bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin signaling and antioxidant proteins in adipose tissue explants from dairy cows challenged with hydrogen peroxide are altered by supplementation of arginine or arginine plus methionine
Authors: Ma Nana , Liang Yusheng , Cardoso Fabiana F , Parys Claudia , Cardoso Felipe C , Shen Xiangzhen , Loor Juan J
Published: February 2022

Arginine (Arg) and methionine (Met) can elicit anti-inflammatory and antioxidant effects in animals. Unlike Met, however, it is unknown if the supply of Arg can impact key aspects of adipose tissue (AT) function in dairy cows. Since Met and Arg metabolism are linked through the synthesis of polyamines, it is also possible that they have a complementary effect on aspects of AT function during a stress challenge. In this experiment, subcutaneous AT was harvested from four lactating multiparous Holstein cows (~27.0 kg milk per day, body condition score 3.38 ± 0.23) and used for incubations (4 h) with the following: control medium with an “ideal” profile of essential amino acids (IPAA; CTR; Lys:Met 2.9:1), IPAA plus 100 μM H2O2 (HP), H2O2 plus greater Arg supply (HPARG; Lys:Arg 1:1), or H2O2 plus greater Arg and methionine (Met) supply (HPARGMET; Lys:Met 2.5:1 and Lys:Arg 1:1). Western blotting was used to measure abundance of 18 protein targets associated with insulin and AA signaling, nutrient transport, inflammation, and antioxidant response. Reverse transcription polymerase chain reaction (RT-PCR) was used to assess effects on genes associated with Arg metabolism. Among the protein targets measured, although abundance of phosphorylated (p) AKT serine/threonine kinase (P = 0.05) and p-mechanistic target of rapamycin (P = 0.04) were lowest in HP explants, this effect was attenuated in HPARG and especially HPARGMET compared with CTR. Compared with HP, incubation with HPARG led to upregulation of the AA transporter solute carrier family 1 member 3 (L-glutamate transporter; P = 0.03), the reactive oxygen species detoxification-related enzyme glutathione S-transferase mu 1 (GSTM1; P = 0.03), and fatty acid synthase (P = 0.05). Those effects were accompanied by greater abundance of solute carrier family 2 member 4 (insulin-induced glucose transporter) in explants incubated with HPARG and also HPARGMET (P = 0.04). In addition, compared with other treatments, the peak response in abundance of the intracellular energy sensor 5ʹ-prime-AMP-activated protein kinase was detected with HPARGMET (P = 0.003). There was no effect of Arg or Arg plus Met on the mRNA abundance of genes associated with Arg metabolism (ARG1, NOS2, AMD1, SMS, and SRM). Overall, supplementation of Arg alone or with Met partially alleviated the negative effects induced by H2O2. More systematic studies need to be conducted to explore the function of Arg supply with or without Met on AT function.
Simultaneous Analysis of Zolpidem, Four Hydroxyzolpidems and Two Zolpidem Carboxylic Acids in Postmortem Urine Using Liquid Chromatography--Tandem Mass Spectrometry
Authors: Yamaguchi Koji , Ohno Youkichi , Kanawaku Yoshimasa
Published: February 2022

Zolpidem (ZOL) is a short-acting hypnotic that is sometimes used in drug-facilitated crimes such as sexual assaults, robbery and homicides. Therefore, it is important to understand the metabolism of ZOL. This study quantified ZOL and its metabolites, including two carboxylic acids (zolpidem phenyl-4-carboxylic acid [M1] and 6-carboxylic acid [M2]) and four hydroxyzolpidems (4-(hydroxymethyl)phenyl zolpidem [M3], 6-hydroxymethyl zolpidem [M4], 7-hydroxyzolpidem [7OH] and 8-hydroxyzolpidem [8OH]) in postmortem urine using liquid chromatography--triple quadrupole mass spectrometry. The concentration of M1 was highest in all cases, followed by total 7OH in five of six samples. The concentrations of M2 and total M4 were relatively high. Most of M4 and 8OH were excreted as conjugates, whereas up to 55% of 7OH was excreted in its free form. Peaks corresponding to zolpidem dihydrodiol (ZHDH), dihydro(hydroxy)zolpidem cysteine adduct (DHZCys) and zolpidem cysteine adduct (ZCys) were also detected in all the urine samples. ZDHD was excreted as conjugates, whereas almost all DHZCys and ZCys were in their free form.
Drafting Investment Law: Patterns of Influence in the Regional Comprehensive Economic Partnership (RCEP)
Authors: Chaisse Julien , Elsig Manfred , Jusoh Sufian , Lugg Andrew
Published: February 2022

The investment chapter in the recently signed Regional Comprehensive Economic Partnership (RCEP) has the potential to affect investment decisions in the Asia-Pacific region and beyond. Yet, we know relatively little about the pathways through which countries determine the content of investment law in preferential trade agreements (PTAs). In this article, we use quantitative text analysis to test theoretically informed conjectures about the negotiation process. We focus on which of the signatories’ past agreements most influenced RCEP, and whether countries chose to draw more from treaty practice through their previous PTAs or bilateral investment treaties (BITs). Our analyses yield several noteworthy findings. First, we show that no single country dominated the negotiation process, instead RCEP represents an effort to reconcile overlapping agreements around a more common template. Second, contrary to the fears of some observers, we show that larger powers such as China and Japan did not overwhelmingly impact the agreement, instead portions were influenced by Association of Southeast Asian Nations agreements, the Comprehensive and Progressive Trans-Pacific Partnership, and others. Finally, we show that, on average, countries drew more from PTAs than BITs, but that they switch strategically between them to reuse language that they deem important for the development of investment law.
Incidence and Implications of Twin Gestational Surrogacy at Two Large U.S. Military Hospitals: A 10-Year Retrospective Cohort Study
Authors: Osmundsen Elizabeth B , Shaw-Williams Michelle M , Lutgendorf Monica A , Thagard Andrew S
Published: February 2022

Introduction

Individuals seeking a gestational surrogate often turn to U.S. military dependents due to favorable insurance coverage. Surrogate pregnancies, including multiple gestations, may be at increased risk for adverse outcomes. The objectives of this study were to determine the incidence of surrogacy in a twin population conceived by assisted reproductive technology (ART), assess the impact on the military healthcare system, and determine if there is an increased rate of complications in twin surrogacy pregnancies.

Materials and Methods

We conducted a 10-year retrospective cohort study of ART-conceived twin gestations at two military hospitals. Charts were reviewed for demographic data, surrogacy status, and obstetric complications. Number of prenatal visits and formal sonograms were tabulated for surrogate pregnancies. Complication rates were compared between groups using Fisher’s exact test.

Results

Over the 10-year period, 36 of the 249 pregnancies were identified as gestational surrogates, equating to a rate of 14.4%. Surrogate mothers were younger than non-surrogates (29.58 years vs. 33.11 years, P < .001). Care of surrogate pregnancies required a total of 306 prenatal visits and 98 formal ultrasounds. The incidence of gestational diabetes was higher among surrogates compared to other ART-conceived twin pregnancies at 27.8% vs. 12.2% (P < .05), while other complications did not significantly differ.

Conclusions

Approximately one in seven ART-conceived twin gestations were surrogacy pregnancies, requiring significant clinical resources. The incidence of gestational diabetes was higher among surrogate gestations.
CCD photometry of galactic open clusters - II. NGC 2243
Authors: Bonifazi A , Fusi Pecci F , Romeo G , Tosi M
Published: February 2022

New CCD photometry of 607 stars in the old open cluster NGC 2243 is presented. The resulting colour-magnitude diagram establishes the presence of a fraction of binary stars up to 30 per cent of the total population. Three additional features in the stellar distribution of the diagram are confirmed to be significant: a gap just below the top of the main sequence, six blue straggler candidates and an incipient red horizontal branch (curiously split into two almost parallel substructures).

The detailed comparison of the observational colour-magnitude diagram with the synthetic ones derived from various models of stellar evolution has allowed us to determine the main parameters of NGC 2243 and to infer interesting indications for the models themselves.

The cluster metallicity is Z = 0.003−0.006, the age is in the range 3−5 Gyr, the reddening E(B-V) = 0.06 − 0.08 and the distance modulus (m − M)0 = 12.7 − 12.8. The dependence of all these quantities on the adopted stellar evolution models is discussed, emphasizing in particular that the large difference in the derived ages depends on whether or not overshooting from convective cores is taken into account in the stellar interior. It is also worth noting that the gap is not predicted by overshooting models and that even the standard models do not reproduce it exactly.
Spectral variations in the broad-line region of NGC 6814
Authors: Sekiguchi K , Menzies J W
Published: February 2022

We present optical spectroscopy of the Seyfert galaxy NGC 6814 obtained at the SAAO over a two-year period from 1983 May to 1985 October. During this period, the spectrum changed from Seyfert 1 to more closely resemble that of Seyfert 1.8-1.9. The Hβ flux decreased by more than a factor of 2 within two months. The decrease in the broad Balmer emission line strength was coupled with a decrease in the X-ray output.
The evolutionary status of the peculiar variable star V348 Sagittarii
Authors: Pollacco D L , Tadhunter C N , Hill P W
Published: February 2022

We present new long-slit and narrow-band imaging observations of the nebula surrounding the peculiar variable star V348 Sgr. These show that the overall ionization state of the nebula is low, but the extent, structure and physical conditions are all typical of old planetary nebulae. An analysis of the abundances shows a pronounced helium enrichment, indicating that the system is highly evolved. Further clues to the past evolution of the system are provided by models which demonstrate that the ionization structure of the nebula is incompatible with ionization by a central star of temperature 20000 K and luminosity 3500 L⊙ as suspected for V348 Sgr. As there are no indications of a hotter star in the system, we are forced to accept that the star must have been hotter in the very recent past (nebular recombination time-scale is 120 < τrec < 2300 yr). Given all the observational facts, the evolutionary status of V348 Sgr is interpreted as a white dwarf that has suffered a last thermal pulse, reigniting a helium-burning shell. The lower limit for τrec is probably just consistent with the post-pulse crossing time required to reach the AGB, while the upper limit suggests the star may have already reached the AGB and is currently evolving to higher temperatures again. The present data do not allow us to differentiate between these two scenarios.
Non-Gaussian initial conditions in cosmological N-body simulations — I. Space-uncorrelated models
Authors: Messina Antonio , Moscardini Lauro , Lucchin Francesco , Matarrese Sabino
Published: February 2022

Results are reported on N-body simulations of the large-scale structure of the Universe starting from non-Gaussian, space-uncorrelated, initial conditions: specifically, we consider two hierarchical models and the lognormal statistics for the initial probability distribution. These models share two common properties: they fulfil the positive mass constraint (δM ≥ − 1) and they have positive skewness (〈δM3〉>0). The resulting distributions, both in space and velocity, are analysed by means of many statistical tests, and compared with an evolved reference Poisson model. The different starting conditions keep their effects after many expansion times as shown in particular by the cluster analysis and by the quadrupole statistics: the evolved nonGaussian distributions show the existence of elongated and/or flattened configurations in excess of the evolved Poisson model. The velocity field, analysed in terms of the cosmic Mach number, does not reveal relevant changes with respect to the initially Gaussian model. In general we find that the different models are better discriminated by their geometry (like the percolation curve and the amount of filamentariness) than by their clustering properties.
Mass decomposition of spiral galaxies from disc kinematics
Authors: Persic Massimo , Salucci Paolo
Published: February 2022

We devise a method for the disc/halo mass decomposition of the rotation curves of spiral galaxies that was outlined by us in a previous paper. Upon application to a larger sample of 58 spirals, we confirm our earlier results. In particular, we find that the disc-to-halo mass ratio at the optical radius, Mdisc/Mhalo, is a strong function of luminosity, Mdisc/Mhalo α LB2/3.
Models of elliptical galaxies: NGC 3379, 4261, 4278 and 4472
Authors: van der Marel Roeland P , Binney James , Davies Roger L
Published: February 2022

We investigate whether the observed kinematics and surface photometry for the elliptical E1/E2 galaxies NGC 3379, 4261, 4278 and 4472 can be modelled under the assumptions of (i) axisyrnmetry, (ii) a distribution function of the form f = f (E, Lz,) and (iii) constant mass-to-light ratio. The methods used are an extension of the work of Binney, Davies & Illingworth (Paper I).

Models satisfying the above assumptions fit the observations of all four galaxies remarkably well. For all galaxies, the rotation curves rule out isotropic velocity dispersion tensors. However, an excellent fit to the data can usually be obtained by including a measure velocity of anisotropy. Only in the case of NGC 4472 do the velocity dispersion profiles suggest that the radial and vertical dispersions are decoupled and thus the distribution function depends upon a third integral. In NGC 4278 the rotation velocity changes sign at R ⋍ 30 arcsec. Such behaviour is allowed by our models, but since it is associated with a large isophote twist, it is likely that it indicates a triaxial figure. We have developed a prolate model for NGC 4261 which accurately predicts the kinematics, although the comparison is limited to the rms line-of-sight velocities.

We investigate how the predicted kinematics vary as a galaxy’s isophotes are varied from ‘boxy’ to ‘discy’ in shape merely by deforming the bulge rather than introducing a thin disc. A discy model rotates faster on the major axis than the equivalent boxy system, but the effect is too small to account for Bender’s suggested correlation of (v/σ)* with disciness (which exhibits a large scatter). In boxy galaxies the rotation velocity falls more slowly away from the equatorial plane than in the equivalent discy galaxies.
Interstellar chemistry: hot-ion reactions
Authors: Brown Ronald D , Cragg Dinah M , Bettens Ryan P A
Published: February 2022

We have explored the possible significance on interstellar chemistry of translationally excited ions (‘hot ions’) produced in exothermic reactions, focusing on weaknesses that remain in existing gas-phase models of cloud chemistry. Particular instances are the lack of success in accounting for observed abundances of NH3, N2H+ and cyanopolyacetylenes.

When ‘hot-ion’ reactions are included in the ion-molecule model we obtain predicted abundances in cold clouds like TMC-1, agreeing very well with observations (to better than one order of magnitude) for virtually all smaller molecules included in the model. In particular, the discrepancies for NH3, N2H+ and cyanopolyacetylenes no longer arise. This occurs in the time regime 106.3–106.5 yr [note that this is not the time where the abundance of complex species go through a maximum (˜ 105.5 yr) but somewhat later] and not for very old clouds (age > 107.5 yr).

If we use rate constants for hydrogen atom abstraction reactions based on current estimates of their activation energies, then the ‘hot-ion’ reactions do not lead to a noticeable increase in the production of longer chain hydrocarbons. However, for smaller values of these activation energies (for example, those that might make the rate constants around 10−11 cm3 s−1), such hot-ion reactions could dramatically increase the efficiency of carbon-chain building by gas-phase reactions. Therefore, these hot-ion processes may ultimately prove to be the basis of the build-up of these larger species in cold clouds.

If the build-up of long chains is to be attributed to the effect of these hot-ion reactions, then the unexpectedly gradual decline in the abundances of CnH, with increasing n, is readily explained. It seems plausible to attribute the irregular variation in these abundances to the enhanced rate of ion-dipolar processes as compared with ion-non-polar reactions, although such influences are more pronounced at greater cloud ages (> 107.5 yr).
Asteroseismic inference of the near-core magnetic field strength in the main-sequence B star HD 43317
Authors: Lecoanet Daniel , Bowman Dominic M , Van Reeth Timothy
Published: February 2022

About 10 per cent of intermediate- and high-mass dwarf stars are observed to host a strong large-scale magnetic field at their surface, which is thought to be of fossil field origin. However, there are few inferences as to the magnetic field strength and geometry within the deep interiors of stars. Considering that massive stars harbour a convective core whilst on the main sequence, asteroseismology of gravity (g) modes is able to provide constraints on their core masses, yet it has so far not been used to probe the strength of their interior magnetic fields. Here, we use asteroseismology to constrain an upper limit for the magnetic field strength in the near-core region of the pulsating and magnetic B star HD 43317, based on the expected interaction of a magnetic field and its g modes. We find a magnetic field strength of order 5 × 105 G is sufficient to suppress high-radial order g modes and reproduce the observed frequency spectrum of HD 43317, which contains only high-frequency g modes. This result is the first inference of the magnetic field strength inside a main-sequence star.
Abatacept ameliorates both glandular and extraglandular involvements in patients with Sjögren’s syndrome associated with rheumatoid arthritis: Findings from an open-label, multicentre, 1-year, prospective study: The ROSE (Rheumatoid Arthritis with Orencia Trial Toward Sjögren’s Syndrome Endocrinopathy) and ROSE II trials
Authors: Tsuboi Hiroto , Toko Hirofumi , Honda Fumika , Abe Saori , Takahashi Hiroyuki , Yagishita Mizuki , Hagiwara Shinya , Ohyama Ayako , Kondo Yuya , Nakano Kazuhisa , Tanaka Yoshiya , Shimizu Toshimasa , Nakamura Hideki , Kawakami Atsushi , Fujieda Yuichiro , Atsumi Tatsuya , Suzuki Yasunori , Kawano Mitsuhiro , Nishina Naoshi , Kaneko Yuko , Takeuchi Tsutomu , Kobayashi Hitomi , Takei Masami , Ogasawara Michihiro , Tamura Naoto , Takasaki Yoshinari , Yokota Kazuhiro , Akiyama Yuji , Mimura Toshihide , Murakami Kosaku , Mimori Tsuneyo , Ohshima Shiro , Azuma Naoto , Sano Hajime , Nishiyama Susumu , Matsumoto Isao , Sumida Takayuki
Published: February 2022

Objective

To clarify the efficacy and safety of intravenous abatacept for glandular and extraglandular involvements in Sjögren’s syndrome (SS) associated with rheumatoid arthritis (RA).

Materials and methods

We performed an open-label, prospective, 1-year, observational multicenter study (ROSE and ROSE II trials). The primary endpoint was the remission rate as measured by SDAI at 52 weeks. The secondary endpoints included the changes in the Saxon’s test, Schirmer’s test, ESSDAI and ESSPRI. Adverse events and adherence rates were also analyzed.

Results

68 patients (36 in ROSE and 32 in ROSE II, all women) were enrolled. SDAI decreased significantly from 23.6 ± 13.2 at baseline to 9.9 ± 9.5 at 52 weeks. Patients with SDAI remission increased from 0 (0 weeks) to 19 patients (27.9%) at 52 weeks. Saliva volume increased significantly at 24 weeks. Tear volume increased significantly at 52 weeks. Both ESSDAI and ESSPRI were significantly decreased at 12 weeks, and these responses were maintained up to 52 weeks. The rate of adherence to abatacept over the 52-week period was 83.8%. Twenty-two adverse events occurred in 15 patients.

Conclusion

Abatacept ameliorated both glandular and extraglandular involvements, as well as the systemic disease activities and patient-reported outcomes based on composite measures, in SS associated with RA.
CMTR1 is recruited to transcription start sites and promotes ribosomal protein and histone gene expression in embryonic stem cells
Authors: Liang Shang , Silva Joana C , Suska Olga , Lukoszek Radoslaw , Almohammed Rajaei , Cowling Victoria H
Published: February 2022

CMTR1 (cap methyltransferase 1) catalyses methylation of the first transcribed nucleotide of RNAPII transcripts (N1 2′-O-Me), creating part of the mammalian RNA cap structure. In addition to marking RNA as self, N1 2′-O-Me has ill-defined roles in RNA expression and translation. Here, we investigated the gene specificity of CMTR1 and its impact on RNA expression in embryonic stem cells. Using chromatin immunoprecipitation, CMTR1 was found to bind to transcription start sites (TSS) correlating with RNAPII levels, predominantly binding at histone genes and ribosomal protein (RP) genes. Repression of CMTR1 expression resulted in repression of RNAPII binding at the TSS and repression of RNA expression, particularly of histone and RP genes. In correlation with regulation of histones and RP genes, CMTR1 repression resulted in repression of translation and induction of DNA replication stress and damage. Indicating a direct role for CMTR1 in transcription, addition of recombinant CMTR1 to purified nuclei increased transcription of the histone and RP genes. CMTR1 was found to be upregulated during neural differentiation and there was an enhanced requirement for CMTR1 for gene expression and proliferation during this process. We highlight the distinct roles of the cap methyltransferases RNMT and CMTR1 in target gene expression and differentiation.
Neurotoxicity following CD19/CD28ζ CAR T-cells in children and young adults with B-cell malignancies
Authors: Shalabi Haneen , Martin Staci , Yates Bonnie , Wolters Pamela L , Kaplan Claire , Smith Hannah , Sesi Christopher R , Jess Jennifer , Toledo-Tamula Mary Anne , Struemph Kari , Delbrook Cindy P , Khan Omar I , Mackall Crystal L , Lee Daniel W , Shah Nirali N
Published: February 2022

Background

Neurotoxicity is an established toxicity of CD19 CAR T-cell therapy; however, there is little information on neurotoxicity in children, adolescents, and young adults (CAYA) receiving CD19/CD28ζ CAR T-cells for B-cell malignancies.

Methods

We analyzed neurotoxicity of CD19/CD28ζ CAR T-cells in CAYA treated on a phase I study (NCT01593696). Assessments included daily inpatient monitoring, caregiver-based neuro-symptom checklist (NSC), exploratory neurocognitive assessments, clinically-indicated imaging, CSF analysis, and systematic cytokine profiling, outcomes of which were associated with cytokine release syndrome (CRS) and treatment response postinfusion. Patients with active CNS leukemia were included.

Results

Amongst 52 patients treated, 13 patients had active CNS leukemia at infusion. Neurotoxicity was seen in 11/52 (21.2%) patients, with an incidence of 29.7% (11/37) in patients with CRS. Neurotoxicity was associated with the presence and severity of CRS. Those with neurotoxicity had higher levels of peak serum IL-6, IFNγ, and IL-15. Additionally, CNS leukemia was effectively eradicated in most patients with CRS. Pilot neurocognitive testing demonstrated stable-to-improved neurocognitive test scores in most patients, albeit limited by small patient numbers. The NSC enabled caregiver input into the patient experience.

Conclusions

This is the first systematic analysis of neurotoxicity utilizing a CD19/CD28ζ CAR construct in CAYA, including in those with active CNS involvement. The experience demonstrates that the neurotoxicity profile was acceptable and reversible, with evidence of anti-leukemia response and CNS trafficking of CAR T-cells. Additionally, neurocognitive testing, while exploratory, provides an opportunity for future studies to employ systematic evaluations into neurotoxicity assessments and validation is needed in future studies.
Tumor-related molecular determinants of neurocognitive deficits in patients with diffuse glioma
Authors: van Kessel Emma , Berendsen Sharon , Baumfalk Anniek E , Venugopal Hema , Krijnen Eva A , Spliet Wim G M , van Hecke Wim , Giuliani Fabrizio , Seute Tatjana , van Zandvoort Martine J E , Snijders Tom J , Robe Pierre A
Published: February 2022

Background

Cognitive impairment is a common and debilitating symptom in patients with diffuse glioma, and is the result of multiple factors. We hypothesized that molecular tumor characteristics influence neurocognitive functioning (NCF), and aimed to identify tumor-related markers of NCF in diffuse glioma patients.

Methods

We examined the relation between cognitive performance (executive function, memory, and psychomotor speed) and intratumoral expression levels of molecular markers in treatment-naive patients with diffuse glioma. We performed a single-center study in a consecutive cohort, through a two-step design: (1) hypothesis-free differential expression and gene set enrichment analysis to identify candidate oncogenetic markers for cognitive impairment. Nineteen molecular markers of interest were derived from this set of genes, as well as from prior knowledge; (2) correlation of cognitive performance to intratumoral expression levels of these nineteen molecular markers, measured with immunohistochemistry.

Results

From 708 included patients with immunohistochemical data, we performed an in-depth analysis of neuropsychological data in 197, and differential expression analysis in 65 patients. After correcting for tumor volume and location, we found significant associations between expression levels of CD3 and IDH-1 and psychomotor speed; between IDH-1, ATRX, NLGN3, BDNF, CK2Beta, EAAT1, GAT-3, SRF, and memory performance; and between IDH-1, P-STAT5b, NLGN3, CK2Beta, and executive functioning. P-STAT5b, CD163, CD3, and Semaphorin-3A were independently associated after further correction for histopathological grade.

Conclusion

Molecular characteristics of glioma can be independent determinants of patients’ cognitive functioning. This suggests that besides tumor volume, location, and histological grade, variations in glioma biology influence cognitive performance through mechanisms that include perturbation of neuronal communication. These results pave the way towards targeted cognition improving therapies in neuro-oncology.
Raising the Bar: Improving Antimicrobial Resistance Detection by Clinical Laboratories by Ensuring Use of Current Breakpoints
Authors: Simner Patricia J , Rauch Carol A , Martin Isabella W , Sullivan Kaede V , Rhoads Daniel , Rolf Robin , She Rosemary , Souers Rhona J , Wojewoda Christina , Humphries Romney M
Published: February 2022

Background

Antimicrobial resistance (AMR) is a pressing global challenge detected by antimicrobial susceptibility testing (AST) performed by clinical laboratories. AST results are interpreted using clinical breakpoints, which are updated to enable accurate detection of new and emerging AMR. Laboratories that do not apply up-to-date breakpoints impede global efforts to address the AMR crisis, but the extent of this practice is poorly understood.

Methods

A total of 1490 clinical laboratories participating in a College of American Pathologists proficiency testing survey for bacterial cultures were queried to determine use of obsolete breakpoints.

Results

Between 37.9% and 70.5% of US laboratories reported using obsolete breakpoints for the antimicrobials that were queried. In contrast, only 17.7%–43.7% of international laboratories reported using obsolete breakpoints (P < .001 for all comparisons). Use of current breakpoints varied by AST system, with more laboratories reporting use of current breakpoints in the US if the system had achieved US Food and Drug Administration clearance with current breakpoints. Among laboratories that indicated use of obsolete breakpoints, 55.9% had no plans to update to current standards. The most common reason cited was manufacturer-related issues (51.3%) and lack of internal resources to perform analytical validation studies to make the update (23.4%). Thirteen percent of laboratories indicated they were unaware of breakpoint changes or the need to update breakpoints.

Conclusions

These data demonstrate a significant gap in the ability to detect AMR in the US, and to a lesser extent internationally. Improved application of current breakpoints by clinical laboratories will require combined action from regulatory agencies, laboratory accreditation groups, and device manufacturers.
Culture Yield in the Diagnosis of Native Vertebral Osteomyelitis: A Single Tertiary Center Retrospective Case Series With Literature Review
Authors: Weihe Rachel , Taghlabi Khaled , Lowrance Maren , Reeves Alan , Jackson Sean R , Burton Douglas C , El Atrouni Wissam
Published: February 2022

Background

Vertebral osteomyelitis is a serious condition that requires prompt diagnosis to avoid delays in proper management. There is no well-defined gold standard for diagnosis. We describe the current diagnostic approach at our institution, with a focus on the yield of image-guided vertebral biopsy.

Methods

We performed a single-centre 10-year retrospective case series, including adults with imaging suggestive of vertebral osteomyelitis/discitis, with either positive blood cultures, and/or a vertebral biopsy. We defined positive histopathology as our gold standard for test characteristic evaluation of biopsy cultures.

Results

Out of 694 patients identified, 221 met our inclusion criteria, and 173/221 (78.2%) patients underwent a spinal biopsy. Of those patients with biopsies, 113 (65%) had received antibiotics within 2 weeks preceding their evaluation. Six of 43 (13.9%) bone specimens were positive by culture, while 66/152 (43.4%) of disc specimens were culture positive. Forty-seven of 84 (55.9%) histopathology (bone or disc) specimens were diagnostic for osteomyelitis/discitis. The sensitivity of bone and disk culture were 30.0% and 56.0%, respectively, with specificities of 92.8% and 75.0%, respectively. Twenty-three (13.4%) patients had repeat biopsies, including 10 bone specimens and 14 disc specimens, and 11 (47.8%) specimens had histopathology performed which diagnosed an additional 3/23 patients (13% additional diagnostic yield).

Conclusions

Culture of percutaneous biopsy of disc resulted in the highest diagnostic yield. Histopathology added to the diagnostic yield in culture-negative specimens. Histopathologic evaluation of bone had better yield than bone culture. A repeat biopsy can add to the diagnostic yield.
The Impact of Infection Versus Colonization on Clostridioides difficile Environmental Contamination in Hospitalized Patients With Diarrhea
Authors: Warren Bobby G , Turner Nicholas A , Addison Rachel , Nelson Alicia , Barrett Aaron , Addison Bechtler , Graves Amanda , Smith Becky , Lewis Sarah S , Weber David J , Sickbert-Bennett Emily E , Anderson Deverick J
Published: February 2022

Background

Patients with Clostridioides difficile infections (CDIs) contaminate the healthcare environment; however, the relative contribution of contamination by colonized individuals is unknown. Current guidelines do not recommend the use of contact precautions for asymptomatic C difficile carriers. We evaluated C difficile environmental contamination in rooms housing adult inpatients with diarrhea based on C difficile status.

Methods

We performed a prospective cohort study of inpatient adults with diarrhea who underwent testing for CDI via polymerase chain reaction (PCR) and enzyme immunoassay (EIA). Patients were stratified into cohorts based on test result: infected (PCR+/EIA+), colonized (PCR+/EIA−), or negative/control (PCR−). Environmental microbiological samples were taken within 24 hours of C difficile testing and again for 2 successive days. Samples were obtained from the patient, bathroom, and care areas.

Results

We enrolled 94 patients between November 2019 and June 2021. Clostridioides difficile was recovered in 93 (38%) patient rooms: 44 (62%) infected patient rooms, 35 (43%) colonized patient rooms (P = .08 vs infected 38 patient rooms), and 14 (15%) negative patient rooms (P < .01 vs infected; P < .01 vs colonized). Clostridioides difficile was recovered in 40 (56%), 6 (9%), and 20 (28%) of bathrooms, care areas and patient areas in 40 infected patient rooms; 34 (41%), 1 (1%), and 4 (5%) samples in colonized patient rooms; and 12 (13%), 1 (1%), and 3 (3%) of samples in negative patient rooms, respectively.

Conclusions

Patients colonized with C difficile frequently contaminated the hospital environment. Our data support the use of contact precautions when entering rooms of patients colonized with C difficile, especially when entering the bathroom.
Identifying Enablers and Obstacles for Knowledge Management in a Police Organization: Case Study of Abu Dhabi Police
Authors: Al Dhanhani Mohamed Ali , Al Naqbi Shamma
Published: February 2022

Knowledge management and its effectiveness may be a potential catalyst for achieving project goals for optimum success and speed, or it may be a major cause of project failure when knowledge is inadequately managed. Recent scientific research has touched on the failure to facilitate the application of knowledge management mechanisms in all project phases due to the temporary status of projects as well as deficiencies in applying the concept of accountability among specialists. This paper reports on one element of a wider research project undertaken with Abu Dhabi Police to identify enablers and barriers to knowledge management in police projects. The research was qualitative in nature and focused directly on addressing mechanisms and methods of integrating management knowledge to improve project success and develop the capability of human capital in policing. The results of the research identified nine enablers that support successful knowledge management in policing projects: A policy for the management of knowledge, institutional leadership in support of open communication and motivation, highlighting the value of knowledge management, linking knowledge management content with job descriptions, establishment of specific channels for communicating with project stakeholders, adequate technology resources, communication systems to manage knowledge between teams in separate locations, enable social interaction to facilitate the process of knowledge management in daily operations, and apply processes for assessment and measurement in the use of social networks for knowledge management.
‘Invisible’ orthodontics by polymeric ‘clear’ aligners molded on 3D-printed personalized dental models
Authors: Yu Xiaoye , Li Guanghui , Zheng Yikan , Gao Jingming , Fu Ye , Wang Qunsong , Huang Lei , Pan Xiaogang , Ding Jiandong
Published: February 2022

The malalignment of teeth is treated classically by metal braces with alloy wires, which has an unfavorable influence on the patients appearance during the treatment. With the development of digitization, computer simulation and three-dimensional (3D) printing technology, herein, a modern treatment was tried using clear polymeric aligners, which were fabricated by molding polyurethane films via thermoforming on the 3D-printed personalized dental models. The key parameters of photocurable 3D printing of dental models and the mechanical properties of the clear aligner film material were examined. The precision of a 3D-printed dental model mainly relied on characteristics of photocurable resin, the resolution of light source and the exposure condition, which determined the eventual shape of the molded clear aligner and thus the orthodontic treatment efficacy. The biocompatibility of the polyurethane film material was confirmed through cytotoxicity and hemolysis tests in vitro. Following a series of 3D-printed personalized dental models and finite element analysis to predict and plan the fabrication and orthodontic processes, corresponding clear aligners were fabricated and applied in animal experiments, which proved the efficacy and biocompatibility in vivo. Clinical treatments of 120 orthodontic cases were finally carried out with success, which highlights the advantage of the clear aligners as an esthetic, compatible and efficient appliance.
The False Dichotomy of Sex and Religion in America
Authors: Burke Kelsy
Published: February 2022

Religion and sexuality are polysemic categories. While conservative religion often fights against progressive sexual politics in contemporary America, this “usual story” is fractured and destabilized by people navigating the relationship between religion and sexuality as complex social creatures, not pundits or caricatures. Drawing from interdisciplinary scholarship, I examine salient issues of sexual politics—including abortion and reproductive rights, LGBT rights, and pornography—to show how religious actors have been on both sides of these debates. Because of this polysemic complexity, scholars of religion must not only tend to the dynamic interaction between religion and other categories, we must also recognize and study the diversity within the categories themselves.
Perspectives on Training and Working in the VHA: Implications for Primary Care Physician Recruitment and Retention
Authors: Moldestad Megan , Sayre George , Rinne Seppo , Kaboli Peter J. , Reddy Ashok , Sanders Karen M. , Mao Johnny , Henrikson Nora B. , Sterling Ryan , Nelson Karin M. , Wong Edwin S.
Published: February 2022

Purpose

The primary care physician shortage in the United States presents significant challenges for health systems seeking to maintain a sufficient primary care workforce. Perspectives on training or working in primary care in the Veterans Health Administration (VHA) may yield insights into strategic recruitment to make the VHA and other health systems more attractive to primary care physicians. The authors sought to understand the experiences of resident and staff physicians with limited tenure within VHA primary care to identify factors to guide health systems in improving recruitment and retention.

Method

This qualitative exploratory study was conducted from June 2018 to October 2019 with 24 internal medicine residents and 30 staff physicians in VHA primary care. Heterogeneity was ensured by sampling for geographical region, rurality, and gender within each cohort. The authors conducted semistructured interviews to ascertain perspectives on training and employment preferences at VHA and non-VHA sites. Combined content analysis was used to generate findings.

Results

The authors identified 4 key themes, centered around shared values and the VHA’s mission-driven culture: the VHA “community” was perceived as unique and a major contributor to job satisfaction; facility-level leadership support was important to perceptions of workplace culture around harassment; the VHA primary care delivery model allowed residents and staff physicians to get patients needed care but did not always live up to its potential; and VHA employment was better than expected, but the process of getting hired was a challenge.

Conclusions

Mission and workplace culture may serve important roles in the desirability of health systems for prospective physicians and the job satisfaction of physicians who work in these systems. Physician recruitment efforts based on these attributes may yield the most success in maintaining a sufficient physician workforce.
Implementation of a Case Investigation and Contact Tracing Program at an Academic Medical Center in New York City
Authors: Bruno Denise M. , Afable Aimee , Pervil-Ulysse Mona , Putman Jeffrey S. , Demissie Kitaw
Published: February 2022

Problem

In the spring of 2020, New York City was an epicenter of COVID-19 infections, hospitalizations, and mortality. One of the hardest hit areas in New York City was central Brooklyn, where State University of New York (SUNY) Downstate is located. As the severity of the initial wave of the COVID-19 pandemic waned in New York City, SUNY Downstate Health Sciences University planned to institute COVID-19 surveillance on campus to limit its spread among employees and students.

Approach

In collaboration with university leadership and students across schools, the SUNY Downstate Contact Tracing Corps was established in July 2020. Using guidance from the Centers for Disease Control and Prevention and the New York State Department of Health, protocols for case and contact investigations, including scripts, were developed. Students were recruited and trained in remote and confidential case and contact investigations.

Outcomes

From August 1, 2020, to March 23, 2021, there were 185 COVID-19 cases referred to the contact tracing program; of these, 180 were successfully investigated and isolated (97%). Case investigations identified 111 Downstate close contacts; 105 were investigated and quarantined (94.5%). There were 122 exposure-only investigations referred to the program, and 121 were successfully investigated and quarantined (99%).

Next Steps

The SUNY Downstate Contact Tracing Corps transitioned to a core group of tracers in January 2021 and has been maintained at 4 to 6 tracers since that time. With the emergence of COVID-19 variants, the threat of new variants, and variable COVID-19 vaccination rates across Brooklyn, Downstate employees and students remain vulnerable to COVID-19 transmission. Given this, the SUNY Downstate Contact Tracing Corps will continue to conduct case and contact investigations.
Cannabidiol Effect on Anxiety Symptoms and Stress Response in Individuals With Cocaine Use Disorder: Exploratory Results From a Randomized Controlled Trial
Authors: Mongeau-Pérusse Violaine , Rizkallah Elie , Morissette Florence , Brissette Suzanne , Bruneau Julie , Dubreucq Simon , Gazil Guillaume , Trépanier Annie , Jutras-Aswad Didier
Published: February 2022

Objectives

Individuals with a cocaine use disorder (CUD) are more likely to present anxiety, which in turn negatively impacts substance use outcomes. Some evidence suggests that cannabidiol (CBD) presents anxiolytic properties and could be a treatment for substance use disorders. This study explores CBD’s effect on stress biomarker (cortisol) and anxiety symptoms in people with CUD.

Methods

Exploratory analyses were conducted using data from a randomized, double-blind, placebo-controlled trial evaluating CBD’s efficacy to treat CUD. We randomized 78 individuals with CUD into receiving a daily oral dose up to 800 mg CBD (n = 40) or placebo (n = 38). The trial was divided into 2 phases: an inpatient detoxification lasting 10 days and an outpatient follow-up lasting 12 weeks. Anxiety symptoms and stress response were assessed using a visual analog scale, the Beck Anxiety Inventory, and cortisol levels at multiple time points throughout the study. We also measured anxiety after a stressful and a cocaine-cue scenarios. We used generalized estimating equations models and multiple linear regression to assess CBD’s effects on anxiety and cortisol levels.

Results

Both treatment groups had similar mean anxiety scores according to the Beck Anxiety Inventory (P = 0.27) and the visual analog scale (P = 0.18). CBD did not decrease anxiety after a stressful (P = 0.14) and a cocaine (P = 0.885) scenarios compared with placebo. No statistically significant group difference was found in cortisol levels (P = 0.76).

Conclusions

We found no evidence for 800 mg of CBD to be more efficacious than placebo for modulating anxiety symptoms and cortisol levels in individuals with CUD.
Transosseous Suture With an All-FiberWire Technique in Patellar Fracture Fixation
Authors: Wongthongsalee Ponrachai , Chobpenthai Thanapon
Published: February 2022

Background:

Patellar fractures account for 0.5% to 1.5% of all bone fractures. Tension band wiring with heavy gauge steel wire and K-wires is traditionally procedure for treating patellar fractures. However, this method is associated with implant-related complications. Present study aimed to evaluate functional clinical outcomes of patellar fracture fixation with transosseous suture using an all-FiberWire technique.

Methods:

This was a retrospective study involving 16 patellar fractures patients were repaired by open reduction and internal fixation with FiberWire using a 3-transosseous tunnel technique. The functional outcomes were evaluated with Tegner-Lysholm and Bostman scoring. We also evaluated clinical and radiologic outcomes.

Results:

The mean time to bony union was 8.87±1.54 weeks (range, 7 to 12 wk). The mean Bostman score at final follow-up was 27.13±2.5 (range, 21 to 30), and mean Lysholm score at final follow-up was 90.69±5.75 (range, 83 to 100). Fractures healed in all patients, with no fixation failures. Minor loss of reduction (<2 mm) were observed in 3 patients (18.75%). No patient has reoperation. One patient developed knee stiffness, with an infected hematoma 10 weeks postoperatively. None of patients developed anterior knee pain postoperatively. Two patients (12.5%) developed mild localized pain from prominent suture knots. There were no significant implant-related complications and no repeat surgery was necessary.

Conclusions:

The use of nonmetallic sutures with an all-FiberWire technique in patellar fracture fixation avoids implant-associated complications and possibility of a second surgery to remove metal implants. Nonmetallic high-resistance FiberWire matches traditional metallic fixation, with a reduced risk of postoperative complications.

Level of Evidence:

Level IV (therapeutic).