Greater Burden Research Articles

Development and characterisation of a 13-plex binding assay to detect Shigella antibodies in human samples

Abstract Shigella is the leading bacterial cause of diarrhea worldwide, with increasing levels of antibiotic resistance. The greatest burden is among children under five in low- and middle-income countries, and efforts are ongoing to develop vaccines against this pathogen. One of the challenges associated with the development of a vaccine against Shigella is the need for a multivalent vaccine covering the most prevalent Shigella serotypes. Epidemiological studies to better understand the prevalence of the different Shigella serotypes and inform vaccination schedules are very useful, together with clinical data showing the ability of vaccines to elicit cross-reactive antibodies. Here, we set up a Luminex-based method able to reproducibly measure antibodies specific to 13 different Shigella antigens in human sera. This method will allow to rapidly collect large amounts of data from analysis of serum samples from vaccinated subjects or people naturally exposed to Shigella, supporting the development of a vaccine against this disease.

Nutrition and diet in children with orofacial clefts in Africa: a scoping review

Background and aimThe burden of orofacial clefts (OFCs) has declined globally except in sub-Saharan Africa, with a great disease burden in North Africa. Children with OFCs have a high risk of malnutrition, and African countries have some of the highest malnutrition rates. This scoping review assessed the status of research on OFCs and nutrition and feeding among children living in African countries.MethodsWe followed the Joanna Briggs Institute guidelines for conducting scoping reviews. We searched eleven databases for articles on malnutrition and feeding among children with OFCs living in African countries. No restriction was done by type of study or publication date. Books, book chapters, and reviews were excluded. Only publications in English language were included. We extracted information about the publication year, study design, setting, location, participants’ age, data collection methods, international collaboration, and funding. We classified articles into studies assessing (1) the impact of nutritional deficiencies during pregnancy on OFCs, (2) the impact of OFCs on malnutrition, (3) feeding problems in children with OFCs, and (4) the impact of nutritional status on OFCs repair outcomes. We calculated frequencies and used bar charts and a map.ResultsOut of 208 search results, 36 were duplicates, and 25 eventually fit the inclusion criteria, with 52% retrieved from Google Scholar. About 80% of the studies were from four countries: Nigeria, South Africa, Ghana, and Uganda; 72% were hospital-based and 52% were cross-sectional. The most frequent data collection method was clinical examination and questionnaires. Most studies focused on feeding problems in children with OFCs (44%) and the impact of OFCs on malnutrition (32%). International collaboration was observed in six studies, with one study showing South-South collaboration. Only two studies were funded.ConclusionsThere is a predominance of under-funded descriptive research not indexed by international databases. Minimal research has been directed to population-level OFC preventive programs in primary healthcare settings and assessing interventions supporting children with OFCs. A research agenda is needed to prioritize research needs and secure funds to support South-South collaboration to address the nutrition and feeding-related problems associated with OFCs.

The Effect of Effort During a Resistance Exercise Session on Glycemic Control in Individuals Living With Prediabetes or Type 2 Diabetes: Protocol for a Crossover Randomized Controlled Trial.

Type 2 diabetes (T2D) is preceded by prediabetes, and these conditions place a great burden on patients and society. These conditions are significantly associated with poor glycemic control, which is improved by resistance exercise. It has been suggested that resistance exercise should be performed with a high degree of effort to improve glucose metabolism, but this is associated with negative psychological responses that might lead to lower long-term adherence. This study aimed to investigate the effect of the degree of effort during a resistance exercise session on glycemic control and psychological responses in individuals living with prediabetes or T2D. This study will be a crossover, 3-arm, randomized controlled trial. A total of 15 participants living with prediabetes or T2D will be thoroughly familiarized with 7 resistance exercises; afterward, they will perform 3 randomized experimental sessions, each lasting approximately 48 hours each, separated by at least 4 washout days. In 2 of these sessions, supervised resistance exercise will be performed, but the sessions will differ in the degree of effort in each set (high vs low) and will be equalized in terms of total weight lifted and session duration. For this, proximity to failure will be manipulated by changing the number of sets per exercise, the number of repetitions per set, and the resting interval between sets and exercises. Participants will also complete a sedentary (control) session, where they will not perform any exercise. In response to each session, psychological responses will be assessed (exertion, affect, enjoyment, self-efficacy, and discomfort). Glycemic control will be assessed by a continuous glucose monitoring device every 5 minutes, throughout the approximately 48 hours of each experimental session. Food and drink will be individually prescribed by a registered dietitian nutritionist and provided to participants, in order to control for the confounding effect of energy intake and diet composition. Physical activity levels will be assessed by accelerometry. Randomization will be done using the opaque, sequentially numbered envelopes technique. Participants and researchers will be blinded for continuous glucose monitoring and accelerometry data, and data will be analyzed by a blinded statistician. This study has been funded, and data collection is expected to take place between June 2024 and May 2025. Final manuscript submission should happen by August 2025. The results of this project might encourage individuals living with prediabetes and T2D to engage in resistance exercise while better informing exercise specialists on how to best incorporate resistance exercise in their client's or patient's routine. ClinicalTrials.gov NCT06208189; https://clinicaltrials.gov/study/NCT06208189. PRR1-10.2196/63598.

Health care resource utilization and costs across stages of amyotrophic lateral sclerosis in the United States.

People living with ALS (plwALS) experience motor control loss, speech/swallowing difficulties, respiratory insufficiency, and early death. Advancing disease stage is typically associated with a greater burden on the health care system, and delays in diagnosis can result in substantial health care resource utilization (HCRU). To estimate HCRU and cost burden of plwALS across disease stages from a US payer perspective we assessed HCRU and costs in early-, mid-, and late-stage ALS. Using insurance claims data from the IBM MarketScan Databases between January 2013 and December 2019, we identified plwALS as having at least 2 claims at least 27 days apart with an ALS International Classification of Diseases, Ninth or Tenth Revision diagnosis code (335.20/G12.21) or at least 1 ALS diagnosis code and prescription filled for riluzole/edaravone. Eligible plwALS were aged at least 18 years and had at least 12 months of enrollment data before and at least 6 months after the index date (date diagnosis criteria met). plwALS were grouped into disease stages using an ALS severity-based staging algorithm developed using ALS symptom and staging survey data from 142 neurologists reporting on 880 plwALS. The starting date of each severity stage was defined as the first date of an ALS symptom within the early-, mid-, and late-stage categories, respectively. The ending date for a severity stage was defined as the day before the first date of an ALS symptom from a more severe category. plwALS could transition to more severe stages, with reverse transition of severity excluded. Mixed regression modeling was used to assess differences in HCRU and costs per person-year between severity stages, adjusted for age and sex. 2,273 plwALS were included in the total ALS study sample, with 1,215 early-stage, 1,511 midstage, and 1,186 late-stage plwALS. 90% of early-stage plwALS had ALS symptoms before diagnosis, and 27% of late-stage plwALS had a late-stage symptom before diagnosis. In the evaluation period, later-stage ALS groups had more overall hospital admissions (early = 0.15, middle = 0.23, and late = 0.74; P < 0.01), outpatient visits/service (early = 26.81, middle = 32.78, and late = 48.54; P < 0.01), emergency department visits (early = 0.46, middle = 0.69, and late = 1.03; P < 0.01), and total prescription count (early = 9.23, middle = 11.37, and late = 12.72; P < 0.01) over 12 months. Annualized costs increased as ALS progressed (early = $31,411, middle = $51,481, and late = $121,903; P < 0.01), which was primarily driven by higher frequency of and cost per hospital admission. HCRU and costs increased with ALS progression, with diagnosis frequently occurring even after experiencing late-stage symptoms. These findings highlight the potential value of delaying progression into a more resource-intensive stage by diagnosing and adequately treating plwALS earlier in the disease course.

Role of the PGAM5-CypD mitochondrial pathway in methylglyoxal-induced bone loss in diabetic osteoporosis

Diabetic osteoporosis (DOP) is a skeletal complication with a high rate of disability. It results in a great burden to the patient's family and society. Methylglyoxal (MG) is a toxic by-product of the glycolytic process that occurs during diabetic conditions. It causes osteoblastic injury and con-tributes to the initiation and development of DOP. Disruption of mitochondrial homeostasis has been implicated as a cause of dysregulated osteo-blastogenesis, an essential step in bone formation. It is unclear whether mitochondrial dysfunction is involved in MG-induced osteoblast dysfunction. In this study, we showed that mitochondrial dysfunction contributes to MG-induced MC3T3-E1 cell apoptosis and impaired differentiation. A significant reduction of mitochondrial membrane potential (MMP) and ATP production occurred in MG-induced osteoblasts as well as increasing mitochondrial reactive oxygen species (mtROS) and intracellular Ca2+. Classical antioxidant N-Acetylcysteine (NAC) significantly attenuated mitochondrial dysfunction as well as osteoblast apoptosis and osteogenic differentiation damage induced by MG. More importantly, we found that activating phosphoglycerate mutase family member 5 (PGAM5) and cyclophilin D (CypD), which contributes to mitochondrial homeostasis, is involved in MG-induced osteoblast injury. Both PGAM5 and CypD knockdown effectively reversed osteoblast viability and function, whereas PGAM5 or CypD overexpression aggravated osteoblast injury caused by MG. Moreover, the result of co-transfection revealed that PGAM5 is an upstream signaling molecule of CypD. By constructing type I diabetes mouse models, we further found that the expression of PGAM5 and CypD were both increased in the femur along with a reduction of ATP and increased TUNEL-positive cells. These results, for the first time, suggest that MG-induced mitochondrial dysfunction induces osteoblast injury through the PGAM5-CypD pathway. This study provides insight into the prevention and treatment of DOP. Lay summaryThis study highlights the role of mitochondria in regulating osteoblast viability and function under conditions of diabetic osteoporosis (DOP). We found that the PGAM5-CypD mitochondrial pathway is activated following glycolytic by-product methylglyoxal (MG) treatment, which contributes to mitochondrial dysfunction and osteogenic dysfunction. This mechanism implicates mitochondria as a potential therapeutic target for osteoporosis.

The Impact of Double Reduction Policy on College Entrance Examination Performance: Empirical Evidence

In China, the College Entrance Examination weights great in both students' and parents' hearts, which is even recognized as the rare chance to change a people's fate. At this circumstances, heavy homework, countless tests, little break time, burning night oils and even extracurricular tutoring on the weekends have become the daily routine for Chinese high school students, which have hurt their health conditions and added great burden on their mental health. To curb this long-standing issue caused by this phenomenon, a new educational policy called Double Reduction was released by the Chinese government on 2021 and nine Chinese cities are selected as the national policy pilot areas to test the effect in advance. This paper aims to verify the impact of the Double Reduction Policy in some provinces in which lie the selected policy pilot areas. Through continuous difference-indifference method, this study found no significant correlation between the Double Reduction and the College Entrance Examination performance in these areas. Policy makers should make proper actions to implement this new policy, in order to lighten the physical and mental burden of students and the financial burden of parents while take students learning effectiveness into consideration meanwhile.

Hyperbaric Oxygen Improves Cognitive Impairment Induced by Hypoxia via Upregulating the Expression of Oleic Acid and MBOAT2 of Mice

Cognitive impairment (CI) causes severe impairment of brain function and quality of life of patients, which brings a great burden to society. Cerebral hypoxia is an important factor in the pathogenesis of CI. Hyperbaric oxygen (HBO) therapy may mitigate hypoxia-induced CI, but its efficacy and mechanisms are not fully understood. In this study, a mice model of CI induced by hypoxia environment was established, then behavioral tests, pathological examination, metabolomic and lipidomic analyses, and molecular biology were used to assess the impact of HBO on hypoxia-induced CI. HBO was found to alleviate CI and pathological damage of hypoxia mice. Metabolomic, lipidomic, and molecular biology analyses showed that HBO increased the levels of oleic acid (OA) and membrane-bound O-acyltransferase 2 (MBOAT2), thereby altering the composition of membrane phospholipids (PLs) and reducing hypoxia-induced neuronal ferroptosis (FPT) to interfere with cognitive function in mice. In vitro experiments confirmed that OA and MBOAT2 led to membrane PL remodeling in a mutually dependent manner, affecting cell resistance to hypoxia-FPT. The results emphasized the combined effect value of OA and MBOAT2 in HBO for hypoxia-induced CI, and provided a novel perspective for the treatment of CI by HBO.

"I don't want hear about that": Treatment wishes/preferences of elderly patients regarding possible treatment goals in acute life-threatening illness or acute organ failure

Abstract Background In many people with acutely life-threatening illnesses, the will to undergo treatment is not known with sufficient precision. It is often unclear whether the person concerned would have consented to life-sustaining measures or would have preferred to die with palliative care. This applies in particular to the vulnerable group of elderly, chronically ill/fragile people. It is not uncommon for people to reject the risks/burdens of medical treatment, even if there is a chance of success. On the other hand, there are many people who fight to continue living, even if this can be associated with great burdens and the outcome is rather uncertain. Aim of the study is to determine the characteristics of cardiologic patients who refuse to discuss treatment wishes/preferences in case of acute emergencies, temporary (e.g. in the context of intensive care unit (ICU) treatment), or permanent (vegetative state) inability to consent. Methods Prospective, questionnaire-based cross-sectional study including Hospital Anxiety and Depression Scale (HADS) and assessment of quality of life using the 12-item Short Form Health Survey (SF-12) on normal cardiology wards. Results 455 cardiologic patients were interviewed (mean age 71.2 ± 12.9 years, 39.6% female), 76.1% had moderate-severe concomitant diseases according to the Carlsson Comorbidity Index (4.3 ± 2.4 points) (see Table I). 23.5 % of respondents did not wish to address the above-mentioned question, they were significantly older (74.6 ± 13.1 vs. 69.9 ± 12.8 years; p=0.0009), had more comorbidities, were less likely to have a high level of education (university degree: 13.0 % vs. 30.6 %; p=0.0021) and were less likely to be employed (11.7 % vs. 25.8 %; p=0.0026). Furthermore, these patients live alone more frequently (45.8% vs. 30.6%; p=0.0048) and are less likely to live in a partnership (52.0% vs. 68.0%; p=0.0043). Refusal of an advance directive was also more common (22.5% vs. 10.7%; p=0.05), quality of life was impaired (42.4 ± 9.8 vs. 45.9 ± 10.5 points; p=0.0022), and the HADS-score levels were higher (15.6 ± 7.3 vs. 12.7 ± 7.8 points; p=0.0007). Conclusions A relevant proportion of our patients refuse to discuss treatment wishes/preferences in case of acute emergencies, temporary or permanent inability to consent. Paradoxically, these were patients for whom it would make particular sense (older, sicker, and more socially isolated patients). Those patients are also prone to anxiety and depression, and have a reduced quality of life.

Selective Hydrogenolysis Conversion of Polyethylene into Alkyl Oil Over Iridium-based Catalyst.

Plastic not only brings convenience but also places a great burden on the environment. Utilizing plastic as a low-cost feed-stock for producing valuable chemicals and fuels is one of the most attractive directions. Among the huge types of plastics, polyolefins (PO), especially polyethylene (PE), were the most abundant type and the most difficult to upgrade. Hydrocracking and hydrogenolysis operate at relatively low reaction temperatures which show promising applications. Herein, Iridium-based catalysts were developed and proved to be effective in PE hydrogenolysis under relatively mild conditions. Catalysts were characterized by TEM, HRTEM, SEM, HAADF-STEM, XPS, CO chemisorption and H2 chemisorption etc. The Ir catalysts showed similar reactivity but better selectivity for liquid products than Ru under similar conditions. A highest 92.7 % percent of liquid products could be obtained under 250 °C, 3 MPa of H2 in 8 hours with Ir/γ-Al2O3 catalyst. The support could also affect the performance, including Lewis acid amount, surface areas, and morphology. And we suppose Iridium catalysts could serve as another choice for plastic hydrogenolysis under mild conditions.

D1-like dopamine receptors promote B-cell differentiation in systemic lupus erythematosus

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease that currently cannot be completely cured with a great health burden. Since the production of autoantibodies plays a key role in the pathogenesis of SLE, discovering the underlying immunoregulation mechanism of B cells will be helpful for developing promising immunotherapy for SLE. In recent studies, dopamine receptors (DRDs), G protein-coupled receptors that include D1-like and D2-like subtypes, are expressed on B cells and participate in various physiological processes, involving immune responses. However, the regulatory effect of DRDs on B cells has not been determined.MethodsThis study explored the expression of DRDs on B-cell subsets from SLE patients and healthy individuals. The effects of D1-like receptor on B-cell activation and differentiation were further explored using D1-like receptor agonists or antagonists. RNA-seq and bioinformatics analyses were used to identify specific molecular mechanisms involved.ResultsThe D1-like DRDs on B cells of SLE patients were highly expressed compared with those of healthy controls (HCs). D1-like receptor agonist treatment exacerbated lupus-like symptoms in pristane-induced lupus-like mice, while D1-like receptor antagonists alleviated the lupus-like phenotypes. Inhibition of D1-like receptor signals impeded B-cell differentiation, while activation of D1-like receptor signals could promote B cell differentiation. Further RNA-seq confirmed that PTGS2, a gene related to B-cell differentiation, was up-regulated once the D1-like receptor signals were activated, while BMP6 and IL-24 were up-regulated once the D1-like receptor signals were inhibited.ConclusionD1-like receptors probably promote B-cell differentiation through the PTGS2/PRDM1 pathway.

Sequential bias-corrected weighted least squares solution of mixed additive and multiplicative error models

In the era of big data, the number of observations in adjustment calculations may reach tens or even hundreds of thousands. When dealing with these large dataset problems, many matrix operations are often required. At this time, the dimensions of the matrix will be large, which will generate a great computational burden. At present, no research results have been published on the computational efficiency of bias-corrected weighted least squares (bcWLS) for mixed additive and multiplicative error models (MAMEM). Sequential adjustment (SEA) groups the observations for calculation and can provide the same computational precision while greatly improving computational efficiency. This paper applies the idea of SEA to the calculation of bcWLS and proposes an iterative solution for sequential bcWLS (SEbcWLS). Using three simulation experiments to verify the effectiveness of our method, it was found that when the number of observations is 10000, the effect is better when the number of groups does not exceed 100, achieving the same precision as the original method while having high computational efficiency. The calculation results of line fitting and plane fitting are not affected by the number of grouping groups. For DEM (Digital elevation model) experiments with strong nonlinearity, when the number of grouping groups is too large, the effect is not very good, but the calculation efficiency is also higher than the original method, and the difference in calculation results is not significant.

UNDERSTANDING THE MANAGEMENT OF MALIGNANT GLIOMAS DURING COVID-19 PANDEMIC IN A HIGH VOLUME TERTIARY GOVERNMENT HOSPITAL IN THE PHILIPPINES

Abstract AIMS Malignant glioma is a common primary brain tumor with a great burden of disease. When COVID-19 set in, it became a challenge to manage an already difficult treatment process in low-resource-setting centers. Despite this, conventional recommendations and standard treatment protocols are followed. However, outcomes were perceived to deviate from the convention, hence the reason for this study which is to understand the nature of outcomes in the management of malignant gliomas during the COVID-19 pandemic in Southern Philippines Medical Center (SPMC), the largest government tertiary hospital in the Philippines. METHOD A retrospective chart review of nine clinically and histologically diagnosed cases of malignant gliomas admitted in SPMC between April 2020 to September 2021 was performed. The clinical presentations, image correlation, and outcomes were listed. Then, classified as desirable, undesirable but acceptable, or unacceptable based on factors identified. Qualitative analysis by deduction including outcomes determining possible modifications in treatment of future cases was done. RESULTS Of the nine cases, one was listed as desirable, one with unacceptable outcome due to management complications, and the rest were labeled as undesirable but acceptable either because of advanced disease or poor KPS score. Three major factors were determined: the roles of pre-hospital and initial treatment delays, the decision for surgical treatment, and the COVID-19 pandemic. CONCLUSION The shift in the outcomes of malignant gliomas during COVID-19 shows the management challenge in low resource centers. There is an increase in highly malignant cases with guarded prognosis due to lack of education, support, and resources in terms of early diagnosis, treatment, and post-surgical care. This was aggravated by the restrictions imposed by the pandemic and financial crisis, especially for patients below the poverty line. Delays in management show a significant influence on prognosis regardless of treatment. As such, possible modifications in the current treatment algorithm are hereby recommended.

The Effect of Platelet Fibrin Plasma (PFP) on Postoperative Refractory Wounds: Physiologically Concentrated Platelet Plasma in Wound Repair.

Surgical wounds that can't complete primary healing three weeks after surgery are called postoperative refractory wounds. Postoperative refractory wounds would bring great physical and life burdens to the patients and seriously affect their quality of life. To investigate the effect of platelet fibrin plasma (PFP) on postoperative refractory wound healing. The composition of PFP was analyzed using blood routine and blood biochemicals. Clinical data were collected that met the inclusion criteria after treatment with PFP, and the efficacy of PFP was evaluated by wound healing rate and days to healing. Next, growth factor content in PFP, PRP, and PPP was analyzed using ELISA, and PFP-treated cells were applied to investigate the effect of PFP on fibroblast and endothelial cell function. PFP component analysis revealed no statistical difference between platelet concentration in PFP and physiological concentration. Clinical statistics showed that PFP treatment was effective in the postoperative refractory wound (four-week wound healing rate > 90%), significantly better than continuous wound dressing. Meanwhile, our result also proved that PFP treatment significantly enhanced vascularization by upregulated the expression level of CD31 and improved granulation tissue thickness. Activated PFP, PRP, and PPP could continuously release growth factors in vitro and the amount of growth factors released by PRP and PFP was significantly higher than PPP. In vitro studies demonstrated that active PFP could improve cell proliferation, migration, adhesion, and angiogenesis in fibroblasts and endothelial cells. Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The modified PFP (responsible for accelerating wound healing and enhancing the migration and proliferation of fibroblasts and endothelial cells) was prepared and analyzed for its clinical effectiveness in postoperative refractory wounds. Physiologically concentrated platelet plasma promoted wound healing and improved related cellular functions. The preparation of PFP could significantly reduce the amount of prepared blood, with a good application value for postoperative wounds. PFP can be considered a treatment option, especially for postoperative refractory wounds.

The impact of children’s dental anxiety on dentists

INTRODUCTION. According to statistics, medical workers and, in particular, dentists are exposed to stressful factors in the workplace on a daily basis. Due to the specifics of their daily activities, pediatric dentists experience a great emotional burden, especially when treating children who are not adapted to dental care, which leads to the development of an emotional burnout syndrome among specialists. AIM. To determine the effect of children’s dental anxiety on emotional stability during admission and psychoemotional status after admission by dentists with emotional burnout syndrome.MATERIALS AND METHODS. The study involved 76 pediatric dentists and 68 patients aged 6–7 years. The psychoemotional state of dentists was assessed using the Maslach Burnout Questionnaire and a Visual Analog Scale. The behavior of children at the dental appointment was recorded according to the evaluation scale of the behavioral profile of the Melamed.RESULTS. According to the results of the Maslach questionnaire, burnout syndrome of varying severity was detected in all specialists. Deterioration of the psychoemotional state after receiving a patient who was not adapted to dental treatment was observed in 16%.CONCLUSIONS. The study shows that in order to prevent burnout syndrome in pediatric dentists, it is necessary to reduce professional stress through methods of adapting children to treatment, correcting patient behavior and reducing dental anxiety.

SFRP2 modulates functional phenotype transition and energy metabolism of macrophages during diabetic wound healing.

Diabetic foot ulcer (DFU) is a serious complication of diabetes mellitus, which causes great health damage and economic burden to patients. The pathogenesis of DFU is not fully understood. We screened wound healing-related genes using bioinformatics analysis, and full-thickness skin injury mice model and cellular assays were used to explore the role of target genes in diabetic wound healing. SFRP2 was identified as a wound healing-related gene, and the expression of SFRP2 is associated with immune cell infiltration in DFU. In vivo study showed that suppression of SFRP2 delayed the wound healing process of diabetic mice, impeded angiogenesis and matrix remodeling, but did not affect wound healing process of control mice. In addition, suppression of SFRP2 increased macrophage infiltration and impeded the transition of macrophages functional phenotypes during diabetic wound healing, and affected the transcriptome signatures-related to inflammatory response and energy metabolism at the early stage of wound healing. Extracellular flux analysis (EFA) showed that suppression of SFRP2 decreased mitochondrial energy metabolism and increased glycolysis in injury-related macrophages, but impeded both glycolysis and mitochondrial energy metabolism in inflammatory macrophages. In addition, suppression of SFRP2 inhibited wnt signaling-related genes in macrophages. Treatment of AAV-SFRP2 augmented wound healing in diabetic mice and demonstrated the therapeutic potential of SFRP2. In conclusions, SFRP2 may function as a wound healing-related gene in DFU by modulating functional phenotype transition of macrophages and the balance between mitochondrial energy metabolism and glycolysis.

Effects of pulsed electromagnetic fields on bone fractures: a systematic review update.

Fractures are common bone injuries, which have a great burden on global health. Fracture healing is a long-term process that may be influenced by a number of factors. The 10-15% of all bone fractures may be complicated by an impaired healing (i.e. delayed union or non-union). The application of weak electromagnetic fields has been proposed to have different effects on bones such as enhancing proliferation - orientation - migration of osteoblast-like cells and supporting osteogenic differentiation in bone marrow-derived mesenchymal stem cells. Despite the amount of evidence on cellular and histological effects, to date the application of pulsed electromagnetic fields has not achieved univocal consensus in daily practice. The purpose of this systematic review update is to research, select, analyze and summarize the most recent scientific evidence regarding the effects of pulsed electromagnetic fields in the treatment of acute bone fractures. A systematic review using the following MeSH terms (Magnetic Field Therapy; Electromagnetic Fields; Bone and Bones; Fractures, Bone; Fractures Healing) and strings {("Magnetic Field Therapy [mh]" OR "Electromagnetic Fields [mh]) OR "magnetotherapy" OR "pulsed electromagnetic field") and ("Fractures, bone [mh]" OR "Bone and Bones [mh]") and ("Fractures Healing [mh]")} was conducted on PubMed, Cochrane Library, Epistemonikos and Scopus electronic databases. Only full articles published in English between January 2014 and December 2022 were considered. Eligibility criteria were defined according to the Population, Intervention, Comparison, Outcomes, and Study (PICOS) design framework. Case reports, case series, uncontrolled studies and expert opinions were excluded. All articles were checked for quality and risk of bias. Three randomized controlled trials were included (197 patients in total). None of the studies found significant effects of pulsed electromagnetic fields on the acute bone healing process. Contradictory results about pain relief emerged. Only one study showed a transitory positive effect of pulsed electromagnetic fields on strength and range of motion recovery in patients with acute bone fracture. This systematic review update does not support the use of pulsed electromagnetic fields for improving the bone healing process in patients with acute fractures. Controversial evidence was found about the effects of pulsed electromagnetic fields on pain and functional recovery. Considering the scant and heterogenous literature published to date, which represents a limit for our conclusion, further studies with rigorous and high-quality methodology are needed.

Automated Analysis of Thoracic Aortic Aneurysms Based on Chest Computed Tomography Data: a Population Study in Moscow

Background. Cardiovascular diseases remain a pressing issue associated with great economic burden and loss of earning capacity. Among them, thoracic aortic aneurysms pose a serious threat as they commonly develop asymptomatically. Patients with aneurysms are often diagnosed late, which contributes to higher mortality rates due to complications. For this reason, conducting new epidemiological studies on this problem in our country is relevant.Objective: to study the prevalence of pathological dilatation of the thoracic aorta in Moscow by means of artificial intelligence technologies (AITs) using chest computed tomography (CT) data.Material and methods. A retrospective analysis of chest CT data from 227,149 patients obtained in the period from October 2022 to October 2023 was performed using AITs.Results. The analysis revealed that 13.3% of patients exhibited signs of thoracic aortic dilatation, while 0.8% had aneurysm signs. The prevalence of thoracic aortic aneurysms in Moscow was 12.4 cases per 100,000 individuals. Males were more susceptible than females; aneurysms of the descending aorta were more typical for them, while aneurysms of the ascending aorta were more common in females. The incidence of thoracic aortic dilatation increased with age. Potential causes and strategies to minimize AIT errors were discussed.Conclusion. The results highlight the importance of opportunistic screening for thoracic aortic aneurysms to ensure timely detection and prevention of complications. It would be especially beneficial to men and elderly population. The effectiveness of AITs to support decision-making by radiologists analyzing chest CT results was confirmed. The study provides an important update to the data on the prevalence of thoracic aortic aneurysms in asymptomatic patients in Russia. The identified features make it possible to direct the diagnostic and prevention efforts more effectively.

Impact of COVID-19 infection on genitourinary cancer management. SOGUG-COVID-19: A spanish, multicenter, observational study.

The COVID-19 pandemic is a great burden worldwide, but its impact on patients with genitourinary cancer (GUC) is poorly characterized. This study aimed to characterize the clinical features and evolution of GUC patients affected by COVID-19 in Spain. SOGUG-COVID-19 was an observational ambispective non-interventional study that recruited patients with SARS-CoV-2 infection who had been treated for GUC in 32 Spanish hospitals. Data were collected from patients' medical records in a short period of time, coinciding with the first waves of COVID-19, when the mortality was also higher in the general population. From November 2020 to April 2021, 408 patients were enrolled in the study. The median age was 70years, and 357 patients (87.5%) were male. Most frequent Cancer Origin was: prostate (40.7%), urothelial (31.4%) and kidney (22.1%). Most patients (71.3%) were diagnosed at the metastatic stage, and 33.3% had poorly differentiated histology. Anticancer treatment during the infection was reported in 58.3% of patients, and 21.3% had received immunotherapy prior to or concurrent with the infection. The most frequent COVID-19 symptoms were pyrexia (49.0%), cough (38.2%) and dyspnea (31.9%). Median age was higher for patients with pneumonia (p < 0.001), patchy infiltrates (p = 0.005), ICU admission (p < 0.001) and death (p < 0.001). Tumor stage was associated with complications (p = 0.006). The fatality rate was 19.9% and the 6-month COVID-19-specific survival rate was 79.7%. Patients with genitourinary cancers seem exceptionally vulnerable to COVID-19 regardless of tumor type or anticancer therapy. Age and tumor stage were the only identified risk factors for severe COVID-19.

The Impact of Multiple Births on Fertility: Stopping and Spacing in the United States During the Demographic Transition

Multiple births strain mothers’ and families’ resources in ways that should highlight preferences for family size, birth spacing, and parity-dependent stopping behavior. Couples with surviving twins reach their target family size sooner than other couples and should be more likely to practice family limitation. Twins are also a greater burden on the mother's time and health, which could lead to postponing the next birth, even among couples who want additional children. We examine these hypotheses by analyzing families with twins in the 1900 and 1910 U.S. Censuses. Using reconstructed birth histories for more than 7 million women in the IPUMS full-count 1900 and 1910 datasets and event-history methods (Kaplan–Meier curves, cure models), we find clear evidence of family limitation following a multiple birth. Couples who had twins or triplets were more likely to stop childbearing, and those who continued having children delayed their next birth. Responses to multiple births were larger in groups previously identified as leaders in the transition to smaller families, and roughly one third of couples stopped after one or two children. We find no evidence that some groups relied primarily on birth spacing to reduce family size while others relied primarily on stopping.

Long-term remission of Hailey-Hailey disease by Er:YAG ablative laser therapy.

Hailey-Hailey disease (HHD) is a rare genetic therapy-resistant blistering disease with great disease burden. Treatment is currently focused on symptomatic relief. Er:YAG ablative laser therapy is a therapeutic modality with promising results, though evidence is currently scarce. To analyse the effect of Er:YAG ablative laser therapy on clinical remission of erosive plaques in HHD and on patient's quality of life (QoL). In this observational study eight patients were included and 77 erosive plaques were treated once only by Er:YAG laser and assessed for clinical remission. QoL was evaluated by obtaining Skindex-29 and DLQI questionnaires before laser therapy, 6 weeks and 3 years after laser therapy. Skin biopsies were taken to evaluate the depth of laser ablation. The intercellular distance between keratinocytes, the number of desmosomes and intermediate filament distribution were studied by electron microscopy before and after laser therapy and in clinically uninvolved skin and were compared to subjects without HHD. One single Er:YAG laser ablation to mid-dermis resulted in complete remission of 97.4% of HHD plaques (75/77) after median 38 months (range 7-63 months) and significantly improved QoL. Laser therapy restored the number of desmosomes, decreased intercellular distance and diminished perinuclear retraction of keratin filaments to a level comparable to the patient's clinically uninvolved skin. After laser ablation, the skin showed significantly fewer ultrastructural aberrations compared to the patient's clinically uninvolved skin and rather resembled the skin of healthy control individuals. One single Er:YAG laser treatment resulted in long-term remission of HHD and significantly improved QoL. Our findings support a greater role for ablative laser surgery in the management of this recalcitrant disorder.