Bifurcations of mixed-mode oscillations in three-timescale systems: An extended prototypical example.

We study a class of multi-parameter three-dimensional systems of ordinary differential equations that exhibit dynamics on three distinct timescales. We apply geometric singular perturbation theory to explore the dependence of the geometry of these systems on their parameters, with a focus on mixed-mode oscillations (MMOs) and their bifurcations. In particular, we uncover a novel geometric mechanism that encodes the transition from MMOs with single epochs of small-amplitude oscillations (SAOs) to those with double-epoch SAOs; the former feature SAOs or pseudo-plateau bursting either "below" or "above" in their time series, while in the latter, SAOs or pseudo-plateau bursting occur both "below" and "above." We identify a relatively simple prototypical three-timescale system that realizes our mechanism, featuring a one-dimensional S-shaped 2-critical manifold that is embedded into a two-dimensional S-shaped critical manifold in a symmetric fashion. We show that the Koper model from chemical kinetics is merely a particular realization of that prototypical system for a specific choice of parameters; in particular, we explain the robust occurrence of mixed-mode dynamics with double epochs of SAOs therein. Finally, we argue that our geometric mechanism can elucidate the mixed-mode dynamics of more complicated systems with a similar underlying geometry, such as a three-dimensional, three-timescale reduction of the Hodgkin-Huxley equations from mathematical neuroscience.

Changes of Hippocampal Noradrenergic Capacity in Stress Condition.

This study aimed to investigate the effects of chronic restraint stress (CRS) on the protein levels of dopamine-ß-hydroxylase (DBH), noradrenaline transporter (NET), vesicular monoamine transporter 2 (VMAT2) and brain-derived neurotrophic factor (BDNF), as well as the concentration of noradrenaline (NA) in the rat hippocampus. The investigated parameters were quantified by Western blot analyses and ELISA kits. We found that CRS increased the protein levels of DBH by 30 %, VMAT2 by 11 %, BDNF by 11 % and the concentration of NA by 104 %, but decreased the protein levels of NET by 16 % in the hippocampus of chronically stressed rats. The molecular mechanisms by which CRS increased the hippocampal NA level are an important adaptive phenomenon of the noradrenergic system in the stress condition.

Newly diagnosed cases of HIV in those aged 50 years and older and those less than 50: 2008-2017.

BACKGROUND: Canada's population is aging, with nearly forty percent of Canadians aged 50 years or more. As the population ages, unique challenges related to health are becoming evident, including increasing rates of sexually transmitted and bloodborne infections. Understanding the epidemiology of HIV in older adults is important to guide prevention and control programs. OBJECTIVE: To assess trends in newly diagnosed cases of HIV in Canada among those aged 50 years and older (≥50 years) and those aged less than 50 (<50 years), and to compare their basic demographic characteristics and exposure categories for the period of 2008 to 2017. METHODS: National surveillance of HIV is conducted by the Public Health Agency of Canada through voluntary submission of data by provincial/territorial public health authorities. Descriptive analyses were conducted on reported cases of HIV between January 1, 2008, to December 31, 2017 to compare the demographic profiles and exposure category for the two age groups. RESULTS: Between 2008 and 2017, the proportion of newly diagnosed HIV cases among those ≥50 years increased from 15.1% to 22.8%. The HIV diagnosis rates for both older males and older females increased over time, with a relatively higher increase for females. A higher proportion of newly diagnosed HIV cases were male in the older group (81.2%) compared to the younger group (74.6%). Among both older and younger males, the most common exposure category for HIV was being gay, bisexual and other men who have sex with men (gbMSM), followed by heterosexual contact and injection drug use; however, the relative proportions varied by age with the gbMSM category being higher in the <50 group. CONCLUSION: In Canada, over 20% of all newly diagnosed cases of HIV are now in people 50 years of age and older. HIV testing and prevention initiatives, historically aimed at younger populations, may not have the same impact for older populations. These data can be used to inform future public health actions designed to address HIV in older populations.

HIV in Canada-Surveillance Report, 2018.

BACKGROUND: Human immunodeficiency virus (HIV) is a global public health issue, with an estimated 36.9 million people living with HIV in 2017. HIV has been reportable in Canada since 1985 and the Public Health Agency of Canada (PHAC) continues to monitor trends in new HIV diagnoses. OBJECTIVE: The objective of this surveillance report is to provide an overview of the epidemiology of all reported diagnoses of HIV in Canada since 1985 with a focus on 2018 overall, and by geographic location, age group, sex, and exposure category. METHODS: PHAC monitors HIV through the national HIV/AIDS Surveillance System, a passive, case-based system that collates nonnominal data that is voluntarily submitted by all Canadian provinces and territories. Descriptive epidemiological analyses were conducted on national data and those relating to specific populations provided by Immigration, Refugees and Citizenship Canada and the Canadian Perinatal HIV Surveillance Program. RESULTS: In 2018, a total of 2,561 HIV diagnoses were reported in Canada, an increase of 8.2% compared with 2017. The national diagnosis rate increased to 6.9 per 100,000 population in 2018 from 6.5 per 100,000 population in 2017. Saskatchewan reported the highest provincial diagnosis rate at 14.9 per 100,000 population. The 30-39 year age group continued to have the highest HIV diagnosis rate at 15.4 per 100,000 population. Overall, the diagnosis rate for males continued to be higher than that of females (9.8 versus 4.0 per 100,000 population, respectively); however, females experienced a larger increase in reported cases and diagnosis rate. The gay, bisexual and other men who have sex with men (gbMSM) exposure category continued to represent the highest proportion of all reported adult cases (41.4%), though the proportion has decreased over time. Five perinatal HIV transmissions were documented, three were related to the mother not receiving perinatal antiretroviral therapy prophylaxis. CONCLUSION: The number and rate of reported HIV cases in Canada increased in 2018, gbMSM continued to account for the largest exposure category and the number and rate of reported HIV cases among women increased. PHAC will continue to work with its national partners to refine the collection, analysis and publication of national data to better understand the burden of HIV in Canada.

Improving national surveillance of new HIV diagnoses.

The purpose of national HIV surveillance is to track and summarize trends in newly diagnosed cases as an indicator of HIV transmission within Canada, and supports the development and evaluation of programs and policies for prevention, testing and delivery of care. Accurately capturing and interpreting trends in HIV diagnoses within national surveillance becomes complicated when there is movement of people within a country or when individuals are diagnosed with HIV prior to migrating to a new country. This has been identified as an issue in other countries, including Australia, New Zealand and Switzerland. The Public Health Agency of Canada (PHAC) recently assessed this in Canada after noting a rise in new HIV cases in Canada between 2014 to 2017. An environmental scan was conducted to better understand how new and previously diagnosed cases of HIV were recorded by and reported to PHAC from provincial and territorial (PT) public health authorities. It was discovered there was variation with respect to the reporting of cases who had received a new diagnosis of HIV within the province or territory, but who had previously received an HIV diagnosis from another PT or another country. Five PTs included cases previously diagnosed in another Canadian PT within the HIV surveillance data reported to PHAC and nine PTs included people who were diagnosed with HIV outside of Canada. The provincial and territorial public health authorities then reviewed HIV surveillance data from 2007 to 2017 to identify cases using a common definition of "previous HIV-positive test result". This included any case who gave a history, or had laboratory evidence, of an HIV-positive result from another PT or another country before presenting for care in the province or territory where they now resided. When these cases were subtracted from the total, a revised number of new HIV diagnoses was calculated for Canada. Re-analysis of surveillance data using this common definition for 2007 to 2017 explained more than half of the increase in HIV cases that had been documented in Canada over the last four years. In the future, national surveillance data will be calculated adopting this new common definition of a previous positive test result, in order to more accurately describe the trends in HIV transmission occurring in Canada.

Morphometric characteristics of the optic canal and the optic nerve.

BACKGROUND: The optic nerve (ON), a major component of the visual system, is divided into four segments: the intrabulbar (IB), the intraorbital (IO), the intraca- nalicular (ICn) and the intracranial (ICr). The ICr ends with the two nerves partially decussating in the optic chiasm (OCh). The purpose of this study is to provide a detailed description of the dimensions of the OC (the diameter and the surface area of its foramina and the central segment, as well as the length of the OC and the thickness of its walls) as well as the ON (the length of the ON segments, the diameter of the ICn segment of the ON, the angle of decussation in the OCh, as well as the distance between the two ON at the cranial foramen of the OC). MATERIALS AND METHODS: The acquired data was then used to estimate the volu- me of the OC and the ICn segment of the ON. The morphometric research was performed on 25 cadavers (17 male and 8 female) and 30 skulls. RESULTS: The surface area of the central segment of the OC was significantly smaller than the cranial foramen (p = 0.02) and the orbital foramen (p = 0.009). The inferior wall of the OC was significantly shorter than the other OC walls (p < 0.0001). The IO segment of the ON was the longest, where the difference to the ICn and ICr was statistically significant (p < 0.0001). The surface area of the ON at the cranial foramen was significantly larger than the surface area at the central segment of the OC (p = 0.02) and orbital foramen (p < 0.0001). The difference between the surface areas of the ON at the orbital foramen and the central segment of the OC was also statistically significant (p = 0.01). The estimated volume of the OC was calculated to be 190.72 mm3, and the volume of the ICn segment of the ON was estimated to be 50.25 mm3. CONCLUSIONS: It is absolutely crucial to open the central segment of the OC when decompressing the ON, due to the narrowing of the OC in this segment.

Video analysis of acute injuries and referee decisions during the 24th Men's Handball World Championship 2015 in Qatar.

Although handball is a contact sport with a high risk of acute match injuries, their mechanisms have not yet been investigated. We aimed to describe the mechanisms of acute match injuries in elite male handball and evaluate referee performance in injury situations. Based on injury surveillance from the 24th Men's Handball World Championship 2015 in Qatar, injury situations and the referee decisions were identified on video footage. A total of 55 injury situations and 37 referee decisions were included for analysis. The injury situations were analyzed individually by five handball experts, followed by a consensus meeting. An expert referee panel performed individual blinded evaluation of the referee decisions, followed by an online consensus meeting. Injuries were evenly distributed among attackers (n = 29) and defenders (n = 26). The most frequent injury cause was contact trauma due to a tackle (n = 27). At the time of injury, attackers were most frequently performing a jump shot (n = 9), while defenders were completing a tackle (n = 10). Defenders most commonly tackled the throwing arm (n = 7) or toward the head/face region (n = 6) of injured attackers, while attackers most frequently hit injured defenders with the knee during jump shots (n = 5). Agreement between the referees and the expert panel was weak (kappa: 0.22, 95% CI 0.07 to 0.36), with substantially more lenient rule interpretation by the referees. Our results suggest that stricter refereeing and rule amendments should be considered to prevent acute match injuries in elite handball, especially in relation to tackling episodes when an attacker is performing a jump shot.

Antioxidant status and sex hormones in women with complex endometrial hyperplasia.

Endometrial tissue is under a strong influence of sex hormones. These hormones are considered as developmental factors of endometrial hyperplasia and endometrial cancer. We examined the influence of gonadotropins (follicle-stimulating and luteinizing hormone) and sex hormones (estradiol, progesterone) on oxidant/antioxidant parameters in blood and endometrial tissue of women with complex endometrial hyperplasia. In blood, superoxide dismutase activity was significantly higher in luteal phase and postmenopause compared to the follicular phase. A significant phase-related difference of glutathione peroxidase and glutathione reductase activity was recorded in the endometrium. Both enzymes had lower activity in luteal phase and postmenopause compared to the follicular phase. The linear regression analysis of individual hormonal variables against antioxidant parameters showed negative correlation between glutathione peroxidase activity and gonadotropin concentrations in the endometrium. The regression of hyperplastic to normal endometrium is the purpose of conservative treatment based on administration of progestogens or gonadotropin-releasing hormone analogues. Our findings indicate that gonadotropins influence the antioxidant enzymes activity in women with complex endometrial hyperplasia, which may affect disease development. Further studies are needed to clarify the molecular basis of hormone action on antioxidant system that may potentially initiate a development of treatments based on redox-dependent mechanism.

Sewage sludge toxicity assessment using earthworm Eisenia fetida: can biochemical and histopathological analysis provide fast and accurate insight?

Sewage sludge (SS) is a complex organic by-product of wastewater treatment plants. Deposition of large amounts of SS can increase the risk of soil contamination. Therefore, there is an increasing need for fast and accurate assessment of SS toxic potential. Toxic effects of SS were tested on earthworm Eisenia fetida tissue, at the subcellular and biochemical level. Earthworms were exposed to depot sludge (DS) concentration ratio of 30 or 70 %, to undiluted and to 100 and 10 times diluted active sludge (AS). The exposure to DS lasted for 24/48 h (acute exposure), 96 h (semi-acute exposure) and 7/14/28 days (sub-chronic exposure) and 48 h for AS. Toxic effects were tested by the measurements of multixenobiotic resistance mechanism (MXR) activity and lipid peroxidation levels, as well as the observation of morphological alterations and behavioural changes. Biochemical markers confirmed the presence of MXR inhibitors in the tested AS and DS and highlighted the presence of SS-induced oxidative stress. The MXR inhibition and thiobarbituric acid reactive substance (TBARS) concentration in the whole earthworm's body were higher after the exposition to lower concentration of the DS. Furthermore, histopathological changes revealed damage to earthworm body wall tissue layers as well as to the epithelial and chloragogen cells in the typhlosole region. These changes were proportional to SS concentration in tested soils and to exposure duration. Obtained results may contribute to the understanding of SS-induced toxic effects on terrestrial invertebrates exposed through soil contact and to identify defence mechanisms of earthworms.

Combined reconstruction of atrial morphology and paracardial fat depositions to study remodeling in atrial fibrillation.

Atrial fibrillation (AF) is the most frequent sustained cardiac arrhythmia. AF is shown to be a progressive disease, which is strongly associated with important structural (morphological and histological), electrical and mechanical remodeling of the left atrium (LA). Adipose tissue accumulation has been shown to be a risk factor in AF. We set out to explore the connection between adipose tissue coverage of the LA surface, for both the complete LA and specific regions and the progression of AF. In this study we propose a methodology to study the regional coverage of the left-atrial wall with adipose tissue based on magnetic resonance data. Validation was performed in a sheep model. While the total amount of left-atrial adipose tissue was higher in the sheep with AF, no changes in regional coverage were observed.

Antioxidant status in blood of gynaecological patients: influence of diagnosis and reproductive factors.

Cancer of the reproductive tract is an important cause of morbidity and mortality among women worldwide. In this study we evaluated the influence of diagnostic categories, age and reproductive factors on antioxidant enzymes and lipid hydroperoxides in the blood of gynaecological patients diagnosed with endometrial polyp, myoma, hyperplasia simplex, hyperplasia complex and endometrial adenocarcinoma. Multivariate regression analysis was used to assess the association of diagnosis, age, parity, abortions and abnormal uterine bleeding with the examined parameters. Diagnosis provided the best predictive model for superoxide dismutase, catalase and glutathione peroxidase activities, and also for the lipid hydroperoxide level. Abortions fitted the best predictive model for superoxide dismutase activity. A significant correlation was also found between the predictor variables themselves. This study showed that reproductive and other factors may be associated, at least partially, with antioxidant capacity and ability to defend against the oxidative damage in gynaecological patients with various diagnoses.

Outbreak of West Nile virus infection among humans in Serbia, August to October 2012.

We describe the first reported outbreak of West Nile virus (WNV) infection in humans in Serbia in August to October 2012 and examine the association of various variables with encephalitis and fatal outcome. Enzyme-linked immunosorbent assay (ELISA) was used for detection of WNV-specific IgM and IgG antibodies in sera and cerebrospinal fluid. A total of 58 patients (mean age: 61 years; standard deviation: 15) were analysed: 44 were from Belgrade and its suburbs; 52 had neuroinvasive disease, of whom 8 had meningitis, while 44 had encephalitis. Acute flaccid paralysis developed in 13 of the patients with encephalitis. Age over 60 years and immunosuppression (including diabetes) were independently associated with the development of encephalitis in a multivariate analysis: odds ratio (OR): 44.8 (95% confidence interval (CI): 4.93­408.59); p=0.001 (age over 60 years); OR: 10.76 (95% CI: 1.06­109.65); p=0.045 (immunosuppression including diabetes). Respiratory failure requiring mechanical ventilation developed in 13 patients with encephalitis. A total of 35 patients had completely recovered by the time they were discharged; nine patients died. The presence of acute flaccid paralysis, consciousness impairment, respiratory failure and immunosuppression (without diabetes) were found to be associated with death in hospital in a univariate analysis (p<0.001, p=0.007, p<0.001 and p=0.010, respectively).

Cross-sectional study of hepatic CYP1A and CYP3A enzymes in hybrid striped bass, channel catfish and Nile tilapia following oxytetracycline treatment.

Terramycin for Fish® (oxytetracycline, OTC) is one of three approved drugs for therapeutic treatment of fish in the United States. Nothing is known, however, of the effects of this therapeutic on drug metabolizing enzymes in fish post-treatment. The main purpose of the study was to examine whether the fish CYP1A and CYP3A enzymes would cross-react with antibodies to known mammalian cytochrome P-450 forms (CYP1A1 and CYP3A). Observational feeding studies of OTC effects were conducted in hybrid striped bass, channel catfish and Nile tilapia. Oxytetracycline was mixed into the feed to achieve a daily dose of 82.8 mg per kg body weight at a feeding rate of 1% body weight per day. Hepatic microsomes of each fish were prepared and Western blotting of CYP1A1 and CYP3A4 and enzyme assays of CYP1A2 and CYP3A4 were performed prior to OTC treatment and on post-treatment days 1, 6, 11 and 21. Both goat anti-rat CYP1A1 and rabbit anti-human CYP3A4 showed good cross-reactivity with all three species in this study. All three species exhibited distinct perturbations in one or more of the variables examined on day 1 post-treatment. Immediately following the 10-day medication period, relative liver weight (RLW) of hybrid striped bass was increased 44% and remained elevated through post-treatment day 21. Increased CYP3A4 enzyme activity and protein abundance were noted in channel catfish and Nile tilapia, respectively. This observational approach demonstrated species differences both in control activities and in the timing and extent of hepatic responses to OTC. The unique perturbations of hepatic CYP450 enzymes in different fish species to OTC treatment observed in this study may have relevance for the use of additional antibiotics or other therapeutics used in aquaculture.

[Challenges and advances in the care of injuries in the Republic of Serbia].

There are many problems that trauma care system in Serbia is facing today. Few of them are: 1) Lack of categorization of trauma centers; 2) Diversity in managing of trauma patients among institutions; 3) There is no trauma management training, 4) Inappropriate cooperation between pre hospital trauma care and hospital trauma care; 5) There is no standard in managing of trauma patients as well as procedures. To improve trauma care quality throughout the country we must learn from the experiences of other countries. The aim of this paper was to report representative data about organization, management, stuff and equipment of ambulance and emergency services in Serbia. We analyzed 12 out of 138 parameters we obtained from the relevant institutions.

[Damage control surgery in abdominal trauma].

The damage control laparotomy is an advancement in the management of massively injured trauma patients. Massive liver injuries, pelvic trauma and some retroperitoneal injuries are some of the indications for this approach. The damage control laparotomy is the phased approach to severe abdominal injury that might best be described with the acronym STIR (Staged Trauma Injury Repair). The initial procedure requires rapid abdominal exploration with hemorrhage and contamination control, using suture repair combined with abdominal packing. Temporary abdominal wall closure without tension is recommended. After abrevated initial surgical procedure, the patient is transferred to the intensive care unit where continued resuscitation is performed. Careful replacement of blood and blood products along with correction of hypothermia, acidosis and optimalization of oxygen transport represents a critical phase in this management approach. Once the coagulation profile has normalized, planned re-intervention, with repeat abdominal exploration to remove the packs and perform definitive surgical repair and reconstruction takes place. When applied judiciously, the damage control laparotomy with the staged abdominal repair and reconstruction for severe trauma is associated with an improved outcome in the selected group of patients.

[Postoperative use of nonsteroidal anti-inflammatory agents in orthopedic surgery].

Nonsteroidal antiinflamatory drugs (NSAIDs) lead to satisfactory acute and chronic pain relief. Besides that, they exert potent antiinflamatory effect. Their analgesic potency is dose related and limited. Orthopedic patients are often on these medications preoperatively and experience opioid-sparing effect in the postoperative period. Chronic NSAIDs use is related to higher rate of sistemic adverse effects, but even short time exposure in the postoperative period is not risk-free. Although Coxibs reduce GIT bleeding incidence due to prolonged use of NSAIDs, there has to be judicious decision considering their cardiovascular adverse effects. There is evidence that NSAIDs producing moderate, dose-dependent increased bleeding time within normal values. High risk of bleeding have patients with established coagulopathy, alcohol abuse and on anticoagulant treatment. There is no strong evidence on influence of NSAIDs on bone growth. Nevertheless, there is evidence that NSAIDs do prevent heterotropic ossification. Prostaglandins are vital contributors for maintainig tissue homeostasis and NSAIDs use can lead to many unwanted effects. Those adverse effect are more common with prolonged exposure, are dose-related and risks have to be carefully and individually assesed in the postoperative pain management.

[Blood replacement in severely injured patients].

Haemorrhage remains a leading cause of early death in injured and application of concentrated RBC transfusion in the treatment of multiple injuries is the basis and potential component of saving lives. The aim of this study was to analyze the received amount reimbursed blood in patients with severe trauma, depending on the outcome, severity and mechanism of injury. Collected data on gender, age and age as the mechanism of injury, amount of blood recovered intraoperatively and during the first six days of hospitalization, which were analyzed according to outcome of treatment, ISS, AIS, and APACHE II score. Results showed that patients with lethal outcome received a larger amount of blood, there is a statistically significant correlation with ISS and AIS score for extremity injuries, and that larger amount of blood received patients injured in the traffic accidents, as pedestrians and motorcycle riders/bike, and there is no correlation with APACHE II score. Based on the importance of this topic for further research are necessary in this area in order to more accurately define indications and dosage and method of reimbursement of blood in patient with severe trauma.

[Open fracture of the shin as an occupational injury and work capacity evaluation--case report].

Injuries at work (occupational injuries) represent a big social and economic problem. This case report presents the patient who suffered occupational injury--open fracture of the left shin. He has been hospitalized for several times at Orthopedic-Surgical Hospital "Banjica" and underwent several surgical procedures, physical therapy and Hyperbaric Oxygen Therapy. After this treatment, he was hospitalized at Institute of Occupational Health for disability evaluation and work capacity evaluation.