Tobinpritchard5568

Based on engineered or bacterial nucleases, the development of genome editing technologies has opened up the possibility of directly targeting and modifying genomic sequences in almost all eukaryotic cells. Genome editing has extended our ability to elucidate the contribution of genetics to disease by promoting the creation of more accurate cellular and animal models of pathological processes and has begun to show extraordinary potential in a variety of fields, ranging from basic research to applied biotechnology and biomedical research. Recent progress in developing programmable nucleases, such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas-associated nucleases, has greatly expedited the progress of gene editing from concept to clinical practice. Here, we review recent advances of the three major genome editing technologies (ZFNs, TALENs, and CRISPR/Cas9) and discuss the applications of their derivative reagents as gene editing tools in various human diseases and potential future therapies, focusing on eukaryotic cells and animal models. Finally, we provide an overview of the clinical trials applying genome editing platforms for disease treatment and some of the challenges in the implementation of this technology.BACKGROUND Hesperidin (HPD) is a bioflavonoid found in citrus fruits. This study aimed to investigate the effects of HPD on cerebral morphology and cognitive behavior in sevoflurane anesthetized neonatal rats and the molecular mechanisms involved. MATERIAL AND METHODS Sixty neonatal Sprague-Dawley rats were divided into five groups, including the untreated control group, and the sevoflurane anesthesia groups untreated and treated with 25 mg/kg/day of HPD (HPD25), 50 mg/kg/day of HPD (HPD50), and 100 mg/kg/day of HPD (HPD100). The rat model was created by the administration of sevoflurane on the sixth postnatal day (P6) and for a further three days. Neonatal rats pre-treated with HPD for 19 days were given sevoflurane 30 minutes beforehand (P3 to P21). Rat hippocampal tissue specimens were investigated using the TUNEL assay for apoptosis. Hippocampal tissue homogenates underwent Western blot for the quantification of markers of neuroinflammation and oxidative stress. The neonatal rats were also investigated for behavior, learning, and memory. RESULTS HPD significantly reduced sevoflurane-induced neuronal apoptosis and protein expression of cleaved caspase-3, BAD, BAX, NF-kappaB, TNF-alpha, IL-6, and IL-1ß (p less then 0.05). HPD significantly increased the expression of Bcl-xL and Bcl-2 (p less then 0.05), and activated the PI3/Akt pathway. Learning and memory were significantly improved following HPD treatment (p less then 0.05). HPD treatment modulated the PI3/Akt/PTEN and NF-kappaB signaling pathways, and reduced oxidative stress (p less then 0.05). CONCLUSIONS In the sevoflurane anesthetized neonatal rat model, treatment with HPD reduced neuronal degeneration, hippocampal inflammation, and improvised memory, learning, and cognitive responses by modulating the PI3/Akt/PTEN and NF-kappaB signaling pathways.BACKGROUND Iliacus muscle abscess is a rare condition that frequently presents with nonspecific clinical symptoms. Abscesses in the iliacus muscle can arise from contiguous spread from adjacent structures or from distant sites via hematogenous or lymphatic routes. CASE REPORT We report a case of iliacus muscle abscess in a 22-year-old female microbiologist who presented to the emergency department with severe back pain and lower-extremity weakness after returning from a trip to Mexico. She was found to have urinary tract infection due to Salmonella. The patient was found to have left iliacus muscle abscess and septic arthritis of the sacroiliac joint. She was initially treated with piperacillin-tazobactam, vancomycin, and metronidazole, which were later switched to intravenous ceftriaxone and oral levofloxacin. She was successfully treated with antibiotics, with a complete resolution of the multiple tiny abscesses. CONCLUSIONS Iliacus muscle abscess presents with nonspecific symptoms that can mimic neurologic diseases such as spinal cord compression. A high index of suspicion is required to make an early diagnosis and initiate prompt treatment with antibiotics and abscess drainage, if accessible. A detailed history is essential to assess risk factors and establish likely causative organisms. Delay in treatment can lead to an increase in morbidity and mortality. Long-term follow-up is crucial, as the incidence of relapse is high.The central nervous system efficacy of dacomitinib, a key agent used in the treatment of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC), is unclear. We herein present our experience in the use of dacomitinib for the treatment of multiple brain metastatic lesions from EGFR-mutation-positive NSCLC in an elderly patient. ALK inhibitor clinical trial This case report demonstrates that dacomitinib can be an essential treatment option for patients with brain metastases.Objective Epidemic myalgia associated with human parechovirus type 3 (EM-HPeV3) is characterized by severe muscle pain and weakness on the limbs and trunk with a fever. No outbreak of EM-HPeV3 has been reported since 2016, and its clinical characteristics have not been sufficiently clarified. We herein report a series of EM-HPeV3 cases during the summer of 2019 and clarify the clinical characteristics of EM-HPeV3. Methods The diagnosis of EM-HPeV3 was established when the patients met both of the following criteria1 Patients developed severe muscle pain and weakness with a fever within a week, and those symptoms resolved within a month; and2 HPeV3 was detected in either a throat swab or fecal specimen of the patient by polymerase chain reaction. We reviewed the medical records of these patients retrospectively. Result Seven patients met the criteria (6 men and 1 woman, age 34 to 47 years old). Myalgia was observed on the thigh, lower legs, upper arms, and forearms in seven, five, two, and five patients, respectively. Four patients showed distal dominant weakness on the arms, while none of the patients showed proximal dominant weakness on the arms. Of the six patients examined, five showed reduced tendon reflexes on all four limbs. One patient showed slight myogenic change and increased insertion activities on needle electromyography. Conclusion We observed seven cases of EM-HPeV3 during the summer of 2019. Reduced tendon reflexes and distal dominancy of muscle pain and weakness on the arms are considered its distinct clinical features.