Cardiovascular risk factors: The effects of ageing and smoking on the immune system, an observational clinical study.

Currently immunomodulatory compounds are under investigation for use in patients with cardiovascular disease, caused by atherosclerosis. These trials, using recurrent cardiovascular events as endpoint, require enrollment of large patient groups. We investigated the effect of key risk factors for atherosclerosis development, ageing and smoking, on the immune system, with the objective to identify biomarkers differentiating between human populations, and potentially serving as endpoints for future phase 1B trials with immunomodulatory compounds. Blood was collected from young healthy volunteers (aged 18-25 years, n=30), young smokers (18-25 years, n=20), elderly healthy volunteers (>60 years, n=20), heavy smokers (>45 years, 15 packyears, n=11) and patients with stable coronary artery disease (CAD) (>60 years, n=27). Circulating immune cell subsets were characterized by flow cytometry, and collected plasma was evaluated by proteomics (Olink). Clear ageing effects were observed, mostly illustrated by a lower level in CD8+ and naïve CD4+ and CD8+ T cells, with an increase in CD4+ and CD8+ effector memory T cells in elderly healthy volunteers compared to young healthy volunteers. Heavy smokers showed a more inflammatory cellular phenotype, especially a shift in Th1/Th2 ratio: higher Th1 and lower Th2 percentages compared to young healthy volunteers. A significant decrease in circulating atheroprotective oxLDL-specific IgM was found in patients with CAD compared to young healthy volunteers. Elevated pro-inflammatory and chemotactic proteins TREM1 and CCL11 were observed in elderly volunteers compared to young volunteers. In addition, heavy smokers had an increase in pro-inflammatory cytokine IL-6 and lysosomal protein LAMP3. These data show that ageing and smoking are associated with an inflammatory immunophenotype, and that heavy smokers or aged individuals may serve as potential populations for future clinical trials investigating immunomodulatory drugs targeted for cardiovascular disease.

Towards remote monitoring in pediatric care and clinical trials-Tolerability, repeatability and reference values of candidate digital endpoints derived from physical activity, heart rate and sleep in healthy children.

BACKGROUND: Digital devices and wearables allow for the measurement of a wide range of health-related parameters in a non-invasive manner, which may be particularly valuable in pediatrics. Incorporation of such parameters in clinical trials or care as digital endpoint could reduce the burden for children and their parents but requires clinical validation in the target population. This study aims to determine the tolerability, repeatability, and reference values of novel digital endpoints in healthy children. METHODS: Apparently healthy children (n = 175, 46% male) aged 2-16 were included. Subjects were monitored for 21 days using a home-monitoring platform with several devices (smartwatch, spirometer, thermometer, blood pressure monitor, scales). Endpoints were analyzed with a mixed effects model, assessing variables that explained within- and between-subject variability. Endpoints based on physical activity, heart rate, and sleep-related parameters were included in the analysis. For physical-activity-related endpoints, a sample size needed to detect a 15% increase was calculated. FINDINGS: Median compliance was 94%. Variability in each physical activity-related candidate endpoint was explained by age, sex, watch wear time, rain duration per day, average ambient temperature, and population density of the city of residence. Estimated sample sizes for candidate endpoints ranged from 33-110 per group. Daytime heart rate, nocturnal heart rate and sleep duration decreased as a function of age and were comparable to reference values published in the literature. CONCLUSIONS: Wearable- and portable devices are tolerable for pediatric subjects. The raw data, models and reference values presented here can be used to guide further validation and, in the future, clinical trial designs involving the included measures.

Glucose pump test can be used to measure blood flow rate of native arteriovenous fistula in chronic hemodialysis.

PURPOSE: In chronic hemodialysis patients, the low flow of vascular access may leads to inadequate dialysis, increased rate of hospitalization, morbidity, and mortality. It was found that surveillance should be performed for native arteriovenous (AV) should not be performed for AV graft in various studies. However, surveillance was done in graft AV fistulas in most studies. Doppler ultrasonography (US) was suggested for surveillance of AV fistulas by the last vascular access guideline of National Kidney Foundation Disease Outcomes Quality Initiative (NKF KDOQI). The aim of study is to determine whether glucose pump test (GPT) is used for surveillance of native AV fistulas by using Doppler US as reference. METHODS: In 93 chronic hemodialysis patients with native AV fistula, blood flow rates were measured by Doppler US and GPT. For GPT, glucose was infused to 16 mL/min by pump and was measured at basal before the infusion and 11 s after the start of the infusion by glucometer. Doppler US was done by an expert radiologist. Used statistical tests were Mann-Whitney U test, Friedman test, regression analysis, and multiple regression analysis. RESULTS: Median values of blood flow rates measured by GPT (707 mL/min) and by Doppler US (700 mL/min) were not different (Z = 0.414, P = 0.678). Results of GPT and Doppler US measurements were positive correlate by regression analysis. The mean GPT value of diabetic patients (n = 39; 908 mL/min) was similar to that of nondiabetic patients (n = 54; 751 mL/min; Z = 1.31, P = 0.188). GPT values measured at three different dialysis session did not differ from each other that by Friedman test (F = 0.92, P = 0.39). This showed that GPT was stable and reliable. CONCLUSIONS: Glucose pump test can be used to measure blood flow rate of native AV fistula. GPT is an accurate and reliable test.

Treatment of industrial estate wastewater by the application of electrocoagulation process using iron electrodes.

In this study electrocoagulation (EC) of industrial estate wastewater taken from the inlet of wastewater treatment plant was investigated using sacrificial iron electrodes. Employing a pole changer to homogenous consumption of electrodes, studies on the parameters such as current density, supporting electrolyte concentration and initial pH, which have significant effects on COD removal and hence the energy consumption, were performed. Hydrogen peroxide was used in different concentrations to observe its effects on COD removal efficiency and the energy consumption. Sludge productions were also calculated for all experiments. COD removal efficiency of ∼92% was obtained at the best experimental conditions (i = 30 mA/cm2, SE = 3 mM Na2SO4, pH = original pH (∼6) of the wastewater, 1500 mg/L H2O2) with an energy cost of €3.41/m3 wastewater treated and the sludge production of 5.45 g per g COD removed.

Disturbed endometrial NF-κB expression in women with recurrent implantation failure.

OBJECTIVE: This study was planned to investigate whether expression levels of endometrial NF-κB1 and NFκB p65 changes in women with recurrent implantation failure (RIF). PATIENTS AND METHODS: The study group consists of 30 RIF patients having at least three previous failed IVF cycles. The control group comprises of 30 patients having one or no previous failed attempt. Endometrial samples were obtained from all participants during hysteroscopy at the late follicular phase. Samples underwent ELISA analysis and immunohistochemical staining. The semi-quantitative H-Score method was used for analyzing the intensity of endometrial NF-κB p65 expression. RESULTS: The concentrations of endometrial NF-κB1 were found to be significantly increased when compared to control subjects. Likewise, significantly increased NF-κB p65 immunoreactivity was detected in the cytoplasm of luminal and glandular epithelial cells. The H-Score of NF-κB p65 in RIF women was found to be significantly increased when compared to control group. CONCLUSIONS: Increased levels of NF-κB1 and NF-κB p65 in the endometrium of RIF women can disturb physiological inflammation which is known to be positive modulator of endometrial receptivity.

The role of S100B protein, neuron-specific enolase, and glial fibrillary acidic protein in the evaluation of hypoxic brain injury in acute carbon monoxide poisoning.

The main purpose of this study was to assess the role of S100B protein, neuron-specific enolase (NSE), and glial fibrillary acidic protein (GFAP) in the evaluation of hypoxic brain injury in acute carbon monoxide (CO)-poisoned patients. This cross-sectional study was conducted among the patients with acute CO poisoning who referred to the emergency department in a 1-year period. Serum levels of S100B protein, NSE, and GFAP were determined on admission. A total of 55 CO-poisoned patients (mean age ± standard deviation, 45 ± 20.3 years; 60% women) were included in the study. The control group consisted of 25 healthy adults. The patients were divided into two groups according to whether they were conscious or unconscious. The serum levels of S100B, NSE, and GFAP were higher in patients than that in the control group. There was no significant difference between unconscious and conscious patients with respect to these markers. There was a statistically significant difference between the conscious and unconscious patients and the control group in terms of S100B and NSE levels. There was also a statistically significant difference between the unconscious patients and the control group in terms of GFAP levels. Increased serum S100B, NSE, and GFAP levels are associated with acute CO poisoning. These biomarkers can be useful in assessing the clinical status of patients with CO poisoning.

Therapeutic effect of magnesium sulphate on carbon monoxide toxicity-mediated brain lipid peroxidation.

BACKGROUND: Carbon monoxide (CO) toxicity primarily results from cellular hypoxia caused by impedance of oxygen delivery. Studies show that CO may cause brain lipid peroxidation and leukocyte-mediated inflammatory changes in the brain. AIM: The aim of this study was to investigate whether magnesium sulphate could prevent or diminish brain lipid peroxidation caused by carbon monoxide toxicity in rats. MATERIALS AND METHODS: Fourty rats were divided into five groups of 8 rats each. Group l was not received any agent during the experiment. Group 2 was inhaled CO gas followed by intraperitoneally normal saline 30 minutes (min) later. Group 3 was inhaled CO gas followed by 100 mg/kg magnesium sulphate intraperitoneally 30 min later. Group 2 and Group 3 rats was undergone laparotomy and craniotomy while still under anesthesia at 6 hour, and tissue sample was obtained from the cerebrum. Group 4 was inhaled CO gas followed by intraperitoneally normal saline 30 min later. Group 5 was inhaled CO gas followed by 100 mg/kg magnesium sulphate intraperitoneally 30 min later. Group 4 and Group 5 rats was undergone laparotomy and craniotomy while still under anesthesia at 24 hour, and tissue sample was obtained from the cerebrum. RESULTS: Nitric oxide levels were no significantly different between all groups. Malonyldialdehyde levels increased in intoxication group (group 2) and decreased in treatment group (group 3). Activities of superoxide dismutase decreased in intoxication group (group 2) and increased in treatment group (group 3). Activities of catalase increased in intoxication group (group 2) and decreased in treatment group (group 3). Activities of glutathione peroxidase (GSH-Px) decreased in intoxication group (group 4) and increased in treatment group (group 5). CONCLUSIONS: CO poisoning caused significant damage, detected within the first 6 hours. Due to antioxidant enzymes, especially GSH-Px activity reaching the top level within 24th hours, significant oxidative damage was not observed. The protective effect against oxidative damage of magnesium sulfate has been identified within the first 6 hours.

Can exposure to manganese and extremely low frequency magnetic fields affect some important elements in the rat teeth?

BACKGROUND: Length and level of exposure to electromagnetic fields (EMFs) is increasing in association with the widespread use of electrical and electronic devices and technological progress. The undesirable effects of extremely low frequency magnetic fields (ELF-MFs) on health have attracted considerable interest. MATERIALS AND METHODS: Sixty-four four-month-old male Wistar rats divided into eight groups of eight rats each were used. Seven groups were exposed to varying dosages of manganese (Mn) and a 50 Hz magnetic field (MF) of approximately 1 mT, while the last group was set aside as the cage control group and not subjected to any procedure. This study was intended to investigate the interactions between the application of MF and Mn and the elements Ca, Zn, Mg, and P thought to be involved in caries, in rat teeth. RESULTS: Levels of Ca, Mg, Zn, and P in the experimental group rats were different to those in the control group. CONCLUSIONS: The results demonstrate that ELF-MF and Mn can have significant effects on levels of elements in rat teeth. Further experimental and epidemiological studies of ELF-MF and Mn are needed in order to evaluate their dental effects.

Hypothalamic obesity in children.

Hypothalamic obesity is an intractable form of obesity syndrome that was initially described in patients with hypothalamic tumours and surgical damage. However, this definition is now expanded to include obesity developing after a variety of insults, including intracranial infections, infiltrations, trauma, vascular problems and hydrocephalus, in addition to acquired or congenital functional defects in central energy homeostasis in children with the so-called common obesity. The pathogenetic mechanisms underlying hypothalamic obesity are complex and multifactorial. Weight gain results from damage to the ventromedial hypothalamus, which leads, variously, to hyperphagia, a low-resting metabolic rate; autonomic imbalance; growth hormone-, gonadotropins and thyroid-stimulating hormone deficiency; hypomobility; and insomnia. Hypothalamic obesity did not receive enough attention, as evidenced by rarity of studies in this group of patients. A satellite symposium was held during the European Congress of Obesity in May 2011, in Istanbul, Turkey, to discuss recent developments and concepts regarding pathophysiology and management of hypothalamic obesity in children. An international group of leading researchers presented certain aspects of the problem. This paper summarizes the highlights of this symposium. Understanding the central role of the hypothalamus in the regulation of feeding and energy metabolism will help us gain insights into the pathogenesis and management of common obesity.

Are we hitting immunity targets? The 2006 age-specific seroprevalence of measles, mumps, rubella, diphtheria and tetanus in Belgium.

Susceptibility to vaccine-preventable diseases in Belgium in 2006 was estimated from a serum survey. Immunoglobulins against measles, mumps, rubella (MMR) and diphtheria at all available ages (1-65 years), and against tetanus in >40-year-olds, were measured by ELISA. Age-standardized overall seronegativity for MMR was low (3·9%, 8·0%, 10·4%, respectively). However, the World Health Organization's targets for measles elimination were not met in 5- to 24-year-olds and about 1 in 7 women at childbearing age (15-39 years) were seronegative for rubella. In adults >40 years, tetanus immunity (87·2%, >0·16 IU/ml) largely exceeded diphtheria immunity (20-45%, >0·1 IU/ml). Despite free universal vaccination against MMR for more than 20 years and against diphtheria and tetanus for almost 60 years, our study revealed specific age groups remaining at risk for infection with these pathogens.

Navigation in laparoscopy--prototype research platform for improved image-guided surgery.

The manipulation of the surgical field in laparoscopic surgery, through small incisions with rigid instruments, reduces free sight, dexterity, and tactile feedback. To help overcome some of these drawbacks, we present a prototype research and development platform, CustusX, for navigation in minimally invasive therapy. The system can also be used for planning and follow-up studies. With this platform we can import and display a range of medical images, also real-time data such as ultrasound and X-ray, during surgery. Tracked surgical tools, such as pointers, video laparoscopes, graspers, and various probes, allow surgeons to interactively control the display of medical images during the procedure. This paper introduces navigation technologies and methods for laparoscopic therapy, and presents our software and hardware research platform. Furthermore, we illustrate the use of the system with examples from two pilots performed during laparoscopic therapy. We also present new developments that are currently being integrated into the system for future use in the operating room. Our initial results from pilot studies using this technology with preoperative images and guidance in the retroperitoneum during laparoscopy are promising. Finally, we shortly describe an ongoing multicenter study using this surgical navigation system platform.

Two cases of acute endosulfan toxicity.

BACKGROUND: Endosulfan is widely used in insect control and is absorbed by both humans and animals through the intestinal tract, the lungs, and the skin. Organochlorine insecticides are highly toxic compounds that are responsible for a number of severe intoxications worldwide, with several deaths. A 9-year analysis by one of Turkey's poison control centers reported that pesticide intoxications accounted for 8.8% of 25,572 poisoning calls, with 80.3% of them relating to insecticides and 19.7% concerning rodenticides. CASE REPORTS: We present two cases of unintentional exposure to endosulfan, one of which presented with neurological manifestations, liver toxicity, and required mechanical ventilation and emergent hemodialysis; the other had only neurological manifestations and liver toxicity. CONCLUSION: In cases of endosulfan poisoning, physicians must be aware of neurological manifestations, seizures, and severe metabolic acidosis. If severe metabolic acidosis is present, we suggest that hemodialysis may be an important intervention and should be performed early.

The prognostic importance of trauma scoring systems for blunt thoracic trauma.

BACKGROUND: Early identification and aggressive management of blunt thoracic trauma are essential to reduce the significant rates of morbidity and mortality. The aim of this study was to evaluate the independent predictive value of 5 different trauma scoring systems (Revised Trauma Score [RTS], Trauma and Injury Severity Score [TRISS], Injury Severity Score [ISS], Lung Injury Scale [LIS], and Chest Wall Injury Scale [CWIS]) with respect to prognostic factors such as tube thoracostomy duration, the need for mechanical support and thoracotomy, the length of hospital and ICU stay, morbid conditions, and deaths of patients with blunt thoracic trauma. METHODS: The records of 152 patients with blunt thoracic trauma were reviewed and data consisting of the patients' age and gender, blood pressure and respiratory rate on admission, the extent of chest wall and intrathoracic injury, types of associated injuries, Glasgow Coma Scale (GCS) scores, the need for mechanical support and thoracotomy, tube thoracostomy duration, length of hospital and ICU stay, morbid conditions, and deaths were collected. The relations between the trauma scoring systems and prognostic factors were evaluated by multivariate analysis. RESULTS: The analysis showed that only TRISS was an independent predictor of mortality and only LIS was an independent predictor of morbidity, the need for thoracotomy, and tube thoracostomy duration. TRISS and LIS were independent predictors of the length of ICU stay. ISS, CWIS, and LIS were independent predictors of the need for mechanical support. RTS, TRISS, ISS and LIS were independent predictors of the length of hospital stay. CONCLUSIONS: The LIS grade appeared to correlate with the severity of blunt thoracic injury and was found to be the most useful scoring system in predicting the outcomes of these patients.

Ergonomic design criteria for a novel laparoscopic tool handle with tactile feedback.

Laparoscopic surgery has many ergonomic disadvantages often not considered in the design of instruments. The poorly designed surgical tools produce inconveniences in both functional and cognitive aspects; including tactile sensation and visual-motor space coordination. The aim of this article is to find out how laparoscopic handle design can be improved by combining classical ergonomic guidelines with tactile feedback related to handle design. The article briefly discusses how the human hand and hand-held tools are used to perform tasks. An ergonomic handle for laparoscopic grasping, with a built-in tactile sensation display, is presented. Our review of laparoscopic instruments reveals important aspects for handle design. It is concluded that there is a need for greater awareness of ergonomic guidelines for users' sensory requirements when designing and manufacturing laparoscopic instruments.

Hemodynamic and tissue blood flow responses to long-term pneumoperitoneum and hypercapnia in the pig.

BACKGROUND: Increased peritoneal blood flow may influence the ability of cancer cells to adhere to and survive on the peritoneal surface during and after laparoscopic cancer surgery. Carbon dioxide (CO2) pneumoperitoneum is associated with a marked blood flow increase in the peritoneum. However, it is not clear whether the vasodilatory effect in the peritoneum is related to a local or systemic effect of CO2. METHODS: In this study, 21 pigs were exposed to pneumoperitoneum produced with either CO2 (n = 7) or helium (He) (n = 7) insufflation at 10 mmHg for 4 h, or to two consecutive levels of hypercapnia (7 and 11 kPa) (n = 7) produced by the addition of CO2 to the inhalational gas mixture. Tissue blood flow measurements were performed using the colored microsphere technique. RESULTS: Blood flow in peritoneal tissue increased during CO2, but not He, pneumoperitoneum, whereas it did not change at any level of hypercapnia alone. There was no change in blood flow in most organs at the partial pressure of CO2 (PaCO2) level of 7 kPa. However, at a PaCO2 of 11 kPa, blood flow was increased in the central nervous system, myocardium, and some gastrointestinal organs. The blood flow decreased markedly in all striated muscular tissues during both levels of hypercapnia. CONCLUSION: The effect of CO2 on peritoneal blood flow during laparoscopic surgery is a local effect, and not attributable to central hemodynamic effects of CO2 pneumoperitoneum or high systemic levels of CO2.

Development of a total colonoscopy rat model with endoscopic submucosal injection of the cecal wall.

BACKGROUND: Experimental models of colorectal tumor require either laparotomy for induction or anastomosis following resection. The long murine cecum avoids the need for an anastomosis, making the cecum the preferred site for induction. This study aimed to evaluate total colonoscopy with submucosal injection of cecal wall (TCWI) in rats in terms of failure rate (FR), complication rate (CR), and reproducibility (R). METHODS: A bolus of bowel prep was given. Anesthesia was injected intraperitoneally. A video fiberscope (5.9 mm outer diameter, 180/90 degrees up/down bending, 100/100 degrees right/left bending, 103 cm working length, 120 degrees view field, and 2.0 mm channel) allowed for irrigation and suction. Saline 1 ml was injected in the cecal wall through a 4-mm-long, 23-gauge needle placed on a 3-mm wire, resulting in a blister. FR was a failure to reach and inject the cecum. Rats were allowed to recover. CR was measured at necropsy. R was assessed by comparing TCWI time, FR, and CR for three investigators. Sample size of 120 (type I error, 0.05; power, 80%) was based on a pilot study. Data are presented as median (range). RESULTS: A total of two of 122 rats (1.6%) died after prep or anesthesia. Bowel prep resulted in 99.1% evacuation of solid feces. A total of 120 male Sprague-Dawley retired breeders weighing 592 g (range, 349-780) underwent TCWI. Scope depth was 28 cm (range, 20-36). Irrigating fluid was 290 ml (range, 100-600). TCWI time was 7 min (range, 4-28). FR was 4%. In three failed cases, the scope reached the ascending colon. CR was 2%. There were two perforations in the ascending colon. All three operators had similar TCWI time (p = 0.673), FR (p > 0.1), and CR (p > 0.1). A total of 98.3% of rats survived to planned sacrifice. At 48-h necropsy, the injection site was macroscopically identified in 118 rats. CONCLUSIONS: A safe and reproducible TCWI rat model has been achieved, which may provide a valuable tool in the future for studies of solid colorectal tumors.

Image-guided laparoscopic surgery. Review and current status.

The main drawback with laparoscopic surgery is that the surgeon is unable to palpate vessels, tumours and organs during surgery. Further-more, the laparoscope only provides a surface view of organs. There is a need for more advanced visualizations techniques that can enhance the display presented to the surgeon so that important information below the surface of the organs is included when planning the procedure as well as for guidance and control during treatment. In this paper, we present a review of the literature and the state of art within image-guided laparoscopic surgery. We describe our own experience using a prototype navigation system for advanced visualizations and guidance during laparoscopic procedures in the retroperitoneum. Furthermore, we show sample images from the Future Operating Room for laparoscopic surgery in Trondheim, where this technology is being further developed and tested in clinical studies. Our system is based on three-dimensional navigation technology, i.e. preoperatively acquired magnetic resonance or computed tomography data used in combination with tracked instruments, allowing the surgeon to interactively control the display of images prior to and during surgery with normal use of the instruments. In summary, we believe that abdominal image navigation using tracked instruments and advanced visualizations has a large potential for improving future laparoscopic surgery, especially in cases where vessels and anatomical relations beyond surfaces is difficult to identify using only a laparoscope. The technology helps the surgeon to better understand the anatomy and locate blood vessels. Accordingly, we believe that this new technology could increase safety and make it easier for the surgeon to perform successful laparoscopic surgery.

Effect of interleukin-10 on pancreatic damage caused by organophosphate poisoning.

Organophosphate poisoning is a common cause of severe morbidity and mortality in emergency departments. Acute pancreatitis is a frequently reported consequence of organophosphate poisoning, but preventing this potentially severe complication has not been the subject of much research. We tested whether interleukin-10, a cytoprotective agent, could prevent or diminish pathological signs of acute pancreatitis caused by organophosphate poisoning. Thirty rats were divided into three equal groups. Group 1 did not receive any agent during the experiment. Group 2 received 0.8 g/kg fenthion intraperitoneally, followed by 6 ml/kg intraperitoneal normal saline 30 min and 3 h later. Group 3 received 0.8 g/kg fenthion intraperitoneally, followed by 2 microg/kg of interleukin-10 intraperitoneally 30 min and 3 h later. All rats underwent laparotomy and thoracotomy while still under anesthesia at 6 h, and tissue samples were obtained from the pancreas. After blood samples were taken by cardiac puncture, the animals were sacrificed. Organophosphate poisoning resulted in significant elevations of serum amylase and glucose. Interleukin-10 significantly reduced pancreatic damage as determined by pathologic scoring, but not by enzyme elevations. Interleukin-10 should be considered for larger studies in other animal models to confirm its ability to decrease pancreatic damage after organophosphate poisoning treatment with interleukin-10.