bluuebunny/crossref_metadata_2025 huggingface dataset:
Liver Protein Expression in NASH Mice on a High-Fat Diet: Response to Multi-Mineral Intervention
Authors: Varani James , McClintock Shannon D. , Knibbs Randall N. , Harber Isabelle , Zeidan Dania , Jawad-Makki Mohamed Ali H. , Aslam Muhammad N.
Published: May 2022

Male MS-NASH mice were maintained on a high-fat diet for 16 weeks with and without red algae-derived minerals. Obeticholic acid (OCA) was used as a comparator in the same strain and diet. C57BL/6 mice maintained on a standard (low-fat) rodent chow diet were used as a control. At the end of the in-life portion of the study, body weight, liver weight, liver enzyme levels and liver histology were assessed. Samples obtained from individual livers were subjected to Tandem Mass Tag labeling / mass spectroscopy for protein profile determination. As compared to mice maintained on the low-fat diet, all high-fat-fed mice had increased whole-body and liver weight, increased liver enzyme (aminotransferases) levels and widespread steatosis / ballooning hepatocyte degeneration. Histological evidence for liver inflammation and collagen deposition was also present, but changes were to a lesser extent. A moderate reduction in ballooning degeneration and collagen deposition was observed with mineral supplementation. Control mice on the high-fat diet alone demonstrated multiple protein changes associated with dysregulated fat and carbohydrate metabolism, lipotoxicity and oxidative stress. Cholesterol metabolism and bile acid formation were especially sensitive to diet. In mice receiving multi-mineral supplementation along with the high-fat diet, there was reduced liver toxicity as evidenced by a decrease in levels of several cytochrome P450 enzymes and other oxidant-generating moieties. Additionally, elevated expression of several keratins was also detected in mineral-supplemented mice. The protein changes observed with mineral supplementation were not seen with OCA. Our previous studies have shown that mice maintained on a high-fat diet for up to 18 months develop end-stage liver injury including hepatocellular carcinoma. Mineral-supplemented mice were substantially protected against tumor formation and other end-state consequences of high-fat feeding. The present study identifies early (16-week) protein changes occurring in the livers of the high-fat diet-fed mice, and how the expression of these proteins is influenced by mineral supplementation. These findings help elucidate early protein changes that contribute to end-stage liver injury and potential mechanisms by which dietary minerals may mitigate such damage.
Higher Intake of Dietary Magnesium Is Inversely Associated With COVID-19 Severity and Symptoms in Hospitalized Patients: A Cross-Sectional Study
Authors: Nouri-Majd Saeedeh , Ebrahimzadeh Armin , Mousavi Seyed Mohammad , Zargarzadeh Nikan , Eslami Mina , Santos Heitor O. , Taghizadeh Mohsen , Milajerdi Alireza
Published: May 2022

Background and Aims

Magnesium is an anti-inflammatory mineral that plays a role in the innate immune system, and the relaxation of bronchial smooth muscle warrants additional attention in COVID-19. This study examined the association between magnesium intake and COVID-19 severity and related symptoms in hospitalized patients.

Methods

A cross-sectional study was done enrolling 250 COVID-19 patients aged 18 to 65 years. A validated 168-item online food frequency questionnaire (FFQ) was used to assess dietary magnesium intake. COVID-19 Treatment Guidelines were used to determine COVID-19 severity, and symptoms were evaluated using a standard questionnaire. Crude and adjusted analyses were performed (Model 1: age, sex, and energy intake; Model 2: Model 1 + physical activity, supplements, corticosteroids, and antiviral drugs; Model 3: Model 2 + body mass index).

Results

The mean age of participants was 44.1 ± 12.1 years, and 46% of them had severe COVID-19. Patients at the highest tertile of dietary magnesium intake had lower serum levels of inflammatory biomarkers, including CRP (11.8 ± 2.2 vs. 29.5 ± 2.1 mg/L, p < 0.001) and ESR (15.8 ± 2.4 vs. 34.7 ± 2.4 mm/hr, p < 0.001), than those at the lowest tertile. After controlling for potential confounders, we observed that a higher dietary magnesium intake was associated with a lower odds of severe COVID-19 (OR: 0.32; 95% CI: 0.15–0.70). Also, we found a significant inverse association between dietary magnesium intake and odds of COVID-19 symptoms.

Conclusion

We found that higher intake of dietary magnesium was inversely associated with COVID-19 severity and symptoms.
The Roles of Diffusion Kurtosis Imaging and Intravoxel Incoherent Motion Diffusion-Weighted Imaging Parameters in Preoperative Evaluation of Pathological Grades and Microvascular Invasion in Hepatocellular Carcinoma
Authors: Wang Fei , Yan Chun yue , Wang Cai hong , Yang Yan , Zhang Dong
Published: May 2022

Background

Currently, there are disputes about the parameters of diffusion kurtosis imaging (DKI), intravoxel incoherent motion (IVIM), and diffusion-weighted imaging (DWI) in predicting pathological grades and microvascular invasion (MVI) in hepatocellular carcinoma (HCC). The aim of our study was to investigate and compare the predictive power of DKI and IVIM-DWI parameters for preoperative evaluation of pathological grades and MVI in HCC.

Methods

PubMed, Web of Science, and Embase databases were searched for relevant studies published from inception to October 2021. Review Manager 5.3 was used to summarize standardized mean differences (SMDs) of mean kurtosis (MK), mean diffusivity (MD), tissue diffusivity (D), pseudo diffusivity (D*), perfusion fraction (f), mean apparent diffusion coefficient (ADCmean), and minimum apparent diffusion coefficient (ADCmin). Stata12.0 was used to pool the sensitivity, specificity, and area under the curve (AUC). Overall, 42 up-to-standard studies with 3,807 cases of HCC were included in the meta-analysis.

Results

The SMDs of ADCmean, ADCmin, and D values, but not those of D* and f values, significantly differed between well, moderately, and poorly differentiated HCC (P < 0.01). The sensitivity, specificity, and AUC of the MK, D, ADCmean, and ADCmin for preoperative prediction of poorly differentiated HCC were 69%/94%/0.89, 87%/80%/0.89, 82%/75%/0.86, and 83%/64%/0.81, respectively. In addition, the sensitivity, specificity, and AUC of the D and ADCmean for preoperative prediction of well-differentiated HCC were 87%/83%/0.92 and 82%/88%/0.90, respectively. The SMDs of ADCmean, ADCmin, D, MD, and MK values, but not f values, showed significant differences (P < 0.01) between MVI-positive (MVI+) and MVI-negative (MVI-) HCC. The sensitivity and specificity of D and ADCmean for preoperative prediction of MVI+ were 80%/80% and 74%/71%, respectively; the AUC of the D (0.87) was significantly higher than that of ADCmean (0.78) (Z = −2.208, P = 0.027). Sensitivity analysis showed that the results of the above parameters were stable and reliable, and subgroup analysis confirmed a good prediction effect.

Conclusion

DKI parameters (MD and MK) and IVIM-DWI parameters (D value, ADCmean, and ADCmin) can be used as a noninvasive and simple preoperative examination method to predict the grade and MVI in HCC. Compared with ADCmean and ADCmin, MD and D values have higher diagnostic efficacy in predicting the grades of HCC, and D value has superior diagnostic efficacy to ADCmean in predicting MVI+ in HCC. However, f value cannot predict the grade or MVI in HCC.
Menstrual Cycle Variation in MRI-Based Quantification of Intraluminal Gas in Women With and Without Dysmenorrhea
Authors: Oh Hyeyoung , Ehrenpreis Eli D. , Tu Frank F. , Dillane Katlyn E. , Garrison Ellen F. , Leloudas Nondas , Prasad Pottumarthi V. , Hellman Kevin M.
Published: May 2022

Women frequently report increased bloating, flatulence, and pain during the perimenstrual period. However, it is unknown whether women have more intraluminal gas during menses. To evaluate whether pain-free women or women with dysmenorrhea have different amounts of intraluminal bowel gas during the menses, we utilized magnetic resonance imaging (MRI) to determine colonic gas volumes throughout the menstrual cycle. To avoid dietary influence, the participants were instructed to avoid gas-producing foods before their scheduled MRI. We verified the measurement repeatability across the reviewers and obtained an intraclass correlation coefficient of 0.92. There were no significant differences in intraluminal gas volume between menses and non-menses scans (p = 0.679). Even among the women with dysmenorrhea, there was no significant difference in the intraluminal gas volume between menses and non-menses (p = 0.753). During menstruation, the participants with dysmenorrhea had less intraluminal gas than participants without dysmenorrhea (p = 0.044). However, the correlation between the bowel gas volume and the pain symptoms were not significant (p > 0.05). Although increased bowel symptoms and bloating are reported in the women with dysmenorrhea during menses, our results do not support the hypothesis that increased intraluminal gas is a contributing factor. Although dietary treatment has been shown in other studies to improve menstrual pain, the mechanism responsible for abdominal symptoms requires further investigation. Our findings demonstrate that the intraluminal bowel gas volume measurements are feasible and are unaffected by menses under a controlled diet. The method described might prove helpful in future mechanistic studies in clarifying the role of intraluminal bowel gas in other conditions.
Juvenile Generalized Myasthenia Gravis With AChR and MuSK Antibody Double Positivity: A Case Report With a Review of the Literature
Authors: Ge XiuShan , Wei CuiJie , Dong Hui , Zhang YueHua , Bao XinHua , Wu Ye , Song DanYu , Hao HongJun , Xiong Hui
Published: May 2022

Myasthenia gravis is an autoimmune disease mediated by B cells and is associated with acetylcholine receptor (AChR) and muscle-specific receptor tyrosine kinase (MuSK) antibodies in the postsynaptic membrane at the neuromuscular junction. The presence of both antibodies in the serum of patients with myasthenia gravis has been rarely reported. Case description: A 9-year-old girl was admitted to our hospital with the chief complaints of reduced facial expression for 3 months and unclear speech and choking from drinking water for 2 months. The diagnosis of generalized myasthenia gravis was made based on clinical manifestations, repetitive electrical nerve stimulation, neostigmine tests, specific antibody tests and other auxiliary examinations. We found the rare coexistence of two key antibodies (anti-AChR and anti-MuSK antibodies) in the patient's serum. The patient experienced myasthenic crisis and received respiratory support even though she was taking prednisone therapy. Due to the poor response to treatment with pyridostigmine bromide, glucocorticoids and IVIG, we administered rituximab therapy, and she responded well and achieved clinical remission. This suggests that clinicians should pay more attention to atypical cases and antibody detection. Rituximab should be considered when conventional treatment fails.
The Association Between Oxygenation Status at 24 h After Diagnosis of Pulmonary Acute Respiratory Distress Syndrome and the 30-Day Mortality among Pediatric Oncological Patients
Authors: Huang Xueqiong , Xu Lingling , Pei Yuxin , Huang Huimin , Chen Chao , Tang Wen , Jiang Xiaoyun , Li Yijuan
Published: May 2022

Background

Pediatric oncology patients with acute respiratory distress syndrome (ARDS) secondary to pneumonia are at high risk of mortality. Our aim was to describe the epidemiology of ARDS in this clinical population and to identify the association between the oxygenation status at 24 h after diagnosis and the 30-day mortality rates, stratified by the severity of ARDS.

Methods

This was a retrospective cohort study of 82 pediatric oncology patients, with a median age of 4 years, admitted to our pediatric intensive care unit with a diagnosis of ARDS between 2013 and 2021. Demographic and clinical factors were compared between the survivor (n = 52) and non-survivor (n = 30) groups. Univariate and multivariate Cox proportional hazards regression models were used to determine the association between the oxygenation status at 24 h after diagnosis and the 30-day mortality rates.

Results

The mean airway pressure at ARDS diagnosis, PaO2/FiO2 (P/F) ratio, oxygenation index (OI) value, peak inspiratory pressure, and lactate level at 24 h after ARDS diagnosis, as well as complications (i.e., septicemia and more than two extrapulmonary organ failures) and adjunctive continuous renal replacement therapy, were significant mortality risk factors. After adjusting for other covariates, the oxygenation status P/F ratio (Hazard ratio [HR] = 0.98, 95% confidence interval [CI] = 0.96–1.00, P = 0.043) and OI value (HR = 1.12, 95% CI = 1.02–1.23, P = 0.016) at 24 h remained independent mortality risk factors. According to the Kaplan–Meier survival curve, a low P/F ratio (≤ 150) and high OI (>10) were associated with a higher risk of 30-day mortality (50.9 and 52.9%, respectively; both P < 0.05)

Conclusion

The P/F ratio and OI value measured at 24 h after ARDS diagnosis can provide a better stratification of patients according to ARDS disease severity to predict the 30-day mortality risk.
Predicting Word Reading Deficits Using an App-Based Screening Tool at School Entry
Authors: Schöfl Martin , Steinmair Gabriele , Holzinger Daniel , Weber Christoph
Published: May 2022

Background

Reading is a crucial competence associated with academic development, mental health, and social adaptation. Reading difficulties are often detected at a late stage, with a possible negative impact on long-term reading development and secondary developmental disadvantages. The first manifestations of reading difficulties can be identified by word reading deficits in first and second grade, paving the way for specific interventions. For widespread implementation, instruments must be easy to use and motivating for children.

Objectives

Development and validation of an economical, well-accepted, and accurate screening tool composed of the domains of phonological information processing, language skills, and non-verbal intelligence in regular school settings.

Design

In 2020, the screening tool was used on a sample of 409 first graders between the second and fifth weeks of school in a one-to-one setting. Additionally, information on parental education and the use of German and/or other languages by the child was collected using a parental questionnaire. A follow-up involving the use of established standardized word reading tests was conducted at the end of the first school year.

Results

A five-variable screening tool consisting of the dimensions of phonological information processing (letter knowledge, rapid naming, and phonological awareness) and linguistic skills (receptive vocabulary and morphosyntax) showed statistical relevance (AUC = 0.78; sensitivity 0.80, specificity 0.74) for predicting word reading problems concerning reading speed (<16th percentile) at the end of first grade, whereas gender, first language, and age of first exposure to the German language did not contribute to the prediction. The instrument was well accepted by the children and screeners and can be administered within an acceptable time frame.

Conclusion

Word reading deficits at the end of first grade can be predicted by the use of an app-based screening tool at school entry that includes phonological information processing and language skills. Further validation and assessment of empirical feasibility data are needed to support the screening instrument for German orthography.
Enteral Feeding Practices for Very Preterm and Very Low Birth Weight Infants in Nigeria and Kenya
Authors: Tongo Olukemi O. , Olwala Macrine A. , Talbert Alison W. , Nabwera Helen M. , Akindolire Abimbola E. , Otieno Walter , Nalwa Grace M. , Andang'o Pauline E. A. , Mwangome Martha K. , Abdulkadir Isa , Ezeaka Chinyere V. , Ezenwa Beatrice N. , Fajolu Iretiola B. , Imam Zainab O. , Umoru Dominic D. , Abubakar Ismaela , Embleton Nicholas D. , Allen Stephen J.
Published: May 2022

Background:

Optimizing nutrition in very preterm (28–32 weeks gestation) and very low birth weight (VLBW; 1,000 g to <1,500 g) infants has potential to improve their survival, growth, and long-term health outcomes.

Aim

To assess feeding practices in Nigeria and Kenya for very preterm and VLBW newborn infants.

Methods

This was a cross-sectional study where convenience sampling was used. A standard questionnaire was sent to doctors working in neonatal units in Nigeria and Kenya.

Results

Of 50 respondents, 37 (74.0%) were from Nigeria and 13 (26.0%) from Kenya. All initiated enteral feeds with breastmilk, with 24 (48.0%) initiating within 24 h. Only 28 (56.0%) used written feeding guidelines. Starting volumes ranged between 10 and 80 ml/kg/day. Median volume advancement of feeds was 20 ml/kg/day (IQR 10–20) with infants reaching full feeds in 8 days (IQR 6–12). 26 (52.0%) of the units fed the infants 2 hourly. Breastmilk fortification was practiced in 7 (14.0%) units, while folate, iron, calcium, and phosphorus were prescribed in 42 (84.0%), 36 (72.0%), 22 (44.0%), 5 (10.0%) of these units, respectively. No unit had access to donor breastmilk, and only 18 (36.0%) had storage facilities for expressed breastmilk. Twelve (24.0%) used wet nurses whilst 30 (60.0%) used formula feeds.

Conclusion

Feeding practices for very preterm and VLBW infants vary widely within Nigeria and Kenya, likely because of lack of locally generated evidence. High quality research that informs the feeding of these infants in the context of limited human resources, technology, and consumables, is urgently needed.
Planned Peri-Extubation Fasting in Critically Ill Children: An International Survey of Practice
Authors: Nabialek Tomasz , Tume Lyvonne N. , Cercueil Eloise , Morice Claire , Bouvet Lionel , Baudin Florent , Valla Frederic V.
Published: May 2022

Introduction

Cumulative energy/protein deficit is associated with impaired outcomes in pediatric intensive care Units (PICU). Enteral nutrition is the preferred mode, but its delivery may be compromised by periods of feeding interruptions around procedures, with peri-extubation fasting the most common procedure. Currently, there is no evidence to guide the duration of the peri-extubation fasting in PICU. Therefore, we aimed to explore current PICU fasting practices around the time of extubation and the rationales supporting them.

Materials and Methods

A cross sectional electronic survey was disseminated via the European Pediatric Intensive Care Society (ESPNIC) membership. Experienced senior nurses, dieticians or doctors were invited to complete the survey on behalf of their unit, and to describe their practice on PICU fasting prior to and after extubation.

Results

We received responses from 122 PICUs internationally, mostly from Europe. The survey confirmed that fasting practices are often extrapolated from guidelines for fasting prior to elective anesthesia. However, there were striking differences in the duration of fasting times, with some units not fasting at all (in patients considered to be low risk), while others withheld feeding for all patients. Fasting following extubation also showed large variations in practice: 46 (38%) and 26 (21%) of PICUs withheld oral and gastric/jejunal nutrition more than 5 h, respectively, and 45 (37%) started oral feeding based on child demand. The risk of vomiting/aspiration and reducing nutritional deficit were the main reasons for fasting children [78 (64%)] or reducing fasting times [57 (47%)] respectively.

Discussion

This variability in practices suggests that shorter fasting times might be safe. Shortening the duration of unnecessary fasting, as well as accelerating the extubation process could potentially be achieved by using other methods of assessing gastric emptiness, such as gastric point of care ultrasonography (POCUS). Yet only half of the units were aware of this technique, and very few used it.
A Review of Economic Models Submitted to NICE’s Technology Appraisal Programme, for Treatments of T1DM & T2DM
Authors: Daly Marie-Josée , Elvidge Jamie , Chantler Tracey , Dawoud Dalia
Published: May 2022

Background: In the UK, 4.7 million people are currently living with diabetes. This is projected to increase to 5 million by 2025. The direct and indirect costs of T1DM and T2DM are rising, and direct costs already account for approximately 10% of the National Health Service (NHS) budget.

Objective: The aim of this review is to assess the economic models used in the context of NICE’s Technology Appraisals (TA) Programme of T1DM and T2DM treatments, as well as to examine their compliance with the American Diabetes Association’s (ADA) guidelines on computer modelling.

Methods: A review of the economic models used in NICE’s TA programme of T1DM and T2DM treatments was undertaken. Relevant TAs were identified through searching the NICE website for published appraisals completed up to April 2021. The review also examined the associated Evidence Review Group (ERG) reports and Final Appraisal Documents (FAD), which are publicly accessible. ERG reports were scrutinised to identify major issues pertaining to the economic modelling. The FAD documents were then examined to assess how these issues reflected on NICE recommendations.

Results: Overall, 10 TAs pertaining to treatments of T1DM and T2DM were identified. Two TAs were excluded as they did not use economic models. Seven of the 8 included TAs related to a novel class of oral antidiabetic drugs (OADs), gliflozins, and one to continuous subcutaneous insulin infusion (CSII) devices. There is a lack of recent, robust data informing risk equations to enable the derivation of transition probabilities. Despite uncertainty surrounding its clinical relevance, bodyweight/BMI is a key driver in many T2DM-models. HbA1c’s reliability as a predictor of hard outcomes is uncertain, chiefly for macrovascular complications. The external validity of T1DM is even less clear. There is an inevitable trade-off between the sophistication of models’ design, their transparency and practicality.

Conclusion: Economic models are essential tools to support decision-making in relation to market access and ascertain diabetes technologies’ cost effectiveness. However, key structural and methodological issues exist. Models’ shortcomings should be acknowledged and contextualised within the framework of technology appraisals. Diabetes medications and other technologies should also be subject to regular and consistent re-appraisal to inform disinvestment decisions. Artificial intelligence could potentially enhance models’ transparency and practicality.
A Lumped Two-Compartment Model for Simulation of Ventricular Pump and Tissue Mechanics in Ischemic Heart Disease
Authors: Koopsen Tijmen , Van Osta Nick , Van Loon Tim , Van Nieuwenhoven Frans A. , Prinzen Frits W. , Van Klarenbosch Bas R. , Kirkels Feddo P. , Teske Arco J. , Vernooy Kevin , Delhaas Tammo , Lumens Joost
Published: May 2022

Introduction: Computational modeling of cardiac mechanics and hemodynamics in ischemic heart disease (IHD) is important for a better understanding of the complex relations between ischemia-induced heterogeneity of myocardial tissue properties, regional tissue mechanics, and hemodynamic pump function. We validated and applied a lumped two-compartment modeling approach for IHD integrated into the CircAdapt model of the human heart and circulation.

Methods: Ischemic contractile dysfunction was simulated by subdividing a left ventricular (LV) wall segment into a hypothetical contractile and noncontractile compartment, and dysfunction severity was determined by the noncontractile volume fraction (NCVF). Myocardial stiffness was determined by the zero-passive stress length (Ls0,pas) and nonlinearity (kECM) of the passive stress-sarcomere length relation of the noncontractile compartment. Simulated end-systolic pressure volume relations (ESPVRs) for 20% acute ischemia were qualitatively compared between a two- and one-compartment simulation, and parameters of the two-compartment model were tuned to previously published canine data of regional myocardial deformation during acute and prolonged ischemia and reperfusion. In six patients with myocardial infarction (MI), the NCVF was automatically estimated using the echocardiographic LV strain and volume measurements obtained acutely and 6 months after MI. Estimated segmental NCVF values at the baseline and 6-month follow-up were compared with percentage late gadolinium enhancement (LGE) at 6-month follow-up.

Results: Simulation of 20% of NCVF shifted the ESPVR rightward while moderately reducing the slope, while a one-compartment simulation caused a leftward shift with severe reduction in the slope. Through tuning of the NCVF, Ls0,pas, and kECM, it was found that manipulation of the NCVF alone reproduced the deformation during acute ischemia and reperfusion, while additional manipulations of Ls0,pas and kECM were required to reproduce deformation during prolonged ischemia and reperfusion. Out of all segments with LGE>25% at the follow-up, the majority (68%) had higher estimated NCVF at the baseline than at the follow-up. Furthermore, the baseline NCVF correlated better with percentage LGE than NCVF did at the follow-up.

Conclusion: We successfully used a two-compartment model for simulation of the ventricular pump and tissue mechanics in IHD. Patient-specific optimizations using regional myocardial deformation estimated the NCVF in a small cohort of MI patients in the acute and chronic phase after MI, while estimated NCVF values closely approximated the extent of the myocardial scar at the follow-up. In future studies, this approach can facilitate deformation imaging–based estimation of myocardial tissue properties in patients with cardiovascular diseases.
Increase in Ca2+-Activated cAMP/PKA Signaling Prevents Hydroxychloroquine-Induced Bradycardia of the Cardiac Pacemaker
Authors: Segal Sofia , Arbel-Ganon Limor , Mazgaoker Savyon , Davoodi Moran , Yaniv Yael
Published: May 2022

Bradycardia or tachycardia are known side effects of drugs that limit their clinical use. The heart pacemaker function which control the heart rate under normal conditions is determined by coupled clock system. Thus, interfering with specific clock mechanism will affect other clock mechanisms through changes in interconnected signaling and can lead to rhythm disturbance. However, upregulation of a different clock components can compensate for this change. We focus here on hydroxychloroquine (HCQ), which has been shown effective in treating COVID-19 patients, however its bradycardic side effect limits its clinical use. We aim to decipher the mechanisms underlying the effect of HCQ on pacemaker automaticity, to identify a potential drug that will eliminate the bradycardia. We used isolated rabbit sinoatrial node (SAN) cells, human-induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) and mouse SAN cells residing in SAN tissue. Further, we employed SAN cell computational model to suggest mechanistic insights of the effect of HCQ on pacemaker function. HCQ increased mean spontaneous beat interval and variability in all three models in parallel to slower intracellular kinetics. The computational model suggested that HCQ affects the pacemaker (funny) current (If), L-type Ca2+ current (ICa,L), transient outward potassium (Ito) and due to changes in Ca2+ kinetics, the sodium-calcium exchanger current (INCX). Co-application of 3’-isobutylmethylxanthine (IBMX) and HCQ prevented the increase in beat interval and variability in all three experimental models. The HCQ-induced increase in rabbit and mice SAN cell and hiPSC-CM spontaneous beat interval, can be prevented by a phosphodiester inhibitor that restores automaticity due to slower intracellular Ca2+ kinetics.
Cytosolic Nudix Hydrolase 1 Is Involved in Geranyl β-Primeveroside Production in Tea
Authors: Zhou Hanchen , Wang Shijie , Xie Hao-Fen , Liu Guofeng , Shamala Lubobi Ferdinand , Pang Jingyi , Zhang Zhengzhu , Ling Tie-Jun , Wei Shu
Published: May 2022

Geraniol is a potent tea odorant and exists mainly as geranyl glycoside inCamellia sinensis. Understanding the mechanisms of geraniol biosynthesis at molecular levels in tea plants is of great importance for practical improvement of tea aroma. In this study, geraniol and its glycosides from tea plants were examined using liquid chromatography coupled with mass spectrometry. Two candidate geraniol synthase (GES) genes (CsTPS) and two Nudix hydrolase genes (CsNUDX1-cytoandCsNUDX1-chlo) from the tea genome were functionally investigated through gene transcription manipulation and gene chemical product analyses. Our data showed that in tea leaves, levels of geranylβ-primeveroside were dramatically higher than those of geranylβ-glucoside, while free geraniol was undetectable in this study. A tempo-spatial variation of geranylβ-primeveroside abundance in tea plants existed, with high levels in young and green tissues and low levels in mature or non-green tissues. Cytosolic CsNUDX1-cyto showed higher hydrolysis activity of geranyl-pyrophosphate to geranyl-monophosphate (GP)in vitrothan did chloroplastidial CsNUDX1-chlo. A transgenic study revealed that expression ofCsNUDX1-cytoresulted in significantly more geranylβ-primeveroside in transgenicNicotiana benthamianacompared with non-transgenic wild-type, whereas expression ofCsNUDX1-chlohad no effect. An antisense oligo-deoxynucleotide study confirmed that suppression ofCsNUDX1-cytotranscription in tea shoots led to a significant decrease in geranylβ-primeveroside abundance. Additionally,CsNUDX1-cytotranscript levels and geranylβ-primeveroside abundances shared the same tempo-spatial patterns in different organs in the tea cultivar “Shucha Zao,” indicating thatCsNUDX1-cytois important for geranylβ-primeveroside formation in tea plants. Results also suggested that neither of the two candidate GES genes in tea plants did not function as GES in transgenicN. benthamiana. All our data indicated thatCsNUDX1-cytois involved in geranylβ-primeveroside production in tea plants. Our speculation about possible conversion from the chemical product of CsNUDX1-cyto to geranylβ-primeveroside in plants was also discussed.
Effects of Long-Term Fertilization and Stand Age on Root Nutrient Acquisition and Leaf Nutrient Resorption of Metasequoia glyptostroboides
Authors: Song Rui , Tong Ran , Zhang Hui , Wang G. Geoff , Wu Tonggui , Yang Xiuqing
Published: May 2022

The plant nutrient acquisition strategies are diverse, such as root nutrient acquisition and leaf nutrient resorption, playing important roles in driving soil processes, vegetation performance as well as ecosystem nutrient cycling. However, it is still in a debate whether there is a synergy or tradeoff between above- and below-ground nutrient acquisition strategy under nitrogen (N) and phosphorus (P) addition, or with stand age. Herein, this study investigated the responses of root-soil accumulation factor (RSAF) and leaf nutrient resorption efficiency (NuRE) to long-term N and P fertilization, and further explored the trade-off between them in Metasequoia glyptostroboides plantations with different stand age. Results showed that under N fertilization in young plantations, leaf N resorption efficiency (NRE) increased, and root-soil accumulation factor for P (RSAF-P) decreased. For young forests under P fertilization, the NRE increased whereas RSAF-P decreased. For middle-aged forests under P fertilization, the NRE and leaf P resorption efficiency (PRE) increased and the RSAF-P decreased. Under P fertilization in young and middle-aged plantations, PRE had a significant positive correlation with RSAF-P. Under N fertilization in young plantations, NRE was significantly positive correlated with root-soil accumulation factor for N (RSAF-N). The covariance-based structural equation modeling (CB-SEM) analysis indicated that stand age had positive effects on PRE whether under N or P fertilization, as well as on RSAF-P under N fertilization, whereas had no effects on the NRE or RSAF-N. Overall, our results can shed light on the nutrient acquisition strategies of M. glyptostroboides plantations under future environmental changes and the results could be applied to the nutrient management practices.
Contextual Support for Less Salient Homophones and Pun Humor Appreciation: Evidence From Eye Movements in Reading Chinese Homophone Puns
Authors: Zheng Wei , Wang Xiaolu
Published: May 2022

Punning is an important means of creating humorous effects by intentionally exploiting semantic ambiguity. Previous psycholinguistic research on puns has mainly focused on the process of meaning retrieval in homograph puns, while it is still not entirely clear how readers dynamically utilize contextual information to understand homophone puns. In the current investigation, 68 native Chinese participants were recruited to read three types of experimental sentences while their eye movements were recorded: (1) the homophone-pun sentences where the less salient homophone was visually presented, (2) the homophone-salient sentences where the salient homophone was used, and (3) the homophone-error sentences where the critical context noun in the homophone puns was replaced with an unrelated word. Humor rating results of the homophone puns and the homophone-salient sentences demonstrated that the less salient homophones rather than the salient ones elicited much larger humor responses when presented visually in the same potential pun context. In addition, the reverse fixation pattern in the homophone area and the spill-over region also suggested that meanings of the salient homophones were more recoverable even when not presented visually. Statistical analyses of the homophone puns and the homophone-error sentences showed that the semantic relatedness between the critical context noun and the less salient homophone could significantly predict the humor rating scores of Chinese readers. Taken together, less salient homophones need to receive more contextual support to balance out the advantages of salient homophones before generating a humorous pun interpretation.
The Depleting and Buffering Effects of Telecommuting on Wellbeing: Evidence From China During COVID-19
Authors: Cheng Jinkai , Zhang Chao
Published: May 2022

Meta-analytical research has demonstrated the benefits brought by telecommuting to wellbeing. However, we argue that such a setup in the course of the coronavirus disease pandemic exerts negative effects. On the basis of conservation of resources theory, this study determined how telecommuting depletes wellbeing (defined by job satisfaction and emotional exhaustion) through obstructing psychological detachment from work. Moreover, we incorporated family interfering with work and family–work enrichment as moderators that can buffer the negative effect of telecommuting on psychological detachment from work. Time-lagged field research was conducted with 350 Chinese employees, and findings largely supported our theoretical hypotheses. The elevated level of telecommuting results in minimal psychological detachment from work, which then leads to low wellbeing. Meanwhile, the negative effect of the extent of telecommuting on psychological detachment from work is reduced by family interfering with work. These findings extend the literature on telecommuting and psychological detachment from work through revealing why teleworkers present negative feelings during the pandemic.
Psychopathological and Neurobiological Overlap Between Anorexia Nervosa and Self-Injurious Behavior: A Narrative Review and Conceptual Hypotheses
Authors: Oudijn Marloes , Linders Jara , Mocking Roel , Lok Anja , van Elburg Annemarie , Denys D.
Published: May 2022

Empirical evidence and clinical observations suggest a strong -yet under acknowledged-link between anorexia nervosa (AN) and non-suicidal self-injurious behavior (NSSI). By reviewing the literature on the psychopathology and neurobiology of AN and NSSI, we shed light on their relationship. Both AN and NSSI are characterized by disturbances in affect regulation, dysregulation of the reward circuitry and the opioid system. By formulating a reward-centered hypothesis, we explain the overlap between AN and NSSI. We propose three approaches understanding the relationship between AN and NSSI, which integrate psychopathology and neurobiology from the perspective of self-destructiveness: (1) a nosographical approach, (2) a research domain (RDoC) approach and (3) a network analysis approach. These approaches will enhance our knowledge of the underlying neurobiological substrates and may provide groundwork for the development of new treatment options for disorders of self-destructiveness, like AN and NSSI. In conclusion, we hypothesize that self-destructiveness is a new, DSM-5-transcending concept or psychopathological entity that is reward-driven, and that both AN and NSSI could be conceptualized as disorders of self-destructiveness.
A Phone Consultation Call Line to Support SBIRT in Pediatric Primary Care
Authors: Levy Sharon , Fuller Alyssa , Kelly Shawn , Lunstead Julie , Weitzman Elissa R. , Straus John H.
Published: May 2022

Background

Screening Brief Intervention Referral to Treatment (SBIRT) is recommended as a routine part of pediatric primary care, though managing patients with positive screens is challenging. To address this problem, the state of Massachusetts created a call line staffed by pediatric Addiction Medicine specialists to provide consultations to primary care providers and access to a behavioral health provider specially trained in managing adolescent substance use.

Objective

To describe the uptake and outcomes of a consultation call line and virtual counseling for managing substance use disorders (SUD) in pediatric primary care.

Methods

Service delivery data from consultations and counseling appointments were captured in an electronic database including substance, medication recommendations, level of care recommendations and number of counseling appointments completed for each patient. Summary data is presented here.

Results

In all, there were 407 encounters to 108 unique families, including 128 consultations and 279 counseling visits in a one-year period. The most common substances mentioned by healthcare providers were cannabis (64%), nicotine (20%), alcohol (20%), vaping (9%) and opioids (5%). Management in primary care was recommended for 87 (68%) of the consultations. Medications for SUD treatment were recommended for 69 (54%) consultations including two for opioid use disorder.

Conclusion

We found that both a statewide consultation call line and virtual counseling to support SBIRT in pediatric primary care were feasible. The majority of consultations resulted in recommendations for treatment in primary care.
The Effects of Immediate vs Gradual Reduction in Nicotine Content of Cigarettes on Smoking Behavior: An Ecological Momentary Assessment Study
Authors: Li Qianling , Chen Xijing , Li Xiuli , Gorowska Monika , Li Zimin , Li Yonghui
Published: May 2022

Background

In recent years, much research has examined the effects of various interventions and treatments for smoking cessation. The results suggest that interventions targeting changes of nicotine content can help smokers reduce tobacco use or quit smoking. A number of clinical studies show that smokers who received an immediate reduction in nicotine content to very low levels have significantly greater reductions in the number of cigarettes smoked and toxic substance exposure compared to those with gradual reductions. However, from the perspective of smoking craving, whether the immediate and gradual reduction in nicotine content reduce smoking by reducing cravings needs further investigation.

Methods

74 eligible Participants were randomly allocated to one of the two experimental conditions: (1) immediate reduction to 0.1 mg of nicotine per cigarette (n = 40); (2) gradual reduction from 1.0 (0.8 g ~ 1.2 mg) to 0.1 mg of nicotine per cigarette (n = 34). All participants completed 1-week baseline period during which they smoked their usual cigarette, followed by 16-week of interventions. The primary outcomes included cigarette cravings and number of cigarettes smoked per day (CPD); secondary outcomes included the number of cigarette-free day and emotional states.

Results

Among the 52 participants [51 (98.1%) men; mean (SD) age, 33.44 (6.71) years; mean (SD) CPD, 16.83 (9.94)] who completed the trial, significantly lower cravings for cigarettes were observed in the immediate (n = 25) vs. gradual nicotine reduction group (n = 27) in the morning (t = −2.072, p = 0.039) and after dinner (t = –2.056, p = 0.041). Compared with the baseline daily smoking, the number of cigarettes smoked per day was significantly reduced at the beginning of week 12 in the immediate nicotine reduction group (p = 0.001) and at week 16 in the gradual nicotine reduction group (p < 0.001). The number of participants with any cigarette-free day was not significantly different between the groups (p = 0.198). The number of cigarette-free days was significantly more in the immediate vs. gradual nicotine reduction group (p = 0.027).

Conclusions

The significantly lower cravings were observed in the immediate vs. gradual nicotine reduction group, and led to faster reduction in the number of CPD, and a significant increase in the number of cigarette-free days. These findings add to the evidence base for reduced nicotine content in cigarettes.

Clinical Trial Registration

ClinicalTrials.gov, identifier: ChiCTR2100048216.
Suicidal Behavior in Emergency Child and Adolescent Psychiatric Service Users Before and During the 16 Months of the COVID-19 Pandemic
Authors: Kirič Barbara , Leben Novak Lara , Lušicky Petra , Drobnič Radobuljac Maja
Published: May 2022

Background

Slovenia is among the countries with the highest suicide rates in the world. The COVID-19 pandemic has had a significant impact on the mental health of children and adolescents. Our hypothesis is that the school closure during the pandemic with a gradual transfer to virtual schooling had an important impact on children's and adolescents' suicidal behavior. Therefore, we aimed to determine possible changes in the frequency of assessments as well as frequency and severity of suicidal behavior in the population of Slovene children and adolescents seeking emergency psychiatric help in correlation with the progression of the pandemic and online schooling.

Methods

We performed a retrospective observational analysis of medical records of all children and adolescents referred to the only 24-h emergency in- and outpatient child and adolescent psychiatry service in Slovenia from March 2019 through the end of July 2021. We extracted number of assessments, number of patients with suicidal ideation and with attempted suicide. A comparison between the same periods prior to the pandemic and during the pandemic was made. The months of school closure due to the COVID-19 restriction measures and the months without closures were also compared.

Results

During this period, 1966 children and adolescents were assessed. There was no statistically significant difference in the observed frequency of emergency visits when we compared all the months with to all the months without school closures, or when individual corresponding months with and without school closures were compared. However, there were statistically significantly more patients with suicidal ideation [t(16) = −2.739, p = 0.015; W = 25.0, p = 0.016] and patients who had attempted suicide [t(16)= −3.412, p= 0.004; W = 14.5, p =0.006] during the pandemic as individually compared to the corresponding pre-pandemic months.

Conclusions

Our results show that the number of Slovene children and adolescents who required emergency psychiatric help with suicidality and attempted suicide increased during the COVID-19 pandemic. The increase was shown only after the first year of the pandemic. The observed increase did not appear to directly correspond to the school closures, but was more likely related to the duration of the pandemic.
Association Between Internet Use, Cognitive Function, and Globus Pallidus Volumes: A Study Among the Elderly in Chinese Communities
Authors: Li Wei , Yue Ling , Xiao Shifu
Published: May 2022

Background

Previous studies have linked internet use with several beneficial outcomes for brain health, but there is little data on this among older Chinese.

Objective

The goal of this study was to explore the association between internet use and cognitive impairment and to explore the possible mechanisms by which internet use prevents cognitive decline.

Methods

The current study consisted of two cohorts: one from the China Longitudinal Aging Study (CLAS), which included 610 older adults with mild cognitive impairment (MCI), 192 with dementia, and 2,218 healthy older adults; the second cohort included 39 healthy adults from the Shanghai brain health foundation (SHBHF2016001), who underwent T1 cranial magnetic resonance imaging at baseline, from which their volumes of the hippocampus, amygdala, and globus pallidus were calculated. Moreover, they were also followed up for 1 year. Through standardized questionnaires, detailed general demographic information and internet use information was obtained. The cognitive diagnosis of each participant was made by attending psychiatrists at baseline, and their overall cognitive function was assessed by the mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA).

Results

In cohort 1, after controlling age, gender, smoker, tea drinker, take exercise, diabetes, and hypertension, we found that internet use was associated with MCI (P = 0.015, OR = 0.478, 95% CI: 0.264~0.867), but not for dementia (P = 0.205, OR = 0.393, 95% CI: 0.093~1.665). In cohort 2, we found that the globus pallidus volume of internet users was significantly larger than that of non-users, and the MMSE change score was lower (P < 0.05). The results of partial correlation analysis (controlled for sex, age and education) showed that the change of MMSE value was positively correlated with the volume of left globus pallidus (r = 0.547, P = 0.004).

Conclusions

Internet use might be a protective factor for mild cognitive impairment among the Chinese elderly, and it may prevent a decline in cognitive decline by affecting the volume of the globus pallidus.
Linking Process and Outcome Measures to Improve Employment Support Programs for Individuals With the Most Significant Disabilities
Authors: Riesen Tim , Remund Corban , Snyder Aubrey
Published: May 2022

Employment agencies and funding systems commonly use distal outcome measures such as employed or not employed, full-time or part-time, and continuous measures such as wage, hours worked, and type of job to document the employment status of individuals with disabilities. These measures continue to demonstrate that individuals with disabilities fall behind individuals without disabilities in all employment outcomes. While there is utility in distal outcome measures, it is difficult to determine what intervention or program variables were responsible for a specific outcome. Moreover, outcome measures do not provide sufficient information about the quality of employment supports and services an individual with disabilities receives. One way to improve accountability in employment support programs is to link outcomes to specific processes for obtaining and maintaining employment. The purpose of this manuscript is to describe how employment programs can link short-term (proximal) and long term (distal) outcomes measures to specific processes for employment. A customized employment framework is used to illustrate how systematically linking outcomes and processes improves accountability in programs that support job seekers with most significant disabilities.