bluuebunny/crossref_metadata_2025 huggingface dataset:
Submitral aneurysm of varied aetiologies: a case series
Authors: Prasad Krishna , Gupta Himanshu , Sihag Bhupendra Kumar , Bootla Dinakar , Panda Prashant , Sharma Arun , Chauhan Rajeev , Gawalkar Atit , Dahiya Neelam
Published: February 2021

Background

Submitral aneurysm is a rare disease initially described in the African population. It is usually considered congenital in origin, due to a defect in the posterior portion of the mitral annulus. However, it can be seen in other diseases like ischaemic heart disease, rheumatic heart disease, infective endocarditis, tuberculosis, and syphilis.

Case presentation

Case 1 was a 29-year-old female, hypertensive undergoing maintenance haemodialysis for chronic kidney disease and on anti-tubercular therapy. She was found to have a large submitral aneurysm with severe mitral regurgitation, moderate left ventricular dysfunction, and pericardial effusion on echocardiogram. Case 2 was a 58-year-old gentleman presented with inferior wall ST-elevation myocardial infarction and was thrombolyzed with streptokinase for the same. Echocardiogram done 6 months later for evaluation of dyspnoea showed a large inferobasal aneurysm. Case 3 was a 56-year-old hypertensive presented with dyspnoea on exertion and echocardiogram showed a large posterolateral region with transmural late gadolinium enhancement. Case 4 was a 13-year-old boy presented with fever and cerebrovascular accident. Echocardiogram revealed vegetation in the mitral valve and a small submitral aneurysm with vegetation inside it.

Discussion

Submitral aneurysm is usually considered congenital in origin. However, it can be due to ischaemic heart disease, rheumatic heart disease, Takayasu arteritis, and tuberculosis. Top dimensional echocardiogram is the investigation of choice. Cardiac magentic resonance imaging helps in identifying the underlying aetiology and delineating the surrounding structures.
Novel findings of respiratory rate increases using the multisensor HeartLogic heart failure monitoring algorithm in COVID-19-positive patients: a case series
Authors: Yapejian Andrea Rebecca , Fudim Marat
Published: February 2021

Background

With the ongoing coronavirus disease 2019 (COVID-19) epidemic, remote monitoring of patients with implanted cardiac devices has become more important than ever, as physical distancing measures have placed limits on in-clinic device monitoring. Remote monitoring alerts, particularly those associated with heart failure trends, have proved useful in guiding care in regard to monitoring fluid status and adjusting heart failure medications.

Case summary

This report describes use of Boston Scientific’s HeartLogic algorithm, which is a multisensor device algorithm in implantable cardioverter-defibrillator devices that is proven to be an early predictor of heart failure decompensation by measuring several variables, including respiratory rate, nighttime heart rate, and heart sounds. We present three cases of patients who were actively surveilled by the various HeartLogic device algorithm sensors and were identified to have increasing respiratory rates high enough to trigger a HeartLogic alert prior to a positive COVID-19 diagnosis.

Discussion

We propose that the HeartLogic algorithm and its accompanying individual physiologic sensors demonstrate potential for use in identifying non-heart failure-related decompensation, such as COVID-19-positive diagnoses.
Current genetic conservation of Chinese indigenous horses revealed with Y-chromosomal and mitochondrial DNA polymorphisms
Authors: Liu Shuqin , Fu Chunzheng , Yang Yunzhou , Zhang Yuanyuan , Ma Hongying , Xiong Zhiyao , Ling Yao , Zhao Chunjiang
Published: February 2021

To investigate the genetic diversity of Chinese indigenous horses and determine the genetic status of extant horse breeds, novel Y chromosomal microsatellite markers and known Y chromosomal SNPs and mtDNA loop sequences, were employed to study the genetic diversity levels of 13 Chinese indigenous horse populations and four introduced breeds. Sixteen Y-chromosomal microsatellite markers, including seven newly identified loci, were used in the genotyping. The results showed that 4 out of the 16 loci were highly polymorphic in Chinese indigenous horse populations, in which the polymorphisms of 3 loci, ECAYP12, ECAYP13, and ECAYCAU3, were first reported in the present study. The polymorphic Y chromosomal microsatellite markers result in 19 haplotypes in the studied horses and formed 24 paternal lines when merged with the 14 Y chromosomal SNPs reported previously. The haplotypes CHT18 and SS24 harboring AMELY gene mutation were the ancestral haplotypes, and other haplotypes were derived from them by one or more mutation steps. The horse populations in mountainous and remote areas of southwestern China have the most ancient paternal lines, which suggests that ancient paternal lines preserved in local populations attributed to less human interventions. Our results also showed that the northern local breeds had higher mtDNA diversity than the southern ones in China. The frequency of haplogroup B, F, and G of mtDNA in Chinese indigenous horses has declined in recent years, and some breeds are in endangered status mainly due to small population sizes. Urgent actions should be taken to conserve the genetic diversity of the indigenous horse populations, especially the rare paternal lines. Our findings help to elucidate the genetic diversity and evolutionary history of Chinese domestic horses, which will facilitate the conservation of the indigenous horses in the future.
A fish with no sex: gonadal and adrenal functions partition between zebrafishNR5A1co-orthologs
Authors: Yan Yi-Lin , Titus Tom , Desvignes Thomas , BreMiller Ruth , Batzel Peter , Sydes Jason , Farnsworth Dylan , Dillon Danielle , Wegner Jeremy , Phillips Jennifer B , Peirce Judy , Dowd John ,   Undiagnosed Diseases Network, Buck Charles Loren , Miller Adam , Westerfield Monte , Postlethwait John H
Published: February 2021

People with NR5A1 mutations experience testicular dysgenesis, ovotestes, or adrenal insufficiency, but we do not completely understand the origin of this phenotypic diversity. NR5A1 is expressed in gonadal soma precursor cells before expression of the sex-determining gene SRY. Many fish have two co-orthologs of NR5A1 that likely partitioned ancestral gene subfunctions between them. To explore ancestral roles of NR5A1, we knocked out nr5a1a and nr5a1b in zebrafish. Single-cell RNA-seq identified nr5a1a-expressing cells that co-expressed genes for steroid biosynthesis and the chemokine receptor Cxcl12a in 1-day postfertilization (dpf) embryos, as does the mammalian adrenal–gonadal (interrenal-gonadal) primordium. In 2dpf embryos, nr5a1a was expressed stronger in the interrenal-gonadal primordium than in the early hypothalamus but nr5a1b showed the reverse. Adult Leydig cells expressed both ohnologs and granulosa cells expressed nr5a1a stronger than nr5a1b. Mutants for nr5a1a lacked the interrenal, formed incompletely differentiated testes, had no Leydig cells, and grew far larger than normal fish. Mutants for nr5a1b formed a disorganized interrenal and their gonads completely disappeared. All homozygous mutant genotypes lacked secondary sex characteristics, including male breeding tubercles and female sex papillae, and had exceedingly low levels of estradiol, 11-ketotestosterone, and cortisol. RNA-seq showed that at 21dpf, some animals were developing as females and others were not, independent of nr5a1 genotype. By 35dpf, all mutant genotypes greatly under-expressed ovary-biased genes. Because adult nr5a1a mutants form gonads but lack an interrenal and conversely, adult nr5a1b mutants lack a gonad but have an interrenal, the adrenal, and gonadal functions of the ancestral nr5a1 gene partitioned between ohnologs after the teleost genome duplication, likely owing to reciprocal loss of ancestral tissue-specific regulatory elements. Identifying such elements could provide hints to otherwise unexplained cases of Differences in Sex Development.
Epigenetic Age Acceleration and Cognitive Decline: A Twin Study
Authors: Vaccarino Viola , Huang Minxuan , Wang Zeyuan , Hui Qin , Shah Amit J , Goldberg Jack , Smith Nicholas , Kaseer Belal , Murrah Nancy , Levantsevych Oleksiy M , Shallenberger Lucy , Driggers Emily , Bremner J Douglas , Sun Yan V
Published: February 2021

Background

Little is known about the role of DNA methylation (DNAm) epigenetic age acceleration in cognitive decline. Using a twin study design, we examined whether DNAm age acceleration is related to cognitive decline measured longitudinally in persons without a clinical diagnosis of dementia.

Methods

We studied 266 paired male twins (133 pairs) with a mean age of 56 years at baseline. Of these, 114 paired twins returned for a follow-up after an average of 11.5 years. We obtained 6 indices of DNAm age acceleration based on epigenome-wide data from peripheral blood lymphocytes. At both baseline and follow-up, we administered a battery of cognitive measures and constructed 2 composite scores, one for executive function and one for memory function. We fitted multivariable mixed regression models to examine the association of DNAm age acceleration markers with cognitive function within pairs.

Results

In cross-sectional analyses at baseline, there was no association between DNAm age acceleration and cognitive function scores. In longitudinal analyses, however, comparing twins within pairs, each additional year of age acceleration using the Horvath’s method was associated with a 3% decline (95% CI, 1%–5%) in the composite executive function score and a 2.5% decline (95% CI, 0.01%–4.9%) in the memory function score. These results did not attenuate after adjusting for education and other risk factors.

Conclusions

Middle-aged men who had older DNAm age relative to their brothers of the same demographic age showed a faster rate of cognitive decline in the subsequent 11.5 years. These results point to the role of epigenetic modifications in cognitive aging.
Computational Learning of microRNA-Based Prediction of Pouchitis Outcome After Restorative Proctocolectomy in Patients With Ulcerative Colitis
Authors: Morilla Ian , Uzzan Mathieu , Cazals-Hatem Dominique , Colnot Nathalie , Panis Yves , Nancey Stéphane , Boschetti Gilles , Amiot Aurélien , Tréton Xavier , Ogier-Denis Eric , Daniel Fanny
Published: February 2021

Background

Ileal pouch-anal anastomosis (IPAA) is the standard of care after total proctocolectomy for ulcerative colitis (UC). However, inflammation often develops in the pouch, leading to acute or recurrent/chronic pouchitis (R/CP). MicroRNAs (miRNA) are used as accurate diagnostic and predictive biomarkers in many human diseases, including inflammatory bowel diseases. Therefore, we aimed to identify an miRNA-based biomarker to predict the occurrence of R/CP in patients with UC after colectomy and IPAA.

Methods

We conducted a retrospective study in 3 tertiary centers in France. We included patients with UC who had undergone IPAA with or without subsequent R/CP. Paraffin-embedded biopsies collected from the terminal ileum during the proctocolectomy procedure were used for microarray analysis of miRNA expression profiles. Deep neural network–based classifiers were used to identify biomarkers predicting R/CP using miRNA expression and relevant biological and clinical factors in a discovery cohort of 29 patients. The classification algorithm was tested in an independent validation cohort of 28 patients.

Results

A combination of 11 miRNA expression profiles and 3 biological/clinical factors predicted the outcome of R/CP with 88% accuracy (area under the curve = 0.94) in the discovery cohort. The performance of the classification algorithm was confirmed in the validation cohort with 88% accuracy (area under the curve = 0.90). Apoptosis, cytoskeletal regulation by Rho GTPase, and fibroblast growth factor signaling were the most dysregulated targets of the 11 selected miRNAs.

Conclusions

We developed and validated a computational miRNA-based algorithm for accurately predicting R/CP in patients with UC after IPAA.
Suboptimal Vaccination Administration in Mothers With Inflammatory Bowel Disease and Their Biologic-Exposed Infants
Authors: Chiarella-Redfern Helene , Lee Sangmin , Jubran Bellal , Sharifi Nastaran , Panaccione Remo , Constantinescu Cora , Benchimol Eric I , Seow Cynthia H
Published: February 2021

Background

Pregnant women with inflammatory bowel disease (IBD) are at increased risk of developing complications from vaccine-preventable infections. We investigated the factors influencing vaccine administration in pregnant women with IBD and their infants, in addition to the safety of vaccination in the infants.

Methods

This retrospective cohort study identified individuals from a tertiary referral clinic whose records were linked to a provincial vaccine database. We conducted χ 2 tests, Fisher exact tests, and logistic regression adjusting for age and disease duration to compare vaccine administration by medication class. Potential rotavirus vaccine adverse events were determined in infants of women with IBD.

Results

We included 303 pregnant women and 262 infants. Vaccines were administered to women on biologic therapy as follows: hepatitis B virus (82.9%), diphtheria-tetanus-pertussis (82.1%), and hepatitis A virus (49.3%). The influenza vaccination was provided peripartum in 50.7% of patients. The measles-mumps-rubella-varicella vaccine was provided to 89.3% of women before biologic initiation. Women treated with a biologic (adjusted odds ratio, 2.50; 95% confidence interval, 1.39-4.35) or immunomodulator (adjusted odds ratio, 4.00; 95% confidence interval, 2.22-7.69) were more likely to receive the Prevnar 13 and Pneumovax 23 vaccines than were unexposed individuals, but the overall proportion vaccinated was low (Prevnar 13, 35.7%; Pneumovax 23, 39.3%). At least 90% of infants received the measles-mumps-rubella-varicella vaccine and inactivated vaccines. Fourteen biologic-exposed children (19.2%) received the live rotavirus vaccine with no significant differences in adverse events compared with biologic-unexposed infants (7.1% vs 8.2%, P = 0.99).

Conclusions

Better education surrounding vaccine recommendations is required for both health care providers and individuals with IBD given poor pneumococcal, hepatitis A virus, and influenza vaccination rates. Inadvertent administration of the rotavirus vaccine in biologic-exposed infants did not result in more adverse events, raising the possibility of safety.
Liver X Receptor Exerts Anti-Inflammatory Effects in Colonic Epithelial Cells via ABCA1 and Its Expression Is Decreased in Human and Experimental Inflammatory Bowel Disease
Authors: Miranda-Bautista José , Rodríguez-Feo Juan A , Puerto Marta , López-Cauce Beatriz , Lara José M , González-Novo Raquel , Martín-Hernández David , Ferreiro-Iglesias Rocío , Bañares Rafael , Menchén Luis
Published: February 2021

Background

Liver X receptor (LXR) exerts anti-inflammatory effects in macrophages. The aim of this study was to explore the expression and function of LXR in the colonic epithelium under inflammatory conditions.

Methods

The expression of LXR was explored by Western blot and immunohistochemistry in colonic biopsies from patients diagnosed with inflammatory bowel disease (IBD) and control patients. In addition, LXR and its target gene expression were analyzed in the colon from interleukin (IL)-10-deficient (IL-10-/-) and wild-type mice. Caco-2 cells were pretreated with the synthetic LXR agonist GW3965 and further challenged with IL-1β, the expression of IL-8 and chemokine (C-C motif) ligand (CCL)-28 chemokines, the activation of mitogen-activated protein (MAP) kinases, and the nuclear translocation of the p65 subunit of nuclear factor kappa B was evaluated. Glibenclamide was used as an ABCA1 antagonist.

Results

We found that LXR expression was downregulated in colonic samples from patients with IBD and IL-10-/- mice. The nuclear positivity of LXR inversely correlated with ulcerative colitis histologic activity. Colonic IL-1β mRNA levels negatively correlated with both LXRα and LXRβ in the colon of IL-10-/- mice, where a decreased mRNA expression of the LXR target genes ABCA1 and FAS was shown. In addition, IL-1β decreased the expression of the LXR target gene ABCA1 in cultured intestinal epithelial cells. The synthetic LXR agonist GW3965 led to a decreased nuclear positivity of the p65 subunit of nuclear factor kappa B, a phosphorylation ratio of the p44-42 MAP kinase, and the expression of CCL-28 and IL-8 in IL-1β-stimulated Caco-2 cells. The pharmacological inhibition of ABCA1 increased the phosphorylation of p44-42 after GW3965 treatment and IL-1β stimulation.

Conclusions

The LXR-ABCA1 pathway exerts anti-inflammatory effects in intestinal epithelial cells and is impaired in the colonic mucosa of patients with IBD and IL-10-/- mice.
Cuticular Hydrocarbon Profile Analyses Help Clarify the Species Identity of Dry-Mounted Cuckoo Wasps (Hymenoptera: Chrysididae), Including Type Material, and Reveal Evidence for a Cryptic Species
Authors: Soon Villu , Castillo-Cajas Ruth F , Johansson Niklas , Paukkunen Juho , Rosa Paolo , Ødegaard Frode , Schmitt Thomas , Niehuis Oliver
Published: February 2021

Cuckoo wasps of the Chrysis ignita species group are difficult to identify at the species level, and the taxonomic status of various taxa has consequently been controversial. COI barcoding has helped clarify some of the taxonomic problems in this group, but also revealed cryptic diversity at the genetic level that remained difficult to interpret taxonomically. Here we show that analysis of cuticular hydrocarbons (CHCs) clarifies the taxonomic status of cuckoo wasp samples with distinct COI haplotypes. The advantages of studying CHCs in insects for taxonomic purposes reside on the fact that CHC profiles evolve quickly and that all proteins required for CHC biosynthesis are encoded by nuclear genes. Using Chrysis pseudobrevitarsis as an example, we show that COI barcoding in combination with analysis of CHCs extracted from freshly collected and from dry-mounted museum specimens (including the lectotype of C. pseudobrevitarsis) provides clear evidence for a separate taxon among samples which were previously considered to be conspecific with C. pseudobrevitarsis. We describe this taxon as Chrysis parabrevitarsis n. sp. and present characters for distinguishing it chemically, genetically, and morphologically (females only) from C. pseudobrevitarsis. CHC profile comparison suggests females of C. pseudobrevitarsis may chemically mimic females of the vespid wasp Euodynerus notatus. Our study demonstrates the value of CHC analyses for supporting taxonomic inferences based on COI barcodes. It additionally underlines the value of dry-mounted collection specimens for chemical analyses and the potential of CHCs for inferring the identity of museum specimens, including type material, in a morphologically noninvasive manner.
Stick Then Carrot: When Do Governments Give Amnesty during Civil War?
Authors: Daniels Lesley-Ann
Published: February 2021

Governments grant amnesties to rebel groups during civil wars and this is a puzzle. Why would the government offer an amnesty, which can be interpreted as a signal of weakness? In certain circumstances, offering amnesty is a rational policy choice. Governments should give amnesties when they are winning: the risk of misinterpreted signals is lessened, costs are low, rebel groups are weakened, and so amnesty can be used instrumentally to encourage defection or division among foot soldiers or as an incentive to leaders. Therefore, the government capitalizes on its military advantage and offers amnesty in a “stick then carrot” tactic. Using a database of amnesties during conflicts from 1990 to 2011, the article shows that governments are more likely to give amnesties following high rebel deaths. The use of amnesty during conflict is nuanced and context is important when understanding strategic choices.
Generals in the Cabinet: Military Participation in Government and International Conflict Initiation
Authors: White Peter
Published: February 2021

How does the presence of military officers in national government affect a state's likelihood of international conflict? We know a great deal about how overall regime type affects international conflict, but there is substantial variation within regime types in the participation of military officers in the government. We know little about how this variation affects a state's conflict propensity. In this Research Note, I examine three competing arguments for the effect of military participation in government on conflict initiation: Military Aggression, Military Conservatism, and Civil–Military Competition. Military Aggression suggests that military involvement in government will tend to guide the state toward conflict, given a military predisposition to favor the use of force. In contrast, Military Conservatism argues that military officers in government will lead the state to less conflict, given their personal familiarity with its costs. Civil–Military Competition holds that when military officers and civilians share political power, a variety of pathologies in national security deliberation and decision-making emerge, increasing conflict propensity. I test these three propositions cross-nationally using data on the number and type of positions held by military officers in cabinets and state councils and international conflict and find the strongest support for Civil–Military Competition.
Targeting of Children in Non-International Armed Conflicts
Authors: Birhane Fikire Tinsae
Published: February 2021

Albeit the prohibition of recruitment and use in hostilities of children is an established norm of international law, recognized under both international humanitarian law and international human rights law, the problem still remains. The main actors responsible for this reality are non-state armed groups (NSAGs), which kept recruiting and involving children in various tasks, including direct participation in hostilities (DPH). This in turn generates a dilemma regarding targetability of such children: whether to extend the special protection afforded to them by international law from being recruited and/or used in hostilities for targeting purposes as well. Additionally, the difficulty to determine targeting rules in the context of non-international armed conflicts (NIACs), which led to controversies as to targetability of even adult members of NSAGs while they do not take a direct part in hostilities, exacerbates the dilemma. This piece, accepting persuasiveness of the proposal in the ICRC Interpretive Guidance that those members of armed groups who have continuous combat function (CCF) are targetable, in addition to civilians taking a direct part in hostilities, questions whether children with such function/role are targetable in the same manner as adults of the same position. It is argued here that though children can be targeted during their DPH or when they have CCF, there is support in the law that the notions of DPH and CCF should be applied to them differently than adults. The piece also analyzes if the same means and methods used to target adults could be lawful when employed against children.
Optimizing the Introduction of Wearable Sensors Into the German Armed Forces for Military Medical Applications
Authors: Scheit Lorenz
Published: February 2021

Introduction

A wide variety of different types of wearable sensors are being developed around the world and introduced into the armed forces for military purposes. Competing states must rapidly develop ready-to-use systems that are robust, functional, valid, and practical. There appears to be potential for optimizing the successful and effective introduction of wearable sensors into the German armed forces (Bundeswehr) for military medical applications. The purpose of this study was to identify specific options for improving and optimizing the introduction of modern technologies such as wearable sensors into the structures of the German armed forces.

Materials and Methods

Nine stakeholders were identified who could provide a qualified statement on the introduction of wearable sensors, of which six agreed to participate in an expert interview. The six qualitative expert interviews, which were conducted for a master’s thesis at the Bundeswehr University in Hamburg, were selected on the basis of their thematic involvement and readiness for an interview and provided the basis for exploring processes that can possibly optimize the introduction of wearable sensors into modern armed forces such as the Bundeswehr. These interviews were carried out and analyzed using the Lamnek’s method.

Results

Six expert interviews were analyzed and the most relevant statements were summarized and presented. Thirteen options for optimization were identified and included, for example, interdisciplinary networking, optimization of information flow, and strategic weighting.

Conclusions

Several potential options have been identified that can optimize the introduction of wearable sensors into the German armed forces to a greater or lesser extent. Bundeswehr experts agree that above all structurally relevant improvements such as “development of data analysis standards,” “legal requirements,” “interdisciplinarity,” “acceleration of development,” and “centralization and structured cooperation” should play an important role in the implementation of wearable sensors.
Sudden and Asymmetric Hearing Loss Among Active Duty Service Members: Underscoring the Importance of Active Screening
Authors: Sommerfeldt John M , Marinelli John P , Spear Samuel A
Published: February 2021

Military personnel are at increased risk of asymmetric hearing loss secondary to noise exposure. This report illustrates the importance of expeditiously evaluating for retrocochlear pathology even in young active duty service members with asymmetric or sudden hearing loss. A 36-year-old male presented with right-sided sudden hearing loss and dizziness. Audiometry revealed profound mid-to-high-frequency sensorineural hearing loss in the right ear. A 10-day course of oral steroid therapy and two intratympanic steroid injections were unsuccessful in restoring hearing. MRI revealed a 4.2 cm contrast-enhancing cerebellopontine angle tumor, consistent with a vestibular schwannoma (VS). Microsurgical resection utilizing a retrosigmoid craniotomy approach was performed with near-total resection of the tumor and preservation of the facial nerve but not the cochlear nerve. Despite preservation of the facial nerve, progression of post-operative facial weakness required gold weight placement to prevent exposure keratopathy. The patient had recovered partial function in all facial nerve branches at last follow-up. In light of the rising global incidence of VS, any asymmetric or sudden hearing loss in military service members should be evaluated with audiometry and referral to otolaryngology for workup of retrocochlear pathology.
The warm-up phase in massive star-forming cores around RCW 120
Authors: Kirsanova M S , Salii S V , Kalenskii S V , Wiebe D S , Sobolev A M , Boley P A
Published: February 2021

We study molecular emission in a massive condensation at the border of the H ii region RCW 120, paying particular attention to the Core 1 and 2 objects, the most massive fragments of the condensation found previously by ALMA. The latter fragment was previously suggested to host a high-mass analogue of Class 0 young stellar object. We present spectra of molecular emission in the 1 mm range made with the APEX telescope. We detect CH3OH and C34S lines in Cores 1 and 2. The CH3CN series and the SO2 lines are only found in Core 2. We estimate gas physical parameters using methanol lines and obtain gas temperature less than 100 K in both regions. Molecular hydrogen number density in Core 2 is in the range of 105−107 cm−3 and is more uncertain in Core 1. However, the detection of the CH3CN lines corresponding to highly excited transitions (Eu > 400 K) in Core 2 indicates that the region contains hot gas, while the abundances of CH3OH, CS, SO2, and CH3CN are quite low for a hot core stage. We propose that Core 2 is in the warm-up phase prior to the establishing of the hot gas chemistry. We suggest that Core 2 is in the beginning of the hot core stage. There are no detected CH3CN lines in Core 1; therefore, it might be on an even less evolved evolutionary stage.
Thrombospondin-1 mimetics are promising novel therapeutics for MYC-associated medulloblastoma
Authors: Chan Tiffany S Y , Picard Daniel , Hawkins Cynthia E , Lu Mei , Pfister Stefan , Korshunov Andrey , Roussel Martine F , Wechsler-Reya Robert J , Henkin Jack , Bouffet Eric , Huang Annie
Published: February 2021

Background

Medulloblastoma (MB) comprises four subtypes of which group 3 MB are the most aggressive. Although overall survival for MB has improved, the outcome of group 3 MB remains dismal. C-MYC (MYC) amplification or MYC overexpression which characterizes group 3 MB is a strong negative prognostic factor and is frequently associated with metastases and relapses. We previously reported that MYC expression alone promotes highly aggressive MB phenotypes, in part via repression of thrombospondin-1 (TSP-1), a potent tumor suppressor.

Methods

In this study, we examined the potential role of TSP-1 and TSP-1 peptidomimetic ABT-898 in MYC-amplified human MB cell lines and two distinct murine models of MYC-driven group 3 MBs.

Results

We found that TSP-1 reconstitution diminished metastases and prolonged survival in orthotopic xenografts and promoted chemo- and radio-sensitivity via AKT signaling. Furthermore, we demonstrate that ABT-898 can recapitulate the effects of TSP-1 expression in MB cells in vitro and specifically induced apoptosis in murine group 3 MB tumor cells.

Conclusion

Our data underscore the importance of TSP-1 as a critical tumor suppressor in MB and highlight TSP-1 peptidomimetics as promising novel therapeutics for the most lethal subtype of MB.
Vascularized Bone Grafts for Spinal Fusion—Part 3: The Occiput
Authors: Bohl Michael A , Reece Edward M , Farrokhi Farrokh , Davis Matthew J , Abu-Ghname Amjed , Ropper Alexander E
Published: February 2021

BACKGROUND

Obtaining successful arthrodesis at the craniocervical junction and atlantoaxial joint can be more challenging than in other segments of the cervical spine. This challenge stems from the relatively hypermobile joints between the occipital condyles, the motion that occurs at C1 and C2, as well as the paucity of dorsal bony surfaces for posterior arthrodesis. While multiple different techniques for spinal fixation in this region have been well described, there has been little investigation into auxiliary methods to improve fusion rates.

OBJECTIVE

To describe the use of an occipital bone graft to augment bony arthrodesis in the supraaxial cervical spine using a multidisciplinary approach.

METHODS

We review the technique for harvesting and placing a vascularized occipital bone graft in 2 patients undergoing revision surgery at the craniocervical junction.

RESULTS

The differentiation from nonvascularized bone graft, either allograft or autograft, to a bone graft using vascularized tissue is a key principle of this technique. It has been well established that vascularized bone heals and fuses in the spine better than structural autogenous grafts. However, the morbidity and added operative time of harvesting a vascularized flap, such as from the fibula or rib, precludes its utility in most degenerative spine surgeries.

CONCLUSION

By adapting the standard neurosurgical procedure for a suboccipital craniectomy and utilizing the tenets of flap-based reconstructive surgery to maintain the periosteal and muscular blood supply, we describe the feasibility of using a vascularized and pedicled occipital bone graft to augment instrumented upper cervical spinal fusion. The use of this vascularized bone graft may increase fusion rates in complex spine surgeries.
Local adaptation optimizes photoprotection strategies in a Neotropical legume tree under drought stress
Authors: Cordero Irene , Jiménez María Dolores , Delgado Juan Antonio , Balaguer Luis , Pueyo José J , Rincón Ana
Published: February 2021

Photoprotection is a plant functional mechanism to prevent photooxidative damage by excess light. This is most important when carbon assimilation is limited by drought, and as such, it entails a trade-off between carbon assimilation vs stress avoidance. The ecological adaptation of plants to local water availability can lead to different photoprotective strategies. To test this, we used different provenances of Caesalpinia spinosa (Mol.) Kuntze (commonly known as ‘tara’) along a precipitation gradient. Tara is a Neotropical legume tree with high ecological and commercial value, found in dry tropical forests, which are increasingly threatened by climate change. Morphological and physiological responses of tara provenances were analysed under three different treatments of drought and leaflet immobilization, i.e., light stress, in a common garden greenhouse experiment. Tara quickly responded to drought by reducing stomatal conductance, evapotranspiration, photochemical efficiency, carbon assimilation and growth, while increasing structural and chemical photoprotection (leaflet angle and pigments for thermal dissipation). Leaflet closure was an efficient photoprotection strategy with overall physiological benefits for seedlings as it diminished the evaporative demand and avoided photodamage, but also entailed costs by reducing net carbon assimilation opportunities. These responses depended on seed origin, with seedlings from the most xeric locations showing the highest dehydration tolerance, suggesting local adaptation and highlighting the value of different strategies under distinct environments. This plasticity in its response to environmental stress allows tara to thrive in locations with contrasting water availability. Our findings increase the understanding of the factors controlling the functional ecology of tara in response to drought, which can be leveraged to improve forecasts of changes in its distribution range, and for planning restoration projects with this keystone tree species.
The challenges and facilitators of self-management in pediatric asthma
Authors: Pité Helena , Carvalho Sara , Morais-Almeida Mário
Published: February 2021

Purpose of review

Self-management education in asthma can dramatically reduce asthma morbidity, but specific pediatric challenges need to be addressed. The purpose of this review is to discuss the most recent and significant advances regarding self-management interventions in pediatric asthma.

Recent findings

Recent evidence supports school-based programs including asthma self-management skills for children to significantly improve asthma control. A defined theoretical intervention framework, parent involvement, child satisfaction, and running the intervention outside the child's own free time are suggested drivers of successful implementation. Real-time telemedically delivered asthma education may also improve asthma-related outcomes in children. Moreover, mobile applications supporting self-management are generally welcomed by children and parents. Current evidence supports the use of models of health behaviors change in mobile application design and content development; self-monitoring alone is ineffective but useful when coupled with decision support for proactive care.

School-based and e-health interventions are potential facilitators for the implementation of successful self-management asthma programs, providing access to large numbers of children with asthma. This supports the healthcare practitioners to work together with researchers to promote these interventions, while following current recommendations for the effective transition of children into competent and confident adults to continue to successfully self-manage their asthma.
Donation after circulatory death: opportunities on the horizon
Authors: Potter Kenneth F. , Cocchiola Brian , Quader Mohammed A.
Published: February 2021

Purpose of review

Organ transplantation remains the gold standard therapy for many end-organ diseases. The demand for donor organs continues to grow to far exceed supply. This review summarizes recent protocols, procedures, and ethics surrounding the increased utilization of donors after circulatory death for transplantation.

Recent findings

An increasing number of centers are utilizing donation after circulatory death, and outcomes are improving. Although outcomes from donors after brain death continue to be the primary source of donation, circulatory death outcomes continue to improve approaching the level of brain death donors.

Donation after circulatory death offers a real opportunity to narrow the supply and demand issue with organ donation. Outcomes are improving, and protocols continue to evolve.
Ethical dilemmas in anesthesia mission trips
Authors: Thompson Nicole C.P. , Weinerman Zachary , Solola Jasmine
Published: February 2021

Purpose of review

Health inequities continue to exist globally especially when it comes to surgical and anesthesia services. Due to the lack of physician anesthesiologists in low- and middle-income countries, there has been an increase in the number of medical mission trips. Although these volunteers are attempting to fulfill a need they must be mindful and remember to adhere to ethical principles as they work collaboratively with host institutions. We will review the ethical dilemmas inherent in anesthesia mission trips.

Recent findings

Physician volunteers for medical missions may cause significant harm to patients and host communities if they do not work in tandem with host institutions.

Medical missions fulfill acute medical needs and have the opportunity to make a positive contribution to host communities by fulfilling local needs and supporting educational efforts for local providers.
Pathophysiology of sepsis
Authors: Arina Pietro , Singer Mervyn
Published: February 2021

Purpose of review

To provide a current overview of sepsis pathophysiology.

Recent findings

The emphasis on sepsis pathophysiology has moved away from the pathogen - the initiating factor - and instead is focussed upon the abnormal and exaggerated host response. Instead of targeted eradication of the infection, the host response activates or suppresses multiple downstream pathways, leading to multiple organ dysfunction.

Sepsis represents a dysregulated host response to infection leading to organ dysfunction. Here, the pathogen triggers an initial exaggerated inflammatory-immune response that leads to activation or suppression of multiple endothelial, hormonal, bioenergetic, metabolic, immune, and other pathways. These, in turn, produce the circulatory and metabolic perturbations resulting in organ dysfunction. This review will provide an overview of underlying mechanisms and propose that these processes, whereas superficially viewed as dysfunctional, may actually be adaptive/protective in the first instance, though spilling over into maladaptation/harm depending on the magnitude of the host response.
Hospital-based Buprenorphine/Naloxone Initiation in a Patient With Limited Communication Abilities: A Case Report
Authors: Milden Julia , Dickhout Piper , Nolan Seonaid
Published: February 2021

North America's opioid crisis highlights the profound need for low-barrier access to opioid agonist therapy (OAT) for the treatment of opioid use disorder (OUD). This case describes a 33-year-old female with a history of opioid and stimulant use disorder admitted to hospital after a left middle cerebral artery ischemic stroke with resulting aphasia. After medical stabilization, she consented to buprenorphine/naloxone through limited verbal and written communication. After 14 days of titration, she was stabilized on 14 to 3.5 milligrams of buprenorphine/naloxone daily. Buprenorphine/naloxone initiation and titration is patient-based and symptom guided, typically requiring active communication between the patient and care provider. This case illustrates successful buprenorphine/naloxone initiation in a patient with limited receptive and expressive language abilities, emphasizing the feasibility of offering this medication to individuals with limited communication to ensure timely access to evidence-based OUD treatment.
Perceptions of Signs of Addiction Among Opioid Naive Patients Prescribed Opioids in the Emergency Department
Authors: Serina Peter T. , Lank Patrick M. , Kim Howard S. , Cameron Kenzie A. , Courtney Daniel Mark , Opsasnick Lauren A. , Curtis Laura M. , Wolf Michael S. , McCarthy Danielle M.
Published: February 2021

Objectives:

Patient knowledge deficits related to opioid risks, including lack of knowledge regarding addiction, are well documented. Our objective was to characterize patients’ perceptions of signs of addiction.

Methods:

This study utilized data obtained as part of a larger interventional trial. Consecutively discharged English-speaking patients, age >17 years, at an urban academic emergency department, with a new opioid prescription were enrolled from July 2015 to August 2017. During a follow-up phone interview 7 to 14 days after discharge, participants were asked a single question, “What are the signs of addiction to pain medicine?” Verbatim transcribed answers were analyzed using a directed content analysis approach and double coding. These codes were then grouped into themes.

Results:

There were 325 respondents, 57% female, mean age 43.8 years, 70.1% privately insured. Ten de novo codes were added to the 11 DSM-V criteria codes. Six themes were identified: (1) effort spent acquiring opioids, (2) emotional and physical changes related to opioid use, (3) opioid use that is “not needed, (4) increasing opioid use, (5) an emotional relationship with opioids, and (6) the inability to stop opioid use.

Conclusions:

Signs of addiction identified by opioid naive patients were similar to concepts identified in medical definitions. However, participants’ understanding also included misconceptions, omissions, and conflated misuse behaviors with signs of addiction. Identifying these differences will help inform patient-provider risk communication, providing an opportunity for counseling and prevention.
Initiation of Low-threshold Buprenorphine in Nontreatment Seeking Patients With Opioid Use Disorder Engaged in Hepatitis C Treatment
Authors: Hill Kristi , Nussdorf Laura , Mount Julia D. , Silk Rachel , Gross Chloe , Sternberg David , Bijole Phyllis , Jones Miriam , Kier Randy , Mccullough Dana , Mathur Poonam , Kottilil Shyam , Masur Henry , Kattakuzhy Sarah , Rosenthal Elana S.
Published: February 2021

Objective:

The ANCHOR program offered buprenorphine treatment to people who inject drugs engaged in hepatitis C (HCV) treatment at a Washington, DC harm reduction organization. This analysis describes the program model and outcomes of the opioid care continuum at 1 year.

Methods:

Primary outcomes were initiation of buprenorphine and retention in care, defined by an active buprenorphine prescription at given time points. Secondary outcomes included treatment interruptions, reasons for treatment noninitiation and termination, buprenorphine and opiate use, and HIV risk behaviors. Buprenorphine and opiate use were measured by urine toxicology screens and HIV risk behavior was quantified using a validated survey.

Results:

Of 67 patients receiving HCV treatment not on opioid agonist therapy at baseline, 96% (n = 64) were interested and 73% (n = 49) initiated buprenorphine. Retention was 82% (n = 40), 65% (n = 32), and 59% (n = 29) at months 1, 6, and 12, respectively. Retention at 12 months was associated with self-reported engagement in routine medical care (P < 0.01), but was not associated with gender, stable housing, past opioid agonist therapy, or past overdose. Among retained patients, urine screens positive for opioids were 73% (n = 29), 56% (n = 18), and 79% (n = 23) at months 1, 6, and 12. There was a significant mean decrease in HIV risk-taking behavior scores over the treatment period, primarily driven by reduced injection frequency.

Conclusions:

Patients engaged in HCV treatment at a harm reduction organization showed a high rate of initiation of buprenorphine treatment, with retention comparable to other treatment settings. Although most patients continued using opioids on treatment, there was a reduced frequency of injection drug use, a significant driver of OUD-related risk. These data support the use of low-threshold buprenorphine access alongside HCV treatment to reduce morbidity and mortality in people with OUD.
Peer Recovery Support Services Across the Continuum: In Community, Hospital, Corrections, and Treatment and Recovery Agency Settings – A Narrative Review
Authors: Stack Erin , Hildebran Christi , Leichtling Gillian , Waddell Elizabeth Needham , Leahy Judith M. , Martin Eric , Korthuis Phillip Todd
Published: February 2021

In this narrative review, we outline the literature describing the history, training, certification, and role of peer recovery support specialists working with people with substance use disorders at different stages of active use and recovery. We explore the impact of peer recovery support specialists serving people in various settings, including the community, hospitals and emergency departments, jails and prisons, and treatment and recovery agencies; and describes considerations for future expansion of peer recovery support services, including supervision needs, compassion fatigue and burnout, and scope of practice. Finally, we make recommendations to support the broad implementation of peer recovery support services as a sustainable, cohesive, and replicable component of harm reduction and addiction services. We also make recommendations for research to continue to evaluate peer recovery support specialist interventions across settings and outcomes.
Treatment Disruption and Childcare Responsibility as Risk Factors for Drug and Alcohol Use in Persons in Treatment for Substance Use Disorders During the COVID-19 Crisis
Authors: Huhn Andrew S. , Strain Eric C. , Jardot Jasmyne , Turner Gavin , Bergeria Cecilia L. , Nayak Sandeep , Dunn Kelly E.
Published: February 2021

Objectives:

The novel 2019 coronavirus (COVID-19) crisis has caused considerable upheaval in the U.S. healthcare system. The current study examined patient-reported experiences in substance use disorder (SUD) treatment during the early stages of the COVID-19 crisis.

Methods:

Participants in SUD treatment were recruited via online crowdsourcing from April 14, 2020 to May 26, 2020, during the early stages of the COVID-19 crisis. Participants reported disruptions in SUD treatment, stress and anxiety caused by these disruptions on a 0-100 point visual analogue scale (VAS), stress associated with childcare responsibilities on a 0–100 VAS, current stress on the Perceived Stress Scale (PSS), anxiety symptoms on the Beck Anxiety Inventory (BAI), sleep disturbances on the Insomnia Severity Index (ISI), and whether they used drugs or alcohol during the COVID-19 crisis.

Results:

Participants (N = 240) endorsed that at least 1 SUD treatment was switched to telemedicine (63.7%), had some appointments cancelled (37.5%), or was discontinued due to COVID-19 (29.6%). Participants who did versus did not endorse drug/alcohol use reported difficulty obtaining medications to treat their SUD (OR = 2.47, 95% CI, 1.17–5.22, χ2 = 5.98, P = .016), greater scores on VAS treatment-related stress (F
1,197 = 5.70, P = .018) and anxiety (F
1,197 = 4.07, P = .045), greater VAS stress related to childcare (F
1,107 = 10.24, P = .002), and greater scores on the PSS (F
1,235 = 19.27, P < .001), BAI (F
1,235 = 28.59, P < .001), and ISI (F
1,235 = 14.41, P < .001).

Conclusions:

Providers and public health officials should work to improve continuity and quality of care during the COVID-19 crisis, with special attention on addressing childcare difficulties and providing remote methods to improve stress, anxiety, and sleep for persons in SUD treatment.