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The prevalence of child emotional and behavioral problems is an international problem but is higher in low‐ and middle‐income countries (LMIC) where there are often less mental health supports for families. Parenting programs can be an effective means of prevention, but must be low‐cost, scalable, and suitable for the local context. The RISE project aims to systematically adapt, implement, and evaluate a low‐cost parenting program for preventing/reducing child mental health problems in three middle‐income countries in Southeastern Europe. This small pre–post pilot study is informed by the Reach, Efficacy, Adoption, Implementation, and Maintenance (RE‐AIM) framework and tested the feasibility of the intervention, the implementation, and evaluation procedures: Phase 1 of the three‐phase Multiphase Optimization Strategy (MOST) for program adaptation. Local facilitators delivered the Parenting for Lifelong Health (PLH) for Young Children program to parents of children aged 2–9 in North Macedonia, the Republic of Moldova and Romania in 2018. Parents completed assessments pre‐ and post‐program. Results demonstrated positive pre–post change for participating families (N = 140) on various outcomes including child externalizing and internalizing symptoms and parenting behavior, in all three countries, all in the expected direction. Program participation was associated with positive outcomes in participating families. Based on the experiences of this pilot study, we outline the practical implications for the successful implementation of parenting programs in the three countries that will inform our next study phases, factorial experiment, and RCT. [ABSTRACT FROM AUTHOR]

Para famílias que vivem em contexto migratório, a educação bilíngue, nomeadamente o bilinguismo de herança, é uma questão relevante e que, dependendo das políticas linguísticas locais, traz consigo diferentes desafios, demandando planejamento e engajamento familiar. Este estudo apresenta resultados parciais de uma investigação mais alargada sobre a transmissão do Português como Língua de Herança (PLH), em contexto não-formal, na Baviera, Alemanha. Com base em narrativas visuais de crianças bilingues (idade: 4-14 anos) associadas a análise de conteúdo no âmbito de um focus proup com elas, pretende-se conhecer e analisar as suas representações de brasilidade. Foram colhidos 20 desenhos junto aos frequentadores de um projeto socioeducativo para o ensino do PLH, signado “Mala de Herança”. A partir da análise multimodal desses desenhos a par com a análise das transcrições das entrevistas, pretende-se compreender o que essas representações revelam sobre a relação dos aprendentes com o PLH e como percebem seu estatuto. Os resultados apontam para a complementaridade das metodologias revelando o potencial heurístico resultante da combinação dos métodos. Conclui-se que esta abordagem metodológica oferece uma eficaz alternativa na pesquisa com crianças plurilíngues, por permitir maior aproximação com o objeto estudado e, abarcando uma dimensão social, por ser uma técnica pouco invasiva.

Abstract Background Hope or hopefulness enhances coping and improves quality of life in persons with chronic or incurable illnesses. Lack of hope is associated with depression and anxiety, which impact negatively on quality of life. In Tanzania, where HIV prevalence is high, the rates of depression and anxiety are over four times higher among people living with HIV (PLH) compared to persons not infected and contribute annual mortality among PLH. Tanzania has a shortage of human resources for mental health, limiting access to mental health care. Evidence-based psychosocial interventions can complement existing services and improve access to quality mental health services in the midst of human resource shortages. Facilitating hope can be a critical element of non-pharmacological interventions which are underutilized, partly due to limited awareness and lack of hope measures, adapted to accommodate cultural context and perspectives of PLH. To address this gap, we developed and validated a local hope measure among PLH in Tanzania. Methods Two-phased mixed methods exploratory sequential study among PLH. Phase I was Hope-related items identification using deductive, inductive approaches and piloting. Phase II was an evaluation of psychometric properties at baseline and 24 months. Classical test theory, exploratory, confirmatory factor analysis (CFA) were used. Results Among 722 PLH, 59% were women, mean age was 39.3 years, and majority had primary school level of education. A total of 40 hope items were reduced to 10 in a three-factor solution, explaining 69% of variance at baseline, and 93% at follow-up. Internal consistency Cronbach's alpha was 0.869 at baseline and 0.958 at follow-up. The three-factor solution depicted: positive affect; cognition of effectiveness of HIV care; and goals/plans/ future optimism. Test-retest reliability was good (r = 0.797) and a number of indices were positive for CFA model fit, including Comparative Fit Index of 0.984. Conclusion The developed local hope scale had good internal reliability, validity, and its dimensionality was confirmed against expectations. The fewer items for hope assessment argue well for its use in busy clinical settings to improve HIV care in Tanzania. Hope in this setting could be more than cognitive goal thinking, pathway and motivation warranting more research. Trial registration The intervention was registered in USA ClinicalTrials.gov on September 26, 2012, Registration number: NCT01693458.

Abstract Background Psychosocial factors have been linked with loss to follow-up (LTFU) and clinical outcomes among people living with HIV (PLH), however little is known about the effect of psychosocial support on LTFU among PLH in treatment and care. The purpose of this study was to explore the effect of NAMWEZA (“Yes, together we can”) friends’ psychosocial support intervention on clinical outcomes and LTFU among PLH. NAMWEZA is based on a novel program using “appreciative inquiry”, positive psychology approaches to empower, promote positive attitudes and foster hope. Methods PLH participating in the NAMWEZA intervention in HIV care clinics in Dar es Salaam Tanzania were compared with non-exposed PLH obtained from facilities that routinely collect clinical information and both followed longitudinally for 24 months. Baseline sociodemographic, clinical measures (CD4 cell count, hemoglobin (HGB), weight), and LTFU measures were collected. Chi square, Fisher’s exact tests, and t-tests were used to compare the frequencies for categorical variables and the means of continuous variables from the intervention and the comparison groups to identify variables that were significantly different across the two groups. Random effects models were performed to examine the bivariate associations between the intervention status and clinical outcomes. Results At the end of 24 months of follow-up mean CD4 count and HGB levels increased significantly in both intervention and comparison groups (p = 0.009 and p

Este artigo apresenta uma análise sobre as ideologias linguísticas que representam a nova posição da língua portuguesa dentro de duas comunidades portuguesas instaladas na América do Norte: em Montreal, Québec, no Canadá, e na cidade de Bridgeport, Connecticut, nos Estados Unidos da América. Enquanto as matrículas nas escolas comunitárias dentro dos dois grupos estão diminuindo, os atores destas instituições estão mobilizando discursos sobre o poder do português como uma língua de negócios, uma língua global. Utilizando uma abordagem etnográfica, observamos discursos das instituições e dos próprios falantes que deixam a posição de língua de herança (LH) para ‘vender’ uma nova língua do futuro. Observamos, então, como se mantém um paradigma nacionalista que vê uma nação equivaler ao uso duma língua, que nesse caso prevê o uso duma norma, para reforçar esta nova posição. A nossa metodologia qualitativa, baseada na observação participante e em entrevistas semiestruturadas, nos permitiu articular à análise discursiva com uma análise das práticas linguísticas, com enfoque na perceção e na identificação do que é o ‘bom’ português. As práticas mistas ou híbridas continuam a ser interrogadas segundo os repertórios de cada falante e em cada contexto, permitindo pôr em questão as ideologias de ‘pureza’ da língua.

Although a number of HIV prevention programs have been implemented, such as mass media campaigns, high rates of unprotected and concurrent sexual partnerships, as well as low uptake HIV testing and limited HIV knowledge, persist in Tanzania. We examined the effect and predicting factors of HIV prevention communication among people living with HIV (PLH) exposed to NAMWEZA intervention, and their at-risk social network members (NMs) Quantitative data were collected from 326 participants at baseline and 24 months of follow-up. In-depth interviews with 20 PLH were conducted at follow-up. Results indicated specific communication about condom use and HIV testing increased; (mean increase of 0.28 (SD = 0.14) scores, P = 0.012 and 0.42 (SD = 0.11) scores, p

Although a number of HIV prevention programs have been implemented, such as mass media campaigns, high rates of unprotected and concurrent sexual partnerships, as well as low uptake HIV testing and limited HIV knowledge, persist in Tanzania. We examined the effect and predicting factors of HIV prevention communication among people living with HIV (PLH) exposed to NAMWEZA intervention, and their at-risk social network members (NMs) Quantitative data were collected from 326 participants at baseline and 24 months of follow-up. In-depth interviews with 20 PLH were conducted at follow-up. Results indicated specific communication about condom use and HIV testing increased; (mean increase of 0.28 (SD = 0.14) scores, P = 0.012 and 0.42 (SD = 0.11) scores, p < 0.001 respectively while general discussion about protecting other people from HIV did not change significantly; mean increase was 0.01 scores (SD = 0.005), p = 0.890. Positive predictors of communication included being single; OR = 1.10, p = 0.01, female; OR = 1.15, p = 0.03, aged 30 years or older; OR = 1.23, p < 0.01, HIV knowledge, dose of NAMWEZA participation; OR = 1.01, p < 0.001, and high self-efficacy for condom use; OR = 1.4, p < 0.001. Stigma demonstrated a significant but negative association with communication for condom use; OR = 1.01, p < 0.01.Qualitative data reflected perceived possession of more individual skills and ability to address some personal/cultural obstacles to communicating about HIV prevention including those observed in the quantitative data. NAMWEZA improved communication about HIV prevention among PLH with their at-risk-NMs. The approach is a promising complement to media campaigns in similar populations. Future research and program evaluation efforts should explore how communities perceive and communicate about protecting others from HIV. [ABSTRACT FROM AUTHOR]

Background: Psychosocial factors have been linked with loss to follow-up (LTFU) and clinical outcomes among people living with HIV (PLH), however little is known about the effect of psychosocial support on LTFU among PLH in treatment and care. The purpose of this study was to explore the effect of NAMWEZA ("Yes, together we can") friends' psychosocial support intervention on clinical outcomes and LTFU among PLH. NAMWEZA is based on a novel program using "appreciative inquiry", positive psychology approaches to empower, promote positive attitudes and foster hope. Methods: PLH participating in the NAMWEZA intervention in HIV care clinics in Dares Salaam Tanzania were compared with non-exposed PLH obtained from facilities that routinely collect clinical information and both followed longitudinally for 24 months. Baseline sociodemographic, clinical measures (CD4 cell count, hemoglobin (HGB), weight), and LTFU measures were collected. Chi square, Fisher's exact tests, and t-tests were used to compare the frequencies for categorical variables and the means of continuous variables from the intervention and the comparison groups to identify variables that were significantly different across the two groups. Random effects models were performed to examine the bivariate associations between the intervention status and clinical outcomes. Results: At the end of 24 months of follow-up mean CD4 count and HGB levels increased significantly in both intervention and comparison groups (p = 0.009 and p < 0.0001, respectively). Weight increased significantly only in the intervention group (p = 0.003). Cumulative LTFU was three times higher in the comparison compared to the intervention (p < 0.001) group. Having a low CD4 count, extremes of weight, low HGB, younger age, and male gender were significantly associated with LTFU among the unexposed group, while being on ART for duration of 12 months or more was protective against LTFU in those intervened. Conclusion: Among PLH on ART, exposed or not exposed to NAMWEZA intervention, clinical care outcomes improved over time. LTFU was much higher in the comparison group with factors commonly known to predict LTFU only apparent in the comparison group. NAMWEZA could be a promising peer-facilitated model to reduce LTFU among PLH in care that can be integrated in ART services; however, more research is needed to evaluate its longer term effects. [ABSTRACT FROM AUTHOR]

Background: Timely and enduring access to antiretroviral therapy (ART) by HIV-infected individuals has been shown to substantially reduce HIV transmission risk, HIV-related morbidity and mortality. However, there is evidence that in addition to limited supply of antiretrovirals (ARVs) and linkage to ART in many low-income countries, HIV+ persons often encounter barriers in accessing ART-related services even in contexts where these services are freely available. In Ghana, limited research evidence exists regarding the barriers HIV+ persons already linked to ART face. This paper explores ART access-related barriers that HIV+ persons linked to care in southern Ghana face. Methods: A mixed method study design, involving a cross-sectional survey and qualitative in-depth interviews, was conducted to collect data from four healthcare providers and a total of 540 adult HIV+ persons receiving ART at four treatment centres in Ghana. We used univariate analysis to generate descriptive tabulations for key variables from the survey. Data from qualitative in-depth interviews were thematically analysed. Results from the survey and in-depth interviews were brought together to illuminate the challenges of the HIV+ persons. Results: All (100%) the HIV+ persons interviewed were ARV-exposed and linked to ART. Reasons for taking ARVs ranged from beliefs that they will suppress the HIV virus, desire to maintain good health and prolong life, and desire to prevent infection in unborn children, desire both to avoid death and to become good therapeutic citizens (abide by doctors' advice). Despite this, more than half of the study participants (63.3%) reported seven major factors as barriers hindering access to ART. These were high financial costs associated with accessing and receiving ART (26%), delays associated with receiving care from treatment centres (24%), shortage of drugs and other commodities (23%), stigma (8.8%), fear of side effects of taking ARVs (7.9%), job insecurity arising from regular leave of absence to receive ART (5.3%), and long distance to treatment centres (4.9%). Conclusions: The results in this study suggest that efforts to provide and scale-up ART to all HIV+ persons must be accompanied by interventions that address structural and individual level access barriers. [ABSTRACT FROM AUTHOR]

Experiments were done to determine the ovarian response and embryo production following superstimulation of wood bison. In Experiment 1 (Anovulatory season), the efficacy of pLH vs. hCG for inducing ovulation was compared in wood bison superstimulated with a single dose of pFSH in 0.5% hyaluronan and the effect of exogenous progesterone (PRID) on superovulatory response and embryo quality was examined. In Experiment 2 (Ovulatory season), the efficacy of pLH vs. hCG for the induction of ovulation was compared in wood bison superstimulated with pFSH in a single intramuscular dose vs. a two-dose regimen 48 h apart (split dose) in 0.5% hyaluronan. In Experiment 1, the number of CL was greater ( P < 0.05) in bison treated with hCG than pLH (6.6 ± 1.8 vs. 2.8 ± 0.8) and in those that were not given PRID (6.0 ± 1.5 vs. 2.7 ± 1.0). There was no effect of progesterone treatment on embryo quality. In Experiment 2, the number of CL was greater (P < 0.05) in bison treated with hCG than with pLH (6.3 ± 0.8 vs. 3.8 ± 1.2) and in bison superstimulated with split dose vs. single dose of FSH (7.1 ± 0.9 vs. 3.0 ± 0.8). The number of ova/embryos and freezable embryos did not differ among groups in either experiment. In conclusion, hCG induced a greater ovulatory response than pLH in both seasons. Two doses of FSH induced the greatest superovulatory response during the ovulatory season. Exogenous progesterone did not improve embryo quality during the anovulatory season. [ABSTRACT FROM AUTHOR]

As part of the development of a germplasm biobank to preserve the genetic diversity of threatened wood bison ( Bison bison athabascae ), a 2 × 2 factorial study was designed to determine the effects of ovulation induction agent and follicle maturity on the ovulatory response in wood bison during the anovulatory season. Bison ( n = 32) were assigned randomly to four groups ( n = 8/group) and treated with either pLH or hCG when a growing dominant follicle was either 8–9 mm or ≥10 mm. The ovaries were examined daily by ultrasonography to determine the timing of ovulation, and 7 days post-treatment to assess CL development. The proportion of bison that ovulated was greater in bison treated with hCG than pLH ([15/16] 94% vs. [8/16] 50%; P < 0.05), and when the dominant follicle was ≥10 mm vs. 8–9 mm at the time of treatment (88% vs. 56%; P < 0.05). The interval from treatment to ovulation was 37.0 ± 1.3 h and was not affected by induction agent or follicle size. However, synchrony of ovulation tended to be greater ( P = 0.10) in the ≥10 mm group vs. the 8–9 mm group, and the ensuing corpus luteum was larger (15.3 ± 0.43 mm vs. 13.4 ± 0.36; P < 0.05). In conclusion, both ovulation inducing agent and follicle size influenced the ovulatory response in bison during the anovulatory season. Treatment with hCG was more effective than pLH for inducing ovulation in wood bison, and the effect was greater when treatment was given when the growing dominant follicle was ≥10 mm. [ABSTRACT FROM AUTHOR]

Since the mid-1990s, many developing countries have introduced and expanded the availability of combination antiretroviral therapy (cART) to persons living with HIV (PLH). However, AIDS-related mortality continues to be high particularly among drug users. In this article, we present results from in-depth interviews with 13 HIV medical providers and 29 crack cocaine and alcohol using PLH in El Salvador. Providers endorsed negative attitudes toward substance using PLH and warned PLH that combining cART with drugs and alcohol would damage their livers and kidneys resulting in death. Upon diagnosis, PLH received little information about HIV treatment and many suffered depression and escalated their drug use. PLH reported suspending cART when they drank or used drugs because of providers’ warnings. Substance using PLH were given few strategies and resources to quit using drugs. Messages from medical providers discourage drug users from initiating or adhering to antiretroviral therapy (ART) and may contribute to treatment abandonment. [ABSTRACT FROM AUTHOR]

Abstract: The overall objective was to evaluate the use of porcine luteinizing hormone (pLH) for synchronization of ovulation in cyclic gilts and its effect on reproductive function. In an initial study, four littermate pairs of cyclic gilts were given altrenogest (15mg/d for 14d). Gilts received 500μg cloprostenol (Day 15), 600IU equine chorionic gonadotropin (eCG) (Day 16) and either 5mg pLH or saline (Control) 80h after eCG. Blood samples were collected every 4h, from 8h before pLH/saline treatment to the end of estrus. Following estrus detection, transcutaneous real-time ultrasonography and AI, all gilts were slaughtered 6d after the estimated time of ovulation. Peak plasma pLH concentrations (during the LH surge), as well as the amplitude of the LH surge, were greater in pLH-treated gilts than in the control (P =0.01). However, there were no significant differences between treatments in the timing and duration of estrus, or the timing of ovulation within the estrous period. In a second study, 45 cyclic gilts received altrenogest for 14–18d, 600IU eCG (24h after last altrenogest), and 5mg pLH, 750IU human chorionic gonadotropin (hCG), or saline, 80h after eCG. For gilts given pLH or hCG, the diameter of the largest follicle before the onset of ovulation (mean±S.E.M.; 8.1±0.2 and 8.1±0.2mm, respectively) was smaller than in control gilts (8.6±0.2mm, P =0.05). The pLH and hCG groups ovulated sooner after treatment compared to the saline-treated group (43.2±2.5, 47.6±2.5 and 59.5±2.5h, respectively; P <0.01), with the most synchronous ovulation (P <0.01) in pLH-treated gilts. Embryo quality (total cell counts and embryo diameter) was not significantly different among groups. In conclusion, pLH reliably synchronized ovulation in cyclic gilts without significantly affecting embryo quality. [Copyright &y& Elsevier]

Abstract: Porcine FSH/LH stimulation successfully induced development of multiple large (≥4mm) antral follicles in 10 of 11 common wombats. A mean of 5.5 metaphase II (MII) oocytes were aspirated from wombats that were stimulated during the follicular phase of the oestrous cycle (n =3) or after pouch young removal (n =3). Three subadults (n =3) and two anoestrus adults did not produce MII oocytes despite pFSH/pLH administration. In vitro maturation of immature oocytes at the time of aspiration doubled the number of MII oocytes that could be collected from pFSH/pLH stimulated wombats. Immature oocytes with cumulus attached, matured more readily to the MII stage than immature oocytes without cumulus. Following intracytoplasmic sperm injection (ICSI), approximately 5% of the oocytes that were MII at the time of collection cleaved. Approximately 5% of those that were matured by in vitro maturation (IVM) formed two polar bodies following ICSI, although they not cleave. Parthenogenesis cannot be excluded. This demonstrates that assisted reproductive technologies may be applicable to the common wombat. [Copyright &y& Elsevier]

Abstract: The objective was to analyze and report field data focusing on the effect of type of progesterone-releasing vaginal insert and dose of pLH on embryo production, following a superstimulatory protocol involving fixed-time artificial insemination (FTAI) in Nelore cattle (Bos taurus indicus). Donor heifers and cows (n =68; 136 superstimulations over 2 years) received an intravaginal, progesterone-releasing insert (CIDR® or DIB®, with 1.9 or 1.0g progesterone, respectively) and 3–4mg of estradiol benzoate (EB) i.m. at random stages of the estrous cycle. Five days later (designated Day 0), cattle were superstimulated with a total of 120–200mg of pFSH (Folltropin-V®), given twice daily in decreasing doses from Days 0 to 3. All cattle received two luteolytic doses of PGF2α at 08:00 and 20:00h on Day 2 and progesterone inserts were removed at 20:00h on Day 3 (36h after the first PGF2α injection). Ovulation was induced with pLH (Lutropin-V®, 12.5 or 25mg, i.m.) at 08:00h on Day 4 with FTAI 12, 24 and in several cases, 36h later. Embryos were recovered on Days 11 or 12, graded and transferred to synchronous recipients. Overall, the mean (±S.E.M.) number of total ova/embryos (13.3±0.8) and viable embryos (9.4±0.6) and pregnancy rate (43.5%; 528/1213) did not differ among groups, but embryo viability rate (overall, 70.8%) was higher in donors with a DIB (72.3%) than a CIDR (68.3%, P =0.007). In conclusion, the administration of pLH 12h after progesterone removal in a progestin-based superstimulatory protocol facilitated fixed-time AI in Nelore donors, with embryo production, embryo viability and pregnancy rates after embryo transfer, comparable to published results where estrus detection and AI was done. Results suggested a possible alternative, which would eliminate the need for estrus detection in donors. [Copyright &y& Elsevier]

Background: Despite reducing pneumonia and other infections, antibody replacement does not appear to treat pulmonary lymphoid hyperplasia (PLH) in patients with common variable immunodeficiency (CVID). The pathogenesis and optimal treatments remain to be clarified., Objective: We aimed to better understand the pathology of CVID-associated lung disease. Tertiary lymphoneogenesis, although a component of interstitial lung disease associated with autoimmune diseases, has not previously been explored in patients with CVID., Methods: We examined the clinical characteristics and pathologic findings of 6 patients with CVID with nodular/infiltrative lung disease who had biopsy specimens demonstrating PLH., Results: In these subjects regions of PLH contained distinct B- and T-cell zones, with B-cell predominance in 1 patient and T-cell predominance in the others. Colocalization of Ki67, Bcl6, and CD23 within this ectopic lymphoid architecture demonstrated tertiary lymphoneogenesis with active centers of cellular proliferation. One patient received rituximab with improved pulmonary radiologic findings., Conclusion: Ectopic lymphoid tissue forming germinal centers suggest tertiary lymphoneogenesis in CVID-associated lung disease. B cell-targeted therapy might disrupt CVID-associated lymphoid hyperplasia., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Nanocrystals is one of effective technologies used to improve solubility and dissolution behavior of poorly soluble drugs. Clarithromycin is classified in BCS class II having low bioavailability due to very low dissolution behavior. The main purpose of this study was to investigate an efficiency of clarithromycin nanocrystals preparation by precipitation-lyophilization-homogenization (PLH) combination method in comparison with high pressure homogenization (HPH) method. The factors influencing particle size reduction and physical stability were assessed. The results showed that the PLH technique provided an effective and rapid reduction of particle size of nanocrystals to 460 ± 10 nm with homogeneity size distribution after only the fifth cycle of homogenization, whereas the same size was attained after 30 cycles by the HPH method. The smallest nanocrystals were achieved by using the combination of poloxamer 407 (2%, w/v) and SLS (0.1%, w/v) as stabilizers. This combination could prevent the particle aggregation over 3-month storage at 4 °C. The results from SEM showed that the clarithromycin nanocrystals were in cubic-shaped similar to its initial particle morphology. The DSC thermogram and X-ray diffraction pattern of nanocrystals were not different from the original drug except for intensity of peaks which indicated the presenting of nanocrystals in the crystalline state and/or partial amorphous form. In addition, the dissolution of the clarithromycin nanocrystals was dramatically increased as compared to the coarse clarithromycin., (Copyright © 2013 Elsevier B.V. All rights reserved.)

We previously showed that short-term hypo- and hyperthyroidism induce changes in neuropeptide glutamic-acid-isoleucine-amide (NEI) concentrations in discrete brain areas in male rats. To investigate the possible effects of hypo- and hyperthyroidism on NEI concentrations mainly in hypothalamic areas related to reproduction and behavior, female rats were sacrificed at different days of the estrous cycle. Circulating luteinizing hormone (LH), estradiol and progesterone concentrations were measured in control, hypothyroid (hypoT, treated with PTU during 7-9 days) and hyperthyroid (hyperT, l-T4 during 4-7 days) animals. Both treatments blunted the LH surge. Hypo- and hyperthyroidism increased estradiol concentrations during proestrus afternoon (P-PM), although hypoT rats showed lower values compared to control during proestrus morning (P-AM). Progesterone levels were higher in all groups at P-PM and in the hyperT during diestrus morning (D2). NEI concentrations were lower in hypoT rats during the estrous cycle except in estrus (E) in the peduncular part of the lateral hypothalamus (PLH). They were also reduced by both treatments in the perifornical part of the lateral hypothalamus (PeFLH) during P-PM. Hypothyroidism led to higher NEI concentrations during P-PM in the organum vasculosum of the lamina terminalis and anteroventral periventricular nucleus (OVLT+AVPV). The present results indicate that NEI concentration is regulated in a complex manner by hypo- and hyperthyroidism in the different areas studied, suggesting a correlation between NEI values and the variations of gonadal steroid levels during estrous cycle. These changes could be, in part, responsible for the alterations observed in the hypothalamic-pituitary-gonadal axis in these pathologies., (Copyright © 2013 Elsevier Inc. All rights reserved.)

To broaden the understanding of the neural control and evolution of the sleep-wake cycle in mammals, the distribution and interrelations of sleep associated nuclei with neurons and terminal networks expressing the calcium-binding proteins parvalbumin, calbindin and calretinin were explored in a rodent that lacks a significant visual system. The sleep-associated nuclei explored include the cholinergic basal forebrain and pontine nuclei, the catecholaminergic locus coeruleus complex, the serotonergic dorsal raphe nuclear complex, the hypothalamic orexinergic nuclei, and the thalamic reticular nucleus. Zambian mole-rat brains were sectioned and stained in a one in nine series for Nissl, myelin, choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), serotonin (5HT), orexin (OrxA), calbindin (CB), calretinin (CR) and parvalbumin (PV). We observed that while the density of immunopositive calbindin (CB+) neurons and terminal networks varied in the different sleep related nuclei, they were found in all nuclei apart from the compact and diffuse subdivisions of the subcoeruleus, which lacked CB+ neurons but evinced a CB+ terminal network. The density of calretinin immunopositive (CR+) neurons and terminal networks varied between the sleep related nuclei, but was present in all nuclei examined. Neurons and terminal networks associated with PV immunoreactivity were the most sparsely distributed in these nuclei, but were present in the majority of nuclei. The thalamic reticular nucleus had the highest density of PV+ neurons and terminal networks, while PV+ neurons were absent in the cholinergic pontine nuclei, and PV+ neurons and terminal networks were absent in the orexinergic nuclei. The increased presence of neurons and terminal networks expressing the calcium binding proteins in comparison to that seen in the laboratory rat, specifically in the brainstem, may account for the prominent muscle twitches during REM sleep previously observed in this subterranean African rodent., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Artificial insemination (AI) in cats traditionally uses equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG) to induce follicular development and ovulation, with subsequent bilateral laparoscopic intrauterine insemination. However, long-acting hCG generates undesirable secondary ovulations in cats. Uterine AI also requires relatively high numbers of spermatozoa for fertilization (~8 × 10(6) sperm), and unfortunately, sperm recovery from felids is frequently poor. Using short-acting porcine luteinizing hormone (pLH) instead of hCG, and using the oviduct as the site of sperm deposition, could improve fertilization success while requiring fewer spermatozoa. Our objectives were to compare pregnancy and fertilization success between 1) uterine and oviductal inseminations and 2) eCG/hCG and eCG/pLH regimens in domestic cats. Sixteen females received either eCG (100 IU)/hCG (75 IU) or eCG (100 IU)/pLH (1000 IU). All females ovulated and were inseminated in one uterine horn and the contralateral oviduct using fresh semen (1 × 10(6) motile sperm/site) from a different male for each site. Pregnant females (11/16; 69%) were spayed approximately 20 days post-AI, and fetal paternity was genetically determined. The number of corpora lutea (CL) at AI was similar between hormone regimens, but hCG increased the number of CL at 20 days post-AI. Numbers of pregnancies and normal fetuses were similar between regimens. Implantation abnormalities were observed in the hCG group only. Finally, oviductal AI produced more fetuses than uterine AI. In summary, laparoscopic oviductal AI with low sperm numbers in eCG/hCG- or eCG/pLH-treated females resulted in high pregnancy and fertilization percentages in domestic cats. Our subsequent successes with oviductal AI in eCG/pLH-treated nondomestic felids to produce healthy offspring supports cross-species applicability.

The purpose of the present investigation was to develop and evaluate a self-microemulsifying drug delivery system (SMEDDS) for improving the oral absorption of a pranlukast hemihydrate (PLH), a very poorly water-soluble drug. An efficient self-microemulsifying vehicle for PLH was selected and optimized using solubility testing and phase diagram construction. The formulations were characterized by assessing self-emulsification performance, droplet size analysis, in vitro drug release characteristics and formulation stability studies. Optimized formulations for in vitro dissolution and bioavailability assessment were Triethylcitrate (TEC; 10%), Tween 20 (50%), Span 20 (25%), triethanolamine (5%), and benzyl alcohol (10%). The SMEDDS readily released the lipid phase to form a fine oil-in-water microemulsion with a narrow distribution size. Saturated solubilities of PLH from SMEDDS in water, pH 4.0 and 6.8, were over 150 times greater than that of plain PLH. The release of 100% PLH from SMEDDS was considerably greater compared to only 1.12% in simulated intestinal fluid (pH 6.8) from plain PLH after 2 hours. The PLH suspension with 0.5% sodium carboxymethylcellulose or 3% PLH-loaded SMEDDS was administrated at a dose of 40 mg/kg as PLH to fasted rats. The absorption of PLH from SMEDDS resulted in about a threefold increase in bioavailability compared with plain PLH aqueous suspension. Our studies illustrated that the potential use of the new SMEDDS can be used as a possible alternative to oral delivery of a poorly water-soluble drug such as PLH.