High Mortality Research Articles

Acetylsalicylic Acid with Ascorbate: A Promising Combination Therapy for Solid Tumors.

Cancer is a deadly disease with high mortality rates in developing countries. A recent preclinical study found promising results in treating hepatocellular carcinoma (HCC) by combining acetylsalicylic acid (ASA) and ascorbate (AS), which might offer a safer alternative to expensive clinical chemotherapeutics; however, the impact of this combination on other tumors remains unexplored. Therefore, this study aims to investigate the effectiveness of combining ASA and AS in treating Ehrlich solid tumors. Eighty female Swiss albino mice were divided into eight groups (10 mice/group): four healthy groups (healthy, AS, ASA, and AS+ASA) and four groups with carcinoma (Ehrlich ascites carcinoma [EAC], EAC+AS, EAC+ASA, and EAC+AS+ASA). AS was injected intraperitoneally (4g/kg) daily for 10 days, whereas ASA was ingested orally at 60 mg/kg/day for 10 days. Carcinoma was induced by subcutaneous injection of 1×106 EAC cells/mouse once. Treatment of carcinoma started after 10 days of tumor inoculation. Blood, livers, and tumors were obtained, and tumor weights, volumes, and levels of hemoglobin, aminotransferases, albumin, bilirubin, urea, creatinine, lipid profile, malondialdehyde, nitric oxide, glutathione, catalase, total antioxidant capacity, lactate dehydrogenase, and creatine kinase were estimated. The percentage increase in lifespan was also assessed. Tumor treatment alleviated tumor burden. Tumor size was reduced, lifespan increased, organs (liver, kidney, and heart) functions adjusted, hemoglobin, lipid profile improved, and oxidative stress decreased. Combining ASA with AS showed more effective antitumor effects than only ASA or AS alone. After more validation research, combining ASA with AS may provide benefit in cancer treatment.

Childhood interstitial lung diseases: current understanding of the classification and imaging findings.

Childhood interstitial lung diseases (chILDs) encompass a diverse group of disorders with a high mortality rate and severe respiratory morbidities. Recent investigations have revealed that the classification of adult ILDs is not valid for chILDs, particularly for ILDs of early onset. Therefore, Children's Interstitial Lung Disease Research Cooperative of North America proposed a new classification of chILDs for affected children under 2years of age, and later another classification for affected individuals between 2 and 18years of age. In this review, we provide an overview of the imaging findings of chILDs by classification. Most infantile ILDs have unique clinical, radiological, and molecular findings, while the manifestation of pediatric ILDs overlaps with that of adult ILDs.

Dysfunctional host cellular immune responses are associated with mortality in melioidosis.

Melioidosis is a tropical infection caused by the intracellular pathogen Burkholderia pseudomallei, an underreported and emerging global threat. As melioidosis-associated mortality is frequently high despite antibiotics, novel management strategies are critically needed. Therefore, we sought to determine whether functional changes in the host innate and adaptive immune responses are induced during acute melioidosis and are associated with outcome. Using a unique whole blood stimulation assay developed for use in resource-limited settings, we examined induced cellular functional and phenotypic changes in a cohort of patients with bacteremic melioidosis prospectively enrolled within 24 hours of positive blood culture and followed for 28 days. Compared to healthy controls, melioidosis survivors generated an IL-17 response mediated by Th17 cells and terminally-differentiated effector memory CD8+ T cells (P < 0.05, both), persisting to 28-days after enrollment. Furthermore, melioidosis survivors developed polyfunctional cytokine production in CD8+ T cells (P < 0.01). Conversely, a reduction in CCR6+ CD4+ T cells was associated with higher mortality, even after adjustments for severity of illness (P = 0.004). Acute melioidosis was also associated with a profound acute impairment in monocyte function as stimulated cytokine responses were reduced in classical, intermediate and non-classical monocytes. Impaired monocyte cytokine function improved by 28-days after enrollment. These data suggest that IL-17 mediated cellular responses may be contributors to host defense during acute melioidosis, and that innate immune function may be impaired. These insights could provide novel targets for the development of therapies and vaccine targets in this frequently lethal disease.

Morbidity and Mortality of Hospital-Onset SARS-CoV-2 Infections Due to Omicron Versus Prior Variants : A Propensity-Matched Analysis.

Many hospitals have scaled back measures to prevent nosocomial SARS-CoV-2 infection given large decreases in the morbidity and mortality of SARS-CoV-2 infections for most people. Little is known, however, about the morbidity and mortality of nosocomial SARS-CoV-2 infections for hospitalized patients in the Omicron era. To estimate the effect of nosocomial SARS-CoV-2 infection on hospitalized patients' outcomes during the pre-Omicron and Omicron periods. Retrospective matched cohort study. 5 acute care hospitals in Massachusetts, December 2020 to April 2023. Adults testing positive for SARS-CoV-2 on or after hospital day 5, after negative SARS-CoV-2 test results on admission and on hospital day 3, were matched to control participants by hospital, service, time period, days since admission, and propensity scores that incorporated demographics, comorbid conditions, vaccination status, primary diagnosis category, vital signs, and laboratory test values. Primary outcomes were hospital mortality and time to discharge. Secondary outcomes were intensive care unit (ICU) admission, need for advanced oxygen support, discharge destination, hospital-free days, and 30-day readmissions. There were 274 cases of hospital-onset SARS-CoV-2 infection during the pre-Omicron period and 1037 cases during the Omicron period (0.17 vs. 0.49 cases per 100 admissions). Patients with hospital-onset SARS-CoV-2 infection were older and had more comorbid conditions than those without. During the pre-Omicron period, hospital-onset SARS-CoV-2 infection was associated with increased risk for ICU admission, increased need for high-flow oxygen, longer time to discharge (median difference, 4.7 days [95% CI, 2.9 to 6.6 days]), and higher mortality (risk ratio, 2.0 [CI, 1.1 to 3.8]) versus matched control participants. During the Omicron period, hospital-onset SARS-CoV-2 infection remained associated with increased risk for ICU admission and increased time to discharge (median difference, 4.2 days [CI, 3.6 to 5.0 days]). The association with increased hospital mortality was attenuated but still significant (risk ratio, 1.6 [CI, 1.2 to 2.3]). Residual confounding may be present. Hospital-onset SARS-CoV-2 infection during the Omicron period remains associated with increased morbidity and mortality. Harvard Medical School Department of Population Medicine.

Air Pollution Increases Risk of Occurrence of Intracerebral Haemorrhage but Not of Subarachnoid Haemorrhage: Time-Series Cross-Sectional Study

(1) Background: Haemorrhagic strokes (HS), including intracerebral (ICH) and subarachnoid haemorrhages (SAH), account for approximately 10–15% of strokes worldwide but are associated with worse functional outcomes and higher rates of mortality, and financial burden than ischemic stroke. There is evidence that confirmed poor air quality may increase the incidence of haemorrhagic strokes. The aim of our study was to evaluate the association between individual ambient air pollutants and the risk of haemorrhagic stroke in an urban environment without high levels of air pollution. (2) Methods: A time-series cross-sectional study design was used. A daily air pollution concentration (Agency of Regional Air Quality Monitoring in the Gdansk Metropolitan Area) and incidence of haemorrhagic strokes (National Health Fund) were obtained and covered the time period from 1 January 2014 to 31 December 2018. A generalised additive model with Poisson regression was used to estimate the associations between 24-h mean concentrations of SO2, NO, NO2, NOx, CO, PM10, PM2.5, and O3 and a daily number of haemorrhagic strokes. (3) Results: The single-day lag model results showed that NO2, NO and NOx exposure was associated with increased risk of ICH (88% events) with RR of 1.059 (95% CI: 1.015–1.105 for lag0), 1.033 (95% CI: 1.007–1.060 for lag0) and 1.031 (95% CI: 1.005–1.056 for lag0), but not for SAH (12% events). Exposure to CO was related to a substantial and statistically significant increase in incidence for 1.031 (95% CI: 1.002–1.061 for lag0) but not for SAH. Higher SO2, PM10, PM2.5, and O3 exposures were not significantly related to both ISC and SAH. (4) Conclusions: In this time-series cross-sectional study, we found strong evidence that supports the hypothesis that transient elevations in ambient NO2, NO and CO are associated with a higher relative risk of intracerebral but not subarachnoid haemorrhage.

Breast cancer preventive practices and associated factors among reproductive age women in Wadila District, North East Ethiopia: community based cross-sectional study

BackgroundCancer is one of the leading causes of morbidity and mortality worldwide. Among all cancer types, breast cancer stands out as the most common and is characterized by distinct molecular characteristics. This disease poses a growing public health concern, particularly in low and middle-income countries where it is associated with high mortality rates. Despite these challenges, there is a paucity of data on breast cancer preventive practices and associated factors among reproductive-age women in Wollo, Ethiopia. Hence, this study aimed to evaluate the level of breast cancer awareness, preventive practices, and associated factors among women of reproductive age residing in Wadila district, Wollo, Ethiopia in the year 2022.MethodA cross-sectional community-based study involving 352 women of reproductive age in Wadila district was carried out between May and June 2022. Participants were selected using a systematic random sampling technique, and data analysis was conducted using Statistical Package for Social Science (SPSS) version 23 software. Logistic regression analysis was utilized to determine the odds ratio for variable associations, with statistical significance set at p < 0.05.ResultThe prevalence of breast-examination among women of reproductive age was determined to be 40.1% (95% Interval [CI]: 34.94–45.18). Factors such as educational status (Adjusted Odds Ratio [AOR]: 0.28, 95% CI: 0.13–0.6), income (AOR: 0.19, 95% CI: 0.11–0.33), and family history of breast conditions in reproductive-age women (AOR: 1.90, 95% CI: 1.08–3.34) were significantly linked to the practice of breast self-examination in this population.ConclusionThe study highlighted a decline in regular breast self-examination among women of reproductive age. It revealed that the reduced frequency of regular breast self-examination was a prevalent concern among women in this age group and the broader community. Educational level, monthly income, and family history of cancer among women of reproductive age were identified as significant factors linked to the practice of regular breast examination.

Duffy Antigen Receptor for Chemokines (DARC) Nanodisc-Based Biosensor for Detection of Staphylococcal Bicomponent Pore-Forming Leukocidins.

Staphylococcus aureus (S. aureus) is an opportunistic infectious pathogen, which causes a high mortality rate during bloodstream infections. The early detection of virulent strains in patients' blood samples is of medical interest for rapid diagnosis. The main virulent factors identified in patient isolates include leukocidins that bind to specific membrane receptors and lyse immune cells and erythrocytes. Duffy antigen receptor for chemokines (DARC) on the surface of specific cells is a main target of leukocidins such as gamma-hemolysin AB (HlgAB) and leukocidin ED (LukED). Among them, HlgAB is a conserved and critical leukocidin that binds to DARC and forms pores on the cell membranes, leading to cell lysis. Current methods are based on ELISA or bacterial culture, which takes hours to days. For detecting HlgAB with faster response and higher sensitivity, we developed a biosensor that combines single-walled carbon nanotube field effect transistors (swCNT-FETs) with immobilized DARC receptors as biosensing elements. DARC was purified from a bacterial expression system and successfully reconstituted into nanodiscs that preserve binding capability for HlgAB. Dynamic light scattering (DLS) and scanning electron microscopy (SEM) showed an increase of the DARC-containing nanodisc size in the presence of HlgAB, indicating the formation of HlgAB prepore or pore complexes. We demonstrate that this sensor can specifically detect the leukocidins HlgA and HlgAB in a quantitative manner within the dynamic range of 1 fM to 100 pM with an LOD of 0.122 fM and an LOQ of 0.441 fM. The sensor was challenged with human serum spiked with HlgAB as simulated clinical samples. After dilution for decreasing nonspecific binding, it selectively detected the toxin with a similar detection range and apparent dissociation constant as in the buffer. This biosensor was demonstrated with remarkable sensitivity to detect HlgAB rapidly and has the potential as a tool for fundamental research and clinical applications, although this sensor cannot differentiate between HlgAB and LukED as both have the same receptor.

Nursing Student Knowledge Related to Sepsis in Croatian, Cypriot, and Greek Universities: A Cross-Sectional European Study

Background: Although the treatment of sepsis has advanced during the past 20 years there is still a high incidence and high mortality, which make sepsis one of the leading public health problems. Adequate knowledge of sepsis and the sepsis guidelines is still the most important pillar for nurses because of the long time they spend with critically ill patients. Given their frontline role in patient care, nurses are pivotal in early sepsis recognition, timely intervention, and ensuring adherence to treatment protocols. Aim: This study aimed to investigate nursing students’ knowledge of sepsis and the symptoms of sepsis, and to compare the results of nursing students from several European universities (Croatia, Cyprus, Greece). Methods: A cross-sectional design was used, with a sample of 626 undergraduate nursing students from Croatian, Cypriot, and Greek universities from 2022 to 2023. Demographic features (gender, age, employment, year of study) and a questionnaire provided by Eitze et al. were utilized as instruments. Results: There was a statistically significant difference among the countries (F(2.625) = 4.254, p = 0.015) in average knowledge about sepsis, with Scheffe’s post hoc test indicating that the Cypriot students had a higher average knowledge than the Greek students (p = 0.016), while students from neither country were significantly different from Croatian students (both p &gt; 0.05). Conclusions: This study showed the still limited knowledge of nursing students and the differences among the educational programs for nursing students. The educational curricula of nursing studies should increase the number of sepsis lectures and use innovative techniques.

Polyamidoamine Dendrimers: Brain-Targeted Drug Delivery Systems in Glioma Therapy

Glioma is the most common primary intracranial tumor, which is formed by the malignant transformation of glial cells in the brain and spinal cord. It has the characteristics of high incidence, high recurrence rate, high mortality and low cure rate. The treatments for glioma include surgical removal, chemotherapy and radiotherapy. Due to the obstruction of the biological barrier of brain tissue, it is difficult to achieve the desired therapeutic effects. To address the limitations imposed by the brain’s natural barriers and enhance the treatment efficacy, researchers have effectively used brain-targeted drug delivery systems (DDSs) in glioma therapy. Polyamidoamine (PAMAM) dendrimers, as branched macromolecular architectures, represent promising candidates for studies in glioma therapy. This review focuses on PAMAM-based DDSs in the treatment of glioma, highlighting their physicochemical characteristics, structural properties as well as an overview of the toxicity and safety profiles.

Santalum album L. alleviates cardiac function injury in heart failure by synergistically inhibiting inflammation, oxidative stress and apoptosis through multiple components

BackgroundHeart failure (HF) is a complex cardiovascular syndrome with high mortality. Santalum album L. (SAL) is a traditional Chinese medicine broadly applied for various diseases treatment including HF. However, the potential active compounds and molecular mechanisms of SAL in HF treatment are not well understood. MethodsThe active compounds and possible mechanisms of action of SAL were analyzed and validated by a systems pharmacology framework and an ISO-induced mouse HF model.ResultsWe initially confirmed that SAL alleviates heart damage in ISO-induced HF model. A total of 17 potentially active components in SAL were identified, with Luteolin (Lut) and Syringaldehyde (SYD) in SAL been identified as the most effective combination through probabilistic ensemble aggregation (PEA) analysis. These compounds, individually and in their combination (COMB), showed significant therapeutic effects on HF by targeting multiple pathways involved in anti-oxidation, anti-inflammation, and anti-apoptosis. The active ingredients in SAL effectively suppressed inflammatory mediators and pro-apoptotic proteins while enhancing the expression of anti-apoptotic factors and antioxidant markers. Furthermore, the synergistic effects of SAL on YAP and PI3K-AKT signaling pathways were further elucidated.ConclusionsMechanistically, the anti-HF effect of SAL is responsible for the synergistic effect of anti-inflammation, antioxidation and anti-apoptosis, delineating a multi-targeted therapeutic strategy for HF.Graphical

Contrasting responses of drosophila pupal parasitoids to heat waves in the larval and adult stages

Abstract The life history of parasitoids is divided into a parasitic immature stage living in or on a host invertebrate and a free‐living adult stage. We still have little consensus on how larvae and adult parasitoids differ in their responses to environmental heat waves. We tested the performance of two cosmopolitan drosophila pupal parasitoids, Pachycrepoideus vindemiae (Hymenoptera: Pteromalidae) and Trichopria drosophilae (Hymenoptera: Diapriidae), when exposed to 35 and 40°C heat waves in the larval and adult stage, respectively. Additionally, we tested if heat hardening in the larval stage influenced the thermal tolerance of adult parasitoids. P. vindemiae had a higher tolerance to heat waves than T. drosophilae in both the larval and adult stages. We did not find significantly increased thermal tolerance of adult wasps that experienced heat hardening during the larval stage. A 35°C heat wave had no effect on P. vindemiae. Larval T. drosophilae that experienced a 35°C heat wave had longer development times, but individuals that survived showed no significant decrease in longevity and fecundity compared with those without warming experience. By contrast, adult T. drosophilae suffered less mortality from the 35°C heat wave, but individuals that survived had significantly reduced longevity and fecundity. A 40°C heat wave resulted in higher mortality in the larval stage than in the adult stage for both parasitoid species. Our study clearly revealed the contrasting responses to heat waves in the larval and adult stages of two parasitoids and highlighted the importance of ontogenetic differences in thermal tolerance in predicting parasitoid distributions and population dynamics.

Clinical Profile and Predictors Affecting Outcome in Community-Acquired Acute Kidney Injury: A 3 Months Follow-Up Study

Background Community-Acquired Acute Kidney Injury (CA-AKI) is often a devastating clinical syndrome allied with high hospital mortality. Moreover, only limited prospective data exist on the outcomes of CA-AKI. Hence, this follow-up study was conducted to assess clinical profiles and the factors affecting outcomes in CA-AKI. Materials and Methods A prospective study enrolling 283 participants was conducted from the year 2021 to 2022. AKI patients defined as per Kidney Disease Improving Global Outcomes (KDIGO) criteria were included. Data were collected on demographics, clinical features, and etiological factors. Patients were followed for three months. Univariate and multinomial analyses were done to predict outcomes. The Cox regression model was fitted to identify predictors of mortality. Results The mean age of patients was 41.67±16.21 years with male predominance. Most of the patients required non-ICU (81.9%) care. Around 36% and 39.6 % of AKI patients were oliguric and required dialysis, respectively. Most patients had a single etiology, with sepsis being the most common cause. Most patients were in KDIGO stage 3, followed by stage 2. At three months of follow-up, 40.6%, 12.3%, and 4.2% had complete, partial, and non-recovery, respectively, and 30.4% died. Age, single etiology, hepatorenal syndrome, sepsis, requirement of mechanical ventilation and vasopressors, comorbidities and glomerulonephritis were significantly associated with mortality. Conclusion CA-AKI is significantly associated with higher mortality, even for those patients who require non-ICU care on presentation. This highlights the pressing need for AKI prevention, early detection, and intervention to mitigate reversible risk factors and optimize clinical outcomes.

Management of Cytomegalovirus Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Cytomegalovirus (CMV) is a type of double-stranded deoxyribonucleic acid virus belonging to the herpesviridae family. Following a primary infection, the virus becomes latent in various types of white blood cells. Cytomegalovirus infection can remain latent or become active, especially in immunocompromised individuals, such as those undergoing hematopoietic stem cell transplantation (HSCT), where CMV reactivation can occur. In this context, CMV infection is common and associated with high rates of morbidity and mortality. Pneumonia is one of the most serious complications, with mortality rates exceeding 50%. Additionally, even in the absence of organ-specific disease, CMV infection is related to increased mortality unrelated to hematologic neoplasm recurrence. Given the frequency and severity of this infection in HSCT patients, it is crucial to implement effective strategies for monitoring, prevention, and treatment. This guideline was developed to identify patient groups that benefit from a systematic approach to CMV infection and to define the most appropriate strategy for each group. Monitoring CMV viral load in peripheral blood is crucial, especially in patients at moderate to high risk of active infection. Primary prophylaxis with letermovir (an antiviral drug) is recommended to reduce the incidence of active infection, especially in high-risk patients. Secondary prophylaxis with valganciclovir (antiviral drug) is recommended after an episode of active infection, while preemptive and disease treatment is based on monitoring viral load and clinical response. The aim of this guideline is to improve the approach to CMV infection in HSCT patients, ensuring an effective and safe preventive and therapeutic approach.

Association of both depressive symptoms scores and specific depressive symptoms with all-cause and cardiovascular disease mortality

BackgroundThe presence of depression related to an increased risk of all-cause and cardiovascular disease (CVD) mortality has been reported. However, studies conducted on certain specific depressive symptoms are scarce. Our purpose was to assess the effect of both depressive symptoms scores and certain specific depressive symptoms on all-cause and CVD mortality.MethodsIn the present cohort study, all participants, aged 18 years or older, were enrolled in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2014. Depressive symptoms score was assessed using the validated 9-item Patient Health Questionnaire Depression Scale (PHQ-9), which ranges from 0 to 27, with a PHQ-9 score ≥ 10 diagnosed as depression. The outcome events were all-cause and CVD mortality, which were followed up from 2005 to 2014. The associations of both depressive symptoms score and certain specific depressive symptoms with all-cause and CVD mortality were examined by weighted multivariable proportional hazards models.ResultsA total of 26,028 participants aged ≥ 18 years were included in the statistical analysis, including 12,813 (49.2%) males and 13,215 (50.8%) females, with a mean (SD) age of 47.34 (18.86) years. During the 9.32 (3.20) years of mean (SD) follow-up, 3261 deaths were recorded, of which 826 were cardiovascular deaths. All-cause mortality was 16.87/1000 person-years in subjects with depression. In terms of CVD mortality, these figures were 4.53/1000 person-years. In the full model (model 3), elevated depressive symptoms scores were independently associated with an increased risk of all-cause mortality (Highest depression symptom score group: adjusted hazard ratio, 1.63; 95% CI 1.44–1.85) and CVD mortality (Highest depression symptom score group: adjusted hazard ratio, 1.73; 95% CI 1.34–2.24). All 9 specific depressive symptoms that make up the PHQ-9 were related to an increased risk of all-cause mortality. However, only 3 symptoms, including trouble sleeping or sleeping too much, poor appetite or overeating, and suicidal ideation, were no significantly associated with an increased risk of CVD mortality.ConclusionsThe elevated depressive symptoms scores were strongly associated with an increased risk of all-cause and CVD mortality in US adults. Furthermore, all 9 specific depressive symptoms were associated with high all-cause mortality. However, trouble sleeping or sleeping too much, poor appetite or overeating, and suicidal ideation might not increase the risk of CVD mortality.

A contemporary view on vascular resections and reconstruction during hepatectomies.

Oncological hepatic surgery carries the possibility to perform vascular reconstructions for advanced tumours with vessel invasion since surgery often represents the only potentially curative approach for these tumours. An extended review was conducted in an attempt to understand and clarify the latest trends in hepatectomies with vascular resections. We searched bibliographic databases including PubMed, Scopus, references from bibliographies and Cochrane Library. Information and outcomes from worldwide clinical trials were collected from qualified institutions performing hepatectomies with vascular resection and reconstruction. Careful patient selection and thorough preoperative imaging remain crucial for correct and safe surgical planning. A literature analysis shows that vascular resections carry different indications in different diseases. Despite significant advances made in imaging techniques and technical skills, reports of hepatectomies with vascular resections are still associated with high postoperative morbidity and mortality. The trend of complex liver resection with vascular resection is constantly on the increase, but more profound knowledge as well as further trials are required. Recent technological developments in multiple fields could surely provide novel approaches and enhance a new era of digital imaging and intelligent hepatic surgery.

Enzymatic testing for mucopolysaccharidosis type I in Kuwaiti newborns: a preliminary study toward newborn screening

Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder characterized by deficient or absent α-L-iduronidase (IDUA) enzyme activity due to pathogenic variants in the IDUA gene. Early treatment with hematopoietic stem cell transplantation and/or enzyme replacement therapy is associated with improved outcomes in this progressive multisystem disease. The diagnosis is usually delayed due to late presentation and non-specific symptoms, which result in high morbidity and mortality. The incidence of MPS I is unknown in Kuwait. This pilot study was undertaken to screen MPS I in all Kuwaiti neonates born at Farwaniya Hospital (FH), a major center in Kuwait, over 12 months. This study examined the incidence of MPS I for inclusion in the national newborn screening (NBS) to enable its early detection and adequate treatment. All Kuwaiti neonates born at FH between December 2021 and December 2022 were screened for MPS I. The screening consisted of determining IDUA enzyme activity in dried blood spot-derived samples using tandem mass spectrometry. A follow-up genetic analysis of the IDUA gene has been planned to screen the cases with diminished IDUA enzyme activity as second-tier testing. A total of 618 newborns, including 331 (54%) boys and 287 (46%) girls, were screened. Of them, 20 had deficient IDUA enzyme activity but showed negative genetic testing. However, we have diagnosed one additional female infant with MPS I who belonged to FH, but the parents chose to deliver in a private hospital. The molecular genetic study revealed the presence of a previously reported pathogenic nonsense variant in the IDUA c.1882C&amp;gt;T, which is associated with severe phenotype. That being included, MPS I is estimated to be approximately 0.2% of all screened cases in Kuwait. Our study is the first to evaluate the incidence of MPS I in Kuwait. Given the single center, small number of screened infants, and the short study duration thus far, it is premature to calculate the incidence. It is anticipated that as the study continues, we would be able to estimate the incidence in our population correctly. Screening newborns in all maternity hospitals in Kuwait is necessary to calculate the actual incidence of this severe disorder. Still, our preliminary data support the inclusion of MPS I in national NBS program to allow early initiation of treatment and thus improve disease outcome.

CD147 TagSNP is associated with the vulnerability to lung cancer in the Chinese population: a case–control study

BackgroundLung cancer, with its high morbidity and mortality, presents a major significant public health challenge. CD147, linked to cancer progression and metastasis, is a promising therapeutic target, including for lung cancer. The genetic variation may influence the expression of the gene and consequently the risk of lung cancer. This study aims to investigate single nucleotide polymorphisms (SNPs) in CD147 to understand their association with the risk of developing lung cancer in the Han Chinese population.MethodsA hospital-based case–control investigation was conducted, enrolling 700 lung cancer patients and 700 cancer-free controls. TagSNPs were selected using Haploview v4.2, and genotype data from the 1000 Genomes Project database were utilized. The selected SNPs (rs28992491, rs67945626, and rs79361899) within the CD147 gene were evaluated using the improved multiple ligation detection reaction method. Statistical analysis included chi-square tests, logistic regression models, and interaction analyses.ResultsBaseline characteristics of the study population showed no significant differences in gender distribution between cases and controls, but there was a notable difference in smoking rates. No significant associations were found between the three TagSNPs and lung cancer susceptibility in the codominant model. However, stratification analyses revealed interesting findings. Among females, the rs79361899 AA/AG genotype was associated with an increased risk of lung cancer. In individuals aged ≥ 65 years old, the rs28992491 GG and rs79361899 AA genotypes were linked to a higher susceptibility. Furthermore, an interaction analysis demonstrated significant genotype × gender interactions in the rs79361899 recessive model, indicating an increased lung cancer risk in female carriers of the heterozygous or homozygous polymorphic genotype.ConclusionsCD147 polymorphisms play an important role in lung cancer development, particularly in specific subgroup of age and gender. These findings highlight the significance of incorporating genetic variations and their interactions with demographic factors in comprehending the intricate etiology of lung cancer.

Exploring TRIM proteins’ role in antiviral defense against influenza A virus and respiratory coronaviruses

Numerous tripartite motif (TRIM) proteins, identified as E3 ubiquitin ligases, participate in various viral infections through ubiquitylation, ISGylation, and SUMOylation processes. Respiratory viruses, particularly influenza A virus (IAV) and respiratory coronaviruses (CoVs), have severely threatened public health with high morbidity and mortality, causing incalculable losses. Research on the regulation of TRIM proteins in respiratory virus infections is crucial for disease prevention and control. This review introduces TRIM proteins, summarizes recent discoveries regarding their roles and molecular mechanisms in IAV and CoVs infections, discusses current research gaps, and explores potential future trends in this rapidly developing field. It aims to enhance understanding of virus–host interactions and inform the development of new molecularly targeted therapies.

Very Low Calorie Ketogenic Diet: What Effects on Lipid Metabolism?

This review aims to critically examine how VLCKD affects plasma lipoprotein, lipid and cholesterol metabolism. Cardiovascular disease is a worldwide health problem affecting millions of people and leading to high rates of mortality and morbidity. There is a well-established association between cardiovascular disease and circulating cholesterol. Various dietary recommendations are currently available for the management of dyslipidemia. The very low-calorie ketogenic diet (VLCKD) is becoming increasingly popular as a treatment option for several pathological conditions, including dyslipidemia. In addition to being low in calories, the VLCKD's main feature is its unique calorie distribution, emphasizing a reduction in carbohydrate consumption in favor of fat as the primary calorie source. Lowering calorie intake through a VLCKD can reduce the endogenous production of cholesterol. However, if the foods consumed are from animal sources, dietary cholesterol intake may increase due to the higher fat content of animal products. When combined, these dietary practices may have opposing effects on plasma cholesterol levels. Studies investigating the impact of VLCKD on plasma cholesterol and low-density lipoprotein cholesterol levels report contradictory findings. While some studies found an increase in low-density lipoprotein cholesterol levels, others showed a decrease in total cholesterol and low-density lipoprotein cholesterol, along with an increase in high-density lipoprotein cholesterol.

Effect of recurrent severe insulin-induced hypoglycemia on the cognitive function and brain oxidative status in the rats

BackgroundEpisodes of recurrent or severe hypoglycemia can occur in patients with diabetes mellitus, insulinoma, neonatal hypoglycemia, and medication errors. However, little is known about the short-term and long-term effects of repeated episodes of acute severe hypoglycemia on the brain, particularly in relation to hippocampal damage and cognitive dysfunction.MethodsThirty-six wistar rats were randomly assigned to either the experimental or control group. The rats were exposed to severe hypoglycemia, and assessments were conducted to evaluate oxidative stress in brain tissue, cognitive function using the Morris water maze test, as well as histopathology and immunohistochemistry studies. The clinical and histopathological evaluations were conducted in the short-term and long-term.ResultsThe mortality rate attributed to hypoglycemia was 34%, occurring either during hypoglycemia or within 24 h after induction. Out of the 14 rats monitored for 7 to 90 days following severe/recurrent hypoglycemia, all exhibited clinical symptoms, which mostly resolved within three days after the last hypoglycemic episode, except for three rats. Despite the decrease in catalase activity in the brain, the total antioxidant capacity following severe insulin-induced hypoglycemia increased. The histopathology findings revealed that the severity of the hippocampal damage was higher compared to the brain cortex 90 days after hypoglycemia. Memory impairments with neuron loss particularly pronounced in the dentate gyrus region of the hippocampus were observed in the rats with severe hypoglycemia. Additionally, there was an increase in reactive astrocytes indicated by GFAP immunoreactivity in the brain cortex and hippocampus.ConclusionRecurrent episodes of severe hypoglycemia can lead to high mortality rates, memory impairments, and severe histopathological changes in the brain. While many histopathological and clinical changes improved after three months, it seems that the vulnerability of the hippocampus and the development of sustained changes in the hippocampus were greater and more severe compared to the brain cortex following severe and recurrent hypoglycemia. Furthermore, it does not appear that oxidative stress plays a central role in neuronal damage following severe insulin-induced hypoglycemia. Further research is necessary to assess the consequences of repeated hypoglycemic episodes on sustained damage across various brain regions.