Impact of the 2008 economic crisis on the burden of hepatitis B and C diseases in Southern European countries.

BACKGROUND: The economic crisis that began in 2008 has severely affected Southern (Greece, Italy, Portugal, Spain) Western European (SWE) countries of Western Europe (WE) and may have affected ongoing efforts to eliminate viral hepatitis. This study was conducted to investigate the impact of the economic crisis on the burden of HBV and HCV disease. METHODS: Global Burden of Diseases 2019 data were used to analyse the rates of epidemiological metrics of HBV and HCV acute and chronic infections in SWE and WE. Time series modelling was performed to quantify the impact of healthcare expenditure on the time trend of HBV and HCV disease burden in 2000-2019. RESULTS: Declining trends in incidence and prevalence rates of acute HBV (aHBV) and chronic HBV were observed in SWE and WE, with the pace of decline being slower in the post-austerity period (2010-2019) and mortality due to HBV stabilised in SWE. Acute HCV (aHCV) metrics and chronic HCV incidence and mortality showed a stable trend in SWE and WE, whereas the prevalence of chronic HCV showed an oscillating trend, decreasing in WE in 2010-2019 (p < 0.001). Liver cancer due to both hepatitis infections showed a stagnant burden over time. An inverse association was observed between health expenditure and metrics of both acute and chronic HBV and HCV. CONCLUSIONS: Epidemiological metrics for HBV and HCV showed a slower pace of decline in the post-austerity period with better improvement for HBV, a stabilisation of mortality and a stagnant burden for liver cancer due to both hepatitis infections. The economic crisis of 2008 had a negative impact on the burden of hepatitis B and C. Elimination of HBV and HCV by 2030 will be a major challenge in the SWE countries.

Association between ultra-processed foods consumption and the risk of hypertension: An umbrella review of systematic reviews.

BACKGROUND: Several systematic reviews (SRs) have investigated the association between ultra-processed foods (UPFs) and the risk of hypertension in various populations. However, the quality of the evidence remains unclear. This umbrella review was thus conducted to fill this gap. METHODS: We searched for SRs with and without meta-analyses comparing high UPF versus low UPF consumption on the risk of hypertension in the Cochrane Library, Embase, PubMed, and Web of Science from inception to August 2022. This study was registered in PROSPERO (No. CRD42022352934). The A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR-2) tool and the Preferred Reporting Item for Systematic Review and Meta-analysis 2009 (PRISMA 2009) statement were used to evaluate the methodological and reporting quality of the included SRs. Stata 15/SE was used to reanalyse the data using the random-effects model, and the risk of bias of observational studies from included SRs was reassessed using the Newcastle-Ottawa Scale (NOS) tool. The certainty of the evidence body was assessed using the GRADE recommendation. RESULTS: Seven SRs were included in the umbrella review. Among them, nine observational studies (5 cross-sectional and 4 cohort studies), whose available data were resynthesised using meta-analysis. The methodological and reporting quality of the included SRs were relatively poor. The meta-analysis results revealed suggestive evidence of an association between high UPF consumption and the incidence of hypertension (odds ratio: 1.23, 95% confidence interval: 1.11 to 1.37, p < 0.001, 95% prediction interval: 0.92 to 1.64, critically low certainty) compared to low UPF consumption. CONCLUSION: High UPF consumption is associated with an increased risk of hypertension. However, well-conducted SRs, including high-quality prospective cohort studies, are needed to further verify these findings.

DNA origami: a tool to evaluate and harness transcription factors.

Alongside other players, such as CpG methylation and the "histone code," transcription factors (TFs) represent a key feature of gene regulation. TFs are implicated in critical cellular processes, ranging from cell death, growth, and differentiation, up to intranuclear signaling of steroid and other hormones, physical entities, and hypoxia regulation. Notwithstanding an extensive body of research in this field, several questions and therapeutic options remain unanswered and unexplored, respectively. Of note, many of these TFs represent therapeutic targets, which are either difficult to be pharmacologically tackled or are still not drugged via traditional approaches, such as small-molecule inhibition. Upon providing a brief overview of TFs, we focus herein on how synthetic biology/medicine could assist in their study as well as their therapeutic targeting. Specifically, we contend that DNA origami, i.e., a novel synthetic DNA nanotechnological approach, represents an excellent synthetic biology/medicine tool to accomplish the above goals, since it can harness several vital characteristics of DNA: DNA polymerization, DNA complementarity, DNA "programmability," and DNA "editability." In doing so, DNA origami can be applied to study TF dynamics during DNA transcription, to elucidate xeno-nucleic acids with distinct scaffolds and unconventional base pairs, and to use TFs as competitors of oncogene-engaged promoters. Overall, because of their potential for high-throughput design and their favorable pharmacodynamic and pharmacokinetic properties, DNA origami can be a novel armory for TF-related drug design. Last, we discuss future trends in the field, such as RNA origami and innovative DNA origami-based therapeutic delivery approaches.

How can cancer research be illuminated by brain research (and vice versa)?

Cancer and brain research have historically followed concrete pathways and converged mostly to studying brain cancer. Nowadays, the fields of neuro-oncology and neuroendocrine regulation of tumorigenesis are both emerging fields of intense research and promising applications. An increasing body of evidence suggests that somatic mutations in cancer-related genes are prevalent in several noncancerous brain disorders. These findings highlighting that certain aspects of cancer development/progression and pathologies of the nervous system share molecular alterations, could assist in elucidating the unique hallmarks of cancer and in cancer drugs repurposing for brain disorders. In so doing, identifying the commonalities in these conditions could be crucial not only for better understanding the basis of these pathologies but also for considering the previously underappreciated and/or neglected possibility of using drugs known to be effective in one type of pathology for the other type.

Do 'cancer mutations' stand only for cancer? Translational and clinical implications.

DNA mutations represent a hallmark of cancer. However, next-generation sequencing (NGS) approaches have revealed that similar somatic mutations are present in healthy tissues as well as in those of several diseases, aging, abnormal vascular formation, and in placental development. These findings call for a reappraisal of whether such mutations are pathognomonic for cancer and provide further mechanistic, diagnostic, and therapeutic implications.

Applications of artificial intelligence-machine learning for detection of stress: a critical overview.

Psychological distress is a major contributor to human physiology and pathophysiology, and it has been linked to several conditions, such as auto-immune diseases, metabolic syndrome, sleep disorders, and suicidal thoughts and inclination. Therefore, early detection and management of chronic stress is crucial for the prevention of several diseases. Artificial intelligence (AI) and Machine Learning (ML) have promoted a paradigm shift in several areas of biomedicine including diagnosis, monitoring, and prognosis of disease. Here, our review aims to present some of the AI and ML applications for solving biomedical issues related to psychological stress. We provide several lines of evidence from previous studies highlighting that AI and ML have been able to predict stress and detect the brain normal states vs. abnormal states (notably, in post-traumatic stress disorder (PTSD)) with accuracy around 90%. Of note, AI/ML-driven technology applied to identify ubiquitously present stress exposure may not reach its full potential, unless future analytics focus on detecting prolonged distress through such technology instead of merely assessing stress exposure. Moving forward, we propose that a new subcategory of AI methods called Swarm Intelligence (SI) can be used towards detecting stress and PTSD. SI involves ensemble learning techniques to efficiently solve a complex problem, such as stress detection, and it offers particular strength in clinical settings, such as privacy preservation. We posit that AI and ML approaches will be beneficial for the medical and patient community when applied to predict and assess stress levels. Last, we encourage additional research to bring AI and ML into the standard clinical practice for diagnostics in the not-too-distant future.

Spatially resolved transcriptomics: a comprehensive review of their technological advances, applications, and challenges.

The ability to explore life kingdoms is largely driven by innovations and breakthroughs in technology, from the invention of the microscope 350 years ago to the recent emergence of single-cell sequencing, by which the scientific community has been able to visualize life at an unprecedented resolution. Most recently, the Spatially Resolved Transcriptomics (SRT) technologies have filled the gap in probing the spatial or even three-dimensional organization of the molecular foundation behind the molecular mysteries of life, including the origin of different cellular populations developed from totipotent cells and human diseases. In this review, we introduce recent progresses and challenges on SRT from the perspectives of technologies and bioinformatic tools, as well as the representative SRT applications. With the currently fast-moving progress of the SRT technologies and promising results from early adopted research projects, we can foresee the bright future of such new tools in understanding life at the most profound analytical level.

MICROGLIA AND INFILTRATING T-CELLS ADOPT LONG-TERM, AGE-SPECIFIC, TRANSCRIPTIONAL CHANGES AFTER TRAUMATIC BRAIN INJURY IN MICE.

ABSTRACT: Aged traumatic brain injury (TBI) patients suffer increased mortality and long-term neurocognitive and neuropsychiatric morbidity compared with younger patients. Microglia, the resident innate immune cells of the brain, are complicit in both. We hypothesized that aged microglia would fail to return to a homeostatic state after TBI and adopt a long-term injury-associated state within aged brains compared with young brains after TBI. Young and aged male C57BL/6 mice underwent TBI via controlled cortical impact versus sham injury and were sacrificed 4 months post-TBI. We used single-cell RNA sequencing to examine age-associated cellular responses after TBI. Brains were harvested, and CD45+ cells were isolated via fluorescence-activated cell sorting. cDNA libraries were prepared using the 10x Genomics Chromium Single Cell 3' Reagent Kit, followed by sequencing on a HiSeq 4,000 instrument and computational analyses. Post-injury, aged mice demonstrated a disparate microglial gene signature and an increase in infiltrating T cells compared with young adult mice. Notably, aged mice post-injury had a subpopulation of age-specific, immune-inflammatory microglia resembling the gene profile of neurodegenerative disease-associated microglia with enriched pathways involved in leukocyte recruitment and brain-derived neurotrophic factor signaling. Meanwhile, post-injury, aged mice demonstrated heterogeneous T-cell infiltration with gene profiles corresponding to CD8 effector memory, CD8 naive-like, CD8 early active T cells, and Th1 cells with enriched pathways, such as macromolecule synthesis. Taken together, our data showed that the aged brain had an age-specific gene signature change in both T-cell infiltrates and microglia, which may contribute to its increased vulnerability to TBI and the long-term sequelae of TBI.

Diagnostic significance of IgG and albumin indices versus oligoclonal band types in demyelinating disorders.

AIMS: The laboratory diagnosis of demyelinating inflammatory disorders (DIDs) relies on both intrathecal oligoclonal band (OCB) positivity and IgG index. Although OCB typing remains the gold-standard test for DIDs, it can be laborious and ambiguous, complicating diagnostics, and unduly increasing diagnostic time. We examined whether serum or cerebrospinal fluid (CSF) parameters can classify OCB types and, thus, be used as a replacement test to standard OCB typing. METHODS: We retrospectively analysed >1000 prospectively collected samples of patients with DIDs and quantified albumin and IgG levels in the CSF and serum. We determined OCB types by isoelectric focusing combined with immunofixation and evaluated the diagnostic accuracies of IgG and albumin indices in discriminating OCB types by receiver operating characteristic curves and multinomial regression. RESULTS: An IgG index cut-off of 0.589 differentiated types 2/3 from types 1/4 (area under the curve 0.780, 95% CI 0.761 to 0.812, p<0.001; specificity: 71.10%, sensitivity: 73.45%). Albumin quotient cut-off values of 6.625 and of 6.707 discriminated type 1 from type 4 and type 2 from type 3, respectively (specificity: <55%, sensitivity: <75%). Female sex, age, IgG index, CSF IgG and serum albumin were associated with different OCB types. CONCLUSIONS: Our study reveals that IgG and albumin index can differentiate OCB types with adequate accuracy, especially if refined by age and gender.

TREM2 R47H variant and risk for Alzheimer's disease: assessment in a Greek population and updated meta-analysis.

INTRODUCTION: Rare coding variants in TREM2 and their association with the susceptibility towards Alzheimer's disease (AD) were recently studied in various ethnic groups with contradictory results. The T allele of the rs75932628 (p.R47H variant) has shown a positive risk association with AD in several studies; however, neither a study in Greece nor an updated meta-analysis have been conducted. OBJECTIVE: To assess the association between TREM2 rs75932628 and late-onset (sporadic) AD in a Greek population, and perform a meta-analysis of current data. MATERIALS AND METHODS: The rs75932628 was genotyped in a total of 327 patients with AD and 700 cognitively healthy controls. A systematic search and meta-analyses of studies presenting data regarding rs75932628 in AD cases and controls were also performed. RESULTS: Three patients vs. none of the controls were found to carry the heterozygous risk allele of the rs75932628, yielding a significant association (p = 0.032), in the Greek sample. In the meta-analysis, the overall odds ratio (OR) under a fixed-effects model was 2.98 (Confidence Interval (CI):2.52-3.53) showing a significant association of the rs75932628-T allele with AD in the overall dataset, based on data from 27 studies (26200 AD cases and 142084controls). Caucasian population-only studies (n = 16) revealed a similar OR of 2.93 (CI:2.45-3.51), whereas Asian population-only studies (n = 5) had a non-significant OR of 0.84 (CI:0.19-3.74). CONCLUSION: The rs75932628 was associated with AD in the Greek sample. Our meta-analysis, covering a total population of over 168,000 people, also showed a significant association of the allele with AD in Caucasian populations.

Kanglaite (Coix Seed Extract) as Adjunctive Therapy in Cancer: Evidence Mapping Overview Based on Systematic Reviews With Meta-Analyses.

Background: Several quantitative systematic reviews of Kanglaite (KLT), an herb preparation used to treat cancer and malignant pleural effusion, have been published in recent years. However, the clinical evidence reported in these studies has not been pursued further and the methodological quality of these meta-analyses remains unknown. Therefore, an overview was designed to map the evidence landscape based on the published meta-analyses on KLT in cancer treatment. Methods: Two bibliographic databases (PubMed and Embase) were searched from inception to 25 November 2021. Two independent reviewers were involved in study selection, data abstraction, and methodological quality assessment using AMSTAR 2. The principal features of publications and the clinical outcomes of efficacy and safety were synthesized narratively, and results of methodological quality were reported as frequencies and percentages with the corresponding 95% confidence intervals. The evidence map was used to visualize the overall quality. Excel 2016 and Stata 17/SE were used for data analysis. Results: Thirteen meta-analyses published in English were included for in-depth analysis. Among them, the year of publication ranged from 2008 to 2021, and the number of included patients ranged from 488 to 2,964. Regarding the cancer type, seven articles focused on non-small cell lung cancer, two on malignant pleural effusion, and four reviews on digestive system malignancies, such as hepatocellular carcinoma and pancreatic cancer. Almost all included meta-analyses reported that KLT as adjunctive therapy could improve various efficacy outcomes (such as disease response rates, quality of life, immune indicators) and reduce the rate of occurrence of adverse reactions, such as nausea and vomiting, leukopenia, and anemia. In terms of their methodological quality, three meta-analyses were of low quality, whereas 10 studies were critically low in quality. The methodological flaws main involved items 2 ("predesigned protocol and registration informatio''), 3 ("rationale of study design for inclusion"), 4 ("comprehensive search strategy''), 5 ("literature selection in duplicate''), 7 ("list of excluded studies with reasons''), 8 ("adequate information on included studies''), 10 ("funding support for included primary studies''), and 12 ("evaluation of the potential impact of risk of bias'') based on the AMSTAR 2 tool. Conclusion: Current evidence reveals that KLT is effective and safe as an adjunctive treatment for non-small cell lung cancer, malignant pleural effusion, and digestive system malignancies (such as hepatocellular carcinoma). However, the results assessed in this overview should be further verified using well-designed and clearly reported clinical trials and meta-analyses of KLT.

Could COVID-19's Aftermath on Children's Health Be Felt into the 22nd Century?

The COVID-19 pandemic has massively affected people's health, societies, and the global economy. Our lives are no longer as they were before COVID-19, and, most likely, will never be the same again. We hypothesize that the effect of the COVID-19 pandemic on population health and the economy will last for a very long time and will still be felt in the 22nd century. Our hypothesis is based on evidence from the 1918-1919 influenza pandemic, the Dutch famine during the Second World War, and the 2007-2008 economic crisis, as well as from the rationally predicted impact of COVID-19 on human development. We expect that the COVID-19 pandemic, including the mitigation measures taken against it, will affect children's development in multiple ways, including obesity, both while in utero and during critical and sensitive windows of development, including the early childhood years and those of puberty and adolescence. The psychosocial and biological impact of this effect will be considerable and unequally distributed. The implications will last at least a lifetime, and, through inter-generational transmission, will likely take us to future generations, into the 22nd century. We argue for the urgent need of designing and initiating comprehensive longitudinal cohort studies to closely monitor the long-term effects of COVID-19 on children conceived, born, and raised during the pandemic. Such an approach requires a close and effective collaboration between scientists, healthcare providers, policymakers, and the younger generations, and it will hopefully uncover evidence necessary to understand and mitigate the impact of the pandemic on people's lives in the 21st and 22nd centuries.

BMC Endocrine Disorders' collection of articles on "Reducing inequalities in the Management of Endocrine Disorders".

Endocrine disorders represent a large component of the so-called "chronic non-communicable diseases", which are responsible for the lion share of morbidity and mortality in contemporary societies. As discussed in this retrospective collection of articles, solid evidence from diabetes mellitus, the exemplar of common chronic endocrine disorders, highlights profound inequity in all aspects of endocrine disorders' management and outcomes that should be considered and addressed at large.

Cytomegalovirus DNA detection in pregnant women with a high IgG avidity index: a valuable tool for diagnosing non-primary infections?

BACKGROUND/AIM: Congenital human cytomegalovirus infection (cCMV) is the commonest congenital infection, and it can result in hearing loss and neurodevelopmental delay. Even if primary infections are more frequent and cause more severe congenital cCMV manifestations compared to NPIs, and despite partial protection from maternal immunity, the highest birth prevalence of cCMV is observed in seropositive women with non-primary CMV infection (NPI). Given that NPI contribute significantly to the overall burden of cCMV, their accurate diagnosis of NPI remains clinically important. Considering that the serological testing for CMV infection is not always reliable, we sought to determine whether detection of CMV DNA in pregnant women with a high IgG avidity index (AI) can help diagnose NPI. MATERIALS AND METHODS: Human CMV serology screening (IgG, IgM, and IgG AI) was performed for confirmation of CMV infection in serum samples from mainly pregnant women with indications of CMV infection due to IgG+ and IgM+-positive samples in other laboratories. Pregnant women (or those with termination of pregnancy during the last period) with adequate IgG levels to perform IgG AI were included. Demographic data and mean gestation week at the time of screening were recorded. Serological testing was performed using CE-IVD commercial kits. CMV DNAemia detection by real time PCR (RT-PCR) was applied to confirm suspected CMV infection. RESULTS: Nine-hundred and thirty-four pregnant women CMV IgG positive with adequate IgG titers for AI testing were included in the study. The percentage of women with a high AI was 71.8% (671/934); among them, nearly 2.4% (16/671) had presence of CMV DNA. Also, 12.4% of women (116/934) had intermediate IgG AI and 15.7% of women (147/934) had low IgG AI. The presence of CMV DNA was observed in 13.8% (16/116) and 39.5% (58/147) of the groups with intermediate and low IgG AI, respectively. A high CMV IgG AI was associated with a negative CMV PCR status (p-value <.00001). CONCLUSIONS: CMV DNA was present in 2.4% of seropositive women with high IgG AI, indicating active NPI and thus, harboring the risk of cCMV sequelae to the fetus. Moreover, the incidence of NPI may have been underestimated due to single timepoint testing. In order to detect CMV NPI in a seropositive woman, regular and frequent serology testing as well as detection of CMV DNAemia are required which render the whole diagnostic process impractical and not cost-effective.

A novel variant in DYNC1H1 could contribute to human amyotrophic lateral sclerosis-frontotemporal dementia spectrum.

Amyotrophic lateral sclerosis (ALS) belongs to the ALS-frontotemporal dementia (FTD) spectrum and is hallmarked by upper and lower motor neuron degeneration. Here, we present a patient with a cytoplasmic dynein 1 heavy chain 1 (DYNC1H1) pathogenic variant who fulfilled the ALS El Escorial criteria, and we review relevant literature. Using whole-exome sequencing, we identified a deleterious point variant in DYNC1H1 (c.4106A > G (p. Q1369R)) as a likely contributor to the ALS phenotype. In silico structural analysis, molecular dynamics simulation, and protein stability analysis predicted that this variant may increase DYNC1H1 protein stability. Moreover, this variant may disrupt binding of the transcription factor TFAP4, thus potentially acting as duon. Because (a) DYNC1H1 forms part of a ubiquitous eukaryotic motor protein complex, and (b) disruption of dynein function by perturbation of the dynein-dynactin protein complex is implicated in other motor neuron degenerative conditions, this variant could disrupt processes like retrograde axonal transport, neuronal migration, and protein recycling. Our findings expand the heterogenous spectrum of the DYNC1H1 pathogenic variant-associated phenotype and prompt further investigations of the role of this gene in ALS.

A Case of Otomycosis Associated With a Sugar-Loaded Traditional Medicine Solution and Other Factors.

OBJECTIVE: The aim of this case report is to illustrate how multiple co-existing factors can contribute to otomycosis and to highlight possible new etiologies for this common condition. CASE REPORT: We report the case of a woman with otomycosis in which a) several factors could have played an additive, contributing role, and b) with all other clinical parameters being equal (ceteris paribus) before and after otomycosis-specific treatment, a home-made, sugar-loaded medicinal solution could also have contributed to its pathogenesis. CONCLUSION: Our case highlights that traditional medicines must be used with caution since they might cause side-effects and that history-taking must include enquiry about their use. This case also highlights that a ceteris paribus approach can be useful when interpreting case reports, which lack the methodological robustness of case-control or interventional studies.