bluuebunny/crossref_metadata_2025 huggingface dataset:
Revealing hidden variability in PWNe with spectral index maps
Authors: Guest Benson T , Safi-Harb Samar
Published: August 2020

Pulsar wind nebulae (PWNe) are the synchrotron bubbles inflated by the rotational energy of a neutron star. Observing variability within them has previously been limited to cases of significant brightening, or the few instances where transient features are interpreted in terms of intrinsic motion or associated with variability from the pulsar. Jet and torus morphology are also only visible in cases of differing brightness with respect to the surrounding nebula and favourable alignment with our line of sight. Spectral map analysis involves binning observations with an adaptive algorithm to meet a signal limit and colouring the results based on the desired model parameter fits. Minute changes in spectral index become therefore apparent even in cases where brightness images alone do not suggest any underlying changes. We present a Chandra X-ray study of the PWNe in G21.5–0.9, Kes 75, G54.1+0.3, G11.2–0.3, and 3C 58, using archival observations accumulated over the ∼20-yr lifetime of the mission. With the spectral map analysis technique, we discover evidence for previously unknown variability opening a new window into viewing PWNe.
Galactic extinction laws – II. Hidden in plain sight, a new interstellar absorption band at 7700 Å broader than any known DIB
Authors: Maíz Apellániz J , Barbá R H , Caballero J A , Bohlin R C , Fariña C
Published: August 2020

We have detected a broad interstellar absorption band centred close to 7700 Å and with a full width at half-maximum (FWHM) of 176.6 ± 3.9 Å. This is the first such absorption band detected in the optical range and is significantly wider than the numerous diffuse interstellar bands (DIBs). It remained undiscovered until now because it is partially hidden behind the A telluric band produced by O2. The band was discovered using STIS@HST spectra and later detected in a large sample of stars of diverse type (OB stars, BA supergiants, red giants), using further STIS and ground-based spectroscopy. The EW of the band is measured and compared with our extinction and K i λλ7667.021, 7701.093 measurements for the same sample. The carrier is ubiquitous in the diffuse and translucent Galactic interstellar medium (ISM) but is depleted in the environment around OB stars. In particular, it appears to be absent or nearly so in sightlines rich in molecular carbon. This behaviour is similar to that of the σ-type DIBs, which originate in the low/intermediate-density UV-exposed ISM but are depleted in the high-density UV-shielded molecular clouds. We also present an update on our previous work on the relationship between E(4405–5495) and R5495 and incorporate our results into a general model of the ISM.
Star cluster formation in the most extreme environments: insights from the HiPEEC survey
Authors: Adamo A , Hollyhead K , Messa M , Ryon J E , Bajaj V , Runnholm A , Aalto S , Calzetti D , Gallagher J S , Hayes M J , Kruijssen J M D , König S , Larsen S S , Melinder J , Sabbi E , Smith L J , Östlin G
Published: August 2020

We present the Hubble imaging Probe of Extreme Environments and Clusters (HiPEEC) survey. We fit HST NUV to NIR broad-band and H α fluxes to derive star cluster ages, masses, and extinctions and determine the star formation rate (SFR) of six merging galaxies. These systems are excellent laboratories to trace cluster formation under extreme gas physical conditions, rare in the local Universe, but typical for star-forming galaxies at cosmic noon. We detect clusters with ages of 1–500 Myr and masses that exceed 107 M⊙. The recent cluster formation history and their distribution within the host galaxies suggest that systems such as NGC 34, NGC 1614, and NGC 4194 are close to their final coalescing phase, while NGC 3256, NGC 3690, and NGC 6052 are at an earlier/intermediate stage. A Bayesian analysis of the cluster mass function in the age interval 1–100 Myr provides strong evidence in four of the six galaxies that an exponentially truncated power law better describes the observed mass distributions. For two galaxies, the fits are inconclusive due to low number statistics. We determine power-law slopes β ∼ −1.5 to −2.0 and truncation masses, Mc, between 106 and a few times 107 M⊙, among the highest values reported in the literature. Advanced mergers have higher Mc than early/intermediate merger stage galaxies, suggesting rapid changes in the dense gas conditions during the merger. We compare the total stellar mass in clusters to the SFR of the galaxy, finding that these systems are among the most efficient environments to form star clusters in the local Universe.
FASTQINS and ANUBIS: two bioinformatic tools to explore facts and artifacts in transposon sequencing and essentiality studies
Authors: Miravet-Verde Samuel , Burgos Raul , Delgado Javier , Lluch-Senar Maria , Serrano Luis
Published: August 2020

Transposon sequencing is commonly applied for identifying the minimal set of genes required for cellular life; a major challenge in fields such as evolutionary or synthetic biology. However, the scientific community has no standards at the level of processing, treatment, curation and analysis of this kind data. In addition, we lack knowledge about artifactual signals and the requirements a dataset has to satisfy to allow accurate prediction. Here, we have developed FASTQINS, a pipeline for the detection of transposon insertions, and ANUBIS, a library of functions to evaluate and correct deviating factors known and uncharacterized until now. ANUBIS implements previously defined essentiality estimate models in addition to new approaches with advantages like not requiring a training set of genes to predict general essentiality. To highlight the applicability of these tools, and provide a set of recommendations on how to analyze transposon sequencing data, we performed a comprehensive study on artifacts corrections and essentiality estimation at a 1.5-bp resolution, in the genome-reduced bacterium Mycoplasma pneumoniae. We envision FASTQINS and ANUBIS to aid in the analysis of Tn-seq procedures and lead to the development of accurate genome essentiality estimates to guide applications such as designing live vaccines or growth optimization.
Blood Viral Load (VL) Not Clinically Meaningful in Symptomatic Congenital Cytomegalovirus (cCMV) Infection
Authors: Marsico Concetta , Aban Inmaculada , Kuo Huichien , Sanchez Pablo J , Ahmed Amina , Arav-Boger Ravit , Michaels Marian , Ashouri Negar , Englund Janet , Estrada Benjamin , Jacobs Richard , Romero Jose R , Sood Sunil , Whitworth Suzanne , James Scott H , Jester Penny , Whitley Richard , Kimberlin David W ,   Collaborative Antiviral Study Group (CASG)
Published: August 2020

Background

Sensorineural hearing loss (SNHL) and neurodevelopmental (ND) outcomes are favorably impacted by antiviral therapy in infants with symptomatic cCMV disease. We correlated blood VL before and during therapy with clinical findings at presentation and follow-up in this population.

Methods

Post-hoc analysis of two clinical trials conducted by the CASG from 2002 to 2013 evaluating valganciclovir therapy. 120 subjects (73 treated × 6 weeks, 47 treated × 6 months) were included. Whole blood VL was determined by real-time PCR at a central laboratory before therapy (baseline, BL) and periodically for 6 months.

Results

In subjects treated for 6 months, increases in BL VL correlated with decreased probability of better hearing outcomes at 12 months (Figure 1), but clinically meaningful VL thresholds that predict SNHL were not identified (Table 1). Subjects treated for 6 weeks had no correlation between BL VL and SNHL. No correlation was found between BL VL and Bayley ND testing at 12 and 24 months for subjects receiving either treatment duration. Subjects treated for 6 months who achieved and sustained VL suppression (<2.5 log) between treatment day 14 and month 4 had better hearing outcomes at 6, 12, and 24 months (89% vs. 56%, P = 0.01; 100% vs. 63%, P = 0.0007; 94% vs. 68%, P = 0.04), but 56%–68% of subjects not achieving suppression still had improved hearing. Higher BL VL correlated with BL CNS involvement, thrombocytopenia, and transaminase elevation for subjects receiving either treatment duration, but with substantial overlap in quantity of virus detected (Figure 2). Subjects with >3 symptoms of congenital CMV at presentation had higher BL VL than subjects with ≤3 symptoms (3.75 log, range 1.00–5.65, vs. 3.38 log, range 1.00–5.36; P = 0.005).

Conclusion

Blood VL at BL and during therapy has little clinically meaningful predictive value for long-term outcomes in symptomatic congenital CMV.

Disclosures

J. Englund, Gilead: Consultant and Investigator, Research support; Chimerix: Investigator, Research support; Alios: Investigator, Research support; Novavax: Investigator, Research support; MedImmune: Investigator, Research support; GlaxoSmithKline: Investigator, Research support
Carbapenem-Resistant Enterobacteriaceae Infections in Patients on Renal Replacement Therapy
Authors: Eilertson Brandon , Cober Eric , Richter Sandra S , Perez Federico , Salata Robert A , Kalayjian Robert C , Watkins Richard R , Doi Yohei , Kaye Keith S , Evans Scott , Fowler Vance G , Bonomo Robert A , DeHovitz Jack , Kreiswirth Barry , van Duin David ,   Antibacterial Resistance Leadership Group
Published: August 2020

Background

Patients on chronic intermittent renal replacement therapy (RRT) are at risk for infection with carbapenem-resistant Enterobacteriaceae (CRE). However, the impact of RRT on outcomes after CRE infections remains to be defined. Here we perform a comparison of outcomes for CRE-infected patients with preserved renal function compared with CRE-infected patients on RRT.

Methods

Cases and controls were defined from a prospective cohort of CRE-infected patients from the Consortium on Resistance against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE). Cases were defined as CRE-infected patients on RRT at hospital admission, while controls were defined as CRE-infected patients with serum creatinine <2 mg/dL and not receiving RRT at admission. Risk factors for 28-day in-hospital mortality were assessed using multivariable logistic regression. An ordinal ranking of outcomes by desirability analysis was performed.

Results

Patients on RRT were more likely to have diabetes mellitus and cardiac disease than controls. Urinary sources of infection were less common in the RRT group. In RRT patients, 28-day in-hospital mortality was increased as compared with controls: 22/71 (31%) vs 33/295 (11%). RRT remained significantly associated with 28-day in-hospital mortality after adjustment for source of infection, prehospitalization origin, and severity of illness (adjusted odds ratio, 2.27; 95% confidence interval [CI], 1.09–4.68; P = .03). Using univariable desirability of outcome ranking analysis, RRT status was associated with a 68% (95% CI, 61%–74%) chance of a worse disposition outcome.

Conclusions

Chronic RRT in CRE-infected patients is associated with increased in-hospital mortality and worse disposition outcomes at 28 days.
HIV and Chagas Disease Coinfection, a Tractable Disease?
Authors: Guidetto Betiana , Tatta Melisa , Latini Veronica , Gonzales Milene , Riarte Adelina , Tavella Silvina , Warley Eduardo , Altclas Javier
Published: August 2020

We present 2 patients born in Argentina who were newly diagnosed with advanced HIV disease and Chagas disease reactivation with central nervous system involvement. The patients received concurrent benznidazole treatment and antiretroviral therapy, showing good response. Improvement in morbidity and mortality due to early treatment makes this treatment appropriate for coinfected patients.
Infection of a prosthetic knee joint with Clostridium bifermentans
Authors: Barrett Lisa F , Saragadam Sailaja Devi , DiMaria Christina N , Delgado-Daza Alejandro
Published: August 2020

We present the first reported case of prosthetic joint infection caused by Clostridium bifermentans, which was treated with total joint washout and debridement allowing for the patient to retain his prosthesis and achieve full recovery. Clostridium bifermentans is a gram-positive, anaerobic, spore-forming bacterium. This organism was once considered to be non-pathogenic, but has recently been associated with cases of septic arthritis, empyema, osteomyelitis, soft tissue infection, brain abscess, bacteremia and endocarditis.
Vaping-induced lung injury: brief report for the practicing clinician
Authors: Khiatah Bashar , Murdoch Alex , Hubeny Charles , Constantine Carl , Frugoli Amanda
Published: August 2020

The USA is witnessing an outbreak of vaping-induced lung injuries associated with the drastic rise in e-cigarette use, especially among teenagers and young adults. Our understanding of the harmful effects of these products is expanding as an increasing amount of consumers seek medical care for lung-related illnesses. The knowledge of the long-term sequelae of e-cigarette use is limited due to their novelty, but a growing association exists between use and acute lung injury. We describe a case vignette of vaping-induced lung injury to increase physician awareness and discuss the applicability of preliminary diagnostic criteria.
A successful treatment of severe lupoid cutaneous leishmaniasis in an elderly man: a case report
Authors: Ahmad Sulafa , Suleiman Hamid , Al-Shehabi Zuheir
Published: August 2020

Lupoid cutaneous leishmaniasis (LCL) is a rare, atypical presentation of cutaneous leishmaniasis (CL). In this report, the authors present the case of a severe LCL in an elderly patient who presented to our dermatology department with severe, painful ulcerated lesion on his midface with cosmetic deformity to his nose. He had a history of CL 3 years ago at the same place. Histopathologic examination showed epidermal and dermal changes with chronic inflammatory infiltrate and no leishmaniasis bodies were detected. He was admitted and treated with systemic glucantime (60 mg/kg) for a month followed by hydroxychloroquine (200 mg twice a day) for another month with favorable outcome. Countries with endemic CL should consider LCL in patients with a history of leishmaniasis and a similar clinical presentation, especially that it could be misdiagnosed with other granulomatous cutaneous conditions, thus leading to cosmetic deformities that can be avoided with early adequate treatment.
Implications of household-level evidence for policy models: the case of macro-financial linkages
Authors: Muellbauer John
Published: August 2020

Macroeconomic policy models should track the different channels of monetary transmission, providing a framework for Monetary Policy Committees. They should also be useful for assessing risks to financial stability, including for designing macroprudential stress tests and instrument settings in the new macroprudential toolkits. Current policy models, including the ‘semi-structural’ non-DSGE econometric models such as FRB-US, are seriously deficient in these respects, failing to capture the credit channel and the role of real estate in the financial accelerator that operated in the global financial crisis, and in key transmission channels in the recovery. Furthermore, developments in economic theory, greatly encouraged by new evidence, have rendered redundant the previously accepted micro-foundations for household behaviour in these policy models.

A multi-purpose policy model needs to include a household-housing sub-system. This should contain a consumption function broadly consistent with the micro-evidence with equations for permanent income, for the balance sheet drivers, and for residential investment. To capture the credit channel, this block of the model needs to embed common credit conditions in the equations. Sub-system estimation is required to impose the cross-equation restrictions implied by these common factors.
Radiation of waves by a thin cap submerged in ice-covered ocean
Authors: Das Arijit , De Soumen , Mandal B N
Published: August 2020

The present article is concerned with the radiation of flexural gravity waves due to a thin cap submerged in the ice-covered ocean. The problem is reduced to a system of hypersingular integral equations using the boundary perturbation method. The first-order approximation has only been considered. The effects of the rigidity of the ice sheet and depth of submergence on the added mass and damping coefficient have been analysed. Two types of caps (for example, concave upwards and concave downwards) have been considered for the numerical results. The effect of the concavity on added mass and damping coefficient has also been studied. The present study should be helpful to understand the nature of waves generated by a heaving submerged body in an ice-covered ocean.
Speed or Accuracy Instructions During Skill Learning do not Affect the Acquired Knowledge
Authors: Vékony Teodóra , Marossy Hanna , Must Anita , Vécsei László , Janacsek Karolina , Nemeth Dezso
Published: August 2020

A crucial question in skill learning research is how instruction affects the performance or the underlying representations. Little is known about the effects of instructions on one critical aspect of skill learning, namely, picking-up statistical regularities. More specifically, the present study tests how prelearning speed or accuracy instructions affect the acquisition of non-adjacent second-order dependencies. We trained 2 groups of participants on an implicit probabilistic sequence learning task: one group focused on being fast and the other on being accurate. As expected, we detected a strong instruction effect: accuracy instruction resulted in a nearly errorless performance, and speed instruction caused short reaction times (RTs). Despite the differences in the average RTs and accuracy scores, we found a similar level of statistical learning performance in the training phase. After the training phase, we tested the 2 groups under the same instruction (focusing on both speed and accuracy), and they showed comparable performance, suggesting a similar level of underlying statistical representations. Our findings support that skill learning can result in robust representations, and they highlight that this form of knowledge may appear with almost errorless performance. Moreover, multiple sessions with different instructions enabled the separation of competence from performance.
The α-Subunit of the Chloroplast ATP Synthase of Tomato Reinforces Resistance to Gray Mold and Broad-Spectrum Resistance in Transgenic Tobacco
Authors: Gong Chao , Cheng Mo-zhen , Li Jing-fu , Chen Hong-yu , Zhang Zhen-zhu , Qi Hao-nan , Zhang Yao , Liu Jiayin , Chen Xiu-ling , Wang Ao-xue
Published: August 2020

Chloroplast ATP synthase (cpATPase) is responsible for ATP production during photosynthesis. Our previous studies showed that the cpATPase CF1 α subunit (AtpA) is a key protein involved in Clonostachys rosea-induced resistance to the fungus Botrytis cinerea in tomato. Here, we show that expression of the tomato atpA gene was upregulated by B. cinerea and Clonostachys rosea. The tomato atpA gene was then isolated, and transgenic tobacco lines were obtained. Compared with untransformed plants, atpA-overexpressing tobacco showed increased resistance to B. cinerea, characterized by reduced disease incidence, defense-associated hypersensitive response-like reactions, balanced reactive oxygen species, alleviated damage to the chloroplast ultrastructure of leaf cells, elevated levels of ATP content and cpATPase activity, and enhanced expression of genes related to carbon metabolism, photosynthesis, and defense. Incremental Ca2+ efflux and steady H+ efflux were observed in transgenic tobacco after inoculation with B. cinerea. In addition, overexpression of atpA conferred enhanced tolerance to salinity and resistance to the fungus Cladosporium fulvum. Thus, AtpA is a key regulator that links signaling to cellular redox homeostasis, ATP biosynthesis, and gene expression of resistance traits to modulate immunity to pathogen infection and provides broad-spectrum resistance in plants in the process.
A Giant Squamous Cell Carcinoma Arising in a Patient with Hidradenitis Suppurativa
Authors: Özkur Ezgi , Altunay İlknur Kivanç , Celayir Mustafa Fevzi , Çerman Asli Aksu , Uçak Ramazan
Published: August 2020

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease of follicular pilosebaceous units. Chronic, active, and poorly controlled disease may lead to squamous cell carcinoma (SCC). The diagnosis and treatment of SCC in HS is particularly challenging because SCC lesions may be easily mistaken for HS lesions. Current medical literature recommends aggressive surgical excision with at least 2-cm margins. In this article, the authors describe a giant perianal SCC arising in a patient with HS who was treated with surgical resection and radiotherapy.
A Review of Remdesivir for COVID-19: Data to Date
Authors: Mehta Monica , Shyh Grace I.
Published: August 2020

Severe acute respiratory coronavirus-2 (SARS-CoV-2) is responsible for one of the greatest public health challenges of our lifetime, the coronavirus disease 2019 (COVID-19) pandemic. Because of the complicated postinfection sequelae and grave consequences, the search for effective therapies has become a worldwide priority. The antiviral agent remdesivir has become a viable option and is now available in the United States for hospitalized patients through an emergency use authorization. This article describes remdesivir’s historical background, pharmacology, key trials, adverse events, and issues regarding accessibility.
Sexual and Reproductive Health Service Utilization and Sexuality for Teens on the Autism Spectrum
Authors: Graham Holmes Laura , Shattuck Paul T. , Nilssen A. Renee , Strassberg Donald S. , Himle Michael B.
Published: August 2020

Objectives:

Health care providers and educators play critical roles in supporting healthy sexuality development for youth with autism spectrum disorder. There is limited information about the sexual behavior of these youth, especially girls, and about their access to sexuality education or health care services.

Methods:

This study addressed these gaps by surveying parents of youth with autism aged 12–18 years (N = 298, 52.7% boys) with a range of intellectual functioning.

Results:

According to parent report, most youth experienced sexual attraction and were interested in relationships, including same-sex attraction or relationships (13.2%). Girls were more likely than boys to have had a romantic relationship and less likely to have experienced school or legal consequences for sexual behavior. Around one-fifth of youth had engaged in a socially inappropriate sexual behavior, whereas 6.4% had a known sexual abuse history and 14.5% were bullied by peers for lack of sexual knowledge. Almost 40% received no sex education in school or in the community, including 60.9% of youth with parent-reported intelligence quotient under 70. Some parents consulted with school personnel (36.4%) or health care providers (55.9%) about sexuality issues, whereas 19.5% reported taking no action aside from talking to their child about sexuality. Utilization models including predisposing, enabling, and needs-related factors were applied to parent consultation with providers and use of school-based sexuality education programming.

Conclusion:

The results suggest unmet needs for sexual and reproductive health services, particularly among youth who are younger, those who have co-occurring intellectual disability, or those who are homeschooled or who attend private, charter, or therapeutic versus public schools.
A Large, Open-Label, Phase 3 Safety Study of DaxibotulinumtoxinA for Injection in Glabellar Lines: A Focus on Safety From the SAKURA 3 Study
Authors: Green Jeremy B. , Mariwalla Kavita , Coleman Kyle , Ablon Glynis , Weinkle Susan H. , Gallagher Conor J. , Vitarella Domenico , Rubio Roman G.
Published: August 2020

BACKGROUND

SAKURA 3 was a Phase 3, open-label, repeat-dose safety study of DaxibotulinumtoxinA for Injection (DAXI); a component of the largest Phase 3 clinical development program of an aesthetic neuromodulator in glabellar lines.

OBJECTIVE

To evaluate the use of DAXI (40U) up to 3 treatments for moderate or severe glabellar lines.

METHODS

Eligible subjects rolled over from the placebo-controlled trials (n = 477) or were de novo (n = 2,214) and received 1 to 3 treatments over a maximum of 84 weeks. Safety and efficacy were evaluated at least every 4 weeks up to Week 36 (Treatments 1 and 2) and Week 12 (Treatment 3). Select subjects could be retreated after Week 12 if glabellar lines returned to baseline.

RESULTS

Safety results are reported for 2,691 subjects, of which 882 received a second treatment and 568 a third. Treatment-related adverse events (AEs) occurred in 17.8% of subjects, which were generally mild and resolved. No serious AEs were treatment-related. Eyelid ptosis occurred in 0.9% of treatments. Adverse events were consistent across treatments and no new safety signals were observed.

CONCLUSION

The safety of DAXI in this large open-label safety study confirms the findings from the pivotal Phase 3 trials, providing reassurance in its overall safety profile.
A Survey on National Pediatric Antibiotic Stewardship Programs, Networks and Guidelines in 23 European Countries
Authors: Kopsidas Ioannis , Vergnano Stefania , Spyridis Nikos , Zaoutis Theoklis , Patel Sanjay
Published: August 2020

Background:

Misuse, overuse of antimicrobials and increasing rates of antimicrobial resistance are well-recognized problems throughout Europe. The aim of this survey was to describe the current pediatric antibiotic stewardship (PAS) landscape across Europe and identify gaps, in terms of national programs, networks and guidelines.

Methods:

A survey of 17 questions was circulated in July 2019 among 24 European pediatric infectious disease researchers and clinicians, professors and heads of department on the existence of PAS programs, national networks and meetings, established competencies, metrics and guidelines.

Results:

We received responses from 23 countries. National guidelines on the management of children with common infections treated in hospital settings exist in 15 of 23 (70%); only 8 of 15 (53%) had been updated within the previous 4 years. Most provide guidance on antibiotic initiation and duration (14 of 15, 93%), but few on when to transition from intravenous to oral antibiotics (7 of 15, 47%). National PAS competencies have only been developed in 4 countries; only 1 addressed both community and hospital prescribing. Organized national PAS networks are only established in the United Kingdom and Germany; 21 of 23, 91% countries had no agreed metric for antibiotic prescribing in children; 2 of 23 were based on daily defined doses.

Conclusions:

Fragmented implementation of PAS programs, no agreed metrics, lack of established PAS competencies and national PAS networks along with inexistent funding is alarming in view of existing high rates of antimicrobial resistance in Europe.
Two Cases of SARS-CoV-2 Infection in Pediatric Oncohematologic Patients in Spain
Authors: Pérez-Heras Iñigo , Fernandez-Escobar Verónica , Del Pozo-Carlavilla María , Díaz-Merchán Raquel , Valerio-Alonso María Eli , Domínguez-Pinilla Nerea
Published: August 2020

Since December 2019, severe acute respiratory syndrome coronavirus 2 infection has spread worldwide. We all are concerned about immunocompromised children, especially hematologic and oncologic pediatric patients. We want to share our experience with 2 pediatric cancer patients with severe acute respiratory syndrome coronavirus 2 infection. Both presented mild disease and good outcome. No respiratory symptoms were identified, but both developed diarrhea, one probably secondary to lopinavir/ritonavir. Pediatric cancer patients may have milder disease than adults, but larger studies are needed to make conclusions.
SARS-CoV-2 Encephalitis in a 20-year old Healthy Female
Authors: Babar Aneeqa , Lewandowski Ula , Capin Ivana , Khariton Megan , Venkataraman Akila , Okolo Nwanneka , Sharma Dolly
Published: August 2020

We report a 20-year-old female with SARS-CoV-2 encephalitis who presented with 4 days of upper respiratory symptoms, fevers and sudden acute altered mental status. An extensive work up led to the most likely cause for the neurologic decompensation to be viewed as SARS-CoV-2 symptomology.
Arterial stiffness late after Kawasaki disease in children: Assessment by performing brachial–ankle pulse wave velocity
Authors: Chien Kuang-Jen , Huang Hurng-Wern , Weng Ken-Pen , Huang Shih-Hui , Li Sung-Chou , Lin Chu-Chuan , Hsieh Kai-Sheng
Published: August 2020

Background:

Whether low-risk Kawasaki disease (KD) patients are at increased risk of cardiovascular disease later in life remains controversial. The purpose of this study is to examine the arterial stiffness and exercise performance of KD patients in chronic stage.

Methods:

This study included 158 subjects. They were divided into three groups: 37 KD patients with regressed coronary artery lesions (CALs) (M/F 23/14, 13.6 ± 6.5 years) (group I), 43 KD patients without CALs (M/F 26/17, 13.9 ± 6.2 years) (group II), and 78 age- and gender-matched normal controls (M/F 44/34, 13.2 ± 6.9 years) (group III). They all underwent brachial–ankle pulse wave velocity (baPWV), an exercise test, and blood sampling to measure the levels of high-sensitivity C-reactive protein (hs-CRP), triglycerides (TG), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and total cholesterol (TC). The differences among the groups were compared.

Results:

There were significant differences among the three groups in terms of right and left baPWV (p < 0.01 respectively), HDL level (p < 0.05), TC/HDL ratio (p < 0.05), and oxygen consumption (VO2) peak (p < 0.05). Moreover, group I subjects had significantly higher right and left baPWV (p < 0.05 respectively), lower HDL level (p < 0.05), and lower VO2 peak (p < 0.05) than group II subjects. Furthermore, baPWV was significantly correlated with TG level (r = 0.326, p < 0.05), TC/HDL ratio (r = 0.483, p < 0.01), LDL level (r = 0.386, p < 0.01), and VO2 peak (r = −0.385, p < 0.05) in group I subjects. Only the TC/HDL ratio was found to be a significant correlating factor for an increase of baPWV (beta = 0.68, p < 0.05) in KD patients after multiple linear regression.

Conclusion:

Our results suggest that arterial stiffness is present late after KD and may adversely affect exercise performance, especially in patients with regressed CALs. Regular measurement of baPWV may be indicated in the long-term follow-up of KD patients.
Smartphone frailty screening: Development of a quantitative early detection method for the frailty syndrome
Authors: Chen Hung-Ju , Chen Po-Yin , Kao Chung-Lan , Sung Wen-Hsu
Published: August 2020

Background:

Frailty syndrome in older population generates formidable social cost. The early detection of “prefrail” stage is essential so that interventions could be performed to prevent deterioration. The purpose of this study was to organize appropriate physical performance tests into a computerized early frailty screening platform, called frailty assessment tools (FAT) system, to detect individuals who are in the prefrail stage.

Methods:

Four switches, one distance meter, and one power measure were adopted to build the FAT system that could perform six physical performance tests including single leg standing (SLS), repeated chair rise, timed up and go, self-selected walking speed, functional reach, and grip power. Participants over 65 years old were recruited and classified into three groups according to Fried criteria. The differences in variables between prefrail and robust groups were compared by the χ2 test, independent samples t test, and Mann-Whitney U test, for nominal variables, normal, and non-normal distributive continuous variables, respectively. The statistically significant level was set at 0.05 (α = 0.05).

Results:

Only SLS did not reach significance to distinguish prefrail from robust. Among 35 participants (73.23 ± 5.70 years old), the FAT score predicted that 90.73 ± 19.95% of pre-frail subjects and 15.01 ± 25.25% of robust subjects were in the prefrail stage.

Conclusion:

The FAT system, which provides results immediately, is an advantageous alternative to traditional manual measurements. The use of the FAT score for predicting the prefrail stage will help to provide early intervention to prevent individuals from progressing into frailty. The FAT system provides a more convenient and comprehensive frailty screening. Using this computerized automatic screening platform, it may be possible to expand the scope of frailty prevention.
Cancer incidence and mortality following treatment of hyperthyroidism with radioactive iodine
Authors: Evron Josh M. , Esfandiari Nazanene H. , Papaleontiou Maria
Published: August 2020

Purpose of review

Hyperthyroidism is a commonly encountered clinical issue. Radioactive iodine is one of the treatment modalities employed over the last 80 years. Prior studies are conflicting as to whether radioactive iodine is associated with an increased risk of subsequent malignancy and associated mortality. The present article reviews recent publications on this subject.

Recent findings

Two recent studies make meaningful contributions to the existing literature; however, data remain inconsistent. The first, conducted using the Clalit Health Services database, evaluated solid tumor incidence after radioactive iodine and found no association with increased risk of solid tumor malignancy. The second, which is an updated analysis of the Cooperative Thyrotoxicosis Therapy Follow-up Study, concluded that there is a dose-dependent increased risk of solid tumor mortality using a novel method of estimating organ-specific radiation exposure.

In patients with hyperthyroidism, radioactive iodine is a popular and effective treatment option. Prior studies reach conflicting conclusions on the potential relationship between radioactive iodine and both subsequent cancer incidence and mortality. We review recent publications that add to our understanding of this important clinical question.
The problem of vaccination refusal: a review with guidance for pediatricians
Authors: Tokish Hannah , Solanto Mary V.
Published: August 2020

Purpose of review

In the wake of multiple recent outbreaks of the measles and other vaccine-preventable diseases, it is crucial to understand and address parental concerns about vaccination. The purposes of this review are: to identify the causes of vaccine resistance, to elucidate the variables that have led to the success or failure of interventions to date, and to consider implications for pediatricians treating children whose parents are vaccination-resistant.

Recent findings

Recent research draws on insights from cognitive science to understand vaccine resistance and to develop more effective interventions. Studies show that vaccine resistors are more likely to value lifestyle liberty, to favor individualistic over hierarchical worldviews, and to believe in conspiracy theories. Interventions that seek primarily to correct erroneous beliefs about the dangers of vaccination are likely to fail or even backfire. On the other hand, intervention strategies, such as motivational interviewing, in which the provider elicits and shows respect for parents’ values and concerns while empowering them to make well informed and well reasoned decisions, are more likely to be successful. Parents cite a trusting relationship with their pediatrician as the most important factor influencing their decision to vaccinate.

Pediatricians are in the best position to successfully apply insights from cognitive science and intervention research to overcome vaccination-hesitancy.
Current status of porcine islet xenotransplantation
Authors: Coe Taylor M. , Markmann James F. , Rickert Charles G.
Published: August 2020

Purpose of review

Human islet transplantation has proven to be a highly effective treatment for patients with labile type 1 diabetes mellitus, which can free patients from daily glucose monitoring and insulin injections. However, the shortage of islet donors limits its’ broad application. Porcine islet xenotransplantation presents a solution to the donor shortage and recent advances in genetic modification and immunosuppressive regimens provide renewed enthusiasm for the potential of this treatment.

Recent findings

Advances in genetic editing technology are leading to multigene modified porcine islet donors with alterations in expression of known xenoantigens, modifications of their complement and coagulation systems, and modifications to gain improved immunological compatibility. Recent NHP-based trials of costimulation blockade using CD154 blockade show promising improvements in islet survival, whereas results targeting CD40 are less consistent. Furthermore, trials using IL-6 receptor antagonism have yet to demonstrate improvement in glucose control and suffer from poor graft revascularization.

This review will detail the current status of islet xenotransplantation as a potential treatment for type I diabetes mellitus, focusing on recent advances in porcine xenogeneic islet production, assessment in nonhuman primate preclinical models, the outcome of human clinical trials and review barriers to translation of xenoislets to the clinic.
Giardiasis treatment: an update with a focus on refractory disease
Authors: Mørch Kristine , Hanevik Kurt
Published: August 2020

Purpose of review

Giardiasis remains a common cause of diarrhea and intestinal enteropathy globally. Here we give an overview of clinical treatment studies and discuss potential mechanisms and molecular targets for in-vitro testing of drug resistance.

Recent findings

Giardia is a cause of disease both in diarrheal and nondiarrheal cases. The prevalence of treatment refractory giardiasis is increasing. Recent studies reveal 5-nitroimidazole refractory infection occurs in up to 50% of cases. Mechanisms of drug resistance are not known. Placebo controlled studies of drug efficacy, taking the self-limiting course of giardiasis into account, has not been reported. No randomized controlled trials of treatment of refractory infection have been performed the last 25 years. Based on the clinical studies reported, combination treatment with a 5-nitroimidazole and a benzimidazole is more effective than repeated courses of 5-nitroimidazole or monotherapies in refractory cases. Quinacrine is effective in refractory cases, but potentially severe side effects limit its use.

A combination of a 5-nitroimidazole and albendazole or mebendazole, and quinacrine monotherapy, are rational choices in nitroimidazole refractory infections, but randomized controlled studies are needed. Further research into more recent clinical isolates is necessary to uncover mechanisms for the increase in metronidazole refractory giardiasis observed during the last decade.
The Development and Natural History of Hiatal Hernias
Authors: Abdelmoaty Walaa , Dunst Christy , Fletcher Reid , Doan Huy , Tugulan Carmen , Walters Jarvis , Davila-Bradley Daniel , Reavis Kevin , Swanstrom Lee , DeMeester Steven
Published: August 2020

Objective:

The aim of this study was to use barium upper gastrointestinal series (UGI) to evaluate the development and natural history of a hiatal hernia.

Summary of Background Data:

Hiatal hernias are common but the natural history of sliding and paraesophageal type hernias is poorly understood.

Methods:

We reviewed UGI reports from 1987 to 2017 using a word scanning software program to identify individuals that had a hiatal hernia. Only those with at least 2 UGI studies 5 or more years apart were selected. The studies were then reviewed.

Results:

There were 89 individuals that met inclusion criteria. Twenty-one people had no hiatal hernia on initial UGI and over a median of 99 months a sliding hiatal hernia (SHH) developed in 16 and a PEH developed in 5 people. A SHH was present on initial UGI in 55 people and at a median of 84 months subsequent UGI showed the SHH was stable in 11 (20%), increased in size in 30 (55%), and changed to a PEH in 14 people (25%). In 13 people a PEH was present on initial UGI and over a median of 97 months it was stable in 5 and increased in size in 8 people (62%).

Conclusions:

We showed that both SHH and PEH can develop over time and that the majority of both increased in size on follow-up UGI study. Further, 25% of SHH became a PEH over time. Recognizing an increase in size or change in type of a hiatal hernia may be clinically relevant to help understand changing or worsening symptoms in an individual.
Molecular pathogenesis of spinal bulbar muscular atrophy (Kennedy's disease) and avenues for treatment
Authors: Grunseich Christopher , Fischbeck Kenneth H.
Published: August 2020

Purpose of review

The aim of this study was to illustrate the current understanding and avenues for developing treatment in spinal and bulbar muscular atrophy (SBMA), an inherited neuromuscular disorder caused by a CAG trinucleotide repeat expansion in the androgen receptor (AR) gene.

Recent findings

Important advances have been made in characterizing the molecular mechanism of the disease, including the disruption of protein homeostasis, intracellular trafficking and signalling pathways. Biomarkers such as MRI quantification of muscle volume and fat fraction have been used to track disease progression, and will be useful in future clinical studies. Therapies tested and under development have been based on diverse strategies, including targeting mutantARgene expression, stability and activity, and pathways that mitigate disease toxicity.

We provide an overview of the recent advances in understanding the SBMA disease mechanism and highlight efforts to translate these insights into well tolerated and effective therapy.
Immunogenicity and Safety of a SARS-CoV-2 Inactivated Vaccine in Healthy Adults Aged 18-59 years: Report of the Randomized, Double-blind, and Placebo-controlled Phase 2 Clinical Trial
Authors: Zhang Yanjun , Zeng Gang , Pan Hongxing , Li Changgui , Kan Biao , Hu Yaling , Mao Haiyan , Xin Qianqian , Chu Kai , Han Weixiao , Chen Zhen , Tang Rong , Yin Weidong , Chen Xin , Gong Xuejie , Qin Chuan , Hu Yuansheng , Liu Xiaoyong , Cui Guoliang , Jiang Congbing , Zhang Hengming , Li Jingxin , Yang Minnan , Lian Xiaojuan , Song Yan , Lu Jinxing , Wang Xiangxi , Xu Miao , Gao Qiang , Zhu Fengcai
Published: August 2020

BACKGROUND

The top priority for the control of COVID-19 pandemic currently is the development of a vaccine. A phase 2 trial conducted to further evaluate the immunogenicity and safety of a SARS-CoV-2 inactivated vaccine (CoronaVac).

METHODS

We conducted a randomized, double-blind, placebo-controlled trial to evaluate the optimal dose, immunogenicity and safety of the CoronaVac. A total of 600 healthy adults aged 18-59 years were randomly assigned to receive 2 injections of the trial vaccine at a dose of 3 μg/0.5 mL or 6 μg /0.5mL, or placebo on Day 0,14 schedule or Day 0,28 schedule. For safety evaluation, solicited and unsolicited adverse events were collected after each vaccination within 7 days and 28 days, respectively. Blood samples were taken for antibody assay.

RESULTS

CoronaVac was well tolerated, and no dose-related safety concerns were observed. Most of the adverse reactions fell in the solicited category and were mild in severity. Pain at injection site was the most frequently reported symptoms. No Grade 3 adverse reaction or vaccine related SAEs were reported. CoronaVac showed good immunogenicity with the lower 3 μg dose eliciting 92.4% seroconversion under Day 0,14 schedule and 97.4% under Day 0,28 schedule. 28 days after two-dose vaccination, the Nab levels of individual schedules range from 23.8 to 65.4 among different dosage and vaccination schedules.

CONCLUSIONS

Favorable safety and immunogenicity of CoronaVac was demonstrated on both schedules and both dosages, which support the conduction of phase 3 trial with optimum schedule/dosage per different scenarios.
Newborn Life Support Course: Does it make me more confident when resuscitating a newborn?
Authors: Renesme Laurent , Merched Maria , Tandonnet Olivier , Naud Julien
Published: August 2020

Objective

To describe the effectiveness of the Neonatal Life Support (NLS) course in terms of attendees’ knowledge, perceived self-efficacy, and clinical applicability.

Methods

We conducted an electronic survey of NLS course attendees (NLS+ group). The survey had six themes: i) demographic characteristics; ii) NLS clinical applicability; iii) attendee’s perceived proficiency at neonatal resuscitation; iv) attendee’s perceived experience of fluency, security, and quality of care during neonatal resuscitation; v) knowledge (multiple-choice questions); and vi) perceived personal and professional impact of the NLS course. A control group (NLS−) was recruited via our regional perinatal network. The survey data were analysed anonymously. Multiple linear regression analysis examined the following: NLS course, job tenure, maternity level, and profession.

Results

The survey completion rate was 62% (200/323) for the NLS+ group. Among participants, 84% had participated in neonatal resuscitation since their course. The scores for positive perceived experience for neonatal resuscitation (fluency, security, and quality of care delivered) were higher in the NLS+ group than the NLS− group (p < 0.006). After adjustment, the independent factors associated with a higher positive perceived experience were the NLS course, work in tertiary level maternity ward, and job tenure > 5 years. The multiple-choice questions score (n = 10) was 8.2 ± 1.3 (NLS+) vs. 6.7 ± 1.5 (NLS−) (p < 0.0001). NLS course, medical degree, and work in a tertiary level maternity ward were independently associated with higher knowledge scores.

Conclusion

The NLS course was associated with better knowledge of, and a positive perceived experience regarding, neonatal resuscitation.
SARS-CoV-2 and the Role of Orofecal Transmission: Systematic Review
Authors: Heneghan C , Spencer EA , Brassey J , Jefferson T
Published: August 2020

Background

How SARS-CoV-2 is transmitted is of key public health importance. SARS-CoV-2 has been detected in the feces of some Covid-19 patients which suggests the possibility that the virus could additionally be transmitted via the orofecal route.

Methods

This review is part of an Open Evidence Review on Transmission Dynamics of Covid-19. We conduct ongoing searches using LitCovid, medRxiv, Google Scholar and Google for Covid-19; assess study quality based on five criteria and report important findings on an ongoing basis. Where necessary authors are contacted for further details or clarification on the content of their articles.

Results

We found 59 studies: nine reviews and 51 primary studies or reports (one cohort study also included a review) examining the potential role of orofecal transmission of SARS-CoV-2. Half (n=29) were done in China. Thirty seven studies reported positive fecal samples for SARS-CoV-2 based on RT-PCR results (n=1,034 patients). Six studies reported isolating the virus from fecal samples of nine patients, one study isolated the virus from rectal tissue and one laboratory study found that SARS-CoV-2 productively infected human small intestinal organoids. Eleven studies report on fecal samples found in sewage, and two sampled bathrooms and toilets.

Conclusions

Various observational and mechanistic evidence support the hypothesis that SARS-CoV-2 can infect and be shed from the human gastrointestinal tract. Policy should emphasize the importance of strict personal hygiene measures, and chlorine-based disinfection of surfaces in locations where there is presumed or known SARS-CoV-2 activity.