12-day Course Research Articles

Repair of a right coronary artery rupture with perforated right ventricle following spontaneous pseudoaneurysm: a case report

BackgroundFollowing the rupture of a coronary artery, a patient’s condition usually deteriorates rapidly due to cardiac tamponade. A pseudoaneurysm due to a coronary artery rupture is rare; however, when a spontaneous coronary artery pseudoaneurysm occurs without tamponade, it creates a fistula in the right ventricle, often requiring surgical repair.Case presentationThis report describes the case of a 68-year-old man who presented with chest discomfort after a 12-day course of antibiotic treatment for bacteremia. Following coronary angiography, echocardiography, and enhanced computed tomography, he was diagnosed with a right coronary artery pseudoaneurysm accompanied with perforation of the right ventricle. Severe adhesions were observed during emergency surgery surrounding the entire heart. The patient presented with risk factors for coronary artery disease, including hypertension and smoking history. His coronary artery was severely calcified due to end-stage renal failure requiring dialysis; thus, a covered stent could not fit inside the arterial lumen. Consequently, coronary artery bypass grafting to the right coronary artery and right ventricle repair were performed. Unfortunately, the patient died postoperatively due to sepsis from intestinal translocation. This rare development was hypothesized to be an incidental result of the combination of severe post-inflammatory adhesions, extensive coronary artery calcification, and rupture of the calcification crevices.ConclusionsIn the case of a severe post-inflammatory response, shock without cardiac tamponade may require further scrutiny by assuming the possibility of inward rupture. For patients in poor condition, two-stage surgical treatment might be considered after stabilization with a covered stent.

Case report: atypical presentation of mpox with massive hematochezia and prolonged viral shedding despite tecovirimat treatment

BackgroundThe outbreak of mpox that occurred between 2022 and 2023 is primarily being transmitted through sexual contact. As of now, there is no consensus on the recommended duration of isolation to prevent sexual transmission of the virus. Moreover, this particular mpox outbreak has presented with distinct complications in comparison to previous occurrences. In this report, we present a case involving severe rectal bleeding from an ulcer in a mpox patient with a history of engaging in receptive sexual contact.Case presentationA 30-year-old Korean man presented at the hospital with complaints of fever, multiple skin lesions, and anal pain. Monkeypox virus polymerase chain reaction (PCR) results were positive for skin lesions on the penis and wrist. The patient received a 12-day course of tecovirimat due to anal symptoms and perianal skin lesions. Following isolation for 12 days and after all skin scabs had naturally fallen off, with no new skin lesions emerging for a consecutive 48 hours—conforming to the criteria of the Korean Disease Control and Prevention Agency—the patient was discharged. However, 1 day after discharge, the patient returned to the hospital due to hematochezia. His hemoglobin level had significantly dropped from 14.0 g/dL to 8.2 g/dL. Sigmoidoscopy unveiled a sizable rectal ulceration with exposed blood vessels, prompting the application of hemostasis through metal clipping. Subsequent monkeypox virus real-time PCR conducted on rectal tissue and swabs yielded positive results (with cycle threshold values of 28.48 and 31.23, respectively). An abdominal CT scan exposed a perirectal abscess, for which ampicillin-sulbactam was administered.ConclusionThis case underscores the importance of monitoring for bleeding complications and confirming the resolution of rectal lesions before discharging patients from isolation, particularly in cases where patients have a history of engaging in receptive sexual contact with men or are presenting with anal symptoms.

Inter-alpha-trypsin inhibitor (IαI) and hyaluronan modifications enhance the innate immune response to influenza virus in the lung

The inter-alpha-trypsin inhibitor (IαI) complex is composed of the bikunin core protein with a single chondroitin sulfate (CS) attached and one or two heavy chains (HCs) covalently linked to the CS chain. The HCs from IαI can be transferred to hyaluronan (HA) through a TNFα-stimulated gene-6 (TSG-6) dependent process to form an HC•HA matrix. Previous studies reported increased IαI, HA, and HC•HA complexes in mouse bronchoalveolar lavage fluid (BALF) post-influenza infection. However, the expression and incorporation of HCs into the HA matrix of the lungs during the clinical course of influenza A virus (IAV) infection and the biological significance of the HC•HA matrix are poorly understood. The present study aimed to better understand the composition of HC•HA matrices in mice infected with IAV and how these matrices regulate the host pulmonary immune response. In IAV infected mice bikunin, HC1–3, TSG-6, and HAS1–3 all show increased gene expression at various times during a 12-day clinical course. The increased accumulation of IαI and HA was confirmed in the lungs of infected mice using immunohistochemistry and quantitative digital pathology. Western blots confirmed increases in the IαI components in BALF and lung tissue at 6 days post-infection (dpi). Interestingly, HCs and bikunin recovered from BALF and plasma from mice 6 dpi with IAV, displayed differences in the HC composition by Western blot analysis and differences in bikunin's CS chain sulfation patterns by mass spectrometry analysis. This strongly suggests that the IαI components were synthesized in the lungs rather than translocated from the vascular compartment. HA was significantly increased in BALF at 6 dpi, and the HA recovered in BALF and lung tissues were modified with HCs indicating the presence of an HC•HA matrix. In vitro experiments using polyinosinic-polycytidylic acid (poly(I:C)) treated mouse lung fibroblasts (MLF) showed that modification of HA with HCs increased cell-associated HA, and that this increase was due to the retention of HA in the MLF glycocalyx. In vitro studies of leukocyte adhesion showed differential binding of lymphoid (Hut78), monocyte (U937), and neutrophil (dHL60) cell lines to HA and HC•HA matrices. Hut78 cells adhered to immobilized HA in a size and concentration-dependent manner. In contrast, the binding of dHL60 and U937 cells depended on generating a HC•HA matrix by MLF. Our in vivo findings, using multiple bronchoalveolar lavages, correlated with our in vitro findings in that lymphoid cells bound more tightly to the HA-glycocalyx in the lungs of influenza-infected mice than neutrophils and mononuclear phagocytes (MNPs). The neutrophils and MNPs were associated with a HC•HA matrix and were more readily lavaged from the lungs. In conclusion, this work shows increased IαI and HA accumulation and the formation of a HC•HA matrix in mouse lungs post-IAV infection. The formation of HA and HC•HA matrices could potentially create specific microenvironments in the lungs for immune cell recruitment and activation during IAV infection.

Teplizumab and β-Cell Function in Newly Diagnosed Type 1 Diabetes

BackgroundTeplizumab, a humanized monoclonal antibody to CD3 on T cells, is approved by the Food and Drug Administration to delay the onset of clinical type 1 diabetes (stage 3) in patients 8 years of age or older with preclinical (stage 2) disease. Whether treatment with intravenous teplizumab in patients with newly diagnosed type 1 diabetes can prevent disease progression is unknown.MethodsIn this phase 3, randomized, placebo-controlled trial, we assessed β-cell preservation, clinical end points, and safety in children and adolescents who were assigned to receive teplizumab or placebo for two 12-day courses. The primary end point was the change from baseline in β-cell function, as measured by stimulated C-peptide levels at week 78. The key secondary end points were the insulin doses that were required to meet glycemic goals, glycated hemoglobin levels, time in the target glucose range, and clinically important hypoglycemic events.ResultsPatients treated with teplizumab (217 patients) had significantly higher stimulated C-peptide levels than patients receiving placebo (111 patients) at week 78 (least-squares mean difference, 0.13 pmol per milliliter; 95% confidence interval [CI], 0.09 to 0.17; P<0.001), and 94.9% (95% CI, 89.5 to 97.6) of patients treated with teplizumab maintained a clinically meaningful peak C-peptide level of 0.2 pmol per milliliter or greater, as compared with 79.2% (95% CI, 67.7 to 87.4) of those receiving placebo. The groups did not differ significantly with regard to the key secondary end points. Adverse events occurred primarily in association with administration of teplizumab or placebo and included headache, gastrointestinal symptoms, rash, lymphopenia, and mild cytokine release syndrome.ConclusionsTwo 12-day courses of teplizumab in children and adolescents with newly diagnosed type 1 diabetes showed benefit with respect to the primary end point of preservation of β-cell function, but no significant differences between the groups were observed with respect to the secondary end points. (Funded by Provention Bio and Sanofi; PROTECT ClinicalTrials.gov number, NCT03875729.)

Efficacy and safety of colchicine treatment in patients with COVID-19: A prospective, multicenter, randomized clinical trial.

Colchicine has shown clinical benefits in the management of COVID-19 via its anti-inflammatory effect. However, the exact role of colchicine in COVID-19 patients is unknown. The current clinical trial was performed on 202 patients with moderate to severe COVID-19. Patients were randomly assigned in a 1:1 ratio to receive up to a 3-day course of 0.5mg colchicine followed by a 12-day course of 1mg colchicine in combination with standard care or a 15-day course of standard care. Among 202 randomized patients, 153 completed the study and received colchicine/standard care or continued standard care (M age, 54.72 [SD, 15.03] years; 93 [63.1%] men). On day 14, patients in the colchicine/standard care group had significantly higher odds of a better clinical status distribution on chest CT evaluation (p= .048). Based on NYHA classification, the percentage change of dyspnea on day 14 between groups was statistically significant (p= .026), indicating a mean of 31.94% change in the intervention group when compared with 19.95% in the control group. According to this study, colchicine can improve clinical outcomes and reduce pulmonary infiltration in COVID-19 patients if contraindications and precautions are considered and it is prescribed at the right time and in appropriate cases.

Нейроендокринно-імунний супровід діуретичного ефекту бальнеотерапії на курорті Трускавець

Мета: виявити супутні зміни параметрів нейроендокринно-імунного комплексу і мікробіоценозу товстого кишечника, що супроводжують діуретичний ефект бальнеотерапії на курорті Трускавець. Результати. У спостереженні за 22 чоловіками, хворими на хронічний пієлонефрит в поєднанні з холециститом, виявлено, що 10–12-денний курс бальнеотерапії (пиття біоактивної води «Нафтуся», аплікації озокериту, мінеральні ванни) збільшує добовий діурез на 28 % (p &lt; 0,001). Це поєднується із збільшенням екскреції фосфатів на 103 % (p &lt; 0,001), кальцію — на 76 % (p &lt; 0,01), креатиніну — на 32 % (p &lt; 0,02), сечової кислоти — на 29 % (p &lt; 0,001), сечовини — на 21 % (p &lt; 0,01), магнію — на 19 % (p = 0,05) при відсутності суттєвих змін екскреції хлориду, калію і натрію. При цьому знижується рівень у плазмі креатиніну на 14 % (p &lt; 0,001) і сечовини на 11 % (p &lt; 0,01). Лейкоцитурія зменшується на 16 % (p &lt; 0,02). Екскреторно-депураційний і протизапальний ефекти бальнеотерапії супроводжуються відчутною модуляцією параметрів нейроендокринно-імунного комплексу. Зокрема, зменшується як абсолютна, так і відносна щільність спектральної потужності (PSD) δ- і α-ритмів (p &lt; 0,05–0,01), і підвищується відносна PSD β-ритму (p &lt; 0,05–0,02) базальної електроенцефалограми. Разом з тим знижуються індекси варіабельності ритму серця: (VLF + LF)/HF — на 34 % (p &lt; 0,05) і LF/HF — на 32 % (p &gt; 0,05) за рахунок підвищення PSD HF більшою мірою, ніж LF. Базальний рівень у плазмі кортизолу знижується на 20 % (p &lt; 0,01), тестостерону — на 15 % (p = 0,01), натомість підвищується рівень трийодтироніну — на 4 % (p &lt; 0,05) і особливо кальцитонінової активності — на 92 % (p &lt; 0,001), розрахованої за екскрецією з сечею фосфатів і кальцію. Лейкоцитарний індекс адаптації Поповича зростає на 46 % (p &lt; 0,02). Стосовно параметрів фагоцитарної функції нейтрофілів констатовано підвищення зниженого індексу кілінгу ними Staphylococcus aureus на 19 % (p &lt; 0,001) і Escherichia coli на 18 % (p &lt; 0,01) за відсутності змін початково нормальних фагоцитарних індексів. Мікробне число стосовно Staphylococcus aureus залишається нормальним, а початково підвищена на 15 % інтенсивність фагоцитозу Escherichia coli знижується на 8 % (p &lt; 0,05). Стосовно параметрів імунітету виявлено значуще підвищення рівня в крові лише CD16+ лімфоцитів (+17 %, p &lt; 0,01) при відсутності змін рівнів CD3+CD4+ і CD3+CD8+ Т-лімфоцитів і CD19+ В-лімфоцитів. Не змінюються суттєво ні рівні в сироватці Ig G, M, A, ні циркулюючих імунних комплексів. Імунотропний ефект супроводжується редукцією проявів дисбактеріозу: вміст Bifidumbacter зростає на 19 % (p &lt; 0,02), Lactobacter — на 20 % (p &lt; 0,05), а Escherichia coli — на 48 % (p &lt; 0,01), при цьому доля штамів з ослабленими ферментативними властивостями зменшується на 47 % (p &lt; 0,001), з гемолітичними властивостями — на 77 % (p &lt; 0,01). Висновок. Бальнеотерапія на курорті Трускавець чинить відчутний діуретичний ефект, що поєднується з активацією екскреторної і депураційної функцій нирок та бактерицидної функції нейтрофілів, редукцією дисбактеріозу товстого кишечника, лейкоцитурії і нейроендокринних проявів стресу.

FTACMT study protocol: a multicentre, double-blind, randomised, placebo-controlled trial of faecal microbiota transplantation for autism spectrum disorder

IntroductionAutism spectrum disorder (ASD) is a complicated diffuse developmental disorder that commonly involves gastrointestinal distress and dysbacteriosis. Emerging lines of evidence have shown faecal microbiota transplantation (FMT) to be a...

Abstract 170: Deferoxamine Treatment Decreases Levels Of Reactive Oxygen Species And Cellular Apoptosis In Irradiated Skin

Purpose: Radiation therapy is a cornerstone of oncologic treatment. Unfortunately, radiation can lead to pain and ulceration in the acute phase, as well as stiffness and fibrosis in the chronic phase. Deferoxamine (DFO) is an FDA approved iron chelator that has been shown to increase skin vascularization by stabilizing hypoxia-inducible factor 1-alpha levels and improve radiation-induced fibrosis. However, it is unclear whether there are other mechanisms underlying the therapeutic effects that DFO exhibits on the skin. Previous work has shown that DFO delivered transdermally improves healing in diabetic ulcer wounds by decreasing oxidative stress and cellular apoptosis. This study evaluates the effects of transdermal DFO on reactive oxygen species and cell death in the context of irradiation (IR) to skin. Methods: CD-1 nude immunodeficient mice (n=8) were randomized to one of two conditions: 1. Control patch (IR only) (n=4) and 2. DFO patch (n=4). The study period consisted of a 14-day pre-IR period, followed by a 12-day course of fractionated IR which delivered a total of 30 Gray to all mice. The control group received patches without DFO and the DFO group received patches containing DFO throughout the experiment with patches changed daily. Mouse scalp skin was harvested one day after the completion of IR. Tissue samples were either fixed in 4% PFA, snap frozen in OCT, or directly stored at -80°C. Fixed samples were embedded in paraffin, sectioned, and stained for iron with Prussian blue. Snap frozen samples were cryosectioned at 10um, mounted, stained with dihydroethidium (DHE), and imaged with confocal microscopy. DHE detects reactive oxygen species. Stored samples were mechanically homogenized and enzyme-linked immunosorbent assays (ELISAs) were performed to measure levels of human Bax and Cleaved Caspase-3, markers of apoptosis. Results: Treatment with DFO was associated with decreased levels of iron in the skin, confirming DFO’s role as an iron chelator. DHE fluorescence was more intense in the control patch group than in the DFO patch group (***p<0.0001), indicating that ROS generation decreased with DFO treatment. Similarly, apoptosis was highest in the control group and lowest in the DFO group as shown by higher human Bax protein (*p=0.028) and Cleaved Caspase-3 (**p=0.0038) levels. Conclusions: DFO delivered transdermally leads to a dose-dependent decrease in reactive oxygen species and apoptotic markers. These results provide further insight into the mechanisms underlying its restorative effects on irradiated skin. Future work will investigate the relationship of reactive oxygen species and fibroblast subpopulations in the skin.

Pertussis and the Minnesota State Fair: Demonstrating a Novel Setting for Efficiently Conducting Seroepidemiologic Studies.

Seroepidemiologic studies, which measure serum antibody levels produced in response to infection and/or vaccination, can be valuable tools for gaining insight into population level dynamics of infectious diseases. However, because seroepidemiologic studies are expensive and logistically challenging, they are not routinely conducted for surveillance purposes. We have identified a novel venue, state fairgrounds, in which annual sera samples from a population may be rapidly collected with minimal recruitment expenses. We conducted a pilot pertussis seroepidemiologic study over the course of 3days at the 2016 Minnesota State Fair to determine if this setting, which hosts nearly 2million visitors over 12days each year, is viable for facilitating larger seroepidemiologic studies. A total of 104 adults and children were enrolled to provide a finger stick blood sample for serologic testing and to take a written survey regarding recent cough illness and pertussis vaccination. The survey was used to distinguish between antibodies induced by vaccination and pertussis infection. Elevated antibodies suggestive of recent infection were found among two adults. The prevalence of undetectable antibodies, suggestive of susceptibility, was 72.3% (95% CI 59.6, 85.1%) among 7-17year olds, 53.8% (95% CI 26.7, 80.9%) among 1-6year olds, and 23.3% (95% CI 8.2, 38.5%) among adults. Our ability to rapidly enroll participants and collect satisfactory specimens suggests that seroepidemiologic studies with 1000-2000 participants could efficiently be completed over the 12-day course of the Minnesota State Fair. This setting raises the possibility of efficiently conducting annual population-based seroepidemiologic studies to supplement traditional public health surveillance in estimating disease prevalence, monitoring vaccine impact, and identifying at-risk groups.

A 12-Day Course of Imiquimod 5% for the Treatment of Actinic Keratosis: Effectiveness and Local Reactions

Introduction and objectivesImiquimod is an excellent option for patients with actinic keratosis, although its use may be limited by the long course of treatment required (4 weeks) and the likelihood of local skin reactions. The objectives of the present study were to demonstrate the effectiveness of a 12-day course of imiquimod 5% for the treatment of actinic keratosis and to examine the association between treatment effectiveness and severity of local reactions. Patients and methodsWe included patients with at least 8 actinic keratoses treated with imiquimod 5% cream for 12 consecutive days. Local reactions were classified as mild, moderate, or severe. The statistical analysis of the association between local reactions and clinical response was based on the Pearson χ2 test and the Spearman rank correlation test. ResultsSixty-five patients completed the study. Complete response was recorded in 52.3% and partial response in 75.4%. We found a statistically significant association between severity of the local reaction and response to treatment in both the Pearson χ2 test and the Spearman rank correlation test. ConclusionsA 12-day course of imiquimod 5% proved effective for the treatment of actinic keratosis. Severity of local reactions during treatment was correlated with clinical response.

An immersive flipped classroom for learning Mandarin Chinese: design, implementation, and outcomes

ABSTRACTOnline kindergarten to twelfth grade (K-12) language learners have usually been found to hold more negative perceptions of their courses and to perform less well academically than their face-to-face counterparts, despite the well-attested benefits of computer-mediated communication in language learning. In an attempt to improve upon such outcomes, this study designed, implemented, and evaluated a 12-day immersive online high-school Chinese-language course that included daily synchronous sessions and interactive technology-enhanced tasks, with a special emphasis on engaging the students in meaningful social interactions. Based on the analysis of the 35 participants’ survey responses and their language performance, they had a very positive experience of the course, felt satisfied by it, and showed statistically significant improvement in their language skills. These findings are discussed in relation to prior studies’ findings and current online-education policies and practices.

Tratamiento con imiquimod al 5% durante 12 días para las queratosis actínicas: estudio de la eficacia y la reacción local

Introduction and objectivesImiquimod is an excellent option for patients with actinic keratosis, although its use may be limited by the long course of treatment required (4 weeks) and the likelihood of local skin reactions. The objectives of the present study were to demonstrate the effectiveness of a 12-day course of imiquimod 5% for the treatment of actinic keratosis and to examine the association between treatment effectiveness and severity of local reactions. Patients and methodsWe included patients with at least 8 actinic keratoses treated with imiquimod 5% cream for 12 consecutive days. Local reactions were classified as mild, moderate, or severe. The statistical analysis of the association between local reactions and clinical response was based on the Pearson χ2 test and the Spearman rank correlation test. ResultsSixty-five patients completed the study. Complete response was recorded in 52.3% and partial response in 75.4%. We found a statistically significant association between severity of the local reaction and response to treatment in both the Pearson χ2 test and the Spearman rank correlation test. ConclusionsA 12-day course of imiquimod 5% proved effective for the treatment of actinic keratosis. Severity of local reactions during treatment was correlated with clinical response.

Developing Senior Eccleasiastical Professionals’ Emotional and Cultural Intelligence - A Longitudinal Preliminary Case Study Research Investigation

Emotional intelligence (EI) and cultural intelligence (CQ) are constructs that have recently received much attention and have been investigated in work contexts. It is possible that a high EI and CQ both contribute generally to improved intercultural and interreligious understanding and dialogue. However, this relationship has hardly been researched in eccleasiastical contexts in Germany. This study investigates the development of EI and CQ during a 12-day training course for developing intercultural and interreligious competencies for senior professionals in an ecclesiastical context over a period of nine months. Pre- and post-test scores of EI and CQ were measured during the training period. Besides the quantitative survey, a literature analysis and participant observation in the training course was used for data collection. It was found that with regard to the EI total scores, all dimensions except the dimension of "appraisal of emotions in the self" improved from the beginning of the training until the end. Looking at the pre- and post-scores of CQ, the scores increased in six participants, and decreased in two.

Effects of Lung Cotransplantation on Cardiac Allograft Tolerance Across a Full Major Histocompatibility Complex Barrier in Miniature Swine.

A 12-day course of high-dose tacrolimus induces tolerance of major histocompatibility complex-mismatched lung allografts in miniature swine but does not induce tolerance of heart allografts unless a kidney is cotransplanted. To determine whether lungs share with kidneys the ability to induce cardiac allograft tolerance, we investigated heart-lung cotransplantation using the same induction protocol. Hearts (n = 3), heart-kidneys (n = 3), lungs (n = 6), and hearts-lungs (n = 3) were transplanted into fully major histocompatibility complex-mismatched recipients treated with high-dose tacrolimus for 12 days. Serial biopsy samples were used to evaluate rejection, and in vitro assays were used to detect donor responsiveness. All heart-kidney recipients and five of six lung recipients demonstrated long-term graft survival for longer than 272 days, while all heart recipients rejected their allografts within 35 days. Tolerant recipients remained free of alloantibody and showed persistent donor-specific unresponsiveness by cell-mediated lympholysis/mixed-lymphocyte reaction. In contrast, heart-lung recipients demonstrated rejection of both allografts (days 47, 55, and 202) and antidonor responsiveness in vitro. In contrast to kidneys, lung cotransplantation leads to rejection of both heart and lung allografts, indicating that lungs do not have the same tolerogenic capacity as kidneys. We conclude that cells or cell products present in kidney, but not heart or lung allografts, have a unique capacity to confer unresponsiveness on cotransplanted organs, most likely by amplifying host regulatory mechanisms.

Creating a system of medical and psychological rehabilitation of extreme professions representatives (firemen-rescuers as a model)

Chumaeva Julia , Golikov а Vladislava, Nekhoroshkova Julia , Ogulenko Alexey , Shafran Leonid. Creating a system of medical and psychological rehabilitation of extreme professions representatives (firemen-rescuers as a model). Journal of Education , Health and Sport . 2015;5(8):1 9 7 - 209 . ISSN 2391-8306 . DOI 10.5281/zenodo.28064 http://dx.doi.org/10.5281/zenodo.28064 http://ojs.ukw.edu.pl/index.php/johs/article/view/2015%3B5%288%29%3A197-209 https://pbn.nauka.gov.pl/works/607738 Formerly Journal of Health Sciences. ISSN 1429-9623 / 2300-665X. Archives 2011–2014 http://journal.rsw.edu.pl/index.php/JHS/issue/archive Deklaracja. Specyfika i zawartośc merytoryczna czasopisma nie ulega zmianie. Zgodnie z informacją MNiSW z dnia 2 czerwca 2014 r., ze w roku 2014 nie bedzie przeprowadzana ocena czasopism naukowych; czasopismo o zmienionym tytule otrzymuje tyle samo punktow co na wykazie czasopism naukowych z dnia 31 grudnia 2014 r. The journal has had 5 points in Ministry of Science and Higher Education of Poland parametric evaluation. Part B item 1089. (31.12.2014). © The Author (s) 2015; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland and Radom University in Radom, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 05.06.2015. Revised 15.07.2015. Accepted: 12.08.2015. CREATING A SYSTEM OF MEDICAL AND PSYCHOLOGICAL REHABILITATION OF EXTREME PROFESSIONS REPRESENTATIVES (FIREMEN-RESCUERS AS A MODEL) Julia Chumaeva 1 , Vladislava Golikovа 1,2 , Julia Nekhoroshkova 1 , Alexey Ogulenko 1 , Leonid Shafran 1 1 Ukrainian Scientific and Research Institute of Transport Medicine, Odessa, Ukraine 2 Odessa National Maritime Academy, Odessa, Ukraine Abstract Background. Working conditions of representatives of extreme professions (firemen-rescuers are a good example), are connected with disregulations and disorders of physiologic functions, fatigue accumulation and disadaptation. The medical and psychological rehabilitation is an effective way for occupational health and reliability restoration. However, last one is characterized by an empirical approach and conducted by priority of medical component, that significantly reduces effectiveness of the undertaken measures. So, it is necessary to develop a system of combined medical and psychological rehabilitation (MPR). Materials and methods. In this progect MPR was carried out in 238 specialists of three professional groups: firemen-rescuers (146), fire-engine drivers (44) and inspectors of fire safety (48 - control). Psychophysiological examination included the computerized program “MORTEST”, variant “SPAS-14” performance, answers to the individual-typological questionnaire (ITQ) and Eysenck personal test (EPT). The levels of epinephrine (Е), norepinephrine (NЕ), dopamine (DА) and dioxyphenylalanine (DOPA) urinal excretion, the vanillylmandelic (VMA) and homovanillic acids (HVA) levels in urine were also defined. The survey is conducted three times: at the beginning, middle and the end of a 12-day rehabilitation course. Statistical data processing was carried out by common programs in Microsoft Excel. Results and discussion. The studies have shown that the attributes to identify individual-typological differences are indicators of extroversion-introversion and anxiety in tests ITO and EPT. The results were divided into three clusters: extroverts with low anxiety (52.9%); ambiverts with low (27.7%) and high anxiety (19.4%). Simultaneously it was assigned different types of SAS response in the rehabilitation process: basic or balanced, epinephrinic, norepinephrinic, and with low secretory activity. Low efficiency of rehabilitation measures occurred in 40.7 ± 5,1% of surveyed firefighters with epinephrinic response type and SAS functional exhaustion. The type of SAS response allocated 3 levels of stress in fire-rescuers: adequate to professional load, with the signs of hormonal and mediatorial dissociation, and dangerous - with the depletion of all links of SAS. Conclusion. According to the results of the performed researches it was developed a system of MPR, which allows to conduct a differentiated remediation of firemen-rescuers in the view of occupational features, individually-typological properties of the rehabilitants’ personality, the nature and degree of changes in the central nervous, autonomic and hormonal systems. The developed approaches included in the elaborated Methodical Guidelines, implemented in practice. Key words: extreme professions, firemen-rescuers, medical and psychological rehabilitation, psychophysiological assessment, psychological markers, catecholamines excretion, effective measures elaboration.

Влияние мексидола и гемисукцината 2-этил-6-метил-3-гидроксипиридина на содержание липофусцина в ткани головного мозга крыс в условиях локальной перманентной ишемии

В опытах на крысах установлено, что курсовое 6- и 12-дневное применение мексидола или гемисукцината 2-этил-6-метил-3-гидроксипиридина (в дозах 200 мг/кг, внутрибрюшинно) предотвращает избыточное накопление липофусцина в ткани мозга после локальной перманентной ишемии, вызванной перевязкой средней мозговой артерии, как в интактном, так и в поврежденном полушариях головного мозга. Мексидол вызывает выраженное снижение уровня липофусцина после 12 дней введения, тогда как гемисукцинат 2-этил-6-метил-3-гидроксипиридин приводит к значительному снижению концентрации липофусцина уже после 6-дневного лечения.

Genetic and environmental modulation of neurotrophic and anabolic stress response: Counterbalancing forces

The serotonin transporter genetic variant 5HTTLPR influences activation and feedback control of the hypothalamic–pituitary–adrenal axis, and has been shown to influence the effect of stressful life events on behavioral health. We recently reported that 5HTTLPR modulates cortisol response in healthy military men exposed to intense stress. Less is known of its combined effects with environmental factors in this context, or of its effect on neuroprotective stress responses. In this follow-up study, we examined the unique and combined effects of 5HTTLPR and prior trauma exposure on neuroprotective (salivary nerve growth factor [sNGF]), anabolic (dehydroepiandrosterone sulfate [DHEAS] and testosterone), and catabolic (cortisol) stress responses. Ninety-three healthy, active-duty military men were studied before, during, and 24h after a stressful 12-day survival course. Distinct and interactive effects of 5HTTLPR long allele carriage [L] versus homozygous short allele carriage [SS]) and prior trauma exposure (low versus high) were evaluated, after which a priori group comparisons were performed between hypothesized high resilience (L/low) and low resilience (SS/high) groups. For sNGF, L/low produced the greatest sNGF throughout stress exposure while SS/high demonstrated the smallest; L/high and SS/low bisected these two extremes and were nearly identical to each other (i.e., SS/high<SS/low=L/high<L/low). Thus, 5HTTLPR and prior trauma exposure demonstrated counterbalancing (additive) forces. Similar patterns were found for DHEAS. To our knowledge, this study is the first to report counterbalancing genetic and environmental effects on novel biomarkers related to resilience in humans exposed to real-world stress. These findings have profound implications for health, performance and training in high-stress occupational settings.

Neuroprotective–neurotrophic effect of endogenous dehydroepiandrosterone sulfate during intense stress exposure

Recent reports demonstrate neurotrophic properties of dehydroepiandrosterone sulfate (DHEAS) in men at rest, as well as profound neurotrophic responses to stress in both men and women. Little is known of neuroprotective–neurotrophic effects of DHEAS during stress exposure, either in men or women. This translational study was designed to examine neuroprotective–neurotrophic effects of DHEAS throughout intense stress exposure in healthy men and women. The study took place within a stressful 12-day military survival course. Utilizing a longitudinal cross-sectional repeated measures design, One hundred sixteen healthy active-duty military personnel (80% male) were studied before, during, and 24h after the course. The dependent variable was the neurotrophin salivary nerve growth factor (sNGF). In terms of total hormone output, the effect of DHEAS on sNGF was mediated by testosterone. Unlike testosterone or cortisol, DHEAS reliably predicted sNGF at each time point, and change in DHEAS predicted change in sNGF across time points. Baseline DHEAS predicted total sNGF output across the stress trajectory. Consistent with preclinical as well as cross-sectional human research, this study demonstrates neuroprotective–neurotrophic effects of DHEAS in healthy men and women exposed to intense stress. Results are evaluated in relation to established criteria for causation.

Genetic variants in serotonin and corticosteroid systems modulate neuroendocrine and cardiovascular responses to intense stress

Common variants in serotonin and corticosteroid receptor genes influence human stress in laboratory settings. Little is known of their combined effects, especially in high stress environments. This study evaluated distinct and combined effects of polymorphisms in the serotonin transporter (5HTTLPRL/S), glucocorticoid receptor (Bcl1C/G), and mineralocorticoid (−2C/G) receptor genes on adrenocortical and cardiovascular responses to intense, realistic stress. One hundred and forty four healthy, active-duty military men were studied before, during, and 24h after a stressful 12-day survival course. Dependent variables were cortisol, heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP). 5HTTLPR SS carriers revealed higher overall cortisol concentrations than L carriers (p=.022). 5HTTLPR L carriers demonstrated higher stress-induced HR than non-carriers (SS) yet rebounded to a lower recovery value (p=.026), while Bcl1 G carriers showed higher mean stress-induced HR than non-carriers (CC) (p=.047). For DBP, 5HTTLPR S carriers showed higher overall values than non-carriers (LL) (p=.043), Bcl1 GG were higher than C carriers (p=.039), and −2C/G G carriers exceeded non-carriers (CC) (p=.028). A “high” composite genotype group revealed substantially higher overall cortisol concentrations than a “low” composite genotype group (p<.001), as was the case for DBP (p=.037). This study revealed a synergistic effect of common polymorphisms on the acute stress response in healthy men. Pending additional study, these findings may have implications for drug discovery, gene therapy, and stress inoculation strategies.

Evidence for a Gene Controlling the Induction of Transplantation Tolerance

Class I mismatched kidney transplantation in Massachusetts General Hospital MHC-defined miniature swine has been studied extensively as a model for induction of systemic allograft tolerance. In a large series of juvenile swine, long-term graft acceptance has been observed consistently following a 12-day course of cyclosporine. It was therefore surprising when three of five recipients in one of our studies rejected their grafts. Examination of the origins of the rejecting animals revealed that they were derived from a subline of the SLA(dd) miniature swine herd that was intentionally being inbred toward full homozygosity and had been inbred for eight generations prior to these experiments. A blinded study of additional class I mismatched renal transplants into animals from this subline confirmed the genetic basis of this rejection. We present here preliminary evidence suggesting that a likely explanation for this phenomenon is that the rejectors in this subline are homozygous for a recessive mutant allele of a gene normally involved in the induction of tolerance. Subsequent studies will be directed toward identification and characterization of the gene(s) involved, since existence of a similar genetic locus in humans might have implications for assessing an individual's likelihood of graft rejection versus tolerance induction prior to organ transplantation.