Publications by authors named "David D"

1,089 Publications

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Migrating down a hard path.

Authors:
Daryl J V David

Nat Cell Biol 2022 Jan;24(1)

Nature Cell Biology, .

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http://dx.doi.org/10.1038/s41556-021-00830-7DOI Listing
January 2022

Targeted protein degradation: from small molecules to complex organelles-a Keystone Symposia report.

Ann N Y Acad Sci 2022 Jan 8. Epub 2022 Jan 8.

Weill Institute of Cell and Molecular Biology and Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York.

Targeted protein degradation is critical for proper cellular function and development. Protein degradation pathways, such as the ubiquitin proteasomes system, autophagy, and endosome-lysosome pathway, must be tightly regulated to ensure proper elimination of misfolded and aggregated proteins and regulate changing protein levels during cellular differentiation, while ensuring that normal proteins remain unscathed. Protein degradation pathways have also garnered interest as a means to selectively eliminate target proteins that may be difficult to inhibit via other mechanisms. On June 7 and 8, 2021, several experts in protein degradation pathways met virtually for the Keystone eSymposium "Targeting protein degradation: from small molecules to complex organelles." The event brought together researchers working in different protein degradation pathways in an effort to begin to develop a holistic, integrated vision of protein degradation that incorporates all the major pathways to understand how changes in them can lead to disease pathology and, alternatively, how they can be leveraged for novel therapeutics.
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http://dx.doi.org/10.1111/nyas.14745DOI Listing
January 2022

SVInterpreter: A Comprehensive Topologically Associated Domain-Based Clinical Outcome Prediction Tool for Balanced and Unbalanced Structural Variants.

Front Genet 2021 1;12:757170. Epub 2021 Dec 1.

Department of Human Genetics, National Health Institute Doutor Ricardo Jorge, Lisbon, Portugal.

With the advent of genomic sequencing, a number of balanced and unbalanced structural variants (SVs) can be detected per individual. Mainly due to incompleteness and the scattered nature of the available annotation data of the human genome, manual interpretation of the SV's clinical significance is laborious and cumbersome. Since bioinformatic tools developed for this task are limited, a comprehensive tool to assist clinical outcome prediction of SVs is warranted. Herein, we present a free Web application, which analyzes both balanced and unbalanced SVs using topologically associated domains (TADs) as genome units. Among others, gene-associated data (as function and dosage sensitivity), phenotype similarity scores, and copy number variants (CNVs) scoring metrics are retrieved for an informed SV interpretation. For evaluation, we retrospectively applied SVInterpreter to 97 balanced (translocations and inversions) and 125 unbalanced (deletions, duplications, and insertions) previously published SVs, and 145 SVs identified from 20 clinical samples. Our results showed the ability of SVInterpreter to support the evaluation of SVs by (1) confirming more than half of the predictions of the original studies, (2) decreasing 40% of the variants of uncertain significance, and (3) indicating several potential position effect events. To our knowledge, SVInterpreter is the most comprehensive TAD-based tool to identify the possible disease-causing candidate genes and to assist prediction of the clinical outcome of SVs. SVInterpreter is available at http://dgrctools-insa.min-saude.pt/cgi-bin/SVInterpreter.py.
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http://dx.doi.org/10.3389/fgene.2021.757170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8671832PMC
December 2021

The GG genotype of the serotonin 4 receptor genetic polymorphism, rs1345697, is associated with lower remission rates after antidepressant treatment: Findings from the METADAP cohort.

J Affect Disord 2022 02 11;299:335-343. Epub 2021 Dec 11.

MOODS Team, CESP, INSERM, Faculté de médecine, Université Paris-Saclay, Le Kremlin Bicêtre, F-94275 France; Service de Génétique Moléculaire, Pharmacogénétique et Hormonologie de Bicêtre, Hôpitaux Universitaires Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Le Kremlin Bicêtre, F-94275 France. Electronic address:

Background: Pharmacological studies have yielded valuable insights into the role of the serotonin 4 receptor (HTR4) in major depressive episodes (MDE) and response to antidepressant drugs (AD). A genetic association has been shown between HTR4 and susceptibility to mood disorders. Our study aims at assessing the association between the HTR4 genetic polymorphism, rs1345697, and improvement in depressive symptoms and remission after antidepressant treatment in MDE patients.

Methods: 492 depressed patients from the METADAP cohort were treated prospectively for 6 months with ADs. The clinical outcomes according to HTR4 rs1345697 were compared after 1 (M1), 3 (M3), and 6 (M6) months of treatment. Mixed-effects logistic regression and adjusted linear models assessed the association between rs1345697 and 17-item Hamilton Depression Rating Scale (HDRS) score improvement and response/remission.

Results: Over the 6 months of treatment, mixed-effects regressions showed lower improvements in HDRS scores (Coefficient=1.52; Confident Interval (CI) 95% [0.37-2.67]; p = 0.009) and lower remission rates (Odds Ratio=2.0; CI95% [1.0-4.1]; p = 0.05) in GG homozygous patients as compared to allele A carriers.

Limitations: The major limitations of our study are the uncertainty of the rs1345697 effect on HTR4 function, the substantial drop-out rate, and the fact that analysis is not based on randomization between polymorphism groups.

Conclusions: In our study, patients who were homozygous carriers of the variant G of the HTR4 rs1345697 had lower depressive symptoms improvement and 2-fold lower remission rates after antidepressant treatment as compared to allele A carriers. Randomization study should be done to confirm these results.
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http://dx.doi.org/10.1016/j.jad.2021.12.012DOI Listing
February 2022

Low Temperature Effect on the Endocrine and Circadian Systems of Adult .

Front Physiol 2021 24;12:707067. Epub 2021 Nov 24.

Laboratory of Comparative Physiology of Pigmentation, Department of Physiology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.

The control of the biological rhythms begins with the activation of photo- and thermosensitive cells located in various organs of the fish such as brain, eye, and skin, but a central clock is still to be identified in teleosts. Thermal changes are stressors which increase cortisol and affect the rhythm of other hormones such as melatonin and growth hormone (GH), in both endo- and ectothermic organisms. Our aim was to investigate how temperature (23°C for 6 days) lower than the optimal (28°C) modulates expression of several gene pathways including growth hormone () and its receptors (), insulin-like growth factor1 () and its receptors (), cortisol and its receptor (), the limiting enzyme of melatonin synthesis (arylalkylamine N-acetyltransferase, ) and melatonin receptors (), as well as their relationship with clock genes in in early light and early dark phases of the day. Lower temperature reduced the expression of the hormone gene , and of the related receptors , and . Cortisol levels were higher at the lower temperature, with a decrease of its receptor () transcripts in the liver. Interestingly, we found higher levels of transcripts in the brain at 23°C. Overall, lower temperature downregulated the transcription of hormone related genes and clock genes. The results suggest a strong correlation of temperature challenge with the clock molecular mechanism and the endocrine systems analyzed, especially the growth hormone and melatonin axes, in tissues.
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http://dx.doi.org/10.3389/fphys.2021.707067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8652057PMC
November 2021

P bodies get viscous.

Authors:
Daryl J David

Nat Cell Biol 2021 Dec;23(12):1215

Nature Cell Biology, .

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http://dx.doi.org/10.1038/s41556-021-00817-4DOI Listing
December 2021

Identification and Genetic Characterization of Viral Pathogens in Ruminant Gestation Abnormalities, Israel, 2015-2019.

Viruses 2021 10 22;13(11). Epub 2021 Oct 22.

Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, 17493 Greifswald-Insel Riems, Germany.

Infectious agents including viruses are important abortifacients and can cause fetal abnormalities in livestock animals. Here, samples that had been collected in Israel from aborted or malformed ruminant fetuses between 2015 and 2019 were investigated for the presence of the following viruses: the reoviruses bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV), the flaviviruses bovine viral diarrhea virus (BVDV) and border disease virus (BDV), the peribunyaviruses Shuni virus (SHUV) and Akabane virus (AKAV), bovine herpesvirus type 1 (BoHV-1) and bovine ephemeral fever virus (BEFV). Domestic (cattle, sheep, goat) and wild/zoo ruminants were included in the study. The presence of viral nucleic acid or antigen could be confirmed in 21.8 % of abnormal pregnancies (213 out of 976 investigated cases), with peribunyaviruses, reoviruses and pestiviruses being the most prevalent. At least four different BTV serotypes were involved in abnormal courses of pregnancy in Israel. The subtyping of pestiviruses revealed the presence of two BDV and several distinct BVDV type 1 strains. The peribunyaviruses AKAV and SHUV were identified annually throughout the study period, however, variation in the extent of virus circulation could be observed between the years. In 2018, AKAV even represented the most detected pathogen in cases of small domestic ruminant gestation abnormalities. In conclusion, it was shown that various viruses are involved in abnormal courses of pregnancy in ruminants in Israel.
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http://dx.doi.org/10.3390/v13112136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619439PMC
October 2021

Optimized Synthesis of New Thiosemicarbazide Derivatives with Tuberculostatic Activity.

Int J Mol Sci 2021 Nov 9;22(22). Epub 2021 Nov 9.

Department of Natural and Synthetic Polymers, Faculty of Chemical Engineering and Environmental Protection, "Gheorghe Sachi" Technical University, 73 Professor Dimitrie Mangeron Blvd., 700050 Iasi, Romania.

Original results are presented in the field of research that addresses the extension of the reaction of residue of acyl-thiosemicarbazide fixation on the structure of 5-nitrobenzimidazole by a sulphonic group. The aim of the study is the increase of new thiosemicarbazide derivatives' applicative potential in the field of biochemistry, with a wide range of medical applications. The newly obtained compounds were characterized by using elemental analysis and spectral analysis (FT-IR and H NMR). A study regarding the optimization of the chemical reactions was made. The performed in vitro biological tests confirmed the tuberculostatic activity of three newly obtained compounds against .
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http://dx.doi.org/10.3390/ijms222212139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8622382PMC
November 2021

Cardiometabolic risk factors and hypovitaminosis D in adolescents with overweight from a sunny region in northeast Brazil: A cross-sectional study.

Nutr Hosp 2021 Nov 15. Epub 2021 Nov 15.

Postgraduate Nutrition Program. Centro de Ciências da Saúde. Universidade Federal do Rio Grande do Norte.

Background: obesity can influence vitamin D levels, which in turn might be associated with cardiometabolic risk factors.

Objectives: this study assessed the association between 25-hydroxyvitamin D [25(OH)D] levels and cardiometabolic risk factors in adolescents with overweight living in a region of northeastern Brazil.

Material And Methods: a cross-sectional study was carried out by non-probabilistic sampling in adolescents diagnosed with overweight or obesity. The subjects were divided according to their 25(OH)D status into two groups: sufficient vitamin D and hypovitaminosis D. Biodemographic, lifestyle, cardiometabolic, and biochemical factors were evaluated. A logistic regression model was applied to determine the predictors of hypovitaminosis D.

Results: we found a high frequency of hypovitaminosis D (45.6 %) in adolescents. Weekly sun exposure was negatively associated with hypovitaminosis D (OR = 0.96; 95 % CI: 0.92-0.99), while significant positive associations were observed between hypovitaminosis D and blood pressure above the 95th percentile (OR = 4.00; 95 % CI: 1.19-13.37), body weight (OR = 1.04; 95 % CI: 1.01-1.07), and fasting insulin (OR = 1.13; 95 % CI: 1.05-1.22).

Conclusion: hypovitaminosis D showed a high prevalence in adolescents with overweight living in a sunny region of northeastern Brazil, and cardiometabolic risk factors such as systemic arterial hypertension, high body weight, and hyperinsulinemia are predictors of hypovitaminosis D.
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http://dx.doi.org/10.20960/nh.03745DOI Listing
November 2021

Long term dual antiretroviral therapy: A real life retrospective countrywide Israeli study.

PLoS One 2021 29;16(10):e0259271. Epub 2021 Oct 29.

Department of Clinical Microbiology and Infectious Diseases, Hadassah AIDS Center, Hadassah Hebrew University Medical Center, Jerusalem, Israel.

Aim: Combined antiretroviral treatment (cART) traditionally consists of three antiretroviral medications, while two-drug regimens (2DR), historically used infrequently, recently been suggested to be non-inferior to three-drug regimens, is emerging as a potential treatment option and is currently a recommended option for treatment initiation in many guidelines.

Purpose: Characterize the indications and clinical efficacy of 2DR use at a real-life setting in a nation-wide survey.

Methods: A cross-sectional survey of Israeli patients treated by 2DR until July 2019, included demographic, immunologic, virologic, genotypic and biochemical/metabolic parameters at diagnosis, ART initiation, 2DR initiation and following 24, 48, 96 and 144 weeks of 2DR treatment.

Results: 176 patients were included in the study. In contrast to historical data implicating ART resistance and adverse effects as the major reasons leading to 2DR switching, treatment simplification was the main reason leading to 2DR treatment in 2019. 2DR that included INSTI and PI were more commonly used in cases of drug resistance, while a combination of INSTI and NNRTI was used in all other 2DR indications. A switch to 2DR induced a mean CD4 T cell increase from 599 cells/μl at treatment initiation to 680 cells/μl at 96 weeks of treatment p<0.001 and viral suppression improvement from 73.9% at initiation to 87.0% at 48 weeks of treatment (p = 0.004). PI and INSTI 2DR was inferior in suppressing viral levels compared to other 2DRs but used for subset of more complex patients.

Conclusions: 2DR in a large-scale real-life nation-wide survey proved to be safe and effective. Most 2DRs, other than PI and INSTI, were similarly effective in suppressing HIV viremia and in elevating CD4 T cell counts.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0259271PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555785PMC
December 2021

Reviving through human hippocampal newborn neurons.

Encephale 2021 Oct 11. Epub 2021 Oct 11.

CESP, MOODS Team, Inserm, faculté de pharmacie, université Paris-Saclay, 92296 Châtenay-Malabry, France. Electronic address:

Recent contradictory data has renewed discussion regarding the existence of adult hippocampal neurogenesis (AHN) in humans, i.e., the continued production of new neurons in the brain after birth. The present review revisits the debate of AHN in humans from a historical point of view in the face of contradictory evidence, analyzing the methods employed to investigate this phenomenon. Thus, to date, of the 57 studies performed in humans that we reviewed, 84% (48) concluded in favor of the presence of newborn neurons in the human adult hippocampus. Besides quality of the tissue (such as postmortem intervals below 26hours as well as tissue conservation and fixation), considerations for assessing and quantify AHN in the human brain require the use of stereology and toxicological analyses of clinical data of the patient.
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http://dx.doi.org/10.1016/j.encep.2021.09.001DOI Listing
October 2021

Resting state predicts neural activity during reward-guided decision making: An fMRI study on Balloon Analogue Risk Task.

Behav Brain Res 2022 Jan 2;417:113616. Epub 2021 Oct 2.

Department of Clinical Psychology and Psychotherapy, Babeş-Bolyai University, Cluj-Napoca, Romania; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, USA.

In our previous work [8], we have shown that resting state (RS) functional connectivity metrics are significantly related with behavioural performance at Balloon Analogue Risk Task (BART). In the present study we investigated the hypothesis of an association between RS metrics and neural activity evoked by BART execution. A group-level whole-brain regression was run to assess whether RS metrics predict brain activation during the BART, in a sample of 35 young healthy adults (mean age 23 ± 2 years, 25 F). Results complete the previous findings showing that RS is also significantly associated with the neural activity during BART execution. Specifically, ALFF is positively associated with the activity of both the right inferior parietal lobule and the left caudate. These new results are coherent with previous evidence indicating RS abnormalities in clinical conditions characterised by symptoms of impulse control disorders, and further suggest that RS might be a stable predictor of both behavioural indices and neural correlates of impulsivity and of reward-guided decision-making.
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http://dx.doi.org/10.1016/j.bbr.2021.113616DOI Listing
January 2022

Endothelial Heterogeneity in Development and Wound Healing.

Cells 2021 09 7;10(9). Epub 2021 Sep 7.

Cancer and Ageing Research Program, School of Biomedical Sciences, Queensland University of Technology, Brisbane 4102, Australia.

The vasculature is comprised of endothelial cells that are heterogeneous in nature. From tissue resident progenitors to mature differentiated endothelial cells, the diversity of these populations allows for the formation, maintenance, and regeneration of the vascular system in development and disease, particularly during situations of wound healing. Additionally, the de-differentiation and plasticity of different endothelial cells, especially their capacity to undergo endothelial to mesenchymal transition, has also garnered significant interest due to its implication in disease progression, with emphasis on scarring and fibrosis. In this review, we will pinpoint the seminal discoveries defining the phenotype and mechanisms of endothelial heterogeneity in development and disease, with a specific focus only on wound healing.
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http://dx.doi.org/10.3390/cells10092338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469713PMC
September 2021

Feed intake, methane yield, and efficiency of utilization of energy and nitrogen by sheep fed tropical grasses.

Trop Anim Health Prod 2021 Sep 18;53(5):452. Epub 2021 Sep 18.

Department of Agricultural Diagnosis and Research, Hulha Negra, RS, Brazil.

Forage allowance impacts dry matter (DM) intake and the use of nutrients by ruminants. The efficient use of protein and energy from pasture is related to better livestock performance and lower environmental impacts. The aims of this study were to evaluate the effect of forage allowance levels on intake, digestibility, nitrogen (N) and energy balance, and methane (CH) emissions by lambs fed fresh pearl millet [Pennisetum americanum (L.) Leeke]. An indoor trial was performed using lambs in a completely randomized design with four treatments [forage allowance at 1.5, 2.0, 2.5 kg DM/100 kg of live weight (LW), and ad libitum allowing 20% of refusals] and four replicates (lambs). Forage intake, digestibility, total urine and feces excretion, and CH emission were measured to calculate N and energy balances. An increase in forage allowance resulted in a linear increase in lamb forage intake, N retention, and metabolizable energy intake. Moreover, lamb CH emission (g/day) also increased with greater forage allowance, while CH yield decreased linearly as forage allowance increased. Our results indicate that maximizing forage intake improves N and energy use efficiency and mitigates CH yield and decreases CH conversion factor (Ym) by lambs fed pearl millet forage. Thus, management strategies that optimize intake of tropical forages by ruminants improve the use of nutrients ingested and mitigates negative impacts to the environment.
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http://dx.doi.org/10.1007/s11250-021-02928-4DOI Listing
September 2021

Sagittal Synostosis and Its Association With Cognitive, Behavioral, and Psychological Functioning: A Meta-analysis.

JAMA Netw Open 2021 09 1;4(9):e2121937. Epub 2021 Sep 1.

Craniofacial Australia, North Adelaide, South Australia, Australia.

Importance: Findings on the cognitive, behavioral, and psychological functioning of individuals with sagittal synostosis (SS) are highly disparate, limiting their clinical utility.

Objective: To identify and review research on individuals with SS and to determine whether, and to what extent, they experience cognitive, behavioral, and psychological difficulties compared with their healthy peers or normative data for each measure.

Data Sources: PubMed, Scopus, Embase, and PsycINFO were searched through January 2021 with no date restrictions. Scopus citation searches and manual checks of the reference lists of included studies were conducted.

Study Selection: Studies included participants of any age who had received a diagnosis of single-suture (isolated or nonsyndromic) SS or scaphocephaly and who had been assessed on cognitive, behavioral, and psychological outcomes.

Data Extraction And Synthesis: Data were independently extracted by 2 reviewers. Case-control outcomes (individuals with SS vs healthy peers or normative data) were compared using random-effects models with 3 effect sizes calculated: weighted Hedges g (gw), odds ratios (ORs), and mean prevalence rates. This study follows the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines.

Main Outcomes And Measures: Findings were categorized by surgical status (conservatively managed, presurgery, postsurgery, or combined); domain (eg, general cognition); type of cognitive, behavioral, or psychological measure (objective or subjective); and source of comparison data (peers or normative data).

Results: Data from 32 studies, involving a pooled sample of 1422 children and adults with SS (mean [SD] age at assessment, 5.7 [6.6] years; median [interquartile range] age, 3.3 [0.5-10.3] years), were analyzed. Data on sex were available for 824 participants, and 642 (78%) were male. Individual study results varied substantially. Objective tests identified significant moderate group differences on 3 of 16 examined domains: presurgical motor functioning (3 studies; gw = -0.42; 95% CI, -0.67 to -0.18; P < .001), postsurgical short-term memory (2 studies; gw = -0.45; 95% CI, -0.72 to -0.17; P < .001), and postsurgical visuospatial ability (6 studies; gw = 0.31; 95% CI, 0.18 to 0.44; P < .001). Prevalence estimates and ORs varied widely, with 15 studies showing prevalence estimates ranging from 3% to 37%, and 3 studies showing ORs ranging from 0.31 (95% CI, 0.01 to 6.12) for processing speed in the conservatively managed sample to 4.55 (95% CI, 0.21 to 98.63) for postsurgical visuospatial abilities.

Conclusions And Relevance: In this meta-analysis, findings for the functioning of participants with SS were highly disparate and often of low quality, with small samples sizes and control groups rarely recruited. Nonetheless, the findings suggest that some individuals with SS experience negative outcomes, necessitating routine assessment.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.21937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438597PMC
September 2021

Increased Capsule Thickness and Hypermotility Are Traits of Carbapenem-Resistant ST3 Strains Causing Fulminant Infection.

Open Forum Infect Dis 2021 Sep 30;8(9):ofab386. Epub 2021 Jul 30.

National Institute for Antibiotic Resistance and Infection Control, Ministry of Health, Tel-Aviv, Israel.

Background: is a successful nosocomial pathogen, causing severe, life-threatening infections in hospitalized patients, including pneumonia and bloodstream infections. The spread of carbapenem-resistant (CRAB) strains is a major health threat worldwide. The successful spread of CRAB is mostly due to its highly plastic genome. Although some virulence factors associated with CRAB have been uncovered, many mechanisms contributing to its success are not fully understood.

Methods: Here we describe strains of CRAB that were isolated from fulminant cases in 2 hospitals in Israel. These isolates show a rare hypermucoid (HM) phenotype and were investigated using phenotypic assays, comparative genomics, and an in vivo model.

Results: The 3 isolates belonged to the ST3 international clonal type and were closely related to each other, as shown by Fourier-transform infrared spectroscopy and phylogenetic analyses. These isolates possessed thickened capsules and a dense filamentous extracellular polysaccharides matrix as shown by transmission electron microscopy (TEM), and overexpressed the capsule polysaccharide synthesis pathway-related gene.

Conclusions: The HM isolates possessed a unique combination of virulence genes involved in iron metabolism, protein secretion, adherence, and membrane glycosylation. HM strains were more virulent than control strains in 2 infection models. In conclusion, our findings demonstrated several virulence factors, all present in 3 CRAB isolates with rare hypermucoid phenotypes.
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http://dx.doi.org/10.1093/ofid/ofab386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423469PMC
September 2021

Isolated torsion of a fallopian tube: an uncommon cause of abdominal pain in an 11-year-old.

BMJ Case Rep 2021 Aug 25;14(8). Epub 2021 Aug 25.

Department of gynecology and obstetrics, Centro Hospitalar e Universitario de Coimbra EPE, Coimbra, Portugal.

This report describes a rare case of isolated fallopian tube torsion (IFTT) in a premenarchal 11-year-old girl. The patient presented with subacute abdominal pain, associated with nausea and vomiting. Sonographic findings revealed left tube enlargement with free intraperitoneal fluid. Doppler mapping was not unequivocal. During exploratory laparoscopy, a large pelvic necrotic mass was found to be a twisted left fallopian tube. After detorsion, salpingectomy was performed and the patient recovered promptly, showing no complications 3 months post operation. IFTT should be considered as a differential diagnosis of lower abdominal pain in adolescent girls with normal-appearing ovaries on ultrasound. Conservative management for fertility preservation is the ideal approach. Therefore, avoiding delay in laparoscopy is crucial.
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http://dx.doi.org/10.1136/bcr-2021-243947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8388290PMC
August 2021

Aliviado Mobile App for Hospice Providers: A Usability Study.

J Pain Symptom Manage 2022 Jan 10;63(1):e37-e45. Epub 2021 Aug 10.

Hartford Institute for Geriatric Nursing, Rory Meyers College of Nursing, New York University, New York, New York, USA.

Context: Evaluation of usability and mobile health content is critical for ensuring effective implementation of technology utilizing interventions tailored to the needs of hospice care providers for people living with dementia in community-based settings.

Objectives: To evaluate the usability, content, and "readiness to launch" of the Aliviado mobile health app for interdisciplinary team members participating in the Hospice Advanced Dementia Symptom Management and Quality of Life.

Methods: Usability of the Aliviado app was assessed in 86 respondents with an adapted IBM Computer Usability Satisfaction Questionnaire following Hospice Advanced Dementia Symptom Management and Quality of Life training and implementation of the mobile app.

Results: More than half of users receiving training employed the mobile app in practice. Users reported use as: Daily-6.3%, Weekly-39.6%, monthly-54.2%. The highest measured attributes were usefulness, value, and effectiveness. Over 90% deemed the app "ready to launch" with no or minimal problems.

Conclusion: This study shows that a newly-developed mobile app is usable and can be successfully adopted for care of people living with dementia.
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http://dx.doi.org/10.1016/j.jpainsymman.2021.07.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766865PMC
January 2022

Effectiveness of Outpatient Rational Emotive Behavior Therapy Over One Decade.

Am J Psychother 2021 Dec 30;74(4):157-164. Epub 2021 Jul 30.

Department of Clinical Psychology and Psychotherapy, Babeş-Bolyai University, Cluj-Napoca, Romania (O. A. David, Cîmpean, Costescu, D. David); Department of Psychology, St. John's University, New York City (DiGiuseppe); Albert Ellis Institute, New York City (DiGiuseppe, Doyle, Hickey).

Objective: The aim of this article was to explore the effectiveness of rational emotive and cognitive-behavioral therapy (REBT) in a clinical setting.

Methods: This study included 349 patients of the Albert Ellis Institute who sought psychotherapy from 2007 to 2016. Analyses were conducted by using the intent-to-treat principle, and outcomes were measured after three sessions of therapy (to measure early response) and at the end of 20 sessions. Outcome Questionnaire-45 was used to measure patient functioning.

Results: Patients reported significant improvements in their functioning after participating in REBT, with a medium effect size for early response after three sessions of psychotherapy and at the end of the 20 sessions.

Conclusions: The authors' findings documented that REBT can be effectively transported from a research setting to clinical practice.
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http://dx.doi.org/10.1176/appi.psychotherapy.20200009DOI Listing
December 2021

Shame and eating disorders symptoms: A meta-analysis.

Int J Eat Disord 2021 11 24;54(11):1899-1945. Epub 2021 Jul 24.

Department of Clinical Psychology and Psychotherapy, Babeş-Bolyai University, Cluj-Napoca, Romania.

Objective: Numerous empirical studies and theoretical models posit that shame is a common experience among individuals across the eating disorder spectrum. In this study we aim to investigate the association between shame and eating disorders symptoms using a meta-analytical approach.

Method: In this meta-analysis, we synthesized findings from 195 studies to examine the proposed association between shame and eating disorders symptoms. We looked at the associations with both general eating disorders symptoms and with specific eating disorders symptoms (i.e., anorexic, bulimic, and binge-eating symptoms). Moderation analyses testing for the effect of type of shame, type of eating symptoms, clinical status, quality of the study, age, and gender were conducted.

Results: Shame was significantly associated with a medium to large effect size with all types of eating disorders symptoms (rs between .40 and .52). Body shame (r = .55) and shame around eating (r = .59) were more strongly related with eating disorders pathology. Type of eating disorders symptoms did not moderate the relationship between shame and disturbed eating.

Discussion: Overall, the magnitude of the effect size of the association between shame and eating disorders symptoms is a medium to large one. Body shame and shame around eating seem to be the types of shame most closely tied with eating disorders symptoms, suggesting that directly targeting them in interventions might be highly beneficial. Findings highlight current gaps in the literature (e.g., mostly correlational studies, low quality studies) with implications for future research.
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http://dx.doi.org/10.1002/eat.23583DOI Listing
November 2021

[Determination of the binding of natural products to the human c-myb oncogene promoter G-quadruplex DNA by capillary electrophoresis and electrospray ionization mass spectrometry].

Se Pu 2020 Sep;38(9):1069-1077

Department of Chemistry, University of British Columbia, Vancouver, BC V6T 1Z1, Canada.

The relationship between a drug and its target directly affects its pharmacology and efficacy. Drug-target binding ability and binding stoichiometry are essential characterization data in pharmaceutical research. The c-myb proto-oncogene encodes a crucial transcription factor that is involved in proliferation, differentiation, and maturation during hematopoiesis. Recent studies have found that the human oncogene c-myb is overexpressed in cancer tissues such as colorectal cancer. C-myb has become a potential therapeutic target for colorectal cancer, leukemia, and other cancers. A guanine (G)-rich DNA sequence located in the promoter region of c-myb can be spontaneously folded to form an intra-molecular G-quadruplex (G4) with cationic induction. The specific recognition of small molecules can stabilize this G4 folding, thus regulating the transcription and expression of c-myb. In this study, pressure assisted capillary electrophoresis frontier analysis (PACE-FA) combined with electrospray ionization mass spectrometry (ESI-MS) was used to investigate the interactions between the human c-myb promoter G4 and natural product molecules. In PACE-FA, an external pressure (no more than 13.8 kPa) in the same direction of the migration of the analyte was used in capillary electrophoresis frontier analysis (CE-FA), which greatly sped up the analysis while maintaining the accuracy of the results. Meanwhile, the combination of PACE-FA and ESI-MS could rapidly determine the affinity and stoichiometric relationship between binding molecules and targets. First, the intramolecular parallel-stranded G4 formation of the c-myb promoter sequence in the presence of cations (K, NH) was investigated by circular dichroism (CD) and ESI-MS. Then, ESI-MS was used to rapidly screen the natural products for candidate molecules that bound the target G4 DNA. The binding interactions were measured by mixing the c-myb DNA with each natural product separately in a 1:4 molar ratio, and then directly infusing these mixtures into the ESI-MS system. From the ESI-MS spectra, values calculated from the relative intensities of DNA and its complex ions were used to probe the binding affinities of the natural products. This parameter denotes the relative binding affinity for a small molecule with the G4 DNA. Three natural products were identified through the screen, and their binding affinities to G4 DNA were ranked as follows:pseudolaric acid B > scopolamine butylbromide > nuciferine. Considering that both specific and non-specific binding existed in the solution phase, a free solution method using PACE-FA was developed to further test the binding ability of these products to the c-myb promoter G4 DNA. In the PACE-FA experiments, the pre-equilibrated mixture of the c-myb G4 DNA and the selected ligand was injected into the capillary prior to separation. Upon applying voltage and an external pressure (6.9 kPa) to the capillary, different species of analytes in the sample migrated at their own rates due to their different sizes and charges. The results showed that scopolamine butylbromide could bind specifically to target G4 DNA with 1:1 stoichiometry and a binding constant of 1.18×10 L/mol. Nuciferine's binding to G4 DNA showed a linear increasing trend due to nonspecific binding; thus nuciferine is a nonspecific binder. Although pseudolaric acid B showed high affinity for the c-myb G4 DNA and 1:1 and 1:2 G4-bound complex ions were observed in ESI-MS measurements, the PACE-FA results indicated that pseudolaric acid B did not bind to target G4 DNA in free solution. Therefore, scopolamine butylbromide could be the best candidate to regulate the transcription of the c-myb oncogene, and is expected to be a precursor for anticancer drugs. In this work, PACE-FA has allowed for significant improvements to the conventional CE-FA technique. This combination of PACE-FA and ESI-MS not only reduced the time needed for binding analysis, but also improved the accuracy and specificity of the affinity analysis compared to conventional binding approaches. Furthermore, this combination could be used to screen other targeted drug candidates and to evaluate their interaction mechanisms.
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http://dx.doi.org/10.3724/SP.J.1123.2020.03001DOI Listing
September 2020

Characterization of Winter Dysentery Bovine Coronavirus Isolated from Cattle in Israel.

Viruses 2021 06 4;13(6). Epub 2021 Jun 4.

Kimron Veterinary Institute, Bet Dagan 50250, Israel.

Bovine coronavirus (BCoV) is the causative agent of winter dysentery (WD). In adult dairy cattle, WD is characterized by hemorrhagic diarrhea and a reduction in milk production. Therefore, WD leads to significant economic losses in dairy farms. In this study, we aimed to isolate and characterize local BCoV strains. BCoV positive samples, collected during 2017-2021, were used to amplify and sequence the S1 domain of S glycoprotein and the full hemagglutinin esterase gene. Based on our molecular analysis, local strains belong to different genetic variants circulating in dairy farms in Israel. Phylogenetic analysis revealed that all local strains clustered together and in proximity to other BCoV circulating in the area. Additionally, we found that local strains are genetically distant from the reference enteric strain Mebus. To our knowledge, this is the first report providing molecular data on BCoV circulating in Israel.
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http://dx.doi.org/10.3390/v13061070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226893PMC
June 2021

A Controlled Pilot Study of the Wish Outcome Obstacle Plan Strategy for Spouses of Persons with Early-Stage Dementia.

J Gerontol B Psychol Sci Soc Sci 2021 Jun 25. Epub 2021 Jun 25.

Geriatrics, Yale School of Medicine, VA Connecticut Healthcare System.

Objectives: Behavioral interventions can reduce distress for couples coping with early-stage dementia. However, most interventions are limited in accessibility and fail to address individualized goals. This pilot study examined the dyadic effects on multiple indicators of well-being of the Wish Outcome Obstacle Plan (WOOP) intervention which guides participants to use Mental Contrasting with Implementation Intentions (MCII) to achieve attainable goals in their daily lives.

Methods: This randomized controlled trial included 45 older persons with early-stage dementia (PWD) and their spousal care partners (CPs: n = 90 individuals). CPs were assigned randomly to WOOP training immediately after baseline (WOOP) or after a three-month follow-up interview (Control; CON). Both groups received a dementia care education booklet. WOOP CPs were instructed to practice WOOP at least once a day for two weeks. All CPs and PWDs completed home surveys (baseline, two-weeks, and three months) measuring perceived stress, depressive symptoms, quality of life, and affect.

Results: Mixed effects models showed significant intervention x time interaction effects with large effect sizes for CPs on three of the five outcomes over three months. Compared to CON, WOOP CPs had decreased perceived stress (δ = 1.71) and increased quality of life (δ = 1.55) and positive affect (δ = 2.30). WOOP PWD showed decreased perceived stress (δ = .87) and increased quality of life (δ = 1.26) but these effects were not statistically significant.

Discussion: WOOP is a promising, brief intervention to improve dementia care partners' well-being that may also positively impact their partners with dementia.
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http://dx.doi.org/10.1093/geronb/gbab115DOI Listing
June 2021

Evaluation of antiangiogenic and antiproliferative potential of ethanolic extracts of using and assays.

J Cancer Res Ther 2021 Apr-Jun;17(2):484-490

Department of Pharmacology, Sri Ramachandra Medical College, Sri Ramachandra Institute of Higher Education And Research (Deemed University), Porur, Chennai, Tamil Nadu, India.

Introduction: Andrographis echioides is a prevalently used medicinal herb in South Asian countries. Scientific researches with the extracts of A. echioides revealed its antipyretic, anti-inflammatory, antimicrobial, ulceroprotective, and hepatoprotective properties. This study was done to elucidate antiproliferative and antiangiogenic potential of ethanolic extracts of A. echioides (EEAE) by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-tetrazolium bromide (MTT) assay and chorioallantoic membrane (CAM) assay.

Materials And Methods: EEAE was prepared using Soxhlet apparatus with ethanol after being sun-dried and powdered. MCF 7 (human invasive breast ductal carcinoma) cell lines retaining attributes of differentiated mammary epithelium with both estrogen and progesterone receptors were treated with EEAE, and antiproliferative effect was seen using Mosmann method of MTT assay using 5-fluorouracil (5-FU) as a comparator. The evaluation of antiangiogenic potential of EEAE was done by comparing mean vessel density (MVD) in chick CAM after treatment with EEAE, thalidomide, and vascular endothelial growth factor (VEGF) using CAM assay, an in ovo assay.

Results: EEAE displayed antiproliferative activity from low to high concentrations with MTT assay. The IC of EEAE and 5-FU was 62.5 and 15.6 μg/ml, respectively (P < 0.05). The exhibition of its antiangiogenic activity increased proportionately with increasing concentration. VEGF increased MVD by 45.94%; thalidomide decreased it by 53.76%. There was a decrease of MVD by 5.91%, 20.46%, and 35.95% at concentrations of 25, 50, and 100 μg of EEAE, respectively.

Conclusion: EEAE possessed significant antiangiogenic and antiproliferative activity, making them a promising substrate in the development of a novel anticancer drug and can be successfully used in the therapy of various cancers after establishment of the anticancer effects in animal models and subsequently in clinical trials.
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http://dx.doi.org/10.4103/jcrt.JCRT_325_19DOI Listing
November 2021

Engaging Nursing Assistants to Enhance Receptivity to the Coronavirus Disease 2019 Vaccine.

J Am Med Dir Assoc 2021 06;22(6):1125-1127

Hartford Institute for Geriatric Nursing, Rory Meyers College of Nursing, New York University, New York, NY, USA.

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http://dx.doi.org/10.1016/j.jamda.2021.03.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169079PMC
June 2021

A prospective cohort study of patients presenting to the emergency department with upper gastrointestinal bleeding.

J Family Med Prim Care 2021 Mar 8;10(3):1431-1436. Epub 2021 Apr 8.

Department of Emergency Medicine, Christian Medical College, Vellore, Tamil Nadu, India.

Background: Upper gastrointestinal (UGI) bleeding is a common presentation to the Emergency Department (ED), and is associated with re-bleeding and significant mortality. Although several studies have described etiology and outcome of UGI bleeding, few have been done in the EDs.

Materials And Methods: This prospective observational cohort study included all patients presenting with hematemesis or melena, between June 2016 and January 2017 to the ED. Demographic data, risk factors, endoscopy findings and prognosticating scores were noted. Patients were followed up through telephonic communication after 3 months to assess re-bleeding rate and mortality.

Results: The study cohort included 210 patients with a male predominance (76.2%). The mean (SD) age was 51 (16.8) years. They presented with either hematemesis (33.8%), melena (28.6%), or both (37.6%). One third (35.7%) had variceal bleed, 21% had peptic ulcer disease (PUD), and 43.3%bled due to other etiology. UGI scopy was performed in 85.2% of patients with banding (25.1%) and sclerotherapy (14%) being the most frequently performed procedures. Endoscopic intervention was not required in 58.6%of patients. Packed red cells were transfused in 46.7% patients. The 48-h re-bleed rate among variceal bleeders was 5.3% and 11.4% among peptic ulcer bleeders. The 3-month re-bleeding rate was 42.9% and the 3-month mortality rate was 17.5% among the variceal bleeders and the same was 5.6% and 2.8%, respectively, among the peptic ulcer bleeders. The overall mortality was 12.4%.

Conclusions: Variceal bleeding and PUD were the predominant causes of UGI bleeding. Overall, a quarter of our patients had a re-bleed within 3 months, with majority being variceal bleeds.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_1996_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140221PMC
March 2021

Blood microbiota and metabolomic signature of major depression before and after antidepressant treatment: a prospective case-control study.

J Psychiatry Neurosci 2021 05 19;46(3):E358-E368. Epub 2021 May 19.

From the INSERM UMRS 996 - Intestinal Microbiota, Macrophages and Liver Inflammation, DHU Hepatinov, Clamart, France (Ciocan, Cassard, Voican, Perlemuter); the University Paris-Saclay, University Paris-Sud, Faculty of Medicine, Le Kremlin-Bicêtre, France (Ciocan, Cassard, Becquemont, Verstuyft, Voican, El Asmar, Colle, Trabado, Chanson, Perlemuter, Corruble); the APHP, Hepato-Gastroenterology and Nutrition, Antoine-Béclère Hospital, Clamart, France (Ciocan, Voican, Perlemuter); the Centre for Clinical Research (CRC), Kremlin-Bicêtre Hospital, AP-HP, Le Kremlin-Bicêtre, France (Becquemont); the INSERM UMR-1178, CESP, "MOODS" Team, Le Kremlin-Bicêtre, France (Becquemont, Verstuyft, El Asmar, David, Corruble); the Department of Molecular Genetics, Pharmacogenetics and Hormones, Kremlin-Bicêtre Hospital, AP-HP, Le Kremlin-Bicêtre, 94275, France (Becquemont, Verstuyft, Trabado); the Psychiatry Department, Kremlin-Bicêtre Hospital, AP-HP, Le Kremlin-Bicêtre, 94275, France (Colle, Corruble); the University Paris-Saclay, University Paris-Sud, Faculty of Pharmacy, Chatenay-Malabry, 92 296, France (David); the INSERM 1185, University Paris-Saclay, University Paris-Sud, Faculty of Medicine, Le Kremlin-Bicêtre, 94276, France (Trabado, Chanson); the Department of Endocrinology, Saint-Antoine Hospital, AP-HP, Sorbonne University, University Paris 6, Paris, France (Feve); the INSERM UMR S_938, Saint-Antoine Research Centre, Paris, France (Feve); and the Department of Endocrinology and Reproductive Diseases, Kremlin-Bicêtre Hospital, AP-HP, Le Kremlin-Bicêtre, 94275, France (Chanson).

Background: The microbiota interacts with the brain through the gut-brain axis, and a distinct dysbiosis may lead to major depressive episodes. Bacteria can pass through the gut barrier and be found in the blood. Using a multiomic approach, we investigated whether a distinct blood microbiome and metabolome was associated with major depressive episodes, and how it was modulated by treatment.

Methods: In this case-control multiomic study, we analyzed the blood microbiome composition, inferred bacterial functions and metabolomic profile of 56 patients experiencing a current major depressive episode and 56 matched healthy controls, before and after treatment, using 16S rDNA sequencing and liquid chromatography coupled to tandem mass spectrometry.

Results: The baseline blood microbiome in patients with a major depressive episode was distinct from that of healthy controls (patients with a major depressive episode had a higher proportion of Janthinobacterium and lower levels of Neisseria) and changed after antidepressant treatment. Predicted microbiome functions confirmed by metabolomic profiling showed that patients who were experiencing a major depressive episode had alterations in the cyanoamino acid pathway at baseline. High baseline levels of Firmicutes and low proportions of Bosea and Tetrasphaera were associated with response to antidepressant treatment. Based on inferred baseline metagenomic profiles, bacterial pathways that were significantly associated with treatment response were related to xenobiotics, amino acids, and lipid and carbohydrate metabolism, including tryptophan and drug metabolism. Metabolomic analyses showed that plasma tryptophan levels are independently associated with response to antidepressant treatment.

Limitations: Our study has some limitations, including a lack of information on blood microbiome origin and the lack of a validation cohort to confirm our results.

Conclusion: Patients with depression have a distinct blood microbiome and metabolomic signature that changes after treatment. Dysbiosis could be a new therapeutic target and prognostic tool for the treatment of patients who are experiencing a major depressive episode.
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http://dx.doi.org/10.1503/jpn.200159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327971PMC
May 2021

Abdominal arterial lesions associated with antiphospholipid antibodies: A comparative cross sectional magnetic resonance angiography study.

Rheumatology (Oxford) 2021 May 6. Epub 2021 May 6.

Louise Coote Lupus Unit, 1st Floor, Counting House, Guy's Hospital, London, . SE1 9RT, UK.

Introduction: Case reports and small case series suggest that stenotic lesions of the renal, coeliac and mesenteric arteries may occur in the antiphospholipid syndrome (APS) resulting in clinical consequences such as hypertension and abdominal angina.

Objective: To determine the prevalence of stenotic lesions in arteries arising from the middle aorta in patients with antiphospholipid antibodies (aPL) compared with healthy, hypertensive and atherosclerotic controls.

Patients And Methods: In a cross-sectional comparative radiological study using magnetic resonance angiography (MRA) we assessed 5 groups of subjects for the prevalence of stenotic lesions in arteries arising from the middle aorta: APS/aPL positive, healthy renal donors, patients with hypertension, patients with atherosclerosis defined radiologically and patients with systemic lupus erythematosus and vasculitis who were negative for aPL. All subjects underwent MRA in suspended respiration and images were assessed by 2 senior radiologists blinded to the clinical details.

Results: In the atherosclerosis group, vascular stenotic lesions were more prevalent (71%) than in any other group (p≤ 0.000002). The prevalence of all stenotic lesions in aPL positive patients (33%) was significantly higher than in the renal donors (18%) and hypertensive patients (19%) (p≤ 0.009). Renal artery stenosis was significantly more prevalent in aPL positive patients than in renal donors (p≤ 0.0006) but similar to the prevalence in hypertensive patients. Coeliac and/or mesenteric lesions were significantly more common in aPL positive patients vs hypertensive patients (p≤ 0.001). Stenoses did not correlate with traditional risk factors.

Conclusion: Arterial stenotic lesions in arteries arising from the middle aorta were highly prevalent in atherosclerotic subjects and were more common in aPL positive patients than hypertensive patients and healthy renal donors.
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http://dx.doi.org/10.1093/rheumatology/keab400DOI Listing
May 2021

Energy-Efficient Ultrasonic Water Level Detection System with Dual-Target Monitoring.

Sensors (Basel) 2021 Mar 23;21(6). Epub 2021 Mar 23.

Department of Civil Engineering, The University of Texas at Arlington, Arlington, TX 76019, USA.

This study presents a developed ultrasonic water level detection (UWLD) system with an energy-efficient design and dual-target monitoring. The water level monitoring system with a non-contact sensor is one of the suitable methods since it is not directly exposed to water. In addition, a web-based monitoring system using a cloud computing platform is a well-known technique to provide real-time water level monitoring. However, the long-term stable operation of remotely communicating units is an issue for real-time water level monitoring. Therefore, this paper proposes a UWLD unit using a low-power consumption design for renewable energy harvesting (e.g., solar) by controlling the unit with dual microcontrollers (MCUs) to improve the energy efficiency of the system. In addition, dual targeting to the pavement and streamside is uniquely designed to monitor both the urban inundation and stream overflow. The real-time water level monitoring data obtained from the proposed UWLD system is analyzed with water level changing rate (WLCR) and water level index. The quantified WLCR and water level index with various sampling rates present a different sensitivity to heavy rain.
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http://dx.doi.org/10.3390/s21062241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061885PMC
March 2021
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