Significant Increase In Mortality Research Articles

Trends in Sickle Cell Disease Mortality: 1979–2020

BACKGROUND AND OBJECTIVES: Although sickle cell disease (SCD)-related childhood mortality in the United States significantly improved in the 1990s, unclear is the trend in SCD-related mortality more recently given the continued disparities faced by this minoritized population. In this analysis, we aimed to (1) compare the overall and age-specific mortality rates from 1999 to 2009 vs 2010 to 2020 with a particular focus on the age of transition and (2) determine the most common causes of death for the US SCD population for 2010 to 2020. METHODS: We analyzed publicly available data from the Centers for Disease Control and Prevention WONDER database, a compilation of national-level mortality statistics from 1979 to 2020 derived from death certificates compiled by the National Center for Health Statistics. We searched by all individuals of all ethnicities, sexes, and ages using the underlying cause of death. RESULTS: The crude mortality rate for individuals with SCD for 2010 to 2020 was 1.6 per 1 000 000 individuals, which was significantly lower than the period 1999 to 2009 (crude rate 1.7 per 1 000 000, P < .0001). In addition, the mean age at mortality of those with SCD was older in 2010 to 2020 (43 years) versus 1999 to 2009 (39 years). However, there remains a significant increase in mortality rate in the 20 to 24 year age group versus 15 to 19 years (1.7 per 1 000 000 versus 0.7 per 1 000 000, P < .0001), corresponding with the age of transition from pediatric to adult centers. In addition, 39% of underlying causes of death were not caused by SCD, but rather primarily chronic conditions, including cardiovascular, cerebrovascular, malignancy, and renal disease. The study has several limitations mostly because of the imperfections of administrative data sources, including inaccuracies in diagnoses codes, risking over or undercounting. CONCLUSIONS: Although the US SCD-related mortality rate continues to decrease, the age of transition to adult care is a particularly vulnerable time in the lives of this marginalized group. Innovative and expanded approaches to care are greatly needed.

FAGOTERAPIA COMO ALTERNATIVA NO COMBATE A INFECÇÕES RESISTENTES: AVANÇOS E DESAFIOS NO TRATAMENTO DE E. COLI UPEC E EPEC

Resistant bacterial infections represent one of the biggest public health challenges today, resulting in a significant increase in morbidity and mortality linked to infectious diseases. On the other hand, Escherichia coli stands out as one of the most significant bacteria, particularly the uropathogenic (UPEC) and enteropathogenic (EPEC) variants. Infections caused by these strains have become a problem due to their ability to develop resistance to various antibiotics, thus harming therapeutic alternatives. The objective of this research was to investigate the effectiveness of phage therapy as an alternative in combating resistant bacterial infections, focusing on UPEC and enteropathogenic EPEC strains of Escherichia coli. Methodologically, it was an exploratory and comparative bibliographic review through qualitative research. As a result, it was found that future directions in phage therapy present a promising outlook, full of technological innovations, research needs and ethical considerations. The success of phage therapy as a viable alternative to treating resistant bacterial infections will depend on collaboration between different disciplines, careful consideration of ethical implications, and a commitment to ensuring that new technologies benefit society as a whole. The development of robust guidelines and regulations, along with increased public awareness, will be critical to the effective integration of phage therapy into clinical practice and public health. It was concluded that progress in this area represents a response to the bacterial resistance crisis, as it opens up new perspectives for biomedical research and clinical practice. Therefore, the continued engagement of researchers, health professionals and policy makers will be essential to ensure that phage therapy is established as an integral component in the fight against bacterial infections, benefiting public health in a broad and effective way.

Hypotension and Adverse Outcomes in Moderate to Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Hypotension in patients with TBI is associated with poorer outcomes. A comprehensive review examining adverse outcomes of hypotension in patients with TBI is needed. To investigate the mortality and incidence of hypotension in patients with TBI. A search of studies published before April 2024 was conducted using MEDLINE, MEDLINE In Process, ePubs, Embase, Classic+Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews for primary research articles in English, including randomized control trials, quasirandomized studies, prospective cohorts, retrospective studies, longitudinal studies, and cross-sectional surveys. Inclusion criteria were patients aged at least 10 years with moderate to severe TBI with hypotension. The exclusion criteria were mild TBI (due to the differences in management principles from moderate to severe TBI). Data were screened using Covidence software with multiple reviewers. This meta-analysis conforms to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines for assessing data quality and validity. Primary outcomes (unadjusted and adjusted odds ratios [ORs]) were calculated using a random-effect model with 95% CIs. Incidence of hypotension was derived using logit transformation. Main outcomes were association of hypotension with death and/or vegetative state within 6 months and incidence of hypotension. Vegetative state was not reported due to lack of data from included studies. Hypothesis testing occurred before data collection. The search strategy identified 17 676 unique articles. The final review included 51 studies (384 329 patients). Pooled analysis of found a significant increase in mortality in patients with hypotension and moderate to severe TBI (crude OR, 3.82; 95% CI, 3.04-4.81; P < .001; I2 = 96.98%; adjusted OR, 2.22; 95% CI, 1.96-2.51; P < .001; I2 = 92.21%). The overall hypotension incidence was 18% (95% CI, 12%-26%) (P < .001; I2 = 99.84%). This meta-analysis of nearly 400 000 patients with TBI found a significant association of greater than 2-fold odds of mortality in patients with hypotension and TBI. This comprehensive analysis can guide future management recommendations, specifically with respect to blood pressure threshold management to reduce deaths when treating patients with TBI.

The impact of recipient hypernatremia on pediatric liver transplantation outcomes.

In pediatric liver transplants, dysnatremias have been found to have an impact on pre- and post-transplant outcomes. However, much of the current literature has focused on wait-list survival, secondary organ damage, and dysnatremia in donors rather than in recipients. To understand the effect of recipient immediate pre-transplant hypernatremia on post-transplant mortality, we conducted a multivariable retrospective review analyzing data from 8,011 pediatric patients undergoing liver transplantation provided by the United Network for Organ Sharing (UNOS). Multivariable analysis of hypernatremia showed an increased risk of mortality (odds ratio [OR]: 2.49, 95% confidence interval [CI]: 1.75, 3.54 for a serum sodium between 150-155mEq/L) while hyponatremia did not show a significant increase in relative risk for mortality (HR: 1.11, 95% CI: 0.75, 1.63 for a serum sodium between 125-130mEq/L). Kaplan-Meier (KM) curves stratified by sodium level showed statistically significant differences in outcomes with progressively increasing mortality associated with increasing serum sodium levels. In particular, there is a statistically significant increase in 90-day mortality with serum sodium levels above 150mEq/L. Hyponatremia had a moderate impact on mortality but was not statistically significant. Our analysis of immediate pre-transplantation resolution of hypernatremia also showed improved survival outcomes with a decreased mortality compared to transplant patients with unresolved hypernatremia. In conclusion, immediate pre-transplant recipient hypernatremia has a substantial impact on pediatric post-liver transplantation survival. Corrected hypernatremia resulted in decreased mortality compared to uncorrected hypernatremia. Recipient hypernatremia is an important indicator of disease processes and a predictor of poor post-transplantation mortality outcomes.

Association between delayed invasive blood pressure monitoring and all-cause mortality in intensive care unit patients with sepsis: a retrospective cohort study

PurposeHaemodynamic management is essential in sepsis management. Invasive blood pressure (IBP) monitoring is the gold standard for blood pressure (BP) assessment. Here, we identified the most advantageous time frame for IBP monitoring to mitigate adverse outcomes in patients with sepsis.MethodsWe included data on patients with sepsis from the Medical Information Mart for Intensive Care IV database. The primary endpoints comprised 28-and 90-day mortality rates, whereas secondary endpoints were acute kidney injury (AKI) rates and continuous renal replacement therapy (CRRT) requirement. To confirm our findings’ robustness, we performed multivariable Cox regression and logistic regression models, augmented by propensity score matching (PSM).ResultsOf 18,326 patients hospitalised for sepsis, 9,056 (49.42%) and 9,270 (50.58%) were included in the early and delayed IBP-monitoring groups, respectively. Our multivariable Cox regression models revealed 20 and 21% significant increases in 28-and 90-day mortality in the delayed IBP monitoring group, respectively [hazard ratios (95% confidence intervals) = 1.20 (1.11–1.31) and 1.21 (1.12–1.31), respectively; both p &amp;lt; 0.001]. Moreover, significant increases were noted in AKI, CRRT and mechanical ventilation requirement risks in the delayed IBP monitoring group [odds ratios (95% confidence intervals) = 1.44 (1.34–1.56), 1.50 (1.26–1.78) and 1.79 (1.67–1.92), respectively; both p &amp;lt; 0.001]. PSM further confirmed the validity of our findings. Delayed IBP monitoring prolonged intensive care unit (ICU) stay without extending vasopressor use duration.ConclusionProlonged delay in IBP monitoring (≥3 h) may increase mortality risks in ICU patients with sepsis. Nevertheless, early IBP monitoring may reduce AKI, CRRT and mechanical ventilation requirement risks and shorten ICU stay. However, these results warrant further validation through randomised controlled trials.

The mobile seniors’ clinic - an innovative transition of care for frail older adults

BackgroundThis study aims to evaluate the impact of Quebec’s first hospital-at-home-inspired mobile Seniors’ Clinic, the “Clinique des Ainés (CDA)”, on frail older adults’ returns to the Emergency Department (ED), mortality, and hospital Length Of Stay (LOS) and rehospitalizations.MethodsDesign: Quasi-experimental pre-post implementation cohort study. Population: Patients aged ≥ 75 years admitted to the short-term geriatric unit after an ED consultation (control) or included by the CDA (intervention). Outcomes: return to ED (RtoED), mortality, ED & hospital LOS, and rehospitalizations. Statistical analyses: Multivariable regression modelling.ResultsOverall, 891 patients were included. At the intervention site (CDA) (n = 437), RtoED were similar at 30 (17.5% & 19.5%, p = 0.58), 90 (34.4% & 37.3%, p = 0.46) and 180 days (47.2% & 54.0%, p = 0.07) in the pre and post-implementation phases. No mortality differences were found. The hospitalization LOS was significantly shorter (28.26 and 14.22 days, p < 0.01). At 90 days, rehospitalization LOS was decreased by 8.51 days (p = 0.02) and by 6.48 days at 180 days (p = 0.03). Compared to the control site (n = 454) in the post-implementation phase, RtoED was 54% at the intervention site compared to 44.1% (p = 0.02) at 180 days. The CDA had a lower adjusted probability of mortality at 90 days compared to the control site (4.8% VS 11.7%, p = 0.03). No rehospitalization LOS differences were noted.ConclusionsThe Clinique des Ainés showed effectiveness in caring for frail older patients in their homes by decreasing their hospital LOS by half and 90 days mortality risk. It was a safe care trajectory without a clinically significant increase in ED returns or mortality.

In-depth analysis and trends of cancer mortality in Kazakhstan: a joinpoint analysis of nationwide healthcare data 2014–2022

BackgroundCancer remains a leading cause of death both globally and in Kazakhstan, making it crucial to track its mortality trends. This study aimed to investigate cancer mortality trends from 2014 to 2022 in Kazakhstan.MethodsThis study utilized data from Kazakhstan’s Unified National Electronic Health System to perform descriptive data analysis and employed Joinpoint regression models to analyze average annual percent change (AAPC) in cancer-related mortality estimates. The authors also examined the mortality-to-incidence ratio (MIR) and proportionate mortality (PM).ResultsThe study analyzed 123,622 cancer-related death reports from 2014 to 2022. Major causes included trachea, bronchus, and lung cancer (16.01%), stomach cancer (11.43%), and colon and rectum cancer (10.05%), accounting for 37.48% of all cancer-related deaths. AAPCs showed a significant increase in mortality for individuals aged 18–44 (1.36%; 95% CI: 0.05%; 2.71%), while those aged 45–59 and 60–74 experienced decreases of -2.02% (95% CI: -3.05%; -0.96%) and − 2.10% (95% CI:-3.22%; -0.96%), respectively. PM was stable until 2019 but decreased from 2020 to 2021, while MIR increased during the same period. A significant decrease in oesophageal cancer mortality was observed in both females (-4.03%; 95% CI: -6.11%; -1.83%) and males (-2.44%; 95% CI: -4.89%; -0.02%), whereas ovarian cancer mortality increased by 0.95% (95% CI: 0.03%; 1.91%). In males, mortality from trachea, bronchus, and lung cancers decreased by -2.14% (95% CI: -3.00%; -1.25%), while “other neoplasms” rose by 6.21% (95% CI: 1.40%; 11.27%). Regional analysis highlighted variability, with the Kyzylorda region showing a pronounced increase in mortality (27.18%; 95% CI: 14.11%; 42.35%).ConclusionsDespite slight increases in MIR during the COVID-19 pandemic, overall cancer mortality trends remained stable. The findings highlight the need for targeted interventions, especially for individuals aged 18–44, ovarian cancer, and “other neoplasms”. Further research is needed to explore regional mortality variations.

Atrial functional and ventricular functional mitral regurgitation: definitions, epidemiology, and prognostic implications

Abstract Background Severe functional mitral regurgitation (fMR) can be divided into two subgroups: fMR of atrial (AfMR) and fMR of ventricular origin (VfMR). Studies on AfMR are scarce and inconsistent, lacking a uniform definition of AfMR. Hence, little is known about its epidemiology, morphological features, associated risk profiles, and prognostic implications. Purpose The objective of this study was to develop and test a uniform definition of fMR based on the morphological correlate and to describe demographic characteristics, detail entity-specific morphological features and to investigate the associated prognostic impact. Methods 13052 patients with severe fMR and those at risk of severe fMR (comprising mild and moderate fMR)were included. Based on the ratio of left atrial volume (LA) to left ventricular end-diastolic volume (LVEDV), those with severe fMR (n=1163) were divided into AfMR and VfMR. The median of this ratio was used for allocation. Therefore, a LA/LVEDV ratio ≤ 0.56 indicated predominantly ventricular eccentric remodelling, whereas a ratio &amp;gt; 0.56 indicated predominantly atrial remodelling. Results AfMR was more frequently observed in female patients and peak age was a decade later, compared to VfMR. AfMR was the predominant fMR subtype in patients with heart failure with preserved (76%) and mildly reduced ejection fraction (61%), but a significant proportion could be observed even in patients with heart failure with reduced ejection fraction (32%). Severe fMR was associated with excess mortality for both entities: VfMR HR 1.31 [95% CI: 1.14-1.50], p&amp;lt;0.001, with a more pronounced impact in patients with AfMR HR 1.68 [95% CI: 1.47-1.91], p&amp;lt;0.001; AfMR vs. VfMR: HR 1.27 [95% CI: 1.06-1.54], p=0.011. The association between fMR and excess mortality persisted even after multivariate adjustment. In both entities, ischaemic heart disease was common and resulted in a significant increase of mortality (VfMR: HR 1.67 [95% CI: 1.40-1.98], p for interaction&amp;lt;0.001; AfMR: HR 2.10 [95% CI: 1.75-2.52], p for interaction=0.006). Conclusion Based on the entity-specific morphological correlate, severe fMR can be classified into AfMR and VfMR. AfMR occurs across the entire HF spectrum, is more frequently observed in elderly and female patients, and exhibits a worse prognosis than VfMR. The presence of ischaemic heart disease is associated with a near doubling of mortality in both subgroups of severe fMR.Prevalence of fMRKaplan-Meier analysis

Expression of myostatin and folistatin as a response to high-load strength training to counteract the loss of muscle mass in heart failure with preserved ejection fraction

Abstract Background and Purpose Muscle loss is a common complication in patients with heart failure (HF) associated with a significant increase in morbidity and mortality. Myokines (muscle proteins) play a crucial role in the pathophysiology of the disease; in particular, an imbalance in myostatin and follistatin has been reported. Although strength training (ST) within a cardiac rehabilitation (CR) program can modulate the expression of these myokines, its effect in patients with HF with preserved ejection fraction (HFpEF) is unknown. We hypothesize that in this population, ST with high load and low repetitions can mitigate muscle cachexia with better myiokine overexpression in this population. Our objective is to evaluate the impact of a CR program with emphasis on high-load, low-repetition ST on the regulation of these muscle proteins, muscle gain and cardiorespiratory fitness (CRFit) in patients with HFpEF. Methods Quasi-experimental study of a CR program (24 sessions of 90 minutes, 3 times a week, for 8 weeks), with the following structure: warm-up (10 minutes), 30-minute ST of high loads (&amp;gt;85% maximum repetition, 1MR) with low repetitions (3-5) and rest times between sets of 2 minutes; then 30 minutes of aerobic resistance training at moderate intensity (60-80% of maximum heart rate) and finally breathing exercises and cool-down (10 minutes). Myokines were determined by immunoassays. Muscular strength was determined by 1MR in biceps, triceps, lateral deltoid, quadriceps, hamstrings, gastrocnemius and soleus. For CRFit, maximum oxygen consumption (VO2) was measured and six-minute walk test protocol was also performed. Pre and post-intervention comparison was made using paired t test, Pearson's correlation was used in data analysis and a value of p&amp;lt;0.05 was considered significant. Results 59 patients were admitted, of which 8 of them left due to decompensation. Of the remaining 51 (62.7% male), the mean age was 66±8 years, all of them with HFpEF (M:55±2.4% vs W:54±2.1%; p=0.743). The other diagnoses in the study population were myocardial revascularization (52.94%), angioplasty (29.41%), valve replacement (11.6%), arterial hypertension (60%) and obesity (35%). After CR program it was observerd an improvement in VO2 (from 9.95±2.6 to 13.32±1.7; p=0.022) and meters traveled (243±41 to 349±14; p=0.002), and a decrease in myostatin levels (3337.1±69.2 to 2448.0±70.6; p=0.001) and elevation of follistatin (2167.4±96.9 to 3231.6±67.7; p=0.001). We found a strong positive correlation between follistatin levels and muscle percentage (r=0.8947 Pearson, graph1) and a strong negative correlation with myostatin and muscle percentage (r= -0.8034 Pearson, graph2). Conclusion A phase II CR program with a ST component based on high loads and low repetitions improved muscle strength and mass, FitCR and distance traveled in patients with HFpEF, without modify hemodynamic function. Follistatin levels increased by 49.09% and myostatin levels decreased by 26.65%.

Serum homocysteine levels and mortality: a cohort study

Abstract Background Homocysteine, an intermediate metabolite derived from dietary methionine, plays a pivotal role in deoxyribonucleic acid expression and contribute to its antioxidant capabilities. Elevated homocysteine levels can increase the risk of cardiovascular disease (CVD), cancer, and neurological disorder; however, low levels of homocysteine are generally not considered harmful. This study evaluates the association between all levels of homocysteine-both low and high-and the risk of all-cause and cause-specific mortality in Korean adult men. Methods A study involving 221,356 Korean adult men categorized them into quintiles based on their homocysteine levels. The main outcomes examined were mortality from all causes, cardiovascular disease (CVD), cancer, and dementia. Hazard ratios (HRs) were determined using Cox proportional hazards models, and the dose-response relationship between homocysteine levels and mortality risk was further analyzed using a restricted cubic splines model. Results Compared to the reference category (Q2, 8.8-9.9 µmol/L), there was a significant increase in all-cause mortality associated with both low and high homocysteine levels after adjusting for multiple variables (Pinteraction=0.002). Furthermore, spline regression revealed a U-shaped relationship between homocysteine levels and both all-cause and CVD mortality, with an inflection point at 9.1 µmol/L. This U-shaped association was not observed in the subgroup that received vitamin supplements. Conclusions Among young and middle-aged Korean adult men, both low and high homocysteine levels were found to increase the risk of all-cause and CVD mortality, demonstrating a U-shaped relationship. However, this association lost statistical significance with vitamin supplementation. These findings underscore the importance of monitoring both low and high homocysteine levels as potential mortality risk factors in men and suggest a possible protective role of vitamins. Key messages • Both low and high levels of homocysteine in young and middle-aged Korean men are associated with increased risks of all-cause and cardiovascular mortality, demonstrating a U-shaped relationship. • Vitamin supplementation appears to nullify this association, suggesting a potential protective effect against mortality.

In-hospital outcomes of acute myocardial infarction patients without standard modifiable cardiovascular risk factors across varying body mass index

Abstract Background Individuals who present with acute myocardial infarction (AMI) in the absence of standard modifiable cardiovascular risk factors (i.e., SMuRF-less) seem to have a significantly increased risk of mortality; however, it remains unclear whether the ‘SMuRF paradox’ would be influenced by patients’ baseline body mass index (BMI) status. Purpose To assess the disparities in the prevalence and prognostic implications of SMuRF-less among patients with newly diagnosed AMI across varying body mass index (BMI). Methods Using data from the Improving Care for Cardiovascular Disease in China–Acute Coronary Syndrome (CCC–ACS) project, we retrospectively analyzed AMI patients with and without SMuRFs and categorized their baseline BMI as underweight (&amp;lt;18.5kg/m2), normal weight (18.5-24kg/m2), overweight (24-28kg/m2), and obese (&amp;gt;28kg/m2). The primary outcome was in-hospital all-cause mortality. Multivariable logistic regression models were used to estimate BMI-stratified associations between SMuRF-less and each outcome, sequentially adjusting for demographic, clinical characteristics, and prevention strategies. Results Between 2014 and 2019, 44,538 adult patients hospitalized for first-presentation AMI were included, of which 4,454 (10.0%) were SMuRF-less. The incidence of SMuRF-less declined from 16.2% to 6.5% as BMI increased by category, and it prevailed more frequently among females and elders regardless of their BMI status. During the median hospital stay of 9 days, SMuRF-less patients had a significant increase in in-hospital mortality than patients with one or more SMuRF (2.1% vs. 1.0%, adjusted odds ratio [OR], 1.750 [95% CI 1.057–2.896], P&amp;lt;0.001). The highest mortality rate was observed in the SMuRF-less underweight group (3.5%). Took ≥1 SMuRF and obese as the reference group as they presented the finest outcome, SMuRF-less underweight group exhibited the highest increase in mortality (3.5% vs 0.5%, adjusted odds ratio [OR], 3.854 [95% CI 2.130–6.973], P&amp;lt;0.001). However, interaction analyses provided no evidence that BMI significantly modifies SMuRF-less’s association with in-hospital mortality (P for interaction=0.247). Conclusion Approximately one-tenth of first-presentation AMI patients had no SMuRF, who were more frequently women, elders, and underweight. Compared with those with at least one SMuRF, SMuRF-less patients have a significantly higher risk of in-hospital mortality, especially in those underweight, while in-hospital survival was the most favorable among ≥1 SMuRF and obese patients.

Epidemiology of Bacteremia in Patients with Hematological Malignancies and Hematopoietic Stem Cell Transplantation and the Impact of Antibiotic Resistance on Mortality: Data from a Multicenter Study in Argentina

The epidemiology of bacteremia and the antibiotic resistance profile (ARP) of Gram-negative bacilli (GNB) in hematological malignancies (HM) and hematopoietic stem cell transplant (HSCT) patients may differ according to geographic region. In addition, multidrug-resistant organisms (MDROs) may impact mortality. This is a prospective, observational, and multicenter study. The first episodes of bacteremia in adult patients with HM or HSCT were included. The risk factors for 30-day mortality were identified. One thousand two hundred and seventy-seven episodes were included (HM: 920; HSCT: 357). GNB were isolated in 60.3% of episodes, with Enterobacterales (46.9%) and P. aeruginosa (8.5%) being the most frequent. Gram-positive cocci were isolated in 41.9% of episodes, with coagulase-negative staphylococci (19.8%) and S. aureus (10.4%) being the most frequent. MDROs were isolated in 40.2% (24.4% GNB). The ARP of GNB in patients with HM vs. HSCT was cefepime: 36.8% vs. 45.7% (p = 0.026); piperacillin–tazobactam: 31.05% vs. 45.2% (p &lt; 0.0001); carbapenems: 18.9% vs. 27.3% (p = 0.012); and aminoglycosides: 9.3% vs. 15.4% (p = 0.017), respectively. Overall mortality between patients with HM and HSCT was 17.5% vs. 17.6% (p = 0.951), respectively. The risk factors for mortality were relapsed and refractory underlying disease, corticosteroids use, respiratory source, septic shock, and GNB resistant to meropenem, while 7-day clinical response was a protective factor for survival. Bacteremia was frequently caused by GNB, with a large proportion of MDROs and a high level of antibiotic resistance, especially in patients with HSCT. Carbapenem-resistant GNB bacteremia was associated with a significant increase in mortality.

Molecular Targets of Plant-Derived Bioactive Compounds in Oral Squamous Cell Carcinoma.

With a significant increase in both incidence and mortality, oral cancer-particularly oral squamous cell carcinoma (OSCC)-is one of the main causes of death in developing countries. Even though there is evidence of advances in surgery, chemotherapy, and radiotherapy, the overall survival rate for patients with OSCC has improved, but by a small percentage. This may be due, on the one hand, to the fact that the disease is diagnosed when it is at a too-advanced stage, when metastases are already present. This review explores the therapeutic potential of natural herbal products and their use as adjuvant therapies in the treatment of oral cancer from online sources in databases (PubMed, Web of Science, Google Scholar, Research Gate, Scopus, Elsevier). Even if classic therapies are known to be effective, they often produce many serious side effects and can create resistance. Certain natural plant compounds may offer a complementary approach by inducing apoptosis, suppressing tumor growth, and improving chemotherapy effectiveness. The integration of these compounds with conventional treatments to obtain remarkable synergistic effects represents a major point of interest to many authors. This review highlights the study of molecular mechanisms and their efficiency in in vitro and in vivo models, as well as the strategic ways in which drugs can be administered to optimize their use in real contexts. This review may have a significant impact on the oncology community, creating new inspirations for the development of more effective, safer cancer therapies with less toxic potential.

Differential sensitivity of hemocyte subpopulations (Mytilus edulis) to aged polyethylene terephthalate micro- and nanoplastic particles

Bivalve hemocytes, particularly granulocytes and hyalinocytes, play a crucial role in cell-mediated immunity. However, their interactions with aged plastic particles, exhibiting altered properties that more closely resemble those in natural environments, remain largely underexplored. This study assesses the differential responses of hemocyte subpopulations (Mytilus edulis) to chemically aged polyethylene terephthalate (PET) microplastic (MPs) and nanoplastic (NPs) particles across multiple cellular effect endpoints. Particle characteristics were analyzed using Single Particle Extinction and Scattering, Raman Spectroscopy, Scanning Electron Microscopy, and Dynamic Light Scattering. In vitro experiments with aged PET MPs (1.9 µm) and NPs (0.68 µm) were conducted at three internally relevant concentrations: 10 (C1), 10³ (C2), and 10⁵ particles/mL (C3). Cellular responses were assessed by measuring lysosomal content stability, reactive oxygen species (ROS) production, cellular mortality, and morphological parameters using flow cytometry at 6, 12, 24, and 48 hours. Our findings provide mechanistic insights into the differential sensitivities of granulocytes and hyalinocytes to aged PET, influenced by particle size and concentration. Specifically, aged PET MPs and NPs induce distinct size and concentration-dependent patterns of lysosomal destabilization, coinciding with the loss of functional integrity. Elevated ROS levels were observed only in granulocytes and hyalinocytes exposed to high concentrations of aged PET NPs, underscoring the effects on oxidative stress. Both aged PET MPs and NPs induce significant increases in cellular mortality, particularly after 24 h of exposure at high concentrations. These findings reveal the complex cellular mechanisms underlying hemocyte functional impairment following exposure to aged PET particles under environmentally and biologically relevant conditions.

Utilization of Gomophia egyptiaca (Red Starfish) in the Biological Control of Aedes aegypti Larvae

Background: Aedes aegypti mosquito spreads many vital diseases to humans. Traditionally, chemical insecticides were used for control. Recently, interest has grown in using aquatic predators, such as the Red Starfish (Gomophia egyptiaca), to target mosquito larvae in water, offering a potential biological control method. Methods: This study investigates the larvicidal potential of G. egyptiaca against Ae. aegypti larvae, a key vector for dengue and other mosquito-borne diseases after 24 hours. Result: The results demonstrate a significant increase in mortality rates with prolonged exposure to G. egyptiaca. After 2 hours, the mortality rate was 6.66%, increasing to 20% at 4 hours, 60% at 12 hours and peaking at 80% after 24 hours. Statistical analysis using one-way ANOVA revealed a highly significant p-value of 3.93, confirming the effectiveness of G. egyptiaca over time. LT50 was determined to be 14.91 hours, with a confidence interval of 12.40 to 18.65 hours. These findings indicate that G. egyptiaca could serve as a powerful alternative to chemical insecticides, offering a sustainable approach to mosquito control. However, field trials and evaluations of non-target impacts are necessary to fully assess its potential in diverse ecological settings. This study supports the integration of G. egyptiaca into mosquito management strategies, particularly where chemical resistance and environmental concerns are prevalent.

Discovery of New Natural Phytocompounds: The Modern Tools to Fight Against Traditional Bacterial Pathogens.

Ongoing competition between disease-causing bacteria and human hosts has resulted in the discovery of a wide array of antibacterials. The advent of antibacterials ushered in a promising period in the realm of microbiology, but its brilliance was short-lived and soon diminished. The excessive and incorrect use of antibacterials results in limited selection pressure on the targeted microorganisms, which in turn promotes the evolution of microbes instead of killing them. Consequently, antibacterial resistance has developed and given rise to strains that are resistant to many drugs, leading to a significant increase in mortality rates. The current review delves into the potential of novel natural phytocompounds as innovative solutions to combat these potential bacterial threats. The review begins by showcasing the modus operandi of conventional antibacterial drugs followed by addressing the mechanisms of resistance to antibacterial agents, which have significantly lowered the efficacy of conventional treatments. In contrast, the review explores the mechanism of antibacterial activity of plant-derived phytochemicals, unraveling the various ways in which natural compounds interact with bacterial targets. Furthermore, the review examines the synergism between plant phytochemicals and conventional antibiotics, showcasing the efficacy of this combinatorial approach in overcoming resistance. The review concludes by summarizing the current research and offering valuable insights into challenges in the use of plant phytochemicals as antibacterial therapeutics. This comprehensive overview reinforces the promise of incorporating modern scientific tools with traditional phytotherapy to develop effective strategies against resistant bacterial pathogens.

Sleep restriction exacerbates cardiac dysfunction in diabetic mice by causing cardiomyocyte death and fibrosis through mitochondrial damage.

Diabetic cardiomyopathy (DCM) is a cardiovascular complication of diabetes mellitus with a poor prognosis and is the leading cause of death in diabetic patients. Sleep deficiency is not only recognized as an important risk factor for the development of type 2 DM, but is also associated with increased morbidity and mortality of cardiovascular disease. The underlying role and mechanisms of sleep restriction (SR) in DCM are far from clear. The KK/Upj-Ay mouse model of T2 DM was used as a study subject, and the small animal ultrasound imaging system was used to detect the function of the heart; immunopathological staining was used to clarify the histo-structural pathological alterations of the heart; and TUNEL staining, qPCR, transmission electron microscopy (TEM), and ELISA kits were used to detect apoptosis, oxidative stress, inflammation, and mitochondrial damage, and related molecular alterations. SR led to a significant increase in mortality, cardiac hypertrophy, necrosis, glycogen deposition and fibrosis further deteriorated in DM KK mice. SR increased cardiomyocyte death in KK mice through the Bax/Bcl2 pathway. In addition to this, SR not only exacerbated the inflammatory response, but also aggravated mitochondrial damage and promoted oxidative stress in KK mice through the PRDM16-PGC-1α pathway. Overall, SR exacerbates structural alterations and dysfunction through inflammation, oxidative stress, and apoptosis in DM KK mice, increasing the risk of death. Clinicians and diabetic patients are prompted to pay attention to sleep habits to avoid accelerating the transition of DCM to heart failure and inducing death due to poor sleep habits.

AVALIAÇÃO DOS DESAFIOS DE ACESSO AOS SERVIÇOS DE SAÚDE PELO SUS PARA PACIENTES ONCOLÓGICAS PORTADORAS DE CÂNCER DE MAMA:UMA REVISÃO INTEGRATIVA.

Breast cancer has been considered an important public health problem in Brazil, with women as the main victims, presenting several risk factors associated with them, such as genetic predisposition, lifestyle, reproductive habits and also the environment. Late diagnosis and the long wait to start treatment have led to a significant increase in mortality from this disease in women. The objective of this research was to identify and analyze, through an integrative literature review, academic productions that address the main causes, complications and challenges faced by cancer patients with breast cancer when using public health services. After applying the inclusion and exclusion criteria, 6 studies were selected from the CAPES, BVS and Scielo Periodical databases using the descriptors “Breast Cancer”, “SUS” and “Health”, with the AND operator, in the time window 2014 to 2024. Thus, it was noted that the main barrir faced by these patients is access to health services, emphasizing that the referral centers are often located in other cities and states, which results in the delay in the start of treatment.

Characterization of CYP303A1 and its potential application based on ZIF-8 nanoparticle-wrapped dsRNA in Nilaparvata lugens (Stål).

RNA interference (RNAi) technology has been put forward as a promising method for pest control and resistance management. Mining highly efficient lethal genes and constructing stable double-stranded RNA (dsRNA) delivery systems are of great significance to improve the application potential of RNAi technology. In this study, we characterized a molting-related gene, NlCYP303A1, in Nilaparvata lugens that was highly expressed in the cuticle and at the end stages of each instar in nymphs. Silencing the expression of NlCYP303A1 in N. lugens resulted in a deformed phenotype and a significant increase in mortality. Furthermore, interfering with NlCYP303A1 changed the relative expression of key genes in the chitin synthesis and degradation pathway. Finally, we used the nanocarrier zeolitic imidazolate framework-8 (ZIF-8) to load dsNlCYP303A1, forming a complex denoted as dsNlCYP303A1@ZIF-8. The results of both feeding and rice-seedling dip experiments indicated that the expression of NlCYP303A1 was dramatically and persistently suppressed by the dsNlCYP303A1@ZIF-8 treatment, compared with treatment with dsNlCYP303A1, suggesting that ZIF-8 can enhance the interference efficiency as well as the stability of dsNlCYP303A1. Our results demonstrate that the lethal gene NlCYP303A1 can be employed as an excellent target for RNAi technology by loading onto a nano-delivery system, and provide new insights into the creation of innovative pest control approaches. © 2024 Society of Chemical Industry.

Exploring the detrimental effects of microplastics on Asian seabass (Lates calcarifer) fingerlings survival and health

Microplastics (MPs) are widely used and disposed of indiscriminately, posing a potential threat to aquatic life. Herein, Asian seabass (Lates calcarifer) fingerlings were exposed to various concentrations (1, 10 and 100 ppt or g/kg) of dietary polyethylene MPs for 16 days. The results indicated a significant increase in mortality among the fish fed with dietary MPs compared to the control. Furthermore, histological analysis of the liver revealed moderate-to-severe morphological alterations, hepatocyte necrosis and vacuolisation as the concentration gradient of MPs increased. The severity of the alterations was highest at a concentration of 100 ppt, indicating a direct correlation between MP and liver damage. In addition, RNA sequencing and Gene Ontology term enrichment analysis revealed that a total of 4137 genes were significantly differentially expressed, with 1958 upregulated and 2179 downregulated genes. The significantly enriched terms included ‘oxidoreductase activity’, ‘endocytosis’, ‘mitochondrial’, ‘immune system process’ and ‘lipid catabolic process’. Moreover, the Kyoto Encyclopaedia of Genes and Genomes enrichment analysis demonstrated that dietary MPs triggered oxidative stress, immune response and adaptive mechanism pathways in fish. Thus, MPs can induce metabolic disorders in L. calcarifer, highlighting their potential threat to aquatic organisms.