bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydropathicity-based prediction of pain-causing NaV1.7 variants
Authors: Xenakis Makros N. , Kapetis Dimos , Yang Yang , Gerrits Monique M. , Heijman Jordi , Waxman Stephen G. , Lauria Giuseppe , Faber Catharina G. , Westra Ronald L. , Lindsey Patrick J. , Smeets Hubert J.
Published: April 2021

Background

Mutation-induced variations in the functional architecture of the NaV1.7 channel protein are causally related to a broad spectrum of human pain disorders. Predicting in silico the phenotype of NaV1.7 variant is of major clinical importance; it can aid in reducing costs of in vitro pathophysiological characterization of NaV1.7 variants, as well as, in the design of drug agents for counteracting pain-disease symptoms.

Results

In this work, we utilize spatial complexity of hydropathic effects toward predicting which NaV1.7 variants cause pain (and which are neutral) based on the location of corresponding mutation sites within the NaV1.7 structure. For that, we analyze topological and scaling hydropathic characteristics of the atomic environment around NaV1.7’s pore and probe their spatial correlation with mutation sites. We show that pain-related mutation sites occupy structural locations in proximity to a hydrophobic patch lining the pore while clustering at a critical hydropathic-interactions distance from the selectivity filter (SF). Taken together, these observations can differentiate pain-related NaV1.7 variants from neutral ones, i.e., NaV1.7 variants not causing pain disease, with 80.5$$\%$$
%
sensitivity and 93.7$$\%$$
%
specificity [area under the receiver operating characteristics curve = 0.872].

Conclusions

Our findings suggest that maintaining hydrophobic NaV1.7 interior intact, as well as, a finely-tuned (dictated by hydropathic interactions) distance from the SF might be necessary molecular conditions for physiological NaV1.7 functioning. The main advantage for using the presented predictive scheme is its negligible computational cost, as well as, hydropathicity-based biophysical rationalization.
Transcriptomic analysis of α-linolenic acid content and biosynthesis in Paeonia ostii fruits and seeds
Authors: Yu Shui-Yan , Zhang Xiao , Huang Liang-Bo , Lyu Yu-Ping , Zhang Ying , Yao Zu-Jie , Zhang Xiao-Xiao , Yuan Jun-Hui , Hu Yong-Hong
Published: April 2021

Background

Paeonia ostii is a potentially important oilseed crop because its seed yield is high, and the seeds are rich in α-linolenic acid (ALA). However, the molecular mechanisms underlying ALA biosynthesis during seed kernel, seed testa, and fruit pericarp development in this plant are unclear. We used transcriptome data to address this knowledge gap.

Results

Gas chromatograph-mass spectrometry indicated that ALA content was highest in the kernel, moderate in the testa, and lowest in the pericarp. Therefore, we used RNA-sequencing to compare ALA synthesis among these three tissues. We identified 227,837 unigenes, with an average length of 755 bp. Of these, 1371 unigenes were associated with lipid metabolism. The fatty acid (FA) biosynthesis and metabolism pathways were significantly enriched during the early stages of oil accumulation in the kernel. ALA biosynthesis was significantly enriched in parallel with increasing ALA content in the testa, but these metabolic pathways were not significantly enriched during pericarp development. By comparing unigene transcription profiles with patterns of ALA accumulation, specific unigenes encoding crucial enzymes and transcription factors (TFs) involved in de novo FA biosynthesis and oil accumulation were identified. Specifically, the bell-shaped expression patterns of genes encoding SAD, FAD2, FAD3, PDCT, PDAT, OLE, CLE, and SLE in the kernel were similar to the patterns of ALA accumulation in this tissue. Genes encoding BCCP, BC, KAS I– III, and FATA were also upregulated during the early stages of oil accumulation in the kernel. In the testa, the upregulation of the genes encoding SAD, FAD2, and FAD3 was followed by a sharp increase in the concentrations of ALA. In contrast, these genes were minimally expressed (and ALA content was low) throughout pericarp development.

Conclusions

We used three tissues with high, moderate, and low ALA concentrations as an exemplar system in which to investigate tissue-specific ALA accumulation mechanisms in P. ostii. The genes and TFs identified herein might be useful targets for future studies of ALA accumulation in the tree peony. This study also provides a framework for future studies of FA biosynthesis in other oilseed plants.
Concentrations of estradiol, progesterone and testosterone in serum and cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage correlate weakly with transcranial Doppler flow velocities
Authors: Martin Jan , Plank Eva , Ulm Bernhard , Gempt Jens , Wostrack Maria , Jungwirth Bettina , Kagerbauer Simone M.
Published: April 2021

Background

The implication of the steroids estradiol, progesterone and testosterone in cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) has not been comprehensively assessed. In rodents, studies suggested beneficial effects of steroids on cerebral vasospasm after experimental SAH. Studies in humans are warranted, however, a general dilemma of human studies on neuroactive substances is that the brain is not directly accessible and that concentrations in the periphery may not adequately parallel concentrations in the central compartments. In the present study, concentrations of estradiol, progesterone and testosterone in serum and cerebrospinal fluid (CSF) of patients with aSAH were determined. Blood flow velocities in cerebral arteries were measured by transcranial Doppler sonography (TCD). The aim of this study was to evaluate the correlations between the cerebral blood flow velocities and levels of estradiol, progesterone and testosterone in CSF and serum.

Results

Samples of serum and CSF of 42 patients with aSAH were collected concomitantly daily or every other day via the arterial line and the external ventricular drainage for two weeks after the hemorrhage. Blood flow velocities in the cerebral arteries were determined by TCD. Total estradiol, progesterone and testosterone concentrations were measured by electro-chemiluminescence immunoassay. The strength of correlation was assessed by Spearman’s rank correlation coefficient. The correlation analysis revealed very weak correlations between cerebral blood flow velocities and concentrations of estradiol, progesterone and testosterone levels in both compartments with correlation coefficients below 0.2.

Conclusions

In humans with aSAH, merely very weak correlations between flow velocities in cerebral arteries and concentrations of estradiol, progesterone and testosterone in serum and CSF were demonstrated. These results suggest a limited influence of the respective steroids on cerebral vascular tone although vasodilatory effects were described in rodent studies. Thus, the implication of steroids in processes of neurological deterioration warrants further clarification.
Circulating miRNA-202-3p is a potential novel biomarker for diagnosis of type 1 gastric neuroendocrine neoplasms
Authors: Dou Dou , Li Xiao-kou , Xia Qi-sheng , Chen Ying-ying , Li Yuan-liang , Wang Chao , Qi Zhi-rong , Tan Huang-ying
Published: April 2021

Background

Currently, there are no circulating diagnostic biomarkers for gastric neuroendocrine neoplasms (g-NENs). In previous studies, we found that miRNA-202-3p is overexpressed in the tumour tissue of type 1 g-NEN. We speculated that miRNA-202-3p is also likely to be highly expressed in circulating blood.

Methods

A total of 27 patients with type 1 g-NEN and 27 age- and sex-matched control participants were enrolled in this study. The miRNA-202-3p levels in serum obtained from the participants were measured by qRT‐PCR. The expression level of miRNA-202-3p in the samples was calculated by comparison with a standard curve.

Results

The clinical characteristics of the patients were similar to those of the patient samples in previous reports. Expression of miRNA-202-3p was significantly higher in the patient group (3.84 × 107copies/nl) than in the control group (0.635 × 107copies/nl). The area under the ROC curve (AUC) was 0.878 (95% CI: 0.788–0.968), and the optimal cut-off point was approximately 1.12 × 107copies/nl. The sensitivity and specificity were 88.9% and 77.8%, respectively.

Conclusion

This study suggests that miRNA-202-3p is potentially useful as a biomarker of type 1 g-NEN; further investigation and verification should be performed in future research.
Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations
Authors: Mikasi Sello Given , Isaacs Darren , Chitongo Rumbidzai , Ikomey George Mondide , Jacobs Graeme Brendon , Cloete Ruben
Published: April 2021

Background

The Integrase (IN) strand transfer inhibitor (INSTI), Dolutegravir (DTG), has been given the green light to form part of first-line combination antiretroviral therapy (cART) by the World Health Organization (WHO). DTG containing regimens have shown a high genetic barrier against HIV-1 isolates carrying specific resistance mutations when compared with other class of regimens.

Methods

We evaluated the HIV-1 CRF02_AG IN gene sequences from Cameroon for the presence of resistance-associated mutations (RAMs) against INSTIs and naturally occurring polymorphisms (NOPs), using study sequences (n = 20) and (n = 287) sequences data derived from HIV Los Alamos National Laboratory database. The possible impact of NOPs on protein structure caused by HIV-1 CRF02_AG variations was addressed within the context of a 3D model of the HIV-1 IN complex and interaction analysis was performed using PyMol to validate DTG binding to the Wild type and seven mutant structures.

Results

We observed 12.8% (37/287) sequences to contain RAMs, with only 1.0% (3/287) of the sequences having major INSTI RAMs: T66A, Q148H, R263K and N155H. Of these,11.8% (34/287) of the sequences contained five different IN accessory mutations; namely Q95K, T97A, G149A, E157Q and D232N. NOPs occurred at a frequency of 66% on the central core domain (CCD) position, 44% on the C-terminal domain (CTD) position and 35% of the N-terminal domain (NTD) position. The interaction analysis revealed that DTG bound to DNA, 2MG ions and DDE motif residues for T66A, T97A, Q148H, N155H and R263K comparable to the WT structure. Except for accessory mutant structure E157Q, only one MG contact was made with DTG, while DTG had no MG ion contacts and no DDE motif residue contacts for structure D232N.

Conclusions

Our analysis indicated that all RAM’s that resulted in a change in the number of interactions with encompassing residues does not affect DTG binding, while accessory mutations E157Q and D232N could affect DTG binding leading to possible DTG resistance. However, further experimental validation is required to validate the in silico findings of our study.
Prevalence of sexually transmitted infections among cervical cancer suspected women at University of Gondar Comprehensive Specialized Hospital, North-west Ethiopia
Authors: Abebe Milkias , Eshetie Setegn , Tessema Belay
Published: April 2021

Background

Sexually transmitted infections (STIs) such as Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), and Syphilis have continued a significant public health problem, especially in areas with substandard infection prevention and control programs. It is known that STIs are largely associated with the increased occurrence of cervical cancer. To date, little is known about the burden of STIs among cervical cancer suspected women in Ethiopia.

Objectives

To assess the seroprevalence of STIs and associated risk factors among cervical cancer suspected women with special emphasis on HIV, HBV, HCV, and Syphilis.

Methods

A hospital-based cross-sectional study was conducted among cervical cancer suspected women at the University of Gondar Comprehensive Specialized Hospital from February to April 2017. A pre-tested and structured questionnaire was used to collect data on patients’ characteristics. The patient’s serum or plasma samples were tested for HIV, HBV, HCV, and syphilis using enzyme-linked immunosorbent assay. In all aspects, the standard operational procedure was strictly followed. Data were analyzed using SPSS version 20 software and presented using tables. Statistical associations were measured using bivariate and multivariable logistic regression. A p-value of below 0.05 was considered statistically significant.

Result

A total of 403 cervical cancer suspected women with the mean age of 42.54 (SD + 11. 24) years were enrolled in the study. The overall prevalence of STIs was 16.6% (67/403) and the prevalence of HIV, HBV, HCV, and syphilis was 36/403 (8.9%), 10/403 (2.5%), 4/403 (1%), and 29/403 (7.2%) respectively. History of multiple sexual partners (Adjusted OR = 3.02, 95%CI 1.57–5.79, P = 0.001), alcohol addiction (Adjusted OR = 2.2, 95%CI 1.07–4.5, P = 0.031), history of STI (Adjusted OR = 3.38; 95% CI: 1.76–6.47, P = 0.00) and not use of condom (Adjusted OR = 4.99; 95% CI: 1.5–16.16, P = 0.007) were significantly associated with STIs.

Conclusion

The prevalence of STIs was generally higher among cervical cancer suspected patients. Health education is encouraged to promote awareness about the prevention of STIs.
Efficacy of galcanezumab in patients with migraine who did not benefit from commonly prescribed preventive treatments
Authors: Kuruppu Dulanji K. , Tobin Joshua , Dong Yan , Aurora Sheena K. , Yunes-Medina Laura , Green A. Laine
Published: April 2021

Background

Galcanezumab is a calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) indicated for the preventive treatment of migraine. While galcanezumab has demonstrated efficacy in patients who did not respond to prior preventive medications in general, its efficacy in patients who did not benefit from individual, commonly prescribed preventive treatments due to inadequate efficacy or safety/tolerability remains unknown.

Methods

CONQUER was a 3-month, randomized, double-blind, placebo-controlled, phase 3b study that enrolled patients with episodic or chronic migraine who had 2 to 4 migraine preventive medication category failures in the past 10 years. Patients were randomly assigned 1:1 to receive placebo (N = 230) or galcanezumab 120 mg/month (240 mg loading dose;N = 232). Post hoc analyses were conducted to determine the efficacy of galcanezumab in patients who had not benefited from six of the most commonly prescribed migraine preventive medications. The mean change from baseline in monthly migraine headache days and ≥ 50 % response rates were assessed over months 1–3. Improvement in Migraine-Specific Questionnaire Role Function-Restrictive (MSQ-RFR) scores were assessed at month 3. The endpoints were estimated via mixed model with repeated measures.

Results

The most common treatment failures due to inadequate efficacy or safety/tolerability, which at least 20 % of patients reported trying without benefit, included topiramate, amitriptyline, propranolol, valproate or divalproex, onabotulinum toxin A, and metoprolol. Patients who had not previously benefited from these treatments had a greater mean reduction in monthly migraine headache days across months 1–3 in the galcanezumab group compared to placebo (allp < 0.01). More patients treated with galcanezumab experienced a ≥ 50 % reduction from baseline in monthly migraine headache days across months 1–3 compared to placebo (allp < 0.05). Galcanezumab-treated patients had a greater improvement in mean MSQ-RFR scores at month 3 compared to placebo (allp < 0.01).

Conclusions

In this population, galcanezumab was effective in reducing monthly migraine headache days, improving response rates, and enhancing quality of life in patients who had not previously benefited from topiramate, amitriptyline, propranolol, valproate or divalproex, onabotulinum toxin A, and/or metoprolol due to inadequate efficacy or safety/tolerability.

Trial registration

ClinicalTrials.govNCT03559257(CONQUER).
Integrating approaches for quality guideline development in LactaMap, an online lactation care support system
Authors: Boss Melinda , Turner Jennifer , Boss Patrick , Hartmann Peter , Pritchard Douglas , Clifford Rhonda
Published: April 2021

Background

Health professionals caring for women and infants experiencing difficulty with breastfeeding have reported deficiencies in evidence-based lactation knowledge. LactaMap is an online lactation care support system with more than 100 clinical practice guidelines to support breastfeeding care. Clinical practice guidelines support medical decision-making by summarising scientific evidence into systematically developed statements for specific clinical circumstances. Both common-sense and theory-based approaches have been used for guideline development and debate continues regarding which is superior. LactaMap clinical practice guidelines were created over the course of 5 years using a common-sense approach that was refined inductively. The aim of this study was to incorporate a theory-based framework approach into the methodology for ongoing update and review of LactaMap clinical practice guidelines.

Methods

The Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument was chosen as the framework-based approach to appraise LactaMap guideline quality. The study was conducted in two phases. The first phase appraised all 103 original LactaMap guidelines. The second phase appraised a subset of 15 updated LactaMap guidelines using improved methodology guided by phase 1, as well as 15 corresponding original (un-updated) guidelines.

Results

Mean Domain scores for 103 LactaMap original guidelines were above 75% in 3 of the 6 AGREE II quality Domains and no mean Domain score rated poorly. Update of guideline methodology was guided by phase 1 appraisals. Improved documentation of methods relating to questions in the Rigour of Development Domain resulted in improvement in mean Domain score from 39 to 72%.

Conclusions

This study showed that a theory-based approach to guideline development methodology can be readily integrated with a common-sense approach. Factors identified by AGREE II theory-based framework provided practical guidance for changes in methodology that were integrated prior to LactaMap website publication. Demonstration of high quality in LactaMap clinical practice guideline methodology ensures clinicians and the public can have trust that the content founded on them is robust, scientific and of highest possible quality.
A high level of lncFGD5-AS1 inhibits epithelial-to-Mesenchymal transition by regulating the miR-196a-5p/SMAD6/BMP axis in gastric Cancer
Authors: Liu Lin , Zhang Cheng , Wang Jizhao , Liu Xu , Qu Hangying , Zhang Guangjian , Liang Ting , Wang Jiansheng , Zhang Jia
Published: April 2021

Background

Long non-coding RNA (lncRNA) was a vital factor in the progression and initiation of human cancers. This study found a new lncRNA, FGD5-AS1, which can inhibit EMT process, proliferation, and metastasis in vitro and in vivo.

Methods

qRT-PCR was employed to test the expression of lncFGD5-AS1 in 30 gastric cancer patients’ cancer tissue and para-cancer tissue. Overexpressed lncFGD5-AS1 cells shown sharply decrease of proliferation, migration, and epithelial-mesenchymal transition (EMT). miR-196a-5p/SMAD6 was confirmed as downstream molecular mechanism of lncFGD5-AS1 by expression correlation analysis and mechanism experiments. In vivo study illustrated overexpression of lncFGD5-AS1 suppression tumor growth.

Results

LncFGD5-AS1 served as a ceRNA of miR-196a-5p to release its inhibition on SMAD6, a conventional inhibitor on the BMP pathway. Comparing with normal gastric cancer cells, FGD5-AS1 overexpressed group had fewer migration cells, lower cell viability, and lower EMT transformation rate. Meanwhile, xenografts nude mice injecting with overexpressed-FGD5-AS1 cells also shown smaller tumor weight and volume.

Conclusion

In conclusion, this research supported the first evidence that FGD5-AS1 suppressed proliferation and metastasis in gastric cancer by regulating miR-196a-5p/SMAD6/BMP axis and suggested a potential therapeutic candidate for gastric cancer.
GNA14 stimulation of KLF7 promotes malignant growth of endometrial cancer through upregulation of HAS2
Authors: Wang Jing , Teng Fei , Chai Hongxia , Zhang Caixia , Liang Xiaolei , Yang Yongxiu
Published: April 2021

Background

Endometrial cancer (UCEC) is one of the most common gynecological malignancies. We previously found that overexpression of G protein α subunit 14 (GNA14) promoted UCEC growth. Krüppel-like factor 7 (KLF7) acts as an oncogene in various cancer types, whereas the connection between GNA14 and KLF7 in UCEC is unclear. We herein explored the involvement of GNA14/KLF7 in UCEC development.

Methods

Clinical relevance of GNA14, KLF7 and HAS2 in UCEC was analyzed from TCGA and by immunohistochemical staining. Knockdown and overexpression of indicated genes were conducted by transfecting the cells with siRNAs and lentivirus, respectively. mRNA and protein expression was detected by qRT-PCR and Western blot. CCK8, colony formation, cell cycle, apoptosis, transwell and wound healing were performed to check cell biology function in vitro. Tumor growth in nude mice was conducted to check in vivo function. RNA sequencing was used to determine dys-regulated genes.

Results

We demonstrated that GNA14 stimulated the expression of KLF7 in UCEC cells. There was a positive correlation between GNA14 and KLF7 in normal and UCEC tissues. In vitro, KLF7 promoted cell proliferation, colony formation, cell cycle progression, and migration of UCEC cells. Apoptosis was inhibited by KLF7. Xenografted tumorigenesis of UCEC cells was suppressed by KLF7 knockdown. Furthermore, RNA sequencing results showed that KLF7 regulated the expression of a large amount of genes, among which hyaluronan synthase 2 (HAS2) was downregulated in KLF7 knockdown cells. Based on TCGA database and immunoblotting assays, KLF7 positively regulated HAS2 in UCEC cells and tissues. Lastly, knockdown of HAS2 reversed the oncogenic role of KLF7 on UCEC cell proliferation, migration, and xenografted tumor development.

Conclusion

Taken together, we reveal that GNA14/KLF7/HAS2 signaling cascade exerts tumor promoting function during UCEC development.
A genomic-clinicopathologic Nomogram for the preoperative prediction of lymph node metastasis in gastric cancer
Authors: Zhong Xin , Xuan Feichao , Qian Yun , Pan Junhai , Wang Suihan , Chen Wenchao , Lin Tianyu , Zhu Hepan , Wang Xianfa , Wang Guanyu
Published: April 2021

Background

Preoperative evaluation of lymph node (LN) state is of pivotal significance for informing therapeutic decisions in gastric cancer (GC) patients. However, there are no non-invasive methods that can be used to preoperatively identify such status. We aimed at developing a genomic biosignature based model to predict the possibility of LN metastasis in GC patients.

Methods

We used the RNA profile retrieving strategy and performed RNA expression profiling in a large GC cohort (GSE62254, n = 300) from Gene Expression Ominus (GEO). In the exploratory stage, 300 GC patients from GSE62254 were involved and the differentially expressed RNAs (DERs) for LN-status were determined using the R software. GC samples in GSE62254 were randomly allocated into a learning set (n = 210) and a verification set (n = 90). By using the Least absolute shrinkage and selection operator (LASSO) regression approach, a set of 23-RNA signatures were established and the signature based nomogram was subsequently built for distinguishing LN condition. The diagnostic efficiency, as well as the clinical performance of this model were assessed using the decision curve analysis (DCA). Metascape was used for bioinformatic analysis of the DERs.

Results

Based on the genomic signature, we established a nomogram that robustly distinguished LN status in the learning (AUC = 0.916, 95% CI 0.833–0.999) and verification sets (AUC = 0.775, 95% CI 0.647–0.903). DCA demonstrated the clinical value of this nomogram. Functional enrichment analysis of the DERs was performed using bioinformatics methods which revealed that these DERs were involved in several lymphangiogenesis-correlated cascades.

Conclusions

In this study, we present a genomic signature based nomogram that integrates the 23-RNA biosignature based scores and Lauren classification. This model can be utilized to estimate the probability of LN metastasis with good performance in GC. The functional analysis of the DERs reveals the prospective biogenesis of LN metastasis in GC.
Screening for marginal food security in young children in primary care
Authors: Bayoumi Imaan , Birken Catherine S. , Nurse Kimberly M. , Parkin Patricia C. , Maguire Jonathon L. , Macarthur Colin , Randall Simpson Janis A. , Borkhoff Cornelia M.
Published: April 2021

Background

Household food insecurity (FI), even at marginal levels, is associated with poor child health outcomes. The Nutrition Screening Tool for Every Preschooler (NutriSTEP®) is a valid and reliable 17-item parent-completed measure of nutrition risk and includes a single item addressing FI which may be a useful child-specific screening tool. We evaluated the diagnostic test properties of the single NutriSTEP® FI question using the 2-item Hunger Vital Sign™ as the criterion measure in a primary care population of healthy children ages 18 months to 5 years.

Results

The sample included 1174 families, 53 (4.5%) of which were marginally food secure. An affirmative response to the single NutriSTEP® question “I have difficulty buying food I want to feed my child because food is expensive” had a sensitivity of 85% and specificity of 91% and demonstrated good construct validity when compared with the Hunger Vital Sign™.

Conclusion

The single NutriSTEP® question may be an effective screening tool in clinical practice to identify marginal food security in families with young children and to link families with community-based services or financial assistance programs including tax benefits.

Trial registration

TARGet Kids! practice-based research network (Registered June 5, 2013 at www.clinicaltrials.gov; NCT01869530); www.targetkids.ca
An exploration of the genetic epidemiology of non-suicidal self-harm and suicide attempt
Authors: Russell Abigail Emma , Hemani Gibran , Jones Hannah J , Ford Tamsin , Gunnell David , Heron Jon , Joinson Carol , Moran Paul , Relton Caroline , Suderman Matthew , Watkins Sarah , Mars Becky
Published: April 2021

Background

Empirical evidence supporting the distinction between suicide attempt (SA) and non-suicidal self-harm (NSSH) is lacking. Although NSSH is a risk factor for SA, we do not currently know whether these behaviours lie on a continuum of severity, or whether they are discrete outcomes with different aetiologies. We conducted this exploratory genetic epidemiology study to investigate this issue further.

Methods

We explored the extent of genetic overlap between NSSH and SA in a large, richly-phenotyped cohort (the Avon Longitudinal Study of Parents and Children;N = 4959), utilising individual-level genetic and phenotypic data to conduct analyses of genome-wide complex traits and polygenic risk scores (PRS).

Results

The single nucleotide polymorphism heritability of NSSH was estimated to be 13% (SE 0.07) and that of SA to be 0% (SE 0.07). Of the traits investigated, NSSH was most strongly correlated with higher IQ (rG = 0.31, SE = 0.22), there was little evidence of high genetic correlation between NSSH and SA (rG = − 0.1, SE = 0.54), likely due to the low heritability estimate for SA. The PRS for depression differentiated between those with NSSH and SA in multinomial regression. The optimal PRS prediction model for SA (NagelkerkeR20.022,p < 0.001) included ADHD, depression, income, anorexia and neuroticism and explained more variance than the optimal prediction model for NSSH (Nagelkerke R20.010,p < 0.001) which included ADHD, alcohol consumption, autism spectrum conditions, depression, IQ, neuroticism and suicide attempt.

Conclusions

Our findings suggest that SA does not have a large genetic component, and that although NSSH and SA are not discrete outcomes there appears to be little genetic overlap between the two. The relatively small sample size and resulting low heritability estimate for SA was a limitation of the study. Combined with low heritability estimates, this implies that family or population structures in SA GWASs may contribute to signals detected.
Sports activities of 60 above Hungarian elderly-explaining and predicting impact of exercise on health
Authors: Lampek Kinga , Csóka László , Hegedüs Réka , Zrínyi Miklós , Törőcsik Mária
Published: April 2021

Background

The proportion of elderly is on the rise both in Europe and in Hungary. The challenge is to increase the number of years spent in good health as well as to improve quality of life of those 60 years and above. This study focuses on the impact of physical activity on this age group.

Methods

A nationally representative sample of 2000 respondents were surveyed in an age range of 15–74. Our data concerns those being 60–74 years of age. The focus of our investigation was level and impact of physical activity in the group above. First, we used Chi-squared tests and correspondence analysis to identify the deviation in the answers of different groups in our sample. After we built a hierarchical linear regression model to get a deeper understanding of the impact of physical activity for elderly.

Results

Those reporting no physical/sports activity at all have to do with the negative culture of exercising. Only 9.3% reported being engaged with any sports; 72% reported no regular exercising throughout their lives. The relationship between sport activity and self-reported health was significant (p = 0.009, Cramer’s V = 0.2). Elderly were characterized by walking, hiking and less intense sports.

Conclusions

Those who actively exercised in this research reported better health outcomes than those who stopped or had never been engaged in any sports. We conclude that of all variables tested, physical activity was most effective to improve personal health of the elderly in this sample. Compared to European data on physical activity of elderly populations, Hungary seems to fall behind and needs to consider concentrated efforts to improve the future health of its senior populace.
Factors associated with crack-cocaine early initiation: a Brazilian multicenter study
Authors: Perrenoud Luciane Ogata , Oikawa Koki Fernando , Williams Anna Virginia , Laranjeira Ronaldo , Fischer Benedikt , Strang John , Ribeiro Marcelo
Published: April 2021

Background

Crack-cocaine dependence is a serious public health issue, related to several psychiatric and psychosocial problems. Crack-cocaine users are usually embedded in a context of great social vulnerability, often associated with violence, poverty, family conflict and easy and early access to alcohol, tobacco and other drugs.

Methods

This cross-sectional study enrolled a consecutive sample of 577 patients admitted to 20 therapeutic communities located in Southern Brazil, between September 2012 and September 2013. A structured interview assessed life-time exposure to risk and protective factors for drug use, such as parental monitoring in childhood, deviant behaviors and peer pressure.

Results

Presence of family conflict (p = 0.002), maltreatment (p = 0.016), and deviant behavior prior to age 15 in a bivariate analysis predicted an earlier age of crack-cocaine initiation, whereas adolescents experiencing parental monitoring during adolescence started use later (p < 0.001). In the multivariate model, perceptions related to ease of access of illicit drugs (marijuana:p = 0.028, 95% CI = − 3.81, − 0.22; crack-cocaine:p < 0.001, 95% CI = − 7.40, − 4.90), and deviant behavior (threatening someone with a gun:p = 0.028, 95% CI = − 2.57, − 0.14) remained independent predictors of early age of crack-cocaine initiation.

Conclusions

Early onset of crack-cocaine use seems to be associated with exposure to family conflict, easy access to drugs and deviant behavior. Treatment and preventive programs should take these factors into account when designing and implementing community interventions.
Knowledge, attitude and practices on cervical cancer screening among undergraduate female students in University of Gondar, Northwest Ethiopia: an institution based cross sectional study
Authors: Getaneh Alem , Tegene Birhanemeskel , Belachew Teshome
Published: April 2021

Background

Cervical cancer is a major public health problem. In the world, cervical cancer is the fourth most common cancer among women and it is one of the leading causes of cancer mortality in females. It is the second most common women cancer in Ethiopia with almost 6300 new cases and 4884 deaths annually. Despite the high burden of new cases and deaths, there is a scarcity of data on knowledge, attitude and practices (KAP) towards cervical cancer screening among female university students in Ethiopia particularly in the study area. Therefore, the present study was aimed to assess the KAP of undergraduate female students towards cervical cancer screening.

Methods

An institution based cross-sectional study was conducted in April 2018 at the University of Gondar, College of Medicine and Health Sciences undergraduate female students. Pretested, self-administered questionnaire was used for data collection. Four hundred and three female students were recruited by a simple random sampling method and the data were entered and analyzed using SPSS version 20 statistical packages. Descriptive data analysis was used to report the results.

Results

More than half of the respondents (59.3.3%) had good knowledge, whereas nearly 67.7% of the respondents had favorable attitude towards cervical cancer. However, less than 1% of the respondents had been screened for cervical cancer.

Conclusion

Although undergraduate female students had apparently good knowledge and favorable attitude, their practices on cervical cancer screening were quite low. Therefore, the health sectors and the gender streaming office of the university mobilize students to strengthen the uptake the cervical cancer screening practice.
The effects of professional continuous glucose monitoring as an adjuvant educational tool for improving glycemic control in patients with type 2 diabetes
Authors: Rivera-Ávila Dulce Adelaida , Esquivel-Lu Alejandro Iván , Salazar-Lozano Carlos Rafael , Jones Kyla , Doubova Svetlana V.
Published: April 2021

Background

The study objective was to evaluate the effects of professional continuous glucose monitoring (CGM) as an adjuvant educational tool for improving glycemic control in patients with type 2 diabetes (T2D).

Methods

We conducted a three-month quasi-experimental study with an intervention (IGr) and control group (CGr) and ex-ante and ex-post evaluations in one family medicine clinic in Mexico City. Participants were T2D patients with HbA1c > 8% attending a comprehensive diabetes care program. In addition to the program, the IGr wore a professional CGM sensor (iPro™2) during the first 7 days of the study. Following this period, IGr participants had a medical consultation for the CGM results and treatment adjustments. Additionally, they received an educational session and personalized diet plan from a dietitian. After 3 months, the IGr again wore the CGM sensor for 1 week. The primary outcome variable was HbA1c level measured at baseline and 3 months after the CGM intervention. We analyzed the effect of the intervention on HbA1c levels by estimating the differences-in-differences treatment effect (Diff-in-Diff). Additionally, baseline and three-month CGM and dietary information were recorded for the IGr and analyzed using the Student’s paired t-test and mixed-effects generalized linear models to control for patients’ baseline characteristics.

Results

Overall, 302 T2D patients participated in the study (IGr, n = 150; control, n = 152). At the end of the three-month follow-up, we observed 0.439 mean HbA1C difference between groups (p = 0.004), with an additional decrease in HbA1c levels in the IGr compared with the CGr (Diff-in-Diff HbA1c mean of − 0.481% points, p = 0.023). Moreover, compared with the baseline, the three-month CGM patterns showed a significant increase in the percentage of time in glucose range (+ 7.25; p = 0.011); a reduction in the percentage of time above 180 mg/dl (− 6.01; p = 0.045), a decrease in glycemic variability (− 3.94, p = 0.034); and improvements in dietary patterns, shown by a reduction in total caloric intake (− 197.66 Kcal/day; p = 0.0001).

Conclusion

Professional CGM contributes to reducing HbA1c levels and is an adjuvant educational tool that can improve glycemic control in patients with T2D.

Trial registration

ClinicalTrials.gov: NCT04667728. Registered 16/12/2020
An analysis of the prevalence of peripheral giant cell granuloma and pyogenic granuloma in relation to a dental implant
Authors: Román-Quesada Nieves , González-Navarro Beatriz , Izquierdo-Gómez Keila , Jané-Salas Enric , Marí-Roig Antonio , Estrugo-Devesa Albert , López-López José
Published: April 2021

Background

The aim of the present investigation was to evaluate the literature recurrence of peripheral giant cell granuloma and pyogenic granuloma associated with dental implants. It’s important to know the characteristics present in these lesions and possible effects on the prognosis of dental implants.

Methods

An electronic search without time restrictions was done in the databases: PubMed/Medline. With the keywords "Granuloma" OR "Granuloma, Giant Cell" OR "peripheral giant cell" OR "Granuloma, Pyogenic” AND "Dental implants" OR "Oral implants”.

Results

After applying the inclusion and exclusion criteria, a total of 20 articles were included, which reported 32 lesions (10 pyogenic granulomas, 21 peripheral giant cell granulomas and one peripheral giant cell granuloma combined with peripheral ossifying fibroma, all associated with implants). According to our review, these lesions are more frequent in males and in the posterior region of the mandible. Both excision and curettage of the lesion, compared to only excision, presented similar recurrences (40%). Explantation of the implant was performed in 41% of cases without additional recurrences. The results are not statistically significant when comparing one lesion to the other in terms of explantation (p = 0.97), recurrence (p = 0.57) or bone loss (p = 0.67).

Conclusions

The main therapeutic approach is tissue excision. The lesions show a high recurrence rate (34.4%), which often requires explantation of the associated implant. This recurrence rate is not affected by curettage after excision.
Association between intimate partner violence and the use of maternal health care services among married Malawian women
Authors: Magombo Praise W. , Ntenda Peter A. M. , Nkoka Owen
Published: April 2021

Background

Maternal and child health care (MCH) services aim at improving the overall health outcomes of both the mother and newborn. Intimate partner violence (IPV) has been linked with poor health outcomes and under usage of MCH services. In Malawi, IPV is a persistent problem, while MCH services’ uptake remains a constant challenge. However, there is limited information on the association between IPV and MCH services in Malawi. The study examined the association between IPV and the use of MCH services among married Malawian women.

Methods

The 2015–16 Malawi demographic and health survey was used to analyze the association of IPV and the use of MCH services among 2712 married Malawian women. Multivariable logistic regression models were used to estimate the strength of association.

Results

Approximately 41.4% of the women reported experiencing IPV. Specifically, 27.8%, 19.3%, and 23.6% reported experiencing physical, sexual, and emotional violence, respectively. Women who reported experiencing any form of IPV had a 34% reduced likelihood of delivering at a health facility [adjusted odds ratio (aOR): 0.66; 95% confidence interval (CI) 0.46–0.96] or were 36% less likely [aOR: 0.64; 95% CI 0.46–0.90] to have had skilled assistance during delivery compared to those who never experienced IPV.

Conclusion

IPV was associated with MCH services use, specifically delivery at a health facility and skilled birth attendants. The high prevalence of IPV underscores the need to design effective programs to raise awareness regarding IPV and reduce IPV. Reducing IPV may be a promising means to support a more integrated and sustainable approach to improve the use of MCH services.
Trichomonas vaginalis as a risk factor for human papillomavirus: a study with women undergoing cervical cancer screening in a northeast region of Brazil
Authors: Belfort Ilka Kassandra Pereira , Cunha Ana Paula Almeida , Mendes Francisco Pedro Belfort , Galvão-Moreira Leonardo Victor , Lemos Renata Gaspar , de Lima Costa Lucas Henrique , Monteiro Pablo , Ferreira Mariele Borges , dos Santos Gerusinete Rodrigues Bastos , Costa Joyce Leal , de Sá Ferreira Alice , Brito Luiz Gustavo Oliveira , Brito Luciane Maria Oliveira , Vidal Flávia Castello Branco , Monteiro Sally Cristina Moutinho
Published: April 2021

Background

Human papillomavirus (HPV) and Trichomonas vaginalis (TV) infections are the most common sexually transmitted infections (STIs) globally. The latter has contributed to a variety of adverse outcomes for both sexes. Moreover, in Brazil, epidemiological studies on patients with STIs are limited. Therefore, this study aimed to determine the prevalence of TV and its association with HPV in women undergoing cervical cancer screening.

Methods

Women with a normal cervix were recruited from a community-based cervical cancer screening program. Gynecological examinations were conducted, and questionnaires were provided. Vaginal canal and uterine cervix samples were collected for cytological examinations (reported using the 2001 Bethesda System) and tested for the presence of TV and HPV DNA.

Results

In total, 562 women who attended public primary healthcare were included in the study. The T. vaginalis was present in 19.0% (107) and HPV DNA was present in 46.8% (263) of women. Among the women of TV 73.8% (79) had a co-infection with HPV (p = 0.001).

Conclusions

We concluded that a TV infection is associated with an HPV infection of the cervix as well as with the cervical cytological abnormalities. Further studies could reveal the mechanisms by which these two organisms interact at the cellular level, with control for shared behavioral risk factors.
Exploring the practice, confidence and educational needs of hospital pharmacists in reviewing antimicrobial prescribing: a cross-sectional, nationwide survey
Authors: Khumra Sharmila , Mahony Andrew A. , Bergen Phillip J. , Page Amy T. , Elliott Rohan A.
Published: April 2021

Background

Antimicrobial stewardship (AMS) programs are usually limited in resources and scope. Therefore, wider engagement of hospital pharmacists in reviewing antimicrobial orders is necessary to ensure appropriate prescribing. We assessed hospital pharmacists’ self-reported practice and confidence in reviewing antimicrobial prescribing, and their knowledge in making AMS interventions.

Methods

We conducted an Australia-wide, cross-sectional survey in October 2017. A link to the online survey was emailed to hospital pharmacists via the Society of Hospital Pharmacists of Australia. Factors associated with higher knowledge scores were explored using linear regression models.

Results

There were 439 respondents, of whom 272 (61.7%) were from metropolitan public hospitals. Pharmacists were more likely to assess the appropriateness of intravenous, broad-spectrum or restricted antibiotics than narrow-spectrum, oral antibiotics within 24–72 h of prescription; p < 0.001. Fifty percent or fewer respondents were confident in identifying AMS interventions related to dose optimization based on infection-specific factors, bug-drug mismatch, and inappropriate lack of spectra of antimicrobial activity. The median knowledge score (correct answers to knowledge questions) was 6 out of 9 (interquartile range, 5–7); key gaps were noted in antimicrobials’ anaerobic spectrum, beta-lactam allergy assessment and dosing in immunocompromised patients. Clinical practice in inpatient areas, registration for 3–5 years and receipt of recent AMS education were associated with higher knowledge scores. More interactive modes of education delivery were preferred over didactic modes; p ≤ 0.01.

Conclusion

Gaps in practice, confidence and knowledge among hospital pharmacists were identified that could inform the design of educational strategies to help improve antimicrobial prescribing in Australian hospitals.
“I would do something if I could!”: experiences and reflections from ethics teachers on how to respond when hearing alarming cases from medical students
Authors: Muhaimin Amalia , Hoogsteyns Maartje , Wicaksono Raditya Bagas , Utarini Adi , Willems Derk Ludolf
Published: April 2021

Background

Previous studies show that teachers can feel disturbed by alarming cases brought up by students during their teaching activities. Teachers may feel uncertain about how to deal with these cases, as they might feel responsible to take action to prevent further harm. This study aims to explore how ethics teachers in medical schools would respond to a student report of unethical or unprofessional behaviour during the clinical training phase (clerkship) that is alarming and potentially harmful for patients or students themselves.

Methods

This study used qualitative methods with purposive sampling. We conducted in-depth interviews with 17 teachers from 10 medical schools in Indonesia. We asked if they had heard any alarming and harmful cases from students and provided two cases as examples.

Results

Four teachers shared their own cases, which they perceived as disturbing and alarming. The cases included power abuse, fraud and deception, violation of patient’s rights and autonomy, and sexual harassment. Regarding teachers’ responses in general, we found three main themes: (1) being assertive, (2) being careful, (3) barriers and facilitators. Most teachers were convinced of the need to take action despite numerous barriers, which they identified, leading to doubts and concerns in taking action. Our study shows that formal education in ethics might not necessarily influence how teachers respond to alarming cases, and that their responses are mainly influenced by how they perceive their role and responsibility as teachers.

Conclusions

Our study suggests that teachers should carefully consider the risks and consequences before taking action upon alarming cases to prevent further harm, and that support from higher authorities might be crucial, especially in the Indonesian context. Our study also shows that taking action as a group might be appropriate in certain cases, while personal approaches might be more appropriate in other cases. Most importantly, school leaders and administrators should develop effective organisational culture and support students and teachers for their ethical responsibility commitment.