bluuebunny/crossref_metadata_2025 huggingface dataset:
Resting-State Functional Connectivity of the Dorsal and Ventral Striatum, Impulsivity, and Severity of Use in Recently Abstinent Cocaine-Dependent Individuals
Authors: Dong Xue , Zhornitsky Simon , Wang Wuyi , Le Thang M , Chen Yu , Chaudhary Shefali , Li Chiang-Shan R , Zhang Sheng
Published: March 2022

Background

Previous studies have focused on both ventral striatum (VS) and dorsal striatum (DS) in characterizing dopaminergic deficits in addiction. Animal studies suggest VS and DS dysfunction each in association with impulsive and compulsive cocaine use during early and later stages of addiction. However, few human studies have aimed to distinguish the roles of VS and DS dysfunction in cocaine misuse.

Methods

We examined VS and DS resting-state functional connectivity (rsFC) of 122 recently abstinent cocaine-dependent individuals (CDs) and 122 healthy controls (HCs) in 2 separate cohorts. We followed published routines in imaging data analyses and evaluated the results at a corrected threshold with age, sex, years of drinking, and smoking accounted for.

Results

CDs relative to HCs showed higher VS rsFC with the left inferior frontal cortex (IFC), lower VS rsFC with the hippocampus, and higher DS rsFC with the left orbitofrontal cortex. Region-of-interest analyses confirmed the findings in the 2 cohorts examined separately. In CDs, VS-left IFC and VS-hippocampus connectivity was positively and negatively correlated with average monthly cocaine use in the prior year, respectively. In the second cohort where participants were assessed with the Barratt Impulsivity Scale (BIS-11), VS-left IFC and VS-hippocampus connectivity was also positively and negatively correlated with BIS-11 scores in CDs. In contrast, DS-orbitofrontal cortex connectivity did not relate significantly to cocaine use metrics or BIS-11 scores.

Conclusion

These findings associate VS rsFC with impulsivity and the severity of recent cocaine use. How DS connectivity partakes in cocaine misuse remains to be investigated.
Transitional Justice in Public and Private: Truth Commission Narratives in Greensboro
Authors: Fox Nicole , Cunningham David
Published: March 2022

In 1979, during an anti-racism march in the city in Greensboro, North Carolina, KKK and Nazi Party members opened fire on demonstrators, killing five and wounding eight. On the cusp of the 25th anniversary of these killings, efforts by community members culminated in the convening of the first Truth and Reconciliation Commission (GTRC) in the US. Drawing on a unique collection of public testimonies and private interviews with GTRC staff, we use a novel relational approach to array and compare discursive accounts offered in these distinct settings. We find that narratives offered in private were more varied, yet also cohesive in locating blame in social actors. Public testimony, in contrast, was more consolidated and singular, placing the majority of culpability on social structures. Based on these significant distinctions, we draw out implications for future research and policy around transitional justice initiatives.
Group B Streptococcus (GBS) Invasive Infections in Women of Childbearing Age, France, 2012–2020: GBS CC-17 Hypervirulence in Intrapartum Infections
Authors: Plainvert Céline , de Saint Salvy-Tabet Yasmina , Dmytruk Nicolas , Frigo Amandine , Poyart Claire , Tazi Asmaa
Published: March 2022

Group B Streptococcus (GBS) is the leading cause of neonatal infections and an important pathogen in pregnancy. However, the features of pregnancy-associated infections are poorly reported. We analyzed 336 cases of GBS invasive infections in women aged 18–50 years, including 242 (72.0%) pregnancy-associated infections. In pregnancy, most cases were intra-amniotic infections (55.8%), occurred preterm (61.3%), and were associated with obstetrical and neonatal complications (81.7%). The GBS clone CC-17 (18.8% of the cases) was overrepresented intrapartum (35.2%; odds ratio, 5.1 [95% confidence interval, 1.6–19.3]). This work highlights the burden of GBS and of the CC-17 clone infections during pregnancy.
Aspergillus Utilizes Extracellular Heme as an Iron Source During Invasive Pneumonia, Driving Infection Severity
Authors: Michels Kathryn , Solomon Angelica L , Scindia Yogesh , Sordo Vieira Luis , Goddard Yana , Whitten Spencer , Vaulont Sophie , Burdick Marie D , Atkinson Carl , Laubenbacher Reinhard , Mehrad Borna
Published: March 2022

Background

Depriving microbes of iron is critical to host defense. Hemeproteins, the largest source of iron within vertebrates, are abundant in infected tissues in aspergillosis due to hemorrhage, but Aspergillus species have been thought to lack heme import mechanisms. We hypothesized that heme provides iron to Aspergillus during invasive pneumonia, thereby worsening the outcomes of the infection.

Methods

We assessed the effect of heme on fungal phenotype in various in vitro conditions and in a neutropenic mouse model of invasive pulmonary aspergillosis.

Results

In mice with neutropenic invasive aspergillosis, we found a progressive and compartmentalized increase in lung heme iron. Fungal cells cultured under low iron conditions took up heme, resulting in increased fungal iron content, resolution of iron starvation, increased conidiation, and enhanced resistance to oxidative stress. Intrapulmonary administration of heme to mice with neutropenic invasive aspergillosis resulted in markedly increased lung fungal burden, lung injury, and mortality, whereas administration of heme analogs or heme with killed Aspergillus did not. Finally, infection caused by fungal germlings cultured in the presence of heme resulted in a more severe infection.

Conclusions

Invasive aspergillosis induces local hemolysis in infected tissues, thereby supplying heme iron to the fungus, leading to lethal infection.
The Cold War Origins of Global IR. The Rockefeller Foundation and Realism in Latin America
Authors: Morcillo Laiz Álvaro
Published: February 2022

The literature on global international relations (IR) has argued that the discipline develops in the footsteps of world politics, but no sustained attention has been given to more immediate causes such as the funders that pay for IR teaching and scholarship. These donor–recipient relations have only attracted the attention of authors interested in cultural hegemony and those contributing to the recent historiography of IR. Among the latter, some have studied how during the Cold War the Rockefeller Foundation attempted to buttress classical realism in the United States and Western Europe. This article connects and moves forward IR historiography and the global IR literature by shedding light on philanthropic foundations’ attempts to further a specific IR theory—classical realism—and area studies in the global south. The article argues that world politics influenced global IR, but this influence was mediated by highly contingent events. Even a proximate cause like science patronage, let alone “world politics,” is not a sufficient cause capable of determining IR theories and disciplinary boundaries. Donors may achieve some impact but only under specific circumstances such as the ones explored here, that is, the donor is a unitary actor determined to advance its agenda by resorting to conditionality, alternative donors and funding are scarce, the discipline is either poorly or not institutionalized, and the recipient perceives the donor's preferences as legitimate. The article uses previously untapped, fine-grained, primary sources to unravel philanthropy's impact on Latin America's first IR center. Because science patronage is exposed to many sources of indeterminacy and to contingency, donors cannot determine scholarship, which makes cultural hegemony all but impossible. Still, IR scholars need to study their patrons to understand their discipline, in and outside Europe and the United States.
Usability of a perioperative medication-related clinical decision support software application: a randomized controlled trial
Authors: Nanji Karen C , Garabedian Pamela M , Langlieb Marin E , Rui Angela , Tabayoyong Leo L , Sampson Michael , Deng Hao , Boxwala Aziz , Minehart Rebecca D , Bates David W
Published: March 2022

Objective

We developed a comprehensive, medication-related clinical decision support (CDS) software prototype for use in the operating room. The purpose of this study was to compare the usability of the CDS software to the current standard electronic health record (EHR) medication administration and documentation workflow.

Materials and Methods

The primary outcome was the time taken to complete all simulation tasks. Secondary outcomes were the total number of mouse clicks and the total distance traveled on the screen in pixels. Forty participants were randomized and assigned to complete 7 simulation tasks in 1 of 2 groups: (1) the CDS group (n = 20), who completed tasks using the CDS and (2) the Control group (n = 20), who completed tasks using the standard medication workflow with retrospective manual documentation in our anesthesia information management system. Blinding was not possible. We video- and audio-recorded the participants to capture quantitative data (time on task, mouse clicks, and pixels traveled on the screen) and qualitative data (think-aloud verbalization).

Results

The CDS group mean total task time (402.2 ± 85.9 s) was less than the Control group (509.8 ± 103.6 s), with a mean difference of 107.6 s (95% confidence interval [CI], 60.5–179.5 s, P < .001). The CDS group used fewer mouse clicks (26.4 ± 4.5 clicks) than the Control group (56.0 ± 15.0 clicks) with a mean difference of 29.6 clicks (95% CI, 23.2–37.6, P < .001). The CDS group had fewer pixels traveled on the computer monitor (59.5 ± 20.0 thousand pixels) than the Control group (109.3 ± 40.8 thousand pixels) with a mean difference of 49.8 thousand pixels (95% CI, 33.0–73.7, P < .001).

Conclusions

The perioperative medication-related CDS software prototype substantially outperformed standard EHR workflow by decreasing task time and improving efficiency and quality of care in a simulation setting.
Direct effect of lipopolysaccharide and histamine on permeability of the rumen epithelium of steers ex vivo
Authors: Gao Shengtao , Zhula Alateng , Liu Wenhui , Lu Zhongyan , Shen Zanming , Penner Gregory B , Ma Lu , Bu Dengpan
Published: February 2022

Disruption of the ruminal epithelium barrier occurs during subacute ruminal acidosis due to low pH, hyper-osmolality, and increased concentrations of lipopolysaccharide and histamine in ruminal fluid. However, the individual roles of lipopolysaccharide and histamine in the process of ruminal epithelium barriers disruption are not clear. The objective of the present investigation was to evaluate the direct effect of lipopolysaccharide and histamine on the barrier function of the ruminal epithelium. Compared with control (CON), histamine (HIS, 20 μM) increased the short-circuit current (Isc; 88.2%, P < 0.01), transepithelial conductance (Gt; 29.7%, P = 0.056), and the permeability of fluorescein 5(6)-isothiocyanate (FITC) (1.04-fold, P < 0.01) of ruminal epithelium. The apparent permeability of LPS was 1.81-fold higher than HIS (P < 0.01). The mRNA abundance of OCLN in ruminal epithelium was decreased by HIS (1.1-fold, P = 0.047). The results of the present study suggested that mucosal histamine plays a direct role in the disruption of ruminal epithelium barrier function, whereas lipopolysaccharide (at a pH of 7.4) has no effect on the permeability of rumen tissues ex vivo.
Bisexual Attract-and-Kill: A Novel Component of Resistance Management for Transgenic Cotton in Australia
Authors: Gregg Peter C , Del Socorro Alice P , Wilson Sarah , Knight Kristen M , Binns Matthew R , Armytage Philip
Published: February 2022

In Australia, destruction of overwintering pupae of Helicoverpa armigera (Hübner) and Helicoverpa punctigera (Wallengren) (Lepidoptera: Noctuidae) has been a key component of mandatory resistance management schemes to constrain development of resistance to Bt toxins in transgenic cotton. This has been accomplished by tillage (‘pupae busting’), but it is expensive and can interfere with farming operations. Bisexual attract-and-kill technology based on plant volatile formulations offers a potential alternative in some circumstances. We discuss strategies for using such products and describe two trials in which three applications of an attract-and-kill formulation substantially reduced the numbers of Helicoverpa spp. moths and the numbers of potentially overwintering eggs they laid. One trial tested a curative strategy in which the last generation of moths emerging from transgenic cotton was targeted. The other tested a preventive strategy which aimed to reduce the numbers of eggs in the last generation. The preventive strategy reduced egg numbers by about 90% and is now included as an optional alternative to pupae busting in resistance management strategies for Australian cotton. It is limited to fields which have not been defoliated prior to 31 March and was developed to be used primarily in southern New South Wales. In the 2020–2021 cotton season, it was adopted on approximately 60% of the eligible cotton area. We describe the process whereby the strategy was developed in collaboration with the transgenic technology provider, supported by the cotton industry, and approved by the regulatory authority.
Narrative review of local prostate and metastasis-directed radiotherapy in the treatment of metastatic prostate cancer
Authors: Terada Naoki , Aizawa Rihito , Nihei Keiji , Shiota Masaki , Kojima Takahiro , Kimura Takahiro , Inoue Takahiro , Kitamura Hiroshi , Sugimoto Mikio , Nishiyama Hiroyuki , Mizowaki Takashi , Kamoto Toshiyuki
Published: March 2022

The role of local treatment in patients with de novo metastatic prostate cancer is controversial. In population-based retrospective studies, metastatic prostate cancer patients who received local treatment with prostate radiotherapy showed a better prognosis than those who did not. In addition, several prospective randomized studies demonstrated that prostate radiotherapy achieves a survival benefit for patients with oligo-metastasis. Moreover, the efficacy of metastasis-directed radiotherapy was evaluated, revealing a potential benefit for patients with oligo-metastasis. Importantly, these radiotherapies may reduce the occurrence of symptomatic local events. In this review, the rationale, efficacy and future perspectives for local prostate and metastasis-directed radiotherapy in the treatment of metastatic prostate cancer were described and summarized.
Mining for allelic gold: finding genetic variation in photosynthetic traits in crops and wild relatives
Authors: Sharwood Robert E , Quick W Paul , Sargent Demi , Estavillo Gonzalo M , Silva-Perez Viridiana , Furbank Robert T
Published: March 2022

Improvement of photosynthetic traits in crops to increase yield potential and crop resilience has recently become a major breeding target. Synthetic biology and genetic technologies offer unparalleled opportunities to create new genetics for photosynthetic traits driven by existing fundamental knowledge. However, large ‘gene bank’ collections of germplasm comprising historical collections of crop species and their relatives offer a wealth of opportunities to find novel allelic variation in the key steps of photosynthesis, to identify new mechanisms and to accelerate genetic progress in crop breeding programmes. Here we explore the available genetic resources in food and fibre crops, strategies to selectively target allelic variation in genes underpinning key photosynthetic processes, and deployment of this variation via gene editing in modern elite material.
Spatiokinematic models of five nova remnants: correlations between nova shell axial ratio, expansion velocity, and speed class
Authors: Santamaría E , Guerrero M A , Zavala S , Ramos-Larios G , Toalá J A , Sabin L
Published: March 2022

We present long-slit intermediate-dispersion spectroscopic observations and narrow-band direct imaging of four classical nova shells, namely T Aur, HR Del, DQ Her, and QU Vul, and the nova-like source CK Vul. These are used to construct models of their nebular remnants using the morphokinematic modelling tool shape to reveal their 3D shape. All these nova remnants but CK Vul can be described by prolate ellipsoidal shells with different eccentricity degree, from the spherical QU Vul to the highly elongated shell with an equatorial component HR Del. On the other hand, CK Vul shows a more complex structure, with two pairs of nested bipolar lobes. The spatiokinematic properties of the ellipsoidal nova shells derived from our models include their true axial ratios. This parameter is expected to correlate with the expansion velocity and decline time t3 (i.e. their speed class) of a nova as the result the interaction of the ejecta with the circumstellar material and rotation speed and magnetic field of the white dwarf. We have compared these three parameters including data available in the literature for another two nova shells, V533 Her and FH Ser. There is an anticorrelation between the expansion velocity and the axial ratio and decline time t3 for nova remnants with ellipsoidal morphology, and a correlation between their axial ratios and decline times t3, confirming theoretical expectations that the fastest expanding novae have the smallest axial ratios. We note that the high expansion velocity of the nova shell HR Del of 615 km s−1 is inconsistent with its long decline time t3 of 250 d.
Planet population synthesis: the role of stellar encounters
Authors: Ndugu N , Abedigamba O P , Andama G
Published: March 2022

Depending on the stellar densities, protoplanetary discs in stellar clusters undergo: background heating; disc truncation-driven by stellar encounter; and photoevaporation. Disc truncation leads to reduced characteristic sizes and disc masses that eventually halt gas giant planet formation. We investigate how disc truncation impacts planet formation via pebble-based core accretion paradigm, where pebble sizes were derived from the full grain-size distribution within the disc lifetimes. We make the best-case assumption of one embryo and one stellar encounter per disc. Using planet population synthesis techniques, we find that disc truncation shifts the disc mass distributions to the lower margins. This consequently lowered the gas giant occurrence rates. Despite the reduced gas giant formation rates in clustered discs, the encounter models mostly show as in the isolated field; the cold Jupiters are more frequent than the hot Jupiters, consistent with observation. Moreover, the ratio of hot to cold Jupiters depend on the periastron distribution of the perturbers with linear distribution in periastron ratio showing enhanced hot to cold Jupiters ratio in comparison to the remaining models. Our results are valid in the best-case scenario corresponding to our assumptions of: only one disc encounter with a perturber, ambient background heating, and less rampant photoevaporation. It is not known exactly of how much gas giant planet formation would be affected should disc encounter, background heating, and photoevaporation act in a concert. Thus, our study will hopefully serve as motivation for quantitative investigations of the detailed impact of stellar cluster environments on planet formations.
Predicting exon criticality from protein sequence
Authors: Desai Jigar , Francis Christopher , Longo Kenneth , Hoss Andrew
Published: February 2022

Alternative splicing is frequently involved in the diversification of protein function and can also be modulated for therapeutic purposes. Here we develop a predictive model, called Exon ByPASS (predicting Exon skipping Based on Protein amino acid SequenceS), to assess the criticality of exon inclusion based solely on information contained in the amino acid sequence upstream and downstream of the exon junctions. By focusing on protein sequence, Exon ByPASS predicts exon skipping independent of tissue and species in the absence of any intronic information. We validate model predictions using transcriptomic and proteomic data and show that the model can capture exon skipping in different tissues and species. Additionally, we reveal potential therapeutic opportunities by predicting synthetically skippable exons and neo-junctions arising in cancer cells.
An EZH2 blocker sensitizes histone mutated diffuse midline glioma to cholesterol metabolism inhibitors through an off-target effect
Authors: Rahal Farah , Capdevielle Caroline , Rousseau Benoit , Izotte Julien , Dupuy Jean-William , Cappellen David , Chotard Guillaume , Ménard Mélissa , Charpentier Justine , Jecko Vincent , Caumont Charline , Gimbert Edouard , Grosset Christophe F , Hagedorn Martin
Published: March 2022

Background

Diffuse Midline Glioma, H3K27M-mutant (DMG) is a rare, highly aggressive pediatric tumor affecting the brainstem, and is one of the deadliest cancers. Currently available treatment options such as chemotherapy and radiotherapy do only modestly prolong survival. In this pathology, H3K27 mutations deregulate Polycomb Repressive Complex 2 (PRC2), including enzymatic activity of EZH2, which is therefore under investigation as a therapeutic target.

Methods

We used a chemical EZH2 inhibitor, GSK126, small interfering RNAs, and a CRISPR/Cas9 knockout approaches in a series of DMG tumor cell lines to investigate metabolic treatment responses by proteomic analysis. A combination strategy was elaborated and studied in primary and established DMG cells, spheroid 3D cultures, and in vivo in a chick chorio-allantoic membrane DMG assay and an orthotopic intracranial DMG mouse model.

Results

GSK126 shows significant (P < .05–.001) inhibitory effects in in vitro cell proliferation assays and induces apoptosis. Chemical targeting of EZH2 induced expression of proteins implicated in cholesterol metabolism. Low-dose GSK126 treatment together with statins revealed strong growth inhibition in combinatorial treatments, but not in single treatments, both in DMG cells in vitro, in DMG spheroid cultures, and in chick and mouse in vivo models (P < .05). All statistical tests were two-sided.

Conclusions

Our results reveal an unexpected GSK126-inducible sensitivity to cholesterol biosynthesis inhibitors in highly aggressive pediatric glioma that warrants further evaluation as treatment strategy. This combinatorial therapy should have few side effects because of the low doses used to achieve significant anti-tumor activity.
Diagnostic performance of DSC perfusion MRI to distinguish tumor progression and treatment-related changes: a systematic review and meta-analysis
Authors: Fu Rongwei , Szidonya Laszlo , Barajas Ramon F , Ambady Prakash , Varallyay Csanad , Neuwelt Edward A
Published: March 2022

Background

In patients with high-grade glioma (HGG), true disease progression and treatment-related changes often appear similar on magnetic resonance imaging (MRI), making it challenging to evaluate therapeutic response. Dynamic susceptibility contrast (DSC) MRI has been extensively studied to differentiate between disease progression and treatment-related changes. This systematic review evaluated and synthesized the evidence for using DSC MRI to distinguish true progression from treatment-related changes.

Methods

We searched Ovid MEDLINE and the Ovid MEDLINE in-process file (January 2005–October 2019) and the reference lists. Studies on test performance of DSC MRI using relative cerebral blood volume in HGG patients were included. One investigator abstracted data, and a second investigator confirmed them; two investigators independently assessed study quality. Meta-analyses were conducted to quantitatively synthesize area under the receiver operating curve (AUROC), sensitivity, and specificity.

Results

We screened 1177 citations and included 28 studies with 638 patients with true tumor progression, and 430 patients with treatment-related changes. Nineteen studies reported AUROC and the combined AUROC is 0.85 (95% CI, 0.81–0.90). All studies contributed data for sensitivity and specificity, and the pooled sensitivity and specificity are 0.84 (95% CI, 0.80–0.88), and 0.78 (95% CI, 0.72–0.83). Extensive subgroup analyses based on study, treatment, and imaging characteristics generally showed similar results.

Conclusions

There is moderate strength of evidence that relative cerebral blood volume obtained from DSC imaging demonstrated “excellent” ability to discriminate true tumor progression from treatment-related changes, with robust sensitivity and specificity.
Prognostic value of O6-methylguanine-DNA methyltransferase methylation in isocitrate dehydrogenase mutant gliomas
Authors: Lam Keng , Eldred Blaine S C , Kevan Bryan , Pianka Sean , Eldred Brittany A , Zapanta Rinonos Serendipity , Yong William H , Liau Linda M , Nghiemphu Phioanh L , Cloughesy Timothy F , Green Richard M , Lai Albert
Published: March 2022

Background

Patients with isocitrate dehydrogenase (IDH) mutant gliomas have been associated with longer survival time than those that are IDH wild-type. Previous studies have shown the prognostic value of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation for glioblastoma multiforme (GBM), which are predominantly IDH wild-type. Little is known of the prognostic value of MGMT methylation status for IDH mutant gliomas.

Methods

We retrospectively identified IDH mutant gliomas patients between 2011 and 2020 that were tested for MGMT promoter methylation. We generated Kaplan–Meier estimator curves and performed Cox proportional hazard models for overall survival (OS) and progression-free survival (PFS) to compare the outcomes of MGMT promoter methylated versus MGMT unmethylated patients.

Results

Of 419 IDH mutant gliomas with MGMT promoter methylation testing, we identified 54 GBMs, 223 astrocytomas, and 142 oligodendrogliomas. 62.3% patients had MGMT methylated tumors while 37.7% were MGMT unmethylated. On Kaplan–Meier analysis, median OS for all MGMT methylated patients was 17.7 years and 14.6 years for unmethylated patients. Median PFS for all MGMT methylated patients was 7.0 years and for unmethylated patients 5.2 years. After univariate subgroup analysis, MGMT methylation is only prognostic for OS and PFS in GBM, and for OS in anaplastic oligodendroglioma and anaplastic oligodendroglioma for OS. In multivariate analysis, MGMT unmethylated GBM patients carry a higher risk of death (HR 7.72, 95% CI 2.10–28.33) and recurrence (HR 3.85, 95% CI 1.35–10.96).

Conclusions

MGMT promoter methylation is associated with better OS and PFS for IDH mutant GBM. MGMT promoter methylation testing for other IDH mutant glioma subtypes may not provide additional information on prognostication.
Blue is a Colour for Help: The Role of Police in De-escalating Threats to a Large University
Authors: Viñas-Racionero Rosa , Scalora Mario J , Ramzah Hassan
Published: March 2022

University police officers often belong to threat assessment teams, which aim to preventing targeted attacks by pre-emptively identifying and managing individuals who pose a threat towards others. This study seeks to describe the partnership formed between a university police department and a research team to examine the effectiveness of threat management practices through analysis of 332 cases (2006–16). Officers in these cases dealt with numerous concerns, including disruptive behaviour, threats, partner violence, sexual aggression, stalking, workplace violence, and extremist activity. Management of concerning individuals required conflict resolution strategies and coordination with other actors such as student affairs, other police agencies, and mental health services. The effectiveness of the threat management interventions was such that the use of physical, academic, or legal sanctions was rarely needed. Individuals generally ceased their threatening behaviour within 3 months of the interventions and virtually all cases resolved without physical violence occurring on the college campus.
Impedance of Extracellular Fluid, Volume, and Local Tissue Water Can Be Reliably Measured in People With Lower Limb Lymphedema
Authors: Jönsson Charlotta , Johansson Karin , Bjurberg Maria , Brogårdh Christina
Published: February 2022

Objective

Lower limb lymphedema (LLL) is a chronic condition. To be able to evaluate changes of LLL over time and effects of interventions, reliable measurement methods are important. Currently, there is limited knowledge of the reliability of commonly used measurement methods in LLL. The study objective was to evaluate the test–retest (intrarater) reliability of impedance of extracellular fluid, volume, and local tissue water measurements in people with unilateral or bilateral LLL and measurement errors both for a group of people and for a single individual.

Methods

Forty-two people with mild to moderate unilateral or bilateral, primary or secondary LLL were measured twice, 2 weeks apart. Impedance of extracellular fluid was measured by bioimpedance spectroscopy and calculated as arm-to-leg ratio, volume with circumference measurements every 4 cm, and local tissue water with tissue dielectric constant at 14 points. Test–retest reliability was evaluated using the intraclass correlation coefficient [ICC(2,1)], changes in the mean, SE of measurement in relative terms (SEM%), and the smallest real difference in relative terms (SRD%).

Results

For the impedance ratio, the reliability was high [ICC(2,1) = 0.79–0.90] and the measurement errors were acceptable (SEM% = 5.0%–5.2%; SRD% = 14.0%–14.4%). For volume, the reliability was high (ICC = 0.99) and the measurement errors were low (SEM% = 1.1%–1.7%; SRD% = 3.1%–4.6%). For the tissue dielectric constant, the reliability was fair to excellent [ICC(2,1) = 0.68–0.96] and the measurement errors were acceptable (SEM% = 4.2%–9.7%; SRD% = 11.7%–26.8%).

Conclusions

Measurements of impedance of extracellular fluid, volume, and local tissue water are reliable in people with mild to moderate LLL. The measurement errors were acceptable in all 3 methods indicating that real, clinical changes in lymphedema can be measured both for a group of people and a single individual.

Impact

The results from this test–retest reliability study can help clinicians and researchers to interpret if real clinical changes in lymphedema occur over time or after an intervention in people with mild to moderate LLL.
Globalization, Gender, and the Family
Authors: Keller Wolfgang , Utar Hale
Published: February 2022

Facing the same labour demand shock through imports from China, we show that men and women make different labour market and family adjustments that result in significant long-run gender inequality. The gender gap is driven by the female biological clock. Using population registers and matched employer-employee data from Denmark, we document that especially women in their late 30s, towards the end of their biological clock, decide to have a baby as the shock causes displacement. High-earning women in leadership positions and women who need to acquire new human capital are central because their new employment would require particularly high investments that are incompatible with having a newborn in the short time remaining on the biological clock. While children penalize women in the labour market, we show that due to the biological clock an otherwise gender-neutral shock leads to a gender gap in the labour market.
Take-home Naloxone at Opioid Treatment Programs: A Lifesaver
Authors: Katzman Joanna G. , Bhatt Snehal , Comerci George D.
Published: February 2022

Opioid-related overdose deaths have increased almost 30% in the US since the COVID-19 pandemic began. Tragically, many of these deaths could be prevented with widespread availability of naloxone. One innocuous harm-reduction strategy would be the federal government mandating the provision of take-home naloxone and brief overdose education to patients at opioid treatment programs.

Take-home naloxone, for instance, may be used by a friend or a family member to save the life of the patient receiving treatment for opioid use disorder. Importantly, many studies demonstrate that patients receiving take-home naloxone at an opioid treatment program will use the naloxone to reverse an overdose of someone in their social network. Other successful indications for mandated take-home naloxone include: federal inmates leaving incarceration if they have an opioid substance use disorder diagnosis and federal police officers on active duty.

This editorial describes the various organizations, medical societies, and governmental agencies who may consider making robust actionable recommendations regarding naloxone for persons with opioid use disorder. The authors strongly recommend that professional organizations include take-home naloxone as a best practice for any patient who may be at an elevated risk for an opioid overdose.
Assessment of Kratom Use Disorder and Withdrawal Among an Online Convenience Sample of US Adults
Authors: Smith Kirsten E. , Dunn Kelly E. , Rogers Jeffrey M. , Garcia-Romeu Albert , Strickland Justin C. , Epstein David H.
Published: February 2022

Introduction

Since 2007, kratom use in the United States has increased, centered around nonmedical self-treatment of pain, psychiatric, and substance use disorder symptoms. Reports of kratom withdrawal have emerged amidst description of therapeutic effects, yet we know little about disordered use. Our objective was to assess Diagnostic and Statistical Manual-5 substance use disorder for kratom (“kratom use disorder,” KUD) and examine kratom withdrawal symptoms among those who ever used regularly. We also sought to identify clinical characteristics of respondents who qualified for current, remitted, or never KUD.

Methods

Between April and May 2021, we re-recruited online respondents who reported lifetime kratom use on an unrelated survey into our cross-sectional kratom survey study, permitting a diverse sample of current and former kratom-using persons.

Results

A total of 129/289 (44.6%) evaluable surveys were obtained. Over half (52.7%) of respondents never met KUD diagnostic criteria; 17.8% were assessed remitted, and 29.5% met current (past-year) KUD threshold. For past-year KUD, severity was: 14.0% mild, 7.0% moderate, and 8.5% severe. Pain, psychiatric symptoms, and polydrug use were found across all groups. KUD symptoms reflected increased use, tolerance, withdrawal, unsuccessful quit attempts, and craving; 9.3% reported decreases in important social, occupational, or recreational activities because of use. Withdrawal symptoms were moderate and included gastrointestinal upset, restlessness, anxiety, irritability, fatigue/low energy, and craving.

Conclusions

As assessed here, tolerance and withdrawal are primary KUD features rather than psychosocial impairments. As kratomis often used among persons with a myriad of health conditions, clinicians should be aware of and assess for kratom use and withdrawal.
Efficacy and Safety of a New Sustained-release Pregabalin Formulation Compared With Immediate-release Pregabalin in Patients With Peripheral Neuropathic Pain
Authors: Han Kyung Ah , Lee Yong-Ho , Son Hyun-Shik , Song Ki-Ho , Kim Sang Yong , Chung Choon Hee , Jang Hak Chul , Lee Kwan-Woo , Cha Bong Yun , Song Kee-Ho , Ko Young Kwon , Lee Pyung-Bok , Kim Beom Joon , Kim Sohee , An Taewon , Kim Yong-Chul
Published: February 2022

Objective:

This study investigated whether a new sustained-release (SR) pregabalin formulation is noninferior to immediate-release (IR) pregabalin in alleviating peripheral neuropathic pain in Korean patients.

Materials and Methods:

This was a randomized, double-blind, active-controlled phase 3 study of patients with diabetic peripheral neuropathy or postherpetic neuralgia from 41 sites in South Korea in 2017-2018. Eligible patients were randomized (1:1) to receive once-daily SR pregabalin or twice-daily IR pregabalin (150 to 600 mg/d) in a double-dummy manner for 12 weeks according to a stratified permuted block randomization scheme. The primary endpoint was the Daily Pain Rating Scale score at the end of treatment, averaged from the last 7 available scores.

Results:

A total of 319 of 371 (86.0%) randomized patients completed the 12-week treatment (SR pregabalin: n=154; IR pregabalin: n=165; per-protocol set: n=296). The least square mean difference between both groups for the primary endpoint was 0.06 (SE 0.19); (95% confidence interval −0.31 to 0.42), with the lower limit of the confidence interval above the pre-specified margin (−0.78; P
noninferiority<0.0001). Drug-related treatment-emergent adverse events (TEAEs) were comparable between both groups. The incidence of drug-related TEAEs leading to treatment discontinuation was low (SR pregabalin: 2.7%; IR pregabalin: 1.1%). No serious drug-related TEAEs or deaths occurred.

Discussion:

The results demonstrate that the new once-daily SR pregabalin formulation is noninferior to twice-daily IR pregabalin in reducing peripheral neuropathic pain and is well tolerated in Korean patients with diabetic peripheral neuropathy or postherpetic neuralgia after 12 weeks of treatment.
How do orthopaedic surgery residency program websites feature diversity? An analysis of 187 orthopaedic surgery programs in the United States
Authors: Cohen Samuel A. , Xiao Michelle , Zhuang Thompson , Michaud John , Wadhwa Harsh , Shapiro Lauren , Kamal Robin N.
Published: February 2022

Background:

The orthopaedic surgery residency program website represents a recruitment tool that can be used to demonstrate a program’s commitment to diversity and inclusion to prospective applicants. The authors assessed how orthopaedic surgery residency programs demonstrated diversity and inclusion on their program websites and whether this varied based on National Institutes of Health (NIH) funding, top-40 medical school affiliation, university affiliation, program size, or geographic region.

Methods:

The authors evaluated 187 orthopaedic surgery residency program websites for the presence of 12 elements that represented program commitment to diversity and inclusion values, based on prior work and Accreditation Council for Graduate Medical Education (ACGME) recommendations. Mann-Whitney U and Kruskal-Wallis tests were used to assess whether NIH funding and other program characteristics were associated with commitment to diversity and inclusion on affiliated residency websites.

Results:

Orthopaedic surgery residency websites included a mean of 4.9±2.1 diversity and inclusion elements, with 21% (40/187) featuring a majority (7+) of elements. Top 40 NIH-funded programs (5.4±2.0) did not have significantly higher website diversity scores when compared with nontop-40 programs (4.8±2.1) (P=0.250). University-based or affiliated programs (5.2±2.0) had higher diversity scores when compared with community-based programs (3.6±2.2) (P=0.003).

Conclusions:

Most orthopaedic surgery residency websites contained fewer than half of the diversity and inclusion elements studied, suggesting opportunities for further commitment to diversity and inclusion. Inclusion of diversity initiatives on program websites may attract more diverse applicants and help address gender and racial or ethnic disparities in orthopaedic surgery.

Level of Evidence:

Level V.
Outcome of distal femoral osteotomy for the correction of varus deformities originating in the distal femur: a prospective study
Authors: Bagherifard Abolfazl , Jabalameli Mahmoud , Tabrizian Pouria , Yahyazadeh Hooman , Salariyeh Mostafa , Mohammadpour Mehdi
Published: February 2022

Background:

The authors hypothesized that implication of distal femur osteotomy (DFO) in patients with varus deformities that originated in the distal femur will reduce the rate of joint-line obliquity, thereby improving the radiographic, clinical, and functional outcomes of the patients. Here, the authors aimed to evaluate the outcome of DFO in the correction of varus deformities that originated in the distal femur.

Methods:

In a prospective study, 27 patients (31 knees) with varus deformities located in the distal femur who underwent a lateral biplane closed wedge DFO were included. Radiographic evaluations included the joint-line obliquity, medial proximal tibial angle (MPTA), lateral distal femoral angle (LDFA), and joint-line convergence angle (JLCA). Lysholm-Tegner score and Knee Injury and Osteoarthritis Outcome Score (KOOS) were used for the evaluation of functional outcome. The union of the osteotomy site was assessed radiographically.

Results:

At the final evaluation session, the mean preoperative varus angle significantly improved from 12.7±3.4 degrees to 1.6±1.6 degrees (P<0.001). The mean preoperative LDFA significantly improved from 96±2.1 degrees to 87.9±1.1 degrees (P<0.001). The mean preoperative JLCA significantly improved from 3.1±0.4 degrees to 2±0.3 degrees (P<0.001). The mean preoperative Lysholm-Tegner scores also improved considerably from 66.4±2 degrees to 88.9±2.6 degrees (P<0.001). The mean KOOS of the patients improved from 63.9±4.1 degrees to 86.1±4.6 degrees. Only one patient (3.2%) was observed to have joint-line obliquity (greater than±4 degrees). Bone union was seen in all patients at an average period of 9±1.9 wk.

Conclusions:

DFO results in small rate of joint-line obliquity, as well as acceptable radiographic, clinical, and functional outcomes in patients with varus deformities located in the distal femur.

Level of Evidence:

Level III.
Surgical outcomes of intramedullary screw fixation for metacarpal fractures: a systematic review
Authors: Wolf G. Jacob , Goodloe J. Brett , Bailey Evan P. , Barcel John A. , Daley Dane N.
Published: February 2022

Background:

Metacarpal fractures account for 33.3% of hand fractures. New surgical techniques have been developed to address this common injury, including retrograde intramedullary (IM) screw fixation. This technique has grown in popularity in recent years and has shown promising results but has been met with skepticism by some surgeons because of the lack of adequate large-scale outcome studies. The purpose of this study was to review all existing literature on clinical and functional outcomes for metacarpal fractures managed operatively with IM screw fixation.

Methods:

A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Clinical and functional outcomes as well as complications were analyzed.

Results:

The database search yielded 12 studies, including a total of 554 metacarpal fractures that were surgically managed with IM screw fixation. Average follow-up after surgery was 23.1 wk. Fracture union rate was 100%. Postoperative grip strength was shown to average 99.3% that of the contralateral uninjured hand. Total active range of motion averaged 249.8 degrees. The overall complication rate was 5.6%, and 3.1% required a second surgery.

Conclusions:

This systematic review demonstrated that intramedullary screw fixation for metacarpal fractures yields excellent clinical and functional outcomes with low complication rates. IM screw fixation provides rigid internal fixation with minimal soft-tissue dissection without extramedullary hardware, thus precluding the need for prolonged postoperative immobilization and limiting the potential for extensor tendon adhesions and digital stiffness. IM screw fixation is a viable and safe option for surgical management of metacarpal fractures.

Level of Evidence:

Level III.
Long-Term Outcomes After Treatment for Type B Ulnar Polydactyly
Authors: Goebel Gunnar J. , Dawson Steven , Loewenstein Scott N. , Adkinson Joshua M.
Published: February 2022

Background:

Type B ulnar polydactyly is a common congenital hand difference and can be treated with either ligation or surgical excision. There is a paucity of literature, however, evaluating long-term patient reported outcomes of these treatments. The purpose of this study was to compare the long-term outcomes after ligation and excision for the management of type B ulnar polydactyly.

Methods:

We created a database of patients who underwent treatment for type B ulnar polydactyly at a single pediatric health system from 2005 to 2014. We administered the Patient Reported Outcomes Measurement Information System (PROMIS) Pediatric Upper Extremity survey to patients through telephone and assessed for their satisfaction.

Results:

We successfully collected outcomes from 69 of 173 eligible patients treated in infancy (40% response rate). The mean follow-up was 11.1±2.5 years, and the average age of the participant at the time of the survey was 11.7±2.6 years of age. Twenty-four patients were treated with in-office ligation and 45 underwent formal surgical excision. Ten patients who were initially treated with ligation required future treatment with surgery because of symptomatic neuroma stump or persistent polydactyly (42%). Patients who were treated with surgical excision rated significantly higher satisfaction with their treatment than those who underwent ligation (P=0.003). Patients in both cohorts rated similar satisfaction with the esthetic appearance of their hand (P=0.07). There was no significant difference in PROMIS-rated hand function between the ligation and surgical cohort (P=0.765) and treated adolescents PROMIS scores were not statistically different than age-matched controls without polydactyly.

Conclusion:

While ligation and surgical excision result in similar function and esthetics, patient satisfaction is higher after surgery. Furthermore, a significant number of patients fail ligation and ultimately undergo surgery for symptomatic neuroma or persistent polydactyly. Counseling parents of patients with type B ulnar polydactyly should include these considerations to assist them in selecting the best treatment for their child.

Level of Evidence:

Level III.
Mode of Anesthesia and Bladder Management Following Orthopaedic Surgery in Children With Cerebral Palsy: A System Level Analysis
Authors: Buckon Cathleen E. , Koscielniak Nikolas J. , Tucker Carole A. , Aiona Michael D.
Published: February 2022

Background:

Postoperative urinary retention (POUR) is a surgical complication more prevalent in children with neurodisability and associated with an increase length of hospitalization. Risk factors include pre-existing bladder dysfunction, type and duration of surgery, anesthesia medications, postoperative opioid pain management, and patient demographics. The purpose of this investigation was (1) to determine the frequency of POUR following hip/lower limb orthopaedic procedures in which epidural analgesia was used for pain management; (2) to explore factors influencing postoperative bladder management.

Methods:

A retrospective analysis of clinical data was performed in an orthopaedic specialty care health care system. A health outcomes network was queried for patients with a diagnoses of cerebral palsy (ICD-9/10 codes) who had one of 57 unique CPT procedure codes corresponding to hip osteotomies or tenotomies from 2011 to 2019. All surgical observations included in analysis required a discrete data element and the confirmation of a secondary proxy. The database was also queried for postoperative medications received and patient demographics of interest.

Results:

A total of 704 surgical procedures met inclusion criteria resulting in a patient population with a mean age of 11 years, 58% male, 53% Caucasian, and 55% classified as quadriplegia [51% Gross Motor Function Classification System (GMFCS) levels IV/V]. Three hundred and thirty-five procedures (48%) involved epidural anesthesia. Sixty-five patients required intermittent catheterization (9.2%) postoperatively following foley catheter removal, of which 23 (3.3%) required recatheterization. The rate of recatheterization was similar regardless of anesthesia mode; 1.8% for general and 1.4% for epidural and was associated with a greater number of pain medications. Epidural anesthesia resulted in significantly longer periods of catheterization. For the total group the time to urinary catheter removal differed significantly among cerebral palsy subtypes, GMFCS Level, race, and ethnicity. Factors identified as significant predictors of the length of catheterization were epidural analgesia, number of pain medications, and osteotomy.

Conclusions:

The number of postoperative pain medications utilized was more predictive of POUR than the mode of analgesia delivery; however, epidural analgesia and the type of surgical procedure did significantly impact the length of catheterization.

Level of Evidence:

Level III.