Assessing Medical Students' Perspectives on Organ Donation: A Cross-Sectional Study.

Background Organ donation is a community service that not only saves lives but also improves the quality of life. The major concerns causing organ shortage in the country are the lack of awareness and correct knowledge among the public and myths and misconceptions clouding organ donation because of religious and cultural barriers. Material and methods A cross-sectional study was conducted among 300 medical students of a private medical college in the Telangana region, India, from July 2019 to October 2019 after approval from the Institutional Ethics Committee (IEC). A total of 300 participants (218 females (72.66%) and 82 males (27.33%)) were included in the study. Respondents completed a three-section questionnaire that included sociodemographic data, 15 questions on knowledge, and 12 questions on the attitude and ethical aspects of organ donation. Statistical tests utilized for investigation were the Student's t-test and one-way ANOVA to compare knowledge and attitude scores. Results The mean knowledge score among the participants was 10.85±1.79, with a P value of 0.45. The mean attitude score concerning organ donation among the participants was 45.5±4.47, with a P value of 0.44. The majority (87.1%) showed a positive attitude in this study. Conclusions The study emphasizes the necessity of interdisciplinary educational interventions for medical students to help them realize the complexities of the problem holistically. Their attitude regarding organ donation is not significantly affected by traditional educational interventions such as lectures and demonstrations. Educated healthcare professionals will play a critical role in motivating the public for the cause of organ donation promotion.

How Do Financial Obstacles Affect Decision-Making Among Potential Living Organ Donors?

Introduction: Living donation increases the organ supply, but associated non-medical expenses can disincentivize donation. Programs aimed at increasing living donation need to better understand how financial obstacles, including lost wages, impact the decision to pursue donation. Methods/Approach: Forty-eight interviews were conducted and analyzed using a grounded theory approach. Findings: Three key themes were identified that influenced decision-making: emotional attachment, temporal flexibility, and job security. These themes emerged when dividing interview participants into 3 groups: close relationship donors, broader network donors, and non-directed donors, representing donation to a family member or friend, a specific person they do not know well or at all, or a non-specified individual, respectively. Most close relationship donors wanted to donate regardless of personal financial cost, based on emotional attachment to the recipient. Wage reimbursement did not typically affect their decision-making but could reduce stress. Since non-directed donors did not donate to a specific individual, they could wait to achieve financial stability before donating, if needed. While wage reimbursement might create more proximate stability, non-directed donors had the flexibility to postpone donations until they could independently achieve financial stability. Lacking emotional attachment and temporal flexibility, broader network donors were particularly active decision-makers and most influenced by wage reimbursement. Across all groups, donors with job security were more resolute about donating. Conclusion: The findings underscore the importance of lost wage reimbursement to facilitate donation and reduce stress, and policies to protect donor job security.

Personalized treatment using predictive biomarkers in solid organ malignancies: A review.

In recent years, the influence of specific biomarkers in the diagnosis and prognosis of solid organ malignancies has been increasingly prominent. The relevance of the use of predictive biomarkers, which predict cancer response to specific forms of treatment provided, is playing a more significant role than ever before, as it affects diagnosis and initiation of treatment, monitoring for efficacy and side effects of treatment, and adjustment in treatment regimen in the long term. In the current review, we explored the use of predictive biomarkers in the treatment of solid organ malignancies, including common cancers such as colorectal cancer, breast cancer, lung cancer, prostate cancer, and cancers associated with high mortalities, such as pancreatic cancer, liver cancer, kidney cancer and cancers of the central nervous system. We additionally analyzed the goals and types of personalized treatment using predictive biomarkers, and the management of various types of solid organ malignancies using predictive biomarkers and their relative efficacies so far in the clinical settings.

Early U.S. Heart Transplant Experience With Normothermic Regional Perfusion Following Donation After Circulatory Death.

BACKGROUND: Heart transplantation following donation after circulatory death (DCD HT) has short-term survival outcomes comparable to donation after brain death and has led to a significant increase in transplantation volume. The U.S. experience with the normothermic regional perfusion (NRP) DCD HT procurement method has not been evaluated. OBJECTIVES: The aim of this study was to examine short-term outcomes associated with NRP vs direct procurement and perfusion (DPP) methods used during DCD HT in the United States. METHODS: The UNOS (United Network for Organ Sharing) registry was queried for all adult (age ≥18 years) heart recipients and corresponding donors of controlled DCD HT from January 2019-December 2023. Transplantations were stratified by NRP or DPP reperfusion methods. The primary outcome was overall survival. RESULTS: A total of 918 heart donors and recipients met inclusion criteria, including 622 (68%) DPP and 296 (32%) NRP transplantations. Unadjusted Kaplan-Meier survival analysis demonstrated improved short-term survival associated with NRP (log-rank P = 0.005). After adjustment, DCD HT with NRP was independently associated with improved survival (HR: 0.39 [95% CI: 0.22-0.70]; P = 0.002). A propensity-matched analysis similarly demonstrated a cumulative survival benefit to NRP (log-rank P = 0.006). CONCLUSIONS: In this largest national series of DCD HT procurement perfusion strategies, NRP is associated with improved short-term survival as compared with DPP. This study evaluates the U.S. early experience with DCD HT, and longer-term follow-up data are needed to further assess the impact of DPP and NRP methods on post-heart transplantation outcomes.

Nucleic acid-based nanotherapeutics for treating sepsis and associated organ injuries.

In recent years, gene therapy has been made possible with the success of nucleic acid drugs against sepsis and its related organ dysfunction. Therapeutics based on nucleic acids such as small interfering RNAs (siRNAs), microRNAs (miRNAs), messenger RNAs (mRNAs), and plasmid DNAs (pDNAs) guarantee to treat previously undruggable diseases. The advantage of nucleic acid-based therapy against sepsis lies in the development of nanocarriers, achieving targeted and controlled gene delivery for improved efficacy with minimal adverse effects. Entrapment into nanocarriers also ameliorates the poor cellular uptake of naked nucleic acids. In this study, we discuss the current state of the art in nanoparticles for nucleic acid delivery to treat hyperinflammation and apoptosis associated with sepsis. The optimized design of the nanoparticles through physicochemical property modification and ligand conjugation can target specific organs-such as lung, heart, kidney, and liver-to mitigate multiple sepsis-associated organ injuries. This review highlights the nanomaterials designed for fabricating the anti-sepsis nanosystems, their physicochemical characterization, the mechanisms of nucleic acid-based therapy in working against sepsis, and the potential for promoting the therapeutic efficiency of the nucleic acids. The current investigations associated with nanoparticulate nucleic acid application in sepsis management are summarized in this paper. Noteworthily, the potential application of nanotherapeutic nucleic acids allows for a novel strategy to treat sepsis. Further clinical studies are required to confirm the findings in cell- and animal-based experiments. The capability of large-scale production and reproducibility of nanoparticle products are also critical for commercialization. It is expected that numerous anti-sepsis possibilities will be investigated for nucleic acid-based nanotherapeutics in the future.

Evaluation of fecal microbiota of late gestation sows in relation to pelvic organ prolapse risk.

Introduction: Sow mortality in the U.S. swine industry has increased in recent years, for which pelvic organ prolapse (POP) is a major contributor, accounting for 21% of all sow mortality. Dysbiosis of microbial communities has been associated with disease and reproductive dysfunction in several species, and previous studies have shown changes in vaginal microbiota in sows with increased risk for POP during late gestation. However, there is insufficient knowledge surrounding the potential relationship between fecal microbiota and POP in sows. Therefore, the study objective was to identify differences in sow fecal microbiota and determine if fecal and vaginal microbial communities are correlated in relation to POP risk. Methods: Sows were evaluated for POP risk using an established perineal scoring system, with a perineal score (PS) of 1 (PS1) presuming little to no risk of POP to a PS of 3 (PS3) presuming high risk of POP. In the current study, 2,864 sows were scored during gestation week 15, and 1.0%, 2.7%, and 23.4% of PS1, PS2, and PS3 sows, respectively, subsequently experienced POP. Fecal swabs (n = 215) were collected between gestation days 108-115, DNA was extracted, and 16S rRNA gene amplicon sequencing libraries were analyzed using mothur, phyloseq and SAS in reference to PS and POP outcome. Additionally, co-occurrence networks were constructed using CoNet to compare fecal and vaginal microbiota from the same cohort of sows and identify correlations between different taxa. Results: Differences in fecal community composition (PERMANOVA; P < 0.05), structure (alpha diversity measurements; P < 0.05), and 13 individual operational taxonomic units (OTUs) were revealed between PS1 and PS3 assigned sows. No differences in fecal microbiota were detected as a result of POP outcome. However, the abundances of several taxa were correlated across sample collection sites, suggesting the fecal and vaginal microbial communities may be related to one another. Discussion: Collectively, fewer differences in the fecal microbiota exist in sows with differing risk for POP compared to the vaginal microbiota, suggesting the vaginal microbiome may be more relevant in relation to POP outcome, although correlations between fecal and vaginal communities may provide insight for strategies to combat POP.

Surgical outcomes of sacrospinous hysteropexy and hysteropreservation for pelvic organ prolapse: a systematic review of randomized controlled trials.

Objective: In several randomized controlled trials (RCTs), sacrospinous hysteropexy and other forms of hysteropreservation have been compared. Nevertheless, there is no definitively best treatment. This study summarized RCT evidence for various uterine preservation surgical procedures. Methods: From each database inception to August 2023, we searched PubMed, Embase, Cochrane Library, and Web of Science for eligible RCTs. A comparison was made between sacrospinous hysteropexy and other hysteropreservation, including vaginal and abdominal surgery. For categorical and continuous variables, relative risks (RRs) and mean differences (MDs) were calculated using random-effects models. Results: We reviewed a total 1,398 studies and ultimately included five RCTs that met all inclusion criteria. These five studies included a total of 1,372 uterine POP cases all of whom received transvaginal surgery and had a follow-up period for assessment of recurrence from 12 months to 5 years. There were no significant differences between sacrospinous hysteropexy and other hysteropreservation for the incidences of recurrence (RR,1.24; 95% CI, 0.58 to 2.63; p = 0.58) or hematoma (RR,0.70; 95% CI, 0.17 to 2.92; p = 0.62). Moreover, neither sacrospinous hysteropexy nor hysteropreservation had any significant effect on the risk of mesh exposure (RR,0.34; 95% CI, 0.03 to 4.31; p = 0.41), dyspareunia (RR,0.45; 95% CI, 0.13 to1.6; p = 0.22), urinary tract infection (RR,0.66; 95% CI, 0.38 to 1.15; p = 0.15), bothersome bulge symptoms (RR,0.03; 95% CI, -0.02 to 0.08; p = 0.24), operative time (MD, -4.53; 95% CI, -12.08 to 3.01; p = 0.24), and blood loss (MD, -25.69; 95% CI, -62.28 to 10.91; p = 0.17). However, sacrospinous hysteropexy was associated with a lower probability of pain (RR,4.8; 95% CI, 0.79 to 29.26; p = 0.09) compared with other hysteropreservation. Conclusion: There was no difference between sacrospinous hysteropexy and hysteropreservation in terms of recurrence, hematoma, mesh exposure, dyspareunia, urinary tract infection, bothersome bulge symptoms, operative time, pain, and blood loss. Systematic Review Registration: PROSPERO [CRD42023470025].

In Defense of Normothermic Regional Perfusion.

Normothermic regional perfusion (NRP) is a relatively new approach to procuring organs for transplantation. After circulatory death is declared, perfusion is restored to either the thoracoabdominal organs (in TA-NRP) or abdominal organs alone (in A-NRP) using extracorporeal membrane oxygenation. Simultaneously, surgeons clamp the cerebral arteries, causing a fatal brain injury. Critics claim that clamping the arteries is the proximate cause of death in violation of the dead donor rule and that the procedure is therefore unethical. We disagree. This account does not consider the myriad other factors that contribute to the death of the donor, including the presence of a fatal medical condition, the decision to withdraw life support, and the physician's actions in withdrawing life support and administering medication that may hasten death. Instead, we claim that physicians play a causative role in many of the events that lead to a patient's death and that these actions are often ethically and legally justified. We advance an "all things considered" view according to which TA-NRP may be considered ethically acceptable insofar as it avoids suffering and respects the wishes of the patient to improve the lives of others through organ donation. We conclude with a series of critical questions related to the practice of NRP and call for the development of national consensus on this issue in the United States.

Supply organ development of young broilers in response to increased carbohydrates and amino acids in the starter period.

The growth of broiler chickens is marked by high fluctuations, varying nutrient requirement, early growth is characterized by high allometric growth rates of supply organs, which if underdeveloped, can impede nutrient efficiency and growth of demand organs like muscle and skeleton. This study aimed to investigate the impact of carbohydrate- and amino-acid-rich diets on the development of supply organs in broiler chickens. Four dietary treatments were used in a 2 × 2 factorial arrangement of treatments with apparent metabolizable energy (AME) at 2 levels (low: 2,750 kcal/kg and high: 3,050 kcal/kg) and standardized ileal digestible (SID) lysine at 2 levels (low: 1.0% and high: 1.2%) in the starter diets. Feed intake (FI) and BW gain were measured weekly; dissections were conducted at d 4 and d 11 to determine supply organ weights. Allometric growth of the liver was higher (P < 0.001) in the high AME and low lysine group compared to the other groups. For the pancreas, the highest (P < 0.001) allometric growth rate was in the high lysine groups. The small intestines responded differently; the duodenum had the highest (P < 0.001) allometric growth rate in the high AME groups and the jejunum in the low lysine groups, whereas the ileum showed an effect of diet density. For performance, high AME from carbohydrates, via maize starch, had a negative effect (P < 0.001) on FI and BW gain. High lysine had a positive effect (P < 0.001) on BW gain and FI, and high lysine alleviated part of the detrimental effect of high AME from carbohydrates. This effect was visible from d 0 to d 11, and persisted till the end of the trial on d 35. In conclusion, feeding a diet with a high AME from carbohydrates has negative consequences for the development of the supply organs of broilers.

Do microplastics accumulate in penguin internal organs? Evidence from Svinnar island, Antarctica.

The prevalence of microplastics (MPs, <5 mm) in natural environments presents a formidable global environmental threat MPs can be found from the Arctic to Antarctica, including glaciers. Despite their widespread distribution, studies on MP accumulation in apex predators inhabiting Polar Regions remain limited. The objective of this study was to conduct a comprehensive examination, for the first time, of MP bioaccumulation in various organs and tissue of Adélie penguins. This investigation comprehends the gastrointestinal tract (GIT), scat, internal organ (lung, trachea, spleen, and liver) and tissue (muscle) samples collected from Svinner Island, Antarctica during the 39th Indian expedition to Antarctica in 2019-2020. Our analyses revealed the presence of 34 MPs across the GIT, scat, lung, and trachea samples, with no MPs detected in muscle, spleen, or liver tissues. Blue-colored microfibers (>50 %) and MPs smaller than 1 mm (38 %) in size were prominently observed. Polymer characterization utilizing µ-FTIR spectroscopy identified low-density polyethylene (LDPE) (~63 %) as the predominant polymer type. The accumulation of MP fibers in the gastrointestinal tract and scat of Adélie penguins may originate from marine ambient media and prey organisms. Furthermore, the presence of LDPE fibers in the trachea and lungs likely occurred through inhalation and subsequent deposition of MPs originating from both local and long-range airborne sources. The identification of fibers ranging between 20 and 100 µm within the trachea suggests a plausible chance of cellular deposition of MPs. Overall our findings provide valuable insights into the organ-specific accumulation of MPs in apex predators. Adélie penguins emerge as promising environmental bio-monitoring species, offering insights into the potential trophic transfer of MPs within frigid environments.

Triglyceride-glucose index improves risk prediction beyond traditional risk factors and hypertension mediated organ damage in healthy adults.

BACKGROUND AND AIMS: Triglyceride-glucose (TyG) index, a surrogate measure of insulin resistance, is associated with hypertension mediated organ damage (HMOD) and cardiovascular disease. This study investigated the association between TyG index and major adverse cardiovascular events (MACE) and its interaction with traditional risk factors and HMOD. METHODS AND RESULTS: Healthy subjects recruited from the general population were thoroughly examined and followed for MACE using nation-wide registries. Cox proportional hazard models were used to calculate the association between TyG index and MACE occurrence. Models were adjusted for Systematic Coronary Risk Evaluation (SCORE) risk factors, pulse wave velocity, left ventricular mass index, carotid atherosclerotic plaque status, and microalbuminuria. Continuous net reclassification and Harrell's Concordance index (C-index) were used to assess the added prognostic value of TyG index. During a follow-up period of mean 15.4 ± 4.7 years, MACE were observed in 332 (17%) of 1970 included participants. TyG index was associated with MACE; HR = 1.44 [95%CI:1.30-1.59] per standard deviation. After adjustment for traditional cardiovascular (CV) risk factors, HR was 1.16 [95%CI:1.03-1.31]. The association between TyG index and MACE remained significant after further adjustment for each HMOD component. However, this finding was evident only in subjects aged 41 or 51 years (HR = 1.39; 95%CI:1.15-1.69). Including TyG index in a risk model based on traditional CV risk factors improved C-index with 0.005 (P = 0.042). CONCLUSION: In this population-based study of healthy middle-aged subjects, TyG index was associated with MACE independently of traditional CV risk factors and HMOD. TyG index may have a potential role in future risk prediction systems.

Clinical Features of Cytokine Storm Syndrome.

Cytokine storm syndrome (CSS) is a severe life-threatening condition characterized by a clinical phenotype of overwhelming systemic inflammation, hyperferritinemia, hemodynamic instability, and multiple organ failure (MOF), and, if untreated, it can potentially lead to death. The hallmark of CSS is an uncontrolled and dysfunctional immune response involving the continual activation and expansion of lymphocytes and macrophages, which secrete large amounts of cytokines, causing a cytokine storm. Many clinical features of CSS can be explained by the effects of pro-inflammatory cytokines, such as interferon (IFN)-γ, tumor necrosis factor (TNF), interleukin (IL)-1, IL-6, and IL-18 [1-7]. These cytokines are elevated in most patients with CSS as well as in animal models of CSS [8, 9]. A constellation of symptoms, signs, and laboratory abnormalities occurs that depends on the severity of the syndrome, the underlying predisposing conditions, and the triggering agent.

Autoinflammatory Contributors to Cytokine Storm.

Cytokine Storm is a complex and heterogeneous state of life-threatening systemic inflammation and immunopathology. Autoinflammation is a mechanistic category of immune dysregulation wherein immunopathology originates due to poor regulation of innate immunity. The growing family of monogenic Systemic Autoinflammatory Diseases (SAIDs) has been a wellspring for pathogenic insights and proof-of-principle targeted therapeutic interventions. There is surprisingly little overlap between SAID and Cytokine Storm Syndromes, and there is a great deal to be inferred from those SAID that do, and do not, consistently lead to Cytokine Storm. This chapter will summarize how illustrations of the autoinflammatory paradigm have advanced the understanding of human inflammation, including the role of autoinflammation in familial HLH. Next, it will draw from monogenic SAID, both those with strong associations with cytokine storm and those without, to illustrate how the cytokine IL-18 links innate immune dysregulation and cytokine storm.

Cytokine Storm and Sepsis-Induced Multiple Organ Dysfunction Syndrome.

There is extensive overlap of clinical features among familial or primary HLH (pHLH), reactive or secondary hemophagocytic lymphohistiocytosis (sHLH) [including macrophage activation syndrome (MAS) related to rheumatic diseases], and hyperferritinemic sepsis-induced multiple organ dysfunction syndrome (MODS); however, the distinctive pathobiology that causes hyperinflammatory process in each condition requires careful considerations for therapeutic decision-making. pHLH is defined by five or more of eight HLH-2004 criteria [1], where genetic impairment of natural killer (NK) cells or CD8+ cytolytic T cells results in interferon gamma (IFN-γ)-induced hyperinflammation regardless of triggering factors. Cytolytic treatments (e.g., etoposide) or anti-IFN-γ monoclonal antibody (emapalumab) has been effectively used to bridge the affected patients to hematopoietic stem cell transplant. Secondary forms of HLH also have normal NK cell number with decreased cytolytic function of varying degrees depending on the underlying and triggering factors. Although etoposide was uniformly used in sHLH/MAS in the past, the treatment strategy in different types of sHLH/MAS is increasingly streamlined to reflect the triggering/predisposing conditions, severity/progression, and comorbidities. Accordingly, in hyperferritinemic sepsis, the combination of hepatobiliary dysfunction (HBD) and disseminated intravascular coagulation (DIC) reflects reticuloendothelial system dysfunction and defines sepsis-associated MAS. It is demonstrated that as the innate immune response to infectious organism prolongs, it results in reduction in T cells and NK cells with subsequent lymphopenia even though normal cytolytic activity continues (Figs. 30.1, 30.2, 30.3, and 30.4). These changes allow free hemoglobin and pathogens to stimulate inflammasome activation in the absence of interferon-γ (IFN-γ) production that often responds to source control, intravenous immunoglobulin (IVIg), plasma exchange, and interleukin 1 receptor antagonist (IL-1Ra), similar to non-EBV, infection-induced HLH.

Etoposide Therapy of Cytokine Storm Syndromes.

Etoposide has revolutionized the treatment of primary as well as secondary hemophagocytic lymphohistiocytosis (HLH), and it is, together with corticosteroids, the most widely used therapy for HLH. In the early 1980s, long-term survival in primary HLH was <5% but with the etoposide-/dexamethasone-based protocols HLH-94 and HLH-2004, in combination with stem cell transplantation, 5-year survival increased dramatically to around 60% in primary HLH, and based on analyses from the HLH-2004 study, there is likely room for further improvement. Biologically, etoposide administration results in potent selective deletion of activated T cells as well as efficient suppression of inflammatory cytokine production. Moreover, etoposide has also been reported to promote programmed cell death (apoptosis) rather than proinflammatory lytic cell death (pyroptosis), conceivably ameliorating subsequent systemic inflammation, i.e., a treatment very suitable for cytokine storm syndromes (CSS). The combination of etoposide and corticosteroids may also be beneficial in cases of severe or refractory secondary HLH (sHLH) with imminent organ failure, such as infection-associated HLH caused by Epstein-Barr virus (EBV) or malignancy-triggered HLH. In CSS associated with rheumatic diseases (macrophage activation syndrome, MAS or MAS-HLH), etoposide is currently used as second- or third-line therapy. Recent studies suggest that etoposide perhaps should be part of an aggressive therapeutic intervention for patients with severe refractory or relapsing MAS, in particular if there is CNS involvement. Importantly, awareness of sHLH must be further increased since treatment of sHLH is often delayed, thereby missing the window of opportunity for a timely, effective, and potentially life-saving HLH-directed treatment.

Assessing the Brain Death/Death by Neurologic Criteria Determination Process in Korea: Insights from 10-Year Noncompleted Donation Data.

BACKGROUND: This study aimed to analyze the current status of brain death/death by neurologic criteria (BD/DNC) determination in Korea over a decade, identifying key areas for improvement in the process. METHODS: We conducted a retrospective analysis of data from the Korea Organ Donation Agency spanning 2011 to 2021, focusing on donors whose donations were not completed. The study reviewed demographics, medical settings, diagnoses, and outcomes, with particular emphasis on cases classified as nonbrain death and those resulting in death by cardiac arrest during the BD/DNC assessment. RESULTS: Of the 5047 patients evaluated for potential brain death from 2011 to 2021, 361 were identified as noncompleted donors. The primary reasons for noncompletion included nonbrain death (n = 68, 18.8%), cardiac arrests during the BD/DNC assessment process (n = 80, 22.2%), organ ineligibility (n = 151, 41.8%), and logistical and legal challenges (n = 62, 17.2%). Notably, 25 (36.8%) of them failed to meet the minimum clinical criteria, and 7 of them were potential cases of disagreement between the two clinical examinations. Additionally, most cardiac arrests (n = 44, 55.0%) occurred between the first and second examinations, indicating management challenges in critically ill patients during the assessment period. CONCLUSIONS: Our study highlights significant challenges in the BD/DNC determination process, including the need for improved consistency in neurologic examinations and the management of critically ill patients. The study underscores the importance of refining protocols and training to enhance the accuracy and reliability of brain death assessments, while also ensuring streamlined and effective organ donation practices.

Flusilazole induced developmental toxicity, neurotoxicity, and cardiovascular toxicity via apoptosis and oxidative stress in zebrafish.

Flusilazole is a well-known triazole fungicide applied to various crops and fruits worldwide. Flusilazole residues are frequently detected in the environment, and many researchers have reported the hazardous effects of flusilazole on non-target organisms; however, the developmental toxicity of flusilazole has not been fully elucidated. In this study, we investigated flusilazole-induced developmental defects in zebrafish, which are used in toxicology studies to assess the toxic effects of chemicals on aquatic species or vertebrates. We confirmed that flusilazole exposure affected the viability and hatching rate of zebrafish larvae, and resulted in morphological defects, reduced body length, diminished eye and head sizes, and inflated pericardial edema. Apoptosis, oxidative stress, and inflammation were also observed. These factors interrupted the normal organ formation during early developmental stages, and transgenic models were used to identify organ defects. We confirmed the effects of flusilazole on the nervous system using olig2:dsRed transgenic zebrafish, and on the cardiovascular system using cmlc2:dsRed and fli1:eGFP transgenic zebrafish. Our results demonstrate the developmental toxicity of flusilazole and its mechanisms in zebrafish as well as the detrimental effects of flusilazole.

A Modified McCall Culdoplasty in Pelvic Organ Prolapse Surgery: Anatomical and Functional Outcomes.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to evaluate anatomical and functional outcomes of a modified McCall culdoplasty compared with the traditional technique for pelvic organ prolapse. METHODS: This prospective clinical observational study was conducted in a secondary referral urogynecological center between October 2021 and October 2022. A modified McCall culdoplasty was performed in 85 patients (group A). It was characterized by dissection of uterosacral ligaments up to the ischial spines, their shortening and attachment to the vaginal apex and both the rectovaginal and the vesicovaginal fascia. Outcomes were compared with those of a group of 86 patients (group B) who underwent the traditional culdoplasty between September 2020 and September 2021. Primary outcome was prolapse recurrence. Secondary endpoints included subjective outcomes, vaginal length, quality of life, and urinary and anal incontinence. Statistical analysis was conducted using Fisher's exact, Mann-Whitney U, and Student's t tests. RESULTS: At 12 months, prolapse recurrence occurred in 2.5% (CI 0.7-8.8%) of patients in group A and in 6.7% (CI 2.9-14.7%) in group B. Postoperative vaginal length was 8.3 ± 0.78 cm in group A and 6.4 ± 1.1 cm in group B (p < 0.001). The Patient Global Impression of Improvement questionnaire revealed that 76 patients (96.2%) in group A versus 64 (85%) in group B were very satisfied (p < 0.03). Both groups showed an improvement in urinary symptoms and quality of life. CONCLUSIONS: The modified McCall culdoplasty showed successful anatomical and functional outcomes, with a tendency towards lower recurrence rates than the traditional McCall procedure. Further long-term studies are needed to confirm our data.

Characteristics of the Cerebrospinal Fluid in Septic Patients with Critical Illness Polyneuropathy - A Retrospective Cohort Study.

Background: Critical illness polyneuropathy (CIP) is a complex disease commonly occurring in septic patients which indicates a worse prognosis. Herein, we investigated the characteristics of cerebrospinal fluid (CSF) in septic patients with CIP. Methods: This retrospective study was conducted between Match 1, 2018, and July 1, 2022. Patients with sepsis who underwent a CSF examination and nerve electrophysiology were included. The levels of protein, glucose, lipopolysaccharide, white blood cell (WBC), interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF) α in CSF were measured. The fungi and bacteria in CSF were also assessed. Results: Among the 175 septic patients, 116 (66.3%) patients were diagnosed with CIP. 28-day Mortality in CIP patients was higher than that in non-CIP patients (25.0% vs. 10.2%, P = 0.02) which was confirmed by survival analysis. The results of propensity score matching analysis (PSMA) indicated a significant difference in the level of protein, WBC, IL-1, IL-6, IL-8, and TNFα present in the CSF between CIP patients and non-CIP patients. The results of the receiver operating characteristic (ROC) analysis showed that IL-1, WBC, TNFα, and their combined indicator had a good diagnostic value with an AUC > 0.8. Conclusion: The increase in the levels of WBC, IL-1, and TNFα in CSF might be an indicator of CIP in septic patients.