bluuebunny/crossref_metadata_2025 huggingface dataset:
Superresolution characterization of core centriole architecture
Authors: Tian Yuan , Wei Chenxi , He Jianfeng , Yan Yuxuan , Pang Nan , Fang Xiaomin , Liang Xin , Fu Jingyan
Published: February 2021

The centrosome is the main microtubule-organizing center in animal cells. It comprises of two centrioles and the surrounding pericentriolar material. Protein organization at the outer layer of the centriole and outward has been studied extensively; however, an overall picture of the protein architecture at the centriole core has been missing. Here we report a direct view of Drosophila centriolar proteins at ∼50-nm resolution. This reveals a Sas6 ring at the C-terminus, where it overlaps with the C-terminus of Cep135. The ninefold symmetrical pattern of Cep135 is further conveyed through Ana1–Asterless axes that extend past the microtubule wall from between the blades. Ana3 and Rcd4, whose termini are close to Cep135, are arranged in ninefold symmetry that does not match the above axes. During centriole biogenesis, Ana3 and Rcd4 are sequentially loaded on the newly formed centriole and are required for centriole-to-centrosome conversion through recruiting the Cep135–Ana1–Asterless complex. Together, our results provide a spatiotemporal map of the centriole core and implications of how the structure might be built.
Endothelial LRP1 protects against neurodegeneration by blocking cyclophilin A
Authors: Nikolakopoulou Angeliki Maria , Wang Yaoming , Ma Qingyi , Sagare Abhay P. , Montagne Axel , Huuskonen Mikko T. , Rege Sanket V. , Kisler Kassandra , Dai Zhonghua , Körbelin Jakob , Herz Joachim , Zhao Zhen , Zlokovic Berislav V.
Published: February 2021

The low-density lipoprotein receptor–related protein 1 (LRP1) is an endocytic and cell signaling transmembrane protein. Endothelial LRP1 clears proteinaceous toxins at the blood–brain barrier (BBB), regulates angiogenesis, and is increasingly reduced in Alzheimer’s disease associated with BBB breakdown and neurodegeneration. Whether loss of endothelial LRP1 plays a direct causative role in BBB breakdown and neurodegenerative changes remains elusive. Here, we show that LRP1 inactivation from the mouse endothelium results in progressive BBB breakdown, followed by neuron loss and cognitive deficits, which is reversible by endothelial-specific LRP1 gene therapy. LRP1 endothelial knockout led to a self-autonomous activation of the cyclophilin A–matrix metalloproteinase-9 pathway in the endothelium, causing loss of tight junctions underlying structural BBB impairment. Cyclophilin A inhibition in mice with endothelial-specific LRP1 knockout restored BBB integrity and reversed and prevented neuronal loss and behavioral deficits. Thus, endothelial LRP1 protects against neurodegeneration by inhibiting cyclophilin A, which has implications for the pathophysiology and treatment of neurodegeneration linked to vascular dysfunction.
Dynein regulates Kv7.4 channel trafficking from the cell membrane
Authors: van der Horst Jennifer , Rognant Salomé , Abbott Geoffrey W. , Ozhathil Lijo Cherian , Hägglund Per , Barrese Vincenzo , Chuang Christine Y. , Jespersen Thomas , Davies Michael J. , Greenwood Iain A. , Gourdon Pontus , Aalkjær Christian , Jepps Thomas A.
Published: February 2021

The dynein motor protein transports proteins away from the cell membrane along the microtubule network. Recently, we found the microtubule network was important for regulating the membrane abundance of voltage-gated Kv7.4 potassium channels in vascular smooth muscle. Here, we aimed to investigate the influence of dynein on the microtubule-dependent internalization of the Kv7.4 channel. Patch-clamp recordings from HEK293B cells showed Kv7.4 currents were increased after inhibiting dynein function with ciliobrevin D or by coexpressing p50/dynamitin, which specifically interferes with dynein motor function. Mutation of a dynein-binding site in the Kv7.4 C terminus increased the Kv7.4 current and prevented p50 interference. Structured illumination microscopy, proximity ligation assays, and coimmunoprecipitation showed colocalization of Kv7.4 and dynein in mesenteric artery myocytes. Ciliobrevin D enhanced mesenteric artery relaxation to activators of Kv7.2–Kv7.5 channels and increased membrane abundance of Kv7.4 protein in isolated smooth muscle cells and HEK293B cells. Ciliobrevin D failed to enhance the negligible S-1–mediated relaxations after morpholino-mediated knockdown of Kv7.4. Mass spectrometry revealed an interaction of dynein with caveolin-1, confirmed using proximity ligation and coimmunoprecipitation assays, which also provided evidence for interaction of caveolin-1 with Kv7.4, confirming that Kv7.4 channels are localized to caveolae in mesenteric artery myocytes. Lastly, cholesterol depletion reduced the interaction of Kv7.4 with caveolin-1 and dynein while increasing the overall membrane expression of Kv7.4, although it attenuated the Kv7.4 current in oocytes and interfered with the action of ciliobrevin D and channel activators in arterial segments. Overall, this study shows that dynein can traffic Kv7.4 channels in vascular smooth muscle in a mechanism dependent on cholesterol-rich caveolae.
Nebulin: Size matters for optimal muscle function
Authors: Pelin Katarina
Published: February 2021

Gohlke et al. show the importance of nebulin size for optimal skeletal muscle function in animals of different body size.
Application of comprehensive geophysical prospecting method in advance geological prediction of limestone tunnel
Authors: Chen Wu , Li Junjie , Zheng Huihua
Published: February 2021

Tunnel seismic prediction(TSP) and ground penetrating radar(GPR) are used in the advance geological prediction of a limestone tunnel. The working principle of two geophysical methods is briefly described. The additional detection work of GPR is carried out in the abnormal area of TSP prediction. The predicted dissolution distribution area of the two methods is relatively consistent. The actual excavation results of the tunnel verify the reliability of the geophysical prediction method. The results show that the velocity of TSP P-wave or S-wave corresponding to the dissolution zone is relatively low, which corresponds to the electromagnetic anomaly with strong amplitude of GPR with hyperbolic event.
Intraindividual Variability of Sleep Opportunity Attitudes, Perceived Norms, Perceived Behavioral Control, and Intentions
Authors: Mead Michael P , Irish Leah A
Published: February 2021

Background

Recent research has used the theory of planned behavior (TPB) to predict sleep. However, this research has focused on between-person effects and has failed to capture the intraindividual variability of sleep-related attitudes, subjective norms, perceived behavioral control, and intentions.

Purpose

The current study sought to characterize the between- and within-day patterns of these constructs.

Methods

Participants (N = 79) completed a 1 week ecological momentary assessment protocol in which they reported their attitudes, subjective norms, perceived behavioral control, and intentions toward nightly sleep opportunity four times per day.

Results

Analyses revealed both between- and within-day variability of these constructs, with perceived behavioral control and intentions demonstrating greater variability than attitudes and subjective norms. Mixed linear models revealed that attitudes and subjective norms significantly increased throughout the week, while perceived behavioral control and intentions significantly decreased throughout the day.

Conclusions

The between- and within-day patterns of the TPB constructs highlight important methodological considerations and provide insight into the potential refinement of sleep promotion efforts.
Multicenter point prevalence evaluation of the utilization and safety of drug therapies for COVID-19 at the onset of the pandemic timeline in the United States
Authors: Rhodes Nathaniel J , Dairem Atheer , Moore William J , Shah Anooj , Postelnick Michael J , Badowski Melissa E , Michienzi Sarah M , Borkowski Jaime L , Polisetty Radhika S , Fong Karen , Spivak Emily S , Beardsley James R , Hale Cory M , Pallotta Andrea M , Srinivas Pavithra , Schulz Lucas T
Published: February 2021

Key points

In a multicenter point-prevalence study, we found that the rate of supportive care was high; among those receiving COVID-19 drug therapies, adverse reactions occurred in 12% of patients.

Purpose

There are currently no FDA-approved medications for the treatment of coronavirus disease 2019 (COVID-19). At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period.

Methods

We conducted a noninterventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19–targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs).

Results

A total of 352 patients treated for COVID-19 at 15 US hospitals From April 18 to May 8, 2020, were included in the study. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies used included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 antagonists (9%). Five patients (7.5%) were receiving combination therapy. The rate of use of COVID-19–directed drug therapy was higher in patients with vs patients without a history of asthma (14.9% vs 7%, P = 0.037) and in patients enrolled in clinical trials (26.9% vs 3.2%, P < 0.001). Among those receiving drug therapy, 8 patients (12%) experienced an ADR, and ADRs were recognized at a higher rate in patients enrolled in clinical trials (62.5% vs 22%; odds ratio, 5.9; P = 0.028).

Conclusion

While we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy, including those enrolled in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 treatments.
Acorus calamus extract and its component α-asarone attenuate murine hippocampal neuronal cell death induced by l-glutamate and tunicamycin
Authors: Mikami Masashi , Takuya Ohba , Yoshino Yuta , Nakamura Shinsuke , Ito Kenichi , Kojima Hiroyuki , Takahashi Tatsuji , Iddamalgoda Arunasiri , Inoue Shintaro , Shimazawa Masamitsu , Hara Hideaki
Published: February 2021

The Asian traditional medicinal plant Acorus calamus and its component α-asarone exhibited various biological activities, such as antiinflammation and antioxidant effects. In the present study, we investigated the in vitro effects of A. calamus extract and α-asarone on oxidative stress- and endoplasmic reticulum (ER) stress–induced cell death in hippocampal HT22 cells. A. calamus extract and α-asarone both significantly suppressed cell death induced by the oxidative stress inducer l-glutamate and ER stress inducer tunicamycin. A. calamus extract and α-asarone also significantly reduced reactive oxygen species (ROS) production induced by l-glutamate. Moreover, A. calamus extract and α-asarone suppressed the phosphorylation of protein kinase RNA-like ER kinase (PERK) induced by tunicamycin. These results suggest that A. calamus extract and α-asarone protect hippocampal cells from oxidative stress and ER stress by decreasing ROS production and suppressing PERK signaling, respectively. α-Asarone has potential as a potent therapeutic candidate for neurodegenerative diseases, including Alzheimer's disease.
Skin-related enzyme inhibitory activity by hydrolyzable polyphenols in water chestnut (Trapa natans) husk
Authors: Yasuda Midori , Ikeoka Masaki , Kondo Shin-ichi
Published: February 2021

Water chestnut is a floating leaf plant native to Asia and Europe. Its fruit has long been used as an edible and herbal medicine. Water chestnut contains many polyphenols and its consumption can prevent lifestyle-related diseases because it has a suppressive effect on postprandial blood glucose elevation; however, its suitability as a cosmetic material is unknown. Therefore, this study aimed at investigating the antiaging effect of polyphenols contained in the husk of the devil water chestnut (Trapa natans). Six hydrolyzable polyphenols—1,6-di-O-galloyl-β-d-glucopyranose, 1,2,6-tri-O-galloyl-β-d-glucopyranose, 1,6-di-O-galloyl-2,3-O-(S)-hexahydroxydiphenoyl-β-d-glucopyranose (nobotanin D), eugeniin, 1,2,3,6-tetra-O-galloyl-β-d-glucopyranose, and trapain—were collected and isolated from the water chestnut husk. These polyphenols showed high antioxidant and antiglycation activities. In addition, inhibitory activities against hyaluronidase, elastase, and collagenase were observed. Especially, eugeniin and trapain, which have many gallic acids and a hexahydroxy-biphenyl group, showed high inhibitory activities. Thus, the polyphenols in water chestnut are beneficial for antiaging effects.
Quantitative analysis of auxin metabolites in lychee flowers
Authors: Kim Ryunhee , Osako Yutaro , Yamane Hisayo , Tao Ryutaro , Miyagawa Hisashi
Published: February 2021

To investigate the modulation of endogenous indole-3-acetic acid (IAA) level by biosynthesis and inactivation during floral development, IAA and its metabolites were analyzed by LC-ESI/MS/MS in Lychee (Litchi chinensis Sonn.) flowers. In the bloomed flowers, the level of free IAA was higher in males than in females. In contrast, the total sum level of IAA metabolites was higher in females than in males, suggesting a higher biosynthetic activity of IAA in the females before the bloom. A detailed time-course analysis from the bud stage to the developing flower stage showed higher levels of IAA in females than males. The major metabolites were oxidized IAA in both sexes. The results suggest that IAA is involved in the maturation of female floral tissues in lychee, and oxidative metabolism plays an essential role in controlling the free IAA levels therein.
Thrombin-deficient mutant of medaka, a model fish, displays serious retardation in blood coagulation
Authors: Watanabe Yuko , Oguri Rina , Suzuki Risa , Meng Qi , Ishikawa Yuta , Tatsukawa Hideki , Hashimoto Hisashi , Hitomi Kiyotaka
Published: February 2021

At the last stage of the blood coagulation cascade, thrombin plays a central role in the processing of fibrinogen for the polymerization and in the additional activation of Factor XIII for the stable cross-linking of fibrin. In addition, thrombin carries out possible multiple roles via processing or interaction with various functional proteins. Several studies conducted in order to elucidate additional physiological significance are ongoing. To clarify further significance of thrombin and to establish an associated disease model, we characterized the orthologue gene for medaka (Oryzias latipes), a research model fish. Tissue distribution of medaka prothrombin has been immunotechnically analyzed. Furthermore, thrombin-deficient medaka mutants were viably established by utilizing a genome-editing method. The established gene-deficient mutants exhibited retarded blood coagulation even in the heterozygous fish. Taking advantage of their ease of handling, this specific model is useful for further investigation in medical research areas on human coagulation diseases.
Cortical Gyrification in Transgender Individuals
Authors: Wang Yanlu , Khorashad Behzad S , Feusner Jamie D , Savic Ivanka
Published: February 2021

Gender incongruence (GI) is characterized by a feeling of estrangement from the own body in the context of self. GI is often described in people who identify as transgender. The underlying mechanisms are unknown. Data from MRI measurements and tests of own body perception triggered us to pose a model that GI in transgender persons (TGI) could be associated with a disconnection within the brain circuits mediating the perception of own body as self. This is a departure from a previous model of sex atypical cerebral dimorphism, introducing a concept that better accords with a core feature of TGI. The present MRI study of 54 hormone naive transmen (TrM), 38 transwomen (TrW), 44 cismen and 41 ciswomen show that cortical gyrification, a metric that reflects early maturation of cerebral cortex, is significantly lower in transgender compared with cisgender participants. This reduction is limited to the occipito-parietal cortex and the sensory motor cortex, regions encoding own body image and body ownership. Moreover, the cortical gyrification correlated inversely with own body-self incongruence in these regions. These novel data suggest that GI in TGI may originate in the neurodevelopment of body image encoding regions. The results add potentially to understanding neurobiological contributors to gender identity.
Binary Tree Encryption with Constant-Size Public Key in the Standard Model
Authors: Feng Shengyuan , Gong Junqing , Chen Jie
Published: February 2021

Binary tree encryption is an intriguing primitive that enables many practical applications to achieve an increasing important security feature, forward security. However, the public key size of existing constructions grows linearly with the depth of the underlying binary tree in the standard model. To support more secret keys associated with nodes, it is often expected that the tree has a sufficiently large depth. This places a burden on employing it implicitly or explicitly in real world. In this work, we show how to compress linear-size public key down to constant-size public key and give our construction featuring constant-size public key in the standard model. We prove that our construction achieves an improved security, adaptive security, under the matrix decision Diffie–Hellman assumption, which is a generalization of standard $k$-Lin assumption. Moreover, our key-generation, key-derivation and encryption algorithms have lower time complexity than that of the prior construction, leading to further efficiency improvements. To illustrate these improvements in practice, we give an implementation of our construction and the prior one and then evaluate the performance in the tree depth.
FlyORF-TaDa allows rapid generation of new lines for in vivo cell-type-specific profiling of protein–DNA interactions in Drosophila melanogaster
Authors: Aughey Gabriel N , Delandre Caroline , McMullen John P D , Southall Tony D , Marshall Owen J
Published: February 2021

Targeted DamID (TaDa) is an increasingly popular method of generating cell-type-specific DNA-binding profiles in vivo. Although sensitive and versatile, TaDa requires the generation of new transgenic fly lines for every protein that is profiled, which is both time-consuming and costly. Here, we describe the FlyORF-TaDa system for converting an existing FlyORF library of inducible open reading frames (ORFs) to TaDa lines via a genetic cross, with recombinant progeny easily identifiable by eye color. Profiling the binding of the H3K36me3-associated chromatin protein MRG15 in larval neural stem cells using both FlyORF-TaDa and conventional TaDa demonstrates that new lines generated using this system provide accurate and highly reproducible DamID-binding profiles. Our data further show that MRG15 binds to a subset of active chromatin domains in vivo. Courtesy of the large coverage of the FlyORF library, the FlyORF-TaDa system enables the easy creation of TaDa lines for 74% of all transcription factors and chromatin-modifying proteins within the Drosophila genome.
Predator stomach contents can provide accurate indices of prey biomass
Authors: Ng Elizabeth L , Deroba Jonathan J , Essington Timothy E , Grüss Arnaud , Smith Brian E , Thorson James T
Published: February 2021

Diet-based annual biomass indices can potentially use predator stomach contents to provide information about prey biomass and may be particularly useful for species that are otherwise poorly sampled, including ecologically important forage fishes. However, diet-based biomass indices may be sensitive to underlying ecological dynamics between predators and prey, such as predator functional responses and changes in overlap in space and time. To evaluate these factors, we fit spatio-temporal models to stomach contents of five Atlantic herring (Clupea harengus) predators and survey catch data for predators and Atlantic herring. We identified drivers of variation in stomach contents, evaluated spatial patterns in stomach content data, and produced predator-specific indices of seasonal Atlantic herring biomass. After controlling for spatio-temporal processes and predator length, diet-based indices of biomass shared similar decadal trends but varied substantially between predators and seasons on shorter time scales. Diet-based indices reflected prey biomass more than prey availability, but weak correlations indicated that not all biological processes were controlled for. Results provide potential guidance for developing diet-based biomass indices and contribute to a body of evidence demonstrating the utility of predator diet data to provide information about relative prey biomass.
Regulation of Reelin functions by specific proteolytic processing in the brain
Authors: Hattori Mitsuharu , Kohno Takao
Published: February 2021

The secreted glycoprotein Reelin plays important roles in both brain development and function. During development, Reelin regulates neuronal migration and dendrite development. In the mature brain, the glycoprotein is involved in synaptogenesis and synaptic plasticity. It has been suggested that Reelin loss or decreased function contributes to the onset and/or deterioration of neuropsychiatric diseases, including schizophrenia and Alzheimer’s disease. While the molecular mechanisms underpinning Reelin function remain unclear, recent studies have suggested that the specific proteolytic cleavage of Reelin may play central roles in the embryonic and postnatal brain. In this review, we focus on Reelin proteolytic processing and review its potential physiological roles.
The Impact of Multidisciplinary Conferences on Treatment Plans for Patients With Inflammatory Bowel Disease in a Tertiary Canadian Centre
Authors: Hartford Luke B , Allen Laura J , Lennox Heather , Jairath Vipul , Van Koughnett Julie Ann M
Published: February 2021

Background

Multidisciplinary conference presentation may provide recommendations for diagnosis, monitoring and treatment for patients with inflammatory bowel disease.

Methods

A prospective observational study was completed evaluating if case presentation resulted in a direct change in management for patients presented over a 2-year period in a tertiary Canadian centre. Change in management was defined as hospital admission, surgery or surgical referral, start/change in biologic therapy or other medication or initiation of parenteral nutrition. Secondary outcomes included the involvement of specialists and other referrals. Data were analyzed using frequencies and means with standard deviations.

Results

In 63 multidisciplinary conferences, 181 patients were presented, of whom 136 patients met the inclusion criteria of inflammatory bowel disease (Crohn’s n = 45, ulcerative colitis n = 88, undifferentiated n = 3). The majority were outpatient cases 110 (81%). Indications included 71 (52%) patients presented for IBD management with diagnosis > 1 year, 37 (27%) with an acute IBD flare in a chronic patient (>1 year since diagnosis) and 24 (18%) with new diagnosis of IBD. Change in management was recommended in 35 (26%) patients. The most common change was referral to surgery in 17 (13%), surgery in 12 (9%) or change in biologic therapy 11 (8%). Compliance with the recommendations was 85%. There was frequent specialist involvement in case discussions (gastroenterologist 100%, surgeon 60%, radiologist 68% and pathologist 32%).

Conclusions

Presentation of complex inflammatory bowel disease cases at multidisciplinary conference leads to a direct change in treatment in one quarter of cases, with surgical referral as the most frequent outcome.
Jejunal perforation secondary to migrated biliary stent
Authors: Tabone Renee , Yuide Peter , Burstow Matthew
Published: February 2021

An 80-year-old female presented with acute left-sided abdominal pain. Cross-sectional imaging demonstrated a contained perforation around a migrated biliary stent within a large incisional hernia. Significant surgical background included an open cholecystectomy complicated by bile leak and insertion of a biliary stent 2.5 years prior. The stent had migrated at the time of attempted retrieval 10 weeks post-insertion. A decision was made to pursue conservative management after which time she remained asymptomatic until her acute presentation. Emergency laparotomy, adhesiolysis, stent removal, small bowel resection and abdominal wall closure were successfully performed in this case. In the setting of the biliary stent migration, it is important to consider individual patient’s risk factors for acute perforation, such as intra-abdominal adhesions or diverticular disease, when deliberating conservative management versus elective surgical intervention for stent retrieval.
Post-translational modifications regulate the activity of the growth-restricting protease DA1
Authors: Chen Ying , Inzé Dirk , Vanhaeren Hannes
Published: February 2021

Plants are a primary food source and can form the basis for renewable energy resources. The final size of their organs is by far the most important trait to consider when seeking increased plant productivity. Being multicellular organisms, plant organ size is mainly determined by the coordination between cell proliferation and cell expansion. The protease DA1 limits the duration of cell proliferation and thereby restricts final organ size. Since its initial identification as a negative regulator of organ growth, various transcriptional regulators of DA1, but also interacting proteins, have been identified. These interactors include cleavage substrates of DA1, and also proteins that modulate the activity of DA1 through post-translational modifications, such as ubiquitination, deubiquitination, and phosphorylation. In addition, many players in the DA1 pathway display conserved phenotypes in other dicot and even monocot species. In this review, we provide a timely overview of the complex, but intriguing, molecular mechanisms that fine-tune the activity of DA1 and therefore final organ size. Moreover, we lay out a roadmap to identify and characterize substrates of proteases and frame the substrate cleavage events in their biological context.
Exact solution of one-dimensional relativistic jet with relativistic equation of state
Authors: Joshi Raj Kishor , Chattopadhyay Indranil , Ryu Dongsu , Yadav Lallan
Published: February 2021

We study the evolution of one-dimensional relativistic jets, using the exact solution of the Riemann problem for relativistic flows. For this purpose, we solve equations for the ideal special relativistic fluid composed of dissimilar particles in flat space-time and the thermodynamics of fluid is governed by a relativistic equation of state. We obtain the exact solution of jets impinging on denser ambient media. The time variation of the cross-section of the jet-head is modelled and incorporated. We present the initial condition that gives rise to a reverse shock. If the jet-head cross-section increases in time, the jet propagation speed slows down significantly and the reverse-shock may recede opposite to the propagation direction of the jet. We show that the composition of jet and ambient medium can affect the jet solution significantly. For instance, the propagation speed depends on the composition and is maximum for a pair-dominated jet, rather than a pure electron-positron or electron-proton jet. The propagation direction of the reverse-shock may also strongly depend on the composition of the jet.
Impact of a Mortality Prediction Rule for Organizing and Guiding Antimicrobial Stewardship Program Activities
Authors: Collins Curtis D , Kollmeyer Scott , Scheidel Caleb , Dietzel Christopher J , Leeman Lauren R , Morrin Cheryl , Malani Anurag N
Published: February 2021

Background

Antimicrobial stewardship program (ASP) surveillance at our hospital is supplemented by an internally developed surveillance database. In 2013, the database incorporated a validated, internally developed, prediction rule for patient mortality within 30 days of hospital admission. This study describes the impact of an expanded ASP review in patients at the highest risk for mortality.

Methods

This retrospective, quasi-experimental study analyzed adults who received antimicrobials with the highest mortality risk score. Study periods were defined as 2011–Q3 2013 (historical group) and Q4 2013–2018 (intervention group). Primary and secondary outcomes were assessed for confounders and analyzed using both unadjusted and propensity score weighted analyses. Interrupted time-series analyses also analyzed key outcomes.

Results

A total of 3282 and 5456 patients were included in the historical and intervention groups, respectively. There were significant reductions in median antimicrobial duration (5 vs 4 days; P < .001), antimicrobial days of therapy (8 vs 7; P < .001), antimicrobial cost ($96 vs $85; P = .003), length of stay (LOS) (6 vs 5 days; P < .001), intensive care unit (ICU) LOS (3 vs 2 days; P < .001), total hospital cost ($10 946 vs $9119; P < .001), healthcare facility-onset vancomycin-resistant Enterococcus (HO-VRE) incidence (1.3% vs 0.3%; P ≤ .001), and HO-VRE infections (0.6% vs 0.2%; P = .018) in the intervention cohort.

Conclusions

Reductions in antimicrobial use, hospital and ICU LOS, HO-VRE, HO-VRE infections, and costs were associated with incorporation of a novel mortality prediction rule to guide ASP surveillance and intervention.
Prospective Associations of Physical Frailty With Future Falls and Fear of Falling: A 48-Month Cohort Study
Authors: Makino Keitaro , Lee Sangyoon , Bae Seongryu , Chiba Ippei , Harada Kenji , Katayama Osamu , Shinkai Yohei , Makizako Hyuma , Shimada Hiroyuki
Published: February 2021

Objective

The present study aimed to examine the prospective associations of physical frailty with future falls and fear of falling (FOF) among community-dwelling older adults.

Methods

A prospective cohort study with a 48-month follow-up was conducted in a Japanese community. Participants were 2469 community-dwelling older adults aged 65 years or older who completed baseline and follow-up assessments at intervals of 48 ± 2 months. Primary outcomes were recent falls (defined as at least one fall within the past year) and FOF (determined by response to “Are you afraid of falling?”) at follow-up survey. Physical frailty, operationalized by the frailty phenotype (slowness, weakness, exhaustion, weight loss, and low activity) based on the criteria of the Japanese version of the Cardiovascular Health Study (J-CHS), was also assessed as a predictor of future falls and FOF.

Results

Multivariable logistic regression showed that prefrailty or frailty increase the risk of not only future falls (odds ratio [OR]: 1.57; 95% CI = 1.20–2.05) but also FOF (OR: 1.33; 95%CI = 1.05–1.69). In addition, the relationship between baseline frailty status and future falls remained significant after adjusting for baseline FOF (OR: 1.55; 95% CI = 1.19–2.02), and the relationship between baseline frailty status and future FOF also remained significant after adjusting for baseline falls (OR: 1.32; 95% CI = 1.04–1.68).

Conclusions

Frailty status may predict future falls and FOF among community-dwelling older adults. Strategies to prevent frailty may be beneficial to prevent not only future falls but also future FOF in a community setting.

Impact

Falls and FOF have a close relationship but a different clinical meaning. Older adults with physical frailty may require monitoring as high risk not only for falls but also for FOF.
Lower vitamin D is associated with metabolic syndrome and insulin resistance in systemic lupus: data from an international inception cohort
Authors: Chew Christine , Reynolds John A , Lertratanakul Apinya , Wu Peggy , Urowitz Murray , Gladman Dafna D , Fortin Paul R , Bae Sang-Cheol , Gordon Caroline , Clarke Ann E , Bernatsky Sasha , Hanly John G , Isenberg David , Rahman Anisur , Sanchez-Guerrero Jorge , Romero-Diaz Juanita , Merrill Joan , Wallace Daniel , Ginzler Ellen , Khamashta Munther , Nived Ola , Jönsen Andreas , Steinsson Kristjan , Manzi Susan , Kalunian Ken , Dooley Mary Anne , Petri Michelle , Aranow Cynthia , van Vollenhoven Ronald , Stoll Thomas , Alarcón Graciela S , Lim S Sam , Ruiz-Irastorza Guillermo , Peschken Christine A , Askanase Anca D , Kamen Diane L , İnanç Murat , Ramsey-Goldman Rosalind , Bruce Ian N
Published: February 2021

Objectives

Vitamin D (25(OH)D) deficiency and metabolic syndrome (MetS) may both contribute to increased cardiovascular risk in SLE. We aimed to examine the association of demographic factors, SLE phenotype, therapy and vitamin D levels with MetS and insulin resistance.

Methods

The Systemic Lupus International Collaborating Clinics (SLICC) enrolled patients recently diagnosed with SLE (<15 months) from 33 centres across 11 countries from 2000. Clinical, laboratory and therapeutic data were collected. Vitamin D level was defined according to tertiles based on distribution across this cohort, which were set at T1 (10–36 nmol/l), T2 (37–60 nmol/l) and T3 (61–174 nmol/l). MetS was defined according to the 2009 consensus statement from the International Diabetes Federation. Insulin resistance was determined using the HOMA-IR model. Linear and logistic regressions were used to assess the association of variables with vitamin D levels.

Results

Of the 1847 patients, 1163 (63%) had vitamin D measured and 398 (34.2%) subjects were in the lowest 25(OH)D tertile. MetS was present in 286 of 860 (33%) patients whose status could be determined. Patients with lower 25(OH)D were more likely to have MetS and higher HOMA-IR. The MetS components, hypertension, hypertriglyceridemia and decreased high-density lipoprotein (HDL) were all significantly associated with lower 25(OH)D. Increased average glucocorticoid exposure was associated with higher insulin resistance.

Conclusions

MetS and insulin resistance are associated with lower vitamin D in patients with SLE. Further studies could determine whether vitamin D repletion confers better control of these cardiovascular risk factors and improve long-term outcomes in SLE.
Extreme Binge Drinking During Adolescence: Associations With Subsequent Substance Use Disorders in American Indian and Mexican American Young Adults
Authors: Ehlers Cindy L. , Wills Derek , Karriker-Jaffe Katherine J. , Gilder David A.
Published: February 2021

Objective:

This study collected retrospective data on adolescent binge drinking (ABD) (5 drinks for boys, 4 for girls per occasion at least once per month) and/or extreme adolescent binge drinking (EABD) (10 or more drinks per occasion at least once per month) and tested for associations with demographic and diagnostics variables including alcohol and other substance use disorders (AUD/SUD).

Methods:

Cross-sectional data were collected from young adult (age 18–30 yrs) American Indians (AI) (n = 534) and Mexican Americans (MA) (n = 704) using a semi-structured diagnostic instrument.

Results:

Thirty percent (30%) of the sample reported ABD and 21% reported EABD. Those having had monthly ABD were more likely to be AI and have less education; those having had EABD were more likely to be AI, male, younger, have less education and lower economic status compared to participants without ABD. ABD/EABD was associated with higher impulsivity, a family history of AUD, and lower level of response to alcohol (ORs = 1.0–2.0), as well as with adult AUD (ORs = 3.7–48), other substance use disorders (ORs = 3.5–9), and conduct disorder/ antisocial personality disorder (ORs = 2.0–2.6), but not with anxiety/depression. Monthly EABD further increased the odds of AUD/SUD.

Conclusions:

Although binge drinking was more common in AI compared to MA, there were little effects of race in individual risk factor analyses. Monthly ABD and EABD were common among these AI/MA as adolescents, and, as with other ethnic groups, these drinking patterns resulted in highly significant increases in the odds of developing alcohol and other substance use disorders in young adulthood.
Rates of Dual Diagnosis in Child and Adolescent Psychiatric Inpatients: A Scoping Review
Authors: Suntharalingam Sinthuja , Johnson Dylan , Suresh Shalini , Thierrault François L. , De Sante Stephanie , Perinpanayagam Pawrnaa , Salamatmanesh Mina , Pajer Kathleen
Published: February 2021

Objectives:

Child and adolescent psychiatric (CAP) inpatient admissions have increased since 2009 and the clinical profile of these patients has become more complex. Unrecognized dual diagnosis, that is, comorbid substance use or substance use disorder (SUD) may contribute to this problem, but the prevalence of dual diagnosis in this population is inadequately understood. The goal of this scoping review was to summarize the range and content of research on this topic.

Methods:

MEDLINE, EMBASE, and PsychINFO databases were systematically searched for studies published from 2008 to 2019 containing information on rates of comorbid substance use or SUD in CAP inpatients.

Results:

A total of 23,326 abstracts were located. After removing duplicates, screening abstracts and full-text papers, and extracting data with full-text reviews, fourteen studies meeting our criteria remained. Rates of substance use or SUD ranged from 0.9% to 54.8%, differing on the basis of: (1) type of outcome; (2) type of data source; and (3) whether samples had a specific diagnostic focus or not. Rates of any type of SUD were reported in approximately 25% of samples from administrative databases, in 17.7% to 38.5% of chart reviews, and in 55% of studies with data from clinical research examinations. The highest rates of substance-specific substance use or SUD were for alcohol, cannabis, and nicotine.

Conclusions:

We located 14 studies, but methodologic heterogeneity precluded quantitative calculation of a single estimate for the prevalence of dual diagnosis. However, most of the rates suggest that this is an important problem in CAP inpatients, meriting further research. We suggest ways to improve future studies.
Increasing Parent Satisfaction With Discharge Planning
Authors: Balasundaram Malathi , Porter Melinda , Miller Stephanie , Sivakumar Dharshi , Fleming Arlene , McCallie Katherine
Published: February 2021

Background:

Neonatal intensive care unit (NICU) families are often overwhelmed by the discharge process. Their anxiety can inhibit learning and contribute to poor infant outcomes and increased healthcare utilization after discharge. Quality of the discharge teaching is the strongest predictor of discharge readiness, so NICUs must develop excellent discharge preparation programs.

Purpose:

This improvement project enhances NICU discharge preparedness by providing consistent, early discharge teaching using technology as a supplemental resource and raises parental satisfaction with the process.

Methods:

Neonatal intensive care unit staff and former NICU parents developed a task force to create technology-based discharge education content. The content was originally uploaded to an e-book and later transferred to the electronic health record inpatient portal. Families were able to view discharge teaching content at their own convenience and pace and review topics as needed with the NICU staff. Postdischarge follow-up phone calls provided insight into parental reaction to the new education format.

Results:

Parent satisfaction top-box scores, reflecting the highest rating in the “Prepared for Discharge” category of the patient satisfaction survey, improved from a baseline of 47% in 2017 to 70% in 2019. Overwhelmingly, 92% of families highly rated the tablet-based discharge teaching during postdischarge phone calls.

Implications for Practice:

A comprehensive, consistent, and early discharge program using technology can lead to more effective and efficient NICU discharge education and improved parent satisfaction.

Implications for Research:

Further studies are needed to generalize hospital-based inpatient portal teaching as an additional resource for parental education in the NICU.
Olecranon osteotomy vs. triceps-sparing for open reduction and internal fixation in treatment of distal humerus intercondylar fracture: a systematic review and meta-analysis
Authors: Lu Shuai , Zha Ye-Jun , Gong Mao-Qi , Chen Chen , Sun Wei-Tong , Hua Ke-Han , Jiang Xie-Yuan
Published: February 2021

Background

The open reduction and internal fixation (ORIF) was a standard treatment approach for fracture at distal humerus intercondylar, whereas the optimal way before ORIF remains inconclusive. We, therefore, performed a systematic review and meta-analysis to assess the efficacy and safety of olecranon osteotomy vs. triceps-sparing approach for patients with distal humerus intercondylar fracture.

Methods

The electronic searches were systematically performed in PubMed, EmBase, Cochrane library, and Chinese National Knowledge Infrastructure from initial inception till December 2019. The primary endpoint was the incidence of excellent/good elbow function, and the secondary endpoints included Mayo elbow performance score, duration of operation, blood loss, and complications.

Results

Nine studies involving a total of 637 patients were selected for meta-analysis. There were no significant differences between olecranon osteotomy and triceps-sparing approach for the incidence of excellent/good elbow function (odds ratio [OR]: 1.37; 95% confidence interval [CI]: 0.69–2.75; P = 0.371), Mayo elbow performance score (weight mean difference [WMD]: 0.17; 95% CI: −2.56 to 2.89; P = 0.904), duration of operation (WMD: 4.04; 95% CI: −28.60 to 36.69; P = 0.808), blood loss (WMD: 33.61; 95% CI: −18.35 to 85.58; P = 0.205), and complications (OR: 1.93; 95% CI: 0.49–7.60; P = 0.349). Sensitivity analyses found olecranon osteotomy might be associated with higher incidence of excellent/good elbow function, longer duration of operation, greater blood loss, and higher incidence of complications as compared with triceps-sparing approach.

Conclusions

This study found olecranon osteotomy did not yield additional benefit on the incidence of excellent/good elbow function, while the duration of operation, blood loss, and complications in patients treated with olecranon osteotomy might be inferior than triceps-sparing approach.
National outcomes and characteristics of patients admitted to Swedish intensive care units for COVID-19
Authors: Chew Michelle S. , Blixt Patrik Johansson , Åhman Rasmus , Engerström Lars , Andersson Henrik , Berggren Ritva Kiiski , Tegnell Anders , McIntyre Sarah
Published: February 2021

BACKGROUND

Mortality among patients admitted to intensive care units (ICUs) with COVID-19 is unclear due to variable follow-up periods. Few nationwide data are available to compare risk factors, treatment and outcomes of COVID-19 patients after ICU admission.

OBJECTIVE

To evaluate baseline characteristics, treatments and 30-day outcomes of patients admitted to Swedish ICUs with COVID-19.

DESIGN

Registry-based cohort study with prospective data collection.

SETTING

Admissions to Swedish ICUs from 6 March to 6 May 2020 with laboratory confirmed COVID-19 disease.

PARTICIPANTS

Adult patients admitted to Swedish ICUs.

EXPOSURES

Baseline characteristics, intensive care treatments and organ failures.

MAIN OUTCOMES AND MEASURES

The primary outcome was 30-day all-cause mortality. A multivariable model was used to determine the independent association between potential predictor variables and death.

RESULTS

We identified 1563 patients with complete 30-day follow-up. The 30-day all-cause mortality was 26.7%. Median age was 61 [52 to 69], Simplified Acute Physiology Score III (SAPS III) was 53 [46 to 59] and 62.5% had at least one comorbidity. Median PaO2/FiO2 on admission was 97.5 [75.0 to 140.6] mmHg, 74.7% suffered from moderate-to-severe acute respiratory failure. Age, male sex [adjusted odds ratio (aOR) 1.5 (1.1 to 2.2)], SAPS III score [aOR 1.3 (1.2 to 1.4)], severe respiratory failure [aOR 3.0 (2.0 to 4.7)], specific COVID-19 pharmacotherapy [aOR 1.4 (1.0 to 1.9)] and continuous renal replacement therapy [aOR 2.1 (1.5 to 3.0)] were associated with increased mortality. Except for chronic lung disease, the presence of comorbidities was not independently associated with mortality.

CONCLUSIONS

Thirty-day mortality rate in COVID-19 patients admitted to Swedish ICUs is generally lower than previously reported despite a severe degree of hypoxaemia on admission. Mortality was driven by age, baseline disease severity, the presence and degree of organ failure, rather than pre-existing comorbidities.

TRIAL REGISTRATION NO

NCT04462393
Prioritizing Cleft/Craniofacial Surgical Care after the COVID-19 Pandemic
Authors: Breugem Corstiaan , Smit Hans , Mark Hans , Davies Gareth , Schachner Peter , Collard Mechelle , Sell Debbie , Autelitano Luca , Rezzonico Angela , Mazzoleni Fabio , Novelli Giorgio , Mossey Peter , Persson Martin , Mehendale Felicity , Gaggl Alexander , van Gogh Christine , Zuurbier Petra , Reinart Siegmar , de Graaff Feike , Meazzini Costanza
Published: February 2021

Background:

It is anticipated that in due course the burden of emergency care due to COVID-19 infected patients will reduce sufficiently to permit elective surgical procedures to recommence. Prioritizing cleft/craniofacial surgery in the already overloaded medical system will then become an issue. The European Cleft Palate Craniofacial Association, together with the European Cleft and Craniofacial Initiative for Equality in Care, performed a brief survey to capture a current snapshot during a rapidly evolving pandemic.

Methods:

A questionnaire was sent to the 2242 participants who attended 1 of 3 recent international cleft/craniofacial meetings.

Results:

The respondents indicated that children with Robin sequence who were not responding to nonsurgical options should be treated as emergency cases. Over 70% of the respondents indicated that palate repair should be performed before the age of 15 months, an additional 22% stating the same be performed by 18 months. Placement of middle ear tubes, primary cleft lip surgery, alveolar bone grafting, and velopharyngeal insufficiency surgery also need prioritization. Children with craniofacial conditions such as craniosynostosis and increased intracranial pressure need immediate care, whilst children with craniosynostosis and associated obstructive sleep apnea syndrome or proptosis need surgical care within 3 months of the typical timing. Craniosynostosis without signs of increased intracranial pressure needs correction before the age of 18 months.

Conclusions:

This survey indicates several areas of cleft and craniofacial conditions that need prioritization, but also certain areas where intervention is less urgent. We acknowledge that there will be differences in the post COVID-19 response according to circumstances and policies in individual countries.