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Objectives: Problematic substance use is one of the most stigmatised health conditions leading research to examine how the labels and models used to describe it influence public stigma. Two recent studies examine whether beliefs in a disease model of addiction influence public stigma but result in equivocal findings – in line with the mixed-blessings model, Kelly et al. (2021) found that whilst the label ‘chronically relapsing brain disease’ reduced blame attribution, it decreased prognostic optimism and increased perceived danger and need for continued care; however, Rundle et al. (2021) conclude absence of evidence. This study isolates the different factors used in these two studies to assess whether health condition (drug use vs. health concern), aetiological label (brain disease vs. problem), and attributional judgement (low vs. high treatment stability) influence public stigma towards problematic substance use. Methods: 1613 participants were assigned randomly to one of eight vignette conditions that manipulated these factors. They completed self-report measures of discrete and general public stigma and an indirect measure of discrimination. Results: Greater social distance, danger, and public stigma but lower blame were ascribed to drug use relative to a health concern. Greater (genetic) blame was reported when drug use was labelled as a ‘chronically relapsing brain disease’ relative to a ‘problem’. Findings for attributional judgement were either inconclusive or statistically equivalent. Discussion: The labels used to describe problematic substance use appear to impact discrete elements of stigma. We suggest that addiction is a functional attribution, which may explain the mixed literature on the impact of aetiological labels on stigma to date.

For the first time, alpha-ketoglutarate (AKG) was used to differentiate Spermatogonial stem cells (SSCs) in the presence of BMP-4 and Retinoic acid. So, SSCs were isolated from testis of 3-6 day-old mice by enzymatic digestion by collagenase and trypsin. The Cell suspension was cultured for one week in DMEM/F12 and 20% FBS in presence of GDNF growth factor. The proliferated cells were divided between control and treatment groups. In the control group, the cells were cultured for three weeks in DMEM/F12 containing 10% FBS in presence of 10-6 M retinoic acid and 40 ng/ml of BMP-4. A dose of 0.1 M AKG was added to the treatment group. The presence of Sertoli cells in culture system was confirmed by positive reaction of vimentin immunocytochemistry. The colonies that appeared on Sertoli cells also showed positive alkaline phosphatase activity and Oct4 immunocytochemistry reaction. qRT-PCR studies showed that the expression of Acrosin and Sycp3 genes was low in two groups after 7 days of culture. 21 days after culture, in the treatment group, the expression of Acrosin and Sycp3 genes was significantly increased rather than control group (p≤0.05). Large number of early spermatids were observed in the treatment group based on TEM studies.

Skin injuries lead to a large burden of morbidity. Although numerous clinical and scientific strategies have been investigated to repair injured skin, optimal regeneration therapy still poses a considerable obstacle. To address this challenge, the decellularized extracellular matrix-based scaffolds recellularized with stem cells offer significant advancements in skin regeneration and wound healing. Herein, a decellularized human placental sponge (DPS) was fabricated using the decellularization and freeze-drying technique, and then re-cellularized with human adipose-derived mesenchymal cells (MSCs). The biological and biomechanical properties and skin full-thickness wound healing capacity of the stem cells-DPS constructs were investigated in vitro and in vivo. The DPS exhibited a uniform three-dimensional microstructure with an interconnected pore network, 89.21% porosity, a low degradation rate, and good mechanical properties. The DPS and MSCs-DPS constructs were implanted in skin full-thickness wound models in mice. An accelerated wound healing was observed in the wounds implanted with MSCs-DPS construct when compared to DPS and control (wounds with no treatment) during 7 and 21 days post-implantation follow-up. In the MSCs-DPS group, the wound was completely re-epithelialized, the epidermis layer was properly organized, and the dermis and epidermis' bilayer structures were restored after 7 days. Our findings suggest DPS is an excellent carrier for MSCs culture and delivery to skin wounds and now promises to proceed with clinical evaluations.

Background: The use of medicinal plants has been one of the most common treatments since ancient times. Various plants are used in traditional and modern medicine, due to their antioxidant, antimicrobial and anticancer properties, and other biological potentials. Objective: In this study, the aerial parts of four species of Salvia including two populations of S. reuteriana Boiss., two populations of S. limbata C.A.Mey. and one population of each S. syriaca L. and S. ceratophylla L. species from Kashan region have been investigated. Methods: The antioxidative activity of the methanol extracts of plant samples were evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. The total phenol and flavonoid contents were determined via the Folin-Ciocalteu and aluminum chloride methods, respectively. The cytotoxic effects of samples on HeLa cells were determined through MTT assay. Results: Based on the results of DPPH assay, IC50 levels of methanolic extracts were in the range of 39.08 ± 0.15 to 163.77 ± 0.63 μg/ml, and total phenol contents were in the range of42.7 ± 3.09 to 105.8 ± 1.15 μg/mg. In addition, the flavonoid contents ranged from 30.07 ± 2.52 to 82.46 ± 2.2 μg/mg. There was a direct relationship between antioxidant activity and phenol compound contents. According to our study, the methanolic extracts of Salvia species showed toxicity effects on HeLa cells. Conclusion: The extracts of two populations of S. reuteriana were associated with the highest cytotoxicity, compared to other species of Salvia. Furthermore, all examined extracts exhibited weak to moderate antioxidant activities. The S. ceratophylla extract was associated with the highest antioxidant activity.

The prevalence and variety complaints of COVID-19 cases in a long term have been investigated in recent studies. The symptoms over the time are various and unpredictable which may persist several weeks after full recovery. The importance of long-COVID-19 manifestations includes its effect on the recovered cases which requires a rational management based on an accurate guideline to handle post-acute COVID-19 state. The aim of this study was to evaluate the incidence of post-acute COVID-19 syndrome and to identify the associated risk factors as well as to compare new and persistent symptoms at different post-acute phases. Totally 254 individuals from Pasteur Institute of Iran (or/and their relatives) were investigated who had a previously confirmed COVID-19 PCR test. The long-term manifestations of the virus were categorized through a time window as acute, ongoing, post-COVID and persistent phases and the individuals were assessed by the face-to-face or the phone call interview according to their complaints. The data were then statistically analyzed to determine the frequency of the symptoms and also the associated factors in which a p value 0.05 was considered significant. Except a small asymptotic group of five, 249 cases progressed the symptoms to acute phase among which 64.1% reported at least one symptom in post-acute phase. Neurological sequelae were found as the most frequent symptom (91.6%). Furthermore, there was a significant association between the underlying diseases, age and acute phase symptoms to the post-acute phase syndrome susceptibility (p 0.05). In conclusion, the increasing number of the reports and studies on long COVID-19 which can hugely affect the life quality should be more investigated and explored in terms of the pathophysiology to achieve appropriate treatments in time. The clusters of symptoms, specially a combination of neurological signs, presenting over months after the recovery impose a huge difficulty to the recovered population.

Streptococcus pneumoniae is a major pathogen in children, elderly subjects and immunodeficient patients. PTX3 is a fluid phase pattern recognition molecule (PRM) involved in resistance to selected microbial agents and in regulation of inflammation. The present study was designed to assess the role of PTX3 in invasive pneumococcal infection. In a murine model of invasive pneumococcal infection, PTX3 was strongly induced in non-hematopoietic (particularly, endothelial) cells. The IL-1β/MyD88 axis played a major role in regulation of the Ptx3 gene expression. Ptx3-/- mice were more susceptible to invasive pneumococcal infection. Although high concentrations of PTX3 had opsonic activity in vitro, no evidence of PTX3-enhanced phagocytosis was obtained in vivo. In contrast, Ptx3-deficient mice showed enhanced recruitment of neutrophils and inflammation. Using P-selectin deficient mice, we found that protection against pneumococcus was dependent upon PTX3-mediated regulation of neutrophil inflammation. In humans, PTX3 genetic polymorphisms were associated with invasive pneumococcal infections. Thus, this fluid phase PRM plays an important role in tuning inflammation and resistance against invasive pneumococcal infection.

Engineering of 3D substrates with maximum similarity to seminiferous tubules would help to produce functional sperm cells in vitro from stem cells. Here, we present a 3D electrospun gelatin (EG) substrate seeded with Sertoli cells and determine its potential for guided differentiation of embryonic stem cells (ESCs) toward germline cells. The EG was fabricated by electrospinning, and its morphology under SEM, as well as cytobiocompatibility for Sertoli cells and ESCs, was confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and cell attachment assay. Embryoid bodies (EBs) were formed from ESCs and co-cultured with Sertoli cells, induced with BMP4 for 3 and 7 consecutive days to induce the differentiation of EBs toward germline cells. The differentiation was investigated by immunocytochemistry (ICC), flow cytometry, and RT-PCR in four experimental groups of EBs (EBs cultured in gelatin-coated cell culture plates); Scaffold/EB (EBs cultured on EG); ESCs/Ser (EBs and Sertoli cells co-cultured on gelatin-coated cell culture plates without EG); and Scaffold/EB/Ser (EBs and Sertoli cells co-cultured on EG). All experimental groups exhibited a significantly increased MVH (germline-specific marker) and decreased c-KIT (stemness marker) expression when compared with the EB group. ICC and flow cytometry revealed that Scaffold/EB/Ser had the highest level of MVH and the lowest c-KIT expression at both 3 and 7 days postdifferentiation compared with other groups. RT-PCR results showed a significant increase in the germline marker (Dazl) and a significant decrease in the ESC stemness marker (Nanog) in Scaffold/EB compared to the EB group. The germline markers Gcna, Stella, Mvh, Stra8, Piwil2, and Dazl were significantly increased in Scaffold/EB/Ser compared to the Scaffold/EB group. Our findings revealed that the EG scaffold can provide an excellent substrate biomimicking the micro/nanostructure of native seminiferous tubules and a platform for Sertoli cell-EB communication required for growth and differentiation of ESCs into germline cells.

Objective: Novel vaccination approaches are required to control human immunodeficiency virus (HIV) infections. The membrane proximal external region (MPER) of Env gp41 subunit and the V3/glycans of Env gp120 subunit were known as potential antigenic targets for anti-HIV-1 vaccines. In this study, we prepared the modified dendritic cells (DCs) and mesenchymal stem cells (MSCs) with HIV-1 MPER-V3 gene using mechanical and chemical approaches. Methods: At first, MPER-V3 fusion DNA delivery was optimized in dendritic cells (DCs) and mesenchymal stem cells (MSCs) using three mechanical (i.e., uniaxial cyclic stretch, equiaxial cyclic stretch and shear stress bioreactors), and two chemical (i.e., TurboFect or Lipofectamine) methods. Next, the modified DCs and MSCs with MPER-V3 antigen were compared to induce immune responses in vivo. Results: Our data showed that the combination of equiaxial cyclic stretch loading and lipofectamine twice with 48 h intervals increased the efficiency of transfection about 60.21 ± 1.05 % and 65.06 ± 0.09 % for MSCs and DCs, respectively. Moreover, DCs and MSCs transfected with MPER-V3 DNA in heterologous DC or MSC prime/ peptide boost immunizations induced high levels of IgG2a, IgG2b, IFN-γ and IL-10 directed toward Th1 responses as well as an increased level of Granzyme B. Indeed, the modified MSCs and DCs with MPER-V3 DNA could significantly enhance the MPER/V3-specific T-cell responses compared to MPER/V3 peptide immunization. Conclusion: These findings showed that the modified MSC-based immunization could elicit effective immune responses against HIV antigen similar to the modified DC-based immunization.

Immunotherapy with DCs as antigen-presenting vehicles have already improved patients' outcome against a variety of tumors. Moreover, MSCs were recently used to develop anti-cancer therapeutic or anti-microbial prophylactic vaccines. The current study evaluated immune responses and anti-tumor effects generated by DCs and MSCs derived from mouse bone marrow which were modified with small heat shock proteins 27 and 20 (sHsp27 and sHsp20) and also E7 oncoprotein in tumor mouse model. Two vaccination strategies were utilized including homologous DC or MSC prime/ DC or MSC boost, and heterologous MSC or DC prime/ protein boost vaccinations. Our data revealed that DCs pulsed with E7+Hsp27 and/or E7+Hsp20 in homologous and heterologous prime/ boost vaccinations could stimulate high levels of IgG2a, IgG2b, IFN-γ and IL-10 directed toward Th1 responses. Moreover, these regimens induced an increased level of Granzyme B, and displayed complete protection more than 60 days after treatment. On the other hand, MSCs transfected with E7+Hsp27 DNA in homologous and heterologous prime/ boost vaccinations could significantly enhance the E7-specific T-cell responses and suppress tumor growth in mice. However, MSCs transfected with E7+Hsp20 DNA did not induce a complete protection against TC-1 tumor compared to DCs pulsed with E7+Hsp20 protein complexes. These results indicated that DC- and MSC-based vaccinations with specific modalities will be a useful approach for immunotherapy and protection against HPV-associated cancers.

Considering the Gaussian noise channel, Costa [4] investigated the concavity of the entropy power when the input signal and noise components are independent. His argument was connected to the first-order derivative of the Fisher information. In real situations, however, the noise can be highly dependent on the main signal. In this paper, we suppose that the input signal and noise variables are dependent. Then, some well-known copula functions are used to define their dependence structure. The first- and second-order derivatives of Fisher information of the model are obtained. Then, by using these derivatives, we will generalize two inequalities based on the Fisher information and a functional that is closely associated to Fisher information for the case when the input signal and noise variables are dependent. We will also show that the previous results for the independent case are recovered as special cases of our result. Several applications are provided to support the usefulness of our results. Finally, the channel capacity of the Gaussian noise channel model with dependent signal and noise is studied.

The aim of this paper was to design and fabricate a novel composite scaffold based on the combination of 3D-printed polylactic acid-based triply periodic minimal surfaces (TPMSs) and cell-laden alginate hydrogel. This novel scaffold improves the low mechanical properties of alginate hydrogel and can also provide a scaffold with a suitable pore size, which can be used in bone regeneration applications. In this regard, an implicit function was used to generate some gyroid TPMS scaffolds. Then the fused deposition modeling process was employed to print the scaffolds. Moreover, the micro computed tomography technique was employed to assess the microstructure of 3D-printed TPMS scaffolds and obtain the real geometries of printed scaffolds. The mechanical properties of composite scaffolds were investigated under compression tests experimentally. It was shown that different mechanical behaviors could be obtained for different implicit function parameters. In this research, to assess the mechanical behavior of printed scaffolds in terms of the strain–stress curves on, two approaches were presented: equivalent volume and finite element-based volume. Results of strain–stress curves showed that the finite-element based approach predicts a higher level of stress. Moreover, the biological response of composite scaffolds in terms of cell viability, cell proliferation, and cell attachment was investigated. In this vein, a dynamic cell culture system was designed and fabricated, which improves mass transport through the composite scaffolds and applies mechanical loading to the cells, which helps cell proliferation. Moreover, the results of the novel composite scaffolds were compared to those without alginate, and it was shown that the composite scaffold could create more viability and cell proliferation in both dynamic and static cultures. Also, it was shown that scaffolds in dynamic cell culture have a better biological response than in static culture. In addition, scanning electron microscopy was employed to study the cell adhesion on the composite scaffolds, which showed excellent attachment between the scaffolds and cells.

"Available online 24 December 2020", Decellularization, preservation protocol and storage time influence the biomechanical and biological properties of allografts and xenografts. Here, we examined the consequences of storage time on the antibacterial, angiogenic and biocompatibility properties of the decellularized placental sponge (DPS) in vitro and in vivo. The DPS samples were preserved for one, three and six months at −20 °C. The decellularized scaffolds showed uniform morphology with interconnected pores compared with not decellularized sponges. Storage time did not interfere with collagen and vascular endothelial growth factor contents, and cytobiocompatibility for Hu02 fibroblast cells. Chorioallantoic membrane assay and subcutaneous implantation indicated a decreased new vessel formation and neovascularization in six months DPS sample compared with other experimental groups. The number of CD4+ and CD68+ cells infiltrated into the six months DPS on the implanted site showed a significant increase compared with one and three months sponges. The antibacterial activities and angiogenic properties of the DPS decreased over storage time. Three months preservation at −20 °C is suggested as the optimal storage period to retain its antibacterial activity and high stimulation of new vessel formation. This storage protocol could be considered for preservation of similar decellularized placenta-derived products with the aim of retaining their biological properties., This study was supported by Iran University of Medical Sciences (grant no; 15535) and Iran National Science Foundation (INSF, 98022911). SCK presently holds European Research Area Chair and Full Professor position at 3Bs Research Group, University of Minho, Portugal supported by the European Union Framework Programme for Research and Innovation HORIZON 2020 under grant agreement no. 668983 - FoReCaST

Engineering of 3D substrates with maximum similarity to seminiferous tubules would help to produce functional sperm cells

strongObjective:/strongEpigenetic and genetic changes have important roles in stem cell achievements. Accordingly, the aim of thisbr /study is the evaluation of the epigenetic and genetic alterations of different culture systems, considering their efficacy inbr /propagating human spermatogonial stem cells isolated by magnetic-activated cell sorting (MACS).br /strongMaterials and Methods:/strongIn this experimental study, obstructive azoospermia (OA) patient-derived spermatogonial cells were divided into two groups. The MACS enriched and non-enriched spermatogonial stem cells (SSCs) were cultured in the control and treated groups; co-culture of SSCs with Sertoli cells of men with OA, co-culture of SSCs with healthy Sertoli cells of fertile men, the culture of SSCs on PLA nanofiber and culture of testicular cell suspension. Gene-specific methylation by MSP, expression of pluripotency (NANOG, C-MYC and OCT-4), and germ cells specific genes (Integrin α6, Integrin β1, PLZF) evaluated. Cultured SSCs from the optimized group were transplanted into the recipient azoospermic mouse.br /strongResults:/strongThe use of MACS for the purification of human stem cells was effective at about 69% with the culture of the testicular suspension, being the best culture system. Upon purification, the germ-specific gene expression was significantly higher in testicular cell suspension and treated groups (P≤0.05). During the culture time, gene-specific methylation patterns of the examined genes did not show any changes. Our data from transplantation indicated the homing of the donor-derived cells and the presence of human functional sperm.br /strongConclusion:/strongOur in vivo and in vitro results confirmed that culture of testicular cell suspension and selection ofbr /spermatogonial cells could be effective ways for purification and enrichment of the functional human spermatogonial cells. The epigenetic patterns showed that the specific methylation of the evaluated genes at this stage remained constant with no alteration throughout the entire culture systems over time.

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The molecular mechanisms of drug use on sexual health are largely unknown. We investigated, the relationship between heroin use disorder and epigenetic factors influencing histone acetylation in sperm cells. The volunteers included twenty-four 20- to 50-year-old men with a normal spermogram who did not consume any drugs and twenty-four age- to BMI-matched men who consume only the drug heroin for more than last four months. HDAC1 and HDAC11 mRNA expression levels in spermatozoa and miR-34c-5p and miR-125b-5p expression levels in seminal plasma were measured. The heroin-user group showed significantly increased white blood cell counts and decreased sperm motility and survival rates (8.61 ± 1.73, 21.50 ± 3.11, 69.90 ± 4.69 respectively) as compared to the control group (1.49 ± 0.32, 38.82 ± 3.05, 87.50 ± 0.99 respectively) (p ≤ .001). An increase in DNA fragmentation index (DFI) (heroin-user group: 41.93 ± 6.59% and control group: 10.14 ± 1.43%, p = .003), a change in frequency of HDAC1 (heroin-user group: 1.69 ± 0.55 and control group: 0.45 ± 0.14, p = .045) and HDAC11 (heroin-user group: 0.29 ± 0.13 and control group: 2.36 ± 0.76, p = .019) in spermatozoa and a significant decrease in seminal miR-125b-5p abundance (heroin-user group: 0.37 ± 0.11 and control group: 1.59 ± 0.47, p = .028) were reported in heroin consumers. Heroin use can lead to male infertility by causing leukocytospermia, asthenozoospermia, DFI elevation in sperm cells and alterations in seminal RNA profile.

This study was performed to evaluate the effects of Lactobacillus acidophilus bacteria as a probiotic on chicken T cell subset populations in peripheral blood and lymphoid tissues. Thirty chickens were divided into three groups and fed sterilised cow milk, a mixture of milk and L. acidophilus (probiotic), or neither, as the control group. Chickens were euthanised after 14 and 21 days, and whole blood and ileal, bursal, and caecal tonsillar tissues were collected. The populations of T cell subsets, including CD4+, CD8+, and TCR1+cells, were evaluated by immunohistochemistry and flow cytometry. After 21 days of treatment the percentage of blood CD4+, CD8+, and TCR1+cells was significantly higher in the probiotic-fed group than in the control group. After 14 days of treatment, a significantly greater number of CD4+T cells were found in the ileum of probiotic-fed chickens than in chickens from the other two groups. This difference was even greater after 21 days. In addition, after 21 days, a significantly greater number of TCR1+cells were found in the caecal tonsils of milk-fed chickens than in chickens from the control group. The findings indicate that probiotics may alter the distribution of T cells in the blood and lymphoid tissues in young chickens; however, transient changes in lymphoid tissues indicate that probiotics likely do not permanently affect mucosal immunity.

Chronic myeloid leukemia (CML) is a malignant blood disease with a particular chromosomal aberration that is known as a common form of leukemia. The chromene family exhibits strong anti-cancer effects. Therefore, the effects of six members of the dihydropyrano [2,3-g] chromene family on cell toxicity and apoptosis induction in K562 cancer cells were investigated and compared with those of normal peripheral blood mononuclear cells (PBMCs). The K562 cells were cultured in the presence of the aforementioned chromene derivatives at concentrations of 40 to 200 μM for 24 to 72 h. The effects of these compounds on the growth and viability of the K562 cell line and PBMCs were studied through MTT assay. Furthermore, apoptosis induction was investigated using flow cytometry. Real-time PCR was used for relative quantification of BCL2, Bax, TP53 and BCR- ABL genes after 48 h of exposing K562 cells and PBMCs to 4-Clpgc. Based on the results, these chromene derivatives inhibited the growth of K562 cells. According to the obtained data, 4-Clpgc was the strongest compound with IC50 values of 102 ± 1.6 μM and 143 ± 9.41 μM in K562 cells and PBMCs, while pgc was the weakest one with IC50 levels of 278 ± 2.7 μM and 366 ± 47 μM in K562 cells and PBMCs (after 72 h), respectively. The results demonstrated that the apoptotic cell percentage in the control group increased from 6.09% to 84.10% and 17.2% to 20.06% in K562 cells and PBMCs after 48 h of treatment, respectively. Moreover, 4-Clpgc treatment increased the expression of Bax and TP53 genes by 42.74 and 35.88 folds in K562 cells and 9.60 and 7.75 folds in PBMCs, respectively. On the other hand, the expression of BCL2 was reduced by 1.47 and 1.38 folds in K562 cells and PBMCs, respectively. These compounds were associated with less toxic effects on normal cells, compared to the cancer cells. In conclusion, these derivatives can be considered as appropriate candidates for leukemia treatment.

Background: More than 30,000 people die every year in the United States, and the number of suicides in excess of 650,000 people is now among eight major deaths in the United States. The rate of suicide among different nations varies from 25 to 10,000 in Scandinavia, Switzerland, Germany, Austria the countries of Eastern Europe and Japan to less than 10 in 10,000 people in Spain, Italy, Ireland, Egypt, and the Netherlands. Suicide in Iran by the forensic organization in 1380 suggests that 5.7 suicides per 100,000 men and 3.1 suicide per 100,000 women occur in the country. Statistics show that suicide rate in men in European and North American countries and South-central Asian countries is lower and in Western Asia is higher than other countries. Furthermore, statistics show that Iran and Georgia have the highest rate of suicide in western Asia. Methods: This was a retrospective descriptive study. The aim of this study was to investigate the epidemiologic pattern of suicide cases referred to hospitals affiliated with Isfahan Health Center No.1 in 1395. The statistics were collected by examining the accident and accident forms and then analyzed using SPSS software package. Results: Of 21239 incidents, 3371 (15.8%) were related to suicide and the second highest accident rate occurred in urban areas, 50% were males and 50% were women. 98% of suicides occurred in urban areas and 2% in rural areas. In terms of the place of suicide, most cases occurred with 99% at home. The highest rate of suicide was found in the age groups of 20-29 years (39.5%), 30-39 (28.6%), 10-19 years (17.6%), 40-49 years (10.3%) and 50-59 years (2.3%). More than 99% of suicides was treated and only 12 people reported death. Conclusions: The results of this study indicate that suicide among accidents has a high percentage which requires a special look as one of the components of social health. However, the existence of suicide at a young age and aged generational and active community of alarm Serious for mental health in the community. Since most suicides have occurred in urban areas and there are several factors such as stress, economic problems, lifestyles and other cultural and economic factors involved in it, more research is needed to accurately identify the causes and factors of suicide and find ways to prevent it. This is underlined by this article. Keywords: Suicide, Active age group, Prevention

Background The innate immune system recalls a challenge to adapt to a secondary challenge, a phenomenon called trained immunity. Training involves cellular metabolic, epigenetic and functional reprogramming, but how broadly trained immunity protects from infections is unknown. For the first time, we addressed whether trained immunity provides protection in a large panel of preclinical models of infections. Methods Mice were trained and subjected to systemic infections, peritonitis, enteritis, and pneumonia induced by Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, Citrobacter rodentium, and Pseudomonas aeruginosa. Bacteria, cytokines, leukocytes, and hematopoietic precursors were quantified in blood, bone marrow, and organs. The role of monocytes/macrophages, granulocytes, and interleukin 1 signaling was investigated using depletion or blocking approaches. Results Induction of trained immunity protected mice in all preclinical models, including when training and infection were initiated in distant organs. Trained immunity increased bone marrow hematopoietic progenitors, blood Ly6Chigh inflammatory monocytes and granulocytes, and sustained blood antimicrobial responses. Monocytes/macrophages and interleukin 1 signaling were required to protect trained mice from listeriosis. Trained mice were efficiently protected from peritonitis and listeriosis for up to 5 weeks. Conclusions Trained immunity confers broad-spectrum protection against lethal bacterial infections. These observations support the development of trained immunity-based strategies to improve host defenses., We used preclinical models to demonstrate that trained immunity confers broad-spectrum protection against bacterial infections. Trained immunity increased myeloid progenitors and circulating inflammatory monocytes and neutrophils, and depletion or neutralization of monocytes/macrophages and interleukin 1 signaling impaired trained immunity-mediated protection.

To evaluate the effects slow-freezing and vitrification on three dimensional in vitro culture of preantral follicles, ovaries of 12-14 days old female NMRI mice were isolated and randomly assigned to fresh control, slow-freezing and vitrification groups. Slow-freezing was performed using programmable freezer. Vitrification was carried out in a medium consisting of ethylene glycol (EG) and dimethyl sulphoxide (Me2SO) by needle immersion method. middle sized preantral follicles were mechanically isolated and cultured for 12 days in 0.7% sodium alginate gel. The follicles development and quantitative expression of oocyte specific genes (Bmp15, Gdf9, Fgf8) and the growth related genes (Igf1, Kit, Kit-l) were assessed after 1, 8 and 12 days of culture. Both cryopreserved groups showed reduction of follicular survival rates compared to the control group on days 8 and 12 of culture (P < 0.05). Antrum formation rates reduced in slow-freezing after 12 days of culture (P < 0.05). Evaluation of gene expression showed reduction of Bmp15, Gdf9, Fgf8, Kit and Kit-l during 12 days of culture (P < 0.05). Kit and Kit-l expression in slow-freezing group significantly reduced on day 8 of culture (p < 0.05). Igf1 expression was lower in slow-freezing group on 1st day of culture than vitrification and control groups (P < 0.05). Finally, intergroup comparison showed same expression pattern of genes after 12 days of culture. Thus, cryopreservation of mouse ovaries by both methods can preserve most developmental parameters and expression of maturation genes. However, vitrification is a better method for cryopreservation of mouse ovaries due to greater antrum formation and expression of growth related markers.

It was proposed that probiotics may influence immune system through direct or indirect exposure. Direct exposure is mostly mediated by surface receptors. Toll-like receptors (TLRs) are conserved molecular sensors which could be triggered via some pathogen associated structures, hence, modulate the immune responses. This study was conducted to elucidate the impact of lactobacillus acidophilus as a common probiotic on the expression level of TLRs in the chicken's cecal tonsil.Thirty one-day-old chicken were selected and separated into three groups as probiotic-fed, dairy-fed and control. In addition to commercial powder supply, each chicken in the probiotic-fed group received 109 CFU/Kg of L. acidophilus daily. While, chickens in the dairy-fed group were provided with commercial powder feed and sterile dairy milk. After 14 and 21 days of oral feeding the cecal tonsil was removed and the expression of TLR2, TLR4 and TLR5 were examined by real-time PCR.At the age of 14-day, there was a slight upregulation in the expression levels of TLR2 (118.9%), TLR4 (129.6%) and TLR5 (123.7%) of the cecal tonsil in the probiotic-fed group; however, these alterations were not statistically significant. At the age of 21-day, a non-significant downregulation was observed in TLR expression level of both dairy-fed (TLR2, 85%; TLR4, 79.5%; and TLR5, 86.5%) and probiotic-fed (TLR2, 88.8%; TLR4, 81%; and TLR5, 87.2%) groups in comparison to controls.The findings revealed that although the probiotic supplementation could be useful but it did not significantly affect innate immunity state through alteration of TLRs.

Objective Headache Impact Test (HIT-6) measures the impact headaches in a 1-month period. We validated the Persian translation of HIT-6, compared the HIT-6 psychometric analysis between migraine and tension-type headache (TTH) patients, and evaluated the capability of HIT-6 to differentiate between TTH, chronic migraine, and episodic migraine. Methods Qualified participants, including 274 patients diagnosed with migraine or TTH, were required to complete HIT-6, SF-36v2, and a symptoms questionnaire on their first visit. At 3 and 8 weeks from first visit, participants completed HIT-6. Internal consistency (Cronbach's α) and test–retest reproducibility (Pearson's correlation coefficient) were used to assess reliability. Convergent validity was also assessed. Results Tension-type headache, episodic, and chronic migraines included 24.5%, 61.9%, and 13.6% of the participants, respectively. Internal consistency among all patients, TTH, and migraine in the first visit were 0.74, 0.77, and 0.73, respectively. Test–retest reliability for HIT-6 between visit 1 and 2 showed a moderate level of correlation (r = 0.50). Convergent validity and also item total correlation were acceptable. There was no significant difference in HIT-6 total score between TTH and migraine. Conclusion Persian HIT-6 is a valid and reliable questionnaire for the evaluation of headache. However, it cannot differentiate between chronic migraine, episodic migraine, and TTH in Iranian population.

Pourbabaei H, Asgari F, Reif A, Abedi R. 2012. Effect of plantations on plant species diversity in the Darabkola, Mazandaran Province, North of Iran. Biodiversitas 13: 72-78. In this study, the effect of plantations on plant species diversity was investigated in Darabkola, Mazandaran province, north of Iran. To conduct the study, a natural mixed forest, a broad–leaved plantation (Alnus subcordata-Acer velutinum) and a coniferous plantation (Cupressus sempervirens var. horizontalis-Pinus brutia) were selected. 35 sampling plots were taken in systematic random method in each area. Data analysis was carried out using Simpson, Hill's N2, Shannon-Wiener and Mc Arthur's N1 diversity indices, Smith and Wilson evenness index and species richness. Results revealed that there were 32 plant species in natural forest and 30 plant species were found in each plantation. Rosaceae and Lamiaceae were the main families in the studied areas. Diversity and evenness indices of all vegetation layers had the most values in the natural forest. Richness of woody plants had the highest value in the natural forest, while herbaceous richness was the highest in coniferous plantation. Mc Arthur's N1 had the highest value among diversity indices and followed by Hill's N2, Shannon-Wiener and Simpson indices, respectively. In addition, results showed that there were significant differences among diversity, evenness and richness indices in all vegetation layers in the three studied areas.

Background: Hypervariability of HCV proteins is an important obstacle to design an efficient vaccine for HCV infection. Multi-epitope vaccines containing conserved epitopes of the virus could be a promising approach for protection against HCV. Objectives: Cellular and humoral immune responses against multi-epitope DNA and peptide vaccines were evaluated in BALB/c mice. Materials and Methods: In this experimental study, multi-epitope DNA- and peptide-based vaccines for HCV infection harboring immunodominant CD8+ T cell epitopes (HLA-A2 and H2-Dd) from Core (132-142), NS3 (1073-1081) and NS5B (2727-2735), a Th CD4+ epitope from NS3 (1248-1262) and a B-cell epitope from E2 (412-426) were designed. Multi-epitope DNA and peptide vaccines were tested in two regimens as heterologous DNA/peptide (group 1) and homologous peptide/peptide (group 2) prime/boost vaccine in BALB/c mice model. Electroporation was used for delivery of the DNA vaccine. Peptide vaccine was formulated with Montanide ISA 720 (M720) as adjuvant. Cytokine assay and antibody detection were performed to analyze the immune responses. Results: Mice immunized with multi-epitope peptide formulated with M720 developed higher HCV-specific levels of total IgG, IgG1 and IgG2a than those immunized with multi-epitope DNA vaccine. IFN-γ levels in group 2 were significantly higher than group 1 (i.e. 3 weeks after the last immunization; 37.61 ± 2.39 vs. 14.43 ± 0.43, P < 0.05). Moreover, group 2 had a higher IFN-γ/IL-4 ratio compared to group 1, suggesting a shift toward Th1 response. In addition, in the present study, induced immune responses were long lasting and stable after 9 weeks of the last immunization. Conclusions: Evaluation of multi-epitope DNA and peptide-vaccines confirmed their specific immunogenicity in BALB/c mice. However, lower Th1 immune responses in mice immunized with DNA vaccine suggests further investigations to improve the immunogenicity of the multi-epitope DNA vaccine through immune enhancers.

Background. There have been few studies on the relation between vitamin D and migraine. We investigated the prevalence of vitamin D deficiency in migraine patients and compared it with a control group. We also evaluated the relationship of vitamin D deficiency with severity of migraine.Methods. 105 newly diagnosed migraine patients and 110 controls, matched for age, sex, socioeconomic status, education, and sun exposure, were enrolled during the spring of 2011. 25-Hydroxy vitamin D [25(OH)D] plasma levels were measured by chemiluminescence immunoassay.Results. The mean ± SE concentration of 25(OH)D was13.55±0.91 ng/mL in cases and13.19±1.19 ng/mL in controls. There was no significant difference in 25(OH)D concentration between cases and controls. We found no relationship between severity of headache and 25(OH)D status.Conclusions. We did not find any association between migraine and vitamin D status; also, severity of headaches was not related to 25(OH)D level. Further studies with larger sample sizes are required to confirm our results.