bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of a Pharmacist-Led Diabetes Management Intervention to Improve Health Equity
Authors: Smith-Ray Renae , Singh Tanya , Makris Evie , Horan Jaime , Taitel Michael
Published: December 2021

The COVID-19 pandemic and Black Lives Matter movement brought increased recognition to the need for health equity. Diabetes, the 7th leading cause of death, is one of many conditions where health inequities are evident. A higher percentage of Black (11.7%) and Hispanic (12.5%) U.S. adults are diagnosed with diabetes compared to non-Hispanic Whites (7.5%). To address this health inequity, a nationwide pharmacy chain implemented telephonic ‘Advanced Care’ (AC) outreach for patients with diabetes. During the AC call, pharmacists used motivational interviewing techniques to counsel patients on the importance of closing gaps in care and reducing barriers to medication adherence. Gaps included timely A1C testing, exams (eye, foot, kidney), immunizations (influenza, pneumonia, Hepatitis B), and recommendation of additional therapies for patients with multiple chronic conditions (ACE/ARB, statins). Medication fill gaps were compared between the Intervention period (8/1/20-1/31/-21) and a pre-intervention period (2/1/20-7/31/20). The AC pilot occurred in 8 Chicago Walgreens locations that primarily serve Black and Hispanic patients. Eight control stores were matched on census block-level household income and race/ethnicity, patient volume, and insurance mix. A pre/post-test vs. control difference-in-difference (DID) analysis was conducted to compare on-time refill rates. Of the 1,009 older patients (age≥50) called, 59.9% were reached. The DID analysis showed that patients in pilot stores had improved pre-post on-time refill rates compared to controls (p<0.0001). Diabetes self-management is key to reducing diabetes-related complications. Early findings from this pilot demonstrate that the Walgreens AC intervention improves medication adherence - an important step toward improving health equity.
A Profile of Black and Latinx Older Adults Receiving Care in Nursing Homes: 2011-2017
Authors: Travers Jasmine , Dick Andrew , Wu Bei , Grabowski David , Agarwal Mansi , Perera Gayani , Stone Patricia
Published: December 2021

Between the years 1999-2008, a substantial increase in nursing home use occurred among Black and Latinx older adults, while white older adults’ use of nursing homes decreased. These disparate trends suggested potential racial and ethnic disparities in options for preferred long-term services and supports (LTSS) settings. Over the last decade, several initiatives have been put in place to support LTSS needs in the community. However, it is unclear whether Black and Latinx older adults are continuing to use nursing home services at disproportionate rates. We used LTCfocus data for 2011-2017 to explore current trends in nursing home use and access among Black and Latinx older adults in light of these current initiatives. Our findings reveal a continued rise in Black and Latinx older adults’ use of nursing homes while white older adults’ use continues to decline. More notably, there has been a decline in nursing homes servicing these minority groups.
Coping and Caregiver Burden and Depression Among Chinese Caregivers of Older Adults With Cognitive Impairment
Authors: Wang Kaipeng , Gao Xiang
Published: December 2021

Coping strategies are important factors that influence caregivers’ mental health outcomes. The purpose of this study is to examine the association between coping strategies and caregiver burden and depression among Chinese caregivers of older adults with cognitive impairment. Data came from structured interviews with 300 primary family caregiver-care recipient dyads in Wuhan, China. We used OLS to examine the association between coping strategies and caregiver burden and depression. More positive reframing and acceptance were associated with lower caregiver burden, whereas more self-distraction was associated with higher caregiver burden. More positive reframing was associated with lower caregiver depression, whereas higher self-distraction and religion were associated with higher caregiver depression. Findings of this study suggest that a psychosocial intervention package that emphasizes on enhancing positive reframing skills and affirming acceptance may be effective in reducing caregiver burden and depression among Chinese caregivers of older adults with cognitive impairment.
Challenges Faced by Nursing Home Direct Care Workers During the COVID-19 Pandemic: A Comparison Across Care Settings
Authors: Bryant Natasha , Cimarolli Verena , Stone Robyn
Published: December 2021

The COVID-19 pandemic has generated awareness of the value of the direct care workforce to provide care in settings serving those most at risk from the disease. However, few studies have gauged the impact of COVID-19 on this workforce and their pandemic-related challenges. The purpose of this study was to examine the challenges and stress experienced by direct care workers (N=1,414) and their perceptions of preparation and quality of employer communication during this health crisis. Nursing home (NH) workers reported separation from family members and understaffing as the top external and work-related challenges. They felt adequately prepared and gave their employers high marks for communicating with them during the pandemic. NH direct care workers were more likely to report increased workload and understaffing as a challenge compared to workers in home and community-based settings. They also experienced a significantly higher number of work-related challenges compared to workers in assisted living.
Job Resignation in Nursing Homes During COVID-19: The Role of Employer Communication and Worker Preparedness
Authors: Cimarolli Verena , Bryant Natasha , Stone Robyn , Falzarano Francesca
Published: December 2021

Although research on factors mitigating the negative impact of strain/stress experienced by nursing home (NH) workers during the pandemic is emerging, there is no research on how COVID-19-related work stress and employer supports influence NH workers decision to resign. The purpose of this study was to investigate if high quality communication related to COVID-19 by the employer – a form of job support - can mitigate the impact of work stress on NH employees (N=1,730) decision to resign by optimizing employees’ preparedness to care for residents with COVID-19. Guided by the Job-Demands-Control-Support Model and employing path analyses, results indicate that higher stress was associated with greater likelihood of resigning, which operated through the paths of communication quality and preparedness. While higher stress was associated with less optimal quality of communication, good quality of communication was associated with more optimal preparedness which was associated with reduced likelihood of leaving one’s job.
Presidential Symposium: From Disruption to Transformation: Challenging and Changing the New Normal
Authors: Waldrop Deborah , Rozario Philip , Greenfield Emily
Published: December 2021

While the refrain “We’re all in this together” is meant to describe a sense of universality of our exposure and adaption to the Covid-19 pandemic life, the deeply rooted racial and economic injustices and ongoing health crises continue to expose the inequities experienced by many older adults. In this symposium, we focus on existing disparities and possibilities for transformation. The first paper discusses systemic racism as a structural driver of practices and policies that influence poverty, poor housing and neighborhood conditions, worse health profiles, relationship loss and social isolation among older Black adults. The second paper illuminates the importance of health equity and collaboration between aging and healthcare systems to improve the well-being outcomes and address disparities of older adults from racial-ly/ethnically diverse backgrounds. The third paper illustrates how the privatization of Medicare has created bureaucratic complexities that increase cost and burdens for beneficiaries. The fourth paper presents the ways that the pandemic has exposed the challenges of a nonexistent Long Term Services and Support system; specifically, in refocusing our attention on the working conditions of in-home and residential workers, such as poor compensation, and high turnover and mounting demands on families. The fifth paper addresses the importance of collaboration between nursing homes and assisted living communities with governmental emergency operations in times of disasters and public health crises. Each paper addresses pressing issues that have created the “new normal” for older adults; together the presenters explore the disruptions and offer solutions for renewed transformation.
Making Medicare Complicated: The Consequences of Privatization
Authors: Herd Pamela
Published: December 2021

Starting with policy changes in the 1980s, Medicare has largely become privatized, with nearly 40 percent of beneficiaries enrolled in private Medicare Advantage plans and another 30 percent with private supplemental coverage, including for prescription drug coverage. As a result, Medicare has become laden with administrative burdens and barriers. Beneficiaries are faced with a confusing array of plans and coverage options when they enroll, and are expected to choose a new plan every year. The choice they make has large implications for their health care costs, as well as their actual access to health care. While we typically think that targeted policies are burdensome and social insurance programs are accessible, Medicare contradicts this easy categorization. Instead, it demonstrates how private sector involvement in public programs can increase complexity and increase burdens for beneficiaries.
Birth Cohort Differences in Multimorbidity Burden Among Aging U.S. Adults
Authors: Bishop Nicholas , Haas Steven , Quiñones Ana
Published: December 2021

Multimorbidity is the co-occurrence of two or more chronic health conditions and affects more than half of the US population aged 65 and older. Recent trends suggest increased risk of poor self-reported health, physical disability, cognitive impairment, and mortality among later born birth cohorts, yet we are unaware of work examining cohort trends in multimorbidity among aging US adults. Observations were drawn from the Health and Retirement Study (2000–2018) and included adults aged 51 and older across 7 birth cohorts (1923 and earlier, 1924–1930, 1931–1941, 1942–1947, 1948–1953, 1954–1959, and 1960–1965). Multimorbidity was measured as a count of 9 chronic conditions including heart disease, hypertension, stroke, diabetes, arthritis, lung disease, cancer (excluding skin cancer), depression, and cognitive impairment. General linear models adjusting for repeated measures and covariates including age, sex, race/ethnicity, and education were used to identify whether trends in multimorbidity varied across birth cohort. 31,923 adults contributed 153,940 total observations, grand mean age was 68.0 (SD=10.09), and mean multimorbidity was 2.19 (SD=1.49). In analyses adjusted for age and other covariates, adults born 1948–1953 reported .34 more chronic conditions (SE=.03, p<.001), adults born 1954–1959 reported .42 more chronic conditions (SE=.03, p<.001), and adults born 1960–1965 reported .55 more chronic conditions (SE=.03, p<.001), than those born 1931–1941, respectively. Our preliminary results confirm increasing multimorbidity among later birth cohorts of older Americans and should help guide policy to manage impending health declines among older Americans.
The Interaction of Life Course Socioeconomic Status and Leisure Activities on Cognitive Performance in Old Age
Authors: Sun Rongjun , Zhang Zhenmei
Published: December 2021

While the separate effects of socioeconomic status and engaging in leisure activities on cognition have been well documented, their interaction effect has rarely been examined. After examining life course socioeconomic status (SES) on cognitive impairment in old age, this paper is focused on exploring the interaction effects between life course SES and leisure activities. We use data from the Chinese Longitudinal Healthy Longevity Survey, which covers five waves of interviews of adults aged 65 or older between 2002 and 2014. Cognitive impairment is measured by the Chinese version of Mini-Mental Status Examination. Two sets of variables are used to reflect an older person’s life course SES in childhood and adulthood, respectively. Seven leisure activities are included in this analysis. We adopt the lagged independent variable approach and a Generalized Linear Mixed Model to examine the association between leisure activity and cognitive impairment over time. Results show that there is an independent impact of SES in both childhood and adulthood on cognitive decline in Chinese older population. Furthermore, as the focus of this study, there are substantial interactions between life course SES and engaging in leisure activities with a consistent pattern: those of higher life course SES enjoy extra benefits from engaging in leisure activities. The interactions between life course SES and leisure activities promise a competing approach accounting for cognitive health inequality among older adults.
Next Level Health: a holistic health and wellbeing program to empower New Zealand women
Authors: Chinn V , Neely E , Shultz S , Kruger R , Hughes R , Page R , Coad J , Thunders M
Published: December 2021

Improving equity in women’s health requires gender-specific and empowering approaches. However, health programs often disempower women by adopting a ‘one-size-fits-all’ approach that emphasizes diet, exercise and weight loss over other important aspects like sleep and mental wellbeing. This article reports on the design of Next Level Health (NLH), a program that aims to empower women through developing a wide range of health behaviors to support their holistic wellbeing. NLH is grounded by ethics, theory and evidence to support women to make achievable, sustainable changes that are relevant to their everyday lives. Women utilized the NLH framework to develop an integrative health routine across six domains: physical activity, sleep, nutrition, eating behavior, self-care and stress management. The framework guided them to set small, incremental goals that were adaptive to their needs and built from their existing circumstances. Participants reflected on their progress with a facilitator during monthly meetings, accessed a social media support page and received monthly text messages. Health programs remain an essential approach to improving women’s health alongside community- and policy-level strategies. The development of NLH exemplifies how evidence may partner with modern health promotion values to inform relevant and ethical program design for women.
Modeling gain-of-function and loss-of-function components ofSPAST-based hereditary spastic paraplegia using transgenic mice
Authors: Piermarini Emanuela , Akarsu Seyma , Connors Theresa , Kneussel Matthias , Lane Michael A , Morfini Gerardo , Karabay Arzu , Baas Peter W , Qiang Liang
Published: December 2021

Hereditary spastic paraplegia (HSP) is a disease in which dieback degeneration of corticospinal tracts, accompanied by axonal swellings, leads to gait deficiencies. SPG4-HSP, the most common form of the disease, results from mutations of human spastin gene (SPAST), which is the gene that encodes spastin, a microtubule-severing protein. The lack of a vertebrate model that recapitulates both the etiology and symptoms of SPG4-HSP has stymied the development of effective therapies for the disease. hSPAST-C448Y mice, which express human mutant spastin at the ROSA26 locus, display corticospinal dieback and gait deficiencies but not axonal swellings. On the other hand, mouse spastin gene (Spast)-knockout (KO) mice display axonal swellings but not corticospinal dieback or gait deficiencies. One possibility is that reduced spastin function, resulting in axonal swellings, is not the cause of the disease but exacerbates the toxic effects of the mutant protein. To explore this idea, Spast-KO and hSPAST-C448Y mice were crossbred, and the offspring were compared with the parental lines via histological and behavioral analyses. The crossbred animals displayed axonal swellings as well as earlier onset, worsened gait deficiencies and corticospinal dieback compared with the hSPAST-C448Y mouse. These results, together with observations on changes in histone deacetylases 6 and tubulin modifications in the axon, indicate that each of these three transgenic mouse lines is valuable for investigating a different component of the disease pathology. Moreover, the crossbred mice are the best vertebrate model to date for testing potential therapies for SPG4-HSP.
Development of a Personalized Intestinal Fibrosis Model Using Human Intestinal Organoids Derived From Induced Pluripotent Stem Cells
Authors: Estrada Hannah Q , Patel Shachi , Rabizadeh Shervin , Casero David , Targan Stephan R , Barrett Robert J
Published: December 2021

Background

Intestinal fibrosis is a serious complication of Crohn’s disease. Numerous cell types including intestinal epithelial and mesenchymal cells are implicated in this process, yet studies are hampered by the lack of personalized in vitro models. Human intestinal organoids (HIOs) derived from induced pluripotent stem cells (iPSCs) contain these cell types, and our goal was to determine the feasibility of utilizing these to develop a personalized intestinal fibrosis model.

Methods

iPSCs from 2 control individuals and 2 very early onset inflammatory bowel disease patients with stricturing complications were obtained and directed to form HIOs. Purified populations of epithelial and mesenchymal cells were derived from HIOs, and both types were treated with the profibrogenic cytokine transforming growth factor β (TGFβ). Quantitative polymerase chain reaction and RNA sequencing analysis were used to assay their responses.

Results

In iPSC-derived mesenchymal cells, there was a significant increase in the expression of profibrotic genes (Col1a1, Col5a1, and TIMP1) in response to TGFβ. RNA sequencing analysis identified further profibrotic genes and demonstrated differential responses to this cytokine in each of the 4 lines. Increases in profibrotic gene expression (Col1a1, FN, TIMP1) along with genes associated with epithelial-mesenchymal transition (vimentin and N-cadherin) were observed in TGFβ -treated epithelial cells.

Conclusions

We demonstrate the feasibility of utilizing iPSC-HIO technology to model intestinal fibrotic responses in vitro. This now permits the generation of near unlimited quantities of patient-specific cells that could be used to reveal cell- and environmental-specific mechanisms underpinning intestinal fibrosis.
A mathematical model to describe antibody-dependent enhancement and assess the effect of limiting cloning for plasma cells in heterologous secondary dengue infection
Authors: Alves Rubio Felipe , Mo Yang Hyun
Published: December 2021

We propose a mathematical model to study the antibody-dependent enhancement (ADE) phenomenon. Here, we explore the interaction between macrophages, dengue virus and plasma cells, especially the effect of a limitation on plasma cell proliferation, which occurs due to immunological memory. The model has up to three equilibrium points: one virus-free equilibrium and two virus-presence equilibrium, depending on the value of two thresholds. We determine the existence regions for the model equilibrium points and their stability, a sensitivity analysis was performed in the model thresholds. Numerical simulations illustrate that ADE can occur even when the basic reproduction number is less than one.
Supplementation With Fish Oil in Pregnancy Reduces Gastroenteritis in Early Childhood
Authors: Horner David , Hjelmsø Mathis Hjort , Thorsen Jonathan , Rasmussen Morten , Eliasen Anders , Vinding Rebecca Kofod , Schoos Ann-Marie Malby , Brustad Nicklas , Sunde Rikke Bjersand , Bønnelykke Klaus , Chawes Bo L , Stokholm Jakob , Bisgaard Hans
Published: December 2021

Background

We hypothesized that insufficient intake of fish oil–derived omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) during pregnancy is a contributing factor to gastroenteritis in early childhood. We examined the effect of n-3 LCPUFA supplementation on gastroenteritis symptoms in the offspring’s first 3 years of life.

Methods

This was a double-blinded, randomized controlled trial whereby 736 mothers were administered n-3 LCPUFA or control from pregnancy week 24 until 1 week after birth. We measured the number of days with gastroenteritis, number of episodes with gastroenteritis, and the risk of having a gastroenteritis episode in the first 3 years of life.

Results

A median reduction of 2.5 days with gastroenteritis (P = .018) was shown, corresponding to a 14% reduction in the n-3 LCPUFA group compared with controls in the first 3 years of life (P = .037). A reduction in the number of gastroenteritis episodes (P = .027) and a reduced risk of having an episode (hazard ratio, 0.80 [95% confidence interval, .66–.97]; P = .023) were also shown.

Conclusions

Fish oil supplementation from the 24th week of pregnancy led to a reduction in the number of days and episodes with gastroenteritis symptoms in the first 3 years of life. The findings suggest n-3 LCPUFA supplementation as a preventive measure against gastrointestinal infections in early childhood.

Clinical Trials Registration

NCT00798226.
Maize PHYTOMELATONIN RECEPTOR1 functions in plant tolerance to osmotic and drought stress
Authors: Wang Lin-Feng , Lu Kai-Kai , Li Ting-Ting , Zhang Yu , Guo Jia-Xing , Song Ru-Feng , Liu Wen-Cheng
Published: December 2021

Phytomelatonin is a universal signal molecule that regulates plant growth and stress responses; however, only one receptor that can directly bind with and perceive melatonin signaling has been identified so far, namely AtPMTR1/CAND2 in Arabidopsis. Whether other plants contain a similar receptor and, if so, how it functions is still unknown. In this study, we identified a new phytomelatonin receptor in the monocot maize (Zea mays), and investigated its role in plant responses to osmotic and drought stress. Using homology searching, we identified a plasma membrane-localized protein, Zm00001eb214610/ZmPMTR1, with strong binding activity to melatonin as a potential phytomelatonin receptor in maize. Overexpressing ZmPMTR1 in Arabidopsis Col-0 promoted osmotic stress tolerance, and rescued osmotic stress sensitivity of the Arabidopsis cand2-1 mutant. Furthermore, ZmPMTR1 also largely rescued defects in melatonin-induced stomatal closure in the cand2-1 mutant, thereby reducing water loss rate and increasing tolerance to drought stress. In addition, we identified a maize mutant of ZmPMTR1, EMS4-06e2fl, with a point-mutation causing premature termination of protein translation, and found that this mutant had lower leaf temperatures, increased rate of water loss, and enhanced drought stress sensitivity. Thus, we present ZmPMTR1 as the first phytomelatonin receptor to be identified and examined in a monocot plant, and our results indicate that it plays an important function in the response of maize to drought stress.
Oncology Patients Who Develop Transfusion-Associated Circulatory Overload: An Observational Study
Authors: Maldonado Marisol , Villamin Colleen E , Murphy Leah E , Dasgupta Amitava , Bassett Roland L , Correa Medina Mayrin , Bates Tonita S , Martinez Fernando , Knopfelmacher Couchonal Adriana M , Klein Kimberly , Kelley James M
Published: December 2021

Background

Transfusion-associated circulatory overload (TACO) is a largely preventable transfusion complication that results in significant morbidity and mortality. Cancers, related treatments, and comorbidities are among the factors that can predispose patients to TACO, but currently there are limited data on this topic in the literature.

Methods

We collected data retrospectively from the electronic health records of 93 adult patients with cancer who met Centers for Disease Control and Prevention (CDC) criteria for TACO from July 1, 2019, through October 31, 2020. The parameters we studied included demographics, comorbidities, treatment modalities, transfusion practices, and outcomes. We summarized data by means and ranges for continuous variables, and proportions for categorical variables.

Results

During the study period, the incidence of TACO among oncology patients was 0.84 per 1000 transfusions (95% CI, 0.68–1.02), representing 6.6% of all reactions. This percentage is high, compared with 1%–6% among other populations. Unique characteristics such as hematology malignancy (75.3%), receipt of cardiotoxic chemotherapy (87.1%), pneumonia (57.0%), preexisting oxygen use (59.1%), dyspnea (62.4%), hypertension (55.9%), renal insufficiency (46.2%), daily use of corticosteroids (43.0%), daily use of diuretics (40.9%), daily use of beta-blockers (36.6%), and elevated NT-proBNP (33.3%) were frequently observed in these group of oncology patients.

Conclusions

Our study indicates that oncology patients have unique factors that may lead to diagnosis of TACO. Developing appropriate guidelines that apply to oncology patients, in addition to those set forth by the CDC, should be considered. Implementation by ordering healthcare providers of a tools that can predict TACO can help in early recognition and mitigation of TACO.
Concussion Knowledge and Attitudes in Reserve Officers’ Training Corps Cadets
Authors: Radzak Kara N , Hunzinger Katherine J , Costantini Katelyn M , Swanik C Buz , Buckley Thomas A
Published: December 2021

Introduction

Military members’ knowledge of concussion signs and symptoms may be critical to appropriate concussion identification and health-seeking behavior, particularly for those in leadership roles. The current study aimed to characterize concussion knowledge and attitudes among future military officers undergoing U.S.-based Reserve Officers’ Training Corps (ROTC) training.

Materials and Methods

Army and Air Force ROTC cadets at 2 large, public universities were utilized for a survey-based observational study. The study was approved by the institutional review board at both university research sites. Cadets completed a modified Rosenbaum Concussion Knowledge and Attitude Survey to obtain cadets’ Concussion Knowledge Index and Concussion Attitude Index, where higher scores are preferable. Cadets’ concussion knowledge and attitudes were characterized via descriptive statistics.

Results

Cadets (n = 110) had a mean Concussion Knowledge Index of 18.8 ± 3.2 (range = 9–23, out of 25). Potentially detrimental misconceptions included: belief that typically concussion symptoms no longer persist after 10 days (79.1%) and brain imaging shows visible physical damage following concussion (74.5%). Mean Concussion Attitude Index was 60.6 ± 7.4 (range = 46–75, out of 75). In general, cadets reported higher agreement with safe concussion behavior than what they believe peers would report.

Conclusions

Cadets were found to have a high concussion knowledge, yet common misconceptions remained. Cadets consistently reported safe choices but were less sure that peers felt similarly; future investigations should evaluate ROTC concussion social norms and education should note peers’ beliefs supporting safe concussion attitudes.
The evolution of the oxygen abundance gradients in star-forming galaxies in the eagle simulations
Authors: Tissera Patricia B , Rosas-Guevara Yetli , Sillero Emanuel , Pedrosa Susana E , Theuns Tom , Bignone Lucas
Published: December 2021

We analyse the evolution of the oxygen abundance gradient of star-forming galaxies with stellar mass ${\rm M_{\ast }}\ge 10^{9}\rm M_{\odot }$ in the eagle simulation over the redshift range z = [0, 2.5]. We find that the median metallicity gradient of the simulated galaxies is close to zero at all z, whereas the scatter around the median increases with z. The metallicity gradients of individual galaxies can evolve from strong to weak and vice versa, since mostly low-metallicity gas accretes on to the galaxy, resulting in enhanced star formation and ejection of metal-enriched gas by energy feedback. Such episodes of enhanced accretion, mainly dominated by major mergers, are more common at higher z and hence contribute to increasing the diversity of gradients. For galaxies with negative metallicity gradients, we find a redshift evolution of $\rm \sim -0.03~dex~kpc^{-1}/\delta z$. A positive mass dependence is found at z ≤ 0.5, which becomes slightly stronger for higher redshifts and, mainly, for ${\rm M_{\ast }}\lt 10^{9.5} \rm M_{\odot }$. Only galaxies with negative metallicity gradients define a correlation with galaxy size, consistent with an inside-out formation scenario. Our findings suggest that major mergers and/or significant gas accretion can drive strong negative or positive metallicity gradients. The first ones are preferentially associated with disc-dominated galaxies, and the second ones with dispersion-dominated systems. The comparison with forthcoming observations at high redshift will allow a better understanding of the potential role of metallicity gradients as a chemical probe of galaxy formation.
Characterizing epochs of star formation across the Milky Way disc using age–metallicity distributions of GALAH stars
Authors: Sahlholdt Christian L , Feltzing Sofia , Feuillet Diane K
Published: December 2021

We provide a detailed map of the ages and metallicities of turn-off stars in the Milky Way disc based on data from GALAH DR3 and Gaia EDR3. From this map, we identify previously undetected features in the age–metallicity distribution of disc stars and interpret these results as indicating a three-phase formation history of the Milky Way. In the first phase, inner disc stars form along a single age–metallicity sequence and are today kinematically hot. The end of this phase is marked by a local minimum in the inner disc age distribution 10 Gyr ago. At this time, we find the stellar populations to transition from high to low alpha-element abundances and from high to low vertical velocity dispersion. In the second phase, stars form across the disc with outwardly decreasing metallicity. In this phase, inner disc stars form at supersolar metallicities in a continuation of the early age–metallicity relation, while outer disc stars begin forming at metallicities at least 0.5 dex lower. Finally, the third phase is associated with a recent burst of star formation across the local disc marked by a local minimum in the age–metallicity distribution 4–6 Gyr ago. Future quantitative comparisons between the observed age–metallicity distribution and those of simulated galaxies could help constrain the processes driving each of the star formation phases.
Role of the radiative stage for cosmic ray acceleration in SNRs
Authors: Zirakashvili V N , Ptuskin V S
Published: December 2021

We consider diffusive shock acceleration in supernova remnants throughout their evolution including a radiative stage. It is found that a more efficient acceleration and fast exit of particles at the radiative stage results in the hardening of the source cosmic ray proton and electron spectra at energies ∼100–500 GeV. The effect is stronger for cosmic ray electrons.
Role of PemI in the Staphylococcus aureus PemIK toxin–antitoxin complex: PemI controls PemK by acting as a PemK loop mimic
Authors: Kim Do-Hee , Kang Sung-Min , Baek Sung-Min , Yoon Hye-Jin , Jang Dong Man , Kim Hyoun Sook , Lee Sang Jae , Lee Bong-Jin
Published: December 2021

Staphylococcus aureus is a notorious and globally distributed pathogenic bacterium. New strategies to develop novel antibiotics based on intrinsic bacterial toxin–antitoxin (TA) systems have been recently reported. Because TA systems are present only in bacteria and not in humans, these distinctive systems are attractive targets for developing antibiotics with new modes of action. S. aureus PemIK is a type II TA system, comprising the toxin protein PemK and the labile antitoxin protein PemI. Here, we determined the crystal structures of both PemK and the PemIK complex, in which PemK is neutralized by PemI. Our biochemical approaches, including fluorescence quenching and polarization assays, identified Glu20, Arg25, Thr48, Thr49, and Arg84 of PemK as being important for RNase function. Our study indicates that the active site and RNA-binding residues of PemK are covered by PemI, leading to unique conformational changes in PemK accompanied by repositioning of the loop between β1 and β2. These changes can interfere with RNA binding by PemK. Overall, PemK adopts particular open and closed forms for precise neutralization by PemI. This structural and functional information on PemIK will contribute to the discovery and development of novel antibiotics in the form of peptides or small molecules inhibiting direct binding between PemI and PemK.
Diverse DNA modification in marine prokaryotic and viral communities
Authors: Hiraoka Satoshi , Sumida Tomomi , Hirai Miho , Toyoda Atsushi , Kawagucci Shinsuke , Yokokawa Taichi , Nunoura Takuro
Published: December 2021

DNA chemical modifications, including methylation, are widespread and play important roles in prokaryotes and viruses. However, current knowledge of these modification systems is severely biased towards a limited number of culturable prokaryotes, despite the fact that a vast majority of microorganisms have not yet been cultured. Here, using single-molecule real-time sequencing, we conducted culture-independent ‘metaepigenomic’ analyses (an integrated analysis of metagenomics and epigenomics) of marine microbial communities. A total of 233 and 163 metagenomic-assembled genomes (MAGs) were constructed from diverse prokaryotes and viruses, respectively, and 220 modified motifs and 276 DNA methyltransferases (MTases) were identified. Most of the MTase genes were not genetically linked with the endonuclease genes predicted to be involved in defense mechanisms against extracellular DNA. The MTase-motif correspondence found in the MAGs revealed 10 novel pairs, 5 of which showed novel specificities and experimentally confirmed the catalytic specificities of the MTases. We revealed novel alternative specificities in MTases that are highly conserved in Alphaproteobacteria, which may enhance our understanding of the co-evolutionary history of the methylation systems and the genomes. Our findings highlight diverse unexplored DNA modifications that potentially affect the ecology and evolution of prokaryotes and viruses in nature.
Neuronal exposure induces neurotransmitter signaling and synaptic mediators in tumors early in brain metastasis
Authors: Deshpande Krutika , Martirosian Vahan , Nakamura Brooke Naomi , Iyer Mukund , Julian Alex , Eisenbarth Rachel , Shao Ling , Attenello Frank , Neman Josh
Published: December 2021

Background

Brain metastases (BM) are responsible for neurological decline and poor overall survival. Although the pro-metastatic roles of glial cells, and the acquisition of neuronal attributes in established BM tumors have been described, there are no studies that investigate the initial interplay between neurons and brain-seeking tumor cells. The aim of this study was to characterize early tumor-neuron interactions and the induced CNS-adaptive changes in tumor cells prior to macro-colonization

Methods

Utilizing pure neuronal cultures and brain-naïve and patient-derived BM tumor cells, we surveyed the early induction of mediators of neurotransmitter (NT) and synaptic signaling in breast and lung tumor cells. Reliance on microenvironmental GABA in breast-to-brain metastatic cells (BBMs) was assessed in vitro and in vivo.

Results

Coculture with neurons induces early expression of classical NT receptor genes (HTR4, GRIA2, GRIN2B, GRM4, GRM8, DRD1) and neuronal synaptic mediators (CNR1, EGR2, ARC, NGFR, NRXN1) in breast and lung cancer cells. NT-dependent classification of tumor cells within the neuronal niche shows breast cancer cells become GABAergic responsive brain metastases (GRBMs) and transition from relying on autocrine GABA, to paracrine GABA from adjacent neurons; while autocrine Dopaminergic breast and lung tumor cells persist. In vivo studies confirm reliance on paracrine GABA is an early CNS-acclimation strategy in breast cancer. Moreover, neuronal contact induces early resurgence in Reelin expression in tumor cells through epigenetic activation, facilitating CNS adaptation.

Conclusion

Tumor-neuron interactions allow for CNS adaptation early in the course of brain metastasis.
Intravenous immunoglobulin for interstitial lung diseases of anti-melanoma differentiation-associated gene 5-positive dermatomyositis
Authors: Wang Li-Mei , Yang Qi-Hua , Zhang Lei , Liu Sheng-Yun , Zhang Pan-Pan , Zhang Xin , Liu Xiao-Jun , Han Li-Shuai , Li Tian-Fang
Published: December 2021

Objective

Rapidly progressive interstitial lung disease (RP-ILD) in DM patients positive for anti-melanoma differentiation-associated gene 5 (anti-MDA5) autoantibody (MDA5-DM) often have a poor prognosis, frequently fatal. As there is a scarcity of data regarding the effect of intravenous immunoglobulin (IVIG) on RP-ILD in MDA5-DM patients (MDA5-RPILD), we conducted this study to determine the efficacy of a IVIG add-on initial treatment.

Methods

Patients with newly-onset MDA5-RPILD from September 2018 to June 2020 were retrospectively reviewed for 6 months in the First Affiliated Hospital of Zhengzhou University. They were divided into two groups: IVIG and non-IVIG groups. The major measurement of treatment outcome was the difference in the mortality in 3-month and 6-month between two group patients. Other relevant indicators were also recorded, including the incidence of infection, the dosages of GCs, the remission rate and the variables in laboratory data.

Results

The IVIG group (n = 31) showed significantly lower 6-month mortality rate than the non-IVIG group (n = 17) (22.6% vs 52.9%; P =0.033). The IVIG group patients had a higher remission rate at 3 months (71.0% vs 41.2%; P =0.044). Gradual reduction was observed in the first 3 months with regard to the titre of anti-MDA5 autoantibody, the serum level of ferritin and the ground glass opacification GGO scores.

Conclusion

IVIG adjunct therapy is a very effective first-line treatment for patients with MDA5-RPILD. IVIG may increase the survival and remission rate by lowering ferritin concentration, anti-MDA5 titre and GGO score.
HIV-related stigma and discrimination by healthcare workers in Egypt
Authors: Galal Yasmine Samir , Khairy Walaa Ahmed , Mohamed Rahma , Esmat Gamal , Negm Mohamed , Alaty Waleed Hamed Abd , Saeed Maysaa A , Fouad Rabab , Elzahaby Amgad Ali , Zaky Samy , Sakr Mohamed A , Cordie Ahmed
Published: December 2021

Background

HIV-related stigma and discrimination (SAD) have imposed serious adverse health consequences on people living with HIV (PLHIV), including limited access to medical care and delayed diagnosis, which in turn limits the prevention and control of the disease. This study was conducted to explore the stigmatizing attitudes and behaviors of healthcare workers (HCWs) towards HIV patients and PLHIV.

Methods

A cross-sectional study targeted HCWs who attended the United Conference of Hepatogastroenterology and Infectious Diseases that was held on 25–28 September 2019 in Cairo governorate. A self-administrated questionnaire was completed by 359 HCWs.

Results

The majority of HCWs reported some discriminatory practices when rendering care to HIV patients, with nurses showing the highest significant number of discriminatory practices. A considerable proportion of HCWs reported witnessing HIV-related SAD at their health facilities.

Conclusions

HIV-related SAD was prevalent among HCWs. Hence, HIV-related training relevant to the needs of different groups of HCWs is recommended. Provision of infection control supplies to protect against occupational exposure is also needed. The setting and enforcement of anti-stigma policies and guidelines in various healthcare settings are crucial.
Cytokine Profile From the Ligamentum Flavum in Patients with Ossification of the Posterior Longitudinal Ligament in the Cervical Spine
Authors: Yayama Takafumi , Mori Kanji , Saito Hideki , Fujikawa Hitomi , Kitagawa Masahiro , Okumura Noriaki , Nishizawa Kazuya , Nakamura Akira , Kumagai Kosuke , Mimura Tomohiro , Imai Shinji
Published: December 2021

Study Design.

Histological, immunohistochemical, and suspension array analyses of cytokine expression in human cervical ossification of the posterior longitudinal ligament (OPLL).

Objectives.

The aim of this study was to determine whether changes in the cytokine profile reflect the maturation of chondrocytes and osteoblasts are associated with OPLL development.

Summary of Background Data.

OPLL progresses gradually over a prolonged period and may lead to serious spinal cord complications. However, treatment methods only include conservative therapy for neurological symptoms or surgical decompression, whereas preventive therapy for OPLL remains nonexistent.

Methods.

Ligamentous samples were harvested from 24 patients with OPLL who underwent spinal surgery, and five control samples from cervical spondylotic myelo/radiculopathy patients without OPLL. Tissue sections were used for immunohistochemical studies and primary cells were cultured from the ligamentous samples for cytokine profiling. Using a suspension array system, concentrations of 27 inflammatory cytokines or growth factors were measured to generate the cytokine profiles.

Results.

Suspension array and immunoblot analysis revealed significant increments in the levels of interleukin (IL)-6, IL-1α, basic fibroblast growth factor, and RANTES in patients with OPLL. Immunohistochemical analysis further revealed that these factors were present in mesenchymal cells within the degenerative portion of the ligamentous matrix.

Conclusion.

Our findings suggest that specific changes in the cytokine profile during ossification promote osteoblast differentiation, thereby providing new insights into OPLL pathogenesis. Moreover, this work supports the development of a new therapeutic method for preventing OPLL progression by regulating the cytokine profiles.

Level of Evidence: 3
Correcting Caudal Septal Deviation with a Modified Horizontal Mattress Suture
Authors: Grover Ritwik , Seyidova Nargiz , Alnaeem Hassan , Lin Samuel J.
Published: December 2021

Correction of caudal septal deviation remains surgically challenging, given its imperative function as a nasal tip stabilizer and factor in tip projection, as well as its impact on the nasolabial angle and length of the nose. Although various procedures have been devised to repair the caudal septum using grafting techniques, correction with minimally invasive isolated suture techniques is limited. In this case report, we describe a modified horizontal mattress suture to correct caudal septal deviation in a patient undergoing revision septorhinoplasty. The patient followed up for 2 years after the surgery, and correction of the anterior caudal septum deviation remained intact.
COVID-19 Infection, Prevention, and Control Considerations in the Obstetric Environment
Authors: Acker Karen , Eagen-Torkko Maria , Riley Laura E. , Saiman Lisa
Published: December 2021

Pregnancy increases the risk of severe illness due to coronavirus disease 2019 (COVID-19). Thus, prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in all obstetrical health care settings requires consistent implementation of multiple evidence-based practices and consideration of local epidemiology, local regulations for COVID-19, and guidance from the Centers for Disease Control and Prevention and Professional Societies. COVID-safe practices should be implemented for patients, visitors/support persons, and health care personnel and include screening, appropriate personal protective equipment, and transmission precautions. Vaccination of all health care personnel, pregnant people, and their support persons remains the best strategy to prevent COVID-19.
Obstetrical Telehealth and Virtual Care Practices During the COVID-19 Pandemic
Authors: Kern-Goldberger Adina R. , Srinivas Sindhu K.
Published: December 2021

The coincidence of a global pandemic with 21st-century telecommunication technology has led to rapid deployment of virtual obstetric care beginning in March of 2020. Pregnancy involves uniquely time-sensitive health care that may be amenable to restructuring into a hybrid of telemedicine and traditional visits to optimize accessibility and outcomes. The coronavirus disease 2019 pandemic has provided an unprecedented natural laboratory to explore how virtual obstetric care programs can be developed, implemented, and maintained, both as a contingency model for the pandemic and potentially for the future. Here, we discuss the role of telehealth and virtual care for pregnancy management in the coronavirus disease 2019 pandemic, as well as anticipated barriers, challenges, and strategies for success for obstetric telemedicine.
Comparative efficacy and safety of antipseudomonal β-lactams for pediatric febrile neutropenia
Authors: Tan Xinmei , Li Yan , Xi Jiaxi , Guo Sitong , Su Henghai , Chen Xiaoyu , Liang Xueyan
Published: December 2021

Background:

Antipseudomonal β-lactams have been used for the treatment of febrile neutropenia (FN); however, the efficacy and safety of antipseudomonal β-lactams in pediatric patients remain unclear. The aim of this study was to comprehensively compare the efficacy and side effects of optional antipseudomonal β-lactams for pediatric FN.

Methods:

PubMed, Embase, Medline, and Cochrane Library were systematically searched from their inception to December 18, 2020. Eligible randomized controlled trials in which pediatric FN patients were treated with an empiric monotherapy of antipseudomonal β-lactams were selected. Data synthesis was performed using WinBUGS 14.0 software and meta packages implemented in R 3.6.2. Random-effects network meta-analysis was performed, and dichotomous data were pooled as odds ratios with 95% confidence intervals. The primary outcome was treatment success without modification; the secondary outcomes were adverse events (AEs), all-cause mortality, and new infections. The GRADE tool was used to assess the quality of the evidence. The protocol was registered with PROSPERO ID CRD42021226763.

Results:

Eighteen studies with 2517 patients were included. The results showed no statistically significant difference between the optional antipseudomonal β-lactams in the outcomes of treatment success without modification, all AEs, all-cause mortality, and new infections for pediatric FN. Based on the results of Bayesian rank probability, meropenem was ranked highest among all the treatment options with regard to treatment success without modification benefit; ceftazidime and meropenem were associated with a lower risk of AEs; cefoperazone/sulbactam and piperacillin/tazobactam were associated with a lower risk of mortality, and piperacillin/tazobactam and meropenem were associated with a lower risk of new infections. The quality of evidence was moderate.

Conclusions:

Meropenem and piperacillin/tazobactam were found to be better with regard to treatment success without modification, with a comparable safety profile. Therefore, our findings support the use of meropenem and piperacillin/tazobactam as a treatment option for pediatric FN patients.