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Background: Relatively few laboratory markers have been evaluated for the detection or monitoring of intestinal inflammation in canine chronic enteropathies, including inflammatory bowel disease (IBD). Previous research found that the intestinal mucosal levels of S100A12 and myeloperoxidase (MPO), as biomarkers of gut inflammation, were elevated in human patients with IBD. To date, the S100A12 and MPO levels in intestinal mucosal samples from either healthy dogs or from dogs suffering from IBD remain unreported. Therefore, this study aimed to evaluate the mucosal S100A12 and MPO levels in four different parts of the intestine (duodenum, jejunum, ileum and colon) in 12 healthy laboratory Beagle dogs using the ELISA and spectrophotometric methods, respectively. Results: Based on histological examinations, the recorded findings for all the samples were considered normal. The mucosal concentration of S100A12 in the ileum was significantly higher than in all other segments of the intestine (p < 0.05). MPO activity was significantly higher in the ileal, jejunal and duodenal than in colonic mucosal samples (p < 0.05). Moreover, its concentration was higher in the jejunum than in the duodenum. Conclusions: This study showed that S100A12 and MPO are reliably detectable in canine intestinal mucosa. The assays used appeared to be sufficient to further evaluate the role of S100A12 and MPO in the pathogenesis of canine chronic enteropathies, including IBD. These biomarkers may play a role in the initial detection of gut inflammation suggesting the need for further investigations to confirm IBD or to differentiate between IBD subtypes. Understanding the role of S100A12 and MPO in the pathogenesis of chronic intestinal inflammation in future may result in an improved understanding of canine chronic intestinal inflammation. [ABSTRACT FROM AUTHOR]

Background Tracheoesophageal fistula (TEF) in dogs is a rare disease with only few reports in the literature. This report aims to contribute to the current literature on suitable diagnostic methods for TEF and to provide follow-up information after successful surgical treatment. Case presentation A seven-month-old intact female Spanish Water Dog was presented for further investigation of recurrent respiratory symptom. Bronchoscopy revealed a small hole-like defect in the tracheal wall at the bifurcation. The finding of the contrast material swallow study under fluoroscopy was indicative of a TEF. To further evaluate the connection between the trachea and esophagus, a computed tomography scan was performed. The TEF was surgically approached by thoracotomy through the right lateral sixth intercostal space. The fistula was identified, double ligated and divided. Histopathology confirmed the process to originate from the esophagus and to be patent. The dog was re-examined two weeks and ten months after surgery, with no evidence of recurring clinical signs. Conclusions Contrast material swallow study using fluoroscopy was the most reliable diagnostic method. Bronchoscopy may allow the fistula to be visualized, but due to a small fistular opening it can lead to a false negative result. Surgical correction by ligation and dividing of the fistula suggests a good prognosis for early diagnosed and operated TEF. [ABSTRACT FROM AUTHOR]

Background: Structural myocardial abnormalities have been extensively documented in hypothyroidism. Experimental studies in animal models have also shown involvement of thyroid hormones in gene expression of myocardial collagen. This study was planned to investigate the ability of ultrasonic tissue characterization, as evaluated by integrated backscatter (IBS), to early identify myocardial involvement in thyroid dysfunction. Patients and Methods: We studied 15 patients with hyperthyroidism (HYPER), 8 patients with hypothyroidism (HYPO), 14 patients with subclinical hypothyroidism (SCH) and 19 normal (N) subjects, who had normal LV systolic function. After treatment, 10 HYPER, 6 HYPO, and 8 SCH patients were reevaluated. IBS images were obtained and analyzed in parasternal short axis (papillary muscle level) view, at left ventricular (LV) posterior wall. The following IBS variables were analyzed: 1) the corrected coefficient (CC) of IBS, obtained by dividing IBS intensity by IBS intensity measured in a rubber phantom, using the same equipment adjustments, at the same depth; 2) cardiac cyclic variation (CV) of IBS - peak-to-peak difference between maximal and minimal values of IBS during cardiac cycle; 3) cardiac cyclic variation index (CVI) of IBS - percentual relationship between the cyclic variation (CV) and the mean value of IBS intensity. Results: CC of IBS was significantly larger (p < 0.05) in HYPER (1.57 ± 0.6) and HYPO (1.53 ± 0.3) as compared to SCH (1.32 ± 0.3) or N (1.15 ± 0.27). The CV (dB) (HYPO: 7.5 ± 2.4; SCH: 8.2 ± 3.1; HYPER: 8.2 ± 2.0) and the CVI (HYPO: 35.6 ± 19.7%; SCH: 34.7 ± 17.5%; HYPER: 37.8 ± 11.6%) were not significantly different in patients with thyroid dysfunction as compared to N (7.0 ± 2.0 and 44.5 ± 15.1%). Conclusions: CC of IBS was able to differentiate cardiac involvement in patients with overt HYPO and HYPER who had normal LV systolic function. These early myocardial structural abnormalities were partially reversed by drug therapy in HYPER group. On the other hand, although mean IBS intensity tended to be slightly larger in patients with SCH as compared to N, this difference was not statistical significant. [ABSTRACT FROM AUTHOR]

Background: Besides cognitive decline, Alzheimer's disease (AD) leads to physical disability, need for help and permanent institutional care. The trials investigating effects of exercise rehabilitation on physical functioning of home-dwelling older dementia patients are still scarce. The aim of this study is to investigate the effectiveness of intensive exercise rehabilitation lasting for one year on mobility and physical functioning of home-dwelling patients with AD. Methods: During years 2008-2010, patients with AD (n = 210) living with their spousal caregiver in community are recruited using central AD registers in Finland, and they are offered exercise rehabilitation lasting for one year. The patients are randomized into three arms: 1) tailored home-based exercise twice weekly 2) group-based exercise twice weekly in rehabilitation center 3) control group with usual care and information of exercise and nutrition. Main outcome measures will be Guralnik's mobility and balance tests and FIM-test to assess physical functioning. Secondary measures will be cognition, neuropsychiatric symptoms according to the Neuropsychiatric Inventory, caregivers' burden, depression and health-related quality of life (RAND-36). Data concerning admissions to institutional care and the use and costs of health and social services will be collected during a two year follow-up. Discussion: To our knowledge this is the first large scale trial exploring whether home-dwelling patients with AD will benefit from intense and long-lasting exercise rehabilitation in respect to their mobility and physical functioning. It will also provide data on cost-effectiveness of the intervention. Trial registration: ACTRN12608000037303 [ABSTRACT FROM AUTHOR]

Background: Double-chambered right ventricle is a rare congenital disease frequently misdiagnosed in the adult patient. An anomalous muscle band divides the right ventricle in two cavities causing variable degree of obstruction. Although echocardiography is considered a useful method for the diagnosis of this pathology in children, it has been recognized the transthoracic scanning limitation in adults. Case presentation: A 29 year-old patient with double-chambered right ventricle presenting mild exercise intolerance referred for follow up of a known ventricular septal defect in whom a complete diagnosis was obtained based only on transthoracic two dimensional echocardiography without the needing of cardiac catheterization. Conclusion: Based on non invasive echocardiographic diagnosis, patient was referred to surgical correction, which was completely successful. [ABSTRACT FROM AUTHOR]

Background: Medicaid expansion via the Affordable Care Act, more recent legislation and Medicaid 1115 waivers offer opportunity to increase health care access among individuals involved in the carceral system. Effective enrollment of new beneficiaries and temporary suspension and reactivation of existing Medicaid benefits upon release is key to the success of these efforts. This study aims to characterize how jails, prisons and Medicaid agencies are implementing Medicaid suspension and enrollment programs and identifies barriers and facilitators to implementation., Methods: We conducted 19 semi-structured interviews with 36 multi-state leaders in carceral facilities, Medicaid agencies, local health departments and national policy experts from 2020 to 2021. Interviews covered 4 domains: (1) the role of policy in influencing carceral and reentry Medicaid practices, (2) implementation strategies to suspend and enroll incarcerated individuals into Medicaid, (3) barriers and facilitators to successful implementation, and (4) variation in implementation between jails and prisons., Results: Participants identified logistical challenges with suspension and enrollment, including limited infrastructure for data sharing between carceral facilities and Medicaid agencies, burdensome bureaucratic requirements, and challenges with Medicaid renewal, particularly in the jail environment. They offered opportunities to overcome barriers, such as the creation of specialized incarcerated Medicaid benefit categories and provision of in-reach services via managed care organizations. Participants also called for improvements to Medicaid reactivation processes, as even when facilities successfully suspended benefits, individuals faced significant challenges and delays reactivating benefits upon release. Participants also called for further loosening of the Medicaid Inmate Exclusion Policy., Discussion: Findings highlight the need to update data sharing infrastructure, which will be critical to the implementation of the 1115 waivers, as carceral facilities will be subject to Medicaid billing and reporting requirements. In addition to investing in the ability to newly enroll and suspend Medicaid benefits, attention towards improving timely reactivation practices is needed, particularly given the highly elevated risk of mortality immediately after release. Participants calls for further reforms to the Medicaid Inmate Exclusion Policy are consistent with proposed legislation., Conclusions: Findings can critically inform the successful implementation of Medicaid-based reforms to improve the health of incarcerated and formerly incarcerated people., Competing Interests: Declarations. Ethics approval and consent to participate: Research protocols were approved by the Johns Hopkins Bloomberg School of Public Health Institutional Review Board. Consent for publication: N/A Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Many members of the oxysterol-binding protein-related protein (ORP) family have been characterized in detail over the past decades, but the lipid transport and other functions of ORP7 still remain elusive. What is known about ORP7 points toward an endoplasmic reticulum and plasma membrane-localized protein, which also interacts with GABA type A receptor-associated protein like 2 (GABARAPL2) and unlipidated Microtubule-associated proteins 1A/1B light chain 3B (LC3B), suggesting a further autophagosomal/lysosomal association. Functional roles of ORP7 have been suggested in cholesterol efflux, hypercholesterolemia, and macroautophagy. We performed a hypothesis-free multi-omics analysis of chemical ORP7 inhibition utilizing transcriptomics and lipidomics as well as proximity biotinylation interactomics to characterize ORP7 functions in a primary cell type, human umbilical vein endothelial cells (HUVECs). Moreover, assays on angiogenesis, cholesterol efflux, and lipid droplet quantification were conducted., Results: Pharmacological inhibition of ORP7 leads to an increase in gene expression related to lipid metabolism and inflammation, while genes associated with cell cycle and cell division were downregulated. Lipidomic analysis revealed increases in ceramides and lysophosphatidylcholines as well as saturated and monounsaturated triacylglycerols. Significant decreases were seen in all cholesteryl ester and in some unsaturated triacylglycerol species, compatible with the detected decrease of mean lipid droplet area. Along with the reduced lipid stores, ATP-binding cassette subfamily G member 1 (ABCG1)-mediated cholesterol efflux and angiogenesis decreased. Interactomics revealed an interaction of ORP7 with AKT1, a central metabolic regulator., Conclusions: The transcriptomics results suggest an increase in prostanoid as well as oxysterol synthesis, which could be related to the observed upregulation of proinflammatory genes. We envision that the defective angiogenesis in HUVECs subjected to ORP7 inhibition could be the result of an unfavorable plasma membrane lipid composition and/or reduced potential for cell division. To conclude, the present study suggests multifaceted functions of ORP7 in lipid homeostasis, angiogenic tube formation, and gene expression of lipid metabolism, inflammation, and cell cycle in primary endothelial cells., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Adverse events occur frequently at emergency departments (ED) because of several risk factors related to varying conditions. It is still unclear, which factors lead to patient safety incident reports. The aim of this study was to explore the root causes behind ED-associated patient safety incidents reported by personnel, and based on the findings, to suggest learning objectives for improving patient safety., Methods: The study material included incident reports (n = 340) which concerned the ED of a teaching hospital over one year. We used a mixed method combining quantitative descriptive statistics and qualitative research by inductive content analysis and deductive Ishikawa root cause analysis., Results: Most (76.5%) incidents were reported after patient transfer from the ED. Nurses reported 70% of incidents and physicians 7.4%. Of the reports, 40% were related to information flow or management. Incidents were evaluated as no harm (29.4%), mild (46%), moderate (19.7%), and severe (1.2%) harm to the patient. The main consequences for the organization were reputation loss (44.1%) and extra work (38.9%). In the qualitative analysis, nine specific problem groups were found: insufficient introduction, adherence to guidelines and protocols, insufficient human resources, deficient professional skills, medication management deficiencies, incomplete information transfer from the ED, language proficiency, unprofessional behaviour, identification error, and patient-dependent problems. Six organizational themes were identified: medical staff orientation, onboarding and competence requirements; human resources; electronic medical records and information transfer; medication documentation system; interprofessional collaboration; resources for specific patient groups such as geriatric, mental health, and patients with substance abuse disorder. Entirely human factor-related themes could not be defined because their associations with system factors were complex and multifaceted. Individual and organizational learning objectives were addressed, such as adherence to the proper use of instructions and adequate onboarding., Conclusions: System factors caused most of the patient safety incidents reported concerning ED. The introduction and training of ED -processes is elementary, as is multiprofessional collaboration. More research is needed about teamwork skills, patients with special needs and non-critical patients, and the reporting of severe incidents., (© 2024. The Author(s).)

Aim: To investigate the associations between insulin use and diabetic retinopathy (DR), and retinal vascular parameters in type 2 diabetes (T2DM)., Methods: A total of 6,374 T2DM patients, consisting of 2,231 patients receiving insulin alone and 4143 patients without any hypoglycemic medication, were included in cross-sectional analyses. Among those without DR at baseline, 791 patients were followed for three years in longitudinal analyses. Fundus photography was taken to diagnose DR and calculate central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), arteriolar-to-venular ratio (AVR), and vascular tortuosity. Inverse probability treatment-weighted analyses were performed., Results: After adjusting for gender, age, body mass index, blood pressure, blood glucose, T2DM duration, smoking, and alcohol use, insulin users showed a higher risk of DR (odds ratio (OR) = 2.27, 95% confidence interval (95%CI) = 2.08-2.48, P < 0.001), larger CRVE (β = 3.92, 95%CI = 2.46-5.37, P < 0.001), smaller AVR (β=-0.0083, 95%CI=-0.0121- -0.0046, P < 0.001), and larger vascular curvature (β = 0.19, 95%CI = 0.05-0.33, P = 0.008). After 3 years, insulin users had a higher risk of developing DR (OR = 1.94; 95% CI = 1.37-2.73, P = 0.002), and greater change in CRVE (β = 3.92, 95%CI = 0.96-6.88, P = 0.009)., Conclusions: The impact of insulin on the retinal microvasculature provides support for linking insulin to the increased risk of DR, as well as cardiovascular events in T2DM., (© 2024. The Author(s).)

Background: Interstitial lung diseases (ILD) include a wide range of diseases impacting lung parenchyma and leading to fibrosis and architectural distortion. Chronic cough and dyspnea are common symptoms which affect the quality of life (QoL) in ILD patients. The mechanisms of cough in ILD patients are still unknown. The aim of this study was to prospectively investigate histological, radiological, and physiological determinants of cough-related QoL in ILD patients who underwent transbronchial lung cryobiopsy (TBLC)., Methods: All patients (n = 111) filled in The Leicester Cough Questionnaire (LCQ) and The St George's Respiratory Questionnaire (SGRQ). They underwent lung function tests, forced vital capacity (FVC), forced vital expiratory volume in 1 s (FEV1), diffusion capacity to carbon monoxide (DLCO), high-resolution computed tomography (HRCT), and blood samples before diagnostic TBLC. Two experienced radiologists assessed the extents of following HRCT patterns: ground-glass opacities (GGO), honeycombing, reticulation, traction bronchiectasis, and emphysema. Histology of TBLC were re-analyzed by two experienced pulmonary pathologists and the presence of fibroblast foci, fibrosis, giant cells, granulomas, and honeycombing were recorded., Results: In the median multivariate regression analysis, BMI (-0.19; 95% CI -0.37- -0.014; p 0.035), GGO (-0.38; 95% CI -0.61- -0.15; p 0.001), granulomas (-3.21; 95% CI -6.12- -0.30; p 0.031), and current smoking (2.49; 95% CI 0.12-4.86; p 0.040) showed independent associations with LCQ total score. BMI (1.3; 95% CI 0.20-2.42; p 0.021) and DLCO (-0.51; 95% CI -0.85 - -0.16; p 0.004) showed independent association with SGRQ total score., Conclusion: Determinants of cough-related QoL in ILD patients are multifactorial including physiological, radiological and histological parameters., (© 2024. The Author(s).)

Background: B3GNT7, a glycosyltransferase of significant importance that is highly expressed in intestinal epithelial cells, plays a pivotal role in intestinal physiological processes. This study elucidates novel insights into the potential role and underlying mechanisms of B3GNT7 in ulcerative colitis (UC)., Methods: An experimental colitis model was induced using DSS in mice to investigate B3GNT7 expression in the colon via transcriptomics and immunohistochemistry. Bioinformatics analysis was employed to delineate the biological functions of B3GNT7. Additionally, the correlation between the transcription levels of B3GNT7 in colonic tissues from patients with UC, sourced from the IBDMDB database, and the severity of colonic inflammation was analyzed to elucidate potential mechanisms., Results: The DSS-induced colitis model was successfully established, and transcriptomic analysis identified a marked downregulation of B3GNT7 expression in the colonic tissues compared to the controls. Functional enrichment analysis indicated B3GNT7's predominant role in mucin O-glycosylation. Protein interaction analysis revealed that B3GNT7 predominantly interacts with members of the mucin MUC family, including MUC2, MUC3, and MUC6. In patients with UC, B3GNT7 transcription levels were significantly reduced, particularly in those with moderate to severe disease activity. The expression level of B3GNT7 exhibited a negative correlation with the endoscopic severity of UC. Gene set enrichment analysis (GSEA) further demonstrated significant enrichment of B3GNT7 in the mucin O-glycosylation synthesis pathway., Conclusion: The downregulation of B3GNT7 expression in the colonic tissues of UC patients may contribute to the compromised mucin barrier function and the exacerbation of colitis., (© 2024. The Author(s).)

Background: Foot health services for people with rheumatoid arthritis (RA) are an important part of their comprehensive care. However, little is known about the perceptions of people with RA have about foot health services. This study aimed to explore how people with RA perceive foot health services., Methods: A descriptive cross-sectional survey design was applied. The electronic survey data were collected in April 2023 from people with RA through a national patients' association (N = 2400, response rate 24%, n = 565). The statistical data were analysed using descriptive statistics and textual data with thematic analysis., Results: Most of the respondents (n = 322, 59%) had used foot health services provided by chiropodist or podiatrist. Those who had used services were mostly satisfied but considered patient education about foot health insufficient. One third reported no visits to foot health services at all because of personal and health service system-related factors., Conclusions: Those people with RA who have access to foot health services value and appreciate the services. However, many people with RA do not use foot health services because they perceive availability of such services limited and thus unequal and hard to access. There is a need to develop foot health services for people with RA so that they are easy to access, correspond to their foot health needs and have seamless care paths at different levels of the health care system., (© 2024 The Authors. Journal of Foot and Ankle Research published by John Wiley & Sons Australia, Ltd on behalf of Australian Podiatry Association and The Royal College of Podiatry.)

Background: Successful ageing is the term often used for depicting exceptional ageing and can be measured with multidimensional models including physical, psychological and social wellbeing. The aim of this study was to test multidimensional successful ageing models to investigate whether these models can predict successful ageing, and which individual subcomponents included in the models are most significantly associated with successful ageing., Methods: Successful ageing was defined as the ability to live at home without daily care at the age of 84 years or over. Data on the participants' physical, psychological and social wellbeing were gathered at baseline and the follow-up period was 20 years. Four successful ageing models were constructed. Backward stepwise logistic regression analysis was used to identify the individual subcomponents of the models which best predicted successful ageing., Results: All successful ageing models were able to predict ageing successfully after the 20-year follow-up period. After the backward stepwise logistic regression analysis, three individual subcomponents of four models remained statistically significant and were included in the new model: having no heart disease, having good self-rated health and feeling useful. As a model, using only these three subcomponents, the association with successful ageing was similar to using the full models., Conclusions: Multidimensional successful ageing models were able to predict successful ageing after a 20-year follow-up period. However, according to the backward stepwise logistic regression analysis, the three subcomponents (absence of heart disease, good self-rated health and feeling useful) significantly associated with successful ageing performed as well as the multidimensional successful ageing models in predicting ageing successfully., (© 2024. The Author(s).)

Background: Discrepancies in the utilization of reactive oxygen species (ROS) between cancer cells and their normal counterparts constitute a pivotal juncture for the precise treatment of cancer, delineating a noteworthy trajectory in the field of targeted therapies. This phenomenon is particularly conspicuous in the domain of nano-drug precision treatment. Despite substantial strides in employing nanoparticles to disrupt ROS for cancer therapy, current strategies continue to grapple with challenges pertaining to efficacy and specificity. One of the primary hurdles lies in the elevated levels of intracellular glutathione (GSH). Presently, predominant methods to mitigate intracellular GSH involve inhibiting its synthesis or promoting GSH efflux. However, a conspicuous gap remains in the absence of a strategy capable of directly and efficiently clearing GSH., Methods: We initially elucidated the chemical mechanism underpinning oridonin, a diminutive pharmacological agent demonstrated to perturb reactive oxygen species, through its covalent interaction with glutathione. Subsequently, we employed the incorporation of maleimide-liposomes, renowned for their capacity to disrupt the ROS delivery system, to ameliorate the drug's water solubility and pharmacokinetics, thereby enhancing its ROS-disruptive efficacy. In a pursuit to further refine the targeting for acute myeloid leukemia (AML), we harnessed the maleic imide and thiol reaction mechanism, facilitating the coupling of Toll-like receptor 2 (TLR2) peptides to the liposomes' surface via maleic imide. This strategic approach offers a novel method for the precise removal of GSH, and its enhancement endeavors are directed towards fortifying the precision and efficacy of the drug's impact on AML targets., Results: We demonstrated that this peptide-liposome-small molecule machinery targets AML and consequently induces cell apoptosis both in vitro and in vivo through three disparate mechanisms: (I) Oridonin, as a Michael acceptor molecule, inhibits GSH function through covalent bonding, triggering an initial imbalance of oxidative stress. (II) Maleimide further induces GSH exhaustion, aggravating redox imbalance as a complementary augment with oridonin. (III) Peptide targets TLR2, enhances the directivity and enrichment of oridonin within AML cells., Conclusion: The rationally designed nanocomplex provides a ROS drug enhancement and targeted delivery platform, representing a potential solution by disrupting redox balance for AML therapy., (© 2024. The Author(s).)

Background: Coccidiosis is one of the most frequently reported diseases in chickens, causing a significant economic impact on the poultry industry. However, there have been no previous studies evaluating the prevalence of this disease in broiler farms in Guangdong province. Therefore, this study aims to conduct an epidemiological investigation into the occurrence of Eimeria species and associated risk factors in intensive management conditions across four regions in Guangdong province, China. A total of 394 fecal samples were collected from 89 broiler farms in Guangdong province. The prevalence of Eimeria species infection was determined using PCR, and the occurrence of Clostridium perfringens type A was assessed using quantitative real-time PCR., Results: The results showed an overall prevalence of 98.88% (88/89) at the farm level and 87.06% (343/394) at the flock level. All seven Eimeria species were identified, with E. acervulina (72.53%; 64/89), E. tenella (68.54%; 61/89), and E. mitis (66.29%; 59/89) at the farm level, and E. acervulina (36.55%; 144/394), E. mitis (35.28%; 139/394), and E. tenella (34.01%; 134/394) at the flock level. The predominant species combination observed was a co-infection of all seven Eimeria species (6.74%; 6/89), followed by a combination of E. acervulina, E. tenella, E. mitis, E. necatrix, E. brunetti, and E. maxima (5.62%, 5/89). A combination of E. acervulina, E. tenella, E. mitis, E. necatrix, E. brunetti, and E. praecox (4.49%; 4/89) was also observed at the farm level. Furthermore, the study identified several potential risk factors associated with the prevalence of Eimeria species, including farm location, chicken age, drinking water source, control strategy, and the presence of C. perfringens type A were identified as potential risk factors associated with prevalence of Eimeria species. Univariate and multivariate analyses revealed a significant association between E. necatrix infection and both grower chickens (OR = 10.86; 95% CI: 1.92-61.36; p < 0.05) and adult chickens (OR = 24.97; 95% CI: 4.29-145.15; p < 0.001) compared to starter chickens at the farm level. Additionally, farms that used groundwater (OR = 0.27; 95% CI: 0.08-0.94; p < 0.05) were less likely to have E. maxima compared to those that used running water. At the flock level, the prevalence of E. tenella was significantly higher in the Pearl River Delta (OR = 2.48; 95% CI: 1.0-6.15; p = 0.05) compared to eastern Guangdong. Interestingly, flocks with indigenous birds were less likely to have E. brunetti (OR = 0.48; 95% CI: 0.26-0.89; p < 0.05) compared to flocks with indigenous crossbred birds. Furthermore, flocks that used anticoccidial drugs (OR = 0.09; 95% CI: 0.03-0.31; p < 0.001) or a combination of vaccines and anticoccidial drugs (OR = 0.06; 95% CI: 0.01-0.25; p < 0.001) were less likely to be positive for E. tenella compared to flocks that only used vaccines. Finally, flocks with C. perfringens type A infection were significantly more likely to have E. necatrix (OR = 3.26; 95% CI: 1.96-5.43; p < 0.001), E. tenella (OR = 2.14; 95% CI: 1.36-3.36; p < 0.001), E. brunetti (OR = 2.48; 95% CI: 1.45-4.23; p < 0.001), and E. acervulina (OR = 2.62; 95% CI: 1.69-4.06; p < 0.001) compared to flocks without C. perfringens type A., Conclusions: This study conducted an investigation on the prevalence, distribution, and risk factors associated with Eimeria species infection in broiler chickens in Guangdong. The farm-level prevalence of Eimeria species was higher than the previous prevalence figures for other areas and countries. E. brunetti was identified at higher prevalence in Guangdong than previously survived prevalence in different regions in China. Farm location, chicken age, drinking water source, control strategy, and the presence of C. perfringens type A were considered as potential risk factors associated with prevalence of Eimeria species. It is imperative to underscore the necessity for further surveys to delve deeper into the occurrence of Eimeria species under intensive management conditions for different flock purposes., (© 2024. The Author(s).)

Background: Assisted death, including euthanasia and physician-assisted suicide (PAS), is under debate worldwide, and these practices are adopted in many Western countries. Physicians' attitudes toward assisted death vary across the globe, but little is known about physicians' actual reactions when facing a request for assisted death. There is a clear gap in evidence on how physicians act and respond to patients' requests for assisted death in countries where these actions are not legal., Methods: A survey including statements concerning euthanasia and PAS and an open question about their actions when facing a request for assisted death was sent to all Finnish physicians. Quantitative data are presented as numbers and percentages. Statistical significance was tested by using the Pearson chi-square test, when appropriate. The qualitative analysis was performed by using an inductive content analysis approach, where categories emerge from the data., Results: Altogether, 6889 physicians or medical students answered the survey, yielding a response rate of 26%. One-third of participants agreed or partly agreed that they could assist a patient in a suicide. The majority (69%) of the participants fully or partly agreed that euthanasia should only be accepted due to difficult physical symptoms, while 12% fully or partly agreed that life turning into a burden should be an acceptable reason for euthanasia. Of the participants, 16% had faced a request for euthanasia or PAS, and 3033 answers from 2565 respondents were achieved to the open questions concerning their actions regarding the request and ethical aspects of assisted death. In the qualitative analysis, six main categories, including 22 subcategories, were formed regarding the phenomenon of how physicians act when facing this request. The six main categories were as follows: providing an alternative to the request, enabling care and support, ignoring the request, giving a reasoned refusal, complying with the request, and seeing the request as a possibility., Conclusions: Finnish physicians' actions regarding the requests for assisted death, and attitudes toward euthanasia and PAS vary substantially. Open discussion, education, and recommendations concerning a request for assisted death and ethics around it are also highly needed in countries where euthanasia and PAS are not legal., (© 2024. The Author(s).)

Background: It is well-established that parental obesity is a strong risk factor for offspring obesity. Further, a converging body of evidence now suggests that maternal weight profiles may affect the developing offspring's brain in a manner that confers future obesity risk. Here, we investigated how pre-pregnancy maternal weight status influences the reward-related striatal areas of the offspring's brain during in utero development., Methods: We used diffusion tensor imaging to quantify the microstructure of the striatal brain regions of interest in neonates (N = 116 [66 males, 50 females], mean gestational weeks at birth [39.88], SD = 1.14; at scan [43.56], SD = 1.05). Linear regression was used to test the associations between maternal pre-pregnancy body mass index (BMI) and infant striatal mean diffusivity., Results: High maternal pre-pregnancy BMI was associated with higher mean MD values in the infant's left caudate nucleus. Results remained unchanged after the adjustment for covariates., Conclusions: In utero exposure to maternal adiposity might have a growth-impairing impact on the mean diffusivity of the infant's left caudate nucleus. Considering the involvement of the caudate nucleus in regulating eating behavior and food-related reward processing later in life, this finding calls for further investigations to define the prognostic relevance of early-life caudate nucleus development and weight trajectories of the offspring., (© 2024. The Author(s).)

Background: Every physician has a unique professional identity. However, little is known about the diversity of identities among physicians. This study aimed to quantitatively assess the professional identity of physicians in Finland using descriptions of professional identity., Methods: This study was part of a larger cross-sectional Finnish Physician 2018 Study. The target population consisted of all Finnish physicians under the age of 70 (N = 24,827) in 2018. The sample was drawn from physicians born on even numbered days (N = 11,336) using the Finnish Medical Association register. A total of 5,187 (46%) physicians responded. Professional identity was examined by 27 given characterisations using a five-point Likert scale. Multivariate logistic regression was used in assessing how place of work, graduation year and gender were associated with identity descriptions., Results: The descriptions which most physicians identified with were "member of a working group/team" (82%), "helper" (82%), and "health expert" (79%); the majority reported these as describing them very or quite well. Identity descriptions such as "prescriber of medications" (68% vs. 45%), "prioritiser" (57% vs. 35%) and "someone issuing certificates" (52% vs. 32%) were more popular among junior than senior physicians. The biggest differences between the genders were found in the descriptions "provider of comfort" (62% vs. 40%) and "someone engaged in social work" (45% vs. 25%), with which women identified more frequently than men., Conclusions: Strong identification as a member of a team is an important finding in the increasingly multiprofessional world of health care. Importantly, most physicians shared several core professional identity descriptions (i.e., helper, health expert) that reflect the traditional image of an exemplary doctor., (© 2024. The Author(s).)

Background: The association between remnant cholesterol (RC) and diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) remains unclear. Morphological changes in retinal vessels have been reported to predict vascular complications of diabetes, including DR., Methods: This cross-sectional study included 6535 individuals with T2DM. The RC value was calculated using the recognized formula. The retinal vascular parameters were measured using fundus photography. The independent relationship between RC and DR was analyzed using binary logistic regression models. Multiple linear regression and subgroup analyses were employed to investigate the link between RC and vascular parameters, including the retinal arteriolar diameter (CRAE), venular diameter (CRVE), and fractal dimension (D f ). Mediation analysis was performed to assess whether the vascular morphology could explain the association between RC and DR., Results: RC was independently associated with DR in patients with a longer duration of T2DM (> 7 years). Patients with the highest quartile RC levels had larger CRAE (5.559 [4.093, 7.025] μm), CRVE (7.620 [5.298, 9.941] μm) and D f (0.013 [0.009, 0.017]) compared with patients with the lowest quartile RC levels. Results were robust across different subgroups. The association between RC and DR was mediated by CRVE (0.020 ± 0.005; 95% confidence interval: 0.012-0.032)., Conclusions: RC may be a risk factor for DR among those who have had T2DM for a longer period of time. Higher RC levels were correlated with wider retinal arterioles and venules as well as higher D f , and it may contribute to DR through the dilation of retinal venules., (© 2024. The Author(s).)

Background: Angiogenesis is crucial for tumor development, progression, and metastasizing. The most important regulator of angiogenesis is the vascular endothelial growth factor (VEGF) family, which is involved in multiple pathways in tumor microenvironment. The objective of this study was to investigate the prognostic value of the VEGF family in patients treated for metastatic breast cancer. The emphasis was on neuropilin-1 (NRP-1) and placental growth factor (PlGF)., Materials and Methods: An analysis of eight members of the VEGF family was performed using baseline plasma samples of 65 patients treated for metastatic HER2 negative breast cancer in a phase II first-line bevacizumab plus chemotherapy trial. The patients were divided into two groups, high or low, according to the median for each VEGF family member. Progression-free survival (PFS) and overall survival (OS) were determined for each VEGF family member., Results: The patients with low plasma levels of NRP-1 and PlGF had a longer OS than those with high plasma levels [multivariable adjusted hazard ratios (HRs) 2.54 (95% confidence interval (CI) 1.11-5.82, p = 0.02) and 3.11 (95% CI 1.30-7.47, p = 0.01), respectively]. The patients with low levels of both NRP-1 and PlGF had a remarkably long OS with HR of 6.24, (95% CI 1.97-19.76, p = 0.002). In addition, high baseline NRP-1 level was associated with a significantly shorter PFS [multivariable adjusted HR 2.90 (95% CI 1.02-8.28, p = 0.04)] than that in the low-level group, and a high baseline vascular endothelial growth factor receptor-2 level was associated with a longer PFS [multivariable adjusted HR 0.43 (95% CI 0.19-0.98, p = 0.04)]., Conclusion: Especially NRP-1 and PlGF have prognostic potential in metastatic breast cancer patients treated with a bevacizumab-taxane combination. Patients with low plasma levels of NRP-1 or PlGF have longer OS than patients with high levels. Patients with both low NRP-1 and PlGF levels appear to have excellent long-term survival., Trial Registration: ClinicalTrials.gov identifier: NCT00979641, registration date 18/09/2009. The regional Ethics Committee: R08142M, registration date 18/11/2008., (© 2024. The Author(s).)

Background: Congenital heart defects (CHD) are structural defects of the heart affecting approximately 1% of newborns. They exhibit low penetrance and non-Mendelian patterns of inheritance as varied and complex traits. While genetic factors are known to play an important role in the development of CHD, the specific genetics remain unknown for the majority of patients. To elucidate the underlying genetic risk, we performed a genome wide association study (GWAS) of CHDs in general and specific CHD subgroups using the FinnGen Release 10 (R10) (N > 393,000), followed by functional fine-mapping through eQTL and co-localization analyses using the GTEx database., Results: We discovered three genome-wide significant loci associated with general CHD. Two of them were located in chromosome 17: 17q21.32 (rs2316327, intronic: LRRC37A2, Odds ratio (OR) [95% Confidence Interval (CI)] = 1.17[1.12-1.23], p = 1.5 × 10 -9 ) and 17q25.3 (rs1293973611, nearest: BAHCC1, OR[95%CI] = 4.48[2.80-7.17], p = 7.0 × 10 -10 ), respectively, and in addition to general CHD, the rs1293973611 locus was associated with the septal defect subtype. The third locus was in band 1p21.2 (rs35046143, nearest: PALMD, OR[95%CI] = 1.15[1.09-1.21], p = 7.1 × 10 -9 ), and it was associated with general CHD and left-sided lesions. In the subgroup analysis, two additional loci were associated with septal defects (rs75230966 and rs6824295), and one with left-sided lesions (rs1305393195). In the eQTL analysis the variants rs2316327 (general CHD), and rs75230966 (septal defects) both located in 17q21.32 (with a LD r2 of 0.41) were both predicted to significantly associate with the expression of WNT9B in the atrial appendage tissue category. This effect was further confirmed by co-localization analysis, which also implicated WNT3 expression in the atrial appendage. A meta-analysis of general CHD together with the UK Biobank (combined N = 881,678) provided a different genome-wide significant locus in LRRC37A2; rs16941382 (OR[95%CI] = 1.15[1.11-1.20], p = 1.5 × 10 -9 ) which is in significant LD with rs2316327., Conclusions: Our results of general CHD and different CHD subcategories identified a complex risk locus on chromosome 17 near BAHCC1 and LRRC37A2, interacting with the genes WNT9B, WNT3 and MYL4, may constitute potential novel CHD risk associated loci, warranting future experimental tests to determine their role., (© 2024. The Author(s).)

Background: The unique life situations of older patients with cancer and their family members requires that health care professionals take a holistic approach to achieve quality care. The aim of this study was to assess the perceptions of older patients with cancer and family members about the quality of care received and evaluate differences between their perceptions. A further aim was to examine which factors explain patients' and family members' levels of satisfaction with the care received., Methods: The study was descriptive and cross-sectional in design. Data were collected from patients (n = 81) and their family members (n = 65) on four wards in a cancer hospital, using the Revised Humane Caring Scale (RHCS). Data were analysed using descriptive statistics, crosstabulation, Wilcoxon signed rank test, and multivariable Analysis of Covariance (ANCOVA)., Results: Family members had more negative perceptions of the quality of care than patients did. Dissatisfaction was related to professional practice (p < 0.001), interaction between patient and health care professionals (p < 0.001), cognition of physical needs (p = 0.024), and human resources (p < 0.001). Satisfaction with overall care was significantly lower among those patients and family members who perceived that they had not been involved in setting clear goals for the patient's care with staff (p = 0.002)., Conclusions: It is important that older patients with cancer and family members receive friendly, respectful, individual care based on their needs and hopes, and that they can rely on professionals. Health care professionals need more resources and education about caring for older cancer patients to provide quality care., (© 2024. The Author(s).)

Background: Ketamine is a novel and exciting putative antidepressant medication for patients with treatment-resistant depression. A complication commonly seen in frequent and heavy recreational use of ketamine is ulcerative cystitis, which presents with lower urinary tract symptoms (LUTS) and upper renal tract damage and can be seen in over 25% of regular users. Although Ketamine-induced cystitis (KIC) is a recognised complication in recreational use of ketamine, its occurrence in therapeutic use of ketamine in depression has so far not been reported. The exact pathogenesis of KIC is currently unknown, making treatment and prevention advice much more difficult. Early diagnosis of KIC and immediate cessation of ketamine has been shown to improve adverse urinary tract symptoms and prevent further damage., Case Presentation: We present a case of a 28-year-old female who was started on ketamine treatment for depression, and who then developed symptoms of KIC, which was confirmed by urine microscopy, culture and analysis., Conclusions: To our knowledge, this is the first reported case of KIC in a patient receiving treatment-dose ketamine as part of their antidepressant therapy., (© 2023. Crown.)

Background: There is a need for better adoption of technology to meet the needs of home care professionals, older people, and informal caregivers., Methods: Mixed methods were used to describe and analyse quantitative and qualitative data in a Finnish governmental programme called KATI. The study was three-fold: it 1) listed what kinds of technologies were piloted and deployed in a national study, 2) provided information from the perspectives of home care professionals about requirements to use technology by using focus-group interviews, and 3) assessed experiences of how the adoption of technology changes work and work processes over time by using repeated surveys. Informants in interviews (n = 25) and surveys (n = 90) were home care professionals, who also described the perspectives of older people and informal caregivers. The conceptual models framing the study were adapted from the Technology Acceptance Model and DirVA PROVE-IT., Results: There were 80 technology pilots, in which variety of technologies were followed in home care. Familiarity with, commitment to and understanding of technology benefits were considered to be requirements for the technology to be used. The adoption of technology provided new skills and information about older people's wellbeing, realisation of treatment and new possibilities in home care. It developed new procedures to focus on older people's needs and motivated professionals by gained concrete aid. It enabled them to leave out some concrete procedures as unnecessary. On the other hand, there were also pessimistic and negative experiences when technology use provided nothing new or did not change anything., Conclusions: The adoption of technology is dependent on the technology and its integration into the prevailing service practice. When they both work, it is possible to leave out unnecessary procedures in care, allocate resources and save time. It is possible to be aware of older people's safety and how they cope at home, find new ways to get involved in older people's lives, gain insight, and make changes at work. Continuous on-site training, modifications in service practices and communication throughout organisations is needed., (© 2023. The Author(s).)

Background: Nemaline myopathy (NM) and related disorders (NMr) form a heterogenous group of ultra-rare (1:50,000 live births or less) congenital muscle disorders. To elucidate the self-reported physical, psychological, and social functioning in the daily lives of adult persons with congenital muscle disorders, we designed a survey using items primarily from the Patient Reported Outcomes Measurement Information System, PROMIS®, and conducted a pilot study in patients with NM and NMr in Finland. The items were linked to International Classification of Functioning, Disability and Health (ICF) categories., Results: In total, 20 (62.5%) out of 32 invited persons resident in Finland participated in the study; 12 had NM and 8 NMr, 15 were women and 5 men aged 19-75 years. Sixteen (80%) were ambulatory and 4 (20%) NM patients used wheelchairs. The results from the PROMIS measuring system and ICF categories both indicated that non-ambulatory patients of this study faced more challenges in all areas of functioning than ambulatory ones, but the differences were smaller in the domains measuring psychological and social functioning than in physical functioning. In addition, the COVID-19 pandemic adversely affected the functioning of non-ambulatory patients more than that of ambulatory patients. The interindividual differences were, however, noticeable., Conclusions: To our knowledge, this pilot study is the first comprehensive survey-based study of the physical, psychological, and social functioning of adult persons with nemaline myopathy or related disorders. The results indicate vulnerability of non-ambulatory patients being at higher risk to a decrease in general functioning during global or national exceptional periods. The responses also gave directions for modifying and improving the survey for future studies., (© 2023. The Author(s).)

Background: Lower urinary tract symptoms (LUTS) are prevalent and distressing concerns for women worldwide. The prevalence of LUTS reaches the first peak during pregnancy and postnatal period. However, less attention has been paid to LUTS around childbirth and little progress has been made in the prevention of LUTS. Understanding the epidemiological characteristics of LUTS around childbirth would inform decision making for health care providers and perinatal women in the prevention of LUTS. The study aims to investigate the epidemiological trends and associated risk factors related to LUTS around childbirth., Methods: Pregnant women were consecutively enrolled during pregnancy in the obstetrical wards of a tertiary hospital and followed up at 6-8 weeks and one year postpartum through a prospective design. Urinary incontinence was assessed with the International Consultation on Incontinence Modular Questionnaire-Urinary Incontinence Short Form. Other symptoms were measured with questions based on definitions of the International Incontinence Society. Multiple logistic regression was used to examine the risk factors for LUTS including urinary incontinence, increased daytime frequency, nocturia and urgency. The report followed the STROBE statement., Results: A total of 1243 pregnant women participated in this study. The prevalence of at least one type of storage symptoms was 94%, 55% and 35% in late pregnancy, at 6-8 weeks and one year postpartum, respectively. The prevalence of urinary incontinence remained at 21% within one year postpartum. The majority of the participants suffered from mild to moderate urinary incontinence. Age, job, BMI before pregnancy, gestational diabetes mellitus, urinary tract infection history, previous history of LUTS, age at first birth and birth mode were predictors of LUTS one year postpartum., Conclusion: LUTS were highly prevalent during pregnancy and postnatal period. The prevalence of urinary incontinence was more stable than that of other LUTS within one year postpartum. Women aged more than 35 years, engaging in manual work, with gestational diabetes mellitus, with a history of urinary tract infection and LUTS, with advanced age at first birth and vaginal delivery were more likely to suffer from LUTS postpartum. The findings provided a novel and deep insight into the epidemiological trends and related risk factors of LUTS around childbirth., (© 2023. The Author(s).)

Background: Long-term mental health (MH) policies in Finland aimed at investing in community care and promoting reforms have led to a reduction in the number of psychiatric hospital beds. However, most resources are still allocated to hospital and community residential services due to various social, economic and political factors. Despite previous research focussing on the number and cost of these services, no study has evaluated the emerging patterns of use, their technical performance and the relationship with the workforce structure., Objective: The purpose of this study was to observe the patterns of use and their technical performance (efficiency) of the main types of care of MH services in the Helsinki-Uusimaa region (Finland), and to analyse the potential relationship between technical performance and the corresponding workforce structure., Methods: The sample included acute hospital residential care, non-hospital residential care and outpatient care services. The analysis was conducted using regression analysis, Monte Carlo simulation, fuzzy inference and data envelopment analysis., Results: The analysis showed a statistically significant linear relationship between the number of service users and the length of stay, number of beds in non-hospital residential care and number of contacts in outpatient care services. The three service types displayed a similar pattern of technical performance, with high relative technical efficiency on average and a low probability of being efficient. The most efficient acute hospital and outpatient care services integrated multidisciplinary teams, while psychiatrists and nurses characterized non-hospital residential care., Conclusions: The results indicated that the number of resources and utilization variables were linearly related to the number of users and that the relative technical efficiency of the services was similar across all types. This suggests homogenous MH management with small variations based on workforce allocation. Therefore, the distribution of workforce capacity should be considered in the development of effective policies and interventions in the southern Finnish MH system., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Several information and communication technologies (ICT) have been developed to enhance social connectedness of older adults aging in place, although they are not accessible for all. Barriers in using ICT might for example relate to health issues, sensory loss, lack of technical skills, or reluctance to use technologies. Though knowledge on these barriers is crucial for the development and implementation of ICT for older adults, no systematic review was found on this subject. The proposed qualitative systematic review aims to explore barriers experienced by older adults aging in place in using ICT for social interaction., Methods: The review will be conducted in accordance with the JBI methodology. Databases for search will include MEDLINE (via PubMed), CINAHL (via EBSCO), and Web of Science (ISI), among others. Included studies focus on older adults ageing in place 60 years or older. Pairs of authors will independently, by following agreed guidelines, assess the eligibility of studies, and extract data. The testing of eligibility criteria and screening of titles, abstracts, and full texts will be performed. The findings will describe for example populations, context, culture, and the phenomena of interest. Qualitative research findings will, where possible, be pooled by using JBI SUMARI for the meta-aggregation approach., Discussion: The mapping of published studies has the potential to identify research gaps in the existing literature, which again may inform developers and stakeholders in designing more user-friendly and adaptive ICT solutions for older people ageing in place., Systematic Review Registration: CRD42022370044., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Coccidiosis, a prominent intestinal protozoan disease, carries significant economic implications for the poultry industry. The aim of this study was to evaluate the effects of Fengqiang Shengtai (BLES), a probiotics product, and coccidiosis vaccine in modulating the intestinal microbiome and providing insight into mitigating the occurrence and management of avian coccidiosis., Methods: Broilers included in the study were divided into four pre-treatment groups: the Pre-Con group (commercial diet), Pre-BLES group (BLES supplement), Pre-Vac group (coccidiosis vaccination) and Pre-Vac-BLES group (combined vaccination and BLES). Body weight gain, feed consumption and feed conversion ratio were monitored from age 25 to 55 days. Cecum contents were collected at 8 and 15 days of age for comparative analysis of intestinal microbiomes. In the Pre-BLES and Pre-Vac-BLES groups, probiotics were administered at a dose of 0.01 g per chicken between ages 3 to 6 days and 10-13 days. At 3 days of age, chickens in the Pre-Vac and Pre-Vac-BLES groups were vaccinated with 1700 sporulated oocysts of the live coccidiosis vaccine per chicken. At the age of 25 days, Eimeria spp. challenge experiments were performed based on the aforementioned immunization strategy, and the oocysts per gram (OPG) in the feces, intestinal lesion score and intestinal pathological characteristics were evaluated. Specifically, 30 chickens were randomly selected from each group and orally administered 34,000 sporulated oocysts of Eimeria spp. per chicken, re-defined as Eimeria group, BLES-Eimeria group, Vac-Eimeria group and Vac-BLES-Eimeria group, respectively. Additionally, 30 chickens were randomly selected from the Pre-Con group and included as negative control without Eimeria spp., Challenge: Intestinal microbiota was sequenced and analyzed when the broilers were 32 days old., Results: A significant improvement was observed in body weight gain of the broilers in the Pre-BLES and Pre-Vac-BLES group at 45 days of age. Analysis of the intestinal microbiota revealed a positive correlation between the experimental groups receiving BLES and coccidiosis vaccines at 8 and 15 days of age with the Enterococcus genus and Lachnospiraceae NK4A136 group, respectively. In addition to the reduced lesion score and OPG values, the combination of coccidiosis vaccine and BLES also reduced the intestinal epithelial abscission induced by coccidiosis vaccines. The results of intestinal microbial function prediction demonstrated that N-glycan biosynthesis and ferroptosis were the prominent signal pathways in the Vac-BLES-Eimeria group., Conclusions: Taken together, the results of the present study suggest that supplementation of BLES with coccidiosis vaccine represents a promising strategy for improving growth performance, alleviating clinical manifestations and inducing favorable alterations to the intestinal microbiota in broiler chickens affected by coccidiosis., (© 2023. The Author(s).)

Whole exome sequencing (WES) can also detect some intronic variants, which may affect splicing and gene expression, but how to use these intronic variants, and the characteristics about them has not been reported. This study aims to reveal the characteristics of intronic variant in WES data, to further improve the clinical diagnostic value of WES. A total of 269 WES data was analyzed, 688,778 raw variants were called, among these 367,469 intronic variants were in intronic regions flanking exons which was upstream/downstream region of the exon (default is 200 bps). Contrary to expectation, the number of intronic variants with quality control (QC) passed was the lowest at the +2 and -2 positions but not at the +1 and -1 positions. The plausible explanation was that the former had the worst effect on trans-splicing, whereas the latter did not completely abolish splicing. And surprisingly, the number of intronic variants that passed QC was the highest at the +9 and -9 positions, indicating a potential splicing site boundary. The proportion of variants which could not pass QC filtering (false variants) in the intronic regions flanking exons generally accord with "S"-shaped curve. At +5 and -5 positions, the number of variants predicted damaging by software was most. This was also the position at which many pathogenic variants had been reported in recent years. Our study revealed the characteristics of intronic variant in WES data for the first time, we found the +9 and -9 positions might be a potentially splicing sites boundary and +5 and -5 positions were potentially important sites affecting splicing or gene expression, the +2 and -2 positions seem more important splicing site than +1 and -1 positions, and we found variants in intronic regions flanking exons over ± 50 bps may be unreliable. This result can help researchers find more useful variants and demonstrate that WES data is valuable for intronic variants analysis., (© 2023. The Author(s).)

Background: Smaller serving sizes of alcoholic drinks could reduce alcohol consumption across populations thereby lowering the risk of many diseases. The effect of modifying the available range of serving sizes of beer and cider in a real-world setting has yet to be studied. The current study assessed the impact on beer and cider sales of adding a serving size of draught beer and cider (2/3 pint) that was between the current smallest (1/2 pint) and largest (1 pint) standard serving sizes., Methods: Twenty-two licensed premises in England consented to taking part in the study. The study used an ABA reversal design, set over three 4-weekly periods, with A representing the non-intervention periods, during which standard serving sizes were served and B the intervention period when a 2/3 pint serving size of draught beer and cider was added to the existing range, along with smaller 1/2 pint and larger 1 pint serving sizes. The primary outcome was the daily volume of beer and cider sold, extracted from sales data., Results: Fourteen premises started the study, of which thirteen completed it. Twelve of those did so per protocol and were included in the primary analysis. After adjusting for pre-specified covariates, the intervention did not have a significant effect on the volume of beer and cider sold per day (3.14 ml; 95%CIs -2.29 to 8.58; p = 0.257)., Conclusions: In licensed premises, there was no evidence that adding a smaller serving size for draught beer and cider (2/3 pint) when the smallest (1/2 pint) and largest (1 pint) sizes were still available, affected the volume of beer and cider sold. Studies are warranted to assess the impact of removing the largest serving size., Trial Registration: ISRCTN: https://doi.org/10.1186/ISRCTN33169631 (08/09/2021), OSF: https://osf.io/xkgdb/ (08/09/2021)., (© 2023. The Author(s).)

Background: Neuronal networks receive and deliver information to regulate bodily functions while the vascular network provides oxygen, nutrients, and signaling molecules to tissues. Neurovascular interactions are vital for both tissue development and maintaining homeostasis in adulthood; these two network systems align and reciprocally communicate with one another. Although communication between network systems has been acknowledged, the lack of relevant in vitro models has hindered research at the mechanistic level. For example, the current used in vitro neurovascular models are typically established to be short-term (≤ 7 days) culture models, and they miss the supporting vascular mural cells., Methods: In this study, we utilized human induced pluripotent stem cell (hiPSC) -derived neurons, fluorescence tagged human umbilical vein endothelial cells (HUVECs), and either human bone marrow or adipose stem/stromal cells (BMSCs or ASCs) as the mural cell types to create a novel 3D neurovascular network-on-a-chip model. Collagen 1-fibrin matrix was used to establish long-term (≥ 14 days) 3D cell culture in a perfusable microphysiological environment., Results: Aprotinin-supplemented endothelial cell growth medium-2 (EGM-2) supported the simultaneous formation of neuronal networks, vascular structures, mural cell differentiation, and the stability of the 3D matrix. The formed neuronal and vascular networks were morphologically and functionally characterized. Neuronal networks supported vasculature formation based on direct cell contacts and by dramatically increasing the secretion of angiogenesis-related factors in multicultures in contrast to cocultures without neurons. Both utilized mural cell types supported the formation of neurovascular networks; however, the BMSCs seemed to boost neurovascular networks to greater extent., Conclusions: Overall, our study provides a novel human neurovascular network model that is applicable for creating in vivo-like tissue models with intrinsic neurovascular interactions. The 3D neurovascular network model on chip forms an initial platform for the development of vascularized and innervated organ-on-chip and further body-on-chip concepts and offers the possibility for mechanistic studies on neurovascular communication both under healthy and in disease conditions. Video Abstract., (© 2023. The Author(s).)

Background: Most patients with idiopathic pulmonary fibrosis (IPF) complain of cough. IPF-associated cough is widely characterized as dry or non-productive. The aim of this study was to compare chronic cough in early stage IPF patients to cough in subjects with chronic cough from a community-based sample and, especially, to investigate whether cough in IPF is less productive than chronic cough in a community-based sample., Methods: The IPF cough population consisted of 46 biopsy-confirmed patients who complained of chronic cough. Control population consisted of subjects with chronic cough, gathered by a community-based email survey sent to public service employees and the Finnish Pensioners' Federation. A case-control setting was applied by having four age, gender, and smoking-status matched subjects from the community sample for each IPF cough patient. A cough specific quality of life questionnaire (Leicester Cough Questionnaire (LCQ)) was filled in by all subjects. The LCQ questionnaire contains 19 questions, each question is scored from 1 to 7 and total score from 3 to 21 with a smaller value indicating more severe impairment., Results: The sputum production frequency, as assessed by LCQ question 2, was 5.0 (3.0-6.0) in the IPF chronic cough population and 5.0 (3.0-6.0) in the community-based chronic cough population (median and interquartile range p= 0.72). The LCQ total score was 14.8 (11.5-18.1) in the IPF chronic cough population and 15.4 (13.0-17.5) in the community-based chronic cough population (p=0.76). The domain impact scores were physical, 4.9 (3.9-6.1) vs. 5.1 (4.5-5.6) (p=0.80); psychological, 4.6 (3.7-5.9) vs. 4.7 (3.9-5.7) (p=0.90); and social, 5.5 (3.7-6.5) vs. 5.5 (4.5-6.3) (p=0.84), respectively. Furthermore, cough response to paint or fumes, cough disturbing sleep, and cough frequency per day did not differ between the groups., Conclusion: Cough in early stage IPF patients was not distinguishable from chronic cough in the community-based population by LCQ. Especially, there was no difference in the self-reported frequency of cough-associated sputum production., (© 2023. The Author(s).)

Background: The immune system interacts with cancer cells in various intricate ways that can protect the individual from overproliferation of cancer cells; however, these interactions can also lead to malignancy. There has been a dramatic increase in the application of cancer immunotherapy in the last decade. However, low immunogenicity, poor specificity, weak presentation efficiency, and off-target side effects still limit its widespread application. Fortunately, advanced biomaterials effectively contribute immunotherapy and play an important role in cancer treatment, making it a research hotspot in the biomedical field., Main Body: This review discusses immunotherapies and the development of related biomaterials for application in the field. The review first summarizes the various types of tumor immunotherapy applicable in clinical practice as well as their underlying mechanisms. Further, it focuses on the types of biomaterials applied in immunotherapy and related research on metal nanomaterials, silicon nanoparticles, carbon nanotubes, polymer nanoparticles, and cell membrane nanocarriers. Moreover, we introduce the preparation and processing technologies of these biomaterials (liposomes, microspheres, microneedles, and hydrogels) and summarize their mechanisms when applied to tumor immunotherapy. Finally, we discuss future advancements and shortcomings related to the application of biomaterials in tumor immunotherapy., Conclusion: Research on biomaterial-based tumor immunotherapy is booming; however, several challenges remain to be overcome to transition from experimental research to clinical application. Biomaterials have been optimized continuously and nanotechnology has achieved continuous progression, ensuring the development of more efficient biomaterials, thereby providing a platform and opportunity for breakthroughs in tumor immunotherapy., (© 2023. The Author(s).)

Background: Stress urinary incontinence during pregnancy is closely related to the occurrence of postpartum and long-term urinary incontinence. Early pelvic floor management is of great significance in promoting the recovery of pelvic floor tissues in pregnant women. However, effective management of urinary incontinence is far from achievable owing to the low adherence of pregnant women in partaking in pelvic floor rehabilitation. As a comprehensive framework for behavioural theory, the Theoretical Domain Framework allows for comprehensive identification of behavioural determinants. Using Theoretical Domain Framework, this study aimed to identify barriers and enablers of pelvic floor rehabilitation behaviours in pregnant women with stress urinary incontinence., Methods: A descriptive, qualitative design was used in this study. Face-to-face semi-structured interviews were conducted with pregnant women with stress urinary incontinence based on the Theoretical Domain Framework. The data were analysed using a combination of inductive and deductive methods., Results: Twenty pregnant women with stress urinary incontinence were interviewed. Seven themes were summarised and used to explain the pelvic floor rehabilitation behaviours of pregnant women with stress urinary incontinence. The seven themes were (1) individual knowledge and experience of pelvic floor management, (2) judgments about expected outcomes, (3) interactions of interpersonal situations, (4) environment, resources, and decision-making processes, (5) personal goal-setting and efforts towards behaviour change, (6) emotional influences on decision-making, and (7) personal characteristics. Besides the "Optimism" domain, 13 of the 14 Theoretical Domains Framework domains were found to influence pregnant patients' pelvic floor rehabilitation behaviours after deductive mapping of themes to the Theoretical Domains Framework. In addition, the inductive analysis generated a theme of personal characteristics that did not map to any of the Theoretical Domains Framework domains., Conclusions: The pelvic floor rehabilitation behaviours of pregnant women with stress urinary incontinence are complex and are affected by many factors. The findings confirm the need for multiple interventions to support pelvic floor management in pregnant women with stress urinary incontinence, focusing on enhancing knowledge and skills in pelvic floor care and using appropriate behaviour change techniques (such as prompts) to provide a supportive environment., (© 2023. The Author(s).)

Background: Endoplasmic reticulum stress (ER stress) may destroy endoplasmic reticulum homeostasis (ER homeostasis) and leads to programmable cell death. Unfolded protein response (UPR) originally stimulated by ER stress is critical for the survival of tumor cells through trying to re-establish ER homeostasis as an adaption to harsh microenvironment. However, mechanisms involving key regulators in modulating UPR remain underexplored., Methods: The expression of LINP1 in cutaneous squamous cell carcinoma (cSCC) tissues and cell lines was assessed. Subsequently, LINP1 was knocked out, knocked down or overexpressed in cSCC cells. CCK-8 assays, colony forming assays, transwell migration assays and invasiveness measurement by matrigel-coated transwell were performed to examine the role of LINP1 in cSCC development through gain-of-function and loss-of-function experiments. Transcriptomic sequencing (RNA-Seq) was conducted and indicated the key downstream signaling events regulated by LINP1 including UPR and apoptosis signaling. Furthermore, the direct interaction between LINP1 and eIF2α to modulate UPR and apoptosis was confirmed by RNA pulldown, RNA immunoprecipitation (RIP), ChIP-qPCR and in vitro phosphorylation assays., Results: In this study, LncRNA in non-homologous end joining pathway 1 (LINP1) was identified to be one of the top ten highest-expressed LncRNAs in cSCC, the second most common cancer in the world. Functional studies using in vitro and in vivo models revealed that LINP1 functions as an oncogene to promote cell proliferation, colony formation, migration and invasiveness while inhibiting cell apoptosis in cSCC. Transcriptomic sequencing after knockdown of LINP1 indicated LINP1 negatively regulates UPR-related pathways involving key effectors for activating UPR and the apoptosis following the prolonged UPR. Mechanistic study showed LINP1 physically interacts with eIF2α to inhibit its phosphorylation for avoiding unmitigated UPR. Loss of LINP1 followed by enhanced eIF2α phosphorylation led to overactivated UPR and induced DDIT3 expression, contributing to ER stress-induced apoptosis and suppression of cSCC development., Conclusions: Our findings demonstrate a novel regulatory hierarchy of UPR by demonstrating LINP1 as a critical modulator for eIF2α phosphorylation and a suppressor of UPR-mediated apoptosis, which suggests a novel therapeutic target for cSCC treatment., (© 2023. The Author(s).)

Background: Successful ageing is the term often used for depicting exceptional ageing but a uniform definition is lacking. The aim was to re-examine and describe the successful agers living at home at the age of 84 years or over after a 20-year follow-up. The purpose was also to identify possible factors leading to their successful ageing., Methods: Successful ageing was defined as the ability to live at home without daily care. Data on the participants' functional ability, objective health, self-rated health and satisfaction with life were gathered at baseline and after a 20-year follow-up period. A measurement of personal biological age (PBA) was established and the difference between the PBA and the chronological age (CA) was counted., Results: The participants' mean age was 87.6 years (Standard deviation 2.5, range 84-96). All analyzed variables depicted poorer physical ability and subjective health at re-examination than at baseline. Still, 99% of the participants were at least moderately satisfied with their lives. The PBA at baseline was 6.5 years younger than CA, and at re-examination, the difference was even more pronounced at 10.5 years., Discussion: Even though the participants were chronologically older, had poorer physical ability and subjective health, they were still satisfied with their lives indicating possible psychological resilience. The difference between the PBA and CA was greater at re-examination than at baseline indicating that they were also biologically successful agers., Conclusions: Successful agers were satisfied with life despite hardships and had a lower biological than chronological age. Further research is needed to evaluate causality., (© 2023. The Author(s).)

Background: A growing number of adolescents seek treatment for mental health problems, a circumstance that stresses the importance of implementing accessible treatment options. This study evaluates the impacts of brief, mental well-being intervention for adolescents in a school environment. As mental health interventions are often targeted at specific disorders, we sought a comprehensive approach to reach adolescents with a range of mental health symptoms., Methods: Single-group intervention study with a pretest-posttest design was utilized and conducted in lower, upper secondary, and vocational schools on adolescents ages 12-18 who sought medical attention for mental health symptoms. The cut-off point for inclusion was ≥ 14, for the Young Persons Clinical Outcomes for routine Evaluation (YP-CORE) measurement. The intervention included six face-to-face visits implemented by psychiatric nurses who received a 3-day training course. The impacts were evaluated after 6 weeks (n = 87) and again at 6 months (n = 68) and assessed using the YP-CORE, Beck Depression Inventory (BDI-II) and Overall Anxiety Severity and Impairment Scale (OASIS)., Results: The participants reported significant levels of mental distress at baseline with a YP-CORE mean score = 21.48, a BDI-II mean score = 23.60, OASIS mean score = 10.98. Post-intervention results at 6 weeks for the primary outcome YP-CORE showed a significant (p < .001) mean score decrease of - 3.82, a medium effect size d = .627. For participants attending upper secondary and vocational schools the YP-CORE scores changed significantly from baseline to 6-weeks (p = .005) and from baseline to 6-months (p < .001). Long-term outcomes at 6-months showed a - 1.14 decrease (p = non-significant), effect size d = .175. After the 6-week intervention, 12% of the participants were assessed as not requiring additional visits., Conclusions: This easily accessible intervention in a school setting indicated improvement for those participants with mild to moderate mental disorder symptoms and attending upper secondary and vocational schools. After the 6-week intervention, significant positive effects were observed. Participants reported substantial levels of mental distress at the baseline, which could contribute to the decline of symptoms and need for extended care during the 6 months follow-up. Trial registration Retrospectively registered with Clinicaltrials.gov identifier NCT05356949., (© 2023. The Author(s).)

Background: Quarantine due to the COVID-19 pandemic may have created great psychological stress among vulnerable populations. We aimed to investigate the prevalence of anxiety and explore the association between physical activities (PA) and anxiety risk in people with non-communicable diseases during the period of COVID-19 lockdown., Methods: We conducted a cross-sectional telephone survey from February 25 to April 20, 2020, the period of COVID-19 lockdown in Shanghai. Up to 8000 patients with type 2 diabetes and/or hypertension were selected using multi-stage cluster random sampling. PA level was measured based on the International Physical Activity Questionnaire using Metabolic Equivalent for Task scores, while symptoms of anxiety were assessed by the 7-item Generalized Anxiety Disorder scale. Multiple logistic regression analyses were performed to evaluate the associations of type and level of PA with the risk of anxiety., Results: Of a total 4877 eligible patients, 2602 (53.4%) reported with anxiety, and 2463 (50.5%), 123 (2.5%) and 16 (0.3%) reported with mild, moderate, and severe anxiety. The prevalence of anxiety was higher in the females, the elders, non-smokers, non-drinkers, and patients with diabetes, and the associations of anxiety with sex, age, smoking, drinking and diagnosis of diabetes were significant. A significant negative association was observed for housework activities (OR 0.53, 95%CI: [0.45, 0.63], p < 0.001) and trip activities (OR 0.55, 95%CI: [0.48, 0.63], p < 0.001) with anxiety, but no significant was found for exercise activities (OR 1.06, 95%CI: [0.94, 1.20], p = 0.321). Compared with patients with a low PA level, those with a moderate (OR 0.53, 95%CI: [0.44, 0.64], p < 0.001) or a high PA level (OR 0.51, 95%CI: [0.43, 0.51], p < 0.001) had a lower prevalence of anxiety., Conclusion: This study demonstrates a higher prevalence of anxiety in patients with hypertension, diabetes, or both during the COVID-19 lockdown. The negative associations of housework and trip activities with anxiety highlight the potential benefit of PA among patients with non-communicable diseases., (© 2023. The Author(s).)

Background: Various indexes have been developed to estimate the risk for mortality, institutionalization, and other adverse outcomes for older people. Most indexes are based on a large number of clinical or laboratory parameters. An index based on only a few parameters would be more practical to use in every-day clinical practice. Our aim was to create an index to predict the risk for mortality and institutionalization with as few parameters as possible without compromising their predictive ability., Methods: A prospective study with a 10-year follow-up period. Thirty-six clinical and fourteen laboratory parameters were combined to form an index. Cox regression model was used to analyze the association of the index with institutionalization and mortality. A backward statistical method was used to reduce the number of parameters to form an easy-to-use index for predicting institutionalization and mortality., Results: The mean age of the participants (n = 1172) was 73.1 (SD 6.6, range 64‒97) years. Altogether, 149 (14%) subjects were institutionalized, and 413 (35%) subjects deceased during the follow-up. Institutionalization and mortality rates increased as index scores increased both for the large 50-parameter combined index and for the reduced indexes. After a backward variable selection in the Cox regression model, three clinical parameters remained in the index to predict institutionalization and six clinical and three laboratory parameters in the index to predict mortality. The reduced indexes showed a slightly better predictive value for both institutionalization and mortality compared to the full index., Conclusions: A large index with fifty parameters included many unimportant parameters that did not increase its predictive value, and therefore could be replaced with a reduced index with only a few carefully chosen parameters, that were individually associated with institutionalization or death., (© 2023. The Author(s).)

Neurodegenerative disorders are accompanied by neuronal degeneration and glial dysfunction, resulting in cognitive, psychomotor, and behavioral impairment. Multiple factors including genetic, environmental, metabolic, and oxidant overload contribute to disease progression. Recent evidences suggest that metabolic syndrome is linked to various neurodegenerative diseases. Metabolic syndrome (MetS) is known to be accompanied by symptoms such as hyperglycemia, abdominal obesity, hypertriglyceridemia, and hypertension. Despite advances in knowledge about the pathogenesis of neurodegenerative disorders, effective treatments to combat neurodegenerative disorders caused by MetS have not been developed to date. Insulin growth factor-1 (IGF-1) deficiency has been associated with MetS-related pathologies both in-vivo and in-vitro. IGF-1 is essential for embryonic and adult neurogenesis, neuronal plasticity, neurotropism, angiogenesis, metabolic function, and protein clearance in the brain. Here, we review the evidence for the potential therapeutic effects of IGF-1 in the neurodegeneration related to metabolic syndrome. We elucidate how IGF-1 may be involved in molecular signaling defects that occurs in MetS-related neurodegenerative disorders and highlight the importance of IGF-1 as a potential therapeutic target in MetS-related neurological diseases., (© 2023. The Author(s).)

Background: Women with perinatal substance problems experience a multitude of barriers to care. They have specific early intervention needs, they endure societal stigma, and both substances and mental health issues influence the way they navigate within support and treatment systems. Early interventions for women with perinatal substance problems are underresearched contexts. The aim of the study is to describe building relationships and engagement within an outreach and low threshold service encounter tailored for pregnant women with SUD (substance use disorder)., Methods: The data consist of online written narratives from 11 workers involved in the program and feedback from 504 families in the recovery process comprising 228 open-ended answers. The data were analyzed with a thematic analysis., Results: The programs are characterized by flexibility and the implementation of inclusive ways to approach families. The themes for enhancing relationships and engagement within outreach and low threshold programs are Acceptance and attitude: a sensitive approach of approval; flexibility within strictness to allow for diversity and individuality; availability and space to ensure a trustful atmosphere; negotiating via doing to build connections; and everyday life changes: imagining recovery. The themes represent the need of being available, focusing on the worker's attitudes and building connections by doing together, and visioning recovery together., Conclusions: The study results can add to the understanding of SUD outreach and low threshold work during pregnancy. The elements described in this study need further theoretical development, research and critical assessment. Building relationships during pregnancy were characterized by connecting within everyday life situations and supporting the development of an attachment relationship between the baby and the parents. To promote recovery, a comprehensive approach in which substance-related issues and mental health conditions are interconnected can be favored. Engaging early on during pregnancy might enhance success during future rehabilitation., (© 2023. The Author(s).)