bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary hyperoxaluria type 1: novel therapies at a glance
Authors: Bacchetta Justine , Lieske John C
Published: December 2021

Primary hyperoxaluria type 1 (PH1) is a rare and severe autosomal recessive disease of oxalate metabolism, resulting from a mutation in the AGXT gene that encodes the hepatic peroxisomal enzyme alanine–glyoxylate aminotransferase (AGT). Until recently, treatment of PH1 was supportive, consisting of intensive hyperhydration, use of crystallization inhibitors (citrate and neutral phosphorus), in a subset of responsive PH1 patients’ pharmacologic doses of vitamin B6 (pyridoxine), and kidney and liver transplantation when patients progressed to kidney failure. Treatment approaches have been similar for PH2 caused by mutations in hepatic glyoxylate reductase/hydroxypyruvate reductase (GR/HPR), although pyridoxine does not have any benefit in this group. PH3 is caused by mutations of mitochondrial 4-hydroxy-2-oxoglutarate aldolase (HOGA1) and was the most recently described. Kidney failure appears less common in PH3, although kidney stones occur as frequently as in PH1 and PH2. Oxalate metabolism in the liver is complex. Novel therapies based on RNA interference (RNAi) have recently emerged to modulate these pathways, designed to deplete substrate for enzymes upstream and decrease/avoid oxalate production. Two hepatic enzymes have been targeted to date in PH: glycolate oxidase (GO) with lumasiran and lactate dehydrogenase A (LDH-A) with nedosiran. Lumasiran was approved for the treatment of PH1 in 2020 by both the European Medicines Agency and the Food and Drug Administration, whilst clinical trials with nedosiran are ongoing. Results with the two RNAi therapies demonstrate a significant reduction of urinary oxalate excretion in PH1 patients, but long-term data on efficacy (preservation of kidney function, decreased stone events) and safety remain to be established. Nevertheless, the hepatically targeted RNAi approach represents a potential ‘game changer’ in the field of PH1, bringing hope to families and patients that they may be able to avoid liver and/or kidney transplantation in the future and suffer fewer stone events, perhaps with less strict therapeutic regimens. Pharmacological compounds directly inhibiting GO or LDH are also under development and could be of special interest in developing countries where RNAi therapies may not be readily available in the near future. Approaches to manipulate the intestinal microbiome with a goal to increase oxalate degradation or to stimulate secretion of oxalate into the intestine from plasma are also under development. Overall, we appear to be entering a new phase of PH treatment, with an array of promising approaches emerging that will need optimization and evaluation to establish long-term efficacy and safety.
Acute measures of upper thermal and hypoxia tolerance are not reliable predictors of mortality following environmental challenges in rainbow trout (Oncorhynchus mykiss)
Authors: Strowbridge Nicholas , Northrup Sara L , Earhart Madison L , Blanchard Tessa S , Schulte Patricia M
Published: December 2021

Anthropogenic climate change threatens freshwater biodiversity and poses a challenge for fisheries management, as fish will increasingly be exposed to episodes of high temperature and low oxygen (hypoxia). Here, we examine the extent of variation in tolerance of acute exposure to these stressors within and among five strains of rainbow trout (Oncorhynchus mykiss) currently being used or under consideration for use in stocking programmes in British Columbia, Canada. We used incipient lethal oxygen saturation (ILOS) as an index of acute hypoxia tolerance, critical thermal maximum (CTmax) as an index of acute upper thermal tolerance and mortality following these two acute exposure trials to assess the relative resilience of individuals and strains to climate change-relevant stressors. We measured tolerance across two brood years and two life stages (fry and yearling), using a highly replicated design with hundreds of individuals per strain and life stage. There was substantial within-strain variation in CTmax and ILOS, but differences among strains, although statistically significant, were small. In contrast, there were large differences in post-trial mortality among strains, ranging from less than 2% mortality in the most resilient strain to 55% mortality in the least resilient. There was a statistically significant, but weak, correlation between CTmax and ILOS at both life stages for some strains, with thermally tolerant individuals tending to be hypoxia tolerant. These data indicate that alternative metrics of tolerance may result in different conclusions regarding resilience to climate change stressors, which has important implications for stocking and management decisions for fish conservation in a changing climate.
Does Higher Education Have Liberalizing or Inoculating Effects? A Panel Study of Anti-Immigrant Sentiment before, during, and after the European Migration Crisis
Authors: Velásquez Paolo , Eger Maureen A
Published: December 2021

Previous research has consistently shown a negative correlation between education and anti-immigrant sentiment. This association is most pronounced when distinguishing between adults with higher education and those without a tertiary degree. Yet it remains unclear whether educational attainment actually matters for attitudes, mainly due to a lack of longitudinal studies. This article investigates the so-called liberalizing effect of education on adults’ attitudes towards immigrants by taking into account individual, regional, and period effects. Using 12 waves of the Norwegian Citizen Panel (2013–2020) combined with contextual data from Statistics Norway, we assess the effects of: (i) educational attainment at the individual level; (ii) the expansion of higher education at the regional level; and (iii) higher education during a time of social upheaval. Results from multilevel cross-classified, repeated measurement models show that within-individual and within-county changes in educational attainment have a small but liberalizing effect on attitudes. Furthermore, individuals with at least 3–4 years of university education do not react as strongly to the highly salient European migration crisis than those with lower levels of education. This finding suggests that higher education inhibits perceptions of threat that may manifest during ‘big events’ such as a dramatic increase in asylum seeking. We interpret these novel results as evidence of an inoculating effect, in that higher education protects individuals against whatever instinct exists to react strongly during such crises.
Stimulation of Dissimilatory Sulfate Reduction in Response to Sulfate in Microcosm Incubations from Two Contrasting Temperate Peatlands near Ithaca, NY, USA
Authors: St James Andrew R , Richardson Ruth E
Published: December 2021

Peatlands are responsible for over half of wetland methane emissions, yet major uncertainties remain regarding carbon flow, especially when increased availability of electron acceptors stimulate competing physiologies. We used microcosm incubations to study the effects of sulfate on microorganisms in two temperate peatlands, one bog and one fen. Three different electron donor treatments were used (13C-acetate, 13C-formate, and a mixture of 12C short-chain fatty acids) to elucidate the responses of sulfate-reducing bacteria (SRB) and methanogens to sulfate stimulation. Methane production was measured and metagenomic sequencing was performed, with only the heavy DNA fraction sequenced from treatments receiving 13C electron donors. Our data demonstrate stimulation of dissimilatory sulfate reduction in both sites, with contrasting community responses. In McLean Bog (MB), hydrogenotrophic Deltaproteobacteria and acetotrophic Peptococcaceae lineages of SRB were stimulated, as were lineages with unclassified dissimilatory sulfite reductases. In Michigan Hollow Fen (MHF), there was little stimulation of Peptococcaceae populations, and a small stimulation of Deltaproteobacteria SRB populations only in the presence of formate as electron donor. Sulfate stimulated an increase in relative abundance of reads for both oxidative and reductive sulfite reductases, suggesting stimulation of an internal sulfur cycle. Together, these data indicate a stimulation of SRB activity in response to sulfate in both sites, with a stronger growth response in MB than MHF. This study provides valuable insights into microbial community responses to sulfate in temperate peatlands and is an important first step to understanding how SRB and methanogens compete to regulate carbon flow in these systems.
Nonconventional yeasts to produce aroma compounds by using agri-food waste materials
Authors: Karaalioğlu Onur , Yüceer Yonca Karagül
Published: December 2021

Nowadays, biotechnological applications are emphasized to ensure sustainable development by reutilizing waste materials to prevent ecological problems and to produce or recover compounds that may have positive effects on health. Yeasts are fascinating microorganisms that play a key role in several traditional and innovative processes. Although Saccharomyces is the most important genus of yeasts, and they are major producers of biotechnological products worldwide, a variety of other yeast genera and species than Saccharomyces that are called ‘non-Saccharomyces’ or ‘nonconventional’ yeasts also have important potential for use in biotechnological applications. Some of the nonconventional yeast strains offer a unique potential for biotechnological applications to produce valuable secondary metabolites due to their characteristics of surviving and growing in such extreme conditions, e.g. wide substrate range, rapid growth, thermotolerance, etc. In this review, we aimed to summarize potential biotechnological applications of some nonconventional yeasts (Kluyveromyces spp., Yarrowia spp., Pichia spp., Candida spp., etc.) to produce industrially important aroma compounds (phenylethyl alcohol, phenylethyl acetate, isobutyl acetate, diacetyl, etc.) by reutilizing agri-food waste materials in order to prevent ecological problems and to produce or recover compounds that may have positive effects on health.
The Myth of Responsibility: Colonial Cruelties and Silence in German Political Discourse
Authors: Augsten Pauline , Glassner Sebastian , Rall Jenni
Published: December 2021

Germany is considered a role model for dealing with past mass atrocities. In particular, the social reappraisal of the Holocaust is emblematic of this. However, when considering the genocide on the Herero and Nama in present-day Namibia, it is puzzling that an official recognition was only pronounced after almost 120 years, in May 2021. For a long time, silence surrounded this colonial cruelty in German political discourse. Although the discourse on German responsibility toward Namibia emerged after the end of World War II, it initially appeared detached from the genocide. That silence on colonial atrocities is to be considered a cruelty itself. Studies on silence have been expanding and becoming richer. Building on these works, the paper sets two goals: First, it advances the theorization of silence by producing a new typology, which is then integrated into discourse-bound identity theory. Second, it applies this theory to the analysis of the silencing and later acknowledging of the genocide on the Herero and Nama by German political elites. To this end, Bundestag debates, official documents, and statements by relevant political actors are analyzed in the period from 1980 to 2021. The results reveal the dynamics between hegemonic and counter-hegemonic discursive formations, how those are shifting in a period of 40 years, and what role silence plays in it. Beyond our emphasis on the genocide on the Herero and Nama, our findings might benefit future studies as the approach proposed in this paper can make silence a tangible research object for global studies.
Mitochondria metabolomics reveals a role of β-nicotinamide mononucleotide metabolism in mitochondrial DNA replication
Authors: Nomiyama Tomoko , Setoyama Daiki , Yasukawa Takehiro , Kang Dongchon
Published: December 2021

Mitochondrial DNA (mtDNA) replication is tightly regulated and necessary for cellular homeostasis; however, its relationship with mitochondrial metabolism remains unclear. Advances in metabolomics integrated with the rapid isolation of mitochondria will allow for remarkable progress in analyzing mitochondrial metabolism. Here, we propose a novel methodology for mitochondria-targeted metabolomics, which employs a quick isolation procedure using a hemolytic toxin from Streptococcus pyogenes streptolysin O (SLO). SLO isolation of mitochondria from cultured HEK293 cells is time- and labor-saving for simultaneous multi-sample processing and has been applied to various other cell lines in this study. Furthermore, our method can detect the time-dependent reduction in mitochondrial ATP in response to a glycolytic inhibitor 2-deoxyglucose, indicating the suitability to prepare metabolite analysis–competent mitochondria. Using this methodology, we searched for specific mitochondrial metabolites associated with mtDNA replication activation, and nucleotides and NAD+ were identified to be prominently altered. Most notably, treatment of β-nicotinamide mononucleotide (β-NMN), a precursor of NAD+, to HEK293 cells activated and improved the rate of mtDNA replication by increasing nucleotides in mitochondria and decreasing their degradation products: nucleosides. Our results suggest that β-NMN metabolism plays a role in supporting mtDNA replication by maintaining the nucleotide pool balance in the mitochondria.
On the professional authority of quality engineers and the gaps in their epistemic and organizational authority
Authors: Anker Sharon , Lurie Yotam
Published: December 2021

The authority of quality engineers as a profession is a contested issue that relates both to the occupation’s internal regulation and to the professional status of quality engineers within the organizations for which they work. In this article, we examine the professional authority of quality engineers from both these perspectives. The issue is addressed first through a conceptual framework, followed by a presentation of an empirical study in which seven experienced quality professionals were interviewed and completed questionnaires. We focus on the situation in Israel as a case study, but our insights are relevant to quality engineers throughout the world. We demonstrate limitations with regard to both (1) the epistemic authority (expertise) of quality engineers vis-à-vis their status as a professional association and (2) the organizational authority of quality engineers vis-à-vis their organizational role as quality managers. These limitations can be attributed to the occupation’s status as a semi-profession; the level of expertise required is not fixed or uniform; the authority of a quality engineer varies from one organizational structure to another. In addition, individual quality engineers are accorded different levels of influence, usually at the discretion of their employing organizations. For these reasons, the expertise of quality engineers as a professional group remains an open issue.
Ionizing radiation alters organoid forming potential and replenishment rate in a dose/dose-rate dependent manner
Authors: Fujimichi Yuki , Otsuka Kensuke , Tomita Masanori , Iwasaki Toshiyasu
Published: December 2021

Intestinal organoids are an in vitro cultured tissue model generated from intestinal stem cells, and they contain a mixture of epithelial cell types. We previously established an efficient ‘one cell/well’ sorting method, and defined organoid-forming potential (OFP) as a useful index to evaluate the stemness of individual cells. In this study, we assessed the response to radiation dose and dose-rate by measuring both OFP and the percentage of stem cells in the crypts. After high-dose-rate (HDR, 0.5 Gy/min) irradiation in vivo, the percentage of stem cells in the harvested crypt cells decreased, and the replenishment of cycling stem cells originating from dormant cells was enhanced, but OFP increased in cells irradiated with a total dose of >1 Gy. In contrast, at a total dose of 0.1 Gy the percentage of stem cells reduced slightly, but neither replenishment rate nor OFP changed. Furthermore, the response to 1 Gy of low-dose-rate (LDR) irradiation was similar to the response to 0.1 Gy HDR irradiation. These results suggest that 0.1 Gy HDR irradiation or 1 Gy LDR irradiation does not alter stemness. Additionally, the OFP increase in the colon in response to irradiation was smaller than that in the duodenum, similar to the percentage of stem cells. Understanding the differences in the response of stem cells between the colon and the duodenum to radiation is important to clarify the mechanisms underlying the development of radiation-associated intestinal cancers.
Dynamics around non-spherical symmetric bodies – I. The case of a spherical body with mass anomaly
Authors: Madeira G , Giuliatti Winter S M , Ribeiro T , Winter O C
Published: December 2021

The space missions designed to visit small bodies of the Solar system boosted the study of the dynamics around non-spherical bodies. In this vein, we study the dynamics around a class of objects classified by us as non-spherical symmetric bodies, including contact binaries, triaxial ellipsoids, and spherical bodies with a mass anomaly, among others. In this work, we address the results for a body with a mass anomaly. We apply the pendulum model to obtain the width of the spin–orbit resonances raised by non-asymmetric gravitational terms of the central object. The Poincaré surface of section technique is adopted to confront our analytical results and to study the system’s dynamics by varying the parameters of the central object. We verify the existence of two distinct regions around an object with a mass anomaly: a chaotic inner region that extends beyond the corotation radius and a stable outer region. In the latter, we identify structures remarkably similar to those of the classical restrict and planar three-body problem in the Poincaré surface of sections, including asymmetric periodic orbits associated with 1:1+p resonances. We apply our results to a Chariklo with a mass anomaly, obtaining that Chariklo rings are probably related to first kind periodic orbits and not with 1:3 spin–orbit resonance, as proposed in the literature. We believe that our work presents the first tools for studying mass anomaly systems.
Neuropsychiatric symptoms associated with the COVID-19 and its potential nervous system infection mechanism: the role of imaging in the study
Authors: Du Yanyao , Zhao Wei , Du Lei , Liu Jun
Published: December 2021

The epidemic of coronavirus disease 2019 (COVID-19) has broken the normal spread mode of respiratory viruses, namely, mainly spread in winter, resulting in over 230 million confirmed cases of COVID-19. Many studies have shown that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can affect the nervous system by varying degrees. In this review, we look at the acute neuropsychiatric impacts of COVID-19 patients, including acute ischemic stroke, encephalitis, acute necrotizing encephalopathy, dysosmia, and epilepsy, as well as the long-term neuropsychiatric sequelae of COVID-19 survivors: mental disorder and neurodegenerative diseases. In particular, this review discusses long-term changes in brain structure and function associated with COVID-19 infection. We believe that the traditional imaging sequences are important in the acute phase, while the nontraditional imaging sequences are more meaningful for the detection of long-term neuropsychiatric sequelae. These long-term follow-up changes in structure and function may also help us understand the causes of neuropsychiatric symptoms in COVID-19 survivors. Finally, we review previous studies and discuss some potential mechanisms of SARS-CoV-2 infection in the nervous system. Continuous focus on neuropsychiatric sequelae and a comprehensive understanding of the long-term impacts of the virus to the nervous system is significant for formulating effective sequelae prevention and management strategies, and may provide important clues for nervous system damage in future public health crises.
From Politics as Vocation to Politics as Business: Populist Social Performance and Narrative Fusion in Trump Rallies
Authors: Karakaya Yagmur , Edgell Penny
Published: December 2021

Populist movements seek to bolster the power of “the people” and undermine elites. In the United States a businessman, Donald Trump, has convinced a significant portion of the population that he is a man of the people. We answer three inter-related questions about what may be Trump’s biggest “win”: the transformation of populist discourse for a new century. How does Trump embed himself inside his followers’ own deep story? How does he fuse their story with a tale of American restoration? And how does he delegitimize politics as a vocation and valorize politics as business? Drawing on a systematic analysis of Trump/MAGA rallies held in four different regions from 2015 to 2021, we analyze how Trump used his performance to crystalize a distinctly American style of populism. We focus on the cultural accomplishment of his performance, particularly the creation of a business-friendly rhetoric that leverages popular cultural idioms to legitimate politics not as a vocation, but as a business. We find that Trump uses the popular idioms of standup comedy and competitive sports culture. This performance contributed to his 2016 win, yet framing politics as a game to be won runs the risk of reducing deliberative democratic process to election-night outcomes, makes political parties into opposing teams, and divides voters into winners and losers.
“I Don’t Have Much Money, but I Have a Lot of Friends”: How Poor Older Latinxs Find Social Support in Peer Friendship Networks
Authors: Plasencia Melanie Z
Published: December 2021

Even though older Latinxs face some of the greatest economic precarity of any demographic group in the nation, little research has focused on this group and how they survive, despite having limited economic means and access to government support. Drawing on two years of ethnographic research in an urban, Latinx community on the East Coast and on 72 in-depth interviews, this study addresses this knowledge gap by focusing on the role of peer friendship networks in the lives of low-income, foreign-born Latinx older adults. I show that peer friendships have the unique ability to prioritize and affirm their identities as Latinxs and older adults and provide returns in the form of medical, economic, and emotional support. Peers often facilitate transportation to medical appointments, provide critical information about medicines and health insurance, and try to uplift one another emotionally, especially when family support is lacking. Understanding the role these networks play in the lives of our most vulnerable has implications for our understanding of aging, poverty, and policy.
The Exposome and Toxicology: A Win–Win Collaboration
Authors: Barouki Robert , Audouze Karine , Becker Christel , Blaha Ludek , Coumoul Xavier , Karakitsios Spyros , Klanova Jana , Miller Gary W , Price Elliott J , Sarigiannis Denis
Published: December 2021

The development of the exposome concept has been one of the hallmarks of environmental and health research for the last decade. The exposome encompasses the life course environmental exposures including lifestyle factors from the prenatal period onwards. It has inspired many research programs and is expected to influence environmental and health research, practices, and policies. Yet, the links bridging toxicology and the exposome concept have not been well developed. In this review, we describe how the exposome framework can interface with and influence the field of toxicology, as well as how the field of toxicology can help advance the exposome field by providing the needed mechanistic understanding of the exposome impacts on health. Indeed, exposome-informed toxicology is expected to emphasize several orientations including (1) developing approaches integrating multiple stressors, in particular chemical mixtures, as well as the interaction of chemicals with other stressors, (2) using mechanistic frameworks such as the adverse outcome pathways to link the different stressors with toxicity outcomes, (3) characterizing the mechanistic basis of long-term effects by distinguishing different patterns of exposures and further exploring the environment-DNA interface through genetic and epigenetic studies, and (4) improving the links between environmental and human health, in particular through a stronger connection between alterations in our ecosystems and human toxicology. The exposome concept provides the linkage between the complex environment and contemporary mechanistic toxicology. What toxicology can bring to exposome characterization is a needed framework for mechanistic understanding and regulatory outcomes in risk assessment.
Veterans Affairs Graduate Medical Education Expansion Addresses U.S. Physician Workforce Needs
Authors: Klink Kathleen A. , Albanese Anthony P. , Bope Edward T. , Sanders Karen M.
Published: December 2021

The United States has a well-trained, highly specialized physician workforce yet continues to have care gaps across the nation. Deficiencies in primary care and mental health specialties are most frequently cited, though critical shortages in multiple disciplines exist, particularly in rural areas. Sponsoring institutions of physician graduate medical education (GME) have created rural residency tracks with modest federal funding and minimal incentives, though efforts targeting shortages in these specialties and geographic locations have been limited. In response to access problems in the Veterans Health Administration, Department of Veterans Affairs (VA), the second largest federal funder of GME with the most expansive clinical education platform, Congress passed the Veterans Access, Choice, and Accountability Act of 2014. This act directed the VA and provided funding to establish 1,500 new positions, a 15% expansion of VA-funded positions at the time. Priority for position selection was given to primary care, mental health, and any other specialties the secretary of VA determined appropriate. Importantly, priority was also given to VA facilities with documented physician shortages, those that did not have GME training programs, those in communities with high concentrations of veterans, and those in health profession shortage areas. Many rural facilities match this profile and were targeted for this initiative.

At the conclusion of fiscal year 2021, 1,490 positions had been authorized, and 21 of the 22 VA medical centers previously without GME activity had added residents or were planning to soon. Of the authorized positions, 42% are in primary care, 24% in mental health, and 34% in critically needed additional specialties.

Targeted GME expansion in the VA, the largest integrated health care system in the nation, has been successful in addressing physician GME training that aligns with physician shortages and may serve as a model to address national physician specialty and geographic workforce needs.
More Than 1 in 3 Patients With Chronic Low Back Pain Continue to Use Opioids Long-term After Spinal Fusion
Authors: Vraa Matthew L. , Myers Christina A. , Young Jodi L. , Rhon Daniel I.
Published: December 2021

Objective:

A common expectation for patients after elective spine surgery is that the procedure will result in pain reduction and minimize the need for pain medication. Most studies report changes in pain and function after spine surgery, but few report the extent of opioid use after surgery. This systematic review aims to identify the rates of opioid use after lumbar spine fusion.

Materials and Methods:

PubMed, CINAHL, Cochrane Central Register of Controlled Trials, and Ovid Medline were searched to identify studies published between January 1, 2005 and June 30, 2020 that assessed the effectiveness of lumbar fusion for the management of low back pain.

Results:

Of 6872 abstracts initially identified, 329 studies met the final inclusion criteria, and only 32 (9.7%) reported any postoperative opioid use. Long-term opioid use after surgery persists for more than 1 in 3 patients with usage ranging from 6 to 85.9% and a pooled mean of 35.0% based on data from 21 studies (6.4% of all lumbar fusion studies).

Discussion:

Overall, opioid use is not reported in the majority of lumbar fusion trials. Patients may expect a reduced need for opioid-based pain management after surgery, but the limited data available suggests long-term use is common. Lack of consistent reporting of these outcomes limits definitive conclusions regarding the efficacy of spinal fusion for reducing long-term opioid. Patient decisions about undergoing surgery may be altered if they had realistic expectations about rates of postsurgical opioid use. Spine surgery trials should track opioid utilization out to a minimum of 6 months after surgery as a core outcome.
Cholesteatoma Is Associated With Pediatric Progressive Sensorineural Hearing Loss
Authors: Racca Jordan M. , Lee John , Sikorski Faith , Crenshaw E. Bryan , Hood Linda J.
Published: December 2021

Objectives:

This study identified an association between cholesteatoma and progressive sensorineural hearing loss using a large pediatric longitudinal audiologic dataset. Cholesteatoma is a potential sequela of chronic otitis media with effusion, a commonly observed auditory pathology that can contribute to hearing loss in children. The purpose of this report is to (i) describe the process of identifying the association between cholesteatoma and progressive sensorineural hearing loss in a large pediatric dataset and (ii) describe the audiologic data acquired over time in patients identified with cholesteatoma-associated progressive sensorineural hearing loss.

Design:

Records of patients included in the Audiologic and Genetics Database (n = 175,215 patients) were examined using specified criteria defining progressive hearing loss. A linear regression model examined the log frequency of all diagnostic codes in the electronic health record assigned to patients for a progressive hearing loss cohort compared with a stable hearing loss group. Based on findings from the linear regression analysis, longitudinal audiometric air (AC) and bone conduction (BC) thresholds were extracted for groups of subjects with cholesteatoma-associated progressive (n = 58 subjects) and stable (n = 55 subjects) hearing loss to further analyze changes in hearing over time.

Results:

The linear regression analyses identified that diagnostic codes for cholesteatoma were associated with progressive sensorineural hearing loss in children. The longitudinal audiometric data demonstrated within-subject changes in masked BC sensitivity consistent with progressive sensorineural hearing loss in children diagnosed with cholesteatoma. Additional analyses showed that mastoidectomy surgeries did not appear to contribute to the observed progressive hearing loss and that a high number of cholesteatoma patients with progressive hearing loss had normal-hearing thresholds at their first test.

Conclusions:

The statistical analyses demonstrated an association between cholesteatoma and pediatric progressive sensorineural hearing loss. These findings inform clinical management by suggesting that children with cholesteatoma diagnoses may be at increased risk for progressive sensorineural hearing loss and should receive continued monitoring even after a normal masked BC baseline has been established.
Elastic stable intramedullary nailing versus submuscular plating in pediatric diaphyseal femur fractures: a randomized controlled trial among children in South India
Authors: James Deeptiman , Martin Dennis , Kumar Anand , Krishnan Srijeeth , Gahukamble Abhay , Madhuri Vrisha , David Thambu , Palocaren Thomas
Published: December 2021

Elastic stable intramedullary nailing (ESIN) is the current preferred method for treating diaphyseal femur fractures in children. Introduction of the submuscular locked plate (SMP) fixation construct has opened the debate on treatment options for pediatric diaphyseal femur fractures in the older children and adolescents. A randomized controlled trial (RCT) protocol was designed to compare ESIN and SMP for diaphyseal femur fractures in children. An open-labelled RCT comparing SMP with ESIN was conducted from January 2013 to June 2016, for children aged 6–15 years with closed, acute femoral diaphyseal fractures. Randomization was done through computer-generated randomization sequence and opaque-sealed envelopes. Rate of adverse surgical events including unplanned re-operations was assessed as the primary outcome and secondary analysis was done for time to union, degree of malunion, limb length discrepancy, functional outcome at 2 years, surgical duration and blood loss, radiation exposure, hospital stay, cost incurred and secondary implant removal procedure. Forty children were randomized with allocation concealment. There were three adverse events in the SMP arm and five in the ESIN arm. Fifteen children with SMP underwent routine implant removal compared to only three children with ESIN (P < 0.001). Both ESIN and SMP are equally safe, viable and effective options for treating pediatric diaphyseal femoral fractures. However, the additional cost of secondary surgery for implant removal in the SMP group proved to be a deterrent factor, which led to ESIN being the preferred option in our resource-limited setting.
Relation of the Sural Nerve and Medial Neurovascular Bundle With the Achilles Tendon in Children With Cerebral Palsy Treated by Percutaneous Achilles Tendon Lengthening
Authors: Erdal Ozan A. , Gorgun Baris , Yontar Necip S. , Terzibaşioğlu Ali E. , Sarikaya Ilker A. , Inan Muharrem
Published: December 2021

Background:

One of the most common treatment options for a short Achilles tendon (AT) in cerebral palsy is percutaneous AT lengthening using 3 hemisections. Because of proximity of neurovascular structures around the tendon, iatrogenic injury to them have been a concern about this technique. The sural nerve (SN) is under risk of injury at the site of the lateral incomplete cut, especially if it is done proximally. The medial neurovascular bundle is under injury risk at medial cuts. The aim of the article was to study the anatomical relations of the SN and medial neurovascular bundle to the AT, and define dangerous levels for injury with the help of magnetic resonance imaging (MRI).

Methods:

Patients operated for percutaneous Achilles lengthening were called for MRI investigation of the SN and medial neruvascular bundle integrity and their anatomical relation with the AT. The distance of 5 mm was taken as the threshold for increased risk of injury. Measurements were done on MRI at each cm from the insertion of the tendon on both medial and lateral sides, and at the level of the middle cut.

Results:

Thirty ankles operated and followed at least 1 year were included to the study. On the medial side, the tibial nerve, and the posterior tibial artery lied more than 5 mm away from the tendon at all levels in all patient. On the lateral side, the first 4 cm were relatively safe for the middle lateral cut, while increased risk of SN damage was detected in more proximal levels. Overall, 6 of 30 ankles had radiographically detectable SN injury.

Conclusions:

The first 4 cm of the AT on the lateral side was detected to be safe for the middle lateral directed cut, while whole tendon length were found to be safe for the first and the third cuts of the percutaneous Achilles lengthening surgery using 3 hemisections in children with cerebral palsy.

Level of Evidence:

Level III.
Spiritual Well-Being and Use of Spiritual Care Interventions of Undergraduate Nursing Students
Authors: Tomsovic Emily , Bond Loretta , Wyant David
Published: December 2021

A survey of undergraduate nursing students investigated their personal spiritual well-being (SWB), their spiritual care of patients, and where students felt spiritually challenged. The survey utilized the Spiritual Health and Life-Orientation Measure (SHALOM), the Nursing Spiritual Care Therapeutics Scale (NSCTS), and a qualitative extended response question. Findings revealed a positive correlation between high SWB and the spiritual care of patients and a significant improvement in the use of spiritual care therapeutics through the nursing program.
Celecoxib and Myrtol
Authors: Vierra Mason , Dhiman Ankit , Witmer Hunter D.D. , Ulrich Leah , Hindi Enal , Fenton Emily , Shergill Ardaman , Polite Blase , Eng Oliver S. , Turaga Kiran K.
Published: December 2021

Background:

Unresectable appendiceal mucinous neoplasms (AMNs) with extensive peritoneal dissemination cause significant morbidity and have limited treatment options. We evaluated a novel combination of Celecoxib and Myrtol in treating such AMNs.

Methods:

Patients with recurrent AMNs with extensive peritoneal disease treated with a daily regimen of 200 mg Celecoxib and 1200 mg Myrtol Standardized were included. Progression-free survival (PFS) and overall survival (OS) were calculated, and carcinoembryonic antigen (CEA) trends were compared pretreatment and post-treatment in terms of percentage change.

Results:

Thirteen patients with extensive, recurrent disease (median peritoneal carcinomatosis index of 36) were included between 2017 and 2020. The median age was 63 years (interquartile range: 55 to 67) and 7 (54%) were male. A total of 85% had undergone prior cytoreductive surgery while 15% underwent cytoreductive surgery >2 times. 54% had received multiple cycles of systemic chemotherapy before starting Celecoxib-Myrtol. After a median follow-up of 8 months, median PFS and OS were 16 months (interquartile range: 5 to 17) and 27 months, respectively. Nine (69.2%) showed improvement in CEA values 3 months after treatment compared with 3-month pretreatment CEA trends. None had adverse events attributable to Celecoxib-Myrtol.

Conclusions:

Our feasibility study suggests that a regimen of Celecoxib-Myrtol is well tolerated and may prolong PFS and OS in patients with recurrent AMNs with peritoneal spread.
Mavacamten: A Novel Disease-Specific Treatment for Hypertrophic Cardiomyopathy
Authors: Capilupi Michael J. , Frishman William H.
Published: December 2021

Hypertrophic cardiomyopathy (HCM) is characterized by an abnormal thickening of the myocardium, leading to left ventricular outflow tract obstruction. Current treatments for HCM include non–disease-specific medications such as beta blockers or invasive interventions. Mavacamten has been studied for its effects on adenosine triphosphatase, myocardial-specific sarcomeric proteins, and myocardial tissue calcium sensitivity. Given these properties, mavacamten could be used as a disease-specific treatment for HCM. Clinical trials of mavacamten have shown improvements in left ventricular outflow tract obstruction among other favorable improvements in biochemical markers and the clinical symptoms of the disease. While trials to date have been relatively small, mavacamten shows promise as a future disease-specific treatment for HCM.
Probable lumbar acute noncompressive nucleus pulposus extrusion: a case report of acute pain caused by a hydrated nucleus pulposus and review of the literature
Authors: Chen Changjun , Gao Xianlei , Li Hao , Pan Xin , Wang Songgang
Published: December 2021

Acute noncompressive nucleus pulposus (NP) extrusion has been widely described in veterinary medicine, especially in dogs and cats; however, cases have rarely been reported in humans. We report a rare case of acute pain caused by a hydrated NP. Magnetic resonance imaging revealed an obvious hyperintense signal on T2-weighted images at the L5/S1 segments, while computed tomography imaging and radiography revealed a mildly herniated disc at the L4/5 level and slight lumbar spondylolisthesis at the L5/S1 segments. The operation was performed to confirm the presence of a red and swollen nerve root on the right side of the hydrated L5/S1 segment. The patient's severe pain disappeared, and full recovery was achieved months after surgery. Thus, our case demonstrated a probable lumbar acute noncompressive NP extrusion in humans and reported associated symptoms and imaging characteristics. In such circumstances, surgical management is indicated and may be associated with a good outcome.
Surveillance-to-Diagnostic Testing Program for Asymptomatic SARS-CoV-2 Infections on a Large, Urban Campus in Fall 2020
Authors: Gibson Greg , Weitz Joshua S. , Shannon Michael P. , Holton Benjamin , Bryksin Anton , Liu Brian , Sieglinger Madeline , Coenen Ashley R. , Zhao Conan , Beckett Stephen J. , Bramblett Sandra , Williamson JulieAnne , Farrell Michael , Ortiz Alexander , Abdallah Chaouki T. , García Andrés J.
Published: December 2021

Background:

Six months into the COVID-19 pandemic, college campuses faced uncertainty regarding the likely prevalence and spread of disease, necessitating large-scale testing to help guide policy following re-entry.

Methods:

A SARS-CoV-2 testing program combining pooled saliva sample surveillance leading to diagnosis and intervention surveyed over 112,000 samples from 18,029 students, staff and faculty, as part of integrative efforts to mitigate transmission at the Georgia Institute of Technology in Fall 2020.

Results:

Cumulatively, we confirmed 1,508 individuals diagnostically, 62% of these through the surveillance program and the remainder through diagnostic tests of symptomatic individuals administered on or off campus. The total strategy, including intensification of testing given case clusters early in the semester, was associated with reduced transmission following rapid case increases upon entry in Fall semester in August 2020, again in early November 2020, and upon re-entry for Spring semester in January 2021. During the Fall semester daily asymptomatic test positivity initially peaked at 4.1% but fell below 0.5% by mid-semester, averaging 0.84% across the Fall semester, with similar levels of control in Spring 2021.

Conclusions:

Owing to broad adoption by the campus community, we estimate that the program protected higher risk staff and faculty while allowing some normalization of education and research activities.
The influence of outdoor PM2.5 concentration at workplace on nonaccidental mortality estimates in a Canadian census-based cohort
Authors: Christidis Tanya , Pinault Lauren L. , Crouse Dan L. , Tjepkema Michael
Published: December 2021

Background:

Associations between mortality and exposure to ambient air pollution are usually explored using concentrations of residential outdoor fine particulate matter (PM2.5) to estimate individual exposure. Such studies all have an important limitation in that they do not capture data on individual mobility throughout the day to areas where concentrations may be substantially different, leading to possible exposure misclassification. We examine the possible role of outdoor PM2.5 concentrations at work for a large population-based mortality cohort.

Methods:

Using the 2001 Canadian Census Health and Environment Cohort (CanCHEC), we created a time-weighted average that incorporates employment hours worked in the past week and outdoor PM2.5 concentration at work and home. We used a Cox proportional hazard model with a 15-year follow-up (2001 to 2016) to explore whether inclusion of workplace estimates had an impact on hazard ratios for mortality for this cohort.

Results:

Hazard ratios relying on outdoor PM2.5 concentration at home were not significantly different from those using a time-weighted estimate, for the full cohort, nor for those who commute to a regular workplace. When exploring cohort subgroups according to neighborhood type and commute distance, there was a notable but insignificant change in risk of nonaccidental death for those living in car-oriented neighborhoods, and with commutes greater than 10 km.

Conclusions:

Risk analyses performed with large cohorts in low-pollution environments do not seem to be biased if relying solely on outdoor PM2.5 concentrations at home to estimate exposure.
Artificial intelligence in pediatric cardiology: taking baby steps in the big world of data
Authors: Van den Eynde Jef , Kutty Shelby , Danford David A. , Manlhiot Cedric
Published: December 2021

Purpose of review

Artificial intelligence (AI) has changed virtually every aspect of modern life, and medicine is no exception. Pediatric cardiology is both a perceptual and a cognitive subspecialty that involves complex decision-making, so AI is a particularly attractive tool for this medical discipline. This review summarizes the foundational work and incremental progress made as AI applications have emerged in pediatric cardiology since 2020.

Recent findings

AI-based algorithms can be useful for pediatric cardiology in many areas, including: (1) clinical examination and diagnosis, (2) image processing, (3) planning and management of cardiac interventions, (4) prognosis and risk stratification, (5) omics and precision medicine, and (6) fetal cardiology. Most AI initiatives showcased in medical journals seem to work well in silico, but progress toward implementation in actual clinical practice has been more limited. Several barriers to implementation are identified, some encountered throughout medicine generally, and others specific to pediatric cardiology.

Despite barriers to acceptance in clinical practice, AI is already establishing a durable role in pediatric cardiology. Its potential remains great, but to fully realize its benefits, substantial investment to develop and refine AI for pediatric cardiology applications will be necessary to overcome the challenges of implementation.
Neuroadrenergic activation in obstructive sleep apnoea syndrome: a new selected meta-analysis - revisited
Authors: Biffi Annalisa , Quarti-Trevano Fosca , Bonzani Matilde , Seravalle Gino , Corrao Giovanni , Mancia Giuseppe , Grassi Guido
Published: December 2021

Background:

Neuroadrenegic overdrive occurs in obstructive sleep apnoea syndrome (OSAS). However, the small sample size of the microneurographic studies, heterogeneity of the patients examined, presence of comorbidities, represented major weaknesses not allowing to precisely define the main features of the phenomenon, particularly in nonobese patients.

Objective:

This meta-analysis detected 14 microneurographic studies based on muscle sympathetic nerve activity (MSNA) quantification in uncomplicated OSAS of different clinical severity.

Methods:

The evaluation was extended to the relationships of MSNA with heart rate, anthropometric and blood pressure values, metabolic variables, apnoea-hypopnea index and oxygen saturation.

Results:

MSNA is activated markedly and almost homogeneously between studies, showing a progressive increase from the healthy state to mild, moderate and severe OSAS (46.03, 48.32, 71.84, 69.27 bursts/100 heart beats). Of special interest are the findings that MSNA is significantly related to the apnoea-hypopnea index, a marker of OSAS severity (r = 0.55, P 
= 0.04) but not to BMI, as it occurs in OSAS associated with obesity, and heart rate is significantly and directly related to MSNA and apnoea-hypopnea index (r = 0.68 and r = 0.60, respectively P = 0.03 and P = 0.02), thus representing a surrogate marker of the sympathetic overdrive.

Conclusion:

OSAS, even when uncomplicated by other cardiometabolic disease, displays a marked sympathetic activation, reflected by the MSNA and heart rate behaviour, becoming a target of therapeutic interventions aimed at exerting sympathomoderating effects, such as continuous positive airway pressure.