Classification of laryngeal diseases including laryngeal cancer, benign mucosal disease, and vocal cord paralysis by artificial intelligence using voice analysis.

Voice change is often the first sign of laryngeal cancer, leading to diagnosis through hospital laryngoscopy. Screening for laryngeal cancer solely based on voice could enhance early detection. However, identifying voice indicators specific to laryngeal cancer is challenging, especially when differentiating it from other laryngeal ailments. This study presents an artificial intelligence model designed to distinguish between healthy voices, laryngeal cancer voices, and those of the other laryngeal conditions. We gathered voice samples of individuals with laryngeal cancer, vocal cord paralysis, benign mucosal diseases, and healthy participants. Comprehensive testing was conducted to determine the best mel-frequency cepstral coefficient conversion and machine learning techniques, with results analyzed in-depth. In our tests, laryngeal diseases distinguishing from healthy voices achieved an accuracy of 0.85-0.97. However, when multiclass classification, accuracy ranged from 0.75 to 0.83. These findings highlight the challenges of artificial intelligence-driven voice-based diagnosis due to overlaps with benign conditions but also underscore its potential.

Immunological link between periodontitis and type 2 diabetes deciphered by single-cell RNA analysis.

BACKGROUND: Type 2 diabetes mellitus (DM) is a complex metabolic disorder that causes various complications, including periodontitis (PD). Although a bidirectional relationship has been reported between DM and PD, their immunological relationship remains poorly understood. Therefore, this study aimed to compare the immune response in patients with PD alone and in those with both PD and DM (PDDM) to expand our knowledge of the complicated connection between PD and DM. METHODS: Peripheral blood mononuclear cells were collected from 11 healthy controls, 10 patients with PD without DM, and six patients with PDDM, followed by analysis using single-cell RNA sequencing. The differences among groups were then compared based on intracellular and intercellular perspectives. RESULTS: Compared to the healthy state, classical monocytes exhibited the highest degree of transcriptional change, with elevated levels of pro-inflammatory cytokines in both PD and PDDM. DM diminished the effector function of CD8+ T and natural killer (NK) cells as well as completely modified the differentiation direction of these cells. Interestingly, a prominent pathway, RESISTIN, which is known to increase insulin resistance and susceptibility to diabetes, was found to be activated under both PD and PDDM conditions. In particular, CAP1+ classical monocytes from patients with PD and PDDM showed elevated nuclear factor kappa B-inducing kinase activity. CONCLUSIONS: Overall, this study elucidates how the presence of DM contributes to the deterioration of T/NK cell immunity and the immunological basis connecting PD to DM.

Differential microbiota network in gingival tissues between periodontitis and periodontitis with diabetes.

Periodontitis and diabetes mellitus (DM) have a bidirectional relationship. Periodontitis is initiated by dysbiosis of oral microorganisms, and in particular, the characteristics of the microorganisms that have penetrated the tissue are directly related to the disease; therefore, we investigated the effect of DM on intragingival microbial profiling of patients with periodontitis. A total of 39 subjects were recruited and divided into three groups in this case control study as follows: healthy (NA, 10), periodontitis only (PD, 18), and periodontitis with DM (PD_DM, 11). Gingival tissue was collected, DNA was extracted, and whole-genome sequencing was performed. PD and PD_DM showed different characteristics from NA in diversity and composition of the microbial community; however, no difference was found between the PD nad PD_DM. PD_DM showed discriminatory characteristics for PD in the network analysis. PD showed a network structure in which six species were connected, including three red complex species, and PD_DM's network was more closely connected and expanded, with six additional species added to the PD network. Although DM did not significantly affect α- and ß-diversity or abundance of phyla and genera of microbiota that invaded the gingival tissue of patients with periodontitis, DM will affect the progression of periodontitis by strengthening the bacterial network in the gingival tissue.

Is it worth applying self-irrigation after third molar extraction? A randomised controlled trial.

In this study, we aimed to examine the effectiveness of self-irrigation following the extraction of mandibular third molars. A randomised controlled clinical trial was conducted with 155 patients who had undergone extraction of a mandibular third molar. The irrigation group was instructed to self-irrigate the extraction socket with tap water using a syringe three times a day, starting seven days after the tooth extraction. The incidence of complications and mouth opening, halitosis, plaque/gingival index, and oral health-related quality of life (OHRQoL) were measured. The irrigation group showed a lower incidence of complications than the non-irrigation group. The halitosis, plaque, and gingival scores were lower by mean (SD) 19.66 (5.19), 0.58 (0.06), and 0.62 (0.08), respectively, in the irrigation group than in the non-irrigation group (p = 0.0001). A greater amount of food packing was associated with higher halitosis, plaque, and gingival scores and poorer OHRQoL (p < 0.05). Further, more frequent irrigation was associated with lower halitosis, plaque, and gingival scores and better OHRQoL (p ≤ 0.016). Self-irrigation of the extraction socket using a syringe containing tap water is a very effective method for keeping the extraction socket clean. This technique reduced halitosis, improved plaque and gingival indices, and increased OHRQoL.

Optimal application of compressive palatal stents following mesiodens removal in pediatric patients: A Randomized Controlled Trial / Aplicación óptima de stents palatinos de compresión después de la extracción del mesiodens en pacientes pediátricos: un ensayo controlado aleatorio

Background: There is no scientific evidence supporting the choice of a palatal stent in patients who underwentremoval of an impacted supernumerary tooth. We aimed to investigate the effects of palatal stents in patients whounderwent supernumerary tooth removal through a palatal approach and to suggest the optimal stent thicknessand material.Material and Methods: We recruited 144 patients who underwent extraction of a supernumerary tooth between themaxillary anterior teeth. Subjects were assigned to a control group (CG) or one of four compressive palatal stentgroups (CPSGs) classified by the thickness and material of the thermoplastic acrylic stent used. Palatal gingivalswelling and objective indices (healing, oral hygiene, gingival, and plaque) were evaluated before surgery and onpostoperative days (PODs) 3, 7, and 14; pain/discomfort and the Child Oral Health Impact Profile (COHIP) wereassessed as subjective indices of the effects of the stent.Results: The CPSGs showed faster healing than did the CG on PODs 7 (P<0.001) and 14 (P=0.043); swelling wasmeasured by 1.64±0.88 mm and 4.52±0.39 mm, respectively. Although swelling was least in the 4-mm hard group(0.92±0.33 mm), the difference compared with that in the 2-mm hard group (1.01±0.18 mm) was not significant(P=0.077). The CPSGs showed better COHIP (P<0.001-0.036) and pain scores (P<0.001) than did the CG onPODs 1-3. Conclusions: Compressive palatal stents reduce discomfort by decreasing pain and alleviating swelling. Althougha stent is effective regardless of its thickness and material, 2-mm hard stents maximized such positive effects withminimal discomfort.(AU)

Hospital length of stay, do not resuscitate orders, and survival for post-cardiac arrest patients in Michigan: A study for the CARES Surveillance Group.

OBJECTIVE: Current guidelines recommend deferring prognostic decisions for at least 72 h following admission after Out of Hospital cardiac arrest (OHCA). Most non-survivors experience withdrawal of life sustaining therapy (WLST), and early WLST may adversely impact survival. We sought to characterize the hospital length of stay (LOS) and timing of Do Not Resuscitate (DNR) orders (as surrogates for WLST), to assess their relationship to survival following cardiac arrest. DESIGN: We performed a retrospective cohort study of probabilistically linked cardiac arrest registries (Cardiac Arrest Registry to Enhance Survival (CARES) and Michigan Inpatient Database (MIDB) from 2014 to 2017. PATIENTS: Adult (≥18 years) patients admitted following OHCA were included. We considered LOS ≤ 3 days (short LOS) and written DNR order with LOS ≤ 3 days (Early DNR) as indicators of early WLST. Our primary outcome was survival to hospital discharge. We utilized multilevel logistic regression clustered by hospital to examine associations of these variables, patient characteristics and survival to hospital discharge. MEASUREMENT AND MAIN RESULTS: We included 3644 patients from 38 hospitals with >30 patients. Patients mean age was 62.4 years and were predominately male (59.3%). LOS ≤ 3 days (ORadj = 0.11) and early DNR (ORadj = 0.02) were inversely associated with survival to discharge. There was a non-significant inverse association between hospital rates of LOS ≤ 3 days and survival (p = 0.11), and Early DNR and survival (p = 0.83). In the multilevel model, using median odd ratios to assess variation in LOS ≤ 3 days and survival, patient characteristics contributed more to variability in surviival than between-hospital variation. However, between-hospital variation contributed more to variability than patient characteristics in the provision of early DNR orders. CONCLUSIONS: We observed that LOS ≤ 3 days for post-arrest patients was negatively-associated with survival, with both patient characteristics and between-hospital variation associated with outcomes. However, between-hospital variation appears to be more highly-associated with provision of early DNR orders than patient characteristics. Further work is needed to assess variation in early DNR orders and their impact on patient survival.

Comparison of time and cost between conventional surgical planning and virtual surgical planning in orthognathic surgery in Korea.

BACKGROUND: The purpose of this study was to measure the time of the conventional surgical planning (CSP) and virtual surgical planning (VSP) in orthognathic surgery and to compare them in terms of cost. MATERIAL AND METHOD: This is a retrospective study of the patients who underwent orthognathic surgery at the OOOOO University Dental Hospital from December 2017 to August 2018. All the patients were analyzed through both CSP and VSP, and all the surgical stents were fabricated through manual and 3-dimensional (3D) printing. The predictor variables were the planning method (CSP vs. VSP) and the surgery type (group I: Le Fort I osteotomy+bilateral sagittal split osteotomy [LFI+BSSO] or group II: only bilateral sagittal split osteotomy [BSSO]), and the outcomes were the time and cost. The results were analyzed using paired t test. RESULTS: Thirty patients (12 females, 18 males) met the inclusion criteria, and 17 patients were excluded from the study due to missing or incomplete data. There were 20 group I patients (LFI+BSSO regardless of genioplasty) and 10 group II patients (BSSO regardless of genioplasty). The average time of CSP for group I was 385±7.8 min, and that for group II was 195±8.33 min. The time reduction rate of VSP compared with CSP was 62.8% in group I and 41.5% in group II. On the other hand, there was no statistically significant cost reduction. CONCLUSIONS: The time investment in VSP in this study was significantly smaller than that in CSP, and the difference was greater in group I than in group II.

Primary repair of untreated cleft palate in an elderly patient: a case report.

Untreated adult or elderly cleft lip and palate patients are rarely seen, but studies on delayed primary palatal closure have been performed in the less developed Asian and African countries, where access to medical care is difficult. A 64-year-old woman visited our clinic with untreated cleft palate with a 40×20-mm-wide defect in the medial palate. Two-flap palatoplasty under general anesthesia was performed to close the cleft palate. After 1 month, the result was favorable without any complications including oronasal fistula. Cleft palate primary repair in an elderly patient is rare and has some surgical problems that are associated with a wide range of defects, but good results can be obtained if surgery is performed well with appropriate considerations.

Comparative study of bone regeneration using fibrin sealant with xenograft in rabbit sinus: pilot study.

BACKGROUND: Stability of the grafted bone volume is one of the important factors to the success of alveolar bone grafts. For this, platelet-rich plasma (PRP) or fibrin sealant is mixed with the bone graft material. Bio-Oss® is a protein-free bovine mineral commonly used in bone graft procedures. The grafting particles are commonly combined with a standard fibrin sealant (Tisseel®) to fabricate a plastic implantable product. The purpose of this experiment was to evaluate the efficacy of fibrin sealant (Tisseel®) in bone regeneration performance in a rabbit maxillary sinus model. METHODS: A total of five 3.5 kg weight New Zealand white rabbits were used for the study. After elevating the sinus membrane in both maxillary sinus cavities, Bio-Oss® mixed with normal saline (group 1) was filled into the right side, and Tisseel® mixed Bio-Oss® (group 2) was inserted into the other side. The bone mineral density and bone volume were analyzed with microscopic computed tomography (micro-CT) and histomorphometric 12 weeks after application. RESULTS: Histologically, new bone formation rate was 14.8%, and grafted bone rate was 70.5% in group 1. In group 2, they were 18.5% and 60.4%, respectively. According to micro-CT analysis, bone mineral density (mg/cm3, BMD) was 2.5% larger in group 1. CONCLUSIONS: The findings from this study suggest that, although the difference in the bone formation between group 1 and group 2 appears to be insignificant, group 2 had an advantage in using smaller amount of bone substances to achieve the reliable bone formation.

A retrospective analysis of risk factors of oromaxillofacial infection in patients presenting to a hospital emergency ward.

BACKGROUND: The purpose of this study was to review the clinical features of oromaxillofacial infections in patients presenting to a hospital emergency ward, to identify the key factors affecting the requirement for hospitalization, and the potential risk factors predisposing to a prolonged length of hospital stay. METHODS: A retrospective medical record review of the 598 patients treated for oromaxillofacial infection from 2013 to 2017 at the oral and maxillofacial surgery department, Yangsan Pusan National University Hospital, was conducted. The following information was collected from each patient: sex, age, past medical history, site of infection, etiology, admission or outpatient care, level of C-reactive protein (mg/dL), fascial spaces involved, treatment method, and duration of hospitalization. Chi-squared tests were used to identify risk factors, which were further analyzed using multivariable logistic regression. RESULTS: A total of 606 patients were eligible for inclusion in the study, of which eight were excluded due to having incomplete charts; thus, 598 patients were included: 55% were male, mean patient age was 47.1 ± 19.9 years, and 12.9% of patients were diabetic. Furthermore, 71.2% of patients had infection originating in the mandible; the most common tooth of origin was lower posterior, and 29.8% of patients were hospitalized. Risk factors for hospital admission were elderly patients with concurrent disease, elevated C-reactive protein level, and multiple-space infection in the oromaxillofacial area. The duration of hospitalization was correlated with both diabetes and age. CONCLUSIONS: The requirement for hospital admission is determined by the severity of the infection; even severe infections, once treated with appropriate surgery, have no relation to the length of hospital stay. The important risk factors for increased duration of hospitalization are diabetes mellitus and older age. The understanding of risk factors associated with a prolonged hospital stay during the treatment of oromaxillofacial infection will aid in treatment planning as well as highlight the importance of adequate diabetes control in patients at risk of such infection.

Comparison of time and cost between conventional surgical planning and virtual surgical planning in orthognathic surgery in Korea.

BACKGROUND: The purpose of this study was to measure the time of the conventional surgical planning (CSP) and virtual surgical planning (VSP) in orthognathic surgery and to compare them in terms of cost. MATERIAL AND METHOD: This is a retrospective study of the patients who underwent orthognathic surgery at the Pusan National University Dental Hospital from December 2017 to August 2018. All the patients were analyzed through both CSP and VSP, and all the surgical stents were fabricated through manual and three-dimensional (3D) printing. The predictor variables were the planning method (CSP vs. VSP) and the surgery type (group I: Le Fort I osteotomy + bilateral sagittal split osteotomy [LFI+BSSO] or group II: only bilateral sagittal split osteotomy [BSSO]), and the outcomes were the time and cost. The results were analyzed using the paired t test. RESULTS: Thirty patients (12 females, 18 males) met the inclusion criteria, and 17 patients were excluded from the study due to missing or incomplete data. There were 20 group I patients (LFI+BSSO regardless of genioplasty) and 10 group II patients (BSSO regardless of genioplasty). The average time of CSP for group I was 385 ± 7.8 min, and that for group II was 195 ± 8.33 min. The time reduction rate of VSP compared with CSP was 62.8% in group I and 41.5% in group II. On the other hand, there was no statistically significant cost reduction. CONCLUSIONS: The time investment in VSP in this study was significantly smaller than that in CSP, and the difference was greater in group I than in group II.

Complications Following Orthognathic Surgery for Patients With Cleft Lip/Palate.

INTRODUCTION: Cleft lip/palate is a facial anomaly caused by an abnormal developmental process. It is also the most common congenital anomaly. Orthognathic surgery is required in 25% of patients with cleft lip and palate for the correction of dentofacial deformity. There are various complications that can occur after orthognathic surgery. Complications that can occur during surgery include bleeding, improper fracture, and injuries to the inferior alveolar nerve (IAN) and lingual nerve. Meanwhile, postoperative complications include hemorrhage, edema, pain, infection, and delayed union or nonunion. This study retrospectively examines the complications that occurred after the orthognathic surgery in cleft lip/palate patients at Pusan National University Dental Hospital. PATIENTS AND METHODS: From June 1, 2008 to July 31, 2017, we selected 17 patients who underwent orthognathic surgery for cleft lip/palate at the Department of Oral and Maxillofacial Surgery, Pusan National University Dental Hospital. The patients were treated at different hospitals for all operations related to cleft lip/palate. RESULT: Intraoperative complications include hemorrhage, inadequate fracture, injury to the IAN and lingual nerve, root damage, and fistula. The patients who were evaluated included 2 patients with inadequate fracture, 3 patients with injury to the IAN, and 1 patient with fistula. Postoperative complications (e.g., as damage of the inferior alveolar nerve and velopharyngeal insufficiency) may occur, and all patients recovered during the follow-up period of 6 months or more after the surgery. The relapse rates were A-N per 14.0%, Pog-N per 15.1%, SNA 24.4%, and SNB 4.6%. There was no statistically significant difference in relapse rate. CONCLUSION: Complications that may occur after the orthognathic surgery in the patients with cleft lip/palate are similar to those without cleft lip/palate.

Complement C3 Plays a Key Role in Inducing Humoral and Cellular Immune Responses to Influenza Virus Strain-Specific Hemagglutinin-Based or Cross-Protective M2 Extracellular Domain-Based Vaccination.

The complement pathway is involved in eliminating antigen immune complexes. However, the role of the C3 complement system remains largely unknown in influenza virus M2 extracellular (M2e) domain or hemagglutinin (HA) vaccine-mediated protection after vaccination. Using a C3 knockout (C3 KO) mouse model, we found that complement protein C3 was required for effective induction of immune responses to vaccination with M2e-based or HA-based vaccines, which include isotype class-switched antibodies and effector CD4 and CD8 T cell responses. C3 KO mice after active immunization with cross-protective nonneutralizing M2e-based vaccine were not protected against influenza virus, although low levels of M2e-specific antibodies were protective after passive coadministration with virus in wild-type mice. In contrast, C3 KO mice that were immunized with strain-specific neutralizing HA-based vaccine were protected against homologous virus challenge despite lower levels of HA antibody responses. C3 KO mice showed impaired maintenance of innate immune cells and a defect in innate immune responses upon exposure to antigens. The findings in this study suggest that C3 is required for effective induction of humoral and cellular adaptive immune responses as well as protective immunity after nonneutralizing influenza M2e vaccination.IMPORTANCE Complement is the well-known innate immune defense system involved in the opsonization and lysis of pathogens but is less studied in establishing adaptive immunity after vaccination. Influenza virus HA-based vaccination confers protection via strain-specific neutralizing antibodies, whereas M2e-based vaccination induces a broad spectrum of protection by immunity against the conserved M2e epitopes. This study revealed the critical roles of C3 complement in inducing humoral and cellular immune responses after immunization with M2e or HA vaccines. C3 was found to be required for protection by M2e-based but not by HA-based active vaccination as well as for maintaining innate antigen-presenting cells. Findings in this study have insight into better understanding the roles of C3 complement in inducing effective innate and adaptive immunity as well as in conferring protection by cross-protective conserved M2e vaccination.

Anti-infective potential of catechins and their derivatives against viral hepatitis.

Polyphenols including catechins from green tea (Camellia sinensis) have been reported to have anti-infective activities against a broad spectrum of viruses and other pathogens. During the last two decades, antiviral activities of catechins with different modes of action have been demonstrated on diverse families of viruses, such as human immunodeficiency virus, Herpes simplex virus, influenza virus, hepatitis B and C virus. In this study, we focused on the antiviral properties of catechins and their derivatives against viral hepatitis which have become a key public health issue due to their serious impact on human health with liver diseases.

Cytoprotective effect of flavonoid-induced autophagy on bisphosphonate mediated cell death in osteoblast.

With rapid economic growth and further developments in medical science, the entry into the aging population is currently increasing, as is the number of patients with metabolic diseases, such as hypertension, hyperlipidemia, heart disease, and diabetes. The current treatments for metabolic bone diseases, which are also on the rise, cause negative side effects. Bisphosphonates, which are used to treat osteoporosis, inhibit the bone resorption ability of osteoclasts and during prolonged administration, cause bisphosphonate-related osteonecrosis of the jaw (BRONJ). Numerous studies have shown the potential role of natural plant products as flavonoids in the protection against osteoporosis and in the influence of bone remodeling. Autophagy occurs after the degradation of cytoplasmic components within the lysosome and serves as an essential cytoprotective response to pathologic stress caused by certain diseases. In the present study, we hypothesized that the cytoprotective effects of flavonoids might be related to those associated with autophagy, an essential cytoprotective response to the pathologic stress caused by certain diseases, in osteoblasts. We demonstrated the cytoprotective effect of flavonoid-induced autophagy against the toxicity of zoledronate and the induction of autophagy by flavonoids to support osteogenic transcription factors, leading to osteoblast differentiation and bone formation. Further studies are necessary to clarify the connections between autophagy and osteogenesis. It would be helpful to shed light on methodological challenges through molecular biological studies and new animal models. The findings of the current study may help to delineate the potential role of flavonoids in the treatment of metabolic bone disease.

Rhabdomyolysis after the free fibular flap operation for mandibular reconstruction: a case report.

BACKGROUND: Free fibular flap is one of the most useful methods in the hard tissue reconstruction of the maxilla-mandible. Free fibular flap presents some advantages in which the reconstruction of both soft and hard tissues can be done at the same time. It also provides a safe and successful bone graft for the reconstruction, along with a low rate of complications. Despite these advantages and the rarity of a postoperative complication, particularly in oral and maxillofacial surgery procedures, a prolonged operation might exhibit some complications related with rhabdomyolysis. We experienced the rare event of rhabdomyolysis after oral cancer surgery. CASE PRESENTATION: In this article, we report the case of a patient who developed rhabdomyolysis after undergoing free fibular flap surgery. CONCLUSIONS: Despite the advantages of the free fibular flap operation, clinicians must be aware of the risk of complications because there are multiple factors that could result in rhabdomyolysis, such as duration of operation, position of the subject, and pre-existing conditions of diabetes and hypertension. Once the diagnosis of rhabdomyolysis is confirmed, a prompt treatment plan should be made and applied as soon as possible. This will increase the chance of a full recovery for the patient who is exhibiting symptoms of rhabdomyolysis.

Cross-Protective Efficacy of Influenza Virus M2e Containing Virus-Like Particles Is Superior to Hemagglutinin Vaccines and Variable Depending on the Genetic Backgrounds of Mice.

Influenza virus M2 extracellular domain (M2e) has been a target for developing cross-protective vaccines. However, the efficacy and immune correlates of M2e vaccination are poorly understood in the different host genetic backgrounds in comparison with influenza vaccines. We previously reported the cross-protective efficacy of virus-like particle (M2e5x VLP) vaccines containing heterologous tandem M2e repeats (M2e5x) derived from human, swine, and avian influenza viruses. In this study to gain better understanding of cross-protective influenza vaccines, we compared immunogenicity and efficacy of M2e5x VLP, H5 hemagglutinin VLP (HA VLP), and inactivated H3N2 virus (H3N2i) in wild-type strains of BALB/c and C57BL/6 mice, and CD4 and CD8 knockout (KO) mice. M2e5x VLP was superior to HA VLP in conferring cross-protection whereas H3N2i inactivated virus vaccine provided high efficacy of homologous protection. After M2e5x VLP vaccination and challenge, BALB/c mice induced higher IgG responses, lower lung viral loads, and less body weight loss when compared with those in C57BL/6 mice. M2e5x VLP but not H3N2i immune mice after primary challenges developed strong immunity against a secondary heterosubtypic virus as a model of future pandemics. M2e5x VLP and HA VLP vaccines were able to raise IgG isotypes in CD4 KO mice. T cells were found to contribute to cross-protection by playing a role in reducing lung viral loads. In conclusion, M2e5x VLP vaccination induced better cross-protection than HA VLP, and its efficacy varied depending on the genetic backgrounds of mice, supporting the important roles of T cells.

Malignant lymphoma on parotid gland: a clinical case.

Non-Hodgkin's lymphoma on the parotid gland is a relatively rare occurrence among head and neck tumors. The mass of parotid gland lymphoma cannot be distinguished from other benign masses of the parotid gland; therefore, it is important to consider lymphoma in the differential diagnosis when examining parotid swellings and masses. Parotid gland lymphoma is most likely to be B-cell, non-Hodgkin's lymphoma of one of three types, which include follicular, marginal zone, and diffuse large B-cell, although other histologic patterns have been described. We present a review of a patient with diffuse large B-cell lymphoma (DLBCL) who presented to the Department of Oral and Maxillofacial Surgery of Pusan National University Hospital (Yangsan, Korea).

Mifepristone/RU486 acts in Drosophila melanogaster females to counteract the life span-shortening and pro-inflammatory effects of male Sex Peptide.

Males with null mutation of Sex Peptide (SP) gene were compared to wild-type males for the ability to cause physiological changes in females that could be reversed by mifepristone. Males from wild-type strains decreased median female life span by average -51%. Feeding mifepristone increased life span of these females by average +106%. In contrast, SP-null males did not decrease female life span, and mifepristone increased median life span of these females by average +14%, which was equivalent to the effect of mifepristone in virgin females (average +16%). Expression of innate immune response transgenic reporter (Drosocin-GFP) was increased in females mated to wild-type males, and this expression was reduced by mifepristone. In contrast, SP-null males did not increase Drosocin-GFP reporter expression in the female. Similarly, mating increased endogenous microbial load, and this effect was reduced or absent in females fed mifepristone and in females mated to SP-null males; no loss of intestinal barrier integrity was detected using dye-leakage assay. Reduction of microbial load by treating adult flies with doxycycline reduced the effects of both mating and mifepristone on life span. Finally, mifepristone blocked the negative effect on life span caused by transgenic expression of SP in virgin females. The data support the conclusion that the majority of the life span-shortening, immune-suppressive and pro-inflammatory effects of mating are due to male SP, and demonstrate that mifepristone acts in females to counteract these effects of male SP.