Effect of General Practitioner Training in a Collaborative Child Mental Health Care Program on Children's Mental Health Outcomes in a Low-Resource Setting: A Cluster Randomized Trial.

Importance: Integrated care for children is rarely studied, especially in low- and middle-income countries, where generalists often provide mental health care. Objectives: To explore the effect of adding a child and youth component to an existing adult collaborative care program on mental health outcomes and receipt of care. Design, Setting, and Participants: This cluster randomized trial was conducted within an adult collaborative care program in Tehran, Iran. General practitioners (GPs), their 5- to 15-year-old patients, and patients' parents were included. Children and youths coming for routine medical visits who scored greater than the cutoff on the Strengths and Difficulties Questionnaire (SDQ) were followed up for 6 months. The study was conducted from May 2018 to October 2019, and analysis was conducted from March 2020 to August 2021. Interventions: GPs were randomized to either a 2.5-day training on managing common child mental health problems (intervention) or refresher training on identification and referral (control). Main Outcomes and Measures: Primary outcome was change in SDQ total problems score; secondary outcomes included discussion of psychosocial issues by the GPs and receipt of mental health care during the follow-up period. Results: Overall, 49 GPs cared for 389 children who scored greater than the cutoff on the SDQ (216 children in intervention group, 173 in control group). Patients' mean (SD) age was 8.9 (2.9) years (range, 5 to 15 years), and 182 (47%) were female patients. At 6 months, children in the intervention group had greater odds of receiving mental health care during the study (odds ratio [OR], 3.0; 95% CI, 1.1 to 7.7), parents were more likely to report that intervention GPs had discussed parent (OR, 2.1; 95% Cl, 1.1 to 3.8) and child (OR, 2.0; 95% Cl, 0.9 to 4.8) psychosocial issues, and intervention GPs were more likely to say they had provided counseling (OR, 1.8; 95% Cl, 1.02 to 3.3). However, there was no greater improvement in SDQ scores among children seen by intervention vs control GPs. Adjusted for clustering within GP, the variables used for balanced allocation (practice size, practice ownership, and study wave), and the other variables associated with change in SDQ scores over time, there was not a significant time-treatment interaction at either the 3- or 6-month follow-up points (linear combination of coefficients for intervention, 0.57 [95% CI, -1.07 to 2.22] and -0.08 [95%CI, -1.76 to 1.56], respectively). In a subgroup of GPs with practices composed of 50% or more children, children seen by intervention GPs improved to a significantly greater extent (-3.6 points; 95% CI, -6.7 to -0.46 points; effect size d = 0.66; 95% CI, 0.30 to 1.01) compared with those seen by control GPs. Conclusions and Relevance: In this cluster randomized trial, GP training on managing common child mental health problems did not demonstrate greater improvement in child SDQ scores. Child mental health training for GPs in collaborative care can improve children's access to mental health care, but prior experience working with children and their families may be required for GPs to use a brief training in a way that improves child outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT03144739.

All-Trans Retinoic Acid-Preconditioned Mesenchymal Stem Cells Improve Motor Function and Alleviate Tissue Damage After Spinal Cord Injury by Inhibition of HMGB1/NF-κB/NLRP3 Pathway Through Autophagy Activation.

Spinal cord injury (SCI) is a significant public health issue that imposes numerous burdens on patients and society. Uncontrolled excessive inflammation in the second pathological phase of SCI can aggravate the injury. In this paper, we hypothesized that suppressing inflammatory pathways via autophagy could aid functional recovery, and prevent spinal cord tissue degeneration following SCI. To this end, we examined the effects of intrathecal injection of all-trans retinoic acid (ATRA)-preconditioned bone marrow mesenchymal stem cells (BM-MSCs) (ATRA-MSCs) on autophagy activity and the HMGB1/NF-κB/NLRP3 inflammatory pathway in an SCI rat model. This study demonstrated that SCI increased the expression of Beclin-1 (an autophagy-related gene) and NLRP3 inflammasome components such as NLRP3, ASC, Caspase-1, and pro-inflammatory cytokines IL-1ß, IL-18, IL-6, and TNF-α. Additionally, following SCI, the protein levels of key autophagy factors (Beclin-1 and LC3-II) and HMGB1/NF-κB/NLRP3 pathway factors (HMGB1, p-NF-κB, NLRP3, IL-1ß, and TNF-α) increased. Our findings indicated that ATRA-MSCs enhanced Beclin-1 and LC3-II levels, regulated the HMGB1/NF-κB/NLRP3 pathway, and inhibited pro-inflammatory cytokines. These factors improved hind limb motor activity and aided in the survival of neurons. Furthermore, ATRA-MSCs demonstrated greater beneficial effects than MSCs in treating spinal cord injury. Overall, ATRA-MSC treatment revealed beneficial effects on the damaged spinal cord by suppressing excessive inflammation and activating autophagy. Further research and investigation of the pathways involved in SCI and the use of amplified stem cells may be beneficial for future clinical use.

MicroRNA-30a-5p promotes differentiation in neonatal mouse spermatogonial stem cells (SSCs).

BACKGROUND: The importance of spermatogonial stem cells (SSCs) in spermatogenesis is crucial and intrinsic factors and extrinsic signals mediate fate decisions of SSCs. Among endogenous regulators, microRNAs (miRNAs) play critical role in spermatogenesis. However, the mechanisms which individual miRNAs regulate self- renewal and differentiation of SSCs are unknown. The aim of this study was to investigate effects of miRNA-30a-5p inhibitor on fate determinations of SSCs. METHODS: SSCs were isolated from testes of neonate mice (3-6 days old) and their purities were performed by flow cytometry with ID4 and Thy1 markers. Cultured cells were transfected with miRNA- 30a-5p inhibitor. Evaluation of the proliferation (GFRA1, PLZF and ID4) and differentiation (C-Kit & STRA8) markers of SSCs were accomplished by immunocytochemistry and western blot 48 h after transfection. RESULTS: Based on the results of flow cytometry with ID4 and Thy1 markers, percentage of purity of SSCs was about 84.3 and 97.4 % respectively. It was found that expression of differentiation markers after transfection was significantly higher in miRNA-30a- 5p inhibitor group compared to other groups. The results of proliferation markers evaluation also showed decrease of GFRA1, PLZF and ID4 protein in SSCs transfected with miRNA-30a-5p inhibitor compared to the other groups. CONCLUSIONS: It can be concluded that inhibition of miRNA-30a-5p by overexpression of differentiation markers promotes differentiation of Spermatogonial Stem Cells.

Children and adolescents' mental health in Iran's primary care: Perspectives of general practitioners, school staff and help seekers.

BACKGROUND: Iran has well-established networks for primary care staffed by general practitioners who provide services to patients across the lifespan. Iran recently established collaborative care networks to build general practitioners' capacity to provide adult mental health services. In an NIH-funded study, we are designing and evaluating a training program for general practitioners (GPs) to extend this collaboration to include services for children and adolescents. In the formative phase of this project, we conducted a qualitative study to obtain information relevant to the design of the training program. METHODS: We conducted semi-structured individual interviews with 28 stakeholders; including 15 GPs working in a collaborative care network, 6 parents and 4 adolescents who had received child mental health care from a GP, and 3 policymakers. We also held a focus group discussion with 8 school teachers and counselors. All interviews were transcribed during the interviews' sessions and then were thematically analyzed. RESULTS: GPs reported seeing a range of child emotional and behavioral problems but felt the need for additional training in diagnosis and management, especially in skills for interviewing and communicating with children. GPs also expressed the need to understand legal issues involved in treating children, including cases of possible child abuse. School staff agreed that GPs could help with children's educational and emotional problems but also believed GPs would need extra training. Parents indicated a preference for GPs over psychiatrists (as did adolescents) as a source of mental health care, and for psychological over pharmacological interventions. Adolescents expressed a preference not to speak about private issues in the presence of their parents, and expressed concern that the GPs did not respect their preference. They also desired a more active role during visits. CONCLUSIONS: Before expanding the scope of practice of Iranian GPs to provide management of common emotional and behavioral problems in children and adolescents, the concerns and specific needs of these practitioners need to be addressed. Parents and youth in the study expressed a preference for mental health care from a GP rather than a specialist. However, they also commented on the need for restructuring the current GP visits to facilitate youth participation. These findings provide directions for expanding the scope of practice of adult collaborative care networks to meet the mental health care needs of children and adolescents more expeditiously and effectively.

Notch signaling pathway in cumulus cells reflecting zygote and embryo quality in polycystic ovary syndrome.

PURPOSE: The present study aimed to explore the associations between the expression pattern of molecules in the Notch pathway in the cumulus cells of polycystic ovary syndrome (PCOS) patients and the quality of zygotes and embryos. METHODS: A total of 200 cumulus complexes surrounding mature oocytes were obtained from 40 patients with and without PCOS undergoing intracytoplasmic sperm injection (ICSI). The expressions of Notch-1, Notch-2, and Notch-3 genes were examined by Reverse Transcription Q-PCR assay. Moreover, immunocytochemistry was performed for the expressions of Jagged-1 and Jagged-2 proteins. The correlations between the Notch receptors and their ligand expressions and the qualities of the zygote and embryo were investigated. RESULTS: The expression levels of Notch-2, Notch-3, Jagged-1, and Jagged-2 were significantly lower in patients with PCOS than in normal women (p < 0.05), while Notch-1 showed no meaningful difference between the groups. A positive correlation was found between Notch-1 and embryo quality. Furthermore, only Notch-2 and Jagged-2 marginally correlated with zygote quality. CONCLUSION: The data of the present study indicated that evaluating the molecules in the Notch pathway in PCOS patients' cumulus cells provides a novel approach to predict the zygote and embryo quality. However, further studies on a larger population are needed to validate this finding.

Aqueous Origanum vulgare Extract Improves the Quality of Cryopreserved Human Spermatozoa Through Its Antioxidant Effects.

Excessive production of reactive oxygen species (ROS) during semen cryopreservation can induce structural and functional changes in spermatozoa. It is well known that antioxidants can mitigate the effect of ROS. Moreover, the application of antioxidants in freezing media is an appropriate strategy for protecting spermatozoa against deleterious effects of ROS during the cryopreservation process. As an example, oregano is a medicinal plant with important activities, with antiseptic, antibacterial, antithrombotic, and antioxidant properties. This study aimed at evaluating the antioxidant effects of oregano extract on cryopreserved human spermatozoa. In the first phase, 13 semen samples with different concentrations of oregano extract (0.0, 50, 100, 150, 300, and 500 µg/mL) were cryopreserved to achieve an optimal dose of oregano extract. Then, motility, viability, and plasma membrane integrity were evaluated. In the second phase, 20 samples were cryopreserved in freezing media supplemented with or without the optimal concentration of oregano (100 µg/mL). After thawing, motility, the levels of ROS, lipid peroxidation, and translocation of phosphatidylserine (PS) were evaluated. The results showed that 100 µg/mL oregano extract significantly increased the total motility in frozen-thawed spermatozoa in comparison with the control group (28.2 ± 4.3 vs. 42.4 ± 1.6, p < 0.05). This concentration significantly decreased the percentage of 2',7'-dichlorofluorescein-positive cells (25.53 ± 1.2 vs. 21.48 ± 1.2) and the malondialdehyde level (4.25 ± 0.7 vs. 0.82 ± 0.4 µM) (p < 0.05). In the oregano group, the percentage of vital spermatozoa without PS externalization was significantly higher than that in the control group (25.88 ± 1.6 vs. 16.8 ± 1.9, p < 0.001), while the percentage of dead spermatozoa with PS externalization spermatozoa was significantly lower than that in the control group (51.65 ± 1.4 vs. 60.36 ± 1.9, p < 0.05). In general, the addition of oregano extract to sperm freezing extender has protective effects against oxidative stress and apoptosis.

The effect of cryopreservation on DNA methylation patterns of the chromosome 15q11-q13 region in human spermatozoa.

Human sperm cryopreservation is a common technique which is used in assisted reproductive technologies. Despite the existence of evidence supporting the production of ROS and DNA fragmentation during sperm cryopreservation, there is little and equivocal information about the cryopreservation effects on methylation of imprinted genes and imprinting control regions. In this study, we have investigated the effects of cryopreservation on DNA methylation in promoter regions of SNURF-SNRPN and UBE3A imprinted genes, PWS-ICR and AS-ICR in the chromosome 15q11-q13 region. Semen samples from 10 healthy normozoospermic men were collected and each sample was divided into four equal aliquots: fresh, cryoprotectant, cryopreservation, and H2O2. We measured the ROS levels and DNA fragmentation using DCFH-DA and TUNEL assay respectively by flow cytometry. DNA methylation in promoter regions of SNURF-SNRPN and UBE3A imprinted genes, PWS-ICR and AS-ICR in the chromosome 15q11-q13 region were evaluated by quantitative methylation-specific PCR technique. Intracellular levels of ROS and percentage of TUNEL-positive spermatozoa significantly increased in cryopreservation group compared to fresh group. Exposure to cryoprotectant had no significant effect on ROS levels and DNA fragmentation. Neither cryopreservation nor exposure to cryoprotectant significantly affected DNA methylation of the selected gene regions. However, DNA fragmentation had positive correlation with DNA methylation of AS-ICR. In conclusion, based on our study, clinical use of sperm cryopreservation for fertility treatments appear to be safe in regard to DNA methylation in the chromosome 15q11-q13 region.

Developing a Comprehensive Evidence-Based Service Package for Toddlers with Autism in a Low Resource Setting: Early Detection, Early Intervention, and Care Coordination.

Objective: The number of children with autism, who have many unmet needs, is increasing dramatically. However, the existing evidence shows that early identification and intervention are effective in reducing the later costs and burdens of autism spectrum disorder (ASD). Thus, the present study aimed to develop evidence-based services for children with autism in Iran to reduce its impacts on the affected children and their families and to decrease its burden on the society. Method : A 3-step study was conducted based on a modification of the Replicating Effective Programs (REP) framework (step 1: need assessment and situation analysis; step 2: identifying current evidence-based services; step 3: designing the first draft of the package and its core elements). Each step was conducted by a specific methodology. Results: By considering the obtained data, it was found that a package of services with 4 core components to respond to the perceived needs in Iran was needed: (1) early detection of at-risk children; (2) care coordination and facilitation of access to current services; (3) implementation of an evidence-based early intervention program; and (4) training interventionists using an effective educational framework based on evidence-based material. Conclusion: REP framework was used in the present study, which has been shown to be effective in adapting and implementing health care services. By considering the preconditions of REP, a comprehensive package of services, with 4 components was designed for toddlers with autism in Iran. The next step will be to study this package using a multicenter hybrid effectiveness-implementation randomized control trial.

Schwann cell transplantation exerts neuroprotective roles in rat model of spinal cord injury by combating inflammasome activation and improving motor recovery and remyelination.

Inflammasome activation in the traumatic central nervous system (CNS) injuries is responsible for propagation of an inflammatory circuit and neuronal cell death resulting in sensory/motor deficiencies. NLRP1 and NLRP3 are known as activators of inflammasome complex in the spinal cord injury (SCI). In this study, cell therapy using Schwann cells (SCs) was applied for targeting NLRP inflammasome complexes outcomes in the motor recovery. These cells were chosen due to their regenerative roles for CNS injuries. SCs were isolated from sciatic nerves and transplanted to the contusive SCI-induced Wistar rats. NLRP1 and NLRP3 inflammasome complexes and their related pro-inflammatory cytokines were assayed in both mRNA and protein levels. Neuronal cell survival (Nissl staining), motor recovery and myelination (Luxol fast blue/LFB) were also evaluated. The groups were laminectomy, SCI, vehicle and treatment. The treatment group received Schwann cells, and the vehicle group received solvent for the cells. SCI caused increased expressions for both NLRP1 and NLRP3 inflammasome complexes along with their related pro-inflammatory cytokines, all of which were abrogated after administration of SCs (except for IL-18 protein showing no change to the cell therapy). Motor deficits in the hind limb, neuronal cell death and demyelination were also found in the SCI group, which were counteracted in the treatment group. From our findings we conclude promising role for cell therapy with SCs for targeting axonal demyelination and degeneration possibly through attenuation of the activity for inflammasome complexes and related inflammatory circuit.

Current Status of Health and Social Services for Children with Autism in Iran: Parents' Perspectives.

Objective: The present study is a part of a larger study that aimed at developing a comprehensive model of service delivery for individuals with autism in Iran based on the local needs and characteristics. In this study, the status of the services provided to those with autism in Iran was investigated based on the perspectives of parents of children with autism. Method : A semi-structured interview was used to qualitatively investigate the status of the services with regards to autism in Iran based on the perspectives of parents of children with autism. Results: This study revealed several barriers, including shortness of eligible professionals, difficulty in access to care for families, high costs, and lack of formal and informal supports, in providing services to those with autism in Iran. Early detection and diagnosis are of prime importance. We also need to train our specialists to diagnose autism based on the standard protocols and tests. Conclusion: In sum, we need a comprehensive program that involves different sectors in charge of health and education in Iran.

Intrathecal transplantation of Wharton's jelly mesenchymal stem cells suppresses the NLRP1 inflammasome in the rat model of spinal cord injury.

After spinal cord injury (SCI) local inflammation is induced following secretion of interleukin-1beta (IL-1ß) and IL-18. It has been described that the secretion of IL-1ß and IL-18 is mediated by a cytoplasmic multiprotein complex, termed inflammasome. Mesenchymal stem cells (MSCs) have been extensively used for treating inflammatory diseases in which they showed immunomodulation characteristics. We utilized the anti-inflammatory potential of Wharton's jelly mesenchymal stem cells (WJ-MSCs) to target inflammasome complex in rat SCI model. Real time-polymerase chain reaction, western blotting, and ELISA assay were done one week after SCI to measure the expression of the inflammasome components including NLRP1, ASC, and active caspase-1 as well as IL-1ß, IL-18, and tumor necrosis factor-α (TNF-α). The histologic alteration and hind-limb locomotion were evaluated three weeks after injury by nissl staining and Basso, Beattie, Bresnahan (BBB), respectively. Our results showed that WJ-MSCs transplantation significantly decreased the SCI-induced expression of the evaluated factors in both mRNA and protein levels. In addition, WJ-MSCs significantly increased the number of normal-appearance neurons in the ventral horn of spinal cord. Noteworthy, these effects resulted in a significant improvement of motor function recovery. We conclude that inflammasome inhibition may be one of the mechanisms for the anti-inflammatory effect of MSCs in the SCI.

Co-Administration of Progesterone and Melatonin Attenuates Ischemia-Induced Hippocampal Damage in Rats.

Stroke is the second leading reason for death worldwide and is one of the fundamental causes of long-term disabilities. The aim of this investigation was to assess the impact of combined administration progesterone (PROG) and melatonin (MEL) on stroke complications. Male Wistar rats (9-10 weeks) weighing 250-300 g were used as a part of this examination. They were randomly separated into eight groups (nine rats for every group). Common carotid arteries on the two sides clamped (BCCAO model) with non-traumatic clips for 20 min. At that point, the rats were treated with 8 mg/kg PROG, 10 mg/kg MEL, and vehicles (sesamoid and normal saline). Morris water maze testing was performed following 2 weeks. At that point, the rats were euthanized, and histological examination was directed. The outcome demonstrated that utilization of PROG and MEL in treatment groups essentially increases the quantity of pyramidal cells and enhances spatial memory compared to non-treatment groups (p < 0.05). Moreover, the neuroleptic factor gene expression and protein concentration were significantly enhanced in the treated groups (p < 0.05). As indicated by the outcomes, co-administration of PROG and MEL can enhance learning and memory by surviving the pyramidal neurons and diminishing neural death by means of increasing neuroleptic factors in the hippocampal CA1 zone.

Flaxseed Can Reduce Hypoxia-Induced Damages in Rat Testes.

BACHGROUND: Hypoxia causes detrimental effects on the structure and function of tissues through increased production of reactive oxygen species that are generated during the re-oxygenation phase of intermittent and continuous hypobaric hypoxia. This study was carried out to evaluate the effects of flaxseed (Fx) in reducing the incidence of hypoxia in rat testes. MATERIALS AND METHODS: In this experimental study, 24 adult Wistar rats were randomly divided into four groups: i. Control group (Co) that received normal levels of oxygen and food, ii. Sham group (Sh) that were placed in hypoxia chamber but received normal oxygen and food, iii. Hypoxia induction group (Hx) that were placed in hypoxia chamber and treated with normal food, iv. Hypoxia induction group (Hx+Fx) that were placed in hypoxia chamber and treated with 10% flaxseed food. Both the Hx and Hx+Fx groups were kept in a hypoxic chamber for 30 days; during this period rats were exposed to reduced pressure (oxygen 8% and nitrogen 92%) for 4 hours/day. Then, all animal were sacrificed and their testes were removed. Malondialdehyde (MDA) and total antioxidant capacity (TAC) levels were evaluated in the testis tissue. Tubular damages were examined using histological studies. Blood samples and sperm were collected to assess IL-18 level and measure sperms parameters, respectively. All data were analyzed using SPPSS-22 software. One way-ANOVA or Kruskal-Wallis tests were performed for statistical analysis. RESULTS: A significant difference was recorded in the testicular mass/body weight ratio in Hx and Hx+Fx groups in comparison to the control (P=0.003 and 0.027, respectively) and Sh (P=0.001 and 0.009, respectively) groups. The sperm count and motility in Hx+Fx group were significantly different from those of the Hx group (P=0.0001 and 0.028, respectively) .Also sperm viability (P=0.0001) and abnormality (P=0.0001) in Hx+Fx group were significantly different from Hx group. CONCLUSION: This study therefore suggests that the oral administration of flaxseed can be useful for prevention from the detrimental effects of hypoxia on rat testes structure and sperm parameters.

Lipid Peroxidation and Its Role in the Expression of NLRP1a and NLRP3 Genes in Testicular Tissue of Male Rats: a Model of Spinal Cord Injury

BAckground: The majority of male patients with spinal cord injury (SCI) suffer from infertility. Nucleotide-binding oligomerization domain-like receptors NOD-like receptors (NLRs) are a kind of receptors that corporate in the inflammasome complex. Recent studies have introduced the inflammasome as the responsible agent for secreting cytokines in semen. Reactive oxygen species (ROS) is one of the elements that trigger inflammasome activation. Genital infections in SCI can lead to ROS generation. We investigated the relation between lipid peroxidation and inflammasome complex activity in testicular tissue of SCI rats. Methods: Adult male rats (n=20), weighting 200-250 g, were included and divided into four groups: three experimental groups, including SCI1, SCI3, and SCI7, i.e. the rats were subjected to SCI procedure and sacrificed after one, three, and seven days, respectively and a control group. We performed a moderate, midline spinal contusion injury at thoracic level 10. The animals were anesthetized, and testes were collected for measurement of gene expression by real-time PCR. Caudal parts of epididymis were collected for malondialdehyde (MDA) measurement. Results: No NLRP1a mRNA over expression was seen in the testes of control and SCI groups. After seven days from SCI surgery, NLRP3 mRNA expression was significantly increased in SCI7 animals (P≤0.05). There was a significant difference in MDA level in SCI7 versus control group, as well as SCI1 and SCI3 animals (P≤0.05). Conclusion: NLRP3 overexpression occurs due to the increased ROS production in testicular tissue of SCI rats.

Melatonin affects membrane integrity, intracellular reactive oxygen species, caspase3 activity and AKT phosphorylation in frozen thawed human sperm.

Cryopreservation is known to induce oxidative stress in spermatozoa. Although melatonin has powerful antioxidant properties, little is known about its effects on human sperm quality during cryopreservation. The present study was undertaken to investigate the effects of melatonin treatment on human sperm parameters essential for fertilization. We first evaluated the effects of various concentrations of melatonin (0-15 mM) on human sperm parameters such as motility, viability and levels of intracellular reactive oxygen species during cryopreservation in order to identify an optimal dose with the greatest effects for further studies. Liquefied semen samples were then divided into three aliquots: cryopreserved without melatonin (control), cryopreserved with 3 mM melatonin and fresh groups. After being thawed, samples were evaluated for motility, viability, membrane integrity, intracellular reactive oxygen species levels, caspase-3 activity and AKT phosphorylation. Treatment of spermatozoa with the various concentrations of melatonin significantly increased their motility and viability and decreased their intracellular reactive oxygen species levels compared with the control group. The optimal melatonin concentration (3 mM) significantly decreased the intracellular reactive oxygen species levels, caspase-3 activity and the percentage of both dead and apoptotic-like sperm cells and increased the vitality, progressive motility and total motility and AKT phosphorylation compared with the control group. Thus, melatonin exerts protective effects against cryodamage during human spermatozoa cryopreservation and may exert its effects via the PI3K/AKT signaling pathway.

The Correlation of Gene Expression of Inflammasome Indicators and Impaired Fertility in Rat Model of Spinal Cord Injury: A Time Course Study.

PURPOSE: Expression assessment of the inflammasome genes in the acute and the chronic phases of Spinal cord injury (SCI) on adult rat testis and examination of associations between inflammasome complex expression and sperm parameters. MATERIALS AND METHODS: In this study, 25 adult male rats were randomly divided into 5 groups. SCI surgery was performed at T10-T11 level of rats' spinal cord in four groups (SCI1, SCI3, SCI7, and SCI56). They were sacrificed after 1day, 3days, 7days and 56 days post SCI, respectively. One group remained intact as control (Co).CASA analysis of sperm parameters and qRT-PCR (ASC and Caspase-1) were made in all cases. RESULTS: Our data showed a severe reduction in sperm count and motility, especially on day 3 and 7. ASC gene expression had a non-significant increase on day 1 and 56 after surgery compared to control group. Caspase-1 expression increased significantly on day 3 post injury versus the control group (P = .009). Moreover, Caspase-1 overexpression, had significant correlations with sperm count (r = -0.555, P = .01) and sperm progressive motility (r = -0.524, P = .02). CONCLUSION: Inflammasome complex expression increase following SCI induction. This overexpression correlates to low sperm parameters in SCI rats.

Apoptotic biomarkers in cumulus cells in relation to embryo quality in polycystic ovary syndrome.

PURPOSE: To investigate associations between gene expression pattern of apoptotic biomarkers in cumulus cells of polycystic ovary syndrome (PCOS) patients and the quality of oocytes and embryos. METHODS: 40 intracytoplasmic sperm injection patients, of whom 20 were PCOS and 20 were healthy women, were included in this study. Serum hormone levels were measured using Radioimmunoassay for each patient. The expression of survivin, caspase-3, and caspase-7 in 200 cumulus complexes surrounding mature oocytes (100 in PCOS versus 100 in control groups) collected individually at pick up was examined by real-time polymerase chain reaction (real-time PCR). RESULTS: The expression levels of survivin were significantly lower in PCOS patients than those of normal women while caspase-3 and caspase-7 expression levels were higher in PCOS patients (p < 0.05). There was a statistically significant correlation between the levels of these genes and embryo quality. CONCLUSIONS: This study reveals that the measurement of survivin, caspase-3, caspase-7 levels in cumulus cells of PCOS patients could be used as genetic biomarkers for oocyte and embryo selection under an ART program. However, further prospective studies are required to elucidate this issue.

E-Learning Model in Chronic Kidney Disease Management: a Controlled Clinical Trial.

INTRODUCTION: Chronic kidney disease (CKD) is a challenging health problem. The present study examined impact of self-care education through e-learning on improving kidney function among individuals with CKD. MATERIALS AND METHODS: The studied population consisted of CKD patients receiving care at 10 centers for treating noncommunicable diseases in Tehran. Three centers were randomly selected and 39 patients with a glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2, minimum education of grade 9, minimum of 2 years of referrals, and computer literacy of the individual or a first-degree relative were included in the study, while 92 patients were assigned into the control group. Changes in GFR were compared after 6 months following an e-learning program for the patients in the intervention group. RESULTS: The mean change in GFR was 7.5 ± 8.9 mL/min/1.73 m2 for the intervention group after the e-learning intervention, while this was -2.3 ± 8.5 mL/min/1.73 m2. The two groups were also significantly different in terms of age, marital status, education level, mean arterial pressure, and serum high-density lipoprotein level, and therefore, multivariable comparison of GFR was made incorporating these factor into the analysis and showed a significant improvement of GFR in the intervention group. CONCLUSIONS: According to the results of this study, effects of the e-learning educational intervention on improvement in kidney function and CKD treatment were established.

Association between Physicians' Adherence to a Pharmacotherapy Guideline and Continuity of Care for Patients with Depression and/or Anxiety Disorder.

OBJECTIVE: The aim of the paper is to investigate the association between physicians' adherence to a pharmacotherapy guideline and continuity of care for patients with depressive and/or anxiety disorders in a collaborative care program. METHODS: This retrospective observational study was conducted using medical records of subjects suffering from depression and/or anxiety disorder visited by 26 general practitioners (GP) working with  Community Mental Health Center (CMHC), who run a collaborative care program in Tehran, Iran. All patients were visited by a general practitioner in private offices from November 2010 to May 2013. A scoring system was utilized to assess physicians' adherence to the pharmacotherapy guideline using medical records. Patients' continuity of care was calculated based on the number of days of being in the collaborative care program. To investigate the association between physicians' adherence to the guideline and the patients' continuity of care, univariate logistic regression analysis, multiple logistic regression analysis and parametric survival analysis were performed using Stata version 11. RESULT:  A total of 3,338 patients were studied. Their mean age was 37 years and 81.6% were female. Being treated by a particular GP was an important factor in patients with depressive and/or anxiety diagnosis as well as having both diagnoses. Furthermore, higher score of adherence to the guideline was associated with less continuity of care in depressive patients. CONCLUSION: Being treated by certain GPs is an effective way of retention of patients in the treatment. The results demonstrate that patients with guideline-based pharmacotherapy need to be told about continuity of care in community mental health program.

Methylation Status of H19/IGF2 Differentially Methylated Region in in vitro Human Blastocysts Donated by Healthy Couples

BACKGROUND: Imprinted genes are a unique subset of few genes that have been differentially methylated region (DMR) in a parental origin-dependent manner during gametogenesis, and these genes are highly protected during pre-implantation epigenetic reprogramming. Several studies have shown that the particular vulnerability of imprinting genes during suboptimal pre- and peri-conception micro-environments often is occurred by assisted reproduction techniques (ART). This study investigated the methylation status of H19/IGF2 DMR at high-quality expanding/expanded human blastocysts donated by healthy individuals to evaluate the risks linked to ART. METHODS: Methylation levels of H19/IGF2 DMR were analyzed by bisulfite conversion and sequencing at 18 CpG sites (CpGs) located in this region. RESULTS: The overall percentage of methylated CpGs and the proportion of hyper-methylated clones of H19/IGF2 DMR in analyzed blastocysts were 37.85±4.87% and 43.75±5.1%, respectively. For validation of our technique, the corresponding methylation levels of peripheral human lymphocytes were defined (49.52±1.86% and 50%, respectively). CONCLUSIONS: Considering the absence of in vivo- produced human embryos, it is not possible to conclude that the methylation found in H19/IGF2 DMR is actually normal or abnormal. Regarding the possible risks associated with ART, the procedures should be optimized in order to at least reduce some of the epigenetic risks.