Effects of Proton Pump Inhibitors and H2 Receptor Antagonists on the Ileum Motility

Objectives. To investigate the effects of proton pump inhibitors (PPIs) and H2 receptor antagonists on ileum motility in rats with peritonitis and compare changes with control group rats. Methods. Peritonitis was induced by cecal ligation and puncture in 8 rats. Another of 8 rats underwent a sham operation and were accepted as controls. Twenty-four hours later after the operation, the rats were killed, and their ileum smooth muscle was excised and placed in circular muscle direction in a 10 mL organ bath. Changes in amplitude and frequency of contractions were analyzed before and after PPIs and H2 receptor blockers. Results. PPI agents decreased the motility in a dose-dependent manner in ileum in both control and intraabdominal sepsis groups. While famotidine had no significant effect on ileum motility, ranitidine and nizatidine enhanced motility in ileum in both control and intraabdominal sepsis groups. This excitatory effect of H2 receptor antagonists and inhibitor effects of PPIs were significantly high in control group when compared to the peritonitis group. The inhibitor effect of pantoprazole on ileum motility was significantly higher than the other two PPI agents. Conclusions. It was concluded that H2 receptor antagonists may be more effective than PPIs for recovering the bowel motility in the intraabdominal sepsis situation

ADAMTS4 and ADAMTS5 Knockout Mice Are Protected from Versican but Not Aggrecan or Brevican Proteolysis during Spinal Cord Injury

The chondroitin sulfate proteoglycans (CSPGs) aggrecan, versican, and brevican are large aggregating extracellular matrix molecules that inhibit axonal growth of the mature central nervous system (CNS). ADAMTS proteoglycanases, including ADAMTS4 and ADAMTS5, degrade CSPGs, representing potential targets for ameliorating axonal growth-inhibition by CSPG accumulation after CNS injury. We investigated the proteolysis of CSPGs in mice homozygous for Adamts4 or Adamts5 null alleles after spinal cord injury (SCI). ADAMTS-derived 50-60 kDa aggrecan and 50 kDa brevican fragments were observed in Adamts4−/−, Adamts5−/−, and wt mice but not in the sham-operated group. By contrast Adamts4−/− and Adamts5−/− mice were both protected from versican proteolysis with an ADAMTS-generated 70 kDa versican fragment predominately observed in WT mice. ADAMTS1, ADAMTS9, and ADAMTS15 were detected by Western blot in Adamts4−/− mice' spinal cords after SCI. Immunohistochemistry showed astrocyte accumulation at the injury site. These data indicate that aggrecan and brevican proteolysis is compensated in Adamts4−/− or Adamts5−/− mice by ADAMTS proteoglycanase family members but a threshold of versican proteolysis is sensitive to the loss of a single ADAMTS proteoglycanase during SCI. We show robust ADAMTS activity after SCI and exemplify the requirement for collective proteolysis for effective CSPG clearance during SCI

Prognostic factors for regorafenib treatment in patients with refractory metastatic colorectal cancer: A real-life retrospective multi-center study

Regorafenib, an oral multikinase inhibitor, has improved survival in metastatic colorectal cancer (mCRC) patients who have progressed on standard therapies. Our study aimed to evaluate prognostic factors influencing regorafenib treatment and assess the optimal dosing regimen in a real-life setting. We retrospectively analysed 263 patients with mCRC from multiple medical oncology clinics in Turkey. Treatment responses and prognostic factors for survival were evaluated using univariate and multivariate analysis. Of the patients, 120 were male, and 143 were female; 28.9% of tumors were located in the rectum. RAS mutations were present in 3.0% of tumors, while BRAF, K-RAS, and N-RAS mutations were found in 3.0%, 29.7%, and 25.9% of tumor tissues, respectively. Dose escalation was preferred in 105 (39.9%) patients. The median treatment duration was 3.0 months, with an objective response rate (ORR) of 4.9%. Grade ≥ 3 treatment-related toxicity occurred in 133 patients, leading to discontinuation, interruption, and modification rates of 50.6%, 43.7%, and 79.0%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.0 and 8.1 months, respectively. RAS/RAF mutation (hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.1-2.3; P = 0.01), pretreatment carcinoembryonic antigen (CEA) levels (HR 1.6, 95% CI 1.1-2.3; P = 0.008), and toxicity-related treatment interruption or dose adjustment (HR 1.6, 95% CI 1.1-2.4; P = 0.01) were identified as independent prognostic factors for PFS. Dose escalation had no significant effect on PFS but was associated with improved OS (P < 0.001). Independent prognostic factors for OS were the initial TNM stage (HR 1.3, 95% CI 1.0-1.9; P = 0.04) and dose interruption/adjustment (HR 0.4, 95% CI 0.2-0.9; P = 0.03). Our findings demonstrate the efficacy and safety of regorafenib. Treatment line influences the response, with dose escalation being more favorable than adjustment or interruption, thus impacting survival

The impact of COVID-19 on emerging stock markets

The goal of this study is to investigate the impact of COVID-19 on emerging stock markets over the period March 10 – April 30, 2020. Findings reveal that the negative impact of pandemic on emerging stock markets has gradually fallen and begun to taper off by mid-April. In terms of regional classification, the impact of the outbreak has been the highest in Asian emerging markets whereas emerging markets in Europe have experienced the lowest. We also find that official response time and the size of stimulus package provided by the governments matter in offsetting the effects of the pandemic

Peptic Ulcer Perforation in Elderly: 10 years' Experience of a Single Institution

Background: Peptic ulcer perforation (PUP) constitutes a unique situation characterized by severe pain, leading almost every patient with this complication to seek help in the hospital. However, clinical features of PUP in elderly patients are different from those of young or in adult patients; indeed, symptoms of PUP may be atypical in old age. Materials and methods: This was a retrospective study of patients who underwent emergency surgery for PUP between 2002 and 2012. The patients were divided into two age groups. Medical conditions of the patients that may have had an effect on the perforation, such as age, gender, concomitant disease, use of drugs, presence of Helicobacter pylori infection, characteristic of pain (vague abdominal pain or severe epigastric pain), smoking status, and duration symptoms at the time of admission, were evaluated. Results: A total of 261 patients were included in this retrospective study. Group I (n = 202) was composed of adults (age <65 years), Group II (n = 59) was composed of geriatric patients (age ≥65 years). Male dominancy was observed in both groups. Primary closure of the perforation was the most common procedure performed. Hypertension (18.3 % and 52.5%, respectively), and diabetes mellitus (11.9% and 15.3%, respectively) were the most frequent comorbidities in both groups, whereas mortality and morbidity rates were higher in elderly group. Conclusions: PUP is a serious condition, particularly in geriatric age requiring emergency surgical management. Primary closure of the perforation was the most common procedure performed in our series

Oxidative stress markers in laparoscopic vs. open appendectomy for acute appendicitis: A double-blind randomized study

Background: Oxidative stress is a complicated process, which was defined as an increase in prooxidants and decrease in antioxidants caused by various mechanisms, including inflammation and surgical trauma. The association between acute appendicitis and oxidative stress has been showed in previous studies. However, comparison of oxidative stress in laparoscopic or open appendectomy (OA) has not been established. Patients and Methods: Patients who were diagnosed as acute appendicitis between October 2012 and January 2013 were randomized to open (OA, n = 50) and laparoscopic appendectomy (LA, n = 50). Blood samples for oxidative stress markers (total oxidant status [TOS] and total antioxidant status [TAS]), C-reactive protein (CRP) and white blood cells (WBC's) were collected just before the surgery and 24 h after surgery. Results: There were no differences in preoperative values of WBC and CRP between LA and OA groups (P = 0.523 and 0.424), however, in postoperative 24th h, CRP was reduced in LA group (P = 0.031). There were no differences in preoperative levels of TOS, TAS, and oxidative stress index (OSI) between LA and OA groups. In the postoperative 24th h, TOS and OSI were found to be significantly higher in OA group when compared to LA group (P = 0.017 and 0.002) whereas no difference was detected in TAS level in the postoperative 24th h (P = 0.172). Conclusions: This double-blind, randomized clinical trial provides evidence that LA for uncomplicated appendicitis is associated with significantly lower oxidative stress compared with OA. Some of the advantages of LA may be attributed to the significant reduction of oxidative stress in these patients

Altered spontaneous contractions of the ileum by anesthetic agents in rats exposed to peritonitis

AIM: To investigate in vitro effects of propofol, midazolam and dexmedetomidine, which are commonly used anaesthesic or sedatives, on spontaneous contractions of the ileum both in normal rats and those exposed to hyperdynamic peritonitis

Paralelní softwarová architektura příští generace kontinuální monitorace glukózy

Diabetes je rozšířené onemocnění. Zvýšená hladina glukózy v krvi dlouhodobě poškozuje mnoho orgánů. V krátkodobém výhledu jsou hypo- a hyperglykemické šoky akutní rizika. Pacienti s diabetem sledují hladinu glukózy pomocí kontinuálních systémů monitorování glukózy. Na jejím základě pacient užívá inzulín ke snížení hladiny glukózy v krvi. S pokrokem v oblasti mobilních počítačů se stále více pacientů s diabetem zabývá vlastními systémy, kterými si počítají dávku inzulínu. Povaha takového systému však vyvolává řadu obav v lékařství a softwarovém inženýrství. Proto jsme navrhnuli softwarovou architekturu pro další generaci monitorování glukózy. Navrhovaná architektura vychází z principů High-Level Architecture. Dekomponujeme celý monitorovací systém glukózy na základní prvky, které jsou buď reálné nebo simulované. Tím se navrhovaná architektura otevírá pro softwarové inženýrství, simulaci a výzkum tolerance chyb. Jako důkaz koncepce předkládáme ilustrativní konfiguraci implementované softwarové architektury, která predikuje budoucí hladiny glukózy v krvi 15 minut předem u pacientů s diabetem 1. typu. Všechny relativní chyby jsou v zónách A + B Clarkova a Parkesova chybového gridi, s téměř 95% chyb v nejbezpečnějších A-zónách obou gridů.Diabetes is a widespread disease. Elevated blood glucose levels continuously damage multiple organs in the long-term. In the shortterm, hypo- and hyperglycemic shocks are acute risks. Diabetes patients monitor their glucose level using continuous glucose monitoring systems. Based on their measured glucose level, the patient take insulin to lower their blood glucose level. With the advances in mobile computing, an increasing number of diabetes patients engage in self-built systems. They read their glucose levels from glucose-monitoring systems and calculate their insulin dosage based on the measured levels. The self-built nature of such a system raises a number of medical and software engineering concerns. Therefore, we propose a software architecture for the next generation of glucose monitoring. The proposed architecture builds on the principles of the high-level architecture. We decompose the entire glucose monitoring system to basic elements, which are either real or simulated. This opens the proposed architecture to software engineering, simulation, and fault-tolerance research. As a proof of concept, we present an illustrative configuration of the implemented software architecture that predicts future blood glucose levels 15 minutes in advance for type-1 diabetes patients. All relative errors are in the A+B zones of Clarke and Parkes error grids, with almost 95% of errors in the safest A-zones of both grids