Conectar
by Oluwafemi Adeleke Ojo, Akingbolabo Daniel Ogunlakin, Christopher Oloruntoba Akintayo, Olaoluwa Sesan Olukiran, Juliana Bunmi Adetunji, Omolola Adenike Ajayi-Odoko, Theophilus Oghenenyoreme Ogwa, Olorunfemi Raphael Molehin, Omolara Olajumoke Ojo, Ramzi A. Mothana, Abdullah R. Alanzi
Background and objectiveDiabetic neuropathy (DN) is a complex type of diabetes. The underlying cause of diabetic nephropathy remains unclear and may be due to a variety of pathological conditions resulting in kidney failure. This study examines the protective effect of the methanolic extract of Spilanthes filicaulis leaves (MESFL) in fructose-fed streptozotocin (STZ)-induced diabetic nephropathy and the associated pathway.
MethodsTwenty-five rats were equally divided randomly into five categories: Control (C), diabetic control, diabetic + metformin (100 mg/kg), diabetic + MESFL 150 mg/kg bw, and diabetic + MESFL 300 mg/kg bw. After 15 days, the rats were evaluated for fasting blood glucose (FBG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea, uric acid, serum creatinine, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (MDA). Gene expression levels of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response element-binding (CREB), cFOS and the antiapoptotic protein Bcl-2 were examined.
ResultsWe observed that MESFL at 150 and 300 mg/kg bw significantly downregulated the protein expression of cAMP, PKA, CREB, and cFOS and upregulated the Bcl-2 gene, suggesting that the nephroprotective action of MESFL is due to the suppression of the cAMP/PKA/CREB/cFOS signaling pathway. In addition, MESFL increases SOD and CAT activities and GSH levels, reduces MDA levels, and reduces renal functional indices (ALP, urea, uric acid, and creatinine).
ConclusionTherefore, our results indicate that MESFL alleviates the development of diabetic nephropathy via suppression of the cAMP/PKA/CREB/cFOS pathways.
Between 2009/2010 and 2019/2020, England witnessed an increase in suspected head and neck cancer (sHNC) referrals from 140 to 404 patients per 100 000 population. 1 in 10 patients are not seen within the 2-week target, contributing to patient anxiety. We will develop a pathway for sHNC referrals, based on the Head and Neck Cancer Risk Calculator. The evolution of a patient-reported symptom-based risk stratification system to redesign the sHNC referral pathway (EVEREST-HN) Programme comprises six work packages (WPs). This protocol describes WP1 and WP2. WP1 will obtain an understanding of language to optimise the SYmptom iNput Clinical (SYNC) system patient-reported symptom questionnaire for sHNC referrals and outline requirements for the SYNC system. WP2 will codesign key elements of the SYNC system, including the SYNC Questionnaire, and accompanying behaviour change materials.
WP1 will be conducted at three acute National Health Service (NHS) trusts with variation in service delivery models and ensuring a broad mixture of social, economic and cultural backgrounds of participants. Up to 150 patients with sHNC (n=50 per site) and 15 clinicians (n=5 per site) will be recruited. WP1 will use qualitative methods including interviews, observation and recordings of consultations. Rapid qualitative analysis and inductive thematic analysis will be used to analyse the data. WP2 will recruit lay patient representatives to participate in online focus groups (n=8 per focus group), think-aloud technique and experience-based codesign and will be analysed using qualitative and quantitative approaches.
The committee for clinical research at The Royal Marsden, a research ethics committee and the Health Research Authority approved this protocol. All participants will give informed consent. Ethical issues of working with patients on an urgent cancer diagnostic pathway have been considered. Findings will be disseminated via journal publications, conference presentations and public engagement activities.
Newborn bloodspot screening (NBS) is a highly successful public health programme that uses biochemical and other assays to screen for severe but treatable childhood-onset conditions. Introducing genomic sequencing into NBS programmes increases the range of detectable conditions but raises practical and ethical issues. Evidence from prospectively ascertained cohorts is required to guide policy and future implementation. This study aims to develop, implement and evaluate a genomic NBS (gNBS) pilot programme.
The BabyScreen+ study will pilot gNBS in three phases. In the preimplementation phase, study materials, including education resources, decision support and data collection tools, will be designed. Focus groups and key informant interviews will also be undertaken to inform delivery of the study and future gNBS programmes. During the implementation phase, we will prospectively recruit birth parents in Victoria, Australia, to screen 1000 newborns for over 600 severe, treatable, childhood-onset conditions. Clinically accredited whole genome sequencing will be performed following standard NBS using the same sample. High chance results will be returned by genetic healthcare professionals, with follow-on genetic and other confirmatory testing and referral to specialist services as required. The postimplementation phase will evaluate the feasibility of gNBS as the primary aim, and assess ethical, implementation, psychosocial and health economic factors to inform future service delivery.
This project received ethics approval from the Royal Children’s Hospital Melbourne Research Ethics Committee: HREC/91500/RCHM-2023, HREC/90929/RCHM-2022 and HREC/91392/RCHM-2022. Findings will be disseminated to policy-makers, and through peer-reviewed journals and conferences.
by Alvaro Torres-Huerta, Katelyn Ruley-Haase, Theodore Reed, Antonia Boger-May, Derek Rubadeux, Lauren Mayer, Arpitha Mysore Rajashekara, Morgan Hiller, Madeleine Frech, Connor Roncagli, Cameron Pedersen, Mary Catherine Camacho, Lauren Hollmer, Lauren English, Grace Kane, David L. Boone
Inflammatory bowel diseases (IBD) result from uncontrolled inflammation in the intestinal mucosa leading to damage and loss of function. Both innate and adaptive immunity contribute to the inflammation of IBD and innate and adaptive immune cells reciprocally activate each other in a forward feedback loop. In order to better understand innate immune contributions to IBD, we developed a model of spontaneous 100% penetrant, early onset colitis that occurs in the absence of adaptive immunity by crossing villin-TNFAIP3 mice to RAG1-/- mice (TRAG mice). This model is driven by microbes and features increased levels of innate lymphoid cells in the intestinal mucosa. To investigate the role of type 3 innate lymphoid cells (ILC3) in the innate colitis of TRAG mice, we crossed them to retinoid orphan receptor gamma t deficient (Rorγt-/-) mice. Rorγt-/- x TRAG mice exhibited markedly reduced eosinophilia in the colonic mucosa, but colitis persisted in these mice. Colitis in Rorγt-/- x TRAG mice was characterized by increased infiltration of the intestinal mucosa by neutrophils, inflammatory monocytes, macrophages and other innate cells. RNA and cellular profiles of Rorγt-/- x TRAG mice were consistent with a lack of ILC3 and ILC3 derived cytokines, reduced antimicrobial factors, increased activation oof epithelial repair processes and reduced activation of epithelial cell STAT3. The colitis in Rorγt-/- x TRAG mice was ameliorated by antibiotic treatment indicating that microbes contribute to the ILC3-independent colitis of these mice. Together, these gene expression and cell signaling signatures reflect the double-edged sword of ILC3 in the intestine, inducing both proinflammatory and antimicrobial protective responses. Thus, Rorγt promotes eosinophilia but Rorγt and Rorγt-dependent ILC3 are dispensable for the innate colitis in TRAG mice.To evaluate registered nurses' beliefs and related factors regarding pain assessment in people living with dementia.
A descriptive cross-sectional survey was conducted between July 2022 and April 2023.
An online survey comprised of demographics, knowledge scale, and beliefs scale relating to pain assessment in dementia was distributed to registered nurses (RNs) caring for people living with dementia in Australia.
RNs (N = 131) completed the survey. Most respondents were females (87.0%) and self-identified as Caucasian (60.3%). The mean beliefs score was 72.60 (±6.39) out of a maximum possible score of 95. RNs' beliefs about pain assessment varied based on their education, dementia pain assessment knowledge, nursing experience, and ethnicity. Hierarchical multiple regression analysis revealed factors significantly related to the beliefs score (i.e. education and dementia pain assessment knowledge).
The relationship between education and knowledge, and the beliefs score indicates the potential to improve RNs' knowledge and overcome their erroneous beliefs about pain assessment in dementia.
Education and training in assessing pain in people living with dementia should be tailored to overcome RNs' misconceived beliefs. These programmes should be integrated into continuous learning programmes.
Some RNs' beliefs about pain assessment in dementia were not evidence-based, and knowledge and educational status were the strongest factors related to RNs' beliefs. RNs' erroneous beliefs about pain assessment in dementia need to be addressed to improve pain assessment and management. Researchers should explore the potential of educational interventions to overcome RNs' misconceived beliefs about pain assessment in dementia.
This study was reported adhering to the Strengthening the Reporting of Observational Studies in Epidemiology checklist.
RNs caring for people living with dementia participated as survey respondents. Additionally, RNs were involved in the pre-testing of the study's survey instrument.
Neoadjuvant chemoimmunotherapy is becoming an increasingly important part of the management of lung cancer to facilitate surgical resection. This study aimed to summarize the treatment-related adverse events (TRAEs) and wound complications of neoadjuvant chemoimmunotherapy in non-small cell lung cancer (NSCLC). Eligible studies of neoadjuvant chemoimmunotherapy for NSCLC were identified from PubMed, Embase and Web of Science. The endpoints mainly included TRAEs and wound complications. Stata18 software was used for statistical analysis with p < 0.05 considered statistically significant. Twenty studies including a total of 1072 patients were eligible for this study. Among the patients who received neoadjuvant chemoimmunotherapy, the pooled prevalence of any grade TRAEs was 77% (95% confidence interval [CI] [0.64–0.86]), grade 1–2 TRAEs was 77% (95% CI [0.58–0.89]) and grade ≥3 TRAEs was 26% (95% CI [0.16–0.38]). Surgery-related complications rate was 22% (95% CI [0.14–0.33]). Among the wound complications, the pooled rate of air leakage was 10% (95% CI [0.04–0.23]), pulmonary/wound infection was 8% (95% CI [0.05–0.13]), bronchopleural fistula was 8% (95% CI [0.02–0.27]), bronchopulmonary haemorrhage was 3% (95% CI [0.01–0.05]), pneumonia was 5% (95% CI [0.02–0.10]), pulmonary embolism was 1% (95% CI [0.01–0.03]), pleural effusion was 7% (95% CI [0.03–0.14]) and chylothorax was 4% (95% CI [0.02–0.09]). Overall, neoadjuvant chemoimmunotherapy in NSCLC results a high incidence of grade 1–2 TRAEs but a low risk of increasing the incidence of ≥3 grade TRAEs and wound complications. These results need to be confirmed by more large-scale prospective randomized controlled trials and studies.
To explore perceptions and attitudes of African immigrants (Ghanaians, Nigerians, Liberians, and Sierra Leoneans) in the Baltimore-Washington, DC, metropolitan area toward cardiovascular health.
This was a qualitative study among African immigrants recruited from religious and community-based organizations in the Baltimore-Washington metro area. A purposive sample of 66 African immigrants originally from Ghana, Nigeria, Liberia, and Sierra Leone completed a sociodemographic survey and participated in focus group discussions. Focus group data were analysed using qualitative description to develop emergent themes.
A total of 66 African immigrants with a mean (±standard deviation) age of 51 (±11.8) years participated in the focus group discussions. Fifty percent were women, 91% had at least a bachelor's degree, 84% were employed, 80% had health insurance, and 75% were married/cohabitating. The majority of the participants (74%) had lived in the US for 10 years or more, 44% of them had hypertension, and 12% had diabetes. Findings from the focus group discussions revealed: gender differences in descriptions of cardiovascular health and healthiness, an emotional response associated with cardiovascular disease (evoking fear and anxiety and associated with family secrecy), positive and negative lifestyle changes after migration, cardiovascular screening behaviours, and facilitators and barriers to cardiovascular disease prevention practices and heart-healthy lifestyle.
Participants understood health to be a holistic state of well-being. Secrecy in disclosing their cardiovascular disease diagnoses informed by historical socio-cultural belief systems, perceived racial discrimination by healthcare providers, communication and health literacy barriers, economic barriers of holding multiple jobs and the exorbitant cost of heart-healthy foods were identified as some barriers to achieving optimal cardiovascular health in this immigrant population.
Our study expanded on the body of knowledge on African immigrants' perceptions and attitudes toward cardiovascular health. Addressing this knowledge gap will provide important intervention opportunities targeted at improving cardiovascular health outcomes in this population.
No patient or public contribution.
To assess the effect of an integrated intervention package compared with routine government health services on the frequency of health facility births.
Three subcounties of Lira district in Northern Uganda.
A cluster randomised controlled trial where a total of 30 clusters were randomised in a ratio of 1:1 to intervention or standard of care.
Pregnant women at ≥28 weeks of gestation.
Participants in the intervention arm received an integrated intervention package of peer support, mobile phone messaging and birthing kits during pregnancy while those in the control arm received routine government health services (‘standard of care’).
The primary outcome was the proportion of women giving birth at a health facility in the intervention arm compared with the control arm. Secondary outcomes were perinatal and neonatal deaths.
In 2018–2019, 995 pregnant women were included in 15 intervention clusters and 882 in 15 control clusters. The primary outcome was ascertained for all except one participant who died before childbirth. In the intervention arm, 754/994 participants (76%) gave birth at a health facility compared with 500/882 (57%) in the control arm. Participants in the intervention arm were 35% more likely to give birth at a health facility compared with participants in the control arm, (risk ratio 1.35 (95% CI 1.20 to 1.51)) and (risk difference 0.20 (95% CI 0.13 to 0.27)). Adjusting for baseline differences generated similar results. There was no difference in secondary outcomes (perinatal or neonatal mortality or number of postnatal visits) between arms.
The intervention was successful in increasing the proportion of facility-based births but did not reduce perinatal or neonatal mortality.
To identify specific facial expressions associated with pain behaviors using the PainChek application in residents with dementia.
This is a secondary analysis from a study exploring the feasibility of PainChek to evaluate the effectiveness of a social robot (PARO) intervention on pain for residents with dementia from June to November 2021.
Participants experienced PARO individually five days per week for 15 min (once or twice) per day for three consecutive weeks. The PainChek app assessed each resident's pain levels before and after each session. The association between nine facial expressions and the adjusted PainChek scores was analyzed using a linear mixed model.
A total of 1820 assessments were completed with 46 residents. Six facial expressions were significantly associated with a higher adjusted PainChek score. Horizontal mouth stretch showed the strongest association with the score, followed by brow lowering parting lips, wrinkling of the nose, raising of the upper lip and closing eyes. However, the presence of cheek raising, tightening of eyelids and pulling at the corner lip were not significantly associated with the score. Limitations of using the PainChek app were identified.
Six specific facial expressions were associated with observational pain scores in residents with dementia. Results indicate that automated real-time facial analysis is a promising approach to assessing pain in people with dementia. However, it requires further validation by human observers before it can be used for decision-making in clinical practice.
Pain is common in people with dementia, while assessing pain is challenging in this group. This study generated new evidence of facial expressions of pain in residents with dementia. Results will inform the development of valid artificial intelligence-based algorithms that will support healthcare professionals in identifying pain in people with dementia in clinical situations.
The study adheres to the CONSORT reporting guidelines.
One resident with dementia and two family members of people with dementia were consulted and involved in the study design, where they provided advice on the protocol, information sheets and consent forms, and offered valuable insights to ensure research quality and relevance.
Australian and New Zealand Clinical Trials Registry number (ACTRN12621000837820).
No abstract available This study aimed to examine (a) changes in coping strategies and vicarious post-traumatic growth (VPTG) across three timepoints of the COVID-19 pandemic among nurses; (b) discrete groups of nurses with unique coping profiles and (c) the association of these coping profiles with VPTG across the timepoints.
Although literature abounds with the negative mental health consequences of the pandemic among healthcare professionals, much less is known about the positive consequences on nurses, the coping strategies that they use, and how these change over time.
This was a cross-sectional web-based survey at three timepoints during the pandemic.
A sample of 429 nurses completed online the Post-Traumatic Growth Inventory (PTGI) and the Brief Coping Orientation to Problems Experienced Inventory (COPE) to measure vicarious post-traumatic growth (VPTG) and coping strategies, respectively. The STROBE checklist was used to report the present study.
Significantly higher VPTG scores were observed during the third timepoint. Different coping strategies were employed across the three timepoints. Nurses responded to the pandemic either with an active, an avoidant or a passive coping profile. Significantly higher VPTG levels were reported by the nurses of the active profile compared to those of the passive profile, whereas the difference between active and avoidant profiles was not significant.
Notwithstanding the preponderance of the nurses with the active coping profile in achieving high VPTG, the avoidant copers had more gains (VPTG) than the passive copers, suggesting that doing something to cope with the stressor—let it be trying to avoid it—was better than doing nothing.
The identification of distinct coping profiles among nurses and their association with VPTG is of particular use to policymakers and practitioners in developing tailored prevention and intervention efforts to help the nurses effectively manage the demands of the pandemic.
No patient or public contribution since the study was exclusively conducted by the authors.
To measure coping strategies and associated psychological distress, burnout and work ability in hospital doctors in Ireland.
National cross-sectional study of randomised sample of trainee and consultant hospital doctors.
Irish publicly funded hospitals and residential institutions.
1749 doctors returned surveys (55% response rate).
Dependent variables were psychological distress (measured using 12-item General Health Questionnaire), burnout (Maslach Burnout Inventory) and work ability (single-item measure). Adaptive and maladaptive coping strategies (Brief Coping Orientation to Problems Experienced) were covariates.
The coping mechanism most frequently reported by this cohort was the adaptive strategy of active planning. Increased mean hours worked (MHW) (OR 1.02; 95% CI 1.01 to 1.03), a low Work Ability Score (OR 3.23; 95% CI 2.47 to 4.23) and maladaptive coping strategies (OR 1.26; 95% CI 1.22 to 1.31) were significantly associated with psychological distress. Adaptive coping was associated with decreased psychological distress (OR 0.98; 95% CI 0.97 to 1.00). Increased MHW (OR 0.98; 95% CI 0.97 to 0.99), insufficient work ability (OR 0.62; 95% CI 0.48 to 0.80) and maladaptive coping (OR 0.87; 95% CI 0.85 to 0.89) were significantly associated with burnout. Increased MHW (OR 0.99; 95% CI 0.98 to 1.00) and maladaptive coping (OR 0.90, 95% CI 0.88 to 0.92) were significantly associated with insufficient work ability.
Adaptive coping is associated with decreased psychological distress but does not mitigate the effect of increased work hours, which are associated with burnout, distress and insufficient work ability, regardless of a doctor’s coping style. The burden of psychological distress on doctors cannot be mitigated meaningfully unless workplace factors are addressed.
To identify how family caregivers adapt to the caregiving role following a relative's COVID-19-related intensive care unit (ICU) hospitalisation.
Family caregiving is often associated with poor health amongst caregivers which may limit their capacity to effectively support patients. Though severe COVID-19 infection has necessitated increasing numbers of persons who require caregiver support, little is known about these caregivers, the persons they are caring for, or the strategies used to effectively adjust to the caregiving role.
A qualitative descriptive study design was adopted, and findings are reported using COREQ.
A secondary analysis of transcripts from semi-structured interviews conducted with recently discharged ICU patients who had COVID-19 (n = 16) and their family caregivers (n = 16) was completed using thematic analysis. MAXQDA 2020 and Miro were used to organise data and complete coding. Analysis involved a structured process of open and closed coding to identify and confirm themes that elucidated adaptation to family caregiving.
Six themes highlight how family caregivers adapt to the caregiving role following an ICU COVID-19-related hospitalisation including (1) engaging the support of family and friends, (2) increased responsibilities to accommodate caregiving, (3) managing emotions, (4) managing infection control, (5) addressing patient independence and (6) engaging support services. These themes were found to be congruent with the Roy adaptation model.
Family caregiving is a stressful transition following a patient's acute hospitalisation. Effective adaptation requires flexibility and sufficient support, beginning with the care team who can adequately prepare the family for the anticipated challenges of recovery.
Clinical teams may improve post-hospitalisation care outcomes of patients by preparing families to effectively adjust to the caregiver role—particularly in identifying sufficient support resources.
Participation of patients/caregivers in this study was limited to the data provided through participant interviews.
by Carla Schenker, Maria M. Wertli, Lorenz Räber, Alan G. Haynes, Arnaud Chiolero, Nicolas Rodondi, Radoslaw Panczak, Drahomir Aujesky
BackgroundAortic valve stenosis (AS) is the most common valvular heart disease and if severe, is treated with either transcatheter (TAVR) or surgical aortic valve replacement (SAVR). We assessed temporal trends and regional variation of these interventions in Switzerland and examined potential determinants of geographic variation.
MethodsWe conducted a population-based analysis using patient discharge data from all Swiss public and private acute care hospitals from 2013 to 2018. We generated hospital service areas (HSAs) based on patient flows for TAVR. We calculated age-standardized mean procedure rates and variation indices (extremal quotient [EQ] and systematic component of variation [SCV]). Using multilevel regression, we calculated the influence of calendar year and regional demographics, socioeconomic factors (language, insurance status), burden of disease, and number of cardiologists/cardiovascular surgeons on geographic variation.
ResultsOverall, 8074 TAVR and 11,825 SAVR procedures were performed in 8 HSAs from 2013 to 2018. Whereas the age-/sex-standardized rate of TAVR increased from 12 to 22 procedures/100,000 persons, the SAVR rate decreased from 33 to 24 procedures during this period. After full adjustment, the predicted TAVR and SAVR rates varied from 12 to 22 and 20 to 35 per 100,000 persons across HSAs, respectively. The regional procedure variation was low to moderate over time, with a low overall variation in TAVR (EQ 1.9, SCV 3.9) and SAVR (EQ 1.6, SCV 2.2). In multilevel regression, TAVR rates increased annually by 10% and SAVR rates decreased by 5%. Determinants of higher TAVR rates were older age, male sex, living in a German speaking area, and higher burden of disease. A higher proportion of (semi)private insurance was also associated with higher TAVR and lower SAVR rates. After full adjustment, 10.6% of the variance in TAVR and 18.4% of the variance in SAVR remained unexplained. Most variance in TAVR and SAVR rates was explained by language region and insurance status.
ConclusionThe geographic variation in TAVR and SAVR rates was low to moderate across Swiss regions and largely explained by differences in regional demographics and socioeconomic factors. The use of TAVR increased at the expense of SAVR over time.
To identify attitudes towards HIV/STI screening guidelines and explore the acceptability of assessing sexual positioning practices among Black sexual minority men (SMM).
Risks for HIV/STIs vary by sexual positioning practices. However, clinicians and Black SMM do not always discuss sexuality with each other. Therefore, HIV/STI screening and testing remain suboptimal.
Qualitative study using focus groups.
Data were obtained from 12 focus groups and one in-depth interview conducted in Baltimore, MD among HIV-negative Black SMM between October 2019 and May 2020 (N = 39). Groups were stratified into three age categories: 18–24, 25–34 and 35+. Participants were given the “5 P's” from the CDC's 2015 Sexual History Screening Guidelines and asked to discuss attitudes towards existing questions regarding sexual positioning practices. Themes were identified using an electronic pile sorting approach.
Most identified as homosexual/gay/same gender-loving (68%), were employed (69%) and single (66%). Additionally, 34% had ever been diagnosed with an STI, of whom 38% had a history of repeated STI acquisition in their lifetime. Participants across age groups said clinicians should use the words “top” and “bottom” to demonstrate cultural familiarity and build trust. Some said that screening for sexual positioning was unnecessary and intrusive; others said that questions should be justified. Younger men wanted clinicians to ask questions in ways that make them feel cared for.
Guidelines should include language for clinicians to use culturally specific language and better ways to prepare Black SMM patients for screening.
Some Black SMM will not discuss sexual positioning practices without clinicians' demonstration of cultural understanding and respect. Screening should incorporate culturally responsive language, justification and convey care.
Consolidated criteria for reporting qualitative research (COREQ).
There was no patient or public involvement in the design or drafting of this discursive paper.
Transforming Growth Factor-Beta (TGF-β) signalling pathway is of paramount importance in the processes of wound healing, epidermal integrity maintenance and development of skin cancer. The objective of this research endeavour was to clarify the impact of gene mutations and variations in expression within TGF-β family on mechanisms of tissue repair, as well as to identify potential targets for therapeutic purposes in non-melanoma skin cancer (NMSC). The methods utilized in this study involved obtaining RNA-seq data from 224 NMSC patients and paired normal skin tissues from the PRJNA320473 and PRJEB27606 databases. The purpose of the differential gene expression analysis was to identify genes whose expression had changed significantly. In order to evaluate the effects and interrelationships of identified gene variants, structural analysis with AlphaFold and PDB data and network analysis with the STRING database were both utilized. Critical gene expression was externally validated through the utilization of the GEPIA database. Tumour tissues exhibited a notable upregulation of genes associated with the TGF-β pathway, specifically MMP1, MMP3, MMP9, EGF, COL3A1 and COL1A2, in comparison with normal tissues. As indicated by the central node status of these genes in the network analysis, they play a crucial role in the progression of NMSCs. The results of the structural analysis suggested that mutations might cause functional disruptions. External validation of the upregulation confirmed the expression trends and emphasized the biomarker potential of the upregulated genes. In conclusion, this research offered thorough examination of molecular modifications that occur in TGF-β family genes, which are linked to cutaneous wound healing and NMSC. The modified expression of the identified hub genes may represent innovative targets for therapeutic intervention.
Pregnant women have been historically excluded from interventional research. While recent efforts have been made to improve their involvement, there remains a disparity in the evidence base for treatments available to pregnant women compared with the non-pregnant population. A significant barrier to the enrolment of pregnant women within research is risk perception and a poor understanding of decision-making in this population.
Assess the risk perception and influences on decision-making in pregnant women, when considering whether to enrol in a hypothetical interventional research study.
Semistructured interviews were undertaken, and thematic analysis was undertaken of participant responses.
Twelve pregnant women were enrolled from an antenatal outpatient clinic.
Participants were unanimously positive about enrolling in the proposed hypothetical interventional study. Risk perception was influenced by potential risks to their fetus and their previous experiences of healthcare and research. Participants found the uncertainty in quantifying risk for new research interventions challenging. They were motivated to enrol in research by altruism and found less invasive research interventions more tolerable.
It is vital to understand how pregnant women balance the perceived risks and benefits of interventional research. This may help clinicians and scientists better communicate risk to pregnant women and address the ongoing under-representation of pregnant women in interventional research.
by Rahim Valani, Fazila Kassam, Shauna Jose, Mario Hanna, Tanmay Sharma, Jhanahan Sriranjan, Yazad Bhathena, Umairah Boodoo, Aashna Agarwal, Suneel Upadhye
BackgroundPediatric patients with pain of various causes present to the emergency department. Appropriate assessment and management of pain are important aspects of emergency department treatment. However, only a few studies have identified the predictors of both outcomes. This study aimed to evaluate the rate of pain assessment at triage and subsequent management and to identify the predictors of each outcome.
MethodsThis was a multi-center retrospective study based at five community emergency departments. Pediatric patients ( Results
There were 4,128 patients with an average age of 9.6 years, and 49.1% of them were female. Only 74.2% of the patients underwent assessment for pain at triage, and 18.3% received analgesia. The median time to analgesia was 95 (IQR: 49–154) min. Most patients presented with head/neck (36.1%), upper limb (21.6%), and lower limb (19.9%) pain. The oral route was the most common analgesia delivery method (67.4%), and ibuprofen and acetaminophen were the primary agents used. Younger age, higher acuity, and presenting with head or neck pain were independent predictors of pain assessment at triage, while children 3–5 years and those with lower extremity pain were more likely to receive analgesia.
ConclusionAlthough pain assessment at triage has improved in pediatric patients, there is still a major deficiency in adequate pain management. Our study highlights predictors of pain assessment and management that can be considered for improved pediatric care.
by Elizabeth Dufourcq Sekatcheff, Christian Godon, Aymeric Bailly, Loïc Quevarec, Virginie Camilleri, Simon Galas, Sandrine Frelon
Wildlife is subject to various sources of pollution, including ionizing radiation. Adverse effects can impact the survival, growth, or reproduction of organisms, later affecting population dynamics. In invertebrates, reproduction, which directly impacts population dynamics, has been found to be the most radiosensitive endpoint. Understanding the underlying molecular pathways inducing this reproduction decrease can help to comprehend species-specific differences in radiosensitivity. From our previous studies, we found that decrease in reproduction is life stage dependent in the roundworm Caenorhabditis elegans, possibly resulting from an accumulation of damages during germ cell development and gamete differentiation. To go further, we used the same experimental design to assess more precisely the molecular determinants of reproductive toxicity, primarily decreases in gamete number. As before, worms were chronically exposed to 50 mGy·h−1 external gamma ionizing radiation throughout different developmental periods (namely embryogenesis, gametogenesis, and full development). To enable cross species extrapolation, conserved molecular pathways across invertebrates and vertebrates were analysed: apoptosis and MAP kinase Ras/ERK (MPK-1), both involved in reproduction and stress responses. Our results showed that these pathways are life-stage dependent, resulting from an accumulation of damages upon chronic exposure to IR throughout the life development. The Ras/ERK pathway was activated in our conditions in the pachytene region of the gonad where it regulates cell fate including apoptosis, but not in the ovulation zone, where it controls oocyte maturation and ovulation. Additionally, assessment of germ cell proliferation via Ras/ERK pathway showed no effect. Finally, a functional analysis of apoptosis revealed that while the decrease of the ovulation rate is caused by DNA-damaged induced apoptosis, this process does not occur in spermatocytes. Thus, sperm decrease seems to be mediated via another mechanism, probably a decrease in germ cell proliferation speed that needs further investigation to better characterize sex-specific responses to IR exposure. These results are of main importance to describe radio-induced reprotoxic effects and contribute as weight of evidence for the AOP #396 “Deposition of ionizing energy leads to population decline via impaired meiosis”.
FreshRSS 