A Survey of Louisiana Pediatricians' Approach to Parenting Teens and Adolescent Reproductive Health.

OBJECTIVE: The American Academy of Pediatrics recommends that pediatricians provide a medical home for adolescent parents, and this study sought to determine pediatricians' compliance with this recommendation within the context of other adolescent reproductive health services provided. METHODS: An Internet-based survey was administered to Louisiana pediatricians. The survey contained 17 Likert scale questions relating to sexual and reproductive health services provided to female and male adolescents, and ascertaining their comfort and experience with issues related to the care of adolescents, including adolescent mothers. Respondents also had the option of describing why they do or do not provide care to adolescent mothers. Lastly, the survey collected demographic characteristics modeled after the American Academy of Pediatrics Periodic Survey of Fellows. RESULTS: There were 101 survey respondents. Seventy-nine percent of pediatricians reported that they provide care to adolescent mothers and they were similar to those who did not with respect to sex, age, race and ethnicity, and training, but they differed by practice community and payer mix. Almost 30% of pediatricians never/rarely test their patients for pregnancy, and nearly 50% never/rarely prescribe contraception. Fifty-four percent agreed that adolescent mothers should continue receiving nonobstetric medical care from their pediatricians, and 70% believed that adolescent fathers should continue receiving medical care from their pediatricians. CONCLUSIONS: Our study suggests that most Louisiana pediatricians provide care to adolescent mothers; however, knowledge gaps and misconceptions related to adolescent reproductive health persist among pediatricians, including those who refuse care to adolescent mothers. Research into provider-level barriers may inform interventions that improve adolescent parents' access to a pediatric medical home.

[Implementation, of multidisciplinary consultations for patients with inflammatory arthritis and treated with subcutaneous biologic DMARDs: Assessment at one year and outlook]. / Mise en place de consultations pluridisciplinaires pour des patients atteints de rhumatisme inflammatoire chronique et traités par biothérapie sous-cutanée : bilan à un an et perspectives.

INTRODUCTION: Biologics (bDMARDs) have revolutionized the prognosis of patients with inflammatory arthritis, but are not without serious side effects. The patient must be able to identify them, acquire self-care abilities or skills and adhere to their treatment. Multidisciplinary consultations, including a pharmaceutical consultation could improve the care of these patients. The pharmaceutical presence make it easier to switch to a biosimilar with etended patient support thanks to the community-hospital network. The return on investment is possible thanks to the more frequent use of biosimilars and the pricing of this type of consultation by the "Forfait de Prestation Intermédiaire". METHODOLOGY: Eligible patients are patients with rheumatoid arthritis or spondyloarthritis, treated with subcutaneous bDMARDs. The criteria assessed were patient's knowledge of their biotherapy using the Biosecure score, their medication adherence using the CQR-5, the total of switch to biosimilars perform and the financial statement of the consultations. An assessment of the actions deployed for the community-hospital network. RESULTS: Two hundred and ninety-five patients (47.4%) benefited multidisciplinary consultation. The mean score of the Biosecure score was 69.6/100 (moderate knowledge) and 261 patients (88.5%) were highly adherent. 57 patients (73%) accepted the switch to biosimilar. 197 pharmacy were contacted, all of witch for patients who receive the switch. Overall patient's satisfaction was 26.9/28. CONCLUSION: Multidisciplinary consultations with involvement of the pharmacist should optimized patient care and the management of outpatients treated with bDMARDs. Patients have already expressed their satisfaction with this course of care and the return on investment is positive.

Photosensitized reactions initiated by 6-carboxypterin: singlet and triplet reactivity.

Pterins, derivatives of 2-aminopteridin-4(3H)-one, are natural photosensitizers, common to many biological systems. Indications that these photosensitizers are also present in the sea-surface microlayer motivated the study of the photophysical and photochemical properties of 6-carboxypterin (CPT), which was chosen as a model for this group of photoactive compounds. The kinetics of excited CPT in the singlet and triplet state in the presence of halides and organics were studied in aqueous solutions at neutral pH by means of steady-state fluorescence and laser-flash photolysis. The fluorescence of CPT was efficiently quenched by two halides (iodide and bromide) and by four carboxylic acids (lactic, malonic, propionic and citric acid) with reaction rates close to the diffusion-controlled limit. In the triplet state, the triplet absorption spectrum was measured and its pH dependence was studied. The triplet state of CPT showed relatively high reactivity towards iodide, but no reaction with bromide or chloride could be observed. No singlet or triplet state quenching in the presence of limonene could be measured. A reaction mechanism is proposed, initiated by electron transfer from the quencher to the excited photosensitizer. This type of photo-induced reaction in the sea-surface microlayer has the potential to trigger the production of many oxidized species, including halogen atoms, in the bulk and gaseous phases.

Ontogeny changes and weaning effects in gene expression patterns of digestive enzymes and regulatory digestive factors in spotted rose snapper (Lutjanus guttatus) larvae.

The study of digestive physiology is an important issue in species that have been introduced in aquaculture like the spotted rose snapper (Lutjanus guttatus). The aims of this study were to describe the expression of digestive enzymes (trypsinogen, chymotrypsinogen, α-amylase, lipoprotein lipase, phospholipase A and pepsinogen) and their relation with orexigenic (neuropeptide Y, NPY) and anorexigenic (cholecystokinin, CCK) factors during the larval development and to evaluate the effect of weaning in their expression. The results showed that the transcripts of all the assayed digestive enzymes, with the exception of pepsinogen, and NPY and CCK were already present in L. guttatus from the hatching stage. The expression of all the enzymes was low during the yolk-sac stage (0-2 days after hatching, DAH), whereas after the onset of exogenous feeding at 2 DAH, their expression increased and fluctuated throughout larval development, which followed a similar pattern as in other marine fish species and reflected changes in different types of food items and the progressive maturation of the digestive system. On the other hand, weaning of L. guttatus larvae from live prey onto a microdiet between 25 and 35 DAH significantly affected the relative expression of most pancreatic digestive enzymes during the first weaning days, whereas chymotrypsinogen 2 and lipoprotein lipase remained stable during this period. At the end of co-feeding, larvae showed similar levels of gene expression regardless of the diet (live prey vs. microdiet), which indicated that larvae of L. guttatus were able to adapt their digestive capacities to the microdiet. In contrast, feeding L. guttatus larvae with live feed or microdiet did not affect the expression of CCK and NPY. The relevance of these findings with regard to current larval rearing procedures of L. guttatus is discussed.

Development of digestive enzyme activity in spotted rose snapper, Lutjanus guttatus (Steindachner, 1869) larvae.

We describe digestive enzyme activity during the larval development of spotted rose snapper, Lutjanus guttatus. Trypsin, chymotrypsin, leucine aminopeptidase, pepsin, amylase, lipase, and acid and alkaline phosphatase activities were evaluated using spectrophotometric techniques from hatching through 30 days. The spotted rose snapper larvae present the same pattern of digestive enzyme activity previously reported for other species in which pancreatic (i.e., trypsin, chymotrypsin, amylase, and lipase) and intestinal (i.e., acid and alkaline phosphatases and leucine aminopeptidase) enzymatic activities are present from hatching allowing the larvae to digest and absorb nutrients in the yolk-sac and live prey by the time of first feeding. The digestive and absorption capacity of the spotted rose snapper increases during the larval development. A significant increase in individual activity of all enzymes occurs at 20 DAH, and around 25 DAH, the juvenile-type of digestion is observed with the appearance of pepsin secreted by the stomach, suggesting that maturation of the digestive function occurs around 20-25 DAH. Our results are in agreement with a previous suggestion that early weaning may be possible from 20 DAH. However, the patterns of enzymatic activities reported in our study should be considered during the formulation of an artificial diet for early weaning of the spotted rose snapper.

Trends in the Incidence of Gestational Diabetes Mellitus Among the Medicaid Population Before and During the COVID-19 Pandemic.

Importance: Although there are many regional and national studies on the trends in the incidence of gestational diabetes mellitus (GDM), the trends in the incidence of GDM among the Medicaid population are lacking, especially before and during coronavirus disease of 2019 (COVID-19). Objective: To investigate the trends in the incidence of GDM before and during COVID-19 pandemic (2016-2021) among the Louisiana Medicaid population. Design, Setting, and Participants: This study included 111,936, Louisiana Medicaid pregnant women of age 18-50 between January 1, 2016, to December 31, 2021. Main Outcomes and Measures: Pregnancies, GDM, and pre-pregnancy diabetes cases were identified by using the Tenth Revisions of the International Classification of Disease code. The annual incidence of GDM and annual prevalence of pre-pregnancy diabetes were calculated for each age and race subgroup. Results: The age-standardized incidence of GDM increased from 10.2% in 2016 to 14.8 in 2020 and decreased to 14.0% in 2021. The age-standardized prevalence of pre-pregnancy diabetes increased from 2.8% in 2016 to 3.4% in 2018 and decreased to 2.3% in 2021. The age-standardized rate of GDM was the highest among Asian women (23.0%), then White women (15.5%), and African American women (13.9%) (p for difference <0.001). The COVID-19 pandemic saw an increase in the incidence of GDM, with a rise in prominent GDM risk factors, such as obesity and sedentary behaviors, suggesting an association. Conclusion and Relevance: The incidence of GDM significantly increased during the COVID-19 pandemic. Potential reasons might include increased sedentary behavior and increased prevalence of obesity. GDM is a major public health issue, and the prevention of GDM is particularly essential for the Louisiana Medicaid population owing to the high prevalence of GDM-related risk factors in this population.

The Utility of Virtual Home Visits to Reduce Asthma Burden in Low-Income Black Communities in Louisiana During the COVID-19 Pandemic.

OBJECTIVES: The Louisiana Department of Health identified a need for greater outreach in low-income Black communities that addressed environmental asthma triggers. We piloted an asthma virtual home visit (VHV) program and evaluated its reach and ability to promote asthma self-management strategies in communities with a high prevalence of poorly controlled asthma. METHODS: Participants from Louisiana were continuously recruited into the VHV program starting in March 2021 and provided with asthma education materials. Participants reporting poorly controlled asthma and environmental triggers were also offered 3 VHVs with a respiratory therapist. All participants were asked to complete a preintervention and postintervention knowledge test, an Asthma Control Test (ACT) (maximum score = 25; scores ≤19 indicate poorly controlled asthma), and a final survey that assessed perceptions about asthma management and reduction of environmental triggers. RESULTS: As of October 2022, 147 participants were enrolled in the program, and 52 had consented to and received ≥1 VHV. Forty VHV recipients (77%) were aged <18 years, 40 (77%) were Black people, and 46 (88%) were from families with extremely low or low incomes. Asthma symptoms improved across all participants, with a median increase of 2.4 points on the ACT. Knowledge tests revealed that 86% of participants learned about ≥1 new asthma trigger; a larger percentage of VHV recipients than nonrecipients (68% vs 36%) had an improved knowledge test score postintervention. Compared with preintervention, about three-quarters of participants reported feeling more empowered to self-manage their asthma and a significant improvement in their quality of life postintervention. CONCLUSIONS: The program provided virtual asthma education to communities with a high burden of asthma and improved asthma outcomes for participants. Similar virtual models can be used to promote health equity, especially in areas with limited access to health care.

A 60 MeV proton beam-line dedicated to research and development programs.

A new proton beam-line dedicated to R&D programs has been developed at CentreAntoine Lacassagne (CAL), in Nice (France), in collaboration with the Centrenational d'études spatiales (CNES). This is the second beam-line of the MEDICYC 65 MeV cyclotron that is currently in operation, the first being the clinical 'eye-line' used for ocular proton therapy. The R&D beam-line is proposed with two configurations, the first producing a Gaussian narrow beam of a few mm width, the second a 100 mm diameter flat beam with a homogeneity better than ±3%. The energy range is (20 - ∼60) MeV, where the exact upper limit depends on the beam configuration being used. The energy spread of the non-degraded beam is (0.3 ± 0.1) MeV. A beam current between 10 pA and 10 µA can be produced with a stability better than 0.2% above 100 pA, and 2% below. The beam can be monitored online at a precision better than 5% in the flux range 1E5 (1E6) - 1E9 (1E10) p/cm2/s for a flat (Gaussian) configuration, although work is in progress to extend this range. Targeted applications for the R&D beam-line are instrumentation research, radiation tolerance tests of components and radiobiology.

30 years of ocular proton therapy, the Nice view.

PURPOSE: Radiotherapy with protons (PT) is a standard treatment of ocular tumors. It achieves excellent tumor control, limited toxicities, and the preservation of important functional outcomes, such as vision. Although PT may appear as one homogenous technique, it can be performed using dedicated ocular passive scattering PT or, increasingly, Pencil Beam Scanning (PBS), both with various degrees of patient-oriented customization. MATERAIAL AND METHODS: MEDICYC PT facility of Nice are detailed with respect to their technical, dosimetric, microdosimetric and radiobiological, patient and tumor-customization process of PT planning and delivery that are key. 6684 patients have been treated for ocular tumors (1991-2020). Machine characteristics (accelerator, beam line, beam monitoring) allow efficient proton extraction, high dose rate, sharp lateral and distal penumbrae, and limited stray radiation in comparison to beam energy reduction and subsequent straggling with high-energy PBS PT. Patient preparation before PT includes customized setup and image-guidance, CT-based planning, and ocular PT software modelling of the patient eye with integration of beam modifiers. Clinical reports have shown excellent tumor control rates (∼95%), vision preservation and limited toxicity rates (papillopathy, retinopathy, neovascular glaucoma, dry eye, madarosis, cataract). RESULTS: Although demanding, dedicated ocular PT has proven its efficiency in achieving excellent tumor control, OAR sparing and patient radioprotection. It is therefore worth adaptations of the equipments and practice. CONCLUSIONS: Some of these adaptations can be transferred to other PT centers and should be acknowledeged when using non-PT options.

Louisiana Pharmacies' Availability of Emergency Contraception and Counseling Accuracy to Adolescent and Physician Callers.

STUDY OBJECTIVE: Adolescents face many barriers to obtaining emergency contraception (EC), despite it being an approved and recommended method to prevent unintended pregnancy. This study examined pharmacy-related barriers to adolescents' access to EC in Louisiana. DESIGN: Prospective, telephone-call secret shopper study to pharmacies to assess same-day EC availability and barriers to purchase. SETTING: A total of 182 pharmacies in 5 Louisiana cities. PARTICIPANTS: Responses provided by pharmacists or other pharmacy staff assessed between July 2018 and November 2019. INTERVENTIONS: Collected data from secret shopper phone calls and compared responses provided to callers between male and female callers and physician and adolescent callers. MAIN OUTCOME MEASURES: Same-day levonorgestrel (LNG) availability, same-day ulipristal acetate (UPA) availability, age restrictions on purchase, requirement of parental consent for purchase, and type of staff member that advised the caller. RESULTS: Of 364 calls to 182 pharmacies, 66% of pharmacists or other pharmacy staff reported same-day LNG access and 5% reported same-day UPA access. An inaccurate age restriction regarding EC purchase was reported in 15% of calls. Female callers were cited this age restriction more frequently than their male counterparts (20% vs 10%). Pharmacists were more likely than other pharmacy staff to counsel female callers compared to male callers (52% vs 27%) and physician callers compared to adolescents (50% vs 30%). CONCLUSIONS: Many pharmacies in Louisiana have limited same-day availability of EC and often report inconsistent and inaccurate age and consent regulations for its use. Continued outreach and education to pharmacies is necessary to address these barriers to adolescent EC access.

Quantifying the incidence of clinically significant respiratory depression in women with and without obesity class III receiving neuraxial morphine for post-cesarean analgesia: a retrospective cohort study.

BACKGROUND: Obesity is a suspected risk factor for respiratory depression following neuraxial morphine for post-cesarean analgesia, however monitoring guidelines for obese obstetric patients are based on small, limited studies. We tested the hypothesis that clinically significant respiratory depression following neuraxial morphine occurs more commonly in women with body mass index (BMI) ≥40 kg/m2 compared with BMI <40 kg/m2. METHODS: We conducted a single-center, retrospective chart review (2006-2017) of obstetric patients with clinically significant respiratory depression following neuraxial morphine, defined as: (1) opioid antagonist administration; (2) rapid response team activation (initiated in April 2010); or (3) tracheal intubation due to a respiratory event. The incidence of respiratory depression was compared between women with BMI ≥40 kg/m2 and BMI <40 kg/m2. RESULTS: In total, 11 327 women received neuraxial morphine (n=1945 BMI ≥40 kg/m2; n=9382 BMI <40 kg/m2). Women with BMI ≥40 kg/m2 had higher rates of sleep apnea, hypertensive disorders, and magnesium administration. Sixteen cases of clinically significant respiratory depression occurred within seven days postpartum. The incidence did not significantly differ between groups (odds ratio 2.2, 95% CI 0.6 to 6.9, P=0.174). Neuraxial morphine was not deemed causative in any case, however women with BMI ≥40 kg/m2 had higher rates of tracheal intubation unrelated to neuraxial morphine (2/1945 vs. 0/9382, P=0.029). CONCLUSIONS: Respiratory depression in this population is rare. A larger sample (∼75 000) is required to determine whether the incidence is higher with BMI ≥40 kg/m2. Tracheal intubation was higher among the BMI ≥40 kg/m2 cohort, likely due to more comorbidities.

Development of digestive enzyme activity in larvae of spotted sand bass Paralabrax maculatofasciatus II: Electrophoretic analysis.

The activities of several digestive enzymes during larval development of the spotted sand bass (Paralabrax maculatofasciatus) were evaluated using electrophoretic techniques. The results show the presence of three isoforms of alkaline protease from day 2 after hatching (ah) and the early appearance of one pepsin-like band from day 12 ah onwards. In addition, two lipase bands first appeared on day 2 ah, and there was a change in the molecular weight of one band from day 15 ah onwards. Several alpha-amylase isoforms were observed from hatching up to day 5 ah. These results indicate that the important digestive enzymes develop rapidly in these larvae, supporting the possibility of early weaning at day 12 ah using artificial diets.

Analysis of Pregnancy and Birth Rates Among Black and White Medicaid-Enrolled Teens.

PURPOSE: In the United States, black teens overall have higher pregnancy and birth rates than whites, and it is commonly believed that minority race and low income account for this disparity. We examined racial differences in pregnancy and birth rates among teens from low-income households using Medicaid-enrollment as a proxy for low income. METHODS: This was a retrospective study of Louisiana Medicaid claims data for female teens aged 15-17 years in 2014 (n = 66,069). Pregnancy and pregnancy outcome codes were identified (n = 2,276) and analyzed for differences by black and white race. We conducted validity analyses with different rate definitions and teens' claims status. RESULTS: The cohort was 36% white and 54% black. More black teens than whites lacked any claims data (15.6% vs. 12.6%; p < .001). Rates calculated as events per 1,000 person-years of Medicaid coverage showed no difference in live birth rates between white and black teens (24.6 vs. 25.8; relative incidence ratio, 1.05; 95% confidence interval, .93-1.18; p = .43); however, pregnancy rates for whites were higher than those for blacks (42.7 vs. 36.1; relative incidence ratio, .85; 95% confidence interval, .77-.93; p < .001). CONCLUSION: In contrast to national trends, which include teens from diverse racial and socioeconomic backgrounds, Louisiana Medicaid-enrolled teens aged 15-17 years had equal birth rates regardless of black or white race, and whites had higher pregnancy rates. Decreased racial disparities in pregnancy and birth rates among these adolescents highlights socioeconomic influences in sexual health behavior and a need to examine the interplay of risk factors contributing to racial disparities seen among adolescents nationally.

Population Geography and Emergency Contraception Access in Louisiana.

We assessed the same-day availability of oral emergency contraception (EC) in five Louisiana communities, and evaluated this data for relationships between availability and local population demographics. Researchers called all retail pharmacies in five municipalities of varying sizes in order to inquire about the same-day stockage of EC products and their availability to teens. Individual pharmacies were then geolocated to a census tract, and call data was analyzed against neighborhood census data regarding population size, income, gender, race, family structure, and educational level. A multivariable logistic regression model was performed to predict the same-day availability of emergency contraception. EC was available on the same day in 66% of all pharmacies. The same-day availability of EC decreased with the local population size (p < 0.001), and the availability increased with higher levels of educational attainment (p = 0.0015). The largest census level predictor of access to same-day EC was the city population, with the availability increasing by 6.6% for every 10,000 person increase in population. Despite changing to over-the-counter sales in 2013, EC is still not widely available in all geographic areas. Its availability is partially predictable by local population demographics, and this difference may represent a health disparity for teens and women seeking EC.

Development of digestive enzyme activity in larvae of spotted sand bass Paralabrax maculatofasciatus. 1. Biochemical analysis.

Spotted sand bass Paralabrax maculatofasciatus is a potential aquaculture species in Northwest Mexico. In the last few years it has been possible to close its life cycle and to develop larviculture technology at on pilot scale using live food, however survival values are low (11%) and improvements in growth and survival requires the study of the morpho-physiological development during the initial ontogeny. In this research digestive activity of several enzymes were evaluated in larvae, from hatching to 30 days after hatching (dah), and in live prey (rotifers and Artemia), by use of biochemical and electrophoretic techniques. This paper, is the first of two parts, and covers only the biochemical analysis. All digestive enzyme activities were detected from mouth opening; however the, maximum activities varied among different digestive enzymes. For alkaline protease and trypsin the maximum activities were detected from 12 to 18 dah. Acid protease activity was observed from day 12 onwards. The other digestive enzymes appear between days 4 and 18 after hatching, with marked fluctuations. These activities indicate the beginning of the juvenile stage and the maturation of the digestive system, in agreement with changes that occur during morpho-physiological development and food changes from rotifers to Artemia. All enzymatic activities were detected in rotifers and Artemia, and their contribution to enhancement the digestion capacity of the larvae appears to be low, but cannot be minimised. We concluded that the enzymatic equipment of P. maculatofasciatus larvae is similar to that of other marine fish species, that it becomes complete between days 12 and 18 after hatching, and that it is totally efficient up to 25 dah.

Health and Social Needs of Young Mothers.

PURPOSE: Teen parenting rates are disproportionately high among minority youth in the Southern United States. We explored barriers and unmet needs relating to medical and social support as perceived by these teen mothers, and elicited suggestions for improving their healthcare through the medical home. STUDY DESIGN AND METHODS: We conducted four focus groups of 18- to 24-year-old mothers in New Orleans with questions designed to prompt discussions on young motherhood and healthcare. All 18 participants identified as African American, became mothers when <20, and their children were <5 at the time of the study. Two researchers independently analyzed focus group transcripts and coded them thematically, revealing various unmet social and health needs. RESULTS: Seven main themes emerged, which revealed a concerning lack of mental healthcare, few with consistent medical homes, inadequate contraceptive knowledge and access, and a desire for parenting education and support groups. Suggestions for improving care largely centered around logistical and material support, such as extended clinic hours, transportation, and baby supplies. CLINICAL IMPLICATIONS: Findings suggest a need for improved medical knowledge, healthcare access, and social support for teen mothers. This may be provided through a multidisciplinary medical home model, such as a Teen-Tot clinic, where the unique challenges of adolescent parenting are continuously considered.

[Systemic safety following intravitreal injections of anti-VEGF]. / Tolérance systémique des injections intravitréennes d'anti-VEGF.

The goal of this manuscript is to assess data suggesting that intravitreal injection of anti-vascular endothelial growth factors (anti-VEGFs) could result in systemic adverse events (AEs). The class-specific systemic AEs should be similar to those encountered in cancer trials. The most frequent AE observed in oncology, hypertension and proteinuria, should thus be the most common expected in ophthalmology, but their severity should be lower because of the much lower doses of anti-VEGFs administered intravitreally. Such AEs have not been frequently reported in ophthalmology trials. In addition, pharmacokinetic and pharmacodynamic data describing systemic diffusion of anti-VEGFs should be interpreted with caution because of significant inconsistencies reported. Thus, safety data reported in ophthalmology trials and pharmacokinetic/pharmacodynamic data provide robust evidence that systemic events after intravitreal injection are very unlikely. Additional studies are needed to explore this issue further, as much remains to be understood about local and systemic side effects of anti-VEGFs.

Neurochemical characterization of pathways expressing plasma membrane monoamine transporter in the rat brain.

Neurotransmitter transporters play an important role in the control of synaptic transmission by ensuring the clearance of transmitters liberated in the synaptic cleft. In the case of monoaminergic neurotransmitters, this clearance is carried out by high-affinity reuptake transporters located in the plasma membrane of the presynaptic terminals. Recently plasma membrane monoamine transporter (PMAT), a transporter from the SLC29 (equilibrative nucleoside transporter) family, was shown to transport in vitro monoaminergic neurotransmitters, in particular dopamine and serotonin, nearly as efficiently as the high-affinity transporters. This transporter, well expressed in CNS, represents an interesting candidate for the control and modulation of aminergic pathways. We performed an extensive study of the distribution of PMAT in the rat brain. Our results highlight PMAT expression in brain regions which play a pivotal role in significant CNS functions and human neuropathologies. Using in situ hybridization immunohistochemistry co-labeling, PMAT mRNA was found in various neuron subtypes, including glutamatergic neurons of the hippocampus, mitral cells of the olfactory bulbs and GABAergic neurons in the substantia nigra pars reticulata and hypothalamus. Paradoxically, rat PMAT mRNA was found in some but not all monoaminergic nuclei. It was on the contrary predominantly expressed in major cholinergic groups throughout the brain, including brainstem motor nuclei, components of the basal forebrain cholinergic system and cholinergic interneurons of the striatum. These systems, implicated in locomotion, associative and spatial memory and reward-related learning, are disrupted at early stages of Parkinson's and Alzheimer's disease. Taken together, our observations support a role for PMAT in monoamine uptake in cholinergic neurons.

Calcineurin (protein phosphatase 2B) is involved in the mechanisms of action of antidepressants.

Calcineurin (PP2B) is a Ca(2+)-dependent protein phosphatase enriched in the brain that takes part in intracellular signaling pathways regulating synaptic plasticity and neuronal functions. Calcineurin-dependent pathways are important for complex brain functions such as learning and memory. More recently, they have been suggested to play a role in the processing of emotional information. The aim of this study was to investigate whether calcineurin may be involved in the effect of antidepressants. We first found that chronic antidepressant treatment in mice leads to an increase of calcineurin levels in the hippocampus. We then studied the behavioral and molecular responses to fluoxetine of mice with a genetic overactivation of calcineurin in the hippocampus (constitutively-activated calcineurin transgenic mouse line #98, CN98 mice). We observed that CN98 mice are more sensitive to the behavioral effect of fluoxetine and desipramine tested in the tail suspension test. Moreover, the basal expression of growth factor brain-derived neurotrophic factor and subunit 1 of AMPA glutamate receptor, GluR1, both of which are modified after chronic antidepressant administration, are altered in the hippocampus of CN98 mice. These results suggest that calcineurin-dependent dephosphorylation plays an important role in the mechanisms of action of antidepressants, providing a new starting point for developing improved therapeutic treatments for depression.