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Colorectal cancers (CRCs) form a heterogenous group classified into epigenetic and transcriptional subtypes. The basis for the epigenetic subtypes, exemplified by varying degrees of promoter DNA hypermethylation, and its relation to the transcriptional subtypes is not well understood. We link cancer-specific transcription factor (TF) expression alterations to methylation alterations near TF-binding sites at promoter and enhancer regions in CRCs and their premalignant precursor lesions to provide mechanistic insights into the origins and evolution of the CRC molecular subtypes. A gradient of TF expression changes forms a basis for the subtypes of abnormal DNA methylation, termed CpG-island promoter DNA methylation phenotypes (CIMPs), in CRCs and other cancers. CIMP is tightly correlated with cancer-specific hypermethylation at enhancers, which we term CpG-enhancer methylation phenotype (CEMP). Coordinated promoter and enhancer methylation appears to be driven by downregulation of TFs with common binding sites at the hypermethylated enhancers and promoters. The altered expression of TFs related to hypermethylator subtypes occurs early during CRC development, detectable in premalignant adenomas. TF-based profiling further identifies patients with worse overall survival. Importantly, altered expression of these TFs discriminates the transcriptome-based consensus molecular subtypes (CMS), thus providing a common basis for CIMP and CMS subtypes.
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Neoplasias Colorrectales , Lesiones Precancerosas , Humanos , Factores de Transcripción , Regulación de la Expresión Génica , Metilación de ADN , Epigénesis GenéticaRESUMEN
Pulmonary arterial hypertension (PAH) is characterized by progressive vascular remodeling of small pulmonary arteries (PAs) causing sustained elevation of PA pressure, right ventricular failure, and death. Similar to cancer cells, PA smooth muscle cells (PASMCs), which play a key role in pulmonary vascular remodeling, have adopted multiple mechanisms to sustain their survival and proliferation in the presence of stress. The histone methyltransferase G9a and its partner protein GLP (G9a-like protein) have been shown to exert oncogenic effects and to serve as a buffer against an exaggerated transcriptional response. Therefore, we hypothesized that upregulation of G9a and GLP in PAH plays a pivotal role in pulmonary vascular remodeling by maintaining the abnormal phenotype of PAH-PASMCs. We found that G9a is increased in PASMCs from patients with PAH as well as in remodeled PAs from animal models. Pharmacological inhibition of G9a/GLP activity using BIX01294 and UNC0642 significantly reduced the prosurvival and proproliferative potentials of cultured PAH-PASMCs. Using RNA sequencing, further exploration revealed that G9a/GLP promotes extracellular matrix production and affords protection against the negative effects of an overactive stress response. Finally, we found that therapeutic treatment with BIX01294 reduced pulmonary vascular remodeling and lowered mean PA pressure in fawn-hooded rats. Treatment of Sugen/hypoxia-challenged mice with BIX01294 also improved pulmonary hemodynamics and right ventricular function. In conclusion, these findings indicate that G9a/GLP inhibition may represent a new therapeutic approach in PAH.
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Hipertensión Arterial Pulmonar , Ratas , Ratones , Animales , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Remodelación Vascular , Proliferación Celular , Hipertensión Pulmonar Primaria Familiar , Modelos Animales de Enfermedad , Miocitos del Músculo Liso , Arteria PulmonarRESUMEN
We sought to better understand the immune response during the immediate post-diagnosis phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by identifying molecular associations with longitudinal disease outcomes. Multi-omic analyses identified differences in immune cell composition, cytokine levels, and cell subset-specific transcriptomic and epigenomic signatures between individuals on a more serious disease trajectory (Progressors) as compared to those on a milder course (Non-progressors). Higher levels of multiple cytokines were observed in Progressors, with IL-6 showing the largest difference. Blood monocyte cell subsets were also skewed, showing a comparative decrease in non-classical CD14-CD16+ and intermediate CD14+CD16+ monocytes. In lymphocytes, the CD8+ T effector memory cells displayed a gene expression signature consistent with stronger T cell activation in Progressors. These early stage observations could serve as the basis for the development of prognostic biomarkers of disease risk and interventional strategies to improve the management of severe COVID-19. BACKGROUND: Much of the literature on immune response post-SARS-CoV-2 infection has been in the acute and post-acute phases of infection. TRANSLATIONAL SIGNIFICANCE: We found differences at early time points of infection in approximately 160 participants. We compared multi-omic signatures in immune cells between individuals progressing to needing more significant medical intervention and non-progressors. We observed widespread evidence of a state of increased inflammation associated with progression, supported by a range of epigenomic, transcriptomic, and proteomic signatures. The signatures we identified support other findings at later time points and serve as the basis for prognostic biomarker development or to inform interventional strategies.
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COVID-19 , Humanos , Multiómica , Proteómica , SARS-CoV-2 , CitocinasRESUMEN
Fibroblast-like synoviocytes (FLS), one of the main cell types of the rheumatoid arthritis (RA) synovium, possess phenotypic and molecular characteristics of transformed cells. JQ1, an inhibitor of the bromodomain and extra terminal domain family that includes BRD2, BRD3, BRD4, and BRDt, has shown efficacy in models of arthritis. We demonstrate that the active isomer of JQ1 but not its inactive isomer inhibits IL-1ß-induced RA-FLS activation and proliferation. To understand the mechanism of JQ1 action, we subjected JQ1-treated RA-FLS to transcriptional profiling and determined BRD2 and BRD4 cistromes by identifying their global chromatin binding sites. In addition, assay for transposable accessible chromatin by high throughput sequencing was employed to identify open and closed regions of chromatin in JQ1-treated RA-FLS. Through an integrated analysis of expression profiling, Brd2/Brd4 cistrome data, and changes in chromatin accessibility, we found that JQ1 inhibited key BRD2/BRD4 superenhancer genes, downregulated multiple crucial inflammatory pathways, and altered the genome-wide occupancy of critical transcription factors involved in inflammatory signaling. Our results suggest a pleiotropic effect of JQ1 on pathways that have shown to be individually efficacious in RA (in vitro, in vivo, and/or in humans) and provide a strong rationale for targeting BRD2/BRD4 for disease treatment and interception.
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OBJECTIVES: Immune and stromal cell communication is central in the pathogenesis of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), however, the nature of these interactions in the synovial pathology of the two pathotypes can differ. Identifying immune-stromal cell crosstalk at the site of inflammation in RA and PsA is challenging. This study creates the first global transcriptomic analysis of the RA and PsA inflamed joint and investigates immune-stromal cell interactions in the pathogenesis of synovial inflammation. METHODS: Single cell transcriptomic profiling of 178 000 synovial tissue cells from five patients with PsA and four patients with RA, importantly, without prior sorting of immune and stromal cells. This approach enabled the transcriptomic analysis of the intact synovial tissue and identification of immune and stromal cell interactions. State of the art data integration and annotation techniques identified and characterised 18 stromal and 14 immune cell clusters. RESULTS: Global transcriptomic analysis of synovial cell subsets identifies actively proliferating synovial T cells and indicates that due to differential λ and κ immunoglobulin light chain usage, synovial plasma cells are potentially not derived from the local memory B cell pool. Importantly, we report distinct fibroblast and endothelial cell transcriptomes indicating abundant subpopulations in RA and PsA characterised by differential transcription factor usage. Using receptor-ligand interactions and downstream target characterisation, we identify RA-specific synovial T cell-derived transforming growth factor (TGF)-ß and macrophage interleukin (IL)-1ß synergy in driving the transcriptional profile of FAPα+THY1+ invasive synovial fibroblasts, expanded in RA compared with PsA. In vitro characterisation of patient with RA synovial fibroblasts showed metabolic switch to glycolysis, increased adhesion intercellular adhesion molecules 1 expression and IL-6 secretion in response to combined TGF-ß and IL-1ß treatment. Disrupting specific immune and stromal cell interactions offers novel opportunities for targeted therapeutic intervention in RA and PsA.
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Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by a sustained elevation of pulmonary artery (PA) pressure, right ventricular failure, and premature death. Enhanced proliferation and resistance to apoptosis (as seen in cancer cells) of PA smooth muscle cells (PASMCs) is a major pathological hallmark contributing to pulmonary vascular remodeling in PAH, for which current therapies have only limited effects. Emerging evidence points toward a critical role for Enhancer of Zeste Homolog 2 (EZH2) in cancer cell proliferation and survival. However, its role in PAH remains largely unknown. The aim of this study was to determine whether EZH2 represents a new factor critically involved in the abnormal phenotype of PAH-PASMCs. We found that EZH2 is overexpressed in human lung tissues and isolated PASMCs from PAH patients compared to controls as well as in two animal models mimicking the disease. Through loss- and gain-of-function approaches, we showed that EZH2 promotes PAH-PASMC proliferation and survival. By combining quantitative transcriptomic and proteomic approaches in PAH-PASMCs subjected or not to EZH2 knockdown, we found that inhibition of EZH2 downregulates many factors involved in cell-cycle progression, including E2F targets, and contributes to maintain energy production. Notably, we found that EZH2 promotes expression of several nuclear-encoded components of the mitochondrial translation machinery and tricarboxylic acid cycle genes. Overall, this study provides evidence that, by overexpressing EZH2, PAH-PASMCs remove the physiological breaks that normally restrain their proliferation and susceptibility to apoptosis and suggests that EZH2 or downstream factors may serve as therapeutic targets to combat pulmonary vascular remodeling.
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Proteína Potenciadora del Homólogo Zeste 2/genética , Proteoma/genética , Hipertensión Arterial Pulmonar/genética , Transcriptoma/genética , Animales , Apoptosis/genética , Proliferación Celular/genética , Ciclo del Ácido Cítrico/genética , Epigénesis Genética/genética , Femenino , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/patología , Humanos , Pulmón/metabolismo , Pulmón/patología , Masculino , Persona de Mediana Edad , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Hipertensión Arterial Pulmonar/patología , Arteria Pulmonar/crecimiento & desarrollo , Arteria Pulmonar/patología , RatasRESUMEN
The pectoralis major myocutaneous flap is considered a workhorse flap in the reconstruction of head and neck defects after cancer ablative surgeries and remains one of the most widely used reconstructive options. Complications at the donor site after the use of this flap, although rare, do occur and are usually restricted to minor infections, hematoma, and seroma formation. Metastasis to the flap donor site is a rare complication with limited documentation. Metastasis at the donor site usually follows local recurrence at the primary site, supporting the probable hypothesis of re-establishment of lymphatic drainage to the primary site by the flap pedicle. Tumor implantation, although a probable cause for metastasis at the donor site, cannot be confidently distinguished from other mechanisms, such as hematogenous spread or lymphogenous metastasis. This report describes a case that supports a seeding or tumor implantation mechanism of metastasis exclusively.
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Carcinoma de Células Escamosas/cirugía , Neoplasias de Cabeza y Cuello/cirugía , Músculo Esquelético/cirugía , Colgajo Miocutáneo , Procedimientos de Cirugía Plástica , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
Introduction Antibiotic prophylaxis for tooth extractions is a common practice in dentistry to prevent postoperative infections. However, the routine use of antibiotics has been questioned due to concerns about bacterial resistance and potential side effects. This study aimed to evaluate the necessity of postoperative antibiotics in patients undergoing orthodontic tooth extraction. Materials and methods This prospective study involved 100 patients requiring orthodontic tooth extraction, divided into two groups. The patients were recruited from Saveetha Dental College and Hospital, Chennai, India, after obtaining approval from the Institutional Human Ethics Committee, Saveetha Dental College (approval number: IHEC/SDC/OMFS-2103/23/293). Group 1 (n = 50) received antibiotics (amoxicillin 500 mg, three times a day for three days) after extraction, while Group 2 (n = 50) did not receive antibiotics. Postoperative infection was assessed on postoperative days (POD) 3 and 7. Data analysis was conducted using IBM SPSS Statistics for Windows, version 26.0 (released 2019, IBM Corp., Armonk, NY). Categorical variables were presented as frequencies and percentages, and differences between groups were assessed using chi-square or Fisher's exact tests. A p-value of <0.05 was considered statistically significant. Results The incidence of postoperative infection was recorded in both groups. In group 1 at POD 3 and POD 7, there were two patients and one patient with infection, respectively. In group 2 at POD 3 and POD 7, there were four patients and two patients with infection, respectively. Conclusion The findings of this study suggest that the routine administration of antibiotics for the non-traumatic extraction of teeth in healthy patients might not be necessary. The absence of postoperative infections in patients who did not receive antibiotics indicates that antibiotics may be avoidable in many cases of orthodontic tooth extraction. These results emphasize the importance of reconsidering the widespread use of antibiotics to combat the growing concern of bacterial resistance. Antibiotics should be prescribed judiciously, only for patients with specific medical conditions who are prone to infection. One of the limitations of this study is the limited sample size; hence, studies with larger and heterogeneous groups should be done to validate the same.
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Introduction Postoperative wound healing is the most important factor in the outcome of any surgical procedure. Wound healing is a dynamic process involving inflammation, neovascularization, granulation, fibroblast proliferation, re-epithelization, and remodeling. It repairs tissue integrity, restoring the body's natural defense barrier. A hastened wound healing will help in the quicker re-establishment of the body's homeostasis. Carica papaya includes vital nutrients and bioactive substances such as minerals, vitamins, and antioxidants. Its primary active ingredient papain causes the enzymatic debridement of wounds. Hemocoagulase is a thrombin-like serine protease that is mostly employed for its procoagulant and wound-healing characteristics. It is derived from the venom of Bothrops species of snakes. This study aims to compare the wound-healing properties of topical Carica papaya leaf extract and Hemocoagulase after dental extractions. Materials & Methods For 48 patients requiring bilateral therapeutic dental extraction for orthodontic intervention, Carica papaya leaf extract (Caripill 275mg/5ml) was topically applied to the extraction socket on one side, and Hemocoagulase 0.2 CU solution (Botroclot) was applied to the extraction socket on the other side. The bilateral premolars were extracted for orthodontic treatment under local anesthesia. Patients were asked to apply the solution topically twice daily for seven days and were called for review on the seventh day. The assessment of the efficacy of both solutions in post-operative wound healing was the objective of the study. Healing was assessed by using a blinded single observer for all patients using Landry's healing index. Results A total of 48 subjects with 96 sites completed the study, with a mean age of 15.4 years. The study population consisted of 24 males and 24 females, which were evenly distributed among the two study groups. On comparison of wound healing index (WHI) scores between the two groups using the Wilcoxon signed rank test, Group A had a significantly higher mean rank than Group B with regards to the wound healing index score, and the results were statistically significant (p = 0.037). Conclusion It can be concluded from the study that Carica papaya leaf extract showed better wound healing in post-extraction sockets compared to Hemocoagulase. This study presents the promising use of natural extracts such as Carica papaya in wound healing because they are easily accessible to patients, more economical, and have no adverse reactions. More studies that focus on natural extracts to promote wound healing are required in the future.
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Odontogenic fibromyxoma typically presents as painless swelling in the jaw, and clinically, it grows slowly, becoming benign and asymptomatic. It causes the cortical plates to expand gradually, which leads to mobility and drifting of the teeth. Root resorption is also common. The tumor is locally aggressive in nature. It is also known to have a high recurrence rate. We present the case of a 30-year-old female patient who was diagnosed and treated for odontogenic fibromyxoma of the maxilla conservatively with enucleation. The radiograph showed a multilocular lesion, which can be confused with ameloblastoma, aneurysmal bone cyst, or odontogenic keratocyst. Hence, with proper clinical, radiographic, and histopathological examination, a correct diagnosis can be made and adequate treatment can be planned.
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Introduction The presence of impacted third molars is a prevalent problem associated with varying degrees of difficulty in extraction and potential consequences, including pain, swelling, and trismus. According to studies, enzymatic combinations, such as bromelain, rutoside, trypsin, and serratiopeptidase, are known to have a very promising role in reducing inflammation and promoting wound healing. This study compared natural enzymatic agents with corticosteroids for postoperative pain, swelling, and trismus in the impacted lower third molar surgery. Objectives The present study aimed to compare the efficacy of prednisolone, a combination of trypsin, chymotrypsin, bromelain, rutoside, and papain, and serratiopeptidase in the postoperative sequelae after surgical extraction of impacted mandibular third molars. The primary objective was to assess the difference in swelling between the three groups. The secondary objectives were to assess the difference in postoperative pain and trismus between the three groups. Materials and methods A total of 150 patients who presented to the department of oral and maxillofacial surgery for surgical removal of an impacted mandibular third molar with a moderately difficult score of 5-7 in the Pederson difficulty index were chosen for a prospective study. Patients were categorized into three groups based on the postoperative drug prescribed. In group 1, prednisolone 10 mg was prescribed; in group 2, a combination of trypsin, chymotrypsin, bromelain, rutoside, and papain was prescribed; and in group 3, serratiopeptidase 15 mg was prescribed. All patients were prescribed a combination drug of aceclofenac 100 mg and paracetamol 325 mg twice daily as a standard analgesic. Swelling, pain, and trismus in each patient were recorded preoperatively and at postoperative day one and day seven. The Friedman test was employed to evaluate the variation in pain levels within the groups over time, while the Kruskal-Wallis test was utilized to investigate the disparity in pain levels between the groups. The difference in swelling and trismus within the groups across the timeline was measured by repeated measures analysis of variance (ANOVA), and the difference in swelling and trismus between the groups was measured by one-way ANOVA. A p-value below 0.05 was deemed to be statistically significant. Results Group 1 showed less swelling, pain, and trismus on both postoperative day one and day seven compared to group 2 and group 3, which was a statistically significant difference (P < 0.05). It was found that swelling, pain, and trismus measurements in postoperative day one and day seven in group 2 were comparatively less than in group 3. Neither group demonstrated any side effects or other complications during the follow-up period. Conclusion It can be concluded that the use of prednisolone postoperatively following surgical removal of the mandibular third molar provided better relief with regard to pain, trismus, and swelling compared to the enzymatic agents. Among enzymatic agents, a combination of trypsin, chymotrypsin, bromelain, rutoside, and papain was better in reducing pain, trismus, and swelling than serratiopeptidase drug.
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BACKGROUND: Pulmonary arterial hypertension (PAH) ultimately leads to right ventricular failure and premature death. The identification of circulating biomarkers with prognostic utility is considered a priority. As chronic inflammation is recognized as key pathogenic driver, we sought to identify inflammation-related circulating proteins that add incremental value to current risk stratification models for long-term survival in patients with PAH. METHODS AND RESULTS: Plasma levels of 384 inflammatory proteins were measured with the proximity extension assay technology in patients with PAH (n=60) and controls with normal hemodynamics (n=28). Among these, 51 analytes were significantly overexpressed in the plasma of patients with PAH compared with controls. Cox proportional hazard analyses and C-statistics were performed to assess the prognostic value and the incremental prognostic value of differentially expressed proteins. A panel of 6 proteins (CRIM1 [cysteine rich transmembrane bone morphogenetic protein regulator 1], HGF [hepatocyte growth factor], FSTL3 [follistatin-like 3], PLAUR [plasminogen activator, urokinase receptor], CLSTN2 [calsyntenin 2], SPON1 [spondin 1]) were independently associated with death/lung transplantation at the time of PAH diagnosis after adjustment for the 2015 European Society of Cardiology/European Respiratory Society guidelines, the REVEAL (Registry to Evaluate Early and Long-Term PAH Disease Management) 2.0 risk scores, and the refined 4-strata risk assessment. CRIM1, PLAUR, FSTL3, and SPON1 showed incremental prognostic value on top of the predictive models. As determined by Western blot, FSTL3 and SPON1 were significantly upregulated in the right ventricle of patients with PAH and animal models (monocrotaline-injected and pulmonary artery banding-subjected rats). CONCLUSIONS: In addition to revealing new actors likely involved in cardiopulmonary remodeling in PAH, our screening identified promising circulating biomarkers to improve risk prediction in PAH, which should be externally confirmed.
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Biomarcadores , Proteómica , Hipertensión Arterial Pulmonar , Humanos , Masculino , Femenino , Biomarcadores/sangre , Proteómica/métodos , Persona de Mediana Edad , Pronóstico , Hipertensión Arterial Pulmonar/sangre , Hipertensión Arterial Pulmonar/mortalidad , Hipertensión Arterial Pulmonar/diagnóstico , Hipertensión Arterial Pulmonar/fisiopatología , Adulto , Animales , Medición de Riesgo , Estudios de Casos y Controles , Receptores del Activador de Plasminógeno Tipo Uroquinasa/sangre , Proteínas Relacionadas con la Folistatina/sangre , Modelos Animales de Enfermedad , Valor Predictivo de las Pruebas , Inflamación/sangre , Mediadores de Inflamación/sangre , Factores de Riesgo , Receptores de Proteínas Morfogenéticas Óseas de Tipo II/sangre , Receptores de Proteínas Morfogenéticas Óseas de Tipo II/genética , Arteria Pulmonar/fisiopatologíaRESUMEN
BACKGROUND AND AIMS: Treatment with siRNAs that target HBV has demonstrated robust declines in HBV antigens. This effect is also observed in the AAV-HBV mouse model, which was used to investigate if two cycles of GalNAc-HBV-siRNA treatment could induce deeper declines in HBsAg levels or prevent rebound, and to provide insights into the liver immune microenvironment. METHODS: C57Bl/6 mice were transduced with one of two different titers of AAV-HBV for 28 days, resulting in stable levels of HBsAg of about 103 or 105 IU/mL. Mice were treated for 12 weeks (four doses q3wk) per cycle with 3 mg/kg of siRNA-targeting HBV or an irrelevant sequence either once (single treatment) or twice (retreatment) with an 8-week treatment pause in between. Blood was collected to evaluate viral parameters. Nine weeks after the last treatment, liver samples were collected to perform phenotyping, bulk RNA-sequencing, and immunohistochemistry. RESULTS: Independent of HBsAg baseline levels, treatment with HBV-siRNA induced a rapid decline in HBsAg levels, which then plateaued before gradually rebounding 12 weeks after treatment stopped. A second cycle of HBV-siRNA treatment induced a further decline in HBsAg levels in serum and the liver, reaching undetectable levels and preventing rebound when baseline levels were 103 IU/mL. This was accompanied with a significant increase in inflammatory macrophages in the liver and significant upregulation of regulatory T-cells and T-cells expressing immune checkpoint receptors. CONCLUSIONS: Retreatment induced an additional decline in HBsAg levels, reaching undetectable levels when baseline HBsAg levels were 3log10 or less. This correlated with T-cell activation and upregulation of Trem2.
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Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Animales , Ratones , Virus de la Hepatitis B/genética , ARN Interferente Pequeño/genética , Hígado , Retratamiento , ADN Viral , Antivirales/uso terapéutico , Glicoproteínas de Membrana , Receptores InmunológicosRESUMEN
Eagle's syndrome, a condition associated with the elongation of the styloid process or calcification of the stylohyoid ligament, is clinically characterized by throat and neck pain radiating into the mastoid region. The diagnosis can be made through a thorough history, correct clinical and pathological correlation and radiographic examination. The elongated styloid process can be treated conservatively or surgically. Conservative treatment options include transpharyngeal injections of steroids and lignocaine, nonsteroidal anti-inflammatory drugs, diazepam, and the application of heat. The surgical management of Eagle's syndrome consists of two major approaches: the transoral and the transcervical approaches. In this paper, we present a comparative study of two cases of classic bilateral elongated styloid process syndrome, treated with transcervical styloidectomy and transoral styloidectomy, their surgical time, intraoperative difficulties and complications, and recovery time. In conclusion, the management of Eagle's syndrome requires a comprehensive approach that includes a thorough preoperative evaluation of the length of the styloid process via imaging and digital palpation. The choice of surgical approach, whether extraoral or transpharyngeal, should be based on factors such as the surgeon's experience and the patient's comorbidities, as well as the length and palpability of the styloid process. Our comparative study of two cases treated with transcervical and transoral styloidectomy demonstrated that the extraoral method offers a direct and well-controlled approach for excessive styloid processes, while the transpharyngeal approach is preferred for cases where the process can be easily identified by palpation. Therefore, proper patient selection and preoperative planning are essential to achieving successful outcomes with minimal complications.
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Introduction The most frequently used local anesthesia administration techniques for extraction of lower teeth in dentistry are local infiltration and inferior alveolar nerve block. Therapeutic extraction of premolars is the most common procedure done for patients undergoing orthodontic treatment. Inferior alveolar nerve block has been used most commonly for extraction of mandibular posterior teeth; however, it is a technique-sensitive procedure and has complications such as facial nerve palsy, trismus, and long duration of anesthesia. Local infiltration is a simple and effective technique for anesthetizing teeth prior to extraction. Aim This study aims to compare the efficacy of local anesthesia administered through inferior alveolar nerve block and local infiltration techniques for extraction of lower premolar teeth for orthodontic purposes. Materials and methods A prospective comparative study was conducted for a period of six months in which a total of 100 patients who were referred for extraction of lower premolar teeth for orthodontic purposes were included. Among 100 patients, 60 patients were males, and 40 patients were females with a mean age of 16.5 ± 1.25 years. The patients were equally divided into two groups, in which Group 1 received local infiltration and Group 2 received an inferior alveolar nerve block. The outcome parameters assessed were pain during injection and pain during extraction using the visual analog scale (VAS) score and Wong-Baker Faces Pain Rating Scale score. Statistical analysis was done using an independent sample t-test with SPSS version 23.0 software (IBM Corp., Armonk, NY) at p < 0.05 considered statistically significant. Results The difference in mean pain scores between the two groups during injection as assessed using the Faces Pain Rating Scale (p = 0.001) and VAS (p = 0.001) was statistically significant, with the infiltration group exhibiting less pain than the inferior alveolar nerve block group. The difference in mean pain scores between the two groups during extraction as assessed using the Faces Pain Rating Scale (p = 0.308) and VAS (p = 0.350) was statistically not significant, with the infiltration group not significantly differing from the inferior alveolar nerve block group. Thus, the pain during local infiltration was significantly lesser when compared to the inferior alveolar nerve block during injection, whereas pain perception during extraction was similar in patients with both injection techniques. Conclusion It can be concluded that local infiltration is less painful for the patient during injection and as efficacious as nerve block for extraction, hence local infiltration can be routinely used for lower premolar orthodontic extractions.
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Introduction Oral and maxillofacial surgeons frequently perform the removal of impacted mandibular third molars. The success of this surgical intervention depends on meticulous surgical technique and the use of appropriate irrigants to minimize complications in the postoperative period. Aim The aim of this study was to evaluate the efficacy of four different irrigation solutions (povidone-iodine, metronidazole, chlorhexidine gluconate (CHX), and normal saline) on postoperative sequelae like pain, trismus, swelling, and alveolar osteitis following surgical extraction of the impacted mandibular third molars. Materials and methods The current research was a randomized study carried out at Saveetha Dental College and Hospital in Chennai, India, from December 2022 to March 2023. The study population consisted of 112 participants who were referred to the Oral and Maxillofacial Surgery for the surgical removal of impacted mandibular third molars. The population was divided into four groups, with 28 in each group. They were categorized as A, B, C, and D based on the final irrigation solution used after surgical removal of the impacted teeth. In group A, patients received 0.5% povidone-iodine as the final irrigation solution; group B received 1% metronidazole; group C received 0.12% chlorhexidine gluconate (CHX); and group D received 0.9% normal saline. Patients were examined on the first and seventh postoperative days to assess pain, swelling, trismus, and alveolar osteitis. The results were analyzed with SPSS Statistics for Windows, Version 23.0 (Released 2015; IBM Corp., Armonk, New York, United States) software for Windows (Microsoft Corporation, Redmond, Washington, United States). A p-value less than 0.05 was considered statistically significant. Results Group B experienced significantly less pain than groups A, C, and D on the first and seventh postoperative days (p<0.05). The facial swelling was significantly less on the first and seventh postoperative day in group B compared to groups A, B, and D (p<0.05). There was no statistically significant variation observed in trismus (mouth opening) across the groups on both the first postoperative and seventh postoperative days. The presence of alveolar osteitis was seen in groups A, C, and D, but no instances were reported in group B. Conclusion It can be concluded that among the four irrigation solutions used in the lower third molar surgery, metronidazole irrigation solution yielded the best results in terms of less pain, swelling, and alveolar osteitis followed by chlorhexidine. There was no difference between povidone-iodine irrigation and normal saline irrigation on the postoperative sequelae. Postoperative trismus does not depend on the irrigation solution used in the third molar surgery.
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The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a rapid response by the scientific community to further understand and combat its associated pathologic etiology. A focal point has been on the immune responses mounted during the acute and post-acute phases of infection, but the immediate post-diagnosis phase remains relatively understudied. We sought to better understand the immediate post-diagnosis phase by collecting blood from study participants soon after a positive test and identifying molecular associations with longitudinal disease outcomes. Multi-omic analyses identified differences in immune cell composition, cytokine levels, and cell subset-specific transcriptomic and epigenomic signatures between individuals on a more serious disease trajectory (Progressors) as compared to those on a milder course (Non-progressors). Higher levels of multiple cytokines were observed in Progressors, with IL-6 showing the largest difference. Blood monocyte cell subsets were also skewed, showing a comparative decrease in non-classical CD14-CD16+ and intermediate CD14+CD16+ monocytes. Additionally, in the lymphocyte compartment, CD8+ T effector memory cells displayed a gene expression signature consistent with stronger T cell activation in Progressors. Importantly, the identification of these cellular and molecular immune changes occurred at the early stages of COVID-19 disease. These observations could serve as the basis for the development of prognostic biomarkers of disease risk and interventional strategies to improve the management of severe COVID-19.
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BACKGROUND: Suppression of HBV DNA, inhibition of HBV surface (HBsAg) production and therapeutic vaccination to reverse HBV-specific T-cell exhaustion in chronic HBV patients are likely required to achieve a functional cure. In the AAV-HBV mouse model, therapeutic vaccination can be effective in clearing HBV when HBsAg levels are low. Using a single-cell approach, we investigated the liver immune environment with different levels of HBsAg and sustained HBsAg loss through treatment with a GalNAc-HBV-siRNA followed by therapeutic vaccination. METHODS: AAV-HBV-transduced C57BL/6 mice were treated with GalNAc-HBV-siRNA to lower HBsAg levels and then vaccinated using a DNA vaccine. We used single-cell RNA and V(D)J sequencing to understand liver immune microenvironment changes. RESULTS: GalNAc-HBV-siRNA, followed by therapeutic vaccination, achieved sustained HBsAg loss in all mice. This was accompanied by CD4 follicular helper T-cell induction, polyclonal activation of CD8 T cells and clonal expansion of plasma cells that were responsible for antibody production. CONCLUSIONS: This study provides novel insights into liver immune changes at the single-cell level, highlighting the correlation between induced reduction of HBsAg levels and clonal expansion of CD4, CD8 T cells and plasma cells in the liver upon HBV siRNA and subsequent therapeutic vaccination.