ABSTRACT
The use of tobacco products is one of the established contributors toward the development and spread of oral cancer. Additionally, recent research has indicated oral microbiome, infections with Human papilloma virus (HPV), Epstein-Barr virus (EBV), Candida as significant contributing factors to this disease along with lifestyle habits. Deregulation of cellular pathways envisaging metabolism, transcription, translation, and epigenetics caused by these risk factors either individually or in unison is manifold, resulting in the increased risk of oral cancer. Globally, this cancer continues to exist as one of the major causes of cancer-related mortalities; the numbers in the developing South Asian countries clearly indicate yearly escalation. This review encompasses the variety of genetic modifications, including adduct formation, mutation (duplication, deletion, and translocation), and epigenetic changes evident in oral squamous cell carcinoma (OSCC). In addition, it highlights the interference caused by tobacco products in Wnt signaling, PI3K/Akt/mTOR, JAK-STAT, and other important pathways. The information provided also ensures a comprehensive and critical revisit to non-tobacco-induced OSCC. Extensive literature survey and analysis has been conducted to generate the chromosome maps specifically highlighting OSCC-related mutations with the potential to act as spectacles for the early diagnosis and targeted treatment of this disease cancer.
Subject(s)
Carcinoma, Squamous Cell , Epstein-Barr Virus Infections , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Herpesvirus 4, Human/genetics , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/genetics , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Phosphatidylinositol 3-Kinases/genetics , Squamous Cell Carcinoma of Head and Neck , Head and Neck Neoplasms/complications , MutationABSTRACT
STUDY DESIGN: This is a retrospective cohort study. OBJECTIVE: The aim was to evaluate differences in readmission rates, number of debridements, and length of antibiotic therapy when comparing bacterial gram type following lumbar spinal fusion infections. SUMMARY OF BACKGROUND DATA: Surgical site infections (SSIs) after spinal fusion serve as a significant source of patient morbidity. It remains to be elucidated how bacterial classification of the infecting organism affects the management of postoperative spinal SSI. METHODS: Patients who underwent spinal fusion with a subsequent diagnosis of SSI between 2013 and 2019 were retrospectively identified. Patients were grouped based on bacterial infection type (gram-positive, gram-negative, or mixed infections). Poisson regressions analyzed the relationship between the type of bacterial infection and the number of irrigation and debridement (I&D) reoperations, and the duration of intravenous (IV) antibiotic therapy. Significance was set at P <0.05. RESULTS: Of 190 patients, 92 had gram-positive (G+) infections, 57 had gram-negative (G-) infections, and 33 had mixed (M) infections. There was no difference in 30 or 90-day readmissions for infection between groups (both P =0.051). Patients in the M group had longer durations of IV antibiotic treatment (G+: 46.4 vs. G-: 41.0 vs. M: 55.9 d, P =0.002). Regression analysis demonstrated mixed infections were 46% more likely to require a greater number of debridements ( P =0.001) and 18% more likely to require an increased duration of IV antibiotic therapy ( P <0.001), while gram-negative infections were 10% less likely to require an increased duration of IV antibiotic therapy ( P <0.001) when compared with G- infections. CONCLUSION: Spinal SSI due to a mixed bacterial gram type results in an increased number of debridements and a longer duration of IV antibiotics required to resolve the infection compared with gram-negative or gram-positive infections. LEVEL OF EVIDENCE: Level III.
Subject(s)
Bacterial Infections , Coinfection , Spinal Diseases , Spinal Fusion , Anti-Bacterial Agents/therapeutic use , Coinfection/drug therapy , Debridement , Humans , Retrospective Studies , Spinal Diseases/surgery , Spinal Fusion/adverse effects , Surgical Wound Infection/diagnosis , Surgical Wound Infection/drug therapy , Surgical Wound Infection/microbiologyABSTRACT
Early in the assembly of eukaryotes the branch-point binding protein (BBP, also called SF1) recognizes the branch point sequence, whereas the heterodimer U2AF, consisting of a 65 and a 35 kDa subunit, contacts the polypyrimidine tract and the AG splice site, respectively. Herein, we identified, cloned and expressed the Trypanosoma cruzi and Trypanosoma brucei U2AF35, U2AF65 and SF1. Trypanosomatid U2AF65 strongly diverged from yeast and human homologues. On the contrary, trypanosomatid SF1 was conserved but lacked the C-terminal sequence present in the mammalian protein. Yeast two hybrid approaches were used to assess their interactions. The interaction between U2AF35 and U2AF65 was very weak or not detectable. However, as in other eukaryotes, the interaction between U2AF65 and SF1 was strong. At the cellular level, these results were confirmed by fractionation and affinity-selection experiments in which SF1 and U2AF65 were affinity-selected with TAP tagged SF1, but not with TAP tagged U2AF35. Silencing one of the three factors affected growth and trans-splicing in the first step of this reaction. Trypanosomes are the first described example of eukaryotic cells in which the interaction of two expressed U2AF factors seemed to be very weak, or not detectable.
Subject(s)
Protein Interaction Mapping , Protozoan Proteins/metabolism , RNA Splicing , RNA-Binding Proteins/metabolism , Trypanosoma brucei brucei/physiology , Trypanosoma cruzi/physiology , Amino Acid Sequence , Animals , Cell Fractionation , Cloning, Molecular , Conserved Sequence , Gene Expression , Gene Silencing , Models, Molecular , Molecular Sequence Data , Protein Structure, Tertiary , Protozoan Proteins/genetics , RNA-Binding Proteins/genetics , Sequence Homology, Amino Acid , Trypanosoma brucei brucei/genetics , Trypanosoma cruzi/genetics , Two-Hybrid System TechniquesABSTRACT
Primary testicular non-Hodgkin's lymphoma was first described as a clinical entity in 1866. It is a rare disease and accounts for 1% of all non-Hodgkin's lymphoma, 2% of all extranodal lymphomas and 5% of all testicular neoplasms. It is the most common testicular tumor in males between sixty and eighty years of age. Testicular non-Hodgkin's lymphoma is unique in its high incidence of bilateral involvement (8-38%), and it is also the most common bilateral testicular tumor. Testicular non-Hodgkin's lymphoma has a predilection for spreading to non-contiguous extranodal sites, especially the central nervous system. Advanced-stage disease is usually managed with doxorubicin-based chemotherapy. For early-stage disease, opinion is divided regarding systemic chemotherapy following orchidectomy. The high incidence of spreading, especially to the central nervous system, leads to advocacy of the use of central nervous system prophylaxis with intrathecal chemotherapy. Prospective multicenter trials incorporating a large number of patients may lead to better guidelines for optimal management of this subtype of non-Hodgkin's lymphoma.
Subject(s)
Lymphoma, Non-Hodgkin/therapy , Testicular Neoplasms/therapy , Central Nervous System Neoplasms/prevention & control , Doxorubicin/therapeutic use , Humans , Lymphoma, Non-Hodgkin/complications , Lymphoma, Non-Hodgkin/etiology , Male , Orchiectomy , Testicular Neoplasms/complications , Testicular Neoplasms/etiology , Time FactorsABSTRACT
Primary testicular non-Hodgkin's lymphoma was first described as a clinical entity in 1866. It is a rare disease and accounts for 1 percent of all non-Hodgkin's lymphoma, 2 percent of all extranodal lymphomas and 5 percent of all testicular neoplasms. It is the most common testicular tumor in males between sixty and eighty years of age. Testicular non-Hodgkin's lymphoma is unique in its high incidence of bilateral involvement (8-38 percent), and it is also the most common bilateral testicular tumor. Testicular non-Hodgkin's lymphoma has a predilection for spreading to non-contiguous extranodal sites, especially the central nervous system. Advanced-stage disease is usually managed with doxorubicin-based chemotherapy. For early-stage disease, opinion is divided regarding systemic chemotherapy following orchidectomy. The high incidence of spreading, especially to the central nervous system, leads to advocacy of the use of central nervous system prophylaxis with intrathecal chemotherapy. Prospective multicenter trials incorporating a large number of patients may lead to better guidelines for optimal management of this subtype of non-Hodgkin's lymphoma.
O linfoma primário do testículo (LPT) foi descrito como uma entidade clínica pela primeira vez em 1866. É uma doença rara e corresponde a 1 por cento de todos os linfomas não-Hodgkin, 2 por cento de todos os linfomas extranodais e 5 por cento de todos as neoplasias testiculares. É o tumor testicular mais comum em homens entre 60 e 80 anos de idade. LPT é único em sua elevada incidência de envolvimento bilateral (8-38 por cento), sendo o tumor testicular bilateral mais comum. Tem uma predileção por disseminação para regiões extranodais não-contíguas, especialmente para o sistema nervoso central (SNC). Estágios avançados da doença são usualmente tratados com quimioterapia à base de doxorubicina. Para os estágios mais precoces, as opiniões são divergentes quanto à quimioterapia associada à orquiectomia. A alta prevalência de disseminação, especialmente para o SNC, sugere o uso de quimioterapia intratecal como profilaxia. Estudos prospectivos multicêntricos incluindo um grande número de pacientes poderiam resolver a questão com relação ao manejo deste subtipo de linfoma não-Hodgkin.