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Indeed, mice deficient in ulk1 in cardiomyocytes and the sinus node also showed early onset of slow atrial impulse conduction with frequent sinus pauses and upregulated CaMKII oxidation following Ang II infusion similar to that seen with PTEN deficiency, or treatment with insulin sensitizers. To further elucidate the role of autophagy in sinus node dysfunction, we treated mice with a peptide D-Tat-beclin1 that enhanced autophagy, which significantly abrogated the frequent sinus pauses and accumulation of oxidized CaMKII induced by insulin sensitizers treatment, or PTEN deficiency in hypertensive animals. Together, these findings provide clear evidence of the detrimental cardiac effects of insulin sensitization that occurs through failure of autophagy-mediated proteolytic clearance.Acetaminophen is known to be generally safe, and the occurrence of anaphylaxis due to acetaminophen has been rarely reported. We report a case of acetaminophen-induced anaphylaxis in a healthy male subject who participated in a clinical trial on the pharmacokinetics of ibandronate. The subject had not experienced an allergic reaction to acetaminophen prior to this incident. The patient received 1300 mg oral acetaminophen at about 12 hours after receiving 150 mg ibandronate. After about 10 minutes, the subject developed whole-body urticaria and hypotension. The temporal association suggested that the anaphylaxis was due to acetaminophen and not ibandronate. Anaphylaxis could occur due to acetaminophen even in the absence of allergic reactions in the first dosing.We have streamlined known in vitro methods used to predict the clearance (CL) of small molecules in humans in this tutorial. There have been many publications on in vitro methods that are used at different steps of human CL prediction. The steps from initial intrinsic CL measurement in vitro to the final application of the well-stirred model to obtain predicted hepatic CL (CLH) are somewhat complicated. Except for the experts on drug metabolism and PBPK, many drug development scientists found it hard to figure out the entire picture of human CL prediction. To help readers overcome this barrier, we introduce each method briefly and demonstrate its usage in the chain of related equations destined to the CLH. Despite efforts in the laboratory steps, huge in vitro (predicted CLH)-in vivo (observed CLH) discrepancy is not rare. A simple remedy to this discrepancy is to correct human predicted CLH using the ratio of in vitro-in vivo CLH obtained from animal species.Exposure of the angle of His (AOH) with liver retraction is one of the key processes during laparoscopic sleeve gastrectomy (LSG). A new internal liver retractor, the LiVac (LiVac, Pty Ltd.) has recently been introduced. This study was conducted to evaluate the feasibility of the LiVac in LSG. We applied the LiVac in 20 patients who received LSG. The feasibility was assessed by exposure of the AOH, operation time, complications, and changes of aspartate transaminase and alanine transaminase. In all 20 patients, exposure of the AOH was successful. The mean operation time was 88 minutes. The changes in preoperative and postoperative aspartate transaminase and alanine transaminase levels were 18.6 and 9.1 U/L, respectively. There were no related morbidities. In LSG, exposure of the AOH using the LiVac was technically feasible.
Autologous adipose tissue-derived stem cells (ASCs) have been proposed for patients with refractory Crohn disease, but research is lacking in pediatric patients. This Phase IV study evaluated the efficacy and safety of ASCs in children with refractory Crohn's fistulae.
Patients with a refractory Crohn's fistula who did not have conventional therapy for more than 3 months or with a recurrent complex Crohn's fistula were included. All patients were at least 14 years old. Patients with infection, poor condition, or active Crohn disease with a disease activity index of 450 and above were excluded. Five patients were treated with ASCs from 2014 to 2015 in Asan Medical Center. ASC administration was adjusted according to fistula size (1 mL per cm
). We evaluated the efficacy and safety 8 weeks after injection and followed patients for 6 months.
Fistulae were healed in 4 patients by 8 weeks after ASC injection. Of these 4 patients, 1 had complete fistula closure and sustainability after 6 months. The other 3 with healing effects had less than 50% fistula closure by 6 months. Ruxolitinib None of these 4 patients have persistent fistulae. One patient had no healing effect, and seton ligation was performed 8 months after ASC injection. There were no adverse effects related to ASC administration.
ASC therapy is a simple and well-tolerated therapeutic option for children with refractory Crohn's complex fistulae. Complete closure was well-sustained. However, more data from a larger number of patients are needed.
ASC therapy is a simple and well-tolerated therapeutic option for children with refractory Crohn's complex fistulae. Complete closure was well-sustained. However, more data from a larger number of patients are needed.
Traumatic kidney injury can be treated surgically or nonsurgically. Nonsurgical treatment options include angiography, embolization, and conservative treatment. We aimed to identify factors that help in making clinical decisions on treatment plans for patients with traumatic kidney injury caused by blunt trauma.
The study included 377 patients aged ≥18 years with traumatic kidney injury caused by blunt abdominal trauma admitted to the emergency room of Wonju Severance Christian Hospital between January 2008 and July 2020. Medical records, laboratory test results, and computed tomography results were retrospectively reviewed.
Multivariable logistic analysis showed diastolic blood pressure at admission and disruption of Gerota's fascia were significantly associated with surgical treatment, and that perinephric hematoma rim distance was the only significant indicator favoring embolization. Receiver operating characteristic curve analysis showed that angiography and embolization should be considered when hematoma size exceeds 2.97 cm.
When a patient with traumatic kidney injury due to blunt trauma visits an emergency room, even when vital signs are stable, Gerota's fascia should be checked by computed tomography prior to deciding on surgical treatment, and angiographic embolization should be considered if perinephric hematoma rim distance exceeds 2.97 cm.
When a patient with traumatic kidney injury due to blunt trauma visits an emergency room, even when vital signs are stable, Gerota's fascia should be checked by computed tomography prior to deciding on surgical treatment, and angiographic embolization should be considered if perinephric hematoma rim distance exceeds 2.97 cm.
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