Transfection of hypoxia-inducible factor-1α mRNA upregulates the expression of genes encoding angiogenic growth factors.

Hypoxia-Inducible Factor-1α (HIF-1α) has presented a new direction for ischemic preconditioning of surgical flaps to promote their survival. In a previous study, we demonstrated the effectiveness of HIF-1a DNA plasmids in this application. In this study, to avoid complications associated with plasmid use, we sought to express HIF-1α through mRNA transfection and determine its biological activity by measuring the upregulation of downstream angiogenic genes. We transfected six different HIF-1a mRNAs-one predominant, three variant, and two novel mutant isoforms-into primary human dermal fibroblasts using Lipofectamine, and assessed mRNA levels using RT-qPCR. At all time points examined after transfection (3, 6, and 10 h), the levels of HIF-1α transcript were significantly higher in all HIF-1α transfected cells relative to the control (all p < 0.05, unpaired Student's T-test). Importantly, the expression of HIF-1α transcription response genes (VEGF, ANG-1, PGF, FLT1, and EDN1) was significantly higher in the cells transfected with all isoforms than with the control at six and/or ten hours post-transfection. All isoforms were transfected successfully into human fibroblast cells, resulting in the rapid upregulation of all five downstream angiogenic targets tested. These findings support the potential use of HIF-1α mRNA for protecting ischemic dermal flaps.

Correlates of post-traumatic growth among persons bereaved from cancer: A systematic review and meta-analysis.

BACKGROUND: Recent research identified that cancer bereavement can lead to post-traumatic growth (PTG). Although PTG and its correlates are well explored in cancer patients and survivors, persons bereaved from cancer have received scant attention. Therefore, the present review attempts to identify the correlates of PTG among persons bereaved from cancer. METHODS: A systematic search in PubMed, Web of Science, APA PsycNet, Science Direct, Scopus, and Wiley was conducted to identify quantitative studies published in English, resulting in 12 eligible reports being included in the final analysis. JBI critical checklists were employed to appraise the risk of bias. RESULTS: The review identified 17 correlates, which were classified into four categories: demographic factors (age, gender, religious status, level of education), loss-related factors (time since death, quality of death, prolonged grief symptoms), interpersonal factors (relationship to the deceased, social support, attachment style, bereavement behaviours) and intrapersonal factors (resilience, coping, rumination, benevolence, meaningfulness, self-worth). Random effects meta-analyses on six correlates revealed correlation coefficients of age = -0.02 (95% CI: -0.35-0.31), gender = 0.27 (95% CI: 0.08-0.45), time since death = 0.09 (95% CI: -0.02-0.20), quality of death = 0.29 (95% CI: -0.01-0.54), prolonged grief symptoms = 0.22 (95% CI: 0.08-0.35) and relationship to the deceased = 0.13 (95% CI: -0.03-0.29). Fixed effects meta-analysis was performed for social support (r = 0.13, 95% CI: 0.04-0.21). However, PTG was found to be significantly associated with gender, prolonged grief symptoms, and social support. CONCLUSIONS: Very few studies examined PTG among persons bereaved from cancer, highlighting the need for increased attention, understanding, and conceptualisation of PTG in the population.

Induced Pluripotent Stem Cell-Derived Extracellular Vesicles Promote Wound Repair in a Diabetic Mouse Model via an Anti-Inflammatory Immunomodulatory Mechanism.

Extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) have recently been explored in clinical trials for treatment of diseases with complex pathophysiologies. However, production of MSC EVs is currently hampered by donor-specific characteristics and limited ex vivo expansion capabilities before decreased potency, thus restricting their potential as a scalable and reproducible therapeutic. Induced pluripotent stem cells (iPSCs) represent a self-renewing source for obtaining differentiated iPSC-derived MSCs (iMSCs), circumventing both scalability and donor variability concerns for therapeutic EV production. Thus, it is initially sought to evaluate the therapeutic potential of iMSC EVs. Interestingly, while utilizing undifferentiated iPSC EVs as a control, it is found that their vascularization bioactivity is similar and their anti-inflammatory bioactivity is superior to donor-matched iMSC EVs in cell-based assays. To supplement this initial in vitro bioactivity screen, a diabetic wound healing mouse model where both the pro-vascularization and anti-inflammatory activity of these EVs would be beneficial is employed. In this in vivo model, iPSC EVs more effectively mediate inflammation resolution within the wound bed. Combined with the lack of additional differentiation steps required for iMSC generation, these results support the use of undifferentiated iPSCs as a source for therapeutic EV production with respect to both scalability and efficacy.

Understanding the Effect of Osteoarthritis on Surgical Treatment Patterns, Healthcare Resource Utilization, and Costs Among Patients With Tenosynovial Giant Cell Tumors.

BACKGROUND: Tenosynovial giant cell tumor (TGCT) may be misdiagnosed as osteoarthritis (OA), or the chronic course of TGCT may lead to development of secondary OA. However, little is known about the effect of comorbid OA on long-term surgical patterns and costs among TGCT patients. METHODS: This cohort study used claims data from the Merative MarketScan Research Databases. The study included adults diagnosed with TGCT from January 1, 2014, to June 30, 2019, who have at least 3 years of continuous enrollment before and after the first TGCT diagnosis (date of the first TGCT diagnosis = index date) and no other cancer diagnosis during the study period. Patients were stratified by the presence of an OA diagnosis relative to the index date. Outcomes included surgical procedure patterns, healthcare resource utilization, and costs in the 3-year pre- and postindex periods. Multivariable models were used to assess the effect of OA on the study outcomes, controlling for baseline characteristics. RESULTS: The study included 2856 TGCT patients: 1153 (40%) had no OA before or after index (OA[-/-]), 207 (7%) had OA before index but not after (OA[+/-]), 644 (23%) had OA after index but not before (OA[-/+]), and 852 (30%) had OA before and after index (OA[+/+]). The mean age was 51.6 years, and 61.7% were female. During the postperiod, joint surgery was more common among OA(-/+) and OA(+/+) patients compared with OA(-/-) and OA(+/-) patients (55.7% vs 33.2%). The mean all-cause total costs in the 3-year postperiod were $19,476 per patient per year. Compared with OA(-/-) patients, OA(-/+) and OA(+/+) patients had a higher risk of undergoing recurrent surgery and higher total healthcare costs postindex. DISCUSSION: Higher rates of surgery and increased healthcare cost observed in TGCT patients with postindex OA underscore the need for effective treatment options to reduce joint damage, especially among patients with comorbid OA.

TOMM20 as a Potential Prognostic Biomarker in Chordoma: Results From a High-Volume, Single-Center Study.

OBJECTIVES: As few large studies identify correlative biomarkers in chordoma, our objective was to use our large, single-center chordoma tumor bank to identify novel signaling pathways. METHODS: Clinical and pathologic data for 73 patients with chordoma were retrospectively collected. Tumor microarrays were built from 61 archived chordoma specimens; immunohistochemistry for TOMM20, TIGAR, and MCT1 were performed; and semiquantitative analysis of staining intensity and percentage of positive tumor cells was performed. Average composite scores of MCT1, TIGAR, and TOMM20 expression were compared by disease status and anatomic location. RESULTS: Higher expression of TOMM20 was seen in recurrent and metastatic chordomas compared with primary lesions. Comparing composite scores of primary lesions in patients with primary disease only vs those with recurrent disease showed that TIGAR and TOMM20 expressions are significantly higher in primary lesions, followed by a history of recurrence. A TOMM20 composite score of greater than or equal to 3 significantly decreased overall survival (hazard ratio [HR], 5.83) and recurrence-free survival (HR, 8.95). CONCLUSIONS: Identifying novel signaling pathways that promote chordoma growth and recurrence is critical for developing targeted therapy for chordoma. TOMM20 may be a biomarker associated with chordoma disease progression.

Induced pluripotent stem cell-derived extracellular vesicles promote wound repair in a diabetic mouse model via an anti-inflammatory immunomodulatory mechanism.

Extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) have recently been widely explored in clinical trials for treatment of diseases with complex pathophysiology. However, production of MSC EVs is currently hampered by donor-specific characteristics and limited ex vivo expansion capabilities before decreased potency, thus restricting their potential as a scalable and reproducible therapeutic. Induced pluripotent stem cells (iPSCs) represent a self-renewing source for obtaining differentiated iPSC-derived MSCs (iMSCs), circumventing both scalability and donor variability concerns for therapeutic EV production. Thus, we initially sought to evaluate the therapeutic potential of iMSC EVs. Interestingly, while utilizing undifferentiated iPSC EVs as a control, we found that their vascularization bioactivity was similar and their anti-inflammatory bioactivity was superior to donor-matched iMSC EVs in cell-based assays. To supplement this initial in vitro bioactivity screen, we employed a diabetic wound healing mouse model where both the pro-vascularization and anti-inflammatory activity of these EVs would be beneficial. In this in vivo model, iPSC EVs more effectively mediated inflammation resolution within the wound bed. Combined with the lack of additional differentiation steps required for iMSC generation, these results support the use of undifferentiated iPSCs as a source for therapeutic EV production with respect to both scalability and efficacy.

Comment on the Marshall-Hoare-Henssge model for estimating the time since death.

Timewise temperature variations in objects that are undergoing unsteady heating or cooling is a commonly encountered problem in the thermal sciences. One particular area of application is the cooling of a body post-death and the use of body temperatures to estimate the time of death. Here, a new approach based on the theory of transient heat transfer is formulated to allow efficient calculation of unsteady conduction problems. The theoretically derived unsteady temperature models are compared with experimentally based correlations (the Marshall-Hoare-Henssge model). The two approaches are found to agree very well. With this new theoretically based approach, timewise temperature variation can be calculated for both large and small Biot number transient problems.

Validation of a new method of providing case-specific time-of-death estimates using cadaver temperatures.

The near ubiquitous presence of numerical simulation has made case-specific calculations of body temperatures following death possible so that accurate calculations of body temperatures can provide valuable information for estimating the time of death and can aid in forensic investigations. Here, a computational approach is described that has been validated against multiple, independent, and experimental investigations. The approach only requires one subjective input parameter (the heat transfer coefficient). A simple algorithm serves as a guidepost to the selection of this parameter. The algorithm incorporates clothing and the space in which the body is housed. Heat transfer coefficients that range from h = 2 W/m2 /°C for bodies that are heavily clothed to h = 9 W/m2 /°C for bodies that are nude (in air). The method also requires setting of ambient temperature conditions (ambient temperature)-however, that input is often available. The paucity of inputs makes this technique remarkably easy to employ. The new method is also able to calculate cadaver cooling rates for situations where the cadaver is in a timewise or spatially changing thermal environment (diurnal temperature variations, bodies partially submerged in water, changes to weather, insolation, etc.). Results from the present calculations are compared with a large body of measurements from the literature; it was found that the predictions and measurements were in excellent agreement, regardless of the ambient temperature conditions and the nature of the clothing of the body. This new calculation approach can be used with reasonable accuracy for determining cadaver cooling and time since death.

Another Year of Record Heat for the Oceans.

Changes in ocean heat content (OHC), salinity, and stratification provide critical indicators for changes in Earth's energy and water cycles. These cycles have been profoundly altered due to the emission of greenhouse gasses and other anthropogenic substances by human activities, driving pervasive changes in Earth's climate system. In 2022, the world's oceans, as given by OHC, were again the hottest in the historical record and exceeded the previous 2021 record maximum. According to IAP/CAS data, the 0-2000 m OHC in 2022 exceeded that of 2021 by 10.9 ± 8.3 ZJ (1 Zetta Joules = 1021 Joules); and according to NCEI/NOAA data, by 9.1 ± 8.7 ZJ. Among seven regions, four basins (the North Pacific, North Atlantic, the Mediterranean Sea, and southern oceans) recorded their highest OHC since the 1950s. The salinity-contrast index, a quantification of the "salty gets saltier-fresh gets fresher" pattern, also reached its highest level on record in 2022, implying continued amplification of the global hydrological cycle. Regional OHC and salinity changes in 2022 were dominated by a strong La Niña event. Global upper-ocean stratification continued its increasing trend and was among the top seven in 2022.

Applications, benefits and challenges of telehealth in India during COVID-19 pandemic and beyond: a systematic review.

BACKGROUND: India, the seventh-largest country in the world and the second-most populated faces enormous challenges when it comes to healthcare. The country's healthcare system was close to collapse due to the detrimental effects of the COVID-19 pandemic. Telehealth, which enables treating patients remotely, played a critical role during these challenging times. This systematic review investigates in detail the role of telehealth during COVID-19 and its application beyond the pandemic. METHODS: Database searches on PubMed, Scopus, Science Direct and Web of Science were carried out for studies published on telehealth, and articles were included if they focused on any audio or video telehealth consultation during the pandemic in India. Findings were synthesised into three main themes: applications, benefits and challenges of telehealth services. Methodological quality was assessed using JBI critical appraisal tools. RESULTS: The initial search on databases yielded 1143 articles. Of those, 19 met the eligibility criteria. Findings highlight the effective utilisation of telehealth across multiple medical specialities. Although insufficient technological infrastructure and other barriers due to the virtual consultation challenge the successful implementation of telehealth in India, it has the potential to bridge the rural-urban healthcare divide with cost-effective and easily accessible services. CONCLUSION: High patient/provider satisfaction underscores the need to integrate telehealth into routine healthcare practices in the country. However, the review urges the government and healthcare practitioners to address the telehealth challenges with prime importance to ensure quality healthcare throughout the nation even after the pandemic.

Understanding Self-Care Behaviours among Type II Diabetes Patients: A Behaviour Change Models' Perspective.

BACKGROUND: Self-care behaviours among diabetes patients is often hindered because of various psycho-social factors which become obstacles to their better diabetes management and its proper outcome. The current study aims to find out these psycho-social factors that influence the execution of self-care behaviours among Type II diabetes patients from the perspective of various behaviour change models. METHODS: The study adopted a correlational research design. A total of 266 participants above the age group of 18 years and diagnosed with type 2 diabetes were selected using purposive sampling from the Indian state of Karnataka. The data were collected using The Health Belief Questionnaire, Theory of Planned Behaviour Questionnaire (TPBQ), Socio-Ecological Model Questionnaire, and Diabetic Self-Care Activities Revised (SDSCA-R). The data were analysed using descriptive statistics, Pearson product-moment correlation and multiple regression. RESULTS: From the findings, it was observed that the domains of perceived susceptibility, cues to action and subjective norms are positively correlated with self-care behaviours significantly at p<0.05 levels, while the domains of socio-ecological theory, personal, interpersonal, media and policy and community organizations are significantly positively correlated with self-care behaviour at p<0.01 levels. The linear regression of the domains of health belief model, theory of planned behaviour and socio-ecological theory on self-care behaviour showed that the statistically significant final model explained 14.9% (R2 =.149), F (3,262) =15.337, p< 0.000. The significant predictors are community at p<0.000 level, self-efficacy and perceived severity at p<0.05 levels. CONCLUSION: The study results ascertain the necessity of a psychosocial approach or the sociocognitive perspective to understand the factors that actually enable a diabetes patient to engage in more self-care behaviours. In the Indian scenario, where health literacy is very minimum, the findings of the study can be used to implement better strategies for diabetes management both at the level of medical/mental health professionals and at the level of media and policy.

Anticoagulation Strategies in Non-Critically Ill Patients with Covid-19.

Anticoagulation in Non-Critically Ill Covid-19 PatientsMcQuilten et al. conducted a randomized clinical trial comparing low-dose, intermediate-dose, low-dose plus aspirin, and therapeutic-dose anticoagulation in patients with Covid-19 of diverse ethnicities in high-, low-, and middle-income countries.

What Contributes to COVID-19 Vaccine Hesitancy? A Systematic Review of the Psychological Factors Associated with COVID-19 Vaccine Hesitancy.

Vaccine hesitancy plays a crucial role in worldwide pandemic-control efforts. The multifaceted nature of vaccine hesitancy entails many psychological factors that are widely discussed in the literature, although few studies specifically compile these factors. Thus, this systematic review aims to synthesize the psychological factors contributing to vaccine hesitancy. As per the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines, a systematic search was conducted on electronic databases PubMed, Scopus, Science Direct, PsycNET, and Web of Science, and a manual search was conducted on Google Scholar. Out of the 2289 articles obtained, 79 studies that met the inclusion criteria were deemed eligible for the review. The findings highlight appraisals of the COVID-19 pandemic, vaccine safety and side effects, vaccine confidence/trust, trust in government and healthcare professionals, scepticism around vaccine production, conspiracy beliefs, emotions, and information and knowledge about the vaccine as the major psychological factors contributing to vaccine hesitancy. Concerningly, misinformation on COVID-19 vaccination spread through social media platforms, increasing vaccine hesitancy. Recommendations for government authorities, healthcare professionals, and implications for future research are also outlined.

Prevalence of mental health problems among rural adolescents in India: A systematic review and meta-analysis.

Adolescent mental health problems have been recognised as a major issue in low-income countries including India. Through a meta-analytic approach, the present review delineate the overall prevalence of each of the most discussed mental health problems among rural adolescents in India, comprising depression, anxiety disorders, generalised anxiety disorder, panic disorder, separation anxiety, social anxiety disorder, suicidality, hyperactivity, emotional problems, conduct problems and peer problems. The review also presents the potential determinants of such mental health problems. Using PRISMA guidelines, a total of thirty-five studies were finalized from databases such as PubMed, Science Direct, JSTOR, Web of Science, Google Scholar and ProQuest. From the findings, it is observed that male and female adolescents does not differ significantly in the prevalence of most mental health problems. However, social anxiety was found to be more prevalent among females when compared to males. In meta-regression, factors like tools used (screening tools vs diagnostic interviews), sample size, setting (school-based vs community-based), sampling technique and year of publication were found to influence the prevalence rates of certain mental health problems, reported in the studies. Major determinants influencing the prevalence of mental health problems in rural adolescents were age, socio-economic status, academic and family environment. Individual factors such as social media usage, physical activity, and substance use also contribute to mental health problems. As India accounts for one-fifth of the world's adolescent population, the findings of this review can have global implications.

Erratum: Author Correction: Surgical Treatment Patterns, Healthcare Resource Utilization, and Economic Burden in Patients with Tenosynovial Giant Cell Tumor Who Underwent Joint Surgery in the United States.

[This corrects the article DOI: 10.36469/jheor.2022.32485.].

Cognitive style and working memory among adolescents with specific learning disability.

BACKGROUND: In a world where education directly influences the quality of life of an individual, educational handicaps are a grave issue that plagues the lives of those affected. The current study aims to find out whether there is a difference in the cognitive style and working memory capacity among adolescents with specific learning disability (SLD) in comparison to their age-matched equivalent group without SLD. The study also targets to find out if there exists any relationship between cognitive style and working memory. MATERIALS AND METHODS: A total of sixty participants were selected (thirty adolescents with learning disability and thirty age-matched adolescents without learning disability) from Bangalore district of Karnataka and Thrissur district of Kerala using purposive sampling method. The tools used were the Indian adaptation of Embedded Figures Test by Nigam (1997) and the Wechsler Intelligence Scale for Children-Fourth Edition by Wechsler (2003). RESULTS: The results showed that there exists a significant difference in cognitive style dimensions of field dependence and independence between adolescents with learning disability (M = 11.6, standard deviation [SD] = 6.52) and adolescents without learning disability (M = 25.2, SD = 7.33) as well as in the working memory capacity between adolescents with learning disability (M = 66.7, SD = 19.26) and adolescents without learning disability (M = 102, SD = 14.93) groups under study (p < 0.01). The results also indicate that there exists no significant relationship between cognitive style and working memory. CONCLUSION: Adolescents with SLD was found to be field dependent and has low working memory capacity than adolescents without learning disability. The results reflect the need for developing cognitive interventions to enhance working memory capacity and cognitive style for helping adolescents with learning disability in all areas of their functioning, such that the society benefits as a whole.

The psychological impact of quarantine due to COVID-19: A systematic review of risk, protective factors and interventions using socio-ecological model framework.

Background: Though quarantine is a pertinent control measure for the spread of COVID-19, it is equally important to consider its negative impacts, as it causes severe psychological, emotional, and financial problems not only for those who are quarantined but also for many others who are directly or indirectly connected to those who are quarantined. There appears to be a need to synthesise the available literature evidence on the psychological impact of quarantine experience, especially the multilevel risk factors that make individuals vulnerable to psychological impact and the protective factors to deal with the negative effects of quarantine. Objective: This systematic review attempted to identify the various psychological impacts associated with the experience of quarantine, the risk and protective factors and list out various psycho-social interventions that can minimise the risks and facilitate the protective factors associated with the experience of quarantine. Methods: A systematic search adhering to the PRISMA guidelines was performed in four databases PubMed, Scopus, PsycNet, Web of Science and 10518 articles related to COVID-19 and quarantine were obtained. After screening processes and quality assessment using standard checklist 74 articles that fulfilled the eligibility criteria were chosen for the final review. Findings: Individuals subjected to quarantine had anxiety, depression, post-traumatic stress symptoms, sleep problems, and somatic difficulties. Some of the key risk factors during quarantine are young age, female gender, low money, fear of infection, poor sleep quality, reduced physical activity, increased sedentary behaviours, and a lack of social support. Financial difficulties and stigma remained risk factors even after the quarantine period had ended. Key protective factors were coping skills, home based exercise, leisure, recreational activities, maintaining relationships using social media and availability of mental health services. The findings also highlight the necessity for tele mental health interventions to address the psychological effects of quarantine. Conclusion: Multilevel interventions are required to minimise the impact of risk factors and enhance protective factors.

Potential Role of Silencing Ribonucleic Acid for Esophageal Cancer Treatment.

INTRODUCTION: Esophageal cancer is an aggressive malignancy with high mortality. Optimal treatment of esophageal cancer remains an elusive goal. Ribonucleic acid (RNA) interference is a novel potential targeted approach to treat esophageal cancer. Targeting oncogenes that can alter critical cellular functions with silencing RNA molecules is a promising approach. The silencing of specific oncogenes in esophageal cancer cells in the experimental setting has been shown to decrease the expression of oncogenic proteins. This has resulted in cell apoptosis, reduction in cell proliferation, reduced invasion, migration, epithelial-mesenchymal transition, decrease in tumor angiogenesis and metastasis, and overcoming drug resistance. The Hedgehog (Hh) signaling pathway has been shown to be involved in esophageal adenocarcinoma formation in a reflux animal model. In addition to Hh, we will focus on other targets with clinical potential in the treatment of esophageal cancer. MATERIALS AND METHODS: We searched for articles published from 2005 to August 2020 that studied the siRNA effects on inhibiting esophageal cancer formation in experimental settings. We used combinations of the following terms for searching: "esophageal cancer," "RNA interference," "small interfering RNA," "siRNA," "silencing RNA," "Smoothened (Smo)," "Gli," "Bcl-2," "Bcl-XL," "Bcl-W,″ "Mcl-1," "Bfl-1," "STAT3,"and "Hypoxia inducible factor (HIF)". A total of 21 relevant articles were found. RESULTS AND CONCLUSIONS: Several proto-oncogenes/oncogenes including Hh pathway mediators, glioma-associated oncogene homolog 1 (Gli-1), Smoothened (Smo), and antiapoptotic Bcl-2 have potential as targets for silencing RNA in the treatment of esophageal cancer.