced BRAF-mutant melanoma. Sarcoid-like reactions (SLRs) have occasionally been described with melanoma systemic treatments such as immunotherapy or the BRAF inhibitor vemurafenib, but very few cases have been reported with dabrafenib and trametinib. Our aim was to better characterize SLR induced by this combination. We conducted a monocentric retrospective observational study among patients treated with dabrafenib and trametinib for BRAF-mutant advanced melanoma from January 2015 to March 2019. Patients presenting with histologically proven SLR were included. We also searched Medline database for all reported cases of SLR induced by targeted therapy. Of 63 patients on dabrafenib/trametinib combination, seven were diagnosed with a SLR. They all had specific cutaneous involvement, and one also displayed mediastinal and salivary glands involvement. None required systemic corticosteroids or dabrafenib/trametinib discontinuation. Three of them (43%) reached melanoma complete remission and are still on targeted therapy; and four patients progressed and died. A literature review yielded 22 additional cases of SLR induced by targeted therapy: the main affected organ was the skin, 11 patients (50%) had systemic involvement, five patients (23%) required systemic corticosteroids to reach partial or complete remission of SLR, 12 (55%) reached partial or complete response of melanoma while six (27%) progressed. BRAF and MEK inhibitors are potential triggers of SLR, although pathological mechanisms remain unclear. The mainstay of treatment is systemic or topical corticotherapy; targeted therapy discontinuation is usually not necessary.
Dilation of Multiple Eccrine Ducts as a Highly Specific Marker for Cicatricial Alopecia
Authors: Tan Timothy L. , Doytcheva Kristina , Guitart Joan , Gerami Pedram , Yazdan Pedram
Published: November 2019

Background:

Eccrine duct dilation (EDD) was recently described to occur more frequently in cicatricial alopecias than noncicatricial alopecias. Because single EDD can be useful in the evaluation of alopecias, we aimed to determine whether dilation of multiple eccrine duct units, or “multiple eccrine duct dilation (MEDD),” could more specifically discriminate between cicatricial and noncicatricial alopecias.

Methods:

We retrospectively evaluated 611 scalp biopsies (342 cicatricial alopecias and 269 noncicatricial alopecias).

Results:

Among cicatricial alopecias, MEDD was found in 21% (25/118) of central centrifugal cicatricial alopecia, 26% (29/109) of lichen planopilaris, 13% (10/73) of discoid lupus erythematosus, 31% (5/16) of acne keloidalis nuchae, and 26% (7/26) of folliculitis decalvans. In noncicatricial alopecias, MEDD was found in 1% (1/102) of androgenetic alopecia, 0.7% (1/150) of alopecia areata, and 0% (0/17) of telogen effluvium. In cicatricial alopecias, MEDD occurred in a significantly higher frequency (22%; 76/342) compared with noncicatricial alopecias (0.7%; 2/269) (P-value <0.0001). The presence of MEDD correlated with a diagnosis of cicatricial alopecia with 22% sensitivity and 99% specificity. MEDD also occurred more frequently in cases with moderate to severe inflammation and fibroplasia, suggesting that EDD is a reactive change secondary to the scarring processes.

Conclusion:

The presence of MEDD on scalp biopsies may be a highly specific marker of cicatricial alopecia and can aid in rendering a more accurate diagnosis. MEDD without other definitive histopathologic features of cicatricial alopecia may compel pathologists to pursue additional workup and/or raise the possibility that a cicatricial alopecia cannot be entirely excluded.
Psychiatric Symptoms: Prevalence, Co-occurrence, and Functioning Among Extremely Low Gestational Age Newborns at Age 10 Years
Authors: Dvir Yael , Frazier Jean A. , Joseph Robert M. , Mokrova Irina , Moore Phoebe S. , O'Shea T. Michael , Hooper Stephen R. , Santos Hudson P. , Kuban Karl ,   for the ELGAN Study Investigators
Published: November 2019

Objective:

To evaluate the percentage of children born extremely preterm (EP) who screen positive for ≥1 DSM-IV psychiatric disorders, the co-occurrence of and sex-related differences in these classifications, and the functional correlates of psychiatric symptoms.

Methods:

The Extremely Low Gestational Age Newborn (ELGAN) Study is a prospective cohort follow-up of children born <28 weeks' gestation. For 871 10-year-old children, parents completed the Child Symptom Inventory-4 (CSI-4), a child educational/medical history questionnaire, and the Pediatric Quality of Life Inventory (PedsQL).

Results:

At age 10 years, ELGANs were more likely to screen positive for a number of psychiatric disorders when compared with normative expectations on the CSI-4, with a few sex-related differences. Fifteen percent of participants screened positive for 1 disorder, 7% for 2, 3% for 3, and 4% for ≥4 psychiatric disorders. Compared with children who did not screen positive for psychiatric disorders, children who screened positive for ≥3 psychiatric disorders were approximately twice as likely to have repeated a grade, have an individualized educational program, have an individual school aide, and to require special remediation classes. Children who screened positive for any psychiatric disorder were 4 times more likely to use 1 or more psychotropic medication, and those who screened positive for ≥2 psychiatric disorders had lower PedsQL scores.

Conclusion:

Among 10-year-old children born EP, rates of psychiatric symptoms exceeded normative expectation, and children who screened positive for more than 1 psychiatric disorder were at increased risk of having multiple functional impairments.
Stress, Social Support, and Mental Health Among Young Adult Hispanics
Authors: Guntzviller Lisa M. , Williamson Lillie D. , Ratcliff Chelsea L.
Published: November 2019

National health goals include assessing and improving mental health in understudied US populations. We surveyed 274 individuals (18-35 years old) of Hispanic/Latino/Spanish origin residing in the United States. Participants reported poor general mental health compared with Healthy People goals. Stress was negatively associated and perceived supportive communication was positively associated with mental health. A 3-way interaction showed perceived supportive communication mitigated the negative effect of stress on mental health, and perceptions of tangible support without supportive communication degraded overall mental health. Theoretical and practical implications for social support and Hispanic population mental health are discussed.
Family and Child Characteristics Associated With Caregiver Challenges for Medically Complex Children
Authors: Mooney-Doyle Kim , Lindley Lisa C.
Published: November 2019

Children with medical complexity, comprising 3% of US children, face elevated risk of adverse medical, developmental, psychosocial, and family outcomes. The purpose of this study was to examine the association between family and child characteristics and caregiver challenges via a retrospective cohort study using data from 2009/2010 National Survey of Children with Special Health Care Needs. Results revealed that most children with medical complexity have 2 or more conditions; region of residence, insurance, and health conditions significantly predict caregiver challenges; and race, ethnicity, and coinsurance status are associated with medical challenges. Results highlight important evidence on connections between family/child characteristics and caregiver challenges among children with medical complexity.
Spatiotemporal Dynamics of Immune Cells in Early Left Ventricular Remodeling After Acute Myocardial Infarction in Mice
Authors: Bejjani Anthony T. , Saab Sally A. , Muhieddine Dina H. , Habeichi Nada J. , Booz George W. , Zouein Fouad A.
Published: November 2019

Myocardial infarction remains a leading cause of morbidity and death. Insufficient delivery of oxygen to the myocardium sets into play a complicated process of repair that involves the temporal recruitment of different immune cells so as to remove debris and necrotic cells expeditiously and to form effective scar tissue. Clearly defined and overlapping phases have been identified in the process, which transitions from an overall proinflammatory to anti-inflammatory phenotype with time. Variations in the strength of the phases as well as in the co-ordination among them have profound consequences. Too strong of an inflammatory phase can result in left ventricular wall thinning and eventual rupture, whereas too strong of an anti-inflammatory phase can lead to cardiac stiffening, arrhythmias, or ventricular aneurisms. In both cases, heart failure is an intermediate consequence with death being the likely outcome. Here, we summarize the role of key immune cells in the repair process of the heart after left ventricular myocardial infarction, along with the associated cytokines and chemokines. A better understanding of the immune response ought to lead hopefully to improved therapies that exploit the natural repair process for mending the infarcted heart.
Promoting Patient Utilization of Outpatient Cardiac Rehabilitation
Authors: Santiago de Araújo Pio Carolina , Beckie Theresa M. , Varnfield Marlien , Sarrafzadegan Nizal , Babu Abraham S. , Baidya Sumana , Buckley John , Chen Ssu-Yuan , Gagliardi Anna , Heine Martin , Khiong Jong Seng , Mola Ana , Radi Basuni , Supervia Marta , Trani Maria R. , Abreu Ana , Sawdon John A. , Moffatt Paul D. , Grace Sherry L.
Published: November 2019

Purpose:

Cardiac rehabilitation (CR) is a recommendation in international clinical practice guidelines given its benefits; however, use is suboptimal. The purpose of this position statement was to translate evidence on interventions that increase CR enrollment and adherence into implementable recommendations.

Methods:

The writing panel was constituted by representatives of societies internationally concerned with preventive cardiology and included disciplines that would be implementing the recommendations. Patient partners served, as well as policy makers. The statement was developed in accordance with AGREE II, among other guideline checklists. Recommendations were based on our update of the Cochrane review on interventions to promote patients' utilization of CR. These were circulated to panel members, who were asked to rate each on a 7-point Likert scale in terms of scientific acceptability, actionability, and feasibility of assessment. A Web call was convened to achieve consensus and confirm strength of the recommendations (based on Grading of Recommendations Assessment, Development, and Evaluation [GRADE]). The draft underwent external review and public comment.

Results:

The 3 drafted recommendations were that to increase enrollment, health care providers, particularly nurses (strong), should promote CR to patients face-to-face (strong), and that to increase adherence, part of CR could be delivered remotely (weak). Ratings (mean ± SD) for the 3 recommendations were 5.95 ± 0.69, 5.33 ± 1.12, and 5.64 ± 1.08, respectively.

Conclusions:

Interventions can significantly increase utilization of CR and hence should be widely applied. We call upon cardiac care institutions to implement these strategies to augment CR utilization and to ensure that CR programs are adequately resourced to serve enrolling patients and support them to complete programs.
Pathophysiology of Exercise Intolerance and Its Treatment With Exercise-Based Cardiac Rehabilitation in Heart Failure With Preserved Ejection Fraction
Authors: Tucker Wesley J. , Angadi Siddhartha S. , Haykowsky Mark J. , Nelson Michael D. , Sarma Satyam , Tomczak Corey R.
Published: November 2019

Heart failure with preserved ejection fraction (HFpEF) is the fastest growing form of heart failure in the United States. The cardinal feature of HFpEF is reduced exercise tolerance (peak oxygen uptake,

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2peak) secondary to impaired cardiac, vascular, and skeletal muscle function. There are currently no evidence-based drug therapies to improve clinical outcomes in patients with HFpEF. In contrast, exercise training is a proven effective intervention for improving

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2peak, aerobic endurance, and quality of life in HFpEF patients. This brief review discusses the pathophysiology of exercise intolerance and the role of exercise training to improve

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2peak in clinically stable HFpEF patients. It also discusses the mechanisms responsible for the exercise training–mediated improvements in

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2peak in HFpEF. Finally, it provides evidence-based exercise prescription guidelines for cardiac rehabilitation specialists to assist them with safely implementing exercise-based cardiac rehabilitation programs for HFpEF patients.
Selective afferent renal denervation mitigates renal and splanchnic sympathetic nerve overactivity and renal function in chronic kidney disease-induced hypertension
Authors: Veiga Amanda C. , Milanez Maycon I.O. , Ferreira Giovanna R. , Lopes Nathalia R. , Santos Camila P. , De Angelis Katia , Garcia Michelle L. , Oyama Lila M. , Gomes Guiomar N. , Nogueira Fernando N. , Carvalho Polliane M. , Campos Ruy R. , Bergamaschi Cássia T. , Nishi Erika E.
Published: November 2019

Background:

Clinical and experimental evidence have shown that renal denervation, by removing both the sympathetic and afferent nerves, improves arterial hypertension and renal function in chronic kidney disease (CKD). Given the key role of renal sympathetic innervation in maintaining sodium and water homeostasis, studies have indicated that the total removal of renal nerves leads to impaired compensatory mechanisms during hemodynamic challenges.

Method:

In the present study, we hypothesized that afferent (or sensory) fibers from the diseased kidney contribute to sympathetic overactivation to the kidney and other target organ, such as the splanchnic region, contributing to hypertension in CKD. We used a method to remove selectively the afferent renal fibers (periaxonal application of 33 mmol/l capsaicin) in a rat model of CKD, the 5/6 nephrectomy.

Results:

Three weeks after afferent renal denervation (ARD), we found a decrease in mean arterial pressure (∼15%) and normalization in renal and splanchnic sympathetic nerve hyperactivity in the CKD group. Interestingly, intrarenal renin--angiotensin system, as well as renal fibrosis and function and proteinuria were improved after ARD in CKD rats.

Conclusion:

The findings demonstrate that afferent fibers contribute to the maintenance of arterial hypertension and reduced renal function that are likely to be mediated by increased sympathetic nerve activity to the renal territory as well as to other target organs in CKD.
Estimation of Radiation Doses for a Case-control Study of Thyroid Cancer Among Ukrainian Chernobyl Cleanup Workers
Authors: Drozdovitch Vladimir , Kryuchkov Victor , Bakhanova Elena , Golovanov Ivan , Bazyka Dimitry , Gudzenko Natalia , Trotsyuk Natalia , Hatch Maureen , Cahoon Elizabeth K. , Mabuchi Kiyohiko , Bouville André , Chumak Vadim
Published: November 2019

Thyroid doses were estimated for 607 subjects of a case-control study of thyroid cancer nested in the cohort of 150,813 male Ukrainian cleanup workers who were exposed to radiation as a result of the 1986 Chernobyl nuclear power plant accident. Individual thyroid doses due to external irradiation, inhalation of 131I and short-lived radioiodine and radiotellurium isotopes (132I, 133I, 135I, 131mTe, and 132Te) during the cleanup mission, and intake of 131I during residence in contaminated settlements were calculated for all study subjects, along with associated uncertainty distributions. The average thyroid dose due to all exposure pathways combined was estimated to be 199 mGy (median: 47 mGy; range: 0.15 mGy to 9.0 Gy), with averages of 140 mGy (median: 20 mGy; range: 0.015 mGy to 3.6 Gy) from external irradiation during the cleanup mission, 44 mGy (median: 12 mGy; range: ~0 mGy to 1.7 Gy) due to 131I inhalation, 42 mGy (median: 7.3 mGy; range: 0.001 mGy to 3.4 Gy) due to 131I intake during residence, and 11 mGy (median: 1.6 mGy; range: ~0 mGy to 0.38 Gy) due to inhalation of short-lived radionuclides. Internal exposure of the thyroid gland to 131I contributed more than 50% of the total thyroid dose in 45% of the study subjects. The uncertainties in the individual stochastic doses were characterized by a mean geometric standard deviation of 2.0, 1.8, 2.0, and 2.6 for external irradiation, inhalation of 131I, inhalation of short-lived radionuclides, and residential exposure, respectively. The models used for dose calculations were validated against instrument measurements done shortly after the accident. Results of the validation showed that thyroid doses could be estimated retrospectively for Chernobyl cleanup workers two to three decades after the accident with a reasonable degree of reliability.
Different Methods of Measuring Neutron Dose/Fluence Generated During Radiation Therapy with Megavoltage Beams
Authors: Farhood Bagher , Ghorbani Mehdi , Abdi Goushbolagh Nouraddin , Najafi Masoud , Geraily Ghazale
Published: November 2019

Medical linear accelerators (linacs) are the most frequently applied radiation therapy machines in the locoregional treatment of cancers by producing either high-energy electron or photon beams. However, with high-energy photons (>8 MeV), interaction of these photons with different high-Z nuclei of materials in components of the linac head unavoidably generates neutrons. On the other hand, the average energy of these generated neutrons has almost the highest radiation-weighting factor. Therefore, the produced neutrons should not be neglected. There are various tools for the measurement of neutron dose/fluence generated in a megavoltage linac, including thermoluminescent dosimeters, solid-state nuclear track detectors, bubble detectors, activation foils, Bonner sphere systems, and ionization chamber pairs. In this review article, each of the above-mentioned dosimetric methods will be described in detail.