bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide identification and expression characterization of the DoG gene family of moso bamboo (Phyllostachys edulis)
Authors: Zhijun Zhang , Peiyao Yu , Bing Huang , Ruifang Ma , Vinod Kunnummal Kurungara , Ramakrishnan Muthusamy
Published: May 2022

Background

The DoG (Delay of Germination1) family plays a key regulatory role in seed dormancy and germination. However, to date, there is no complete genomic overview of the DoG gene family of any economically valuable crop, including moso bamboo (Phyllostachys edulis), and no studies have been conducted to characterize its expression profile. To identify the DoG gene members of moso bamboo (PeDoG) and to investigate their family structural features and tissue expression profile characteristics, a study was conducted. Based on the whole genome and differential transcriptome data, in this investigation, we have scrutinized the physicochemical properties, gene structure, cis-acting elements, phylogenetic relationships, conserved structural (CS) domains, CS motifs and expression patterns of the PeDoG1 family of moso bamboo.

Results

The DoG family genes of moso bamboo were found distributed across 16 chromosomal scaffolds with 24 members. All members were found to carry DoG1 structural domains, while 23 members additionally possessed basic leucine zipper (bZIP) structural domains. We could divide the PeDoG genes into three subfamilies based on phylogenetic relationships. Covariance analysis revealed that tandem duplication was the main driver of amplification of the PeDoG genes. The upstream promoter of these genes containing several cis-acting elements indicates a plausible role in abiotic stress and hormone induction. Gene expression pattern according to transcriptome data revealed participation of the PeDoG genes in tissue and organ development. Analysis using Short Time-series Expression Miner (STEM) tool revealed that the PeDoG gene family is also associated with rapid early shoot growth. Gene ontology (GO) and KEGG analyses showed a dual role of the PeDoG genes. We found that PeDoGs has a possible role as bZIP transcription factors by regulating Polar like1 (PL1) gene expression, and thereby playing a disease response role in moso bamboo. Quantitative gene expression of the PeDoG genes revealed that they were abundantly expressed in roots and leaves, and could be induced in response to gibberellin (GA).

Conclusion

In this study, we found that the PeDoG genes are involved in a wide range of activities such as growth and development, stress response and transcription. This forms the first report of PeDoG genes and their potential roles in moso bamboo.
Comparative transcriptome analysis of resistant and susceptible wheat in response to Rhizoctonia cerealis
Authors: Geng Xingxia , Gao Zhen , Zhao Li , Zhang Shufa , Wu Jun , Yang Qunhui , Liu Shuhui , Chen Xinhong
Published: May 2022

Background

Sheath blight is an important disease caused by Rhizoctonia cerealis that affects wheat yields worldwide. No wheat varieties have been identified with high resistance or immunity to sheath blight. Understanding the sheath blight resistance mechanism is essential for controlling this disease. In this study, we investigated the response of wheat to Rhizoctonia cerealis infection by analyzing the cytological changes and transcriptomes of common wheat 7182 with moderate sensitivity to sheath blight and H83 with moderate resistance.

Results

The cytological observation showed that the growth of Rhizoctonia cerealis on the surface and its expansion inside the leaf sheath tissue were more rapid in the susceptible material. According to the transcriptome sequencing results, a total of 88685 genes were identified in both materials, including 20156 differentially expressed genes (DEGs) of which 12087 was upregulated genes and 8069 was downregulated genes. At 36 h post-inoculation, compared with the uninfected control, 11498 DEGs were identified in resistant materials, with 5064 downregulated genes and 6434 upregulated genes, and 13058 genes were detected in susceptible materials, with 6759 downregulated genes and 6299 upregulated genes. At 72 h post-inoculation, compared with the uninfected control, 6578 DEGs were detected in resistant materials, with 2991 downregulated genes and 3587 upregulated genes, and 7324 genes were detected in susceptible materials, with 4119 downregulated genes and 3205 upregulated genes. Functional annotation and enrichment analysis showed that the main pathways enriched for the DEGs included biosynthesis of secondary metabolites, carbon metabolism, plant hormone signal transduction, and plant–pathogen interaction. In particular, phenylpropane biosynthesis pathway is specifically activated in resistant variety H83 after infection. Many DEGs also belonged to the MYB, AP2, NAC, and WRKY transcription factor families.

Conclusions

Thus, we suggest that the normal functioning of plant signaling pathways and differences in the expression of key genes and transcription factors in some important metabolic pathways may be important for defending wheat against sheath blight. These findings may facilitate further exploration of the sheath blight resistance mechanism in wheat and the cloning of related genes.
Safety and efficacy of immediate heparin reversal with protamine after complex percutaneous coronary intervention
Authors: Choi Jin Hee , Chun Kook Jin , Jung Soon Myung , Lee Soo Yong , Chon Min Ku , Lee Sang Hyun , Hwang Ki Won , Kim Jeong Su , Park Yong-Hyun , Kim June Hong
Published: May 2022

Background

Compared to simple percutaneous coronary intervention (PCI), complex PCI is associated with higher bleeding and thrombotic risk. No previous study has evaluated the use of protamine after PCI with contemporary technologies. This study aimed to evaluate the safety and efficacy of manual compression with and without protamine after transfemoral complex PCI.

Methods

We retrospectively analyzed 160 patients (protamine group, n = 92; non-protamine group, n = 68) who underwent complex PCI via the femoral artery. The primary outcome was a composite of in-hospital death, myocardial infarction, stent thrombosis, stroke/systemic embolism, bleeding requiring blood transfusion, and vascular access complications.

Results

The primary outcome was significantly lower in the protamine group than in the non-protamine group (4.3% vs. 17.6%; p = 0.006). This was driven mainly by the lower incidences of hematoma in the protamine group (3.3% vs. 13.2%, p = 0.020). Furthermore, the protamine group had a significantly shorter hospital stay than the non-protamine group (4.8 ± 3.7 days vs. 8.4 ± 8.3 days, p = 0.001). While > 90% of the patients had acute coronary syndrome, there were no incidences of myocardial infarction or stent thrombosis in either group.

Conclusions

Among patients who underwent complex PCI via transfemoral access, immediate protamine administration was associated with a significantly lower rate of vascular access complications, especially hematoma, and shorter hospital stay than no protamine administration.
Insights into patient characteristics and documentation of the use of sedative-hypnotic/anxiolytics in primary care: a retrospective chart review study
Authors: Gozda Kiana , Leung Joyce , Baum Lindsay , Singer Alexander , Konrad Gerald , McMillan Diana E. , Falk Jamie , Kosowan Leanne , Leong Christine
Published: May 2022

Background

Despite the known safety risks of long-term use of sedative-hypnotic/anxiolytic medications, there has been limited guidance for the safe and effective use of their chronic use in a primary care clinic setting. Understanding the characteristics of patients who receive sedative-hypnotic/anxiolytic medication and the clinical documentation process in primary care is the first step towards understanding the nature of the problem and will help inform future strategies for clinical research and practice.

Objectives

Characterize patients who received a sedative-hypnotic/anxiolytic prescription in primary care, and (2) gain an understanding of the clinical documentation of sedative-hypnotic/anxiolytic indication and monitoring in electronic medical records (EMR).

Methods

A random selection of patients who received a prescription for a benzodiazepine or Z-drug hypnotic between January 2014 and August 2016 from four primary care clinics in Winnipeg were included. Data was collected retrospectively using the EMR (Accuro®). Patient variables recorded included sex, age, comorbidities, medications, smoking status, and alcohol status. Treatment variables included drug type, indication, pattern of use, dose, adverse events, psychosocial intervention, tapering attempts, social support, life stressor, and monitoring parameters for sedative-hypnotic use. Demographic and clinical characteristics were described using descriptive statistics.

Results

Records from a sample of 200 primary care patients prescribed sedative-hypnotic/anxiolytics were analyzed (mean age 55.8 years old, 61.5% ≥ 65 years old, 61.0% female). Long-term chronic use (≥ 1 year) of a sedative-hypnotic/anxiolytic agent was observed in 29.5% of the sample. Zopiclone (30.7%) and lorazepam (28.7%) were the most common agents prescribed. Only 9.5% of patients had documentation of a past tapering attempt of their sedative-hypnotic/anxiolytic. The most common indications for sedative-hypnotic/anxiolytic use recorded were anxiety (33.0%) and sleep (18.0%), but indication was undetermined for 57.0% of patients. Depression (33.5%) and falls (18.5%) were reported by patients after the initiation of these agents.

Conclusions

A higher proportion of females and users 65 years and older received a prescription for a sedative-hypnotic/anxiolytic, consistent with previous studies on sedative-hypnotic use. We found inconsistencies in the documentation surrounding sedative-hypnotic/anxiolytic use. The indication for their use was unclear in a large number of patients. These findings will help us understand the state of the problem in primary care and inform future strategies for clinical research.
Development and validation of a Japanese version of the person-centered primary care measure
Authors: Kaneko Makoto , Okada Tadao , Aoki Takuya , Inoue Machiko , Watanabe Takamasa , Kuroki Makoto , Hayashi Daichi , Matsushima Masato
Published: May 2022

Background

Although primary care (PC) is an indispensable part of the health system, measuring its quality is challenging. A recent measure of PC, Person-Centered Primary Care Measure (PCPCM), covers 11 important domains of PC and has been translated into 28 languages. This study aimed to develop a Japanese version of the PCPCM and assess its reliability and validity.

Methods

We employed a cross-sectional mail survey to examine the reliability and content, structure, criterion-related, and convergent validity of the Japanese version of the PCPCM. This study targeted 1000 potential participants aged 20–74 years, selected by simple random sampling in an urban area in Japan. We examined internal consistency, confirmatory factor analysis, correlation between the Japanese version of the Primary Care Assessment Tool-Short Form (JPCAT-SF), and the association between the PCPCM score and influenza vaccine uptake.

Results

A total of 417 individuals responded to the survey (response rate = 41.7%), and we used the data of 244 participants who had the usual source of care to assess the reliability and validity of the PCPCM. Confirmatory factor analysis demonstrated sufficient structural validity of the original one-factor structure. The overall Cronbach’s alpha was 0.94. The Spearman correlation coefficient between PCPCM and JPCAT-SF was 0.60. Influenza vaccine uptake was not significantly associated with total PCPCM score.

Conclusions

The study showed that the Japanese version of the PCPCM has sufficient internal consistency reliability and structural- and criterion-related validity. The measure can be used to compare the quality of primary care in Japan and other countries.
Isolation, marginalisation and disempowerment – understanding how interactions with health providers can influence smoking cessation in pregnancy
Authors: Fletcher Cherise , Hoon Elizabeth , Gialamas Angela , Dekker Gustaaf , Lynch John , Smithers Lisa
Published: May 2022

Background

Maternal smoking during pregnancy can lead to serious adverse health outcomes for both women and their infants. While smoking in pregnancy has declined over time, it remains consistently higher in women with lower socioeconomic circumstances. Furthermore, fewer women in this group will successfully quit during pregnancy.

Aim

This study explores the barriers to smoking cessation experienced by socially disadvantaged pregnant women and investigates how interactions with health providers can influence their smoking cessation journey.

Methods

Women (either pregnant or birthed in the previous 10 years, who smoked or quit smoking in pregnancy) were recruited from a metropolitan public hospital antenatal clinic in South Australia and community organisations in surrounding suburbs. Seventeen women participated in qualitative semi-structured small focus groups or interviews. The focus groups and interviews were recorded, transcribed and thematically analysed.

Findings

Four interconnected themes were identified: 1) smoking embedded in women’s challenging lives and pregnancies, 2) cyclic isolation and marginalisation, 3) feeling disempowered, and 4) autonomy and self-determination. Themes 3 and 4 are characterised as being two sides of a single coin in that they coexist simultaneously and are inseparable. A key finding is a strong unanimous desire for smoking cessation in pregnancy but women felt they did not have the necessary support from health providers or confidence and self-efficacy to be successful.

Conclusion

Women would like improvements to antenatal care that increase health practitioners’ understanding of the social and contextual healthcare barriers faced by women who smoke in pregnancy. They seek improved interventions from health providers to make informed choices about smoking cessation and would like women-centred care. Women feel that with greater support, more options for cessation strategies and consistency and encouragement from health providers they could be more successful at antenatal smoking cessation. If such changes were made, then South Australian practice could align more with best practice international guidelines for addressing smoking cessation in pregnancy, and potentially improve outcomes for women and their children.
The effect of concurrent use of swaddle and sucrose on the intensity of pain during venous blood sampling in neonate: a clinical trial study
Authors: Talebi Mahla , Amiri Seyedeh Roghayeh Jafarian , Roshan Parvin Aziznejad , Zabihi Ali , Zahedpasha Yadollah , Chehrazi Mohammad
Published: May 2022

Background & objective

Infants undergo painful procedures while receiving care and treatment. Blood sampling is the most common painful procedure for infants. Pain control plays a significant role in preventing unwanted physical and psychological effects. Therefore, this study aimed to investigate the effect of concurrent use of swaddle and sucrose taste on the pain intensity during venous blood sampling in neonates.

Methods

In this clinical trial study, 60 infants admitted to the neonatal ward of Amirkola Hospital were randomly divided into four groups of 15 patients. In the first group, the infants were swaddled before blood sampling. In the second group, sucrose was administered to infants. In the third group, the neonates were swaddled and given sucrose simultaneously, and in the fourth group (control), blood sampling was performed routinely. PIPP pain scale and demographic questionnaire were used to collect the data. Data analysis was performed using SPSS23.

Results

The results showed a significant difference between the mean pain intensity in neonates in the sucrose-swaddle group (4.53 ± 1.30) and the sucrose (7.73 ± 2.73), swaddle (9.86 ± 33.33), and control (12.13 ± 2.06) groups during blood sampling (P < 0.001). Besides, after blood sampling, there was a significant difference between the mean pain intensity in neonates in the sucrose-swaddle group (4.33 ± 1.23) and the sucrose (8.13 ± 2.66), swaddle (7.73 ± 2.78), and control (10.00. ± 1.96) groups (P < 0.001).

Conclusion

The present study showed that pain severity during and after venous blood sampling was lower in the swaddle-sucrose group than in other groups. Therefore, it is recommended that the combined method of swaddle-sucrose be used in infants as a better pain reliever when intravenous blood sampling is performed.
Magnitude and associated factors of depression among people with hypertension in Addis Ababa, Ethiopia: a hospital based cross-sectional study
Authors: Asmare Yonatan , Ali Ahmed , Belachew Ayele
Published: May 2022

Background

The burden of depression is higher among people with chronic illnesses like hypertension and this comorbid condition leads to poor adherence to treatment and failure of compliance to lifestyle modifications, which in turn, increases risk of cardiovascular complications and mortalities. Low income countries, Ethiopia included, suffer from paucity of information describing the burden of hypertension comorbid with depression, which demands studies to narrow this knowledge gap, such as this one.

Methods

Institution based cross-sectional study was conducted in three randomly selected public hospitals in Addis Ababa. Through a systematic random sampling method, a total of 416 known hypertensive patients with follow up in hypertension clinics with in the study period enrolled in the study. Data were collected through structured questionnaire administered by trained interviewer, which latter cleaned, edited and entered in to epi-data version 3.1. Descriptive and bi-variable and binary logistic regression analysis were done using the statistical software, SPSS version 25. Depression was assessed through Hospital Anxiety and Depression Scale (HADs).

Results

The prevalence of depression among hypertensive patients was found to be 37.8% [95% CI (33.4%-42.5%)]. The binary logistic regression model revealed that, female sex [AOR = 5.37, 95% CI (3.089–9.35)], being married [AOR = 0.25, 95% CI (0.08–0.78)], presence of chronic comorbid illnesses [AOR = 3.03, 95% CI (1.78–5.16)], uncontrolled blood pressure [AOR = 2.80, 95% CI (1.65–4.75)], duration of hypertension of 5–10 years [AOR = 3.17, 95% CI (1.61–6.23)] and more than 10 years [AOR = 5.81, 95% CI (2.90–11.65)], family history of depression [AOR = 4.53, 95% CI (2.37–8.66)] and current alcohol consumption [AOR = 1.77, 95% CI (1.02–3.07)] were significantly associated with depression among hypertensive patients.

Conclusion

High proportion of depression was observed among hypertensive patients, and socio-demographic, clinical and behavioral characteristics were found to significantly influence the likelihood of occurrence. Health care providers should consider mental health status of hypertensive patients, and counsel for these factors.
What can be done to improve polycystic ovary syndrome (PCOS) healthcare? Insights from semi-structured interviews with women in Canada
Authors: Ismayilova Miya , Yaya Sanni
Published: May 2022

Background

Polycystic ovary syndrome (PCOS) is a common and perplexing condition affecting metabolic, reproductive, cardiovascular, and psychological health in women. Previous studies point to widespread dissatisfaction and frustration in women with the information and care they receive. Studies have found delays with the diagnosis of PCOS and gaps in knowledge in physicians regarding the diagnosis and management of PCOS. Little has been heard from women on what they think can be improved with PCOS care, especially in Canada. This qualitative study explores women’s experiences navigating the healthcare system and their insights on what could be improved based on their lived experiences.

Methods

Twenty-five participants were interviewed remotely over the phone by the first author between October and December 2018.Interviews were semi-structured and in-depth. Data were analyzed using thematic analysis and interpretive description methodology.

Results

Twenty-five in-depth interviews conducted with participants across Canada (ages 18–63) revealed three overall areas in need of improvement. First, women emphasized a need for greater knowledge and awareness of PCOS in primary care physicians (PCPs) as well as the need for the medical community to prioritize women’s health. Second, participants advocated for greater PCOS awareness and de-stigmatization in the general community and in women and girls, and any individuals with female reproductive systems. Third, participants brought up several needed resources, such as the need for more PCOS research to be funded and undertaken, more PCOS specialists and experts to be available, credible doctor-provided information (e.g., pamphlets, websites), and age-specific support groups and mental health supports to be available. Participants were generally unaware of existing PCOS organizations and brought up the need for established PCOS organizations to aid in the training and retraining of doctors and local awareness-building in communities.

Conclusions

Participants believed that PCPs in Canada needed to be well-versed on how to diagnose and manage PCOS to prevent delays in diagnosis and provide easier access to care. Further, greater awareness and de-stigmatization in the general community are needed so women can identify symptoms early and have access to support from those around them. Overall, PCOS may be an overlooked and under-prioritized condition, both in the Canadian healthcare system and general community.
Randomized study on the effectiveness of nomegestrol acetate plus 17β-estradiol oral contraceptive versus dienogest oral pill in women with suspected endometriosis‑associated chronic pelvic pain
Authors: Caruso Salvatore , Cianci Antonio , Iraci Sareri Marco , Panella Marco , Caruso Giuseppe , Cianci Stefano
Published: May 2022

Background

To evaluate the effects of a combined oral contraceptive containing 1.5 mg 17b-estradiol (E2) and 2.5 mg nomegestrol acetate (NOMAC) or 2 mg/daily dienogest (DNG) oral progestin on endometriosis-associated chronic pelvic pain (CPP) and on the quality of life (QoL) and sexual function, by a randomized study design.

Methods

The E2/NOMAC group and DNG group included 99 and 98 women, respectively. The levels of CPP were measured by the visual analogic scale (VAS). The QoL scores were investigated by the Short Form-36 questionnaire (SF-36). Finally, sexual function was studied using the Female Sexual Function Index (FSFI), while sexual distress was studied by the Female Sexual Distress Scale (FSDS). The study had 3, 6 and 12-month follow-ups.

Results

The intra-group analysis showed an improvement of the VAS score from baseline to the 12-month follow-up in the women of both groups (p < 0.001). The inter-group comparison showed a similar improvement of CPP (p = 0.06). Women on DNG had better SF-36 somatic (p < 0.01) and FSFI scores (p < 0.006) than women on E2/NOMAC at the 6- and 12-month follow-ups.

Conclusions

The results support the efficacy of both hormonal treatments, even if DNG was more effective than E2/NOMAC in a limited intergroup comparison.
Survey of incidence, lifetime prevalence, and treatment of self-reported vulvovaginal candidiasis, United States, 2020
Authors: Benedict Kaitlin , Singleton Alyson L. , Jackson Brendan R. , Molinari Noelle Angelique M.
Published: May 2022

Background

Vulvovaginal candidiasis (VVC) is a common gynecologic problem in the United States but estimates of its true incidence and prevalence are lacking. We estimated self-reported incidence and lifetime prevalence of healthcare provider-diagnosed VVC and recurrent VVC (RVVC), assessed treatment types, and evaluated demographic and health-related risk factors associated with VVC.

Methods

An online survey sent to 4548 U.S. adults; data were weighted to be representative of the population. We conducted descriptive and bivariate analyses to examine demographic characteristics and health related factors associated with having VVC in the past year, lifetime prevalence of VVC, and over-the-counter (OTC) and prescription antifungal treatment use. We conducted multivariate analyses to assess features associated with 1) having VVC in the past year, 2) number of VVC episodes in the past year, and 3) lifetime prevalence of VVC.

Results

Among the subset of 1869 women respondents, 98 (5.2%) had VVC in the past year; of those, 5 (4.7%) had RVVC. Total, 991 (53%) women reported healthcare provider-diagnosed VVC in their lifetime. Overall, 72% of women with VVC in the past year reported prescription antifungal treatment use, 40% reported OTC antifungal treatment use, and 16% reported both. In multivariate analyses, odds of having VVC in the past year were highest for women with less than a high school education (aOR = 6.30, CI: 1.84–21.65), with a child/children under 18 years old (aOR = 3.14, CI: 1.58–6.25), with diabetes (aOR = 2.93, CI: 1.32–6.47), who were part of a couple (aOR = 2.86, CI: 1.42–5.78), and with more visits to a healthcare provider for any reason (aOR = 2.72, CI: 1.84–4.01). Similar factors were associated with increasing number of VVC episodes in the past year and with lifetime prevalence of VVC.

Conclusion

VVC remains a common infection in the United States. Our analysis supports known clinical risk factors for VVC and suggests that antifungal treatment use is high, underscoring the need to ensure appropriate diagnosis and treatment.
Incorporating interactive workshops into bedside teaching: completion of a multi-modal rheumatology rotation significantly increases internal medicine residents’ competency and comfort with comprehensive knee examinations
Authors: Kwiatkowski Alysia , Shakoor Najia , Manadan Augustine , Block Joel A. , Khandelwal Sonali
Published: May 2022

Background

Studies have elucidated the lack of competency in musculoskeletal (MSK) examination skills amongst trainees. Various modalities have been studied, however, there remains a dearth of literature regarding the effectiveness of bedside teaching versus dedicated workshops. Our aim was to determine if incorporating a workshop into a rheumatology rotation would be effective in increasing medicine residents’ competency and comfort with knee examinations when compared to the rotation alone.

Methods

Over 16 months, rotators were randomized to workshop plus rotation versus rotation alone. Participants were tested on their knee examination skills using an objective structured clinical examination (OSCE). Surveys were administered assessing to what degree the rotation was beneficial. Comfort and helpfulness were measured using a 5-point Likert scale. Paired and independent samples t-tests were used for comparisons.

Results

Fifty-seven residents participated. For both groups, there were improvements between pre- and post-OSCE scores (workshop p < 0.001, no workshop p = 0.003), and levels of comfort with examination (workshop p < 0.001, no workshop p < 0.001). When comparing groups, there were differences favoring the workshop in post-OSCE score (p = < 0.001), mean change in OSCE score (p < 0.001) and mean change in comfort with knee examination (p = 0.025).

Conclusion

An elective in rheumatology augmented residents’ MSK competency and comfort. Incorporation of a workshop further increased knowledge, skills and comfort with diagnosis and treatment. Current educational research focuses on alternatives to traditional methods. This study provides evidence that a multi-modal approach, combining traditional bedside and interactive models, is of benefit.
The development and implementation of a guideline-based clinical decision support system to improve empirical antibiotic prescribing
Authors: Akhloufi H. , van der Sijs H. , Melles D. C. , van der Hoeven C. P. , Vogel M. , Mouton J. W. , Verbon A.
Published: May 2022

Background

To describe and evaluate a clinical decision support system (CDSS) for empirical antibiotic therapy using a systematic framework.

Methods

A reporting framework for behavior change intervention implementation was used, which includes several domains: development, evaluation and implementation. Within the development domain a description is given of the engagement of stakeholders, a rationale for how the CDSS may influence antibiotic prescribing and a detailed outline of how the system was developed. Within the evaluation domain a technical validation is performed and the interaction between potential users and the CDSS is analyzed. Within the domain of implementation a description is given on how the CDSS was tested in the real world and the strategies that were used for implementation and adoption of the CDSS.

Results

Development: a CDSS was developed, with the involvement of stakeholders, to assist empirical antibiotic prescribing by physicians. Evaluation: Technical problems were determined during the validation process and corrected in a new CDSS version. A usability study was performed to assess problems in the system-user interaction. Implementation: In 114 patients the antibiotic advice that was generated by the CDSS was followed. For 54 patients the recommendations were not adhered to.

Conclusions

This study describes the development and validation of a CDSS for empirical antibiotic therapy and shows the usefulness of the systematic framework for reporting CDSS interventions. In addition it shows that CDSS recommendations are not always adhered to which is associated with incorrect use of the system.
Hospital nurses’ knowledge about older patients in Turkey: a validation and comparison study
Authors: Harputlu Deniz , Kerstens Sander , Özdemir Funda , Dikken Jeroen
Published: May 2022

Background

In Turkey, nursing care in hospitals has gradually included more older patients, resulting in a need for knowledgeable geriatric nurses. It is unknown, however, whether the nursing workforce is ready for this increase. Therefore, the aim of this study is to validate the Knowledge about Older Patients Quiz (KOPQ) in the Turkish language and culture, to describe Turkish hospital nurses’ knowledge about older patients, and to compare levels of knowledge between Turkish and Dutch hospital nurses.

Method

First, the KOPQ was translated, resulting in the KOPQ-TR. Then, content validity was assessed by 10 geriatric experts using the Lynn method, a pilot test among 10 nurses was conducted, and a Rasch analysis was performed using data from 135 nurses working in two Turkish hospitals. Finally, a comparison between Turkish and Dutch nurses’ levels of knowledge was performed.

Results

The results of the qualitative validation (i.e., content validity by experts and nurses), model fit, item reliability and the item separation index of the KOPQ-TR proved excellent, indicating good content and construct validity. However, the Person Separation Index and Person Reliability of the Rash analysis did not meet the criteria for adequate scale and psychometric validation. The levels of knowledge among Turkish nurses were significantly lower than those of Dutch nurses.

Conclusions

The KOPQ-TR is promising for use in Turkey, although psychometric validation should be repeated using a better targeted sample with a larger ability variance to adequately assess the Person Separation Index and Person Reliability. Currently, education regarding care for older patients is not sufficiently represented in Turkish nursing curricula. However, the need to do so is evident, as the results demonstrate that knowledge deficits and an increase in older patients admitted to the hospital will eventually occur. International comparison and cooperation provides an opportunity to learn from other countries that currently face the challenge of an aging (hospital) population.
Repeat hospital transfers among long stay nursing home residents: a mixed methods analysis of age, race, code status and clinical complexity
Authors: Vogelsmeier Amy , Popejoy Lori , Fritz Elizabeth , Canada Kelli , Ge Bin , Brandt Lea , Rantz Marilyn
Published: May 2022

Background

Nursing home residents are at increased risk for hospital transfers resulting in emergency department visits, observation stays, and hospital admissions; transfers that can also result in adverse resident outcomes. Many nursing home to hospital transfers are potentially avoidable. Residents who experience repeat transfers are particularly vulnerable to adverse outcomes, yet characteristics of nursing home residents who experience repeat transfers are poorly understood. Understanding these characteristics more fully will help identify appropriate intervention efforts needed to reduce repeat transfers.

Methods

This is a mixed-methods study using hospital transfer data, collected between 2017 and 2019, from long-stay nursing home residents residing in 16 Midwestern nursing homes who transferred four or more times within a 12-month timeframe. Data were obtained from an acute care transfer tool used in the Missouri Quality Initiative containing closed- and open-ended questions regarding hospital transfers. The Missouri Quality Initiative was a Centers for Medicare and Medicaid demonstration project focused on reducing avoidable hospital transfers for long stay nursing home residents. The purpose of the analysis presented here is to describe characteristics of residents from that project who experienced repeat transfers including resident age, race, and code status. Clinical, resident/family, and organizational factors that influenced transfers were also described.

Results

Findings indicate that younger residents (less than 65 years of age), those who were full-code status, and those who were Black were statistically more likely to experience repeat transfers. Clinical complexity, resident/family requests to transfer, and lack of nursing home resources to manage complex clinical conditions underlie repeat transfers, many of which were considered potentially avoidable.

Conclusions

Improved nursing home resources are needed to manage complex conditions in the NH and to help residents and families set realistic goals of care and plan for end of life thus reducing potentially avoidable transfers.
Liquid biopsies to occult brain metastasis
Authors: Rehman Asad Ur , Khan Parvez , Maurya Shailendra Kumar , Siddiqui Jawed A. , Santamaria-Barria Juan A. , Batra Surinder K. , Nasser Mohd Wasim
Published: May 2022

Brain metastasis (BrM) is a major problem associated with cancer-related mortality, and currently, no specific biomarkers are available in clinical settings for early detection. Liquid biopsy is widely accepted as a non-invasive method for diagnosing cancer and other diseases. We have reviewed the evidence that shows how the molecular alterations are involved in BrM, majorly from breast cancer (BC), lung cancer (LC), and melanoma, with an inception in how they can be employed for biomarker development. We discussed genetic and epigenetic changes that influence cancer cells to breach the blood-brain barrier (BBB) and help to establish metastatic lesions in the uniquely distinct brain microenvironment. Keeping abreast with the recent breakthroughs in the context of various biomolecules detections and identifications, the circulating tumor cells (CTC), cell-free nucleotides, non-coding RNAs, secretory proteins, and metabolites can be pursued in human body fluids such as blood, serum, cerebrospinal fluid (CSF), and urine to obtain potential candidates for biomarker development. The liquid biopsy-based biomarkers can overlay with current imaging techniques to amplify the signal viable for improving the early detection and treatments of occult BrM.
Melanoma cells with diverse invasive potential differentially induce the activation of normal human fibroblasts
Authors: Mazurkiewicz Justyna , Simiczyjew Aleksandra , Dratkiewicz Ewelina , Pietraszek-Gremplewicz Katarzyna , Majkowski Michał , Kot Magdalena , Ziętek Marcin , Matkowski Rafał , Nowak Dorota
Published: May 2022

Background

The tumor microenvironment consists of stromal cells, extracellular matrix, and physicochemical properties (e.g., oxygenation, acidification). An important element of the tumor niche are cancer-associated fibroblasts (CAFs). They may constitute up to 80% of the tumor mass and share some features with myofibroblasts involved in the process of wound healing. CAFs can facilitate cancer progression. However, their interaction with melanoma cells is still poorly understood.

Methods

We obtained CAFs using conditioned media derived from primary and metastatic melanoma cells, and via co-culture with melanoma cells on Transwell inserts. Using 2D and 3D wound healing assays and Transwell invasion method we evaluated CAFs’ motile activities, while coverslips with FITC-labeled gelatin, gelatin zymography, and fluorescence-based activity assay were employed to determine the proteolytic activity of the examined cells. Western Blotting method was used for the identification of CAFs’ markers as well as estimation of the mediators of MMPs’ (matrix metalloproteinases) expression levels. Lastly, CAFs’ secretome was evaluated with cytokine and angiogenesis proteomic arrays, and lactate chemiluminescence-based assay.

Results

Acquired FAP-α/IL6-positive CAFs exhibited elevated motility expressed as increased migration and invasion ratio, as well as higher proteolytic activity (area of digestion, MMP2, MMP14). Furthermore, fibroblasts activated by melanoma cells showed upregulation of the MMPs’ expression mediators’ levels (pERK, p-p38, CD44, RUNX), enhanced secretion of lactate, several cytokines (IL8, IL6, CXCL1, CCL2, ICAM1), and proteins related to angiogenesis (GM-CSF, DPPIV, VEGFA, PIGF).

Conclusions

Observed changes in CAFs’ biology were mainly driven by highly aggressive melanoma cells (A375, WM9, Hs294T) compared to the less aggressive WM1341D cells and could promote melanoma invasion, as well as impact inflammation, angiogenesis, and acidification of the tumor niche. Interestingly, different approaches to CAFs acquisition seem to complement each other showing interactions between studied cells.
Inhibition of NOS1 promotes the interferon response of melanoma cells
Authors: Chen Xi , Zou Zhiwei , Wang Qianli , Gao Wenwen , Zeng Sisi , Ye Shuangyan , Xu Pengfei , Huang Mengqiu , Li Keyi , Chen Jianping , Zhong Zhuo , Zhang Qianbing , Hao Bingtao , Liu Qiuzhen
Published: May 2022

Background

NOS1 expression predicts poor prognosis in patients with melanoma. However, the molecular function of NOS1 in the type I IFN response and immune escape of melanoma is still unknown.

Methods

The CRISPR/Cas9 system was used to generate NOS1-knockout melanoma cells and the biological characteristics of NOS1-knockout cells were evaluated by MTT assay, clonogenic assay, EdU assay, and flow cytometric assay. The effect on tumor growth was tested in BALB/c-nu and C57BL/6 mouse models. The gene expression profiles were detected with Affymetrix microarray and RNA-seq and KEGG (Kyoto Encyclopedia of Genes and Genomes) and CLUE GO analysis was done. The clinical data and transcriptional profiles of melanoma patients from the public database TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus, GSE32611) were analyzed by Qlucore Omics Explorer.

Results

NOS1 deletion suppressed the proliferation of melanoma A375 cells in culture, blocked cell cycling at the G0/G1 phase, and decreased the tumor growth in lung metastasis nodes in a B16 melanoma xenograft mouse model. Moreover, NOS1 knockout increased the infiltration of CD3+ immune cells in tumors. The transcriptomics analysis identified 2203 differential expression genes (DEGs) after NOS1 deletion. These DEGs indicated that NOS1 deletion downregulated mostly metabolic functions but upregulated immune response pathways. After inhibiting with NOS1 inhibitor N-PLA, melanoma cells significantly increased the response to IFN$$\upalpha $$
α
by upregulation expression of IFN$$\upalpha $$
α
simulation genes (ISGs), especially the components in innate immune signaling, JAK-STAT, and TOLL-LIKE pathway. Furthermore, these NOS1-regulating immune genes (NOS1-ISGs) worked as a signature to predict poor overall survival and lower response to chemotherapy in melanoma patients.

Conclusion

These findings provided a transcriptional evidence of NOS1 promotion on tumor growth, which is correlated with metabolic regulation and immune escape in melanoma cells.
The use of ECMO in pediatric granulomatosis with polyangiitis
Authors: Finkel Rachel , Honig Jesse , Chao Chun P. , Rescoe Erin , Solomon Sonia
Published: May 2022

Background

Granulomatosis with polyangiitis (GPA) vasculitis with pulmonary-renal syndrome rarely presents in children and is associated with high mortality rates.

Case presentation

We present the case of a 13-year-old male with newly diagnosed GPA vasculitis, treated with extracorporeal membrane oxygenation, continuous renal replacement therapy, plasmapheresis, rituximab, cyclophosphamide, and corticosteroids.

Conclusion

This case presentation demonstrates that ECMO can be used as a life supporting therapy in pediatric patients with pulmonary hemorrhage from ANCA vasculitis in conjunction with other therapies.
Copper oxide nanoparticles trigger macrophage cell death with misfolding of Cu/Zn superoxide dismutase 1 (SOD1)
Authors: Gupta Govind , Cappellini Francesca , Farcal Lucian , Gornati Rosalba , Bernardini Giovanni , Fadeel Bengt
Published: May 2022

Background

Copper oxide (CuO) nanoparticles (NPs) are known to trigger cytotoxicity in a variety of cell models, but the mechanism of cell death remains unknown. Here we addressed the mechanism of cytotoxicity in macrophages exposed to CuO NPs versus copper chloride (CuCl2).

Methods

The mouse macrophage cell line RAW264.7 was used as an in vitro model. Particle uptake and the cellular dose of Cu were investigated by transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP-MS), respectively. The deposition of Cu in lysosomes isolated from macrophages was also determined by ICP-MS. Cell viability (metabolic activity) was assessed using the Alamar Blue assay, and oxidative stress was monitored by a variety of methods including a luminescence-based assay for cellular glutathione (GSH), and flow cytometry-based detection of mitochondrial superoxide and mitochondrial membrane potential. Protein aggregation was determined by confocal microscopy using an aggresome-specific dye and protein misfolding was determined by circular dichroism (CD) spectroscopy. Lastly, proteasome activity was investigated using a fluorometric assay.

Results

We observed rapid cellular uptake of CuO NPs in macrophages with deposition in lysosomes. CuO NP-elicited cell death was characterized by mitochondrial swelling with signs of oxidative stress including the production of mitochondrial superoxide and cellular depletion of GSH. We also observed a dose-dependent accumulation of polyubiquitinated proteins and loss of proteasomal function in CuO NP-exposed cells, and we could demonstrate misfolding and mitochondrial translocation of superoxide dismutase 1 (SOD1), a Cu/Zn-dependent enzyme that plays a pivotal role in the defense against oxidative stress. The chelation of copper ions using tetrathiomolybdate (TTM) prevented cell death whereas inhibition of the cellular SOD1 chaperone aggravated toxicity. Moreover, CuO NP-triggered cell death was insensitive to the pan-caspase inhibitor, zVAD-fmk, and to wortmannin, an inhibitor of autophagy, implying that this was a non-apoptotic cell death. ZnO NPs, on the other hand, triggered autophagic cell death.

Conclusions

CuO NPs undergo dissolution in lysosomes leading to copper-dependent macrophage cell death characterized by protein misfolding and proteasomal insufficiency. Specifically, we present novel evidence for Cu-induced SOD1 misfolding which accords with the pronounced oxidative stress observed in CuO NP-exposed macrophages. These results are relevant for our understanding of the consequences of inadvertent human exposure to CuO NPs.
Youth mental health and/or addiction concerns and service needs during the COVID-19 pandemic: a qualitative exploration of caregiver experiences and perspectives
Authors: Markoulakis Roula , Da Silva Andreina , Kodeeswaran Sugy , Levitt Anthony
Published: May 2022

The COVID-19 pandemic has undoubtedly had a significant impact on youth mental health and/or addiction concerns and exacerbated pre-existing gaps in access to mental health and/or addiction care. Caregivers can support their youth in seeking and participating in care, however, their experiences in doing so in the pandemic and their perspectives of their youth’s care needs are not well-understood. A descriptive qualitative study was conducted to better understand youth’s and caregivers’ experiences accessing care during the pandemic, from the caregivers’ standpoint. Participants completed semi-structured qualitative interviews that focused on experiences seeking and accessing mental health and/or addiction services, with specific questions regarding their experiences accessing services during the pandemic. A total of 46 interviews were included in the thematic analysis of the data. Study findings highlight the impacts of the pandemic on everyday life, on youth mental health and/or addiction needs, on caregiver’s experiences seeking and accessing services for their youth, and on service access, including perceptions of virtual care modalities. The discussion highlights the importance of focusing on factors that enable youth’s participation in care, to ensure accessibility of appropriate and timely care that meets youth’s and families’ needs. Also highlighted is the frustration and despair experienced by caregivers seeking critical mental health and addictions supports for their youth during the pandemic, as well as the sense of isolation and of being left behind by the system. Identifying caregiver perspectives of youth mental health and addiction needs and service access during the COVID-19 pandemic provided important insights that can help inform approaches to youth mental health and addictions care during the pandemic and beyond.
Trends of COVID-19 incidence in Manitoba and public health measures: March 2020 to February 2022
Authors: Aboulatta Laila , Kowalec Kaarina , Delaney Joseph , Alessi-Severini Silvia , Leong Christine , Falk Jamie , Eltonsy Sherif
Published: May 2022

Objectives

The increasing spread of severe acute respiratory syndrome coronavirus-2 has prompted Canada to take unprecedented measures. The objective of this study was to examine the impact of the implemented public health measures on the incidence of COVID-19 in Manitoba.

Results

Using the COVID-19 dataset, we examined the temporal trends of daily reported COVID-19 cases and the coinciding public health measures implemented from March 12, 2020 to February 28, 2022. We calculated the 7-day moving average and crude COVID-19 infection rate/100,000 Manitobans. Due to the restrictions applied, the infection rate decreased from 2.4 (April 1) to 0.07 infections (May 1, 2020). Between May 4 and July 17, 2020, the reported cases stabilized, and some restrictions were lifted. However, in November, the cases peaked with infection rate of 29. Additional restrictions were implemented, and the rate dropped to 3.6 infections on March 31, 2021. As of August 2021, 62.8% of eligible Manitobans received two vaccine doses. The infection rate increased to 128.3 infections on December 31, 2021 and mitigation measures were implemented. This study describes how physical distancing in conjunction with other containment measures can reduce the COVID-19 burden. Future studies into the extent of the implementation of the restrictions are necessary.