bluuebunny/crossref_metadata_2025 huggingface dataset:
Taking action against medical accidents: A brief history of AvMA and clinical risk management in the NHS
Authors: Sirrs Christopher
Published: October 2022

Established in 1982, Action against Medical Accidents (AvMA)—originally named Action for Victims of Medical Accidents—was effectively the first charity in Britain dedicated to ‘patient safety’. This article provides a historical analysis of the origins and work of AvMA, situating its background in the medical negligence ‘crisis’ of the 1970s and 1980s, growing consumerism in healthcare, and the significant barriers to justice patients confronted following a clinical incident. It also explores AvMA's impacts on evolving attitudes towards patient harm and safety in the NHS. The article asserts that in addition to supporting patients and campaigning for changes in legal procedures, AvMA played an instrumental role in raising the political profile of adverse health events (‘medical accidents’). By supporting claimant solicitors and increasing their chances of legal success, AvMA contributed to the rising tide of negligence claims, which incentivised NHS trusts and health authorities to introduce clinical risk management (CRM). By 2000, CRM was being framed as part of a broader mission to improve quality and safety in healthcare, and AvMA was recognised as a key stakeholder in the new patient safety agenda.
Concepts of the Divine and the Methodologies of its Venerations in World Religions
Authors: Hebbar B. N.
Published: October 2022

This article deals with, in a comprehensive and cogent a manner as is possible, the concepts of the divine and its multifarious modalities of its veneration in the eleven major historical religions of the world. These religions are Zoroastrianism, Judaism, Christianity (Nestorian, Oriental Orthodox, Eastern Orthodox, Roman Catholic and Protestant), Islam, Hinduism (Vedic and Classical), Jainism, Buddhism (Theravāda, Mahāyāna and Vajrayāna), Sikhism, Daoism, Confucianism, and Shinto.
Visual Cu2+ Detection of Gold-Nanoparticle Probes and its Employment for Cu2+ Tracing in Circuit System
Authors: Ou Tzu-Yu , Lo Chien-Feng , Kuo Kuan-Yi , Lin Yu-Pin , Chen Sung-Yu , Chen Chia-Yun
Published: October 2022

Highly sensitive, simple and reliable colorimetric probe for Cu2+-ion detection was visualized with the L-cysteine functionalized gold nanoparticle (LS-AuNP) probes. The pronounced sensing of Cu2+with high selectivity was rapidly featured with obvious colour change that enabled to visually sense Cu2+ions by naked eyes. By employing systemic investigations on crystallinities, elemental compositions, microstructures, surface features, light absorbance, zeta potentials and chemical states of LS-AuNP probes, the oxidation-triggered aggregation effect of LS-AuNP probes was envisioned. The results indicated that the mediation of Cu2+oxidation coordinately caused the formation of disulfide cystine, rendering the removal of thiol group at AuNPs surfaces. These features reflected the visual colour change for the employment of tracing Cu2+ions in a quantitative way.
Structural and functional analysis of stress-inducible genes and their promoters selected from young oil palm (Elaeis guineensis) under salt stress
Authors: Ferreira Thalita Massaro Malheiros , Ferreira Filho Jaire Alves , Leão André Pereira , de Sousa Carlos Antônio Ferreira , Souza Manoel Teixeira
Published: October 2022

Background

Soil salinity is a problem in more than 100 countries across all continents. It is one of the abiotic stress that threatens agriculture the most, negatively affecting crops and reducing productivity. Transcriptomics is a technology applied to characterize the transcriptome in a cell, tissue, or organism at a given time via RNA-Seq, also known as full-transcriptome shotgun sequencing. This technology allows the identification of most genes expressed at a particular stage, and different isoforms are separated and transcript expression levels measured. Once determined by this technology, the expression profile of a gene must undergo validation by another, such as quantitative real-time PCR (qRT-PCR). This study aimed to select, annotate, and validate stress-inducible genes—and their promoters—differentially expressed in the leaves of oil palm (Elaeis guineensis) plants under saline stress.

Results

The transcriptome analysis led to the selection of 14 genes that underwent structural and functional annotation, besides having their expression validated using the qRT-PCR technique. When compared, the RNA-Seq and qRT-PCR profiles of those genes resulted in some inconsistencies. The structural and functional annotation analysis of proteins coded by the selected genes showed that some of them are orthologs of genes reported as conferring resistance to salinity in other species. There were those coding for proteins related to the transport of salt into and out of cells, transcriptional regulatory activity, and opening and closing of stomata. The annotation analysis performed on the promoter sequence revealed 22 distinct types of cis-acting elements, and 14 of them are known to be involved in abiotic stress.

Conclusion

This study has helped validate the process of an accurate selection of genes responsive to salt stress with a specific and predefined expression profile and their promoter sequence. Its results also can be used in molecular-genetics-assisted breeding programs. In addition, using the identified genes is a window of opportunity for strategies trying to relieve the damages arising from the salt stress in many glycophyte crops with economic importance.
A tandem CCCH type zinc finger protein gene CpC3H3 from Chimonanthus praecox promotes flowering and enhances drought tolerance in Arabidopsis
Authors: Liu Huamin , Xiao Shiqi , Sui Shunzhao , Huang Renwei , Wang Xia , Wu Huafeng , Liu Xia
Published: October 2022

Background

CCCH-type zinc finger proteins play important roles in plant development and biotic/abiotic stress responses. Wintersweet (Chimonanthus praecox) is a popular ornamental plant with strong resistance to various stresses, which is a good material for exploring gene resource for stress response. In this study, we isolated a CCCH type zinc finger protein gene CpC3H3 (MZ964860) from flower of wintersweet and performed functional analysis with a purpose of identifying gene resource for floral transition and stress tolerance.

Results

CpC3H3 was predicted a CCCH type zinc finger protein gene encoding a protein containing 446 amino acids with five conserved C-X8-C-X5-C-X3-H motifs. CpC3H3 was localized in the cell membrane but with a nuclear export signal at the N-terminal. Transcripts of CpC3H3 were significantly accumulated in flower buds at floral meristem formation stage, and were induced by polyethylene glycol. Overexpression of CpC3H3 promoted flowering, and enhanced drought tolerance in transgenic A. thaliana. CpC3H3 overexpression affects the expression level of genes involved in flower inducement and stress responses. Further comparative studies on physiological indices showed the contents of proline and soluble sugar, activity of peroxidase and the rates of electrolyte leakage were significantly increased and the content of malondialdehyde and osmotic potential was significantly reduced in transgenic A. thaliana under PEG stress.

Conclusion

Overall, CpC3H3 plays a role in flowering inducement and drought tolerance in transgenic A. thaliana. The CpC3H3 gene has the potential to be used to promote flowering and enhance drought tolerance in plants.
Regional distribution of Mycobacterium tuberculosis infection and resistance to rifampicin and isoniazid as determined by high-resolution melt analysis
Authors: Wang Zhenzhen , Guo Tengfei , Jiang Tao , Zhao Zhanqin , Zu Xiangyang , li Long , Zhang Qing , Hou Yi , Song Kena , Xue Yun
Published: October 2022

Background

Identifying the transmission mode and resistance mechanism of Mycobacterium tuberculosis (MTB) is key to prevent disease transmission. However, there is a lack of regional data. Therefore, the aim of this study was to identify risk factors associated with the transmission of MTB and regional patterns of resistance to isoniazid (INH) and rifampicin (RFP), as well as the prevalence of multidrug-resistant tuberculosis (MDR-TB).

Methods

High-resolution melt (HRM) analysis was conducted using sputum, alveolar lavage fluid, and pleural fluid samples collected from 17,515 patients with suspected or confirmed MTB infection in the downtown area and nine counties of Luoyang City from 2019 to 2021.

Results

Of the 17,515 patients, 82.6% resided in rural areas, and 96.0% appeared for an initial screening. The HRM positivity rate was 16.8%, with a higher rate in males than females (18.0% vs. 14.1%, p < 0.001). As expected, a positive sputum smear was correlated with a positive result for HRM analysis. By age, the highest rates of MTB infection occurred in males (22.9%) aged 26–30 years and females (28.1%) aged 21–25. The rates of resistance to RFP and INH and the incidence of MDR were higher in males than females (20.5% vs. 16.1%, p < 0.001, 15.9% vs. 12.0%, p < 0.001 and 12.9% vs. 10.2%, p < 0.001, respectively). The HRM positivity rate was much higher in previously treated patients than those newly diagnosed for MTB infection. Notably, males at the initial screening had significantly higher rates of HRM positive, INH resistance, RFP resistance, and MDR-TB than females (all, p < 0.05), but not those previously treated for MTB infection. The HRM positivity and drug resistance rates were much higher in the urban vs. rural population. By multivariate analyses, previous treatment, age < 51 years, residing in an urban area, and male sex were significantly and positively associated with drug resistance after adjusting for smear results and year of testing.

Conclusion

Males were at higher risks for MTB infection and drug resistance, while a younger age was associated with MTB infection, resistance to INH and RFP, and MDR-TB. Further comprehensive monitoring of resistance patterns is needed to control the spread of MTB infection and manage drug resistance locally.
Risk factors associated with esophageal cancers, diagnosed at tertiary level in Afghanistan: a descriptive cross-sectional study
Authors: Saadaat Ramin , Abdul-Ghafar Jamshid , Hanifi Ahmed Nasir , Khalid Saifullah , Khairy Abdul Latif , Ibrahimkhil Abdul Sami , Malakzai Haider Ali , Esmat Esmatullah , Haidari Mujtaba , Hussaini Nasrin , Nasir Najla , Noor Sarah , Haidary Ahmed Maseh
Published: October 2022

Background:

Worldwide, esophageal cancer (EC) is a common cancer in term of incidence and mortality and is the 4th common cancer in Afghanistan. Current study aimed to evaluate the profile of risk factors for EC among patients diagnosed at tertiary level in Afghanistan.

Methodology:

A descriptive cross-sectional study was carried out between January 2019 up to February 2021 including all esophageal cancers diagnosed at pathology department of French Medical Institute for Mothers and Children, Afghanistan.

Result:

240 diagnosed cases were analyzed, in which 59.40% of squamous cell carcinoma and 41.07% Adenocarcinoma. Both histopathological type of were predominantly diagnosed in males. The majority of the patients were residents of rural areas. More than 80% of the patients were illiterate with only less than 2% completing higher education. Majority of the patients were laborers and farmers while less than 10% were employed. According to income assessment, more than 80% were from low-income household, the rest from middle-income and none from high-income family. Oral snuff consumption was noted in 33.9% of squamous cell carcinoma patients and 40% adenocarcinoma patients whereas, family history of esophageal cancer was observed in 37.8% and 36.7% in both types of carcinomas, respectively. More than 60% of both types of carcinomas patients were hot tea drinkers.

Conclusion:

Current study demonstrated that most patients diagnosed with esophageal cancers were male, uneducated, belongs to low-income groups, lives in rural areas. These findings suggest distribution of esophageal cancer in specific socioeconomic groups, clearly demonstrating the need further analytical study.
The impact of logo-therapy on disease acceptance and self-awareness of patients undergoing hemodialysis; a pre-test-post-test research
Authors: Mehrizi Fatemeh Zarezadeh , Bagherian Samaneh , Bahramnejad Ali , Khoshnood Zohreh
Published: October 2022

Background

Acceptance is considered a key variable in chronic diseases such as chronic renal failure. To achieve adaptation and acceptance, people face obstacles, and identifying these obstacles primarily requires self-awareness. logo-therapy can help a person achieve this goal. To this end, this study aimed to investigate the effect of logo-therapy on disease acceptance and self-awareness of patients undergoing hemodialysis referred to a medical centers supervised by Kerman medical science university in 2021.

Methods

This quasi-experimental study was conducted with a pre-test-post-test research design on 80 patients with chronic renal failure undergoing hemodialysis in Kerman. The patients who met the inclusion criteria were selected using convenience sampling and were then randomly assigned to intervention and control groups (40 patients in each group). The logo-therapy training program was performed for the participants in the intervention group during 4 sessions of 45–60 min, individually and three times a week. The instruments used for data collection were a demographic information questionnaire, the Acceptance of Illness Scale (AIS), and the Self-Awareness Outcomes Questionnaire (SAOQ). The collected data were analyzed using SPSS software (version 22).

Results

The analysis didn’t show a significant difference in the acceptance of illness scores in the intervention group before and after the intervention (P > 0.05). Besides, a statistically significant difference was observed between the intervention and control groups in terms of self-awareness, indicating that the intervention improved the dialysis patients’ self-awareness (P < 0.05). Also, the patients’ age, marriage length, and the number of children had statistically significant correlations with self-awareness and acceptance (P < 0.05).

Conclusion

The results of this study showed that meaning therapy intervention can positively affect disease acceptance and self-awareness of patients undergoing hemodialysis. Since logo-therapy has been effective in other patients and the patients in this study, health officials and managers are recommended to use this intervention method to promote disease acceptance and self-awareness in these patients.
Probing key informants’ views of health equity within the World Health Organization’s Urban HEART initiative
Authors: Amri Michelle , O’Campo Patricia , Enright Theresa , Siddiqi Arjumand , Di Ruggiero Erica , Bump Jesse Boardman
Published: October 2022

To date, no studies have assessed how those involved in the World Health Organization’s (WHO) work understand the concept of health equity. To fill the gap, this research poses the question, “how do Urban Health Equity Assessment and Response Tool (Urban HEART) key informants understand the concept of health equity?”, with Urban HEART being selected given the focus on health equity. To answer this question, this study undertakes synchronous electronic interviews with key informants to assess how they understand health equity within the context of Urban HEART. Key findings demonstrate that: (i) equity is seen as a core value and inequities were understood to be avoidable, systematic, unnecessary, and unfair; (ii) there was a questionable acceptance of need to act, given that political sensitivity arose around acknowledging inequities as “unnecessary”; (iii) despite this broader understanding of the key aspects of health inequity, the concept of health equity was seen as vague; (iv) the recognized vagueness inherent in the concept of health equity may be due to various factors including country differences; (v) how the terms “health inequity” and “health inequality” were used varied drastically; and (vi) when speaking about equity, a wide range of aspects emerged. Moving forward, it would be important to establish a shared understanding across key terms and seek clarification, prior to any global health initiatives, whether explicitly focused on health equity or not.
The effect of a randomised controlled lifestyle intervention on weight loss and plasma proneurotensin
Authors: Bennet Louise , Fawad Ayesha , Struck Joachim , Larsson Sara Lönn , Bergmann Andreas , Melander Olle
Published: October 2022

Aims

Proneurotensin (Pro-NT) is a strong predictor of cardiometabolic disease including type 2 diabetes and obesity, however, the effect of lifestyle change on Pro-NT has not been investigated in this context. Middle Eastern (ME) immigrants represent the largest and fastest growing minority population in Europe and are a high-risk population for obesity and type 2 diabetes. In this randomised controlled lifestyle intervention (RCT) addressing ME immigrants to Sweden where weight-loss was previously studied as the main outcome, as a secondary analysis we aimed to study change in Pro-NT during follow-up and if baseline Pro-NT predicted weight loss.

Methods

Immigrants from the Middle East at high risk for type 2 diabetes were invited to participate in this RCT adapted lifestyle intervention of four months’ duration. The intervention group (N = 48) received a culturally adapted lifestyle intervention comprising seven group sessions and a cooking class addressing healthier diet and increased physical activity. The control group (N = 44) received treatment as usual with information to improve lifestyle habits on their own. Data assessed using mixed effects regression.

Outcomes

Primary outcome; change in Pro-NT. Secondary outcome; change in BMI in relation to baseline plasma concentration of Pro-NT.

Results

During the four months follow up, weight was significantly reduced in the intervention (-2.5 kg) compared to the control group (0.8 kg) (β -0.12, 95% CI -0.24 to -0.01, P = 0.028). Pro-NT increased to a significantly greater extent in the intervention compared to the control group during follow up (28.2 vs. 3.5 pmol/L) (β 11.4; 4.8 to 18.02, P < 0.001). Change over time in BMI was associated with baseline Pro-NT (β 0.02; 0.01 to 0.04, P = 0.041).

Conclusion

In consistence with data from surgical weight loss, this RCT paradoxically shows increased levels of Pro-NT during a multifactorial lifestyle intervention resulting in weight loss. Long term studies of Pro-NT following weight loss are needed.

Trial registration

This study is a secondary analysis of the RCT trial registered at www.clinicaltrials.gov. Registration number: NCT01420198. Date of registration 19/08/2011. The performance and results of this trial conform to the CONSORT 2010 guidelines.
Preserved ratio impaired spirometry is associated with small airway dysfunction and reduced total lung capacity
Authors: Zhao Ningning , Wu Fan , Peng Jieqi , Zheng Youlan , Tian Heshen , Yang Huajing , Deng Zhishan , Wang Zihui , Li Haiqing , Wen Xiang , Xiao Shan , Huang Peiyu , Dai Cuiqiong , Lu Lifei , Zhou Kunning , Chen Shengtang , Zhou Yumin , Ran Pixin
Published: October 2022

Background:

Preserved ratio impaired spirometry (PRISm) refers to decreased forced expiratory volume in 1 s (FEV1) in the setting of preserved ratio. Little is known about the role of PRISm and its complex relation with small airway dysfunction (SAD) and lung volume. Therefore, we aimed to investigate the associations between PRISm and SAD and lung volume.

Methods:

We conducted a cross-sectional community-dwelling study in China. Demographic data, standard respiratory epidemiology questionnaire, spirometry, impulse oscillometry (IOS) and computed tomography (CT) data were collected. PRISm was defined as post-bronchodilator FEV1/FVC ≥ 0.70 and FEV1 < 80% predicted. Spirometry-defined SAD was defined as at least two of three of the post-bronchodilator maximal mid-expiratory flow (MMEF), forced expiratory flow 50% (FEF50), and forced expiratory flow 75% (FEF75) less than 65% of predicted. IOS-defined SAD and CT-defined gas trapping were defined by the fact that the cutoff value of peripheral airway resistance R5–R20 > 0.07 kPa/L/s and LAA− 856>20%, respectively. Analysis of covariance and logistic regression were used to determine associations between PRISm and SAD and lung volume. We then repeated the analysis with a lower limit of normal definition of spirometry criteria and FVC definition of PRISm. Moreover, we also performed subgroup analyses in ever smoker, never smoker, subjects without airway reversibility or self-reported diagnosed asthma, and subjects with CT-measured total lung capacity ≥70% of predicted.

Results:

The final analysis included 1439 subjects. PRISm had higher odds and more severity in spirometry-defined SAD (pre-bronchodilator: odds ratio [OR]: 5.99, 95% confidence interval [95%CI]: 3.87–9.27, P < 0.001; post-bronchodilator: OR: 14.05, 95%CI: 8.88–22.24, P < 0.001), IOS-defined SAD (OR: 2.89, 95%CI: 1.82–4.58, P < 0.001), and CT-air trapping (OR: 2.01, 95%CI: 1.08–3.72, P = 0.027) compared with healthy control after adjustment for confounding factors. CT-measured total lung capacity in PRISm was lower than that in healthy controls (4.15 ± 0.98 vs. 4.78 ± 1.05 L, P < 0.05), after adjustment. These results were robust in repeating analyses and subgroup analyses.

Conclusion:

Our finding revealed that PRISm was associated with SAD and reduced total lung capacity. Future studies to identify the underlying mechanisms and longitudinal progression of PRISm are warranted.
Predicting the risk of chest radiograph abnormality 12-weeks post hospitalisation with SARS CoV-2 PCR confirmed COVID-19
Authors: Wallis Tim JM , Welham Benjamin , Kong Alex , Morelli Tommaso , Azim Adnan , Horno Jose , Wilkinson Miranda , Burke Hannah , Freeman Anna , Wilkinson Thomas MA , Jones Mark G , Marshall Benjamin G
Published: October 2022

Background

Routine follow-up of patients hospitalised with COVID-19 is recommended, however due to the ongoing high number of infections this is not without significant health resource and economic burden. In a previous study we investigated the prevalence of, and risk factors for, persistent chest radiograph (CXR) abnormalities post-hospitalisation with COVID-19 and identified a 5-point composite score that strongly predicted risk of persistent CXR abnormality at 12-weeks. Here we sought to validate and refine our findings in an independent cohort of patients.

Methodology

A single-centre prospective study of consecutive patients attending a virtual post-hospitalisation COVID-19 clinic and CXR as part of their standard clinical care between 2nd March – 22nd June 2021. Inpatient and follow-up CXRs were scored by the assessing clinician for extent of pulmonary infiltrates (0–4 in each lung) with complete resolution defined as a follow-up score of zero.

Results

182 consecutive patients were identified of which 31% had persistent CXR abnormality at 12-weeks. Patients with persistent CXR abnormality were significantly older (p < 0.001), had a longer hospital length of stay (p = 0.005), and had a higher incidence of both level 2 or 3 facility admission (level 2/3 care) (p = 0.003) and ever-smoking history (p = 0.038). Testing our composite score in the present cohort we found it predicted persistent CXR abnormality with reasonable accuracy (area under the receiver operator curve [AUROC 0.64]). Refining this score replacing obesity with Age ≥ 50 years, we identify the SHADE-750 score (1-point each for; Smoking history, Higher-level care (level 2/3 admission), Age ≥ 50 years, Duration of admission ≥ 15 days and Enzyme-lactate dehydrogenase (LDH ≥ 750U/L), that accurately predicted risk of persistent CXR abnormality, both in the present cohort (AUROC 0.73) and when retrospectively applied to our 1st cohort (AUROC 0.79). Applied to both cohorts combined (n = 213) it again performed strongly (AUROC 0.75) with all patients with a score of zero (n = 18) having complete CXR resolution at 12-weeks.

Conclusions

In two independent cohorts of patients hospitalised with COVID-19, we identify a 5-point score which accurately predicts patients at risk of persistent CXR abnormality at 12-weeks. This tool could be used by clinicians to identify patients in which radiological follow-up may not be required.
Network evaluation of an innovation platform in continuous quality improvement in Australian Indigenous primary healthcare
Authors: Cunningham Frances Clare , Potts Boyd Alexander , Ramanathan Shanthi Ann , Bailie Jodie , Bainbridge Roxanne Gwendalyn , Searles Andrew , Laycock Alison Frances , Bailie Ross Stewart
Published: October 2022

Background

From 2014 to 2019, the Centre for Research Excellence in Integrated Quality Improvement (CRE-IQI) was evaluated as an innovation platform focusing on continuous quality improvement in Indigenous Australian primary healthcare. Although social network analysis (SNA) is a recognized method for evaluating the functioning, collaboration and effectiveness of innovation platforms, applied research is limited. This study applies SNA to evaluate the CRE-IQI’s functioning as an innovation platform.

Methods

Two surveys (2017, 2019) were conducted using social survey and network methods. Survey items covered respondent characteristics, their perceptions of the CRE-IQI’s performance, and its impact and sociometric relationships. Members’ relationship information was captured for the CRE-IQI at three time points, namely start (retrospectively), midpoint and final year, on three network types (knew, shared information, collaborated). SNA software was used to compute standard network metrics including diameter, density and centrality, and to develop visualizations. Survey and network results were addressed in a workshop held by members to develop improvement strategies.

Results

The response rate was 80% in 2017 and 65% in 2019 (n = 49 and 47, respectively). Between 2017 and 2019, respondents’ mean ratings of the CRE-IQI’s functioning and achievements in meeting its goals were sustained. They perceived the CRE-IQI as multidisciplinary, having effective management and governance, and incorporating Indigenous research leadership, representation and ways of working. Respondents recognized high levels of trust amongst members, rated “good communication and coordination with participants” highly, and “facilitating collaboration” as the CRE’s most strongly recognized achievement. In collaboration and information-sharing networks, average path length remained low in 2017 and 2019, indicating good small-world network properties for relaying information. On average, respondents shared information and collaborated with more CRE members in 2017 than 2019. However, in both 2017 and 2019 there were new collaborations and information-sharing outside of direct collaborations. CRE-IQI outcomes included: evidence generation; knowledge transfer and skills development in quality improvement; research capacity-building, career development; mentoring; grant support; development of new projects; health service support; and policy impact.

Conclusions

This study shows the utility of network analysis in evaluating the functioning, and collaboration, at the individual, organizational and health system levels, of an innovation platform, and adds to our understanding of factors enabling successful innovation platforms.
Steroid receptor coactivator-3 inhibition generates breast cancer antitumor immune microenvironment
Authors: Han Sang Jun , Sung Nuri , Wang Jin , O’Malley Bert W. , Lonard David M.
Published: October 2022

Background

The tumor immune microenvironment (TIME) generated by cancer-infiltrating immune cells has a crucial role in promoting or suppressing breast cancer progression. However, whether the steroid receptor coactivator-3 (SRC-3) modulates TIME to progress breast cancer is unclear. Therefore, the present study evaluates whether SRC-3 generates a tumor-promoting TIME in breast tumors using a syngeneic immune-intact mouse model of breast cancer.

Methods

We employed E0771 and 4T1 breast cancer in immune-intact syngeneic female C57BL/6 and BALB/c mice, respectively. SI-2, a specific small-molecule inhibitor of SRC-3, was administered daily (2.5 mg/kg) to E0771 and 4T1 breast tumor-bearing immune-intact mice. In addition, SRC-3 knockdown (KD)-E0771 and SRC-3 KD-4T1 cells and their parental breast cancer cells were injected into their syngeneic immune-intact female mice versus immune-deficiency mice to validate that the host immune system is required for breast tumor suppression by SRC-3 KD in immune-intact mice. Furthermore, tumor-infiltrating immune cells (such as CD4+, CD8+, CD56+, and Foxp3+ cells) in E0771 and 4T1 breast cancers treated with SI-2 and in SRC-3 KD E0771 and 4T1 breast cancers were determined by immunohistochemistry. Additionally, cytokine levels in SI-2-treated and SRC-3 KD E0771 breast tumors and their control cancers were defined with a Mouse Cytokine Array.

Results

SRC-3 inhibition by SI-2 significantly suppressed the progression of breast cancer cells (E0771 and 4T1) into breast cancers in immune-intact syngeneic female mice. SRC-3 KD-E0771 and -4T1 breast cancer cells did not produce well-developed tumors in immune-intact syngeneic female mice compared to their parental cells, but SRC-3 KD breast cancers were well developed in immune-defective host mice. SRC-3 inhibition by SI-2 and SRC-3 KD effectively increased the numbers of cytotoxic immune cells, such as CD4+ and CD8+ T cells and CD56+ NK cells, and Interferon γ (Ifng) in breast cancers compared to vehicle. However, SI-2 treatment reduced the number of tumor-infiltrating CD4+/Foxp3+ regulatory T (Treg) cells compared to vehicle treatment. In addition, SRC-3 inhibition by SI-2 and SRC-3 KD increased C-X-C motif chemokine ligand 9 (Cxcl9) expression in breast cancer to recruit C-X-C motif chemokine receptor 3 (Cxcr3)-expressing cytotoxic immune cells into breast tumors.

Conclusions

SRC-3 is a critical immunomodulator in breast cancer, generating a protumor immune microenvironment. SRC-3 inhibition by SI-2 or SRC-3 KD activates the Cxcl9/Cxcr3 axis in breast tumors and enhances the antitumor immune microenvironment to suppress breast cancer progression.
Efficacy of domperidone plus renal diet in slowing the progression of chronic kidney disease in dogs with leishmaniosis
Authors: Cavalera Maria Alfonsa , Gernone Floriana , Uva Annamaria , Donghia Rossella , Zizzadoro Claudia , Zatelli Andrea
Published: October 2022

Background

Chronic kidney disease (CKD) represents the main cause of mortality in dogs with leishmaniosis. Domperidone has recently been reported to improve kidney function in leishmaniotic dogs affected by CKD. Serum symmetric dimethylarginine (sSDMA) has also been shown to be a useful biomarker for earlier detection of decreased kidney function when compared to serum creatinine (sCr). This study aimed to assess the efficacy of domperidone plus renal diet in slowing the progression of nephropathy in leishmaniotic dogs with CKD, evaluating sSDMA and sCr as markers of kidney function.

Methods

This study was a therapeutic, prospective, randomized, controlled, 11-month-long field trial. Dogs were recruited if classified as “exposed” to or “infected” with Leishmania infantum and affected by CKD at early stages. After enrolment (T0), dogs were randomized into groups T (treatment) and C (control). All dogs were fed a renal diet and then followed up at 90 (T1), 210 (T2), and 330 (T3) days after inclusion in the study. At T1 and T2, dogs in group T received an oral suspension of domperidone (1 ml/10 kg once a day for up to 28 days).

Results

Twenty-two dogs (i.e., n = 12 in group T and n = 10 in group C) completed the study. At T0, the entire population of enrolled dogs presented a mean sSDMA value of 16.5 ± 3.4 μg/dl. At T1 (i.e., after 3 months of renal diet), sSDMA was significantly decreased in both groups, with an sSDMA of 13.1 ± 4.4 μg/dl for the entire population involved. From T1 to T3, sSDMA gradually increased in group C, while remaining stable in group T, which continued to show a significantly lower value of sSDMA at T3 than at T0. Regarding sCr, at T0 and T1, the mean values of the entire population of dogs were 1.1 ± 0.3 and 1.0 ± 0.4 mg/dl, respectively, with no statistical differences between groups T and C. In group T, sCr decreased significantly from T0 to T1, while returning at T3 to values similar to T0.

Conclusions

In this study, domperidone plus renal diet reduced the progression of kidney disease in leishmaniotic dogs affected by CKD.

Graphical Abstract
Screening of GDM during COVID pandemic in an Italian setting: comparison between IADPSG and WHO ‘99 criteria
Authors: D’Anna Rosario , Di Benedetto Antonio , Palella Stefania , Miceli Alessia , Romeo Paola , Corrado Francesco
Published: October 2022

Background

During pandemic period, a single fast glycemia value (≥ 92 mg/dl) performed within the recommended time window for the risk level defined by the Italian guidelines, was considered an acceptable surrogate for GDM diagnosis following Italian Diabetes Association recomendations.

Methods

All pregnant women who performed an OGTT following Italian Guidelines from march 2020 to september 2021 and then delivered at our University Hospital were prospectively enrolled in this study. Primary outcome of the study was the number of women diagnosed with GDM with only the FPG value (≥ 92 mg/dl), following Italian Diabetes Societies recommendations for COVID 19 pandemic period. At the same time, the data of women who became diabetic according to the 1999 WHO criteria was collected too. The secondary outcome was the comparison of risk factors of women undergoing OGTT according to IADPSG and WHO’99 criteria for the diagnosis of GDM and associated clinical outcomes.

Results

The number of women with a diagnosis of GDM following Italian guidelines in the 18-month period considered was 161. Only 109 (67.7%) had a fast glucose value ≥ 92 mg/dl. No differences between IADPSG and WHO’99 groups in relation to risk factors, with the exception for overweight and obesity, and clinical outcomes.

Conclusion

Recommendations of Italian Diabetes Societis for COVID 19 pandemic failed to recognize one third of GDM diagnosis.

Clinical Trial Registration ClinicalTrials.gov, www.clinicaltrials.gov, NCT05026840, August 30, 2021, ‘retrospectively registered’.
Factors associated with a basic common drug-drug interaction knowledge among emergency department medical personnel
Authors: Tangsuwanaruk Theerapon , Wittayachamnankul Borwon
Published: October 2022

Background

Drug-drug interactions (DDIs) are common but less concerning in clinical practice of time-sensitive situations. We aimed to identify factors associated with a basic common DDI knowledge among an emergency physician (EP), an emergency medicine resident (EMR), and an emergency care nurse (ECN).

Methods

This was a prospective cross-sectional study. EP, EMR, and ECN did the examination (multiple-choice questions, 40 points) about common DDI. Prespecified factors associated with examination scores were profession, longer emergency medicine experience, pharmacological training, last advanced cardiovascular life support (ACLS) training, DDI checker book, and application user experience. The outcome was an examination score to evaluate the ability of DDI knowledge. Univariable and multivariable means regressions were used.

Results

A total of 244 participants were enrolled. Factors associated with high examination score were EP (unadjusted mean difference 3.3 points, 95% confidence interval [CI] 2.1 to 4.5, p < 0.001), EMR (2.1, 95% CI 0.7 to 3.5, p 0.005) compared to ECN. Last ACLS training within 2 years (3.7, 95% CI 0.7 to 6.6, p 0.015), 2–4 years (3.4, 95% CI 0.4 to 6.5, p 0.027), and ≥4 years (4.4, 95% CI 1.2 to 7.6, p 0.007) were higher score than no ACLS training. Moreover, the DDI checker application experience user (1.7, 95% CI 0.6 to 2.8, p 0.003) also had a high score compared to the non-experienced user. After adjustment for all factors, EP (adjusted mean difference 3.3 points, 95% CI 1.8 to 4.7, p < 0.001), EMR (2.5, 95% CI 0.6 to 4.3, p 0.010) were higher scores compared to ECN. Meanwhile, the last ACLS training ≥4 years (3.3, 95% CI 0.1 to 6.6, p 0.042) was a higher score than no ACLS training.

Conclusion

EP, EMR, and the last ACLS training ≥4 years were associated with higher DDI knowledge than ECN and no ACLS training, respectively.
A 3D-printed pneumatic dispenser with monitoring droplet ejection
Authors: Kang Dong Kwan , Park Jeong Woo , Lee Sangmin
Published: October 2022

In this study, a pneumatic dispenser driven by a flexible membrane with a capacitive-type sensor using an SLA-type 3D printer was fabricated. It was confirmed that a single droplet in the range of approximately 400–450 nL could be ejected from the current processed 200-μm-diameter nozzle. The deformation varied according to the magnitude and time of the positive pressure applied to the membrane sensor. In addition, the signals of the normal dispensing and abnormal states, in which the solution was not ejected when the inlet pressure was removed, were measured and compared. The base capacitance-to-digital converter (CDC) value decreased when the inlet pressure was removed. Thus, it was able to confirm the feasibility of monitoring the normal and abnormal ejection status of the pneumatic dispenser.
Low birth weight and its associated factors in East Gojjam Zone, Amhara, Ethiopia
Authors: Walle Birhanie Muluken , Adekunle Adeyemi O. , Arowojolu Ayodele O. , Dugul Tesfaye Tolessa , Mebiratie Akiloge Lake
Published: October 2022

Introduction

Low birth weight is a global public health problem, with 15–20% of all births globally, described by weight at birth of less than 2500 g ensuing fetal and neonatal mortality and morbidity, poor cognitive growth, and an increased risk of chronic diseases later in life. The prevalence is critical in East Africa where about 11% have low birth weight out of 54% of neonates whose weight was measured at birth. There are many causes of low birth weight, including early induction of labor or cesarean birth, multiple pregnancies, infections, diabetes, and high blood pressure. Moreover, socioeconomic factors and unhealthy dietary habits could contribute to low birth weight in areas with poor intake of a diversified diet. This study has indicated the association between poor dietary diversity and low birth weight in the study area for the first time.

Methods

An institutional-based cross-sectional study was conducted on eligible 423 pregnant women recruited from Gestational Age of less than 17 weeks until delivery where the birth outcomes were recorded in health institutions in randomly selected five Woredas in East Gojjam Zone, Amhara, Ethiopia from June 2019 to December 2020. Questionnaires were used to collect data on socio-economic-demographic, dietary diversity scores, and food consumption scores.

Results

The study found a prevalence of low birth weight of 9.6%, low dietary diversity score of 53.2%, low food consumption score of 19.7%, and preterm delivery of 9.1%. Ever attended school and a higher level of education (diploma and above) decreased the risk of low birth weight with an Adjusted Odds Ratio (AOR) of 0.149 (0.024, 0.973) P ≤ 0.042; 0.059 (0.007, 0.513) P ≤ 0.007; whereas low dietary diversity score group and low food consumption group increased the risk of low birth weight with AOR 2.425 (1.342, 6.192) P ≤ 0.011and 2.983 (1.956, 9.084) P ≤ 0.044 respectively.

Conclusion and recommendation

Participants with no formal education, no diploma, and above (no college or university training/degree), low diversity score group, and low food consumption group had an increased risk of low birth weight. Therefore the use of a diversified diet, educating women to a higher educational level, and health education on the intake of a diversified food rich in multiple micronutrients are recommended as strategies that will ameliorate the occurrence of low birth weight.
MAOA-uVNTR variations in schizophrenia: case and control study
Authors: Mardani Moghanaki Maral , Noormohammadi Zahra , Salahshourifar Iman , Mahdavi Hazaveh Niloufar
Published: October 2022

Background

Schizophrenia, a chronic mental disorder, has been recognized as one of the heritable diseases with an increased level of dopamine neurotransmitter. Monoamine oxidase A (MAOA) plays a vital role in the catabolism of dopamine. It is a mitochondrial enzyme which is encoded by the MAOA gene located on the X chromosome. The aim of this study was to detect potential biomarker in order to diagnose schizophrenia. Hence, the association of uVNTR repetitions of the MAOA gene and Schizophrenia was investigated.

Method

Blood samples were collected from 102 schizophrenic patients (67 males and 35 females), and 103 volunteers with mental health (65 males and 38 females). Genomic DNA was extracted and the uVNTR polymorphisms were examined using specific primed PCR.

Results

The analysis indicated that genotype 3/3repetition (rep) showed the highest frequency in females. While genotype 4 and 3.5 reps revealed the highest frequencies among schizophrenic patients and healthy controls in men, respectively. There were no significant statistical differences in the number of uVNTR repeats of the MAOA gene between control and case individuals neither in women (OR = 0.35, 95% CI = 0.60–1.43 P = 0.845) nor in men (OR = 0.36, 95% CI = 0.80–1.64, P = 0.365).

Conclusion

In the current study, the number of uVNTR sequence repetitions located in the promoter of the MAOA gene was not associated with the risk of schizophrenia in Iranian patients.
No serological evidence for neuronal damage or reactive gliosis in neuro-COVID-19 patients with long-term persistent headache
Authors: de Boni Laura , Odainic Alexandru , Gancarczyk Natalie , Kaluza Luisa , Strassburg Christian P. , Kersting Xenia A. K. , Johnson Joseph M. , Wüllner Ullrich , Schmidt Susanne V. , Nattermann Jacob , Petzold Gabor C.
Published: October 2022

Recent studies have indicated that long-term neurological sequelae after COVID-19 are not accompanied by an increase of canonical biomarkers of central nervous system injury in blood, but subgroup stratifications are lacking. This is a particular concern in chronic headache, which can be a leading symptom of Post-COVID diseases associated with neuronal damage such as vasculitis or autoimmune encephalitis. We here compared patients with mild Post-COVID-19 syndrome and persistent headache (persistent Post-COVID-19 headache) lasting longer than 12 weeks after the initial serological diagnosis, to patients with mild and severe COVID-19 and COVID-19-negative controls. Levels of neurofilament light chain and glial fibrillary astrocytic protein, i.e. markers of neuronal damage and reactive astrogliosis, were lower in blood from patients with persistent Post-COVID-19 headache compared to patients with severe COVID-19. Hence, our pilot serological study indicates that long-term Post-COVID-19 headache may not be a sign of underlying neuronal damage or neuroinflammation.
Portomesenteric venous thrombosis as a rare complication of acute appendicitis in pediatric patient: a case presentation and literature review
Authors: Lai Tsz Yan Nancy , Hung Judy WS , Leung Michael WY
Published: October 2022

Background

Appendicitis is one of the most common paediatric surgical emergencies, however complication with acute portomesenteric venous thrombosis is rare. Our aim is to report a case in our locality and review the clinical features and management of such rare complication.

Case presentation

A 12-year-old boy presented with a 5-day history of fever, periumbilical and right lower quadrant abdominal pain, blood-stained diarrhea and vomiting. Physical examination showed tenderness and guarding over right upper quadrant. Laboratory tests showed elevated inflammatory markers and deranged liver function. Contrast computed tomography scan showed acute appendicitis and superior mesenteric vein thrombosis. Our patient was treated with laparoscopic appendicectomy, antibiotics, and anticoagulant, with gradual improvement of thrombus observed.

Conclusion

Our patient and seventeen pediatric case reports regarding the condition since 1990 were included. Atypical presenting symptoms were noted, including RUQ pain (n = 10, 56%), diarrhea (n = 8, 44%), fever (n = 16, 89%), deranged liver function (n = 13, 72%). Patient presenting with RLQ pain were only seen in 22% (n = 4). Diagnosis was made by USG (n = 1, 5%) and computer tomography (n = 15, 83%). Surgical intervention includes early (n = 9, 50%) or interval (n = 4, 22%) laparoscopic or open appendicectomy, laparotomy etc. The most common causative organisms were Escherichiae coli and Bacteroides fragilis. Anticoagulant use and its duration remained controversial. Anticoagulant was used in 14 patients with a mean treatment duration of 7 months, while 4 cases reporting resolution of thrombus without anticoagulant use. A high index of suspicion is needed to diagnose patient with acute appendicitis complicated by portomesenteric thrombosis.
Diversity in mitotic DNA repair efficiencies between commercial inbred maize lines and native Central American purple landraces
Authors: Víquez-Zamora Carlos , Castro-Pacheco Sergio , Viñas María , Bolaños-Villegas Pablo
Published: October 2022

Background

Homologous recombination allows plants to repair double strand breaks in DNA, which if unrepaired may lead to cell death. In this project, we determined the relative DNA repair efficiency of the US inbred lines B73 and Mo17 and Central American purple landraces from Guatemala and Costa Rica with the purpose to uncover genetic differences that may allow for the breeding of new lines better adapted to tolerate DNA damage caused by environmental factors.

Methods

Single cell electrophoresis was used to analyze the relative DNA repair ability of several lines from the US and Central America exposed to radiomimetic agent Zeocin, and these results were in turn compared with High Resolution Melting analyses of key genes for homologous DNA recombination. The significance of differences between treatments was evaluated with the Di Rienzo, Guzmán and Casanoves (DGC) test, while High Resolution Melting and difference curves were generated with the R package “HRM.curve”. Curves were created as a negative first derivative (−d(RFU)/d(T)) using normalized relative fluorescence values (RFUs) after background removal. The kinase geneZeaATM1was amplified and sequenced in B73, Mo17, P1 and P2. Multiple sequence alignment of DNA and aminoacid sequences was performed using ClustalW. Protein sequence analysis was done in UniProt to compare the resulting aminoacid sequences from maize to the available sequences fromArabidopsis thalianaecotype Col-0 (ATM protein code: Q9M3G7).

Results

Single-cell electrophoresis results of statistical significance suggested that the landrace P1-Pujagua Santa Cruz is resistant to damage caused by the radiomimetic agent Zeocin, and landrace P2-Pujagua La Cruz was able to repair all DNA damage after 24 h of treatment and 1 h of recovery time. In contrast, line Mo17 was unable to repair the damage, but B73 and the landraces Jocopilas (Guatemalan), Orotina Congo, and Talamanca were partially able to repair the DNA damage. High resolution melting analysis of the putative homologous DNA repair geneZeaATM1revealed that landraces P1 and P2 may harbor polymorphisms for this gene, and P1 may harbor other polymorphisms for the transcription factorZeaSOG1as well as the tumor suppressorZeaRAD51and recombinaseZeaBRCA1. The kinase geneZeaATM1was sequenced, and results indicate that in lines P1 and P2 there are polymorphisms near and within the FATC domain, a domain required for the activation of ATM1-mediated repair of DNA damage.

Conclusions

Significant differences in DNA repair efficiency exist between inbred lines and landraces of maize and may be linked to allelic diversity in key genes for homologous recombination. Thus, Central American landraces could be used for breeding tolerance to genotoxic stress.