RESUMO
Efforts to battle antimicrobial resistance (AMR) are generally focused on developing novel antibiotics. However, history shows that resistance arises regardless of the nature or potency of new drugs. Here, we propose and provide evidence for an alternate strategy to resolve this problem: inhibiting evolution. We determined that the DNA translocase Mfd is an "evolvability factor" that promotes mutagenesis and is required for rapid resistance development to all antibiotics tested across highly divergent bacterial species. Importantly, hypermutator alleles that accelerate AMR development did not arise without Mfd, at least during evolution of trimethoprim resistance. We also show that Mfd's role in AMR development depends on its interactions with the RNA polymerase subunit RpoB and the nucleotide excision repair protein UvrA. Our findings suggest that AMR development can be inhibited through inactivation of evolvability factors (potentially with "anti-evolution" drugs)-in particular, Mfd-providing an unexplored route toward battling the AMR crisis.
Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/genética , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/efeitos dos fármacos , Evolução Molecular , Fatores de Transcrição/genética , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Animais , Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Células CACO-2 , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Desenho de Fármacos , Farmacorresistência Bacteriana/genética , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos Endogâmicos BALB C , Terapia de Alvo Molecular , Mutagênese/efeitos dos fármacos , Ligação Proteica , Especificidade da Espécie , Fatores de Tempo , Fatores de Transcrição/metabolismoRESUMO
PURPOSE: To document and explain the beneficial effects of non-invasive ventilation in correcting hypoxemia and hypoventilation in severe chronic obstructive pulmonary disease, during spinal anesthesia in the lithotomy position. CLINICAL FEATURES: A morbidly obese patient with severe chronic obstructive pulmonary disease underwent prostate surgery in the lithotomy position under spinal anesthesia. Hypoxemia was encountered during surgery, and a profound decrease of forced vital capacity associated with alveolar hypoventilation and ventilation/perfusion mismatching were observed. In the operating room, an M-mode sonographic study of the right diaphragm was performed, which confirmed that after spinal anesthesia and assuming the lithotomy position, there was a large decrease (-30%) in diaphragmatic excursion. Hypoxemia and alveolar hypoventilation were successfully treated with non-invasive positive pressure ventilation. CONCLUSIONS: Intraoperative application of non-invasive positive pressure ventilation improved diaphragmatic excursion and overall respiratory function, and reduced clinical discomfort in this patient.
Assuntos
Raquianestesia , Hipoventilação/terapia , Obesidade Mórbida/complicações , Respiração com Pressão Positiva/métodos , Alvéolos Pulmonares/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/complicações , Diafragma/diagnóstico por imagem , Humanos , Hipoventilação/complicações , Hipóxia/terapia , Complicações Intraoperatórias/terapia , Masculino , Pessoa de Meia-Idade , UltrassonografiaRESUMO
OBJECTIVE: We will review the contribution to the Medicare Fee Schedule (MFS) by the techniques of intensity of work per unit of time (IWPUT), the building block methodology (BBM), and the work accomplished by the American College of Surgeons General Surgery Coding & Reimbursement Committee (GSCRC) in using IWPUT/BBM to detect undervalued surgical procedures and recommend payment increases. SUMMARY BACKGROUND DATA: The MFS has had a major impact on surgeons' income since its introduction in 1992 by the Centers for Medicare and Medicaid (CMS) and additionally has been adopted for use by many commercial insurers. A major component of MFS is physician work, measured as the relative value of work (RVW), which has 2 components: time and intensity. These components are incorporated by: RVW = time x intensity. METHODS: This work formula can be rearranged to give the IWPUT, which has become a powerful tool to calculate the amount of RVW performed by physicians. Most procedures are valued by the total RVW in the global surgical package, which includes pre-, intra-, and postoperative care for a time after surgery. Summing these perioperative components into RVW is called the building block methodology (BBM). RESULTS: Using these techniques, the GSCRC increased the values for 314 surgery procedures during a recent CMS 5-year review, resulting in an increase to general surgeons of roughly 76 million dollars annually. CONCLUSIONS: The use of IWPUT/BBM has been instrumental to correct payment for undervalued surgical procedures. They are powerful methods to measure RVW across specialties and to solve reimbursement, compensation, and practice management problems facing surgeons.
Assuntos
Tabela de Remuneração de Serviços , Cirurgia Geral/economia , Medicare Part B/economia , Escalas de Valor Relativo , Centers for Medicare and Medicaid Services, U.S. , Humanos , Médicos/economia , Mecanismo de Reembolso , Estados UnidosRESUMO
Isoflurane anesthesia therapy (IAT) has been suggested to have persistent antidepressant activity. In a replication trial, IAT was performed in six patients who had a recurrence of a severe depressive episode, previously treated with ECT. In 21 of 26 IAT sessions, an isoelectric electroencephalogram lasting between 5 and 12 min was recorded. Clinical antidepressant activity was not observed. It is concluded that IAT is not an effective replacement for ECT in the treatment of major depressive disorders.