Investigating the Facilitating Factors of Drug Use Based on Personality and Ethnic Characteristics of Guilan Province

Abstract Background: Identifying ethnic and personality facilitation factors in drug use help to better diagnose and treat addiction identifying facilitation factors. It provides timely counseling, and psychological services can be partially preventable for addicts. This study aimed to investigate factors facilitating drug use based on ethnic and personality characteristics of Guilan province using the Cloninger personality system. Materials and Methods: The study population consisted of four subcultures of Guilak, Talesh (Turk), Kord and others called Fars. The sampling method in this study was a mixed-method; the sample size was at least 200 people. The present study used data in the field section of Cloninger's personality and character questionnaire to determine personality components and their relationship. They were used with current norms. This study used in-depth interviews, observation and review of documents (questionnaires) and conventional oral literature on drug use. Results: This study showed that between ethnic facilitation factors (drug and drug counseling, folk beliefs in oral literature, and beliefs about rituals and companionship) and personality traits (nature and character), except the avoidance factor at the significant level of 0.01, there was a significant and positive relationship. Variables of personality traits/"nature and character" and components of perseverance, novelty, reward-dependence, self-direction, cooperation can predict common beliefs in the propensity to medication and therapy. The personality facilitator variable of "nature and character" and all its components, except for themselves, was able to predict the popular beliefs existing in oral literature. The personality facilitator variable of "nature and character" and the components of novelty, reward-dependence, and cooperation could predict common beliefs about rituals and companionship. Conclusion: Research showed a significant relationship between ethnicity and propensity for drug and drug counseling, popular beliefs in oral literature, and celebration and celebration beliefs

Anthropometric, Body Composition, and Biochemical Measurements in Morbidly Obese Patients Prior to Bariatric Surgery

Background: Obesity is the most important risk factor for occurrence of chronic diseases. Morbid obesity could be accompanied by imbalance of body composition and serum levels of nutrients. Therefore, the aim of this study was to compare body composition and serum levels of nutrients in the bariatric surgery candidates with standard values.Methods: In this cross-sectional study, 100 morbid obese patients (22 men and 78 women) were enrolled. Their anthropometric and biochemical measurements were evaluated based on the standard protocols. Body composition was measured using the dual X-ray absorptiometry (DEXA) method. Independent t-test was used to compare the mean of quantitative variables between genders and measurements with the standard values to estimate any deficiency.Results: Grade 3 obesity (73%), abdominal obesity (100%), abnormal waistto-hip ratios (95%), abnormal body fat and fat-free mass percentages (100%), normal android-to-gynoid fat ratios (96%), and moderate body shape profiles (100%) were prevalent among the participants. Also, a deficiency of vitamin D (91%), vitamin B12 (19%), and iron (17% serum iron and 3% serum ferritin) was noticed. Serum levels of vitamin A (7%) and zinc (4%) were higher than normal among a part of population. There were no significant differences in the distributions of these indicators by gender.Conclusion: People with morbid obesity had abnormal amounts of fat and muscle tissue. Also, they were deficient regarding vitamin D, vitamin B12, and iron. Moreover, vitamin A and zinc levels in some people were higher than normal. Further studies are needed to confirm these findings in larger populations

mTOR-Dependent Oxidative Stress Regulates oxLDL-Induced Trained Innate Immunity in Human Monocytes

Introduction: Cells of the innate immune system particularly monocytes and macrophages have been recognized as pivotal players both during the initial insult as well as the chronic phase of atherosclerosis. It has recently been shown that oxidized low-density lipoprotein (oxLDL) induces a long-term pro-inflammatory response in monocytes due to epigenetic and metabolic reprogramming, an emerging new concept called trained innate immunity. Changes in the cellular redox state are crucial events in the regulation of many physiologic functions in macrophages including transcription, differentiation and inflammatory response. Here we have analyzed the role of reactive oxygen species (ROS) in regulating this proinflammatory monocyte priming in response to oxLDL-treatment.Methods and Results: Human monocytes were isolated and incubated with oxLDL for 24 h. After 5 days of resting, oxLDL treated cells produced significantly more inflammatory cytokines upon restimulation with the TLR2-agonist Pam3cys. Furthermore, oxLDL incubation induced persistent mTOR activation, ROS formation, HIF1α accumulation and HIF1α target gene expression, while pharmacologic mTOR inhibition or siRNA mediated inhibition of the mTORC1 subunit Raptor prevented ROS formation and proinflammatory priming. mTOR dependent ROS formation was associated with increased expression of NAPDH oxidases and necessary for the emergence of the primed phenotype as antioxidant treatment blocked oxLDL priming. Inhibition of cytosolic ROS formation could also block mTOR activation and HIF1α accumulation suggesting a positive feedback loop between mTOR and cytosolic ROS. Although mitochondrial ROS scavenging did not block HIF1α-accumulation at an early time point (24 h), it was persistently reduced on day 6. Therefore, mitochondrial ROS formation appears to occur initially downstream of the mTOR-cytoROS-HIF1α feedback loop but seems to be a crucial factor that controls the long-term activation of the mTOR-HIF1α-axis.Conclusion: In summary, our data demonstrate that mTOR dependent ROS production controls the oxLDL-induced trained innate immunity phenotype in human monocyte derived macrophages. Pharmacologic modulation of these pathways might provide a potential approach to modulate inflammation, associated with aberrant monocyte activation, during atherosclerosis development

Genetics of Host Response to Leishmania tropica in Mice – Different Control of Skin Pathology, Chemokine Reaction, and Invasion into Spleen and Liver

Several hundred million people are exposed to the risk of leishmaniasis, a disease caused by intracellular protozoan parasites of several Leishmania species and transmitted by phlebotomine sand flies. In humans, L. tropica causes cutaneous form of leishmaniasis with painful and long-persisting lesions in the site of the insect bite, but the parasites can also penetrate to internal organs. The relationship between the host genes and development of the disease was demonstrated for numerous infectious diseases. However, the search for susceptibility genes in the human population could be a difficult task. In such cases, animal models may help to discover the role of different genes in interactions between the parasite and the host. Unfortunately, the literature contains only a few publications about the use of animals for L. tropica studies. Here, we report an animal model suitable for genetic, pathological and drug studies in L. tropica infection. We show how the host genotype influences different disease symptoms: skin lesions, parasite dissemination to the lymph nodes, spleen and liver, and increase of levels of chemokines CCL2, CCL3 and CCL5 in serum

Memory T cells: promising biomarkers for evaluating protection and vaccine efficacy against leishmaniasis

Understanding the immune response to Leishmania infection and identifying biomarkers that correlate with protection are crucial for developing effective vaccines. One intriguing aspect of Leishmania infection is the persistence of parasites, even after apparent lesion healing. Various host cells, including dendritic cells, fibroblasts, and Langerhans cells, may serve as safe sites for latent infection. Memory T cells, especially tissue-resident memory T cells (TRM), play a crucial role in concomitant immunity against cutaneous Leishmania infections. These TRM cells are long-lasting and can protect against reinfection in the absence of persistent parasites. CD4+ TRM cells, in particular, have been implicated in protection against Leishmania infections. These cells are characterized by their ability to reside in the skin and rapidly respond to secondary infections by producing cytokines such as IFN-γ, which activates macrophages to kill parasites. The induction of CD4+ TRM cells has shown promise in experimental immunization, leading to protection against Leishmania challenge infections. Identifying biomarkers of protection is a critical step in vaccine development and CD4+ TRM cells hold potential as biomarkers, as their presence and functions may correlate with protection. While recent studies have shown that Leishmania-specific memory CD4+ T-cell subsets are present in individuals with a history of cutaneous leishmaniasis, further studies are needed to characterize CD4+ TRM cell populations. Overall, this review highlights the importance of memory T cells, particularly skin-resident CD4+ TRM cells, as promising targets for developing effective vaccines against leishmaniasis and as biomarkers of immune protection to assess the efficacy of candidate vaccines against human leishmaniasis

Genomická kontrola vnímavosti ke kožní leishmaniáze

6 Abstract Leishmaniasis is a neglected tropical disease, which belongs to the top health problems because it is endemic in 98 countries in Asia, Africa, the Americas and the Mediterranean region, and is gradually expanding to new areas, including Central Europe and USA. Clinical manifestations of leishmaniasis include a diverse range of forms, ranging from non-lethal cutaneous leishmaniasis to potentially lethal visceral leishmaniasis. Asymptomatic cases are known to exist in endemic areas. Different species of Leishmania induce distinct symptoms, but even the patients infected by the same species develop different symptoms and may respond differently to the treatment. Thus, one of the challenges is to explain the observed variability of leishmaniasis that cannot be attributed to the currently known factors. To find novel regulatory factors of the disease we tested molecules that were shown to play role in other infections and mapped loci controlling parasite load after L. major infection. We also determined genetic control of survival after infection with tick-borne encephalitis virus (TBEV) in order to establish whether there are common elements in response to L. major and TBEV. Interferon-induced GTPases (guanylate-binding proteins, GBPs) play an important role in inflammasome activation and mediate...10 Abstrakt Leismanióza je opomíjené tropické onemocnění, které se řadí k nejzávážnějším zdravotnickým problémům. Je endemické v 98 zemích Asie, Afriky, Ameriky a Středomoří a postupně se šíří do nových oblastí včetně střední Evropy a USA. Klinické formy leishmaniózy zahrnují široké spektrum projevů od kožní leishmaniózy až po potenciálně smrtelnou viscerální leishmaniózu. V endemických oblastech je znám výskyt asymptomatických případů. Různé druhy leishmanií indukují různé symptomy, ale dokonce pacienti infikovaní stejným druhem parazita mohou projevovat různé symptomy onemocnění a různě reagovat na léčbu. Proto je jednou z velkých výzev vysvětlení pozorované variability, kterou nelze vysvětlit pomocí současně známých faktorů. Abychom našli nové faktory regulující leishmaniózu, testovali jsme úlohu molekul, o nichž je známo, že se účastní regulace jiných infekcí, a mapovali jsme lokusy kontrolující množství parazitů po infekci L. major. Také jsme determinovali kontrolu přežití po infekci virem klíšťové encefalitidy (TBEV) s cílem určit, zda existují společné prvky v odpovědi k L. major a TBEV. Interferonem indukované GTPázy (guanylate-binding proteins, GBPs) hrají významnou úlohu v aktivaci inflamazómu a zprostředkovávají vrozenou rezistenci proti mnoha vnitrobuněčným patogenům. O jejich roli v...Czech Academy of SciencesAkademie věd ČRPřírodovědecká fakultaFaculty of Scienc

Genetic regulation of Leishmania infection

6 Abstract Leishmaniasis is a neglected tropical disease, which belongs to the top health problems because it is endemic in 98 countries in Asia, Africa, the Americas and the Mediterranean region, and is gradually expanding to new areas, including Central Europe and USA. Clinical manifestations of leishmaniasis include a diverse range of forms, ranging from non-lethal cutaneous leishmaniasis to potentially lethal visceral leishmaniasis. Asymptomatic cases are known to exist in endemic areas. Different species of Leishmania induce distinct symptoms, but even the patients infected by the same species develop different symptoms and may respond differently to the treatment. Thus, one of the challenges is to explain the observed variability of leishmaniasis that cannot be attributed to the currently known factors. To find novel regulatory factors of the disease we tested molecules that were shown to play role in other infections and mapped loci controlling parasite load after L. major infection. We also determined genetic control of survival after infection with tick-borne encephalitis virus (TBEV) in order to establish whether there are common elements in response to L. major and TBEV. Interferon-induced GTPases (guanylate-binding proteins, GBPs) play an important role in inflammasome activation and mediate..

Leishmania tropica: imunopathologie a genetická kontrola

Leishmaniasis is a neglected tropical disease caused by protozoan parasites of the genus Leishmania and transmitted by female sand flies. The outcome of Leishmania infection depends both on host and pathogen factors. Similarly as L. major, L. tropica very often causes cutaneous leishmaniasis in humans, but in rare occasions can also visceralize and cause systemic disease. Leishmaniasis cause by L. tropica has become a major public health problem in different endemic foci due to recent outbreaks in several urban areas and spread to new regions. The complications of the disease and lack of safe and effective drug and vaccine against the L. tropica infection require considerable attention to studies of the host-L. tropica interaction. Until recently, the research of leishmaniasis caused by L. tropica was limited due to lack of suitable inbred model and difficulties in inducing infection in animals. The aims of the present project were development of a suitable mouse model of the infection caused by L. tropica, and the study of mechanisms of the disease, and also mapping controlling genes/loci. We analysed susceptibility to L. tropica infection using recombinant congenic (RC) CcS/Dem mouse strains. These strains differ greatly in susceptibility to L. major due to random distribution of 12.5% of STS...Leishmanióza je opomíjená tropická nemoc způsobená prvočím parazitem rodu Leishmania, který je přenášen samičkami flebotomů. Rozdílné projevy infekce leishmániemi závisí na vlastnostech hostitele i patogenu. Podobně jako L. major i L. tropica často způsobuje u člověka kožní leishmaniózu, ale ve výjimečných případech může také visceralizovat a vést k systémovému onemocnění. Kvůli propuknutí nemoci v několika městských oblastech a jejímu proniknutí do nových regionů se leishmanióza působená parazitem L. tropica stala jedním z hlavních problémů veřejného zdraví v těchto různých endemických ohniscích. Komplikace spojené s nemocí a chybějící bezpečný a efektivní lék a vakcína proti infekci L. tropica vyžadují, aby byla studiu interakcí hostitele a patogenu věnována zvýšená pozornost. Donedávna byl výzkum leishmaniózy působené parazitem L. tropica limitován neexistencí vhodného zvířecího inbredního modelu a problémy při vyvolání infekce u zvířat. Cíle předkládaného projektu zahrnovaly vyvinutí vhodného myšího modelu infekce působené L. tropica, studium mechanismů nemoci a mapování kontrolních genů/lokusů. Analyzovali jsme vnímavost k infekci L. tropica s použitím rekombinantních kongenních (RC) myších kmenů série CcS/Dem. Tyto kmeny se díky náhodné distribuci 12,5% genomu kmene STS na pozadí 87,5% genomu...Department of Immunology and Clinical Biochemistry 3FM CUÚstav imunologie a klinické biochemie 3. LF3. lékařská fakultaThird Faculty of Medicin