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Entomopathogenic fungi infect insects by penetrating through the cuticle into the host body. To breach the host cuticle, some fungal pathogens produce specialized infection cells called appressoria, which develop enormous turgor pressure to allow cuticle penetration. However, regulatory mechanisms underlying appressorium turgor generation are poorly understood. Here, we show that the histone lysine methyltransferase ASH1 in the insecticidal fungus Metarhizium robertsii, which is strongly induced during infection of the mosquito cuticle, regulates appressorium turgor generation and cuticle penetration by activating the peroxin gene Mrpex16 via H3K36 dimethylation. MrPEX16 is required for the biogenesis of peroxisomes that participate in lipid catabolism and further promotes the hydrolysis of triacylglycerols stored in lipid droplets to produce glycerol for turgor generation, facilitating appressorium-mediated insect infection. Together, the ASH1-PEX16 pathway plays a pivotal role in regulating peroxisome biogenesis to promote lipolysis for appressorium turgor generation, providing insights into the molecular mechanisms underlying fungal pathogenesis.
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Proteínas Fúngicas , Peroxissomos , Animais , Peroxissomos/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Insetos/metabolismo , Doenças das Plantas/microbiologiaRESUMO
Insects have evolved diverse interactions with a variety of microbes, such as pathogenic fungi, bacteria, and viruses. The immune responses of insect hosts, along with the dynamic infection process of microbes in response to the changing host environment and defenses, require rapid and fine-tuned regulation of gene expression programs. Epigenetic mechanisms, including DNA methylation, histone modifications, and noncoding RNA regulation, play important roles in regulating the expression of genes involved in insect immunity and microbial pathogenicity. This review highlights recent discoveries and insights into epigenetic regulatory mechanisms that modulate insect-microbe interactions. A deeper understanding of these regulatory mechanisms underlying insect-microbe interactions holds promise for the development of novel strategies for biological control of insect pests and mitigation of vector-borne diseases.
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Lethal toxin (LT) is the critical virulence factor of Bacillus anthracis, the causative agent of anthrax. One common symptom observed in patients with anthrax is thrombocytopenia, which has also been observed in mice injected with LT. Our previous study demonstrated that LT induces thrombocytopenia by suppressing megakaryopoiesis, but the precise molecular mechanisms behind this phenomenon remain unknown. In this study, we utilized 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced megakaryocytic differentiation in human erythroleukemia (HEL) cells to identify genes involved in LT-induced megakaryocytic suppression. Through cDNA microarray analysis, we identified Dachshund homolog 1 (DACH1) as a gene that was upregulated upon TPA treatment but downregulated in the presence of TPA and LT, purified from the culture supernatants of B. anthracis. To investigate the function of DACH1 in megakaryocytic differentiation, we employed short hairpin RNA technology to knock down DACH1 expression in HEL cells and assessed its effect on differentiation. Our data revealed that the knockdown of DACH1 expression suppressed megakaryocytic differentiation, particularly in polyploidization. We demonstrated that one mechanism by which B. anthracis LT induces suppression of polyploidization in HEL cells is through the cleavage of MEK1/2. This cleavage results in the downregulation of the ERK signaling pathway, thereby suppressing DACH1 gene expression and inhibiting polyploidization. Additionally, we found that known megakaryopoiesis-related genes, such as FOSB, ZFP36L1, RUNX1, FLI1, AHR, and GFI1B genes may be positively regulated by DACH1. Furthermore, we observed an upregulation of DACH1 during in vitro differentiation of CD34-megakaryocytes and downregulation of DACH1 in patients with thrombocytopenia. In summary, our findings shed light on one of the molecular mechanisms behind LT-induced thrombocytopenia and unveil a previously unknown role for DACH1 in megakaryopoiesis.
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Antraz , Bacillus anthracis , Leucemia Eritroblástica Aguda , Trombocitopenia , Animais , Humanos , Camundongos , Antígenos de Bactérias/metabolismo , Bacillus anthracis/metabolismo , Fator 1 de Resposta a Butirato/metabolismo , Diferenciação Celular , Trombocitopenia/induzido quimicamente , Trombocitopenia/genéticaRESUMO
The insect gut microbiota plays crucial roles in modulating the interactions between the host and intestinal pathogens. Unlike viruses, bacteria, and parasites, which need to be ingested to cause disease, entomopathogenic fungi infect insects through the cuticle and proliferate in the hemolymph. However, interactions between the gut microbiota and entomopathogenic fungi are unknown. Here we show that the pathogenic fungus Beauveria bassiana interacts with the gut microbiota to accelerate mosquito death. After topical fungal infection, mosquitoes with gut microbiota die significantly faster than mosquitoes without microbiota. Furthermore, fungal infection causes dysbiosis of mosquito gut microbiota with a significant increase in gut bacterial load and a significant decrease in bacterial diversity. In particular, the opportunistic pathogenic bacterium Serratia marcescens overgrows in the midgut and translocates to the hemocoel, which promotes fungal killing of mosquitoes. We further reveal that fungal infection down-regulates antimicrobial peptide and dual oxidase expression in the midgut. Duox down-regulation in the midgut is mediated by secretion of the toxin oosporein from B. bassiana Our findings reveal the important contribution of the gut microbiota in B. bassiana-killing activity, providing new insights into the mechanisms of fungal pathogenesis in insects.
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Culicidae/microbiologia , Controle de Mosquitos/métodos , Controle Biológico de Vetores/métodos , Animais , Anopheles/microbiologia , Anopheles/patogenicidade , Beauveria/metabolismo , Beauveria/patogenicidade , Culicidae/patogenicidade , Microbioma Gastrointestinal , Insetos Vetores/microbiologia , Insetos/microbiologia , Resistência a Inseticidas , Inseticidas , Serratia marcescens/patogenicidade , Esporos Fúngicos/metabolismoRESUMO
BACKGROUND: Neoadjuvant chemoradiation therapy (nCRT) has been indicated for locally advanced rectal cancer. While utilization of laparoscopy in rectal cancer surgery has been popular in recent years, tumors receiving nCRT is still a surgical challenge. Transanal total mesorectal excision (TaTME) has emerged as a focused area of laparoscopic surgery that is becoming an increasingly acceptable approach in the field of rectal surgery. METHODS: Between December 2013 and April 2015, a total of 50 patients (38 males) with post-nCRT middle or lower rectal cancer who then underwent TaTME at two separate institutions were prospectively documented. Overall, 100 matched control cohorts who received conventional laparoscopic rectal surgery (LapTME) were simultaneously retrieved from a prospectively registered database. Four parameters of sex, age, clinical stage, and American Society of Anesthesiologists (ASA) score were matched for surgical outcomes, and short-term oncological results, including complications and pathological outcomes, were analyzed. RESULTS: Both the TaTME and LapTME groups received 5-fluorouracil-based chemotherapy and 5 weeks of long-course radiation therapy. Mean operative time for the TaTME group was 182.1 ± 55.4 min (156.6 ± 37.8 min in two-team-approach cases) and 178.7 ± 34.8 min for the LapTME group. The TaTME group yielded longer distal margin lengths. No significant differences were observed in blood loss, intraoperative complication rate, conversion rate, anastomosis type, and free circumferential margin rate. CONCLUSION: This matched case-control study demonstrated that TaTME is safe and feasible. Compared with LapTME, TaTME not only achieves identical circumferential margin status without compromising other operative and quality parameters but also benefits patients by achieving a longer distal margin. Thus, TaTME has the potential to become an option in managing irradiated rectal cancer.
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Adenocarcinoma/cirurgia , Canal Anal/cirurgia , Quimiorradioterapia Adjuvante , Laparoscopia/métodos , Terapia Neoadjuvante , Neoplasias Retais/cirurgia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Casos e Controles , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Duração da Cirurgia , Complicações Pós-Operatórias , Prognóstico , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/patologia , Neoplasias Retais/radioterapia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) has emerged as the area of focus in laparoscopic surgery. Hybrid NOTES (hNOTES) has some potential advantages for treating rectal cancer. METHODS: Between May 2013 and November 2013, a total of 20 patients (11 males) who received hNOTES at two institutes participating in the study were documented and reviewed. Surgical outcomes, including complications and pathological outcomes, were analyzed. RESULTS: The mean age of patients was 57.8 ± 10.1 years (range 34-78). Eleven patients received preoperative neoadjuvant chemoradiotherapy, with the mean distance between tumor and anal verge being 5.9 ± 1.7 cm (mean 2-8). The mean estimated intraoperative blood loss was 68 ± 106 ml (range 30-500), with one case converted to open procedure due to uncontrolled bleeding. Eight cases underwent simultaneous two-team approach. The mean operative time was 200.8 ± 47.7 min (range 110-285). Circular stapling was performed for 14 cases (70 %) as the anastomosis, and protective stoma performed for 17 cases (85 %). The overall postoperative complication rate was 25 %. Two cases (10 %) develop pelvic abscess due to leakage, which were controlled by medical treatments. The distal and circumferential margins were all free of tumor cells, and the mean distal margin length was 2.4 ± 0.98 cm (range 0.5-4). CONCLUSIONS: Hybrid NOTES for rectal cancer is safe and feasible. Rapid experience-building accelerates its evolution, as reflected here by the high stapling rate and the idea of a two-team approach. It has the potential to become an option of treating rectal cancers.
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Adenocarcinoma/cirurgia , Laparoscopia/métodos , Cirurgia Endoscópica por Orifício Natural/métodos , Tumores Neuroendócrinos/cirurgia , Lesões Pré-Cancerosas/cirurgia , Neoplasias Retais/cirurgia , Reto/cirurgia , Adulto , Idoso , Canal Anal/cirurgia , Anastomose Cirúrgica , Perda Sanguínea Cirúrgica , Colo/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: Nematode-trapping fungi are a unique group of organisms that can capture nematodes using sophisticated trapping structures. The genome of Drechslerella stenobrocha, a constricting-ring-forming fungus, has been sequenced and reported, and provided new insights into the evolutionary origins of nematode predation in fungi, the trapping mechanisms, and the dual lifestyles of saprophagy and predation. RESULTS: The genome of the fungus Drechslerella stenobrocha, which mechanically traps nematodes using a constricting ring, was sequenced. The genome was 29.02 Mb in size and was found rare instances of transposons and repeat induced point mutations, than that of Arthrobotrys oligospora. The functional proteins involved in nematode-infection, such as chitinases, subtilisins, and adhesive proteins, underwent a significant expansion in the A. oligospora genome, while there were fewer lectin genes that mediate fungus-nematode recognition in the D. stenobrocha genome. The carbohydrate-degrading enzyme catalogs in both species were similar to those of efficient cellulolytic fungi, suggesting a saprophytic origin of nematode-trapping fungi. In D. stenobrocha, the down-regulation of saprophytic enzyme genes and the up-regulation of infection-related genes during the capture of nematodes indicated a transition between dual life strategies of saprophagy and predation. The transcriptional profiles also indicated that trap formation was related to the protein kinase C (PKC) signal pathway and regulated by Zn(2)-C6 type transcription factors. CONCLUSIONS: The genome of D. stenobrocha provides support for the hypothesis that nematode trapping fungi evolved from saprophytic fungi in a high carbon and low nitrogen environment. It reveals the transition between saprophagy and predation of these fungi and also proves new insights into the mechanisms of mechanical trapping.
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Ascomicetos/genética , Genoma Fúngico , Animais , Ascomicetos/classificação , Quitinases/genética , Quitinases/metabolismo , Hibridização Genômica Comparativa , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Perfilação da Expressão Gênica , Nematoides/microbiologia , Mutação Puntual , Proteína Quinase C/genética , Proteína Quinase C/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Human health safety and environmental concerns have resulted in the widespread deregistration of several agronomic important nematicides. New and safer nematicides are urgently needed. However, a high-throughput bioassay for screening potential nematicides has not been established. We developed a two-step high-throughput nematicidal screening method to combine a cell-based MTS colorimetric assay with Caenorhabditis elegans embryo cells for preliminary cytotoxicity screening (step 1) followed by in vitro larval assay for nematicidal activity (step 2). Based on three conventional nematicides' test, high correlations were obtained between cell viability and larval viability and "r" values were 0.78 for Avermectin, 0.95 for Fosthiazate, and 0.65 for Formaldehyde solution. Further assays with 60 fungal secondary metabolites (extracts, fractions and pure compounds) also demonstrated the high correlation between cell viability and larval viability (r=0.60) and between the C. elegans cell viability and the juvenile viability of soybean cyst nematode Heterodera glycines (r=0.48) and pine wood nematode Bursaphelenchus xylophilus (r=0.56). Six metabolites with high cytotoxicity have performed high larval mortality with a LC50 range of 6.8-500µg/ml. These results indicate that the proposed two-step screening assay represents an efficient and labor-saving method for screening natural nematicidal products.
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Antinematódeos/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Ensaios de Triagem em Larga Escala/métodos , Animais , Antinematódeos/toxicidade , Bioensaio/métodos , Bioensaio/normas , Caenorhabditis elegans/embriologia , Caenorhabditis elegans/crescimento & desenvolvimento , Colorimetria , Relação Dose-Resposta a Droga , Fungos/química , Ensaios de Triagem em Larga Escala/normas , Larva/efeitos dos fármacos , Dose Letal Mediana , Doenças das Plantas/parasitologia , Doenças das Plantas/prevenção & controle , Plantas/efeitos dos fármacos , Plantas/parasitologia , Tylenchida/efeitos dos fármacos , Tylenchoidea/efeitos dos fármacosRESUMO
Purpose: This study investigates the influence of demographic changes on the effectiveness of hospital nurse staffing policy, measured by the cumulative response of inpatient care quality to adjustments in hospital nurse staffing levels in Taiwan. Methods: The research design utilized in this study aligns with the observational time-series methodology, and a total of 99 monthly time-series observations were collected from multiple databases administered by the Taiwan government over the period from January 2015 to March 2023. Specifically, the time-varying parameter vector autoregressive and autoregressive distributed lag models were employed to investigate the association between age distribution and nurse staffing policy effectiveness. Results: The time-varying impulse responses of the unplanned 14-day readmission rate after discharge to changes in nurse staffing levels indicate a positive association between patient-to-nurse ratios and unplanned 14-day readmission rates across various types of hospitals. Nevertheless, the effectiveness of hospitals' nurse staffing policy is observed to diminish with population aging, particularly evident in medical centers and regional hospitals. Conclusion: Policymakers should establish lower mandated patient-to-nurse ratios, grounded in practical nurse workforce planning, to address the needs of an aging society and enhance inpatient care quality through improved nurse staffing in hospitals.
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In patients with esophageal cancer undergoing neoadjuvant chemoradiotherapy (nCRT), subsequent restaging with F-18-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) can reveal the presence of interval metastases, such as liver metastases, in approximately 10% of cases. Nevertheless, it is not uncommon in clinical practice to observe focal FDG uptake in the liver that is not associated with liver metastases but rather with radiation-induced liver injury (RILI), which can result in the overstaging of the disease. Liver radiation damage is also a concern during distal esophageal cancer radiotherapy due to its proximity to the left liver lobe, typically included in the radiation field. Post-CRT, if FDG activity appears in the left or caudate liver lobes, a thorough investigation is needed to confirm or rule out distant metastases. The increased FDG uptake in liver lobes post-CRT often presents a diagnostic dilemma. Distinguishing between radiation-induced liver disease and metastasis is vital for appropriate patient management, necessitating a combination of imaging techniques and an understanding of the factors influencing the radiation response. Diagnosis involves identifying new foci of hepatic FDG avidity on PET/CT scans. Geographic regions of hypoattenuation on CT and well-demarcated regions with specific enhancement patterns on contrast-enhanced CT scans and MRI are characteristic of radiation-induced liver disease (RILD). Lack of mass effect on all three modalities (CT, MRI, PET) indicates RILD. Resolution of abnormalities on subsequent examinations also helps in diagnosing RILD. Moreover, it can also help to rule out occult metastases, thereby excluding those patients from further surgery who will not benefit from esophagectomy with curative intent.
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Insects and their natural microbial pathogens are intertwined in constant arms races, with pathogens continually seeking entry into susceptible hosts through distinct routes. Entomopathogenic fungi are primarily believed to infect host insects through external cuticle penetration. Here, we report a new variety, Beauveria bassiana var. majus (Bbm), that can infect insects through the previously unrecognized foregut. Dual routes of infection significantly accelerate insect mortality. The pH-responsive transcription factor PacC in Bbm exhibits rapid upregulation and efficient proteolytic processing via PalC for alkaline adaptation in the foregut. Expression of PalC is regulated by the adjacent downstream gene Aia. Compared to non-enteropathogenic strains such as ARSEF252, Aia in Bbm lacks a 249-bp fragment, resulting in its enhanced alkaline-induced expression. This induction promotes PalC upregulation and facilitates PacC activation. Expressing the active form of BbmPacC in ARSEF252 enables intestinal infection. This study uncovers the pH-responsive Aia-PalC-PacC cascade enhancing fungal alkaline tolerance for intestinal infection, laying the foundation for developing a new generation of fungal insecticides to control destructive insect pests.
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Polycaprolactone (PCL) implants in large animals show great promise for tracheal transplantation. However, the longest survival time achieved to date is only about three weeks. To meet clinical application standards, it is essential to extend the survival time and ensure the complete integration and functionality of the implant. Our study investigates the use of three-dimensional (3D)-printed, biodegradable, PCL-based tracheal grafts for large-scale porcine tracheal transplantation, assessing the feasibility and early structural integrity crucial for long-term survival experiments. A biodegradable PCL tracheal graft was fabricated using a BIOX bioprinter and transplanted into large-scale porcine models. The grafts, measuring 20 × 20 × 1.5 mm, were implanted following a 2 cm circumferential resection of the porcine trachea. The experiment design was traditionally implanted in eight porcines to replace four-ring tracheal segments, only two of which survived more than three months. Data were collected on the graft construction and clinical outcomes. The 3D-printed biosynthetic grafts replicated the native organ with high fidelity. The implantations were successful, without immediate complications. At two weeks, bronchoscopy revealed significant granulation tissue around the anastomosis, which was managed with laser ablation. The presence of neocartilage, neoglands, and partial epithelialization near the anastomosis was verified in the final pathology findings. Our study demonstrates in situ regenerative tissue growth with intact cartilage following transplantation, marked by neotissue formation on the graft's exterior. The 90-day survival milestone was achieved due to innovative surgical strategies, reinforced with strap muscle attached to the distal trachea. Further improvements in graft design and granulation tissue management are essential to optimize outcomes.
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Objectives: The study objectives were to test an innovative T-tube procedure involving ablative bronchoscopy for the treatment of total airway occlusion and to orchestrate a safe and nontraumatic maneuver to treat intricate subglottic stenosis amenable for substituting the conventional surgical intervention. Methods: This was an uncontrolled single-center cohort study on 1254 patients from January 2001 to June 2021. Patients underwent the modified T-tube procedure treatment for tracheal stenosis. Only 42 patients were included in the study because they had full records for subglottic total occlusion sitting tracheostomy. The ablative bronchoscopy, aided by a fixed suspending laryngoscope, was applied to retunnel their total airway occlusion. T-tube revision and removal were conducted under general anesthesia with laryngeal mask airway aid during follow-up. Results: The primary outcome was 90-day mortality. The secondary outcome was 90-day morbidity. The 42 patients included in the study had a mean age of 52.29 years (range, 9-84 years) with 22 men (52.38%). Their mean length of hospital stay was 13.67 days (range, 2-45 days). Their mean operation time was 73 minutes (range, 43-256 minutes). Their mean length of the tracheal stenosis was 2.8 cm (range, 0.8-6.3 cm). Outcomes were good in 29 patients (69.05%), satisfactory in 10 patients (23.81%), and considered failures in 3 patients (7.14%). A total of 16 patients (38.10%) underwent decannulation, and 3 patients (7.14%) were shifted to a Shiley tracheostomy. All 42 patients had a median follow-up of 6.2 years (range, 1.5-16.3 years). Conclusions: The modified T-tube procedure, which offered both resilience and versatility, improved the conventional technique in treating those patients experiencing total tracheal stenosis and who were unqualified for conventional open surgery.
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Recent studies showed significant associations between socio-demographic, lifestyle factors, polymorphic variant rs6265, and smoking cessation behaviours. We examined rs6265 TT, TC and CC genotypes and their association with socio-demographic and other variables, including mental health status, drinking, exercise, and smoking behaviour among Taiwanese adults. Data on rs6265 were retrieved from the Taiwan Biobank, which contained genetic data collected between 2008 to 2019 from 20,584 participants (aged 30-70 years). Participants who smoked for more than 6 months prior to enrolment were categorized as smokers. If they had smoked and later quit for more than 6 months, they were classified as former smokers. Information regarding drinking, exercise, depression, and bipolar disorder were obtained through questionnaires and were categorized as either as affirmative (yes) or negative (no) responses. In contrast to previous studies, we found that the association between the polymorphism rs6265 and smoking behaviour was not significant (P-value = 0.8753). Males with lower education levels, young persons, and alcohol drinkers showed significant smoking behaviours (P-value < .0001). This population-based study indicates that rs6265 has no significant correlations with smoking cessation behaviour among adults in Taiwan.
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Abandono do Hábito de Fumar , Adulto , Humanos , Masculino , Estilo de Vida , Fumar/genética , Fumar/epidemiologia , Inquéritos e Questionários , Taiwan/epidemiologia , Fator Neurotrófico Derivado do Encéfalo/genéticaRESUMO
PURPOSE: The objectives of the study were to estimate the incidence and clarify the clinicopathologic feature of sporadic microsatellite instability (MSI)-high (MSI-H) colon cancer. Furthermore, the role of MSI in colon cancer prognosis was also investigated. METHODS: Microsatellite status was identified by genotyping. The clinicopathologic differences between two groups (MSI-H vs. MSI-L/S) and the prognostic value of MSI were analyzed. RESULTS: From 1993 to 2006, 709 sporadic colon cancer patients were enrolled. MSI-H colon cancers showed significant association with poorly differentiated (28.3% vs. 7.2%, p = 0.001), proximally located (76.7% vs. 34.5%, p = 0.001), more high mucin-containing tumor (10.0% vs. 5.1%, p = 0.001) and female predominance (56.7% vs. 30.2%, p = 0.001). In multivariate analysis, MSI-H is an independent factor for better overall survival (HR, 0.459; 95% CI, 0.241-0.872, p = 0.017). CONCLUSIONS: Based on the hospital-based study, MSI-H colon cancers demonstrated distinguished clinicopathologic features from MSI-L/S colon cancers. MSI-H is an independent favorable prognostic factor for overall survival in colon cancer.
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Adenocarcinoma/genética , Adenocarcinoma/patologia , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Instabilidade de Microssatélites , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenocarcinoma/metabolismo , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Idoso , Idoso de 80 Anos ou mais , Colo/patologia , Neoplasias do Colo/metabolismo , Reparo de Erro de Pareamento de DNA , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Intervalo Livre de Doença , Feminino , Genótipo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento , Análise Multivariada , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/genética , Proteína 2 Homóloga a MutS/metabolismo , Estadiamento de Neoplasias , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Prognóstico , Modelos de Riscos Proporcionais , Fatores SexuaisRESUMO
Filamentous fungal pathogens have evolved diverse strategies to infect a variety of hosts including plants and insects. The dynamic infection process requires rapid and fine-tuning regulation of fungal gene expression programs in response to the changing host environment and defenses. Therefore, transcriptional reprogramming of fungal pathogens is critical for fungal development and pathogenicity. Histone post-translational modification, one of the main mechanisms of epigenetic regulation, has been shown to play an important role in the regulation of gene expressions, and is involved in, e.g., fungal development, infection-related morphogenesis, environmental stress responses, biosynthesis of secondary metabolites, and pathogenicity. This review highlights recent findings and insights into regulatory mechanisms of histone methylation and acetylation in fungal development and pathogenicity, as well as their roles in modulating pathogenic fungi-host interactions.
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BACKGROUND: The Taiwanese government implemented a stay-at-home order that restricted all community-based health promotion activities for the elderly by shutting down all community care centers from May 2021 to August 2021 to control the spread of COVID-19. Community-based dementia care centers were barely able to provide dementia care services during that period. METHODS: The data used in this study were collected from a community-based dementia care center that was able to continue their dementia care services through a Tele-Health intervention program. The difference-in-differences methodology was applied to evaluate the effects of the Tele-Health intervention program on home-dwelling persons with dementia or mild cognitive impairment and on their primary caregivers during the COVID-19 pandemic. RESULTS: The Tele-Health intervention program significantly increased the well-being of the participants and their primary caregivers, but the negative correlations between the Tele-Health intervention program and family functioning were also found to be significant. CONCLUSIONS: The significant substitution (negative) effects between the Tele-Health intervention program and family functioning raises the concern that promotion of the Tele-Health intervention program comes at the potential cost of a loss of family functioning. Policymakers should be cautious when considering the Tele-Health intervention program in response to pandemics and demographic transitions.
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Laparoscopic surgery for rectal cancer is technically challenging. Robotic and transanal TME (TaTME) are both novel approaches developed to provide better visualization and dissection. We aim to combine both approaches in a hybrid procedure and evaluate the feasibility as well as patient and oncological outcomes in this study. A review of a prospectively maintained database of patients who underwent a hybrid abdominal robotic approach with TaTME for rectal cancer between January 2016 and October 2018 was undertaken. Patient demographics, tumor characteristics and surgical outcomes were recorded and analyzed. A total of 69 patients (43 males, 26 females) received this hybrid approach. Their median age was 58 years (range 35-87) with a mean BMI of 24.3 kg/m2 (range 16.4-44.2). Median distance from anal verge was 5 cm (range 2-9). The patients had a median hospital length of stay of 7 days (range 5-28). Complication rate was 17.4% (12 patients) with 3 patients (4.3%) requiring a reoperation. TME quality was optimal with all of them either complete (81.2%) or almost complete (18.8%). 65 patients (94.2%) had an R0 resection with 4 patients (5.8%) with involved circumferential resection margins (≤ 1 mm). The median number of lymph nodes harvested was 20 (range 6-37). After a median follow-up of 27.7 months (range 7-42), local recurrence was identified in 2 patients (4%). Three patients (5.2%) had distant recurrence at the 3-year mark. Hybrid robotic abdominal dissection with transanal TME for rectal cancer appears to be feasible with comparable surgical outcomes to other traditional approaches.
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Laparoscopia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Cirurgia Endoscópica Transanal , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Reto/patologia , Reto/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Cirurgia Endoscópica Transanal/métodos , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: The colon is a rare location for gastrointestinal non-Hodgkin's lymphoma. We retrospectively analyzed the demographic data of patients with colonic lymphoma and the possible prognostic factors of the disease. METHODS: We studied data obtained from 6,944 patients and performed a retrospective review of patients with primary colonic lymphoma (PCL) by using a pathology registry database. We employed well-established and accepted diagnostic criteria and clinical staging method. RESULTS: Twenty-nine patients (19 men; 10 women) were diagnosed with PCL. The cecum was the most common tumor location (14/29 patients), and 17 cases (17/29) showed diffuse large-B-cell lymphomas. Four patients died of sepsis within 30 days of an emergency surgery for perforation of intestine. Two-thirds of the patients were in the early disease stages (stages I and II). The overall 5-year survival rate was 47.3%. Disease stage was not a prognostic factor for survival. The overall 5-year survival rate in patients treated with surgery followed by chemotherapy was statistically significant as compared to that in the patients treated with chemotherapy alone. CONCLUSION: PCL is a rare malignancy of the gastrointestinal tract, and surgical resection should be considered a part of the standard treatment to achieve a better outcome.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Linfoma/tratamento farmacológico , Linfoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Seguimentos , Humanos , Linfoma/classificação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: There remains a scarcity of both autografts and allografts for tracheal transplantation after long-segmental resection. Subsequently, tissue engineering has become a promising alternative for tracheal transplantation, which requires successful in vitro chondrogenesis. METHODS: To optimize the protocol for in situ chondrogenesis using the pig-derived whole Umbilical Cord (UC) as the starting material, it must be performed without using the UC-multipotent stromal cell (MSCs) isolation procedure. Nevertheless, chondrogenic induction is performed under a variety of conditions; with or without TGF-ß1 at different concentrations, and also in combination with either a rotatory or hollow organ bioreactor. The engineered explant sections were analyzed using various histochemical and immunohistochemical stains to assess the expression of chondrocyte markers. Cell viability was determined through use of the APO-BrdU TUNEL assay kit. RESULTS: The results showed that culture conditions induced heterogeneous chondrogenesis in various compartments of the UC. Moreover, explants cultured with 10 ng/ml TGF-ß1 under hypoxic (1% O2) in combination with a bioreactor, significantly enhanced the expression of aggrecan and type II collagen, but were lacking in the production of Glycosaminoglycans (GAGs), as evidenced by alcian blue staining. We speculated that whole segment UCs allowed for the differentiation into premature chondrocytes in our tissue-engineered environments. CONCLUSION: This study has provided exciting preliminary evidence showing that a stem cell-rich UC wrapped around an anatomical tracheal scaffold and implanted in vivo can induce nodes of new cartilage growth into a structurally functional tissue for the repairing of long-segmental tracheal stenosis.