bluuebunny/crossref_metadata_2025 huggingface dataset:
MiR398-regulated antioxidants contribute to Bamboo mosaic virus accumulation and symptom manifestation
Authors: Lin Kuan-Yu , Wu Su-Yao , Hsu Yau-Heiu , Lin Na-Sheng
Published: September 2021

Virus infections that cause mosaic or mottling in leaves commonly also induce increased levels of reactive oxygen species (ROS). However, how ROS contributes to symptoms is less well documented. Bamboo mosaic virus (BaMV) causes chlorotic mosaic symptoms in both Brachypodium distachyon and Nicotiana benthamiana. The BaMV △CPN35 mutant with an N-terminal deletion of its coat protein gene exhibits asymptomatic infection independently of virus titer. Histochemical staining of ROS in mock-, BaMV-, and BaMV△CPN35-infected leaves revealed that hydrogen peroxide (H2O2) accumulated solely in BaMV-induced chlorotic spots. Moreover, exogenous H2O2 treatment enhanced yellowish chlorosis in BaMV-infected leaves. Both BaMV and BaMV△CPN35 infection could induce the expression of Cu/Zu superoxide dismutase (CSD) antioxidants at messenger RNA and protein level. However, BaMV triggered the abundant accumulation of full-length NbCSD2 preprotein (prNbCSD2, without transit peptide cleavage), whereas BaMV△CPN35 induced a truncated prNbCSD2. Confocal microscopy showed that majority of NbCSD2-green fluorescent protein (GFP) predominantly localized in the cytosol upon BaMV infection, but BaMV△CPN35 infection tended to cause NbCSD2-GFP to remain in chloroplasts. By 5′-RNA ligase-mediated rapid amplification of cDNA ends, we validated CSDs are the targets of miR398 in vivo. Furthermore, BaMV infection increased the level of miR398, while the level of BaMV titer was regulated positively by miR398 but negatively by CSD2. In contrast, overexpression of cytosolic form NbCSD2, impairing the transport into chloroplasts, greatly enhanced BaMV accumulation. Taken together, our results indicate that induction of miR398 by BaMV infection may facilitate viral titer accumulation, and cytosolic prNbCSD2 induction may contribute to H2O2 accumulation, resulting in the development of BaMV chlorotic symptoms in plants.
TRANS-ACTING SIRNA3-derived short interfering RNAs confer cleavage of mRNAs in rice
Authors: Luo Linlin , Yang Xiaoyu , Guo Mingxi , Lan Ting , Yu Yu , Mo Beixin , Chen Xuemei , Gao Lei , Liu Lin
Published: September 2021

Plant TRANS-ACTING SIRNA3 (TAS3)-derived short interfering RNAs (siRNAs) include tasiR-AUXIN RESPONSE FACTORs (ARFs), which are functionally conserved in targeting ARF genes, and a set of non-tasiR-ARF siRNAs, which have rarely been studied. In this study, TAS3 siRNAs were systematically characterized in rice (Oryza sativa). Small RNA sequencing results showed that an overwhelming majority of TAS3 siRNAs belong to the non-tasiR-ARF group, while tasiR-ARFs occupy a diminutive fraction. Phylogenetic analysis of TAS3 genes across dicot and monocot plants revealed that the siRNA-generating regions were highly conserved in grass species, especially in the Oryzoideae. Target genes were identified for not only tasiR-ARFs but also non-tasiR-ARF siRNAs by analyzing rice Parallel Analysis of RNA Ends datasets, and some of these siRNA–target interactions were experimentally confirmed using tas3 mutants generated by genome editing. Consistent with the de-repression of target genes, phenotypic alterations were observed for mutants in three TAS3 loci in comparison to wild-type rice. The regulatory role of ribosomes in the TAS3 siRNA–target interactions was further revealed by the fact that TAS3 siRNA-mediated target cleavage, in particular tasiR-ARFs targeting ARF2/3/14/15, occurred extensively in rice polysome samples. Altogether, our study sheds light into TAS3 genes in plants and expands our knowledge about rice TAS3 siRNA–target interactions.
Enriched H3K4me3 marks at Pm-0 resistance-related genes prime courgette against Podosphaera xanthii
Authors: Margaritopoulou Theoni , Kizis Dimosthenis , Kotopoulis Dimitris , Papadakis Ioannis E , Anagnostopoulos Christos , Baira Eirini , Termentzi Aikaterini , Vichou Aikaterini-Eleni , Leifert Carlo , Markellou Emilia
Published: September 2021

Powdery mildew (PM) disease, caused by the obligate biotrophic fungal pathogen Podosphaera xanthii, is the most reported and destructive disease on cultivated Cucurbita species all over the world. Recently, the appearance of highly aggressive P. xanthii isolates has led to PM outbreaks even in resistant crops, making disease management a very difficult task. To challenge this, breeders rely on genetic characteristics for PM control. Analysis of commercially available intermediate resistance courgette (Cucurbita pepo L. var. cylindrica) varieties using cytological, molecular, and biochemical approaches showed that the plants were under a primed state and induced systemic acquired resistance (SAR) responses, exhibiting enhanced callose production, upregulation of salicylic acid (SA) defense signaling pathway genes, and accumulation of SA and defense metabolites. Additionally, the intermediate resistant varieties showed an altered epigenetic landscape in histone marks that affect transcriptional activation. We demonstrated that courgette plants had enriched H3K4me3 marks on SA-BINDING PROTEIN 2 and YODA (YDA) genes of the Pm-0 interval introgression, a genomic region that confers resistant to Cucurbits against P. xanthii. The open chromatin of SA-BINDING PROTEIN 2 and YDA genes was consistent with genes’ differential expression, induced SA pathway, altered stomata characteristics, and activated SAR responses. These findings demonstrate that the altered epigenetic landscape of the intermediate resistant varieties modulates the activation of SA-BINDING PROTEIN 2 and YDA genes leading to induced gene transcription that primes courgette plants.
Experiences of Military Primary Care Providers During Chronic Pain Visits: A Qualitative Descriptive Study
Authors: Mathew Asha , McQuinn Honor , Flynn Diane M , Ransom Jeffrey C , Doorenbos Ardith Z
Published: September 2021

Objective

Chronic pain complaints are the second most common reason for outpatient primary care visits, yet a comprehensive assessment of the processes and experiences of providers during a chronic pain visit is still lacking. This qualitative descriptive study aimed to conceptualize the processes and experiences that military primary care providers go through while they assess and manage chronic pain.

Setting

Single U.S. Army medical center.

Methods

Semistructured interviews with 12 military primary care providers. Interviews were audio-recorded, transcribed, and coded with the use of qualitative software. Transcripts were analyzed with thematic analysis to identify emergent themes.

Results

Three broad themes with associated subthemes captured the processes and the providers’ experiences: 1) comprehending the pain story—asking the right questions about pain impact, navigating through the complexities of the pain story, and conveying understanding of the pain story back to the patient; 2) optimizing the pain story—perceiving provider–patient disconnect on pain management goals, resetting realistic goals, creating an optimal individualized treatment plan, and evaluating treatment effectiveness; and 3) empathetic and therapeutic engagement with patients—trusting patients and fostering the patient–provider relationship. A thematic map illustrates these provider experiences.

Conclusions

During chronic pain visits, the provider–patient disconnect on the goals of chronic pain treatment presents a considerable challenge. Further in-depth studies on addressing provider–patient disconnect are warranted to identify solutions, which would help providers communicate realistic chronic pain management expectations to patients. The themes and subthemes described in this study could serve as a guide for directing strategies to improve chronic pain visits in primary care.
Initial impact of the COVID-19 pandemic on public health training: participatory action research to understand experiences in the East Midlands
Authors: Maile E L , Horsley S M , Dunn T , Knight J M ,   The Delphi group registrars, Brough Grace , Davies Nathan , Pierce Elizabeth , Evans Megan S , Rebecca Johnston Helen , Turvey Andrew , Blackmore Claire , Cooper Rosie
Published: September 2021

Background

Specialty public health training consists of 48 months of practice across the domains of health protection, healthcare public health and health improvement.

With the onset of the COVID-19 pandemic, activity pivoted towards pandemic management and the response became a significant element of registrar practice.

This research aimed to understand the impact of this shift in focus on registrars’ role and training.

Methods

Participatory action research comprising (i) a reflective survey sent to all specialty registrars in the East Midlands training region and (ii) Delphi rounds with survey respondents to generate consensus and define themes.

Results

Sixteen (44%) registrars completed the survey with 12 (75%) participating in the Delphi rounds. The early pandemic response stages both challenged and re-affirmed registrars’ role and identity in public health and training while providing unique and diverse learning and development. Underpinning these themes is a variability in experience depending on prior experience, placement and training stage.

Conclusions

The pandemic impacted the practice, training and home-life of registrars who were required to negotiate significant challenge and uncertainty. This original work adds to a growing body of correspondence and opinion pieces articulating the experiences and challenges of medical and public health education during a pandemic.
Morphometric Analysis of Structural MRI Using Schizophrenia Meta-analytic Priors Distinguish Patients from Controls in Two Independent Samples and in a Sample of Individuals With High Polygenic Risk
Authors: Lancaster Thomas M , Dimitriadis Stavros I , Perry Gavin , Zammit Stan , O’Donovan Michael C , Linden David E
Published: September 2021

Schizophrenia (SCZ) is associated with structural brain changes, with considerable variation in the extent to which these cortical regions are influenced. We present a novel metric that summarises individual structural variation across the brain, while considering prior effect sizes, established via meta-analysis. We determine individual participant deviation from a within-sample-norm across structural MRI regions of interest (ROIs). For each participant, we weight the normalised deviation of each ROI by the effect size (Cohen’s d) of the difference between SCZ/control for the corresponding ROI from the SCZ Enhancing Neuroimaging Genomics through Meta-Analysis working group. We generate a morphometric risk score (MRS) representing the average of these weighted deviations. We investigate if SCZ-MRS is elevated in a SCZ case/control sample (NCASE = 50; NCONTROL = 125), a replication sample (NCASE = 23; NCONTROL = 20) and a sample of asymptomatic young adults with extreme SCZ polygenic risk (NHIGH-SCZ-PRS = 95; NLOW-SCZ-PRS = 94). SCZ cases had higher SCZ-MRS than healthy controls in both samples (Study 1: β = 0.62, P < 0.001; Study 2: β = 0.81, P = 0.018). The high liability SCZ-PRS group also had a higher SCZ-MRS (Study 3: β = 0.29, P = 0.044). Furthermore, the SCZ-MRS was uniquely associated with SCZ status, but not attention-deficit hyperactivity disorder (ADHD), whereas an ADHD-MRS was linked to ADHD status, but not SCZ. This approach provides a promising solution when considering individual heterogeneity in SCZ-related brain alterations by identifying individual’s patterns of structural brain-wide alterations.
Brain amyloid burden, sleep, and 24-hour rest/activity rhythms: screening findings from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration Studies
Authors: Spira Adam P , Zipunnikov Vadim , Raman Rema , Choi Jiyoon , Di Junrui , Bai Jiawei , Carlsson Cynthia M , Mintzer Jacobo E , Marshall Gad A , Porsteinsson Anton P , Yaari Roy , Wanigatunga Sarah K , Kim John , Wu Mark N , Aisen Paul S , Sperling Reisa A , Rosenberg Paul B
Published: September 2021

Study Objectives

To examine in a subsample at the screening phase of a clinical trial of a β-amyloid (Aβ) antibody whether disturbed sleep and altered 24-hour rest/activity rhythms (RARs) may serve as markers of preclinical Alzheimer’s disease (AD).

Methods

Overall, 26 Aβ-positive (Aβ+) and 33 Aβ-negative (Aβ−) cognitively unimpaired participants (mean age = 71.3 ± 4.6 years, 59% women) from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) and the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies, respectively, wore actigraphs for 5.66 ± 0.88 24-hour periods. We computed standard sleep parameters, standard RAR metrics (mean estimating statistic of rhythm, amplitude, acrophase, interdaily stability, intradaily variability, relative amplitude), and performed a novel RAR analysis (function-on-scalar regression [FOSR]).

Results

We were unable to detect any differences between Aβ+ and Aβ− participants in standard sleep parameters or RAR metrics with our sample size. When we used novel FOSR methods, however, Aβ+ participants had lower activity levels than Aβ− participants in the late night through early morning (11:30 pm to 3:00 am), and higher levels in the early morning (4:30 am to 8:30 am) and from midday through late afternoon (12:30 pm to 5:30 pm; all p < .05). Aβ+ participants also had higher variability in activity across days from 9:30 pm to 1:00 am and 4:30 am to 8:30 am, and lower variability from 2:30 am to 3:30 am (all p < .05).

Conclusions

Although we found no association of preclinical AD with standard actigraphic sleep or RAR metrics, a novel data-driven analytic method identified temporally “local” RAR alterations in preclinical AD.
Spatial variability in tree-ring carbon isotope discrimination in response to local drought across the entire loblolly pine natural range
Authors: Lin Wen , Noormets Asko , King John S , Marshall John , Akers Madison , Cucinella Josh , Fox Thomas R , Laviner Marshall A , Martin Timothy A , Mcnulty Steve , Meek Cassandra , Samuelson Lisa , Sun Ge , Vogel Jason , Will Rodney E , Domec Jean-Christophe
Published: September 2021

Considering the temporal responses of carbon isotope discrimination (Δ13C) to local water availability in the spatial analysis of Δ13C is essential for evaluating the contribution of environmental and genetic facets of plant Δ13C. Using tree-ring Δ13C from years with contrasting water availability at 76 locations across the natural range of loblolly pine, we decomposed site-level Δ13C signals to maximum Δ13C in well-watered conditions (Δ13Cmax) and isotopic drought sensitivity (m) as a change in Δ13C per unit change of Palmer’s Drought Severity Index (PDSI). Site water status, especially the tree lifetime average PDSI, was the primary factor affecting Δ13Cmax. The strong spatial correlation exhibited by m was related to both genetic and environmental factors. The long-term average water availability during the period relevant to trees as indicated by lifetime average PDSI correlated with Δ13Cmax, suggesting acclimation in tree gas-exchange traits, independent of incident water availability. The positive correlation between lifetime average PDSI and m indicated that loblolly pines were more sensitive to drought at mesic than xeric sites. The m was found to relate to a plant’s stomatal control and may be employed as a genetic indicator of efficient water use strategies. Partitioning Δ13C to Δ13Cmax and m provided a new angle for understanding sources of variation in plant Δ13C, with several fundamental and applied implications.
Less Invasive Surfactant Administration (LISA) vs. Intubation Surfactant Extubation (InSurE) in Preterm Infants with Respiratory Distress Syndrome: A Pilot Randomized Controlled Trial
Authors: Pareek Prince , Deshpande Sujata , Suryawanshi Pradeep , Sah Love Kumar , Chetan Chinmay , Maheshwari Rajesh , More Kiran
Published: September 2021

Objective

There has been an endeavor in recent years, to administer surfactant by minimally invasive techniques to neonates with surfactant deficiency. The objective of this study was to compare the need for intubation and mechanical ventilation after surfactant delivery, using Less Invasive Surfactant Administration (LISA) technique and Intubation SURfactant Extubation (InSurE), in preterm infants with respiratory distress syndrome (RDS).

Methods

We conducted a pilot randomized control trial (RCT) at a tertiary care center over a period of 18 months. Preterm neonates with RDS (gestational age 28–36 weeks) were randomized to receive surfactant within 6 h of birth by InSurE or LISA. The primary outcome was need for intubation and mechanical ventilation within 72 h of birth. Infants were followed until discharge for adverse events and complications.

Results

A total of 40 infants were analyzed (20 in each group). There was no difference in the need for intubation and mechanical ventilation within 72 h of birth between the two groups [InSurE, 6 (30%) and LISA, 6 (30%), relative risk 1.0, 95% confidence interval 0.51–1.97]. About 15% of infants in both groups had adverse events during the procedure. There was no statistically significant difference in the rates of major complications or duration of respiratory support, hospital stay and mortality.

Conclusion

We found LISA to be feasible and equally effective as InSurE for surfactant administration in the treatment of RDS in preterm infants. Future larger RCTs are required to compare the efficacy and long-term outcomes of LISA with the standard invasive methods of surfactant administration.
Alternative Cosmetic and Medical Applications of Injectable Deoxycholic Acid: A Systematic Review
Authors: Liu Chaocheng , Li Monica K. , Alster Tina S.
Published: September 2021

BACKGROUND

Beyond submental fat reduction, injectable deoxycholic acid (DCA) has gained popularity in recent years for various minimally invasive lipolysis applications.

OBJECTIVE

To summarize and evaluate the evidence of off-label uses of injectable DCA.

METHODS

MEDLINE, Embase, CINAHL, Web of Science, and CENTRAL were searched. The outcomes measured included applications of DCA, treatment regimen, and its efficacy. An overall success rate for each condition was calculated based on the improvement defined in the included studies.

RESULTS

Eleven studies evaluated the cosmetic use of DCA for excess adipose tissue on various anatomical locations. The outcomes were evaluated at time points ranging from 1 to 21 months post-treatment, with overall success rates over 85%. Eight case reports and series reported the success of using DCA treating lipomas, xanthelasmas, paradoxical adipose hyperplasia, fibrofatty residue of infantile hemangioma, piezogenic pedal papules, and HIV-associated lipohypertrophy. Although the preliminary efficacies were high, the overall recommendations for off-label uses are weak because of the lack of high-level studies.

CONCLUSION

The review emphasizes the diversity of injectable DCA as a minimally invasive technique for lipolysis. Further high-level studies demonstrating consistent treatment regimens and methods of evaluation are warranted to make more definitive recommendations regarding off-label DCA use.
Comparison of Survival Outcomes With/Without Adjuvant Radiation Therapy in Desmoplastic Melanoma
Authors: Lewis Gary D. , Guzman Anthony K. , Haque Waqar , McLellan Beth N. , Teh Bin S.
Published: September 2021

BACKGROUND

Desmoplastic melanoma (DM) is a rare variant of cutaneous melanoma with a high rate of local recurrence. Recent studies have indicated a potential benefit in local control with the addition of adjuvant radiotherapy (RT).

OBJECTIVE

This study sought to evaluate the outcomes of adjuvant RT for patients with DM.

MATERIALS AND METHODS

The National Cancer Database was queried (2004–2015) for patients with newly diagnosed, nonmetastatic DM. Patients were divided into 2 groups based on the adjuvant therapy they received: RT or observation. Statistics included multivariable logistic regression to determine factors predictive of receiving adjuvant RT, Kaplan–Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS.

RESULTS

There was no difference in median OS between patients treated with RT when compared with patients observed (111.4 months vs 133.9 months, p = .1312). On multivariable analysis, older age, T stage ≥2, N stage ≥1, and no receipt of immunotherapy were associated with worse OS.

CONCLUSION

In this large study evaluating efficacy of adjuvant RT in DM, no overall survival benefit was observed among patients receiving adjuvant RT.
Safety of Laser Hair Removal in Patients Receiving Systemic Isotretinoin for Acne Vulgaris
Authors: Sarigul Guduk Sukran , Tukenmez Demirci Gulsen
Published: September 2021

BACKGROUND

A few reports on scar and keloid formation in patients receiving systemic isotretinoin have encouraged a conservative approach in which laser procedures are delayed during and 6 to 12 months after the completion of treatment.

OBJECTIVE

To assess the safety of laser hair removal with alexandrite, diode, and Nd:YAG lasers in patients receiving systemic isotretinoin treatment.

MATERIALS AND METHODS

Fifty-two patients who underwent laser hair removal during isotretinoin treatment were retrospectively analyzed and compared with a control group for side effects.

RESULTS

There were 48 female and 4 male patients. The average isotretinoin dose was 33.7 mg/d. The average interval between the start of isotretinoin treatment and the first laser hair removal was 39.3 days. The mean number of sessions under treatment was 4.1. Three patients had temporary crusting, and 1 patient had a small area of temporary hypopigmentation. Five (9.6%) patients in the control group had crusting. The incidence of side effects was not significantly different between the 2 groups (p > .05). Neither patients in the isotretinoin group nor those in the control group experienced blistering, pigmentation, ulceration, and scar or keloid formation.

CONCLUSION

Laser hair removal is a safe procedure with alexandrite, diode, and Nd:YAG lasers in patients receiving systemic isotretinoin.
Forehead Movement Discrepancies After Botulinum Toxin Injections: A Review of Etiology, Correction, and Prevention
Authors: Walker Bridget , Hand Matthew , Chesnut Cameron
Published: September 2021

BACKGROUND

Forehead rhytides are a popular target for botulinum toxin injections, but neuromodulation of the frontalis can be fraught with complications because of its anatomic complexity and integral role in brow position and expressivity.

OBJECTIVE

This article explores common forehead movement discrepancies that can occur after neuromodulation of the frontalis, as well as how to correct and prevent them.

METHODS

A review of the literature was conducted and combined with clinical experience to examine underlying forehead anatomy, etiology and correction of forehead movement discrepancies, and important factors to consider before injecting the frontalis with botulinum toxin.

RESULTS AND CONCLUSION

Variable anatomy from person to person necessitates an individualized treatment approach to achieve the best cosmetic results and prevent the occurrence of forehead movement discrepancies.
Upper Margin of the Forehead Flap and Its Correlation With Aesthetic Results in Nasal Reconstruction in Fitzpatrick Skin Type III and IV Chinese
Authors: Yen Cheng-I , Yeow Jenny Yun-Jen , Chang Chun-Shin , Hsiao Yen-Chang
Published: September 2021

BACKGROUND

The forehead flap is one of the most commonly used methods for nose reconstruction.

OBJECTIVE

To determine the ideal upper margin of the flap in nasal reconstruction and its correlation with aesthetic results.

METHODS

From April 2013 to September 2017, 40 patients underwent nasal reconstruction involving the dorsum with a forehead flap. The authors hypothesized 5fdifferent levels as the position to place the upper margin of the forehead flap: (1) glabella, (2) level of the upper eyelid, (3) intercanthal line, (4) horizontal line between the keystone and intercanthal line, and (5) the keystone. Then they photoshopped the upper margins of the forehead flap at 5 different levels and designed a questionnaire. Nasal reconstructive plastic surgeons, medical practitioners, and people without medical backgrounds chose the most aesthetically pleasing photograph for every patient.

RESULTS

The questionnaire showed that the most aesthetically pleasing positions were located at glabella (n = 0), level of upper eyelid (n = 9), intercanthal line (n = 24), the line between keystone and intercanthal line (n = 6), and keystone (n = 1).

CONCLUSION

The authors suggest placing the upper margin of the forehead flap at the level of the intercanthal line in nasal reconstruction involving the dorsum to achieve the best aesthetic results.
Improvement in Quality of Life and Pain in Patients With Hidradenitis Suppurativa After Wide Local Excision: A Prospective Study
Authors: Dick Julika , Kröhl Verena , Enk Alexander , Hartschuh Wolfgang , Gholam Patrick
Published: September 2021

BACKGROUND

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects patients' quality of life (QoL).

OBJECTIVE

To investigate changes in QoL in patients with HS after wide local excision (WLE) and to examine the level of pain, rate of postoperative complications, recurrences, and the time to complete wound closure.

METHODS

Fifty-five patients were enrolled in this prospective study. All patients underwent WLE of HS, followed by secondary wound healing. Dermatologic Life Quality Questionnaire, pain, and wound size were measured 1 day, 3 weeks, 3 months, and 6 months after surgery.

RESULTS

Dermatologic Life Quality Questionnaire and pain scores (mean ± SD) improved significantly (both p < .001) from 14.5 ± 7.3 and 3.7 ± 2.8 at baseline to 5.8 ± 6.9 and 0.8 ± 1.7, 6 months postoperatively, respectively. Wounds were closed completely by secondary intention after 4.4 ± 2.8 months. Sixteen patients (29.1%) experienced postoperative complications, local recurrences in the treated sites were observed in 11 patients (20%), and new lesions in untreated sites were observed in 5 cases (9.1%).

CONCLUSION

Wide local excision significantly improves patients' QoL and pain, and, given its low rate of recurrence and complications, should be considered as a first-line therapy, especially in patients with higher Hurley stages.
Mode of Action of RZL-012, a New Fat-Reducing Molecule
Authors: Blaugrund Eran , Gueta Racheli , Zernov Anton , Bloomenfeld Alon
Published: September 2021

BACKGROUND

RZL-012 (5-[3,6-dibromo-9H-carbazol-9-yl]-N,N,N-trimethylpentan-1-aminium chloride) is a novel investigational drug injected subcutaneously into fat tissues in patients with fat-related disorders (Dercum disease) or subjects seeking aesthetic changes.

OBJECTIVE

Preclinical studies were undertaken to understand RZL-012's mechanism of action.

MATERIALS AND METHODS

The effects of RZL-012 were tested in vitro by measuring adipocyte cell killing, membrane integrity, cytosolic calcium, and mitochondrial membrane potential (MMP). In vivo studies in pigs evaluated RZL-012's adipocyte killing effect and measured pig fat thickness in the injected areas.

RESULTS

RZL-012 triggered adipocyte cell killing with IC50 values ranging from 25 to 106 μM. RZL-012 demonstrated initial effects on membrane integrity and calcium levels with delayed alterations in MMP. Incubation of RZL-012 with nanoghosts increased membrane permeability, culminating in full membrane destruction. Analysis of injected areas in pigs revealed liponecrosis 24 hours after dosing followed by an inflammatory response and formation of fibrotic tissue. Three months after dosing, an 18% reduction in mean fat thickness was observed in RZL-012 treated pigs.

CONCLUSION

RZL-012 destroys adipocytes by directly disrupting cell membrane integrity. Replacement of dead fat tissue by fibrotic tissue enables healing and causes contraction of the injected area. These effects are translated into significant reduction in fat tissue volume.
Electronic Alcohol Screening and Brief Intervention and Referral to Treatment for College Students With Increased Alcohol Use Risk
Authors: Lachance Sonya L. , Becker Ann M. , Zucker Donna M.
Published: September 2021

Objective

The purpose of this study was to provide an understanding of the health care provider's perceptions and experiences with technology adoption in alcohol use disorder and clinical Screening, Brief Intervention, and Referral to Treatment (SBIRT).

Method

The study used an exploratory, multimethod strategy to gain a comprehensive understanding of facilitators and barriers to technology adoption in alcohol SBIRT in a primary care setting. However, although providers state that they understand the importance of screening patients for alcohol use disorder, only 15.4% of providers consistently screen. This study's primary aim was to gain insights of the study participants and what events or experiences help them with SBIRT adoption.

Results

The findings show a gap in the understanding of how to integrate behavioral health screenings in the primary care workflow using the electronic health record system. Providers want to do SBIRT in clinical care, yet time-constrained visits remain an issue.

Conclusions

Taking the time to map the workflow in advance of a practice change is a critical first step toward implementing it in a primary care setting. Time-constrained patient visits remain an ongoing problem and require novel methods to address issues, particularly in early identification of alcohol use disorder.
Internet Gaming Disorder in Children and Associated Factors and Parents' Opinions
Authors: Vayisoglu Sumbule Koksoy , Mutlu Meryem , Oncu Emine
Published: September 2021

Objective

The aim of this study is to determine internet gaming disorder (IGD) prevalence in primary grade students and the associated factors and parents' opinions about their children's gaming habits.

Materials and Methods

This cross-sectional study was conducted between April 1, 2019, and June 1, 2019. In this study, 805 children's and parents' forms were analyzed. Participation rate was 94.5%. Data were collected using “Digital Gaming-Children's Form,” “Digital Gaming-Parents' Form,” and the “Internet Gaming Disorder Scale-Short Form (IGDS9-SF).” Data were analyzed using descriptive statistics and significance tests.

Results

The mean age of the students was 11.24 ± 1.243 years; 42.7% were male. The children's mean IGDS9-SF score was 16.83 ± 6.53. There were only 91 students with a score equal to or above the cutoff point of 36. The mean IGDS9-SF scores varied according to gender, grade level, family environment, and employment status of the father. Analysis of the students' gaming characteristics and mean IGDS9-SF scores showed that their mean IGDS9-SF scores varied depending on computer/phone/tablet gaming status, type of game played, type of connection, mode of connection, frequency of conflicts with parents, and whether families received help to regulate gaming behavior.

Conclusion

It is essential for a family to have information about games and talk to their children about the games they play to provide appropriate supervision. Providing families and children with counseling about digital games, IGD symptoms, and considerations by nurses during home visits can play an important role in preventing IGD.
Factors Influencing Smoking Decisions Among Older Korean American Men
Authors: Sin Mo-Kyung , Ro KumHee
Published: September 2021

Cigarette smoking is highly prevalent among Korean American men. Although the nationwide anti-smoking efforts and American individualism-oriented cultural system seem to help some Korean American men stop smoking, many of them still smoke. Thus, it is necessary to understand factors influencing decisions to continue smoking or stop smoking among older Korean American men. We recruited a convenience sample of 24 Korean American men (12 current smokers, 12 former smokers) who were aged 55–79 years to participate in this qualitative study. Five focus groups and nine individual interviews were conducted. Thematic content analysis was used to analyze the qualitative data. Participants were older (mean age = 69 years) and have lived in the United States an average of 26 years. Average duration of smoking was 41 years among current smokers and 31 years among former smokers. Key themes influencing continuous smoking include stress relief, fear of side effects, difficulty stopping, smoking peers, and misbeliefs about lung cancer and smoking, whereas key themes for decisions to stop smoking include present health issues, family/physician/media recommendation, and smoking-restricted environments. This study reinforces the importance of culturally and age-relevant smoking cessation programs targeting smokers and their families. Future quantitative studies in different geographic areas can validate the study findings.
Gender Differences in Prevalence and Risk Factors Associated With Substance Use in 50- to 65-Year-Old Jamaicans
Authors: Govia Ishtar O. , Doubova Svetlana V. , Younger-Coleman Novie , Atkinson Uki
Published: September 2021

The purpose of this study was to evaluate gender-specific differences in prevalence and risk factors for alcohol, tobacco, and marijuana use among 50- to 65-year-old Jamaicans. We performed secondary analysis of the 2016 Jamaica National Drug Use Prevalence Survey. The dependent variables were self-reported use of tobacco, alcohol, and marijuana in the 30 days before the survey. The independent variables included general, socioeconomic, and community characteristics and concomitant substance use. Gender-stratified multiple Poisson regressions were conducted. The survey included 1,099 individuals aged 50–65 years; 50.3% were men. Reported use was significantly higher in men than in women: alcohol (54.9% vs. 17.8%), marijuana (22.4% vs. 2.2%), and tobacco (19.2% vs. 3.9%). High income was associated with alcohol use in women, whereas low and middle incomes were associated with marijuana use among men. Being employed was associated with tobacco use among women and with alcohol use among men. Rural residence was associated with alcohol use in women and with marijuana use in men. High neighborhood disorder was associated with tobacco use in women and alcohol and marijuana use in men. Concomitant substance use increased the likelihood of alcohol, tobacco, and marijuana use in men and women. We conclude that gender-sensitive strategies to substance use prevention and treatment are needed in Jamaica.
Creating Video-Based Education Modules for Parents of Newly Diagnosed Pediatric Patients With Cancer
Authors: Mills Denise , Zupanec Sue , Breakey Vicky , Chakkalackal Lauren , Cook Sadie , Cox Stephanie , Gibson Paul , Punnett Angela , Sung Lillian
Published: September 2021

Background

Parents of children newly diagnosed with cancer are required to understand a significant amount of new information during a time of distress. Parents of children with cancer have expressed that concise information with visual cues, which can be repeated, positively influences their ability to understand.

Objectives

The primary objective was to develop 2 concise, video-based education modules that are understandable to parents of children with cancer. A secondary objective was to determine feasibility of a future trial evaluating efficacy of video-based education.

Methods

The study was conducted in phases: script development, video creation, and feasibility testing. Topics were “managing fever at home” and “giving medications at home.” Content was developed by pediatric oncology experts and turned into video scripts. Scripts were refined through cognitive interviews with parents of children with cancer. Feasibility testing included recruitment of 20 parents of a child given a diagnosis of cancer within 4 weeks. Parents watched both videos and answered questions that assessed their understanding and perceived confidence.

Results

Final scripts were reviewed by 25 participants. Feasibility was achieved with 20 parents recruited within 7 weeks, with 100% watching both videos and answering knowledge and confidence questions.

Conclusions

We successfully developed 2 educational videos for parents of children newly diagnosed with cancer. A future trial to test the efficacy of video-based education modules is feasible.

Implications to Practice

Delivering quality education to parents of children newly diagnosed with cancer can decrease parental distress and improve safe care during a high-risk time for treatment-related morbidity and mortality.
Effect of Recorded Maternal Voice on Emergence Delirium in Children Under General Anesthesia
Authors: Wang Cong , Wang Wei , Wang Shuo , He Rendong , Yang Haiqi , Jia Yong , Chen Li
Published: September 2021

To determine the effect of recorded maternal voice on emergence delirium (ED) in children under general anesthesia, a three-group randomized trial was conducted. A total of 102 children were randomly assigned to mother recording group (n = 34), stranger recording group (n = 34), and control group (n = 34). All subjects were assessed for ED with the Pediatric Anesthesia Emergence Delirium Scale; pain with the Face, Legs, Activity, Cry, and Consolability Scale; and various recovery durations and hemodynamic parameters at six time points. One-way analysis of variance showed that the ED score was significantly lower in the mother recording group (F = 18.520, p = 0.000), and statistical significance was observed in the duration of eye opening (p = 0.001) and tracheal extubation (p = 0.002). Generalized estimating equations observed interaction effects on heart rate and blood pressure (both p = 0.000). Mothers' voice might help reduce ED in children under general anesthesia.
Gastric Adenocarcinoma and Proximal Polyposis of the Stomach in a Hispanic Pediatric Patient With APC Gene Variant c.-191T>G
Authors: Roberts Annette Gawron , Bujarska Malgorzata , Bauer Mislen , Brathwaite Carole , Pelaez Liset , Reeves-Garcia Jesse
Published: September 2021

Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare gastric polyposis syndrome defined by numerous polyps (>100) in the fundus and body of the stomach with sparing of the lesser curvature and antrum. GAPPS is linked to a variant in the promoter 1B region of the APC gene. These variants carry a high risk of developing gastric adenocarcinoma, which can occur at an early age. We report a case of GAPPS discovered in a 16-year-old Hispanic girl after endoscopy detected extensive fundic gland polyposis. Genetic testing revealed a promoter 1B point mutation of the APC gene, variant c.-191T>G. Although similar variants have been reported (i.e., c.-191T>C, c.-195A>C, c.-192A>G) in association with GAPPS, variant c.-191T>G has not nor has GAPPS ever been described in a Hispanic individual before.
A CLN6-CRMP2-KLC4 complex regulates anterograde ER-derived vesicle trafficking in cortical neurites
Authors: Koh SY , Cain JT , Magee H , White KA , Rechtzigel M , Meyerink B , Leppert H , Timm DJ , Morgan JP , Johnson TB , Grove B , Khanna R , Hensley K , Brudvig J , Weimer JM
Published: September 2021

As neurons establish extensive connections throughout the central nervous system, the transport of cargo along the microtubule network of the axon is crucial for differentiation and homeostasis. Specifically, building blocks such as membrane and cytoskeletal components, organelles, transmembrane receptors, adhesion molecules, and peptide neurotransmitters all require proper transport to the presynaptic compartment. Here, we identify a novel complex regulating vesicular endoplasmic reticulum transport in neurites, composed of CLN6: an ER-associated protein of relatively unknown function implicated in CLN6-Batten disease; CRMP2: a tubulin binding protein important in regulating neurite microtubule dynamics; and KLC4: a classic transport motor protein. We show that this “CCK” complex allows ER-derived vesicles to migrate to the distal end of the axon, aiding in proper neurite outgrowth and arborization. In the absence of CLN6, the CCK complex does not function effectively, leading to reduced vesicular transport, stunted neurite outgrowth, and deficits in CRMP2 binding to other protein partners. Treatment with a CRMP2 modulating compound, lanthionine ketimine ester, partially restores these deficits in CLN6-deficient mouse neurons, indicating that stabilization of CRMP2 interacting partners may prove beneficial in lieu of complete restoration of the CCK complex. Taken together, these findings reveal a novel mechanism of ER-derived vesicle transport in the axon and provide new insights into therapeutic targets for neurodegenerative disease.
Chromosome level genome assembly and annotation of highly invasive Japanese stiltgrass (Microstegium vimineum)
Authors: Ramachandran Dhanushya , Huebner Cynthia D. , Daly Mark , Haimovitz Jasmine , Swale Thomas , Barrett Craig F.
Published: September 2021

The invasive Japanese stiltgrass (Microstegium vimineum) affects a wide range of ecosystems and threatens biodiversity across the eastern USA. However, the mechanisms underlying rapid adaptation, plasticity, and epigenetics in the invasive range are largely unknown. We present a chromosome-level assembly for M. vimineum to investigate genome dynamics, evolution, adaptation, and the genomics of phenotypic plasticity. We generated a 1.12 Gb genome with scaffold N50 length of 53.44 Mb respectively, taking a de novo assembly approach that combined PacBio and Dovetail Genomics Omni-C sequencing. The assembly contains 23 pseudochromosomes, representing 99.96% of the genome. BUSCO assessment indicated that 80.3% of Poales gene groups are present in the assembly. The genome is predicted to contain 39,604 protein-coding genes, of which 26,288 are functionally annotated. Furthermore, 66.68% of the genome is repetitive, of which unclassified (35.63%) and long terminal repeat (LTR) retrotransposons (26.90%) are predominant. Similar to other grasses, Gypsy (41.07%) and Copia (32%) are the most abundant LTR-retrotransposon families. The majority of LTR-retrotransposons are derived from a significant expansion in the past 1-2 million years, suggesting the presence of relatively young LTR-retrotransposon lineages. We find corroborating evidence from Ks plots for a stiltgrass-specific duplication event, distinct from the more ancient grass-specific duplication event. The assembly and annotation of M. vimineum will serve as an essential genomic resource facilitating studies of the invasion process, the history and consequences of polyploidy in grasses, and provides a crucial tool for natural resource managers.

Significance

The current lack of genomic resources for the invasive Japanese stiltgrass—and thousands of other invasive species globally—severely limits our understanding of the invasion process and hinders decision-making for effective management and control. In this study, we present a chromosome-level genome assembly and annotation of Japanese stiltgrass, a problematic weed in eastern North America, identifying a clear history of polyploidy and recent activity of transposable elements. The ultimate goal is to advance genomic studies to better understand the dynamics of non-native species during the various invasion phases, thereby providing insights into effective control strategies to manage current and future invasions.
Mu-opioid receptor system modulates responses to vocal bonding and distress signals in humans
Authors: Sun Lihua , Lukkarinen Lasse , Karlsson Henry , Hirvonen Jussi , Tiihonen Jari , Lauerma Hannu , Scott Sophie , Nummenmaa Lauri
Published: September 2021

Laughter is a contagious prosocial signal that conveys bonding motivation; adult crying conversely communicates desire for social proximity by signalling distress. Endogenous mu-opioid receptors (MORs) modulate sociability in humans and non-human primates. In this combined PET-fMRI study (n=17) we tested whether central MOR tone is associated with regional brain responses to social signals of laughter and crying sounds. MOR availability was measured with positron emission tomography using high-affinity agonist radioligand [11C]carfentanil. Haemodynamic responses to social laughter and crying sounds were measured using functional magnetic resonance imaging (fMRI). Social laughter evoked activation in the auditory cortex, insula, cingulate cortex, amygdala, primary and secondary somatosensory cortex, primary and secondary motor cortex; crying sounds led to more restricted activation in auditory cortex and nearby areas. MOR availability was negatively correlated with the haemodynamic responses to social laughter in primary and secondary somatosensory cortex, primary and secondary motor cortex, posterior insula, posterior cingulate cortex, precuneus, cuneus, temporal gyri, and lingual gyrus. For crying-evoked activations, MOR availability was negatively correlated with medial and lateral prefrontal haemodynamic responses. Altogether our findings highlight the role of MOR system in modulating acute brain responses to both positive and negative social signals.
Adropin confers neuroprotection and promotes functional recovery from ischemic stroke
Authors: Yang Changjun , Lavayen Bianca P. , Liu Lei , Sanz Brian D. , DeMars Kelly M. , Larochelle Jonathan , Pompilus Marjory , Febo Marcelo , Sun Yu-Yo , Kuo Yi-Min , Mohamadzadeh Mansour , Farr Susan A. , Kuan Chia-Yi , Butler Andrew A. , Candelario-Jalil Eduardo
Published: September 2021

Adropin is a highly-conserved peptide that has been shown to preserve endothelial barrier function. Blood-brain barrier (BBB) disruption is a key pathological event in cerebral ischemia. However, the effects of adropin on ischemic stroke outcomes remain unexplored. Hypothesizing that adropin exerts neuroprotective effects by maintaining BBB integrity, we investigated the role of adropin in stroke pathology utilizing loss- and gain-of-function genetic approaches combined with pharmacological treatment with synthetic adropin peptide. Stroke decreased endogenous adropin levels in the brain and plasma. Adropin treatment or transgenic adropin overexpression robustly reduced brain injury and improved long-term sensorimotor and cognitive function in young and aged mice subjected to ischemic stroke. In contrast, genetic deletion of adropin exacerbated ischemic brain injury. Mechanistically, adropin neuroprotection depends on endothelial nitric oxide synthase and is associated with reduced BBB permeability and neuroinflammation. We identify adropin as a novel neuroprotective peptide with the potential to improve stroke outcomes.
Transmembrane Batten disease proteins interact with a shared network of vesicle sorting proteins to regulate synaptic composition and function
Authors: Rechtzigel Mitchell J. , Meyerink Brandon L. , Leppert Hannah , Johnson Tyler B. , Cain Jacob T. , Ferrandino Gavin , May Danielle G. , Roux Kyle J. , Brudvig Jon J. , Weimer Jill M.
Published: September 2021

Batten disease is unique among lysosomal storage disorders for the early and profound manifestation in the central nervous system, but little is known regarding potential neuron-specific roles for the disease-associated proteins. We demonstrate substantial overlap in the protein interactomes of three transmembrane Batten proteins (CLN3, CLN6, and CLN8), and that their absence leads to synaptic depletion of key partners (i.e. SNAREs and tethers) and aberrant synaptic SNARE dynamics in vivo, demonstrating a novel shared etiology.