Stressors, Legal Vulnerability and Bangladeshi Parent and Child Well-Being in New York City.

A growing body of research is documenting the impact of parental legal status on familial and child well-being in the U.S. This study adds to the literature by examining the relation of legal vulnerability with the health and mental health of Bangladeshi immigrant parents and their children. A cross-sectional study with 73 immigrant Bangladeshi families was conducted in New York City. Parents reported on legal status indicators, perceived stressors, health, and child mental health indicators. Parents with greater legal vulnerability reported significantly greater immigration-related stressors and poorer perceived health outcomes for themselves and their children in comparison with parents having less legal vulnerability. Immigration stressors explained a significant amount of variance in parent symptoms of depression, tension, and sleep problems and child mental health indicators, beyond the variance explained by acculturation stress and financial stress. Practitioners should be aware that legal vulnerability and associated immigration stressors are adversely associated with Bangladeshi health and mental health.

Knowledge on, Attitude towards, and Practice of Sexual and Reproductive Health among Older Adolescent Girls in Bangladesh: An Institution-Based Cross-Sectional Study.

Improving the sexual and reproductive health (SRH) of adolescent girls is one of the primary aims of the Sustainable Development Goals (SDGs). Adequate and accurate knowledge, a favorable attitude, safe behavior, and regular practice contribute to adolescent girls' SRH, maternal health, and child health. Considering this, this study aims to explore the level of knowledge, attitudes, and practices (KAP) of SRH among college-going older adolescent girls in Chittagong district, Bangladesh. An institution-based cross-sectional study was conducted in four colleges among the older adolescent girl age group of 16-17 years old (N = 792) attending a higher secondary grade in Chittagong district. Data were collected using a structured and self-administered questionnaire. Descriptive statistics and multiple linear regression analyses were used to summarize the SRH-related KAP and identify the associated factors, respectively. The level of knowledge about puberty, family planning, maternal health, and HIV/AIDS was not satisfactory among the older adolescent girls. Different myths are common in the rural area with regards to menstruation, which impose several restrictions on adolescent girls and adult women. Standardized coefficients of beta (ß) and p value < 0.05 in linear regression analyses demonstrated that being a student of the science group (ß = 0.29, p < 0.001) and reading about or watching SRH issues on media (ß = 0.21, p < 0.001) were significantly associated with older adolescent girls' high level of knowledge in this regard. Furthermore, being a student of the science group (ß = 0.17, p < 0.001), urban residence (ß = 0.20, p < 0.001), regular SRH communication (at least once a month) with a mother/sister/friend (ß = 0.10, p = 0.003), and reading or watching any SRH content on media (ß = 0.22, p < 0.001) appeared as predictors of adolescent girls' positive attitude towards SRH issues. Moreover, being a student of the science group (ß = 0.07, p = 0.048), urban residence (ß = 0.22, p < 0.001), regular SRH discussions with a mother/sister/friend (ß = 0.09, p = 0.005), pre-knowledge on periods before menarche (ß = 0.12, p < 0.001), and reading or watching any SRH content on media (ß = 0.18, p < 0.001) are the most important factors influencing a regular hygienic practice of SRH. This study suggests strengthening SRH-related comprehensive education programs incorporated into the curriculum, the effective use of mass media, and supplying behavioral change communication materials.

Reproductive health communication between mother and adolescent daughter in Bangladesh: a cross-sectional study.

BACKGROUND: Parent-adolescent reproductive health (RH) communication is one of the potential sources of information for adolescents on the topic. Given that female adolescents in Bangladesh are faced with increasing RH-related risks, it is important to understand how parents communicate about RH to their adolescents from the adolescents' perspectives. Therefore, the aim of this study is to explore the status of mother-adolescent daughter communication on reproductive health in Bangladesh. METHODS: A cross-sectional study targeting female students was conducted in five high schools in Chittagong based on a self-administered questionnaire survey. A description method was used to describe the characteristics of mother-adolescent daughters' communication on RH including the frequency, type and the quantity of topics. Bivariate and multivariate logistic regression analyses were performed to explore the factors influencing mother-adolescent daughter communication. RESULTS: In the study, 1174 female students aged from 13 to 19 years old were included. The main source of knowledge on RH was from their mother (62%), and the mother was the person who communicated first on RH with adolescent students. The topics of mother-daughter communication were mainly focused on menstruation issues (> 80%). Multivariate logistic regressions showed that Hindu students, students with good RH knowledge, adolescents' mothers having good RH knowledge, mothers with high media use, good mother-daughter relationship, daughters' regular general communication with mothers, and students' perceiving comfort in RH communication with their mothers were reported as significant predictors for a good RH communication status. On the contrary, students having family members numbering more than four, whose primary source of reproductive health information was friends/classmates as well as media were less likely to have better RH communication with mothers. CONCLUSIONS: The overall communication on reproductive health between adolescent daughters and their mothers was not good. This study suggests for conducting qualitative research investigating the socio-cultural context within which the RH communications happen. and how to address the obstacles that might hinder this communication.

Provision of menstrual regulation with medication among pharmacies in three municipal districts of Bangladesh: a situation analysis.

OBJECTIVE: The objective was to assess the provision of the combination of mifepristone-misoprostol for menstrual regulation (MR) in randomly selected urban pharmacies in Bangladesh. STUDY DESIGN: We conducted a cross-sectional survey among 553 pharmacy workers followed by 548 mystery client visits to the same pharmacies in 3 municipal districts during July 2014-December 2015. RESULTS: The survey found that 99% of pharmacy workers visited had knowledge of MR procedures but only two-thirds (67%) could state the legal time limit correctly; they mentioned misoprostol (86%) over mifepristone-misoprostol combination (78%) as a procedure of MR with medication (MRM); 36% reported knowing the recommended dosage of mifepristone-misoprostol combination; 70% reported providing information on effectiveness of the medicines; 50% reported recommending at least one follow-up visit to them; 63% reported explaining possible complications of using the medications; and 47% reported offering any post-MR contraception to their clients. In contrast, mystery client visits found that the mifepristone-misoprostol combination (69%) was suggested over misoprostol (51%) by the pharmacy workers; 54% provided the recommended dosage of mifepristone-misoprostol combination; 42% provided information on its effectiveness; 12% recommended at least one follow-up visit; 11% counseled on possible complications; and only 5% offered post-MR contraceptives to the mystery clients. CONCLUSIONS: We found knowledge gaps regarding recommended dosage for MRM and inconsistent practice in informing women on effectiveness, follow-up visits, possible complications and provision of post-MR contraceptives among the pharmacy workers, particularly during the mystery client visits. IMPLICATIONS: Pharmacy workers in Bangladesh need to be trained on legal time limits for MR services provision, on providing accurate information on disbursed medicine, and on proper referral mechanisms. A strong monitoring and regulatory system for pharmacy provision of MRM in pharmacies should be established.

Evaluation of phenoxybenzamine in the CFA model of pain following gene expression studies and connectivity mapping.

BACKGROUND: We have previously used the rat 4 day Complete Freund's Adjuvant (CFA) model to screen compounds with potential to reduce osteoarthritic pain. The aim of this study was to identify genes altered in this model of osteoarthritic pain and use this information to infer analgesic potential of compounds based on their own gene expression profiles using the Connectivity Map approach. RESULTS: Using microarrays, we identified differentially expressed genes in L4 and L5 dorsal root ganglia (DRG) from rats that had received intraplantar CFA for 4 days compared to matched, untreated control animals. Analysis of these data indicated that the two groups were distinguishable by differences in genes important in immune responses, nerve growth and regeneration. This list of differentially expressed genes defined a "CFA signature". We used the Connectivity Map approach to identify pharmacologic agents in the Broad Institute Build02 database that had gene expression signatures that were inversely related ('negatively connected') with our CFA signature. To test the predictive nature of the Connectivity Map methodology, we tested phenoxybenzamine (an alpha adrenergic receptor antagonist) - one of the most negatively connected compounds identified in this database - for analgesic activity in the CFA model. Our results indicate that at 10 mg/kg, phenoxybenzamine demonstrated analgesia comparable to that of Naproxen in this model. CONCLUSION: Evaluation of phenoxybenzamine-induced analgesia in the current study lends support to the utility of the Connectivity Map approach for identifying compounds with analgesic properties in the CFA model.

Genetic targeting of ERK1 suggests a predominant role for ERK2 in murine pain models.

The extracellular signal-regulated kinase (ERK) isoforms, ERK1 and ERK2, are believed to be key signaling molecules in nociception and nociceptive sensitization. Studies using inhibitors targeting the shared ERK1/2 upstream activator, mitogen-activated protein kinase kinase (MEK), and transgenic mice expressing a dominant-negative form of MEK have established the importance of ERK1/2 signaling. However, these techniques do not discriminate between ERK1 and ERK2. To dissect the function of each isoform in pain, we used mice with a targeted genetic deletion of ERK1 [ERK1 knock-out (KO)] to test the hypothesis that ERK1 is required for behavioral sensitization in rodent pain models. Despite activation (phosphorylation) of ERK1 after acute noxious stimulation and in models of chronic pain, we found that ERK1 was not required for formalin-induced spontaneous behaviors, complete Freund's adjuvant-induced heat and mechanical hypersensitivity, and spared nerve injury-induced mechanical hypersensitivity. However, ERK1 deletion did delay formalin-induced long-term heat hypersensitivity, without affecting formalin-induced mechanical hypersensitivity, suggesting that ERK1 partially shapes long-term responses to formalin. Interestingly, ERK1 deletion resulted in elevated basal ERK2 phosphorylation. However, this did not appear to influence nociceptive processing, since inflammation-induced ERK2 phosphorylation and pERK1/2 immunoreactivity in spinal cord were not elevated in ERK1 KO mice. Additionally, systemic MEK inhibition with SL327 (alpha-[amino[(4-aminophenyl)thio]methylene]-2-(trifluoromethyl)benzeneacetonitrile) attenuated formalin-induced spontaneous behaviors similarly in wild-type and ERK1 KO mice, indicating that unrelated signaling pathways do not functionally compensate for the loss of ERK1. Together, these results suggest that ERK1 plays a limited role in nociceptive sensitization and support a predominant role for ERK2 in these processes.

The kv4.2 potassium channel subunit is required for pain plasticity.

A-type potassium currents are important determinants of neuronal excitability. In spinal cord dorsal horn neurons, A-type currents are modulated by extracellular signal-regulated kinases (ERKs), which mediate central sensitization during inflammatory pain. Here, we report that Kv4.2 mediates the majority of A-type current in dorsal horn neurons and is a critical site for modulation of neuronal excitability and nociceptive behaviors. Genetic elimination of Kv4.2 reduces A-type currents and increases excitability of dorsal horn neurons, resulting in enhanced sensitivity to tactile and thermal stimuli. Furthermore, ERK-mediated modulation of excitability in dorsal horn neurons and ERK-dependent forms of pain hypersensitivity are absent in Kv4.2(-/-) mice compared to wild-type littermates. Finally, mutational analysis of Kv4.2 indicates that S616 is the functionally relevant ERK phosphorylation site for modulation of Kv4.2-mediated currents in neurons. These results show that Kv4.2 is a downstream target of ERK in spinal cord and plays a crucial role in pain plasticity.

Impaired inflammatory pain and thermal hyperalgesia in mice expressing neuron-specific dominant negative mitogen activated protein kinase kinase (MEK).

BACKGROUND: Numerous studies have implicated spinal extracellular signal-regulated kinases (ERKs) as mediators of nociceptive plasticity. These studies have utilized pharmacological inhibition of MEK to demonstrate a role for ERK signaling in pain, but this approach cannot distinguish between effects of ERK in neuronal and non-neuronal cells. The present studies were undertaken to test the specific role of neuronal ERK in formalin-induced inflammatory pain. Dominant negative MEK (DN MEK) mutant mice in which MEK function is suppressed exclusively in neurons were tested in the formalin model of inflammatory pain. RESULTS: Formalin-induced second phase spontaneous pain behaviors as well as thermal hyperalgesia measured 1 - 3 hours post-formalin were significantly reduced in the DN MEK mice when compared to their wild type littermate controls. In addition, spinal ERK phosphorylation following formalin injection was significantly reduced in the DN MEK mice. This was not due to a reduction of the number of unmyelinated fibers in the periphery, since these were almost double the number observed in wild type controls. Further examination of the effects of suppression of MEK function on a downstream target of ERK phosphorylation, the A-type potassium channel, showed that the ERK-dependent modulation of the A-type currents is significantly reduced in neurons from DN MEK mice compared to littermate wild type controls. CONCLUSION: Our results demonstrate that the neuronal MEK-ERK pathway is indeed an important intracellular cascade that is associated with formalin-induced inflammatory pain and thermal hyperalgesia.

Inflammation persistently enhances nocifensive behaviors mediated by spinal group I mGluRs through sustained ERK activation.

Group I metabotropic glutamate receptors (mGluRs) and their downstream signaling pathways, which involve the extracellular signal-regulated kinases (ERKs), have been implicated as mediators of plasticity in several pain models. In this study, we report that inflammation leads to a long-lasting enhancement of behavioral responses induced by activation of spinal group I mGluRs. Thus, the nocifensive response to intrathecal injection of the group I mGluR agonist (RS)-3,5-Dihydroxyphenylglycine (DHPG) is significantly potentiated seven days following Complete Freund's Adjuvant (CFA)-induced inflammation of the hind paw. This potentiation is not associated with increased mGlu1 or mGlu5 receptor expression but is associated with increased levels of phosphorylated ERK in dorsal horn neurons. We also tested whether the increased behavioral response to DHPG following inflammation may be explained by enhanced coupling of the group I mGluRs to ERK activation. DHPG-induced ERK phosphorylation in the dorsal horn is not potentiated following inflammation. However, inhibiting ERK activation using a MEK inhibitor, U0126, following inflammation attenuates the intrathecal DHPG-induced behavioral responses to a greater extent than in control animals. The results from this study indicate that persistent ERK activation is required for the enhanced behavioral responses to spinal group I mGluR activation following inflammation and suggest that tonic modulation of ERK activity may underlie a component of central sensitization in dorsal horn neurons.

Membrane topology of a metabotropic glutamate receptor.

The metabotropic glutamate receptors (mGluRs) have been predicted to have a classical seven transmembrane domain structure similar to that seen for members of the G-protein-coupled receptor (GPCR) superfamily. However, the mGluRs (and other members of the family C GPCRs) show no sequence homology to the rhodopsin-like GPCRs, for which this seven transmembrane domain structure has been experimentally confirmed. Furthermore, several transmembrane domain prediction algorithms suggest that the mGluRs have a topology that is distinct from these receptors. In the present study, we set out to test whether mGluR5 has seven true transmembrane domains. Using a variety of approaches in both prokaryotic and eukaryotic systems, our data provide strong support for the proposed seven transmembrane domain model of mGluR5. We propose that this membrane topology can be extended to all members of the family C GPCRs.

Differential effects of antisense oligodeoxynucleotides directed against g(zalpha) and g(oalpha) on antinociception produced by spinal opioid and alpha(2) adrenergic receptor agonists.

The present studies assessed the role of G(zalpha) and G(oalpha) in spinal alpha(2) adrenergic receptor agonist-induced antinociception, as well as in antinociceptive synergism between spinal morphine and clonidine. Mice were pretreated with a single intrathecal (i.t.) injection of artificial cerebrospinal fluid (ACSF), antisense oligodeoxynucleotide(s) (ODN) directed against G(zalpha) or G(oalpha), or nonsense ODN. After 48 h, the antinociceptive effects expressed as per cent maximal possible effect (% MPE) of either i.t. morphine alone, clonidine alone or coadministered morphine plus clonidine, were evaluated in the tail flick test. Antisense ODN to G(zalpha) attenuated clonidine- but not morphine-induced antinociception. The ED(50) (95% confidence interval) value for clonidine in ACSF pretreated mice was 6.3 (4.9-8.1) nmol, and in nonsense ODN pretreated mice, it was 4.2 (2.8-6.3) nmol. However, in the G(zalpha) antisense ODN pretreated mice, the highest dose clonidine tested (50 nmol) produced only 41+/-8.5% MPE. Antisense ODN to G(zalpha) also blocked antinociception produced by i.t. UK14, 304 (alpha(2) adrenergic receptor agonist) and [D-Pen(2), D-Pen(5)] enkephalin (DPDPE) (delta opioid receptor agonist), whereas it failed to attenuate i.t. Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol (DAMGO)- (mu opioid receptor agonist) and U50-488 (kappa opioid receptor agonist) -induced antinociception. Pretreatment with antisense ODN to G(oalpha) attenuated both morphine and clonidine induced antinociception and did not affect synergism between the agonists. These results suggest that spinal G(o)alpha mediates antinociception produced by both clonidine and morphine while G(zalpha) mediates alpha(2) adrenergic and delta opioid receptor mediated antinociception, but not antinociception produced by mu or kappa opioid agonists.