Lethality Rate Research Articles

Chemokine profile in the serum of patients with leptospirosis

IntroductionLeptospirosis is a global zoonosis that affects more than one million people per year, with a lethality rate of approximately 15%. Chemokines are crucial in the immune response against Leptospira, recruiting leukocytes to the site of infection and regulating immune activity. In previous studies, we have shown that CCL2, CXCL5, and CCL8 are involved in the leptospirosis process, although the mechanisms are not understood. MethodsIn this study, we present the frequency of Leptospira serovars in human samples. We then evaluated the profile of various chemokines in sera from patients diagnosed with leptospirosis, assessing the possible correlation between them. Moreover, we evaluated the changes in the chemokine profile on different days after the first symptoms. The frequency of the Leptospira serovars in human samples is presented. Results and discussionThe main findings were that CCL5, CXCL5, and CXCL9 are highly expressed during leptospirosis, indicating a special role of these molecules in the immunity and pathogenesis of the disease. The correlation analysis of detected chemokines CXCL11, CXCL9, CCL3, and CCL2 helps to clarify the role of each cytokine in leptospirosis. The possible use of CCL5 as a biomarker for complementary diagnosis of the disease is suggested.

Epidemiological characteristics of the 2019 Measles outbreak in central Tunisia

Abstract Background Measles is still an important public health problem worldwide causing significant morbidity and mortality. Measles represents a vaccine-preventable disease. In Tunisia, vaccination against measles was launched in 1983. In spite of the progress made towards measles elimination, Tunisia experienced an outbreak in 2019. We aimed to describe the measles outbreak in the central region of Tunisia in 2019. Methods We carried out a descriptive study using surveillance data from January to December 2019 in four governorates in Tunisia (Monastir, Mahdia, Kairouan, and Kasserine). All suspected measles cases and declared to regional directorate of primary health care were included. A suspected measles case was defined as any person with fever and generalized maculo-papular rash plus one of the following symptoms: cough or coryza or conjunctivitis. A laboratory confirmed measles case is a suspected case of measles that has been confirmed positive by testing (IgM+). Results A total of 2,688 suspected cases were recorded, of which 369 cases were (14.7%) were confirmed measles through serological testing. The sex ratio was 1.06 for suspected cases and 1.12 for measles cases. Infants under one year old accounted 42.2% of suspected cases. The majority of suspected cases (67.3%) were not vaccinated. Among confirmed measles cases, positivity rates were 81.8% for unvaccinated, 70.0% for those with one dose and 27.2% for those with two doses. The hospitalization rate was 61.5 %; highest rates were observed in infants under one year of age (65.7%) and in the age group over 38 years (69.0%). In total, 27 deaths were reported. The highest lethality rate was observed in the age group under 12 months (2%). Conclusions The 2019 measles outbreak in Tunisia highlighted that this disease remains a serious viral infection. Unvaccinated populations could be a potential source for new outbreaks, imposing substantial public health burdens. Key messages • The country needs to establish a national review committee to monitor measles elimination status. • To address future challenges, immunity gaps in the population should be closed.

Opportunistic Infections among People Living with HIV in the Infectious Disease Department, the University Hospital of Fann in Dakar, Senegal

Aim: The aim of this study was to identify the main infections and opportunistic infections in hospitalized patients living with HIV and to determine the hospital lethality rate. Patients and Methods: This was a retrospective, descriptive study of patients hospitalized in the infectious diseases department of the University Hospital of Fann over a 02-year period from 1 January 2021 to 31 December 2022. Results: We recorded 308 cases, 296 of which were patients living with HIV, out of a total of 1208 patients admitted to the department, a hospital prevalence rate of 24.5%. The average age of the patients was 43.3 ± 13.3 years, with a sex ratio of 0.7. One hundred and thirty-one patients (44.26%) were married. 22.97% had no occupation and 35.5% of patients came from home. The average diagnostic period was 3.9 days ± 4.78 days. Two hundred and five patients (69.26%) were at WHO stage 4. Tuberculosis was the most common bacterial infection, with 114 cases (38.5%), followed by common bacterial pneumonia (7.77%) and septicemia (4.72%). With regard to viral infections, the prevalence of viral hepatitis B was 6.76%, followed by herpes (1.68%). Among parasitic infections, toxoplasmosis was noted in 6.41% and cryptosporidiosis in 2.02%. Candidiasis was the most common fungal opportunistic infection, affecting forty-three patients (14.52%), followed by pneumocystis (7.09%) and cryptococcosis (2.36%). More than a third of our patients (37.84%) had severe anaemia, with haemoglobin levels below 8g/dl. Nearly a quarter of patients (21.28%) had impaired kidney function. Conclusion: HIV infection occurs in young adults at a late stage. Mortality remains high due to opportunistic infection. It is essential to carry out early screening, but above all to make available diagnostic tools and certain molecules for treatment of opportunistic infections.

Lung Damage Induced by Plasmodium berghei ANKA in Murine Model of Malarial Infection is Mitigated by Dietary Supplementation with DHA-Rich Omega-3.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe complications that can occur in infections caused by any Plasmodium species. Due to the high lethality rate and the lack of specific treatment for ALI/ARDS, studies aimed at understanding and searching for treatment strategies for such complications have been fundamental. Here, we investigated the protective role of dietary supplementation with DHA-rich fish oil against lung damage induced by Plasmodium berghei ANKA in a murine model. Our results demonstrated that alveolar vascular damage, lung edema, and histopathological alterations were significantly reduced in mice that received dietary supplementation compared to those that did not receive the supplementation. Furthermore, a significant reduction in the number of CD8+ T lymphocytes, in addition to reduced infiltration of inflammatory cells in the bronchoalveolar lavage fluid was also observed. High levels of IL-10, but not of TNF-α and IFN-γ, were also observed in infected mice that received the supplementation, along with a reduction in local oxidative stress. Together, the data suggest that dietary supplementation with DHA-rich fish oil in malarial endemic areas may help reduce lung damage resulting from the infection, thus preventing worsening of the condition.

In Silico Design of miniACE2 Decoys with In Vitro Enhanced Neutralization Activity against SARS-CoV-2, Encompassing Omicron Subvariants

The COVID-19 pandemic has overwhelmed healthcare systems and triggered global economic downturns. While vaccines have reduced the lethality rate of SARS-CoV-2 to 0.9% as of October 2024, the continuous evolution of variants remains a significant public health challenge. Next-generation medical therapies offer hope in addressing this threat, especially for immunocompromised individuals who experience prolonged infections and severe illnesses, contributing to viral evolution. These cases increase the risk of new variants emerging. This study explores miniACE2 decoys as a novel strategy to counteract SARS-CoV-2 variants. Using in silico design and molecular dynamics, blocking proteins (BPs) were developed with stronger binding affinity for the receptor-binding domain of multiple variants than naturally soluble human ACE2. The BPs were expressed in E. coli and tested in vitro, showing promising neutralizing effects. Notably, miniACE2 BP9 exhibited an average IC50 of 4.9 µg/mL across several variants, including the Wuhan strain, Mu, Omicron BA.1, and BA.2 This low IC50 demonstrates the potent neutralizing ability of BP9, indicating its efficacy at low concentrations.Based on these findings, BP9 has emerged as a promising therapeutic candidate for combating SARS-CoV-2 and its evolving variants, thereby positioning it as a potential emergency biopharmaceutical.

Treatment with lipoxin A4 improves influenza A infection outcome, induces macrophage reprogramming, anti-inflammatory and pro-resolutive responses.

Influenza A is a virus from theOrthomixoviridaefamily responsible for high lethality rates and morbidity, despite clinically proven vaccination strategies and some anti-viral therapies. The eicosanoid Lipoxin A4 (LXA4) promotes the resolution of inflammation by decreasing cell recruitment and pro-inflammatory cytokines release, but also for inducing activation of apoptosis, efferocytosis, and macrophage reprogramming. Here, we evaluated whether a synthetic lipoxin mimetic, designated AT-01-KG, would improve the course of influenza A infection in a murine model. Mice were infected with influenza A/H1N1 and treated with AT-01-KG (1.7μg/kg/day, i.p.) at day 3 post-infection. AT-01-KG attenuated mortality, reducing leukocyte infiltration and lung damage at day 5 and day 7 post-infection. AT-01-KG is a Formyl Peptide Receptor 2 (designated FPR2/3 in mice) agonist, and the protective responses were not observed in fpr2/3-/-animals. In mice treated with LXA4(50μg/kg/day, i.p., days 3-6 post-infection), at day 7, macrophage reprogramming was observed, as seen by a decrease in classically activated macrophages and an increase in alternatively activated macrophages in the lungs. Furthermore, the number of apoptotic cells and cells undergoing efferocytosis was increased in the lavage of treated mice. Treatment also modulated the adaptive immune response, increasing the number of T helper 2 cells (Th2) and regulatory T (Tregs) cells in the lungs of the treated mice. Therefore, treatment with a lipoxin A4analog was beneficial in a model of influenza A infection in mice. The drug decreased inflammation and promoted resolution and beneficial immune responses, suggesting it may be useful in patients with severe influenza.

The effect of layering order of ZIF-8@PCL/PLA composites in electrospinning and electrospraying process on antibacterial wound healing

The imidazolate-zeolite framework-8 (ZIF-8), as a zinc-based metal-organic framework, can act as an antibacterial agent by releasing Zn2+ ions. In this project, utilizing this previously studied fact, a set of wound dressings has been prepared using polycaprolactam and polylactic acid. Electrospinning and electro-spraying processes have been employed to create these samples. In total, five samples were obtained with variations in the layering sequence, and all samples were tested against two bacteria: Staphylococcus aureus and Escherichia coli. The results indicated that all samples were effective against the Gram-positive bacterium S. aureus, with the sample produced by simultaneous electro-spraying and electrospinning exhibiting the highest lethality rate. However, only the sample with the sequence of polycaprolactam layer, polylactic acid, and then ZIF-8 succeeded in eliminating 99 % of E. coli. The produced products were characterized using powder X-ray diffraction, IR spectroscopy, and scanning electron microscopy. The antibacterial effect of these wound dressings was evaluated using direct counting of bacterial colonies.

Enhancement on the lipase activity of M. circinelloides by ARTP mutagenesis for biodiesel production from woody plant oil

The objective is to enhance lipase activity of Mucor circinelloides via atmospheric and room temperature plasma (ARTP). ARTP was employed to treat spores of M. circinelloides for the selection of high lipase producers. With an irradiation time of 100 s at a lethal rate of 95 %, 18 mutants with higher lipase activity were initially selected. Measurements of the lipase activity revealed that a mutant strain LA-26 was characterized by a steady hereditary stability with lipase activity increase to 376.7 U/g. Moreover, the mutant LA-26 was immobilized as whole-cell biocatalyst used in solvent-free system to produce biodiesel. Response surface methodology (RSM) was used to optimize the reaction parameters. With the addition of 8 % biocatalyst, 10 % water content (w/w) and the stepwise addition of methanol (methanol to oil ratio of 4:1), the highest biodiesel (FAME) yield up to 98 % was achieved within 48 h. Immobilized LA-26 can be used for repeated batches, maintaining 70 % FAME yield after 6 cycles. The identified mutant strain LA-26 exhibits great potential for biodiesel production.

Revisiting the COVID-19 Pandemic: Mortality and Predictors of Death in Adult Patients in the Intensive Care Unit.

COVID-19 has generated a global impact due to its contagiousness and high lethality rates, with a large number of deaths occurring in intensive care units (ICUs). This study aimed to verify the occurrence of and understand the factors related to mortality in adult patients with COVID-19 admitted to the ICU in a tertiary hospital. This is a retrospective cohort study, which included COVID-19 patients admitted between March 2020 and December 2021. A total of 588 patients were included, of whom the majority (55.27%) did not survive. Invasive mechanical ventilation was the strongest predictor of the risk of death in the ICU with OR = 97.85 (95% CI = 39.10-244.86; p < 0.001), along with age and Simplified Acute Physiology Score 3 (SAPS3). The length of the ICU stay was protective. Evaluating patients on invasive mechanical ventilation in isolation, using an adjusted model, we found the following risk factors: use of vasopressin, renal replacement therapy, red cell distribution width > 15, use of hydrocortisone, and age in years. Protective factors included the days of mechanical ventilation use, being admitted from another service, and being of female sex. Identifying early predictors of mortality in patients with COVID-19 who require hospitalization is essential in the search for actions to prevent and manage complications, which can increase the survival of these patients and reduce the impact on health services.

ATG10-dependent autophagy is required for DDX10 to regulate cell proliferation, apoptosis and stemness in colorectal cancer

Colorectal cancer (CRC) remains a highly prevalent gastrointestinal neoplasm, presenting significant prevalence and lethality rate. DEAD/H box RNA helicase 10 (DDX10) has been proposed as a potential oncogene in CRC, the specific action mechanism by which DDX10 modulates the aggressive biological cellular events in CRC remains implicitly elucidated, however. During this study, DDX10 expression was detected via RT-qPCR and Western blotting. Cell proliferation was estimated via EDU staining. TUNEL staining and Western blotting appraised cell apoptosis. Cell stemness was evaluated by sphere formation assay, RT-qPCR, Western blotting as well as immunofluorescence staining. Relevant assay kit examined aldehyde dehydrogenase (ALDH) activity. Western blotting and immunofluorescence staining also detected autophagy. DDX10 was hyper-expressed in CRC cells. Down-regulation of DDX10 hampered cell proliferation, aggravated the apoptosis while eliminated the ability to form spheroid cells in CRC. In addition, DDX10 deletion improved ATG10 expression and therefore activated autophagy in CRC cells. Consequently, ATG10 depletion or treatment with autophagy inhibitor 3-Methyladenine (3-MA) partially compensated the influences of DDX10 silencing on the proliferation, apoptosis and stemness of CRC cells. Accordingly, DDX10 deficiency may aggravate autophagy mediated by ATG10 to impede cell proliferation, stemness and facilitate cell apoptosis, hence blocking the progression of CRC.

Chronic Pancreatitis in a Large Developing Country: Temporal Trends of Over 64,000 Hospitalizations from 2009 to 2019.

Chronic pancreatitis (CP) is a progressive inflammatory disorder associated with marked morbidity and mortality and frequently requires hospitalization. This study aimed to investigate the time trends and geographical distribution of hospital admissions, the lethality rate of CP across Brazil, and the potential relationship with social indicators and associated risk factors. Data were retrospectively obtained from the Brazilian Public Health System Registry between January 2009 and December 2019. The prevalence and lethality rates of CP per 100,000 inhabitants in each municipality were estimated from hospitalizations to in-hospital deaths and classified by age, sex, and demographic features. During the study period, 64,609 admissions were retrieved, and most of the patients were males (63.54%). Hospitalization decreased by nearly half (-54.68%) in both sexes. CP rates in males were higher in all age groups. The greatest reduction in admissions (-64%) was also noted in patients ≥ 70y. CP In-hospital lethality remained stable (5-6%) and similar for males and females. Patients ≥ 70y showed the highest lethality. The greatest increase in CP lethality rates (+ 10%) was observed in municipalities integrated into metropolises, which was mainly driven by small-sized municipalities (+ 124%). CP hospitalizations decrease in both urban and rural areas, particularly in the North, Northeast, and Central-West regions, and in those above 70years of age, but are not correlated with lethality rates in the South. This suggests ongoing changes in the environmental and socioeconomic factors in Brazil.

Selenium nanoparticles enhance the anti-tumor immune responses of anti-4-1BB antibody and alleviate the adverse effects on mice

4-1BB agonists for cancer immunotherapy have shown good preliminary efficacy in clinical trials, but several of the first-generation 4-1BB agonistic antibodies entering the clinic have failed due to safety issues. Selenium nanoparticles (SeNPs) exhibit anti-inflammatory, anti-tumor, antioxidant, and immune-modulating properties. In addition, they have been shown to have detoxifying effects and prevent oxidative liver damage. In this study, we used an anti-4-1BB antibody in combination with SeNPs to evaluate the anti-lung cancer effects in in vitro and in vivo experiments and explore the underlying mechanisms by pathological analyses, quantitative PCR, and enzyme-linked immunoassay. We found that 5 μmol·L–1 anti-4-1BB antibody combined with 1 μmol·L–1 SeNPs increased the expression of IFN-γ and promoted the killing effects of peripheral blood mononuclear cells on Lewis lung carcinoma cells, with a lethality rate up to 56.88 %. Experiments in tumor-bearing mice showed that the tumor inhibition rate was 58.61 % after treatment with 3.5 mg/kg anti-4-1BB antibody combined with 0.25 mg/kg SeNPs, and the liver function index returned to normal. When the combined treatment was compared with the antibody treatment alone, detection of immune relevant factors demonstrated that the expression of FOXP3, IL-2, IL-12, and TNF-α in the spleen was downregulated, whereas the expression of IFN-γ in the spleen, serum, and tumor was upregulated, accompanied by increased Fas ligand expression in the tumor tissues. Based on these findings, we get the conclusion that anti-4-1BB antibody combined with SeNPs may alleviate the immunosuppression of regulatory T cells, promote the immune cell proliferation and metastasis to synergistically kill tumor cells. This combination also reduces the inflammatory damage to normal tissues and slows overstimulation of the splenic immune response.

Condições de saúde, taxa de incidência e letalidade por Covid-19 em idosos institucionalizados após primeiro ano da pandemia em Maceió-AL

This study aimed to identify the sociodemographic, clinical, and nutritional profile, as well as to determine the incidence and lethality rate for COVID-19 in elderly residents in Long-Term Care Institutions for the Elderly in the municipality of Maceió – Alagoas, in the period 2020 and 2021. In the first year of the pandemic in Maceió, the reported incidence of COVID-19 was 31/100 residents in LTCFs, while the lethality rate was 6.56%, with elderly males representing the largest number of deaths (62.5%), the variables that presented as risk factors were sex, age, previous diagnosis of DM and low weight (p &lt; 0.050) and the variable education (p = 0.081). The data from this research reinforce results presented by other researchers where the previous diagnosis of diabetes is associated with the outcome death and male gender, age, low education and BMI are associated with the occurrence of the disease.

A high-throughput, polymerase-targeted RT-PCR for broad detection of mammalian filoviruses.

Filoviruses are some of the most lethal viruses in the modern world, and increasing numbers of filovirus species and genera have been discovered in recent years. Despite the potential severity of filovirus outbreaks in the human population, comparably few sensitive pan-filovirus RT-PCR assays have been described that might facilitate early detection and prevention. Here, we present a new pan-filovirus RT-PCR assay targeting the L polymerase gene for detection of all known mammalian filoviruses. We demonstrate the detection of 10 synthetic filovirus RNA templates with analytical sensitivity ranging from 178 to 3,354 copies/mL, without cross-reactivity on 10 non-filoviral human viral species. We verified assay performance on 10 inactivated filovirus isolates, yielding initial sensitivities of 0.012-44.17 TCID50/mL. We coupled this broadly reactive RT-PCR with a deep sequencing workflow that is amenable to high-throughput pooling to maximize detection and discovery potential. In summary, this pan-filovirus RT-PCR assay targets the most conserved filovirus gene, offers the widest breadth of coverage to date, and may help in the detection and discovery of novel filoviruses.IMPORTANCEFiloviruses remain some of the most mysterious viruses known to the world, with extremely high lethality rates and significant pandemic potential. Yet comparably few filovirus species and genera have been discovered to date and questions surround the definitive host species for zoonotic infections. Here, we describe a novel broadly reactive RT-PCR assay targeting the conserved L polymerase gene for high-throughput screening for filoviruses in a variety of clinical and environmental specimens. We demonstrate the assay can detect all known mammalian filoviruses and determine the sensitivity and specificity of the assay on synthetic RNA sequences, inactivated filovirus isolates, and non-filoviral species.

Environmentally persistent microbial contamination in agricultural soils: High risk of pathogenicity and antibiotic resistance

Persistent microbial contamination commonly occurs in the environment. However, the characteristics and associated risks remain largely unknown. The coexistence of virulence factor genes (VFGs) and “last-resort” antibiotic resistance genes (LARGs) on human bacterial pathogens (HBPs) are notorious, creating ecological concerns and health risks. Herein, we explored the pathogenicity and antibiotic resistance levels of LARG-harboring HBPs in agricultural soils. Our findings revealed a high distribution level of VFGs and LARGs in soils (an absolute abundance up to 4.7 × 107 gene copies/g soil) by quantitative PCR (qPCR). Furthermore, most isolated LARG-harboring HBPs exhibited a 100 % lethality rate to Galleria mellonella. LARG-carrying plasmids had a low fitness cost to their host bacteria, implying the high adaptation of these plasmids within the HBPs. Most importantly, multiple LARG and VFG plasmid fusion and core genetic arrangements suggested that these LARG/VFG-linked plasmids endowed the stable and persistent horizontal spread of these genes in and/or cross the species and environments. This study not only unveiled high risk, multisource, compliance and stability aspects of environmentally persistent microbial contamination but also illuminated the importance of linking the phenotype-genotype-niche colonization of environmental microbial contamination within “One Health” framework.

Apt-Conjugated PDMS-ZnO/Ag-Based Multifunctional Integrated Superhydrophobic Biosensor with High SERS Activity and Photocatalytic Sterilization Performance.

Sensitive detection and efficient inactivation of pathogenic bacteria are crucial for halting the spread and reproduction of foodborne pathogenic bacteria. Herein, a novel Apt-modified PDMS-ZnO/Ag multifunctional biosensor has been developed for high-sensitivity surface-enhanced Raman scattering (SERS) detection along with photocatalytic sterilization towards Salmonella typhimurium (S. typhimurium). The distribution of the electric field in PDMS-ZnO/Ag with different Ag sputtering times was analyzed using a finite-difference time-domain (FDTD) algorithm. Due to the combined effect of electromagnetic enhancement and chemical enhancement, PDMS-ZnO/Ag exhibited outstanding SERS sensitivity. The limit of detection (LOD) for 4-MBA on the optimal SERS substrate (PZA-40) could be as little as 10-9 M. After PZA-40 was modified with the aptamer, the LOD of the PZA-40-Apt biosensor for detecting S. typhimurium was only 10 cfu/mL. Additionally, the PZA-40-Apt biosensor could effectively inactivate S. typhimurium under visible light irradiation within 10 min, with a bacterial lethality rate (Lb) of up to 97%. In particular, the PZA-40-Apt biosensor could identify S. typhimurium in food samples in addition to having minimal cytotoxicity and powerful biocompatibility. This work provides a multifunctional nanoplatform with broad prospects for selective SERS detection and photocatalytic sterilization of pathogenic bacteria.

Association of Area Deprivation Index with Prostate Cancer Incidence Outcomes in a Contemporary North American Cohort

Introduction: Socio-economic status and geographical location contribute to disparities in prostate cancer (PCa) outcomes, which are particularly evident for Non-Hispanic Black (NHB) men. The Area of Deprivation Index (ADI) could offer a distinctive and valuable metric for measuring the impact of these factors in underprivileged areas on disparities in cancer outcomes. Our study examined the impact of ADI on Prostate Cancer (PCa) incidence and lethality over a contemporary North American population. Methods: Our institutional database included electronic medical records for all men who received at least one PSA test within Henry Ford Health (HFH), between 1995-2019. An ADI score was assigned to each patient based on their residential census block group, ranked as a percentile of deprivation relative to the national level. All patients were further categorized into ADI quartile, where the highest quartile (Q4: 75-100) represented individuals with the most disadvantageous socio-economic status. The main outcomes were PCa incidence and lethal PCa, defined as any metastatic PCa or death due to PCa occurred within our cohort. Competing-risk cumulative incidence and multivariable regression tested the impact of ADI on PCa outcomes. A formal ADI x race interaction term was introduced to examine whether the relationship between ADI and PCa outcomes varies between NHB and NHW men. Results: We included 134,366 patients, 25% of whom were NHB. Median follow-up was 8.8 years. When NHB patients were categorized based on their ADI quartile, the 20-years PCa incidence rates were 11.5%, 13.5%, 12.6% and 12.1% (p=0.009) for the first, second, third and fourth quartile respectively. For the same quartiles, 20-years incidence rates in NHW were 8.8%, 7.8%, 6.8% and 5.4% (p &lt;0.001). Lethal PCa rates for these quartiles were 2.0%, 1.4%, 1.2% and 2.3% (p&lt;0.001) in NHB, versus 0.92%, 0.79%, 0.93% and 1.2% (p=0.140) in NHW. At multivariate analysis, individuals from the third (ADI 50-74, HR: 0.89, 95% CI: 0.83-0.95) and the fourth quartile (ADI ≥ 75, HR: 0.80, 95% CI: 0.75-0.86) showed significant reduced HRs for PCa incidence, when compared with the first quartile (ADI&lt;25, all p&lt;0.001). NHB (vs NHW) men were persistently at higher hazard for both PCa incidence and lethality accross all ADI strata (all p&lt;0.001), although the interaction term was significant only for PCa incidence Conclusions: Our study is the first comprehensive evaluation of the association between neighborhood deprivation and race in PCa outcomes in a contemporary North American cohort. Living in more deprived areas was associated with a lower hazard for PCa incidence but not for lethality, although individuals in the highest ADI quartiles showed the worst lethal disease rates. NHB men persistently exhibited worse oncological outcomes, when compared with NHW individuals. This racial disparity became more prominent with an increase in ADI, but this trend was observed only for incidence.

Endoskopická submukózní disekce v populaci s nízkým výskytem karcinomu žaludku

Summary: Introduction: Gastric cancer is a serious disease with a decreasing incidence. In the treatment of its early stages, endoscopic methods, especially endoscopic submucosal dissection (ESD), are used signifi cantly. Methods: We present the results of 64 consecutive ESD gastric lesions. We performed ESD using a conventional technique with a circular incision followed by submucosal dissection with the DualKnife tool. In cases of carcinomas, we assessed the outcome of ESD according to the eCura scoring system. Results: We achieved en bloc resection in 88% and R0 resection in 72%. Signifi cant bleeding occurred in 8% and perforation in 3%; we managed all complications conservatively, where the lethal rate was zero. Of the 58 ESD neoplastic lesions, 42 (72%) were curative. We considered 6 (10%) patients for surgery after ESD, and it was performed in 2 (3%). Conclusion: In the conditions of a country with a low incidence of gastric cancer, we consider ESD to be a safe method with signifi cant curative potential. Key words: gastric cancer – endoscopic submucosal dissection – curative resection

Characterization of double-stranded RNA and its silencing efficiency for insects using hybrid deep-learning framework.

RNA interference (RNAi) technology is widely used in the biological prevention and control of terrestrial insects. One of the main factors with the application of RNAi in insects is the difference in RNAi efficiency, which may vary not only in different insects, but also in different genes of the same insect, and even in different double-stranded RNAs (dsRNAs) of the same gene. This work focuses on the last question and establishes a bioinformatics software that can help researchers screen for the most efficient dsRNA targeting target genes. Among insects, the red flour beetle (Tribolium castaneum) is known to be one of the most sensitive to RNAi. From iBeetle-Base, we extracted 12027 efficient dsRNA sequences with a lethality rate of ≥20% or with experimentation-induced phenotypic changes and processed these data to correspond to specific silence efficiency. Based on the first complied novel benchmark dataset, we specifically designed a deep neural network to identify and characterize efficient dsRNA for RNAi in insects. The dna2vec word embedding model was trained to extract distributed feature representations, and three powerful modules, namely convolutional neural network, bidirectional long short-term memory network, and self-attention mechanism, were integrated to form our predictor model to characterize the extracted dsRNAs and their silencing efficiencies for T. castaneum. Our model dsRNAPredictor showed reliable performance in multiple independent tests based on different species, including both T. castaneum and Aedes aegypti. This indicates that dsRNAPredictor can facilitate prescreening for designing high-efficiency dsRNA targeting target genes of insects in advance.

Combined HRAS and NRAS ablation induces a RASopathy phenotype in mice

BackgroundHRASKO/NRASKO double knockout mice exhibit exceedingly high rates of perinatal lethality due to respiratory failure caused by a significant lung maturation delay. The few animals that reach adulthood have a normal lifespan, but present areas of atelectasis mixed with patches of emphysema and normal tissue in the lung.MethodsEight double knockout and eight control mice were analyzed using micro-X-ray computerized tomography and a Small Animal Physiological Monitoring system. Tissues and samples from these mice were analyzed using standard histological and Molecular Biology methods and the significance of the results analyzed using a Student´s T-test.ResultsThe very few double knockout mice surviving up to adulthood display clear craniofacial abnormalities reminiscent of those seen in RASopathy mouse models, as well as thrombocytopenia, bleeding anomalies, and reduced platelet activation induced by thrombin. These surviving mice also present heart and spleen hyperplasia, and elevated numbers of myeloid-derived suppressor cells in the spleen. Mechanistically, we observed that these phenotypic alterations are accompanied by increased KRAS-GTP levels in heart, platelets and primary mouse embryonic fibroblasts from these animals.ConclusionsOur data uncovers a new, previously unidentified mechanism capable of triggering a RASopathy phenotype in mice as a result of the combined removal of HRAS and NRAS.