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Identification of the reporter gene combination that shows high contrast for cellular level MRI

by Naoya Hayashi, Junichi Hata, Tetsu Yoshida, Daisuke Yoshimaru, Yawara Haga, Hinako Oshiro, Ayano Oku, Noriyuki Kishi, Takako Shirakawa, Hideyuki Okano

Currently, we can label the certain cells by transducing specific genes, called reporter genes, and distinguish them from other cells. For example, fluorescent protein such as green fluorescence protein (GFP) is commonly used for cell labeling. However, fluorescent protein is difficult to observe in living animals. We can observe the reporter signals of the luciferin-luciferase system from the outside of living animals using in vivo imaging systems, although the resolution of this system is low. Therefore, in this study, we examined the reporter genes, which allowed the MRI-mediated observation of labeled cells in living animals. As a preliminary stage of animal study, we transduced some groups of plasmids that coded the protein that could take and store metal ions to the cell culture, added metal ions solutions, and measured their T1 or T2 relaxation values. Finally, we specified the best reporter gene combination for MRI, which was the combination of transferrin receptor, DMT1, and Ferritin-M6A for T1WI, and Ferritin-M6A for T2WI.

Physicians’ awareness of medication-related osteonecrosis of the jaw in patients with osteoporosis

by Nachapol Supanumpar, Pagaporn Pantuwadee Pisarnturakit, Natthinee Charatcharoenwitthaya, Keskanya Subbalekha

A serious adverse effect of antiresorptive drugs, which are widely used to treat osteoporosis, is medication-related osteonecrosis of the jaw (MRONJ). Physicians can reduce the risk of MRONJ by educating patients and emphasizing the importance of good oral health. However, limited information is available regarding physicians’ awareness and clinical practices associated with MRONJ. Hence, this study aimed to examine physicians’ awareness related to MRONJ and associated clinical practices. This study was a cross-sectional study conducted from December 2022 to February 2023. An online self-administered questionnaire was sent to physicians in Thailand who prescribed antiresorptive drugs for osteoporosis. Most respondents agreed that antiresorptive drugs might cause MRONJ (92.3%), poor oral health increased the risk of MRONJ (84%), and MRONJ is an important consideration in patients with osteoporosis (85%). Of the respondents, 48.1% and 15.5% always referred patients to dentists before and during antiresorptive therapy, respectively. Approximately 60% of physicians informed patients of the MRONJ risk before prescribing antiresorptive drugs, and 30% inquired about patients’ oral symptoms at the follow-up visit. Overall, 44% of physicians advised patients to receive oral health care; the most common reason for not advising this was that respondents did not consider themselves to be adequately knowledgeable to detect oral health problems. These findings indicate that while most physicians who prescribed antiresorptive drugs for osteoporosis were aware of and considered MRONJ in their practice, several took insufficient action to prevent it. This highlights the need to emphasize clinical practice guidelines and collaboration between physicians and dentists.

Views of family members on using video calls during the hospital admission of a patient: A qualitative study

Abstract

Background

Utilization of video calls on hospital wards to facilitate involvement of and communication with family members is still limited. A deeper understanding of the needs and expectations of family members regarding video calls on hospital wards is necessary, to identify potential barriers and facilitate video calls in practice.

Aim

The aim of this study was to explore the views, expectations and needs of a patient's family members regarding the use of video calls between family members, patients and healthcare professionals, during the patient's hospital admission.

Methods

A qualitative study was carried out. Semi-structured interviews with family members of patients admitted to two hospitals were conducted between February and May 2022. Family members of patients admitted to the surgical, internal medicine and gynaecological wards were recruited.

Results

Twelve family members of patients participated. Family members stated that they perceive video calls as a supplemental option and prefer live visits during hospital admission. They expected video calls to initiate additional moments of contact with healthcare professionals, e.g. to join in medical rounds. When deploying video calls, family members mentioned that adequate instruction and technical support by nurses should be available.

Conclusion

Family members considered video calls valuable when visiting is not possible or to participate in medical rounds or other contacts with healthcare professionals outside of visiting hours.

Implications

Family members need to be supported in options and use of video calls on hospital wards. Additional knowledge about actual participation in care through video calls is needed as well as the effect on patient, family and healthcare professional outcomes.

Impact

Using video calls on hospital wards can provide family members with flexible alternatives for contact and promote family involvement.

Reporting Method

COREQ guidelines.

Patient or Public Contribution

Family members of patients admitted to hospital have contributed by sharing their perspectives in interviews.

What does this paper contribute to the wider global clinical community?

Family members perceive additional value from the use of video calls on hospital wards. For family, use of video calls needs to be facilitated with clear instruction materials and support.

Trial and Protocol Registration

Amsterdam UMC Medical Ethics Review Committee (ref number W21_508 # 21.560).

The impact of different antibiotic injection regimens on patients with severe infections: A meta‐analysis

Abstract

Severe infection is a critical health threat to humans, and antibiotic treatment is one of the main therapeutic approaches. Nevertheless, the efficacy of various antibiotic injection regimens in severe infection patients remains uncertain. This study aimed to comprehensively evaluate the impact of various antibiotic injection strategies on patients with severe infection through a meta-analysis. Relevant research literature was collected by searching databases such as PubMed, Embase, and Cochrane Library. The retrieved literature was screened according to inclusion and exclusion criteria. Relevant data, including study design, sample size, and antibiotic regimens, were extracted from the included studies. The Cochrane Collaboration's Risk of Bias tool was employed to assess the risk of bias in each study. Statistical analysis was performed based on the results of the included studies. A total of 15 articles were included, covering various types of severe infection patients, including pulmonary and abdominal infections. The analysis provided insights into mortality rates, treatment efficacy, adverse reactions (ARs), Acute Physiology and Chronic Health Evaluation (APACHE) scores, among other outcomes. The results indicated that combination therapy was superior to monotherapy in terms of mortality rate, treatment efficacy, and APACHE scores, while the incidence of ARs was lower in the monotherapy group compared to the combination therapy group (p < 0.05). Combination therapy showed better treatment efficacy compared to monotherapy, although it was associated with a higher incidence of ARs.

Challenges and needs in cerebrovascular disease pathway: A qualitative descriptive study from the patients' and healthcare professionals' perspectives

Abstract

Aim(s)

To understand patients' and healthcare professionals' experiences to improve care in and across different domains of the cerebrovascular disease pathway.

Design

A qualitative descriptive study.

Methods

Semi-structured in-person interviews were conducted among 22 patients diagnosed with acute cerebrovascular disease and 26 healthcare professionals taking care of them in a single tertiary-level hospital from August 2021 to March 2022. Data were analysed using deductive and inductive content analysis. The consolidated criteria for reporting qualitative research was used to ensure reliable reporting.

Results

Overall, 19 generic and 79 sub-categories describing perceived challenges with 17 generic and 62 sub-categories describing perceived needs were identified related to primary prevention, organization of stroke services, management of acute stroke, secondary prevention, rehabilitation, evaluation of stroke outcome and quality assessment, and life after stroke.

Conclusion

Several challenges and needs were identified in and across the different domains of the cerebrovascular disease pathway. There is a requirement for adequate resources, early initiation of treatment, early diagnostics and recanalization, dedicated rehabilitation services, long-term counselling and support, and impact evaluation of services to improve cerebrovascular disease care. Future research on caregivers', and clinical leadership experiences in and across the cerebrovascular disease pathway is needed to explore the provision of services.

Implications for the Profession and/or Patient Care

The results of this study can be applied by organizations, managers and research for developing and improving services in the cerebrovascular disease pathway.

Impact

This study identified several patient-related, organizational and logistical needs and challenges, with suggestions for required actions, that can benefit the provision of effective, high-quality cerebrovascular disease care.

Reporting Method

We have adhered to relevant EQUATOR guidelines with the COREQ reporting method.

Patient or Public Contribution

No patient or public involvement.

Consumption of ultra-processed foods and low dietary diversity are associated with sedentary and unhealthy eating behaviors: A nationwide study with Brazilian Schoolchildren

by Giovanna Angela Leonel Oliveira, Vivian Siqueira Santos Gonçalves, Eduardo Yoshio Nakano, Natacha Toral

Background

Consumption of ultra-processed foods and low dietary diversity are risk factors for chronic diseases.

Aim

To evaluate the association between food consumption and sedentary and unhealthy eating behaviors of Brazilian schoolchildren between 6 and 11 years old.

Methods

Cross-sectional study. A prevalence sample was calculated considering the number of children enrolled in elementary school. This sample was distributed proportionally to Brazil’s macro-regions and the type of school (public or private). The questionnaire was developed in Google Forms and disseminated through the snowball technique. The questionnaire was filled in by the children’s parents, with information about the child’s identification and health. Afterward, the child completed a questionnaire by her/himself. We used the previously validated Illustrated Questionnaire on Food Consumption for Brazilian Schoolchildren and the Illustrated Questionnaire on Eating and Sedentary Behaviors. Food consumption was analyzed using the NOVA score and the dietary diversity score. Poisson’s regression with robust variance was performed (p Results

The study included 2,021 dyads. Of these, 27.6% of children reported eating five or more ultra-processed foods and 39.0% four or fewer natural or staple foods the previous day. Using screens, proxy of sedentary behavior (Prevalence Ratio–PR = 1.8, Confidence Interval–CI95%1.2–2.8) and eating at irregular hours (PR = 1.6, CI95%1.2–2.2) were risk factors for high consumption of ultra-processed foods and low dietary diversity in schoolchildren. In addition, eating the three main meals on the previous day (PR = 0.6, CI95%0.4–0.8) was identified as protective factors against the consumption of ultra-processed foods and in favor of dietary diversity among schoolchildren.

Conclusion

Sedentary and unhealthy eating behaviors were associated with the consumption of ultra-processed foods and low dietary diversity in Brazilian schoolchildren.

Antimicrobial resistance, virulence profile, and genetic analysis of ESBL-producing <i>Escherichia coli</i> isolated from Nile tilapia in fresh markets and supermarkets in Thailand

by Woranich Hinthong, Varangkana Thaotumpitak, Jarukorn Sripradite, Nitaya Indrawattana, Thassanee Srisook, Thida Kongngoen, Edward R. Atwill, Saharuetai Jeamsripong

This study investigated the prevalence and antimicrobial resistance (AMR) of Escherichia coli (E. coli) in Nile tilapia from fresh markets and supermarkets. A total of samples (n = 828) were collected from Nile tilapia including fish flesh (n = 276), liver and kidney (n = 276), and intestine (n = 276). Overall prevalence of fecal coliforms (61.6%) and E. coli (53.0%) were observed. High prevalence of E. coli was found in the intestine (71.4%), followed by the liver and kidney (45.7%). The highest prevalence of resistance was commonly found against tetracycline (78.5%), ampicillin (72.8%), and sulfamethoxazole (45.6%) with resistance to only tetracycline (15.2%) as the most common antibiogram. The prevalence of multidrug resistance (MDR) (54.4%) and Extended-spectrum beta-lactamases (ESBLs) (5.7%) were examined. The predominant virulence genes (n = 158) were st (14.6%), followed by eaeA (0.6%). The blaTEM (73.4%), tetA (65.2%), and qnrS (57.6%). There is statistical significance between Nile tilapia from fresh markets and supermarkets. Based on logistic regression analysis, ampicillin-resistant E. coli was statistically associated with the phenotypic resistance to tetracycline and trimethoprim, and the presence of blaTEM and tetA (p

Factors influencing implementation and sustainability of interventions to improve oral health and related health behaviours in adults experiencing severe and multiple disadvantage: a mixed-methods systematic review

Por: John · D. A. · Adams · E. A. · McGowan · L. J. · Joyes · E. C. · Richmond · C. · Beyer · F. R. · Landes · D. · Watt · R. G. · Sniehotta · F. F. · Paisi · M. · Bambra · C. · Craig · D. · Kaner · E. · Ramsay · S. E.
Objectives

Among people experiencing severe and multiple disadvantage (SMD), poor oral health is common and linked to smoking, substance use and high sugar intake. Studies have explored interventions addressing oral health and related behaviours; however, factors related to the implementation of these interventions remain unclear. This mixed-methods systematic review aimed to synthesise evidence on the implementation and sustainability of interventions to improve oral health and related health behaviours among adults experiencing SMD.

Methods

Bibliographic databases (MEDLINE, EMBASE, PsycINFO, CINAHL, EBSCO, Scopus) and grey literature were searched from inception to February 2023. Studies meeting the inclusion criteria were screened and extracted independently by two researchers. Quality appraisal was undertaken, and results were synthesised using narrative and thematic analyses.

Results

Seventeen papers were included (published between 1995 and 2022). Studies were mostly of moderate quality and included views from SMD groups and service providers. From the qualitative synthesis, most findings were related to aspects such as trust, resources and motivation levels of SMD groups and service providers. None of the studies reported on diet and none included repeated offending (one of the aspects of SMD). From the quantitative synthesis, no difference was observed in programme attendance between the interventions and usual care, although there was some indication of sustained improvements in participation in the intervention group.

Conclusion

This review provides some evidence that trust, adequate resources and motivation levels are potentially important in implementing interventions to improve oral health and substance use among SMD groups. Further research is needed from high quality studies and focusing on diet in this population.

PROSPERO registration number

CRD42020202416.

Effect of probiotics or prebiotics on thyroid function: A meta-analysis of eight randomized controlled trials

by Qinxi Shu, Chao Kang, Jiaxin Li, Zhenzhu Hou, Minfen Xiong, Xingang Wang, Hongyan Peng

Background

Microbiome-directed therapies are increasingly utilized to optimize thyroid function in both healthy individuals and those with thyroid disorders. However, recent doubts have been raised regarding the efficacy of probiotics, prebiotics, and synbiotics in improving thyroid function. This systematic review aimed to investigate the potential relationship between probiotics/prebiotics and thyroid function by analyzing the impact on thyroid hormone levels.

Methods

We conducted a comprehensive systematic review and meta-analysis of randomized controlled trials that investigated the effects of probiotics, prebiotics, and synbiotics on free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), and thyroid stimulating hormone receptor antibody (TRAb) levels. We searched for articles from PubMed, Scopus, Web of Science, and Embase up until April 1st, 2023, without any language restriction. Quantitative data analysis was performed using a random-effects model, with standardized mean difference (SMD) and 95% confidence interval as summary statistics. The methods and results were reported according to the PRISMA2020 statement.

Results

A total of eight articles were included in this review. The meta-analysis showed no significant alterations in TSH (SMD: -0.01, 95% CI: −0.21, 0.20, P = 0.93; I2: 0.00%), fT4 (SMD: 0.04, 95% CI: −0.29, 0.21, P = 0.73; I2: 0.00%) or fT3 (SMD: 0.45, 95% CI: −0.14, 1.03, P = 0.43; I2: 78.00%), while a significant reduction in TRAb levels was observed (SMD: -0.85, 95% CI: -1.54, -0.15, P = 0.02; I2: 18.00%) following probiotics/prebiotics supplementation. No indication of publication bias was found.

Conclusions

Probiotics/prebiotics supplementation does not influence thyroid hormone levels, but may modestly reduce TRAb levels in patients with Graves’ disease.

Body temperature in the acute phase and clinical outcomes after acute ischemic stroke

by Satomi Mezuki, Ryu Matsuo, Fumi Irie, Yuji Shono, Takahiro Kuwashiro, Hiroshi Sugimori, Yoshinobu Wakisaka, Tetsuro Ago, Masahiro Kamouchi, Takanari Kitazono, on behalf of the Fukuoka Stroke Registry Investigators

Background

This study aimed to examine whether post-stroke early body temperature is associated with neurological damage in the acute phase and functional outcomes at three months.

Methods

We included 7,177 patients with acute ischemic stroke within 24 h of onset. Axillary temperature was measured daily in the morning for seven days. Mean body temperature was grouped into five quintiles (Q1: 35.1‒36.5°C, Q2: 36.5‒36.7°C, Q3: 36.7‒36.8°C, Q4: 36.8‒37.1°C, and Q5: 37.1‒39.1°C). Clinical outcomes included neurological improvement during hospitalization and poor functional outcome (modified Rankin scale score, 3–6) at three months. A logistic regression analysis was performed to evaluate the association between body temperature and clinical outcomes.

Results

The patient’s mean (SD) age was 70.6 (12.3) years, and 35.7% of patients were women. Mean body temperature was significantly associated with less neurological improvement from Q2 (odds ratios [95% confidence interval], 0.77 [0.65–0.99] vs. Q1) to Q5 (0.33 [0.28–0.40], P for trend 37.0°C.

Conclusions

Post-stroke early high body temperature is independently associated with unfavorable outcomes following acute ischemic stroke.

Association between abdominal adiposity and clinical outcomes in patients with acute ischemic stroke

by Kayo Wakisaka, Ryu Matsuo, Fumi Irie, Yoshinobu Wakisaka, Tetsuro Ago, Masahiro Kamouchi, Takanari Kitazono, on behalf of the Fukuoka Stroke Registry Investigators

Background

It is unclear whether abdominal adiposity has an additional effect on post-stroke outcomes. This study aimed to determine whether waist circumference (WC) is independently associated with clinical outcomes after acute ischemic stroke.

Methods

We enrolled patients with acute ischemic stroke from a multicenter hospital-based stroke registry in Fukuoka, Japan. We measured WC on admission and categorized patients into four groups (Q1–Q4) according to the quartiles in females and males. The clinical outcomes were poor functional outcome (modified Rankin scale score 2–6) and death from any cause. Logistic regression analysis was performed to estimate the odds ratio and 95% confidence interval of the outcomes of interest after adjusting for potential confounding factors, including body mass index (BMI).

Results

A total of 11,989 patients (70.3±12.2 years, females: 36.1%) were included in the analysis. The risk of poor functional outcome significantly decreased for Q2–Q4 (vs. Q1) at discharge and Q2–Q3 (vs. Q1) at 3 months, even after adjusting for potential confounders, including BMI. In contrast, adjustment of BMI eliminated the significant association between WC and all-cause death at discharge and 3 months. The association between high WC and favorable functional outcome was not affected by fasting insulin levels or homeostatic model assessment for insulin resistance and was only found in patients without diabetes (P = 0.02 for heterogeneity).

Conclusions

These findings suggest that abdominal adiposity has an additional impact on post-stroke functional outcome, independent of body weight and insulin action.

Stress and burnout amongst mental health professionals in Singapore during Covid-19 endemicity

by Suyi Yang, Germaine Ke Jia Tan, Kang Sim, Lucas Jun Hao Lim, Benjamin Yong Qiang Tan, Abhiram Kanneganti, Shirley Beng Suat Ooi, Lue Ping Ong

The COVID-19 pandemic has exerted a huge emotional strain on mental health professionals (MHP) in Singapore. As Singapore transited into an endemic status, it is unclear whether the psychological strain has likewise lessened. The aims of this study were to investigate the levels of stress and burnout experienced by MHP working in a tertiary psychiatric hospital in Singapore during this phase of COVID-19 endemicity (2022) in comparison to the earlier pandemic years (2020 and 2021) and to identify factors which contribute to as well as ameliorate stress and burnout. A total of 282 MHP participated in an online survey in 2022, which included 2 validated measures, namely the Perceived Stress Scale and the Oldenburg Burnout Inventory (OLBI). Participants were also asked to rank factors that contributed the most to their stress and burnout. Between-group comparisons were conducted regarding stress and burnout levels among MHP across different demographic groupings and working contexts. In addition, OLBI data completed by MHP in 2020 and 2021 were extracted from 2 published studies, and trend analysis was conducted for the proportion of MHP meeting burnout threshold across 3 time points. We found that the proportion of MHP meeting burnout threshold in 2020, 2021 and 2022 were 76.9%, 87.6% and 77.9% respectively. Professional groups, age, years of experience and income groups were associated with stress and/or burnout. High clinical workload was ranked as the top factor that contributed to stress and burnout while flexible working arrangement was ranked as the top area for improvement so as to reduce stress and burnout. As such, policy makers and hospital management may want to focus on setting clear mental health targets and facilitate manageable clinical workload, build manpower resiliency, optimize resources and provide flexible work arrangements to alleviate stress and burnout among MHP.

Investigation of morbidity, length of stay, and healthcare costs of inpatient paediatric burns

Abstract

Burn injuries are the third most common cause of death in children due to trauma. Hospitalizations related to burn injuries are common. Prolonged hospitalization associated with burn treatment can result in increased resource utilization, leading to higher costs. Thus, it is essential to investigate these areas to reduce costs. The study investigated the morbidity and length of hospital stay of paediatric burn patients, as well as calculated the social security costs of hospitalization and treatment. The retrospective observational descriptive study examined the medical records of 774 paediatric patients treated in a burn intensive care unit at a tertiary medical faculty hospital between 01 March 2019 and 31 March 2022. The invoice records of payments made by the Social Security Institution to the hospital in return for health services provided to patients were examined. The healthcare costs were calculated. A total of 57.6% of the participants were boys and 79.2% were between the ages of 1–4. About 90% of the cases involved burns with a total body surface area (TBSA) of less than 20% and a 2nd-degree burn depth. Scalding was the most common cause of burns (88.2%). Among all patients, the mortality rate was 2.1% (n = 16). The mean length of hospital stay was 10.29 ± 9.59 days. The mean cost per day was 212.02 ± 190.94 US dollars ($US), and the cost per 1% TBSA was 241.70 ± 301.32 $US. According to the causes of burn injury, the mean cost of electricity was 5000.77 ± 8101.85 $US, fire 4818.02 ± 5852.22 $US, and chemical 3285.49 ± 4503.2 $US were observed in the first 3 ranks respectively. According to this study, paediatric burn cases occur due to preventable causes, and even though the mortality rate was low, the severity of burns, TBSA%, and presence of complications caused prolonged lengths of hospital stays, which caused social security costs to rise.

Topical metformin accelerates wound healing by promoting collagen synthesis and inhibiting apoptosis in a diabetic wound model

Abstract

The wound healing process, which is a pathophysiological process that includes various phases, is interrupted in diabetes due to hyperglycemia, and since deterioration occurs in these phases, a normal healing process is not observed. The aim of the current study is to investigate the proliferative and antiapoptotic effects of metformin on wound healing after topical application on diabetic and non-diabetic wounds. For this purpose, we applied metformin topically on the full-thickness excisional wound model we created in diabetic and nondiabetic groups. We investigated the effects of metformin on the apoptotic index by the Terminal deoxynucleotidyl transferase mediated dUTP Nick-End Labeling method and on collagen-I, collagen-III, p53, and c-jun expression levels by quantitative reverse transcription polymerase chain reaction technique in wound biopsy tissues. Our results showed that c-jun and p53 mRNA levels and apoptotic index increased with the effect of diabetes, while collagen synthesis was disrupted. As a result of the study, we showed that metformin increases cellular proliferation and has anti-apoptotic effects by increasing collagen-I/III expression and decreasing p53/c-jun level, especially in diabetic wounds and also in normal wounds. In conclusion, the topical effect of metformin on diabetic wounds reversed the adverse effects caused by diabetes, increasing the wound healing rate and improving the wound repair process.

Creating Subsets of International Classification for Nursing Practice Precoordinated Concepts: Diagnoses/Outcomes and Interventions Categorized Into Areas of Nursing Practice

imageThe International Classification for Nursing Practice is a comprehensive terminology representing the domain of nursing practice. A categorization of the diagnoses/outcomes and interventions may further increase the usefulness of the terminology in clinical practice. The aim of this study was to categorize the precoordinated concepts of the International Classification for Nursing Practice into subsets for nursing diagnoses/outcomes and interventions using the structure of an established documentation model. The aim was also to investigate the distribution of the precoordinated concepts of the International Classification for Nursing Practice across the different areas of nursing practice. The method was a descriptive content analysis using a deductive approach. The VIPS model was used as a theoretical framework for categorization. The results showed that all the precoordinated concepts of the International Classification for Nursing Practice could be categorized according to the keywords in the VIPS model. It also revealed the parts of nursing practice covered by the concepts of the International Classification for Nursing Practice as well as the parts that needed to be added to the International Classification for Nursing Practice. This has not been identified in earlier subsets as they covered only one specific area of nursing.

Development and Evaluation of a Mobile Application to Prevent Recurrent Stroke by Enhancing Self-management on Health Outcomes for Stroke Survivors

imageThis study aimed to develop a Mobile Application to Prevent Recurrent Stroke to prevent recurrent stroke by enhancing self-management and to evaluate its effects on stroke survivors' health outcomes. The Mobile Application to Prevent Recurrent Stroke was developed based on social cognitive theory and the model in order of analysis, design, development, implementation, and evaluation process. The Mobile Application to Prevent Recurrent Stroke consisted of health management contents such as information about stroke, its associated risk factors, and required skills to conduct self-management with tailored support and counseling. A quasi-experimental preintervention and postintervention design was used involving a total of 54 stroke survivors. The experimental group (n = 27) was provided the Mobile Application to Prevent Recurrent Stroke for 8 weeks, whereas the control group (n = 27) received an education booklet. The result revealed that medication adherence (P = .002), healthy eating habit (P

PIK3CA regulates development of diabetes retinopathy through the PI3K/Akt/mTOR pathway

by Ruijuan Guan, Zefeng Kang, Ling Li, Xin Yan, Tianpeng Gao

Objective

To explore their association with the development of diabetes retinopathy (DR), single nucleotide polymorphism (SNP) mutations were screened out by high-throughput sequencing and validated in patients diagnosed with DR. To understand the role of PIK3CA in the pathogenesis of DR and explore the relationship between PIK3CA,phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR),and DR, the effect of PIK3CA.rs17849079 mutation was investigated in a DR cell model.

Methods

Twelve patients diagnosed with DR at the Qinghai Provincial People’s Hospital from September 2020 to June 2021 were randomly selected as the case group, while 12 healthy subjects of similar age and gender who underwent physical examination in Qinghai Provincial People’s Hospital physical examination center during the same period were randomly selected as the control group. Blood samples (2 mL) were collected from both groups using EDTA anticoagulant blood collection vessels and frozen at −20°C for future analysis. SNP mutations were detected by high-throughput sequencing, and the shortlisted candidates were subjected by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The detected SNP candidates were verified by expanding the sample size (first validation: 56 patients in the case group and 58 controls; second validation: 157 patients in the case group and 96 controls). A lentivirus vector carrying mutated or wild-type PIK3CA.rs17849079 was constructed. ARPE-19 cells were cultured in a medium supplemented with 10% fetal bovine serum (FBS) to establish a DR cell model. PIRES2-PIK3CA-MT and PIRES2-PIK3CA-WT vectors were transfected into DR model cells, which were categorized into control, mannitol, model, empty vector, PIK3CA wild-type, and PIK3CA mutant-type groups. Cell activity was detected by the cell counting kit (CCK)-8 assay, and cellular apoptosis was evaluated by flow cytometry. Glucose concentration and levels of cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β were detected using enzyme-linked immunosorbent assay kits. The expression of PIK3CA, AKT1, mTOR, and VEGF genes was detected by real-time quantitative polymerase chain reaction (RT-qPCR), while the expression of PI3K, p-PI3K, AKT1, p-AKT1, mTOR, p-mTOR, and VEGF proteins was detected by western blotting.

Results

The mutated SNPs were mainly enriched in the PI3K/AKT pathway, calcium ion pathway, and glutamatergic synaptic and cholinergic synaptic signaling pathways. Seven SNPs, including PRKCE.rs1533476, DNAH11.rs10485983, ERAP1.rs149481, KLHL1.rs1318761, APOBEC3C.rs1969643, FYN.rs11963612, and KCTD1.rs7240205, were not related to the development of DR. PIK3CA.rs17849079 was prone to C/T mutation. The risk of DR increased with the presence of the C allele and decreased in the presence of the T allele. High glucose induced the expression of PIK3CA and VEGF mRNAs as well as the expression of PI3K, p-PI3K, p-AKT1, p-mTOR, and VEGF proteins in ARPE-19 cells, which led to secretion of inflammatory factors TNF-αand IL-1, cell apoptosis, and inhibition of cell proliferation. The PIK3CA.rs17849079 C allele accelerated the progression of DR. These biological effects were inhibited when the C allele of PIK3CA.rs17849079 was mutated to T allele.

Conclusion

The mutated SNP sites in patients with DR were mainly enriched in PI3K/AKT, calcium ion, and glutamatergic synaptic and cholinergic synaptic signaling pathways. The rs17849079 allele of PIK3CA is prone to C/T mutation where the C allele increases the risk of DR. High glucose activates the expression of PIK3CA and promotes the phosphorylation of PI3K, which leads to the phosphorylation of AKT and mTOR. These effects consequently increase VEGF expression and accelerate the development of DR. The C to T allele mutation in PIK3CA.rs17849079 can play a protective role and reduce the risk of DR.

Persistent symptoms among post‐COVID‐19 survivors: A systematic review and meta‐analysis

Abstract

Background

Single studies support the presence of several post-COVID-19 symptoms; however, there is no evidence for the synthesis of symptoms.

Objective

We attempt to provide an overview of the persistent symptoms that post-COVID-19 patients encounter, as well as the duration of these symptoms to help them plan their rehabilitation.

Design

Systematic review and meta-analysis.

Participants

A total of 16 studies involving 8756 patients post-COVID-19 were included.

Methods

The CINAHL, PubMed, EMBASE, Scopus, and Web of Science databases were searched from 2019 to August 2021. Observational studies that reported data on post-COVID-19 symptoms were included. The methodological quality of the studies was assessed using the Joanna Briggs Institute Critical Appraisal for Observational Studies. We included medium- to high-quality studies. We used a random-effects model for the meta-analytical pooled prevalence of each post-COVID-19 symptom, and I 2 statistics for heterogeneity.

Results

From the 2481 studies identified, 16 met the inclusion criteria. The sample included 7623 hospitalised and 1133 non-hospitalised patients. We found the most prevalent symptoms were fatigue and dyspnea with a pooled prevalence ranging from 42% (27%–58%). Other post-COVID-19 symptoms included sleep disturbance 28% (14%–45%), cough 25% (10%–44%), anosmia/ageusia 24% (7%–47%), fever 21% (4%–47%), myalgia 17% (2%–41%), chest pain 11% (5%–20%), and headache 9% (2%–20%). In addition to physical symptoms, anxiety/depression was also prevalent 27% (8%–53%).

Conclusions

Fatigue and dyspnea were the most prevalent post-COVID-19 symptoms and experienced up to 12 months.

Relevance to clinical practice

Multiple persistent symptoms are still experienced until 12 months of post-Covid 19. This meta-analysis should provide some awareness to nurses to highlights the unmet healthcare needs of post-COVID-19 patients. Long-term monitoring for the evaluation and treatment of symptoms and conditions and rehabilitation programs should be conducted.

The economic burden associated with unmet surgical needs in Liberia: a retrospective macroeconomic analysis based on a nationwide enumeration of surgical procedures

Por: Adde · H. A. · Oghogho · M. D. · van Duinen · A. J. · Grimes · C. E. · Hampaye · T. C. · Quaife · M. · Bolkan · H. A.
Objectives

The economic consequences of untreated surgical disease are potentially large. The aim of this study was to estimate the economic burden associated with unmet surgical needs in Liberia.

Design

A nationwide enumeration of surgical procedures and providers was conducted in Liberia in 2018. We estimated the number of disability-adjusted life years (DALYs) saved by operative activities and converted these into economic losses averted using gross national income per capita and value of a statistical life (VSL) approaches. The total, the met and the unmet needs for surgery were determined, and economic losses caused by unmet surgical needs were estimated. Finally, we valued the economic losses avoided by various surgical provider groups.

Results

A total of 55 890 DALYs were averted by surgical activities in 2018; these activities prevented an economic loss of between US$35 and US$141 million. About half of these values were generated by the non-specialist physician workforce. Furthermore, a non-specialist physician working a full-time position for 1 year prevented an economic loss of US$717 069 using the VSL approach, while a specialist resident and a certified specialist saved US$726 606 and US$698 877, respectively. The burden of unmet surgical need was associated with productivity losses of between US$388 million and US$1.6 billion; these losses equate to 11% and 46% of the annual gross domestic product for Liberia.

Conclusion

The economic burden of untreated surgical disease is large in Liberia. There is a need to strengthen the surgical system to reduce ongoing economic losses; a framework where specialist and non-specialist physicians collaborate may result in better economic return than a narrower focus on training specialists alone.

Decisional needs in people with kidney failure, their relatives and health professionals about end‐of‐life care options: A qualitative interview study

Abstract

Aim

To investigate the decisional needs in Denmark of people with kidney failure, relatives, and health professionals when planning end-of-life care.

Design

A qualitative interview study.

Methods

Individual semi-structured interviews were carried out with people with kidney failure, relatives and health professionals from November 2021 to June 2022. Malterud's systematic text condensation was used to analyse transcripts.

Results

A total of 13 patients, 10 relatives, and 12 health professionals were interviewed. Overall, four concepts were agreed on: (1) Talking about end of life is difficult, (2) Patients and relatives need more knowledge and information, (3) Health professionals need more tools and training, and (4) Experiencing busyness as a barrier to conversations about end of life.

Conclusion

People with kidney failure, relatives, and health professionals shared certain decisional needs while also having some different decisional needs about end-of-life care. To meet these various needs, end-of-life conversations should be systematic and organized according to the patients' needs and wishes.

Impact

Non-systematic end-of-life care decision-making processes limit patients' involvement. Patients and relatives need more knowledge about end-of-life care, and health professionals need more competences and time to discuss decisional needs. A shared decision-making intervention for people with kidney failure when making end-of-life care decisions will be developed.

Reporting Method

This empirical qualitative research is reported according to the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist.

Patient or Public Contribution

Patients, relatives, and health professionals have been involved throughout the research process as part of the research team and advisory board. The patients are people with kidney failure and the relatives are relatives of a person with kidney failure. For this study, the advisory board has particularly contributed to the validation of the invitation letter for participation, the interview guides and the preparation of the manuscript.

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