Ecological implications of allometric relationships in American alligators (Alligator mississippiensis).

Morphometric allometry, the effect of size on morphological variation, has been of great interest for evolutionary biologist and is currently used in fields such as wildlife ecology to inform management and conservation. We assessed American alligator (Alligator mississippiensis) morphological static allometry across the Greater Everglades ecosystem in South Florida, United States using a robust dataset (~ 22 years) and investigated effects of sex, habitat, and sampling area on morphological relationships. Regression models showed very strong evidence of a linear relationship between variables explaining equal to or above 92% of the variation in the data. Most trait-size relationships (8 out of 11 assessed) showed hyperallometry (positive allometry) with slope deviations from isometry between 0.1 and 0.2 units while the other three relationships were isometric. Sampling area, type of habitat, and in a lesser extent sex influenced allometric coefficients (slope and intercept) across several relationships, likely as result of differing landscapes and ecosystem dynamic alterations and sexual dimorphism. We discuss our findings in terms of the biology of the species as well as the usefulness of our results in the context of ecosystem restoration and conservation of the species. Finally, we provide recommendations when using trait-length relationships to infer population nutritional-health condition and demographics.

Body condition as a descriptor of American alligator (Alligator mississippiensis) health status in the Greater Everglades, Florida, United States.

Body condition is used as an indicator of the degree of body fat in an animal but evidence of its actual relationship with health diagnostics (e.g., blood parameters) is usually lacking across species. In American alligators (Alligator mississippiensis), body condition has been used as a performance metric within the Greater Everglades ecosystem to provide insight on hydrological and landscape changes on alligator populations. However, there is no clear evidence that spatial body condition changes relate to different health conditions (low food intake vs sickness) and whether this link can be made when relating body condition values with blood parameters. We assessed the relationship between alligator body condition and 36 hematological and biochemistry (blood) parameters in four areas across two physiographic regions (Everglades and Big Cypress) of the Greater Everglades (sample size = 120). We found very strong to weak evidence of linearity between 7 (Big Cypress) and 19 (Everglades) blood parameters and relative condition factor index, from which cholesterol (38%) and uric acid (41%) for the former and phosphorus (up to 52%) and cholesterol (up to 45%) for the latter (mean absolute error MAE = 0.18 each) were the predictors that individually explain most of the body condition variation. The best combination of blood parameters for the Everglades were cholesterol, phosphorus, osmolality, total protein, albumin, alpha 2, beta, and gamma globulins, and corticosterone accounting for 40% (37 ± 21%, MAE = 0.16) of the variation found in alligator body condition for this region. We found better predictability power in models when analyzed at smaller rather than larger scales showing a potential habitat effect on the body condition-blood parameters relationship. Overall, Everglades alligators in poorer condition are likely dehydrated or have an inadequate diet and the spatial differences found between physiographic regions suggest that these areas differ in prey availability/quality.

Cervicovaginal mucus barrier properties during pregnancy are impacted by the vaginal microbiome.

Introduction: Mucus in the female reproductive tract acts as a barrier that traps and eliminates pathogens and foreign particles via steric and adhesive interactions. During pregnancy, mucus protects the uterine environment from ascension of pathogens and bacteria from the vagina into the uterus, a potential contributor to intrauterine inflammation and preterm birth. As recent work has demonstrated the benefit of vaginal drug delivery in treating women's health indications, we sought to define the barrier properties of human cervicovaginal mucus (CVM) during pregnancy to inform the design of vaginally delivered therapeutics during pregnancy. Methods: CVM samples were self-collected by pregnant participants over the course of pregnancy, and barrier properties were quantified using multiple particle tracking. 16S rRNA gene sequencing was performed to analyze the composition of the vaginal microbiome. Results: Participant demographics differed between term delivery and preterm delivery cohorts, with Black or African American participants being significantly more likely to delivery prematurely. We observed that vaginal microbiota is most predictive of CVM barrier properties and of timing of parturition. Lactobacillus crispatus dominated CVM samples showed increased barrier properties compared to polymicrobial CVM samples. Discussion: This work informs our understanding of how infections occur during pregnancy, and directs the engineering of targeted drug treatments for indications during pregnancy.

Calidad de Vida, Ansiedad, Depresión y Consumo de Alcohol en Adultos con Diabetes Tipo Dos durante la Pandemia por COVID-19 / Quality of Life, Anxiety, Depression, and Alcohol Consumption in Adults with Type 2 Diabetes during the COVID-19 Pandemic

Resumen El objetivo de este estudio fue relacionar la calidad de vida, el consumo de alcohol, la depresión y ansiedad en pacientes con diabetes tipo 2 (DT2) durante la pandemia de COVID-19. Se aplicó una encuesta a un total de 119 pacientes con DT2 seleccionados mediante un muestreo no probabilístico intencional de la zona centro del país, con al menos un año de diagnóstico. Para evaluar la calidad de vida se utilizó la escala diabetes-39, la escala de autoevaluación de la depresión de Zung, la escala de ansiedad de Hamilton y la prueba de identificación de trastornos por uso de alcohol. Los hallazgos son: correlaciones positivas entre la preocupación por la disminución en la calidad de vida en todas las áreas con la ansiedad. Así como consumo de riesgo en hombres y calidad de vida, señalando mayor consumo de alcohol en esta población. Estos resultados indican que tener diabetes tipo 2 es un predisponente para presentar problemas de salud mental como: ansiedad, depresión y consumo de alcohol, lo que señala la importancia de trabajar con esta población en el periodo de postpandemia.

Abstract The aim of this study was to relate quality of life, alcohol consumption, depression, and anxiety in patients with type 2 diabetes (T2D) during the COVID-19 pandemic. A survey was applied to a total of 119 patients with T2D selected by non-probability purposive sampling from the central part of the country, with at least one year of diagnosis. The diabetes-39 quality of life scale, the Zung Depression Self-Assessment Scale, the Hamilton Anxiety Scale and the Alcohol Use Disorders Identification Test were used. The findings are positive correlations between concern for diminished quality of life in all areas with anxiety. As well as risk consumption in men and quality of life, indicating higher alcohol consumption in this population. These results indicate that having type 2 diabetes is a predisposing factor for presenting mental health problems such as anxiety, depression and alcohol consumption, which points to the importance of working with this population in the post-pandemic period.

Incidence, follow-up, and postnatal clinical progress of children with central nervous system anomalies on fetal MRI.

OBJECTIVE: MRI is increasingly employed to assess intrauterine fetal anomalies. Central nervous system (CNS) anomalies are common structural conditions that warrant evaluation with fetal MRI and subsequent prenatal consultation with a pediatric neurosurgeon. As the use of fetal MRI increases, there is greater impetus to understand the most common CNS structural anomalies diagnosed in utero, as well as their natural histories. METHODS: The authors performed a single-center retrospective review of fetal MRI evaluations performed between January 2012 and December 2020. Children who underwent both prenatal and postnatal neurosurgical evaluations of CNS anomalies were included. Specific CNS anomalies on fetal MRI, associated extra-CNS findings, and suspicion for genetic abnormality or syndromes were noted. Postnatal clinical status and interventions were assessed. RESULTS: Between January 2012 and December 2020, a total of 469 fetal MRI evaluations were performed; of these, 114 maternal-fetal pairs had CNS anomalies that warranted prenatal consultation and postnatal pediatric neurosurgical follow-up. This cohort included 67 male infants (59%), with a mean ± SD follow-up of 29.8 ± 25.0 months after birth. Fetal MRI was performed at 27.3 ± 5.8 weeks of gestational age. The most frequently reported CNS abnormalities were ventriculomegaly (57%), agenesis or thinning of the corpus callosum (33%), Dandy-Walker complex (DWC) (21%), neuronal migration disorders (18%), and abnormalities of the septum pellucidum (17%). Twenty-one children (18%) required neurosurgical intervention at a mean age of 2.4 ± 3.7 months. The most common surgical conditions included myelomeningocele, moderate to severe ventriculomegaly, encephalocele, and arachnoid cyst. Corpus callosum agenesis or thinning was associated with developmental delay (p = 0.02) and systemic anomalies (p = 0.05). The majority of prenatal patients referred for DWC had Dandy-Walker variants that did not require surgical intervention. CONCLUSIONS: The most common conditions for prenatal neurosurgical assessment were ventriculomegaly, corpus callosum anomaly, and DWC, whereas the most common surgical conditions were myelomeningocele, hydrocephalus, and arachnoid cyst. Only 18% of prenatal neurosurgical consultations resulted in surgical intervention during infancy. The majority of referrals for prenatal mild ventriculomegaly and DWC were not associated with developmental or surgical sequelae. Patients with corpus callosum abnormalities should be concurrently referred to a neurologist for developmental assessments.

Myelomeningocele Including Fetal Prescription.

Myelomeningocele (MMC) is one of the most common birth defects, affecting 0.2 to 0.4 per 1,000 live births in the United States. The most strongly associated risk factor is low folate level in pregnancy. For this reason, 0.4- to 1.0-mg supplementation with folic acid is recommended in all pregnancies, and high-risk pregnancies are recommended to supplement with 4.0 mg of folic acid daily. The mechanism behind the development of MMC is believed to be failure of the caudal end of the neural tube to close during primary neurulation. Screening for MMC is achieved by using α-fetoprotein levels in maternal serum or amniocentesis in the first and second trimesters of pregnancy. Ultrasonography and fetal magnetic resonance imaging are used to confirm the presence of MMC as well as the location and size of the defect. Based on the results of the Management of Myelomeningocele Study, fetal repair is performed between 23 weeks and 25 weeks and 6 days of gestational age for appropriate candidates. Postnatal repair is more common and is performed 24 to 72 hours after birth. In general, patients with lesions at lower anatomical levels have a better prognosis. Most children with MMC will have neurogenic bladder and bowel dysfunction that affect the patient's and the caregiver's quality of life. Patients with higher levels of mobility, better familial support, and higher economic status report improved quality of life compared with other patients with MMC.

National characteristics, etiology, and inpatient outcomes of pediatric traumatic brain injury: a KID study.

BACKGROUND: Traumatic brain injury (TBI) in pediatric patients is a major burden to public health. Understanding clinical associations with severity and short hospitalization (≤ 1 day length of stay) is needed to better inform management paradigms and optimize triage. METHODS: A retrospective review of the Kids' Inpatient Database (KID) was performed for all data reported between 2006 and 2012 for TBI patients aged ≤ 20 years. Univariate and multivariate regression analyses were performed to identify predictive factors of trauma severity and short hospitalization. RESULTS: A total of 220,777 pediatric TBI cases were identified, with the majority of cases being boys (66%) with a mean age of 11.5 years. Mean length of stay was 5.0 days, with 25% discharged within 1 day, and 83% routinely discharged home. In-hospital mortality occurred in 4% of cases. More severe TBI presentations were significantly and independently associated with older age, weekend admissions, hospital transfers, and in patients with chronic conditions and neurological issues (all P < 0.01). There were 38% of admission that were short hospitalizations. Younger age, male gender, less chronic conditions, fall and assault etiologies, and with milder injury severity all significantly and independently predicted greater likelihood of short hospitalization. CONCLUSIONS: The severity of pediatric TBI admissions to the hospital can be impacted by a number of parameters. Furthermore, there exists a subset of clinical associations for short hospitalization admissions. Proactive identification of these parameters at time of presentation will assist in optimizing the management of pediatric TBI].

Surgical management of quadrigeminal cistern arachnoid cysts: case series and literature review.

OBJECTIVE: Quadrigeminal cistern arachnoid cysts (QACs) are congenital lesions that can cause pineal region compression and obstructive hydrocephalus when sufficiently large. Management of these cysts is controversial and rates of reintervention are high. Given the limited data on the management of QACs, the authors retrospectively reviewed 20 years of cases managed at their institution and performed a literature review on this topic. METHODS: The authors performed a retrospective analysis of patients treated for QAC at their institution between 2001 and 2021. They also performed a literature review of studies published between 1980 and 2021 that reported at least 5 patients treated for QACs. Patient characteristics, radiographic findings, management course, and postoperative follow-up data were collected and analyzed. RESULTS: A total of 12 patients treated for a QAC at the authors' institution met the inclusion criteria for analysis. Median age was 9 months, mean cyst size was 5.1 cm, and 83% of patients had hydrocephalus. Initial treatment was endoscopic fenestration in 92% of these patients, 27% of whom had an endoscopic third ventriculostomy (ETV) performed concurrently. Reintervention was required in 42% of patients. Cases that required reintervention had a statistically significant lower median age at the initial intervention (5 months) than the cases that did not require reintervention (24.33 months; p = 0.018). There were no major complications. At a mean follow-up of 5.42 years, 83% of patients had improvement or resolution of their symptoms. A literature review revealed 7 studies that met the inclusion criteria, totaling 108 patients with a mean age of 8.8 years. Eighty-seven percent of patients had hydrocephalus at presentation. Ninety-two percent of patients were initially treated with endoscopic fenestration, 44% of whom underwent concurrent ETV. Complications occurred in 17.6% of cases, and reintervention was required in 30.6% of cases. The most frequent reason for reintervention was untreated or unresolved hydrocephalus after the initial procedure. CONCLUSIONS: Endoscopic fenestration is the most common treatment for QACs. While generally safe and effective, there is a high rate of reintervention after initial treatment of QACs, which may be associated with a younger age at the first intervention. Additionally, identifying patients who require initial treatment of hydrocephalus is critically important, as the literature suggests that untreated hydrocephalus is a common cause of reintervention.

Macrocephaly in the Primary Care Provider's Office.

Macrocephaly is commonly encountered in the primary care provider's office. It is defined as an occipitofrontal circumference that is greater than 2 standard deviations above the mean for the child's given age. Macrocephaly is a nonspecific clinical finding that may be benign or require further evaluation. An algorithmic approach is useful for aiding in the clinical decision-making process to determine if further evaluation with neuroimaging is warranted. Abnormal findings may signify a harmful underlying cause, requiring referral to a genetic specialist or neurosurgeon.

The Evolution of Telehealth From Pre-COVID-19 Pandemic Through A Hybrid Virtual Care Delivery Model: A Pediatric Hospital's Journey.

The COVID-19 pandemic transformed care delivery and influenced telehealth adoption by rehabilitation professionals and their patients. The purpose of this paper is to describe a pediatric health system's telehealth services pre-pandemic and how those services were scaled during the pandemic. A secondary aim is to provide a roadmap for the operational delivery of telehealth and rehabilitation services, including transition to a hybrid care delivery model. Findings suggested that telehealth can be rapidly scaled to address patient healthcare needs for an early intervention population during a pandemic. Telehealth use during the pandemic helped ensure continuity of care and likely reduced the risk of exposure to patients and staff to the virus. Benefits included enhanced access to care, and savings in time and money for families. Interestingly, as the pandemic declined, the use of telehealth services declined due to patient preference, with many families opting to request a return to in-person care.

GLP-1 receptor signaling in the laterodorsal tegmental nucleus attenuates cocaine seeking by activating GABAergic circuits that project to the VTA.

An emerging preclinical literature suggests that targeting central glucagon-like peptide-1 receptors (GLP-1Rs) may represent a novel approach to treating cocaine use disorder. However, the exact neural circuits and cell types that mediate the suppressive effects of GLP-1R agonists on cocaine-seeking behavior are largely unknown. The laterodorsal tegmental nucleus (LDTg) expresses GLP-1Rs and functions as a neuroanatomical hub connecting the nucleus tractus solitarius (NTS), the primary source of central GLP-1, with midbrain and forebrain nuclei known to regulate cocaine-seeking behavior. The goal of this study was to characterize the role of LDTg GLP-1R-expressing neurons and their projections to the ventral tegmental area (VTA) in the reinstatement of cocaine-seeking behavior, an animal model of relapse. Here, we showed that administration of the GLP-1R agonist exendin-4 (Ex-4) directly into the LDTg significantly attenuated cocaine seeking at a dose that did not affect sucrose seeking, ad libitum food intake, or body weight. In addition, our studies revealed that selectively activating NTS-to-LDTg circuits attenuated cocaine seeking via a GLP-1R-dependent mechanism. We also demonstrated, for the first time, that GLP-1Rs are expressed primarily on GABAergic neurons in the LDTg and that the efficacy of Ex-4 to reduce cocaine seeking depends, in part, on activation of LDTg-to-VTA GABAergic projections. Taken together, these studies identify a central mechanism by which Ex-4 attenuates cocaine seeking and highlight GABAergic GLP-1R-expressing circuits in the midbrain as important anti-craving pathways in regulating cocaine craving-induced relapse.

Administration of a novel high affinity PICK1 PDZ domain inhibitor attenuates cocaine seeking in rats.

Protein interacting with C kinase-1 (PICK1) regulates intra-cellular trafficking of GluA2-containing AMPA receptors, a process known to play a critical role in cocaine-seeking behavior. This suggests that PICK1 may represent a molecular target for developing novel pharmacotherapies to treat cocaine craving-induced relapse. Emerging evidence indicates that inhibition of PICK1 attenuates the reinstatement of cocaine-seeking behavior, an animal model of relapse. Here, we show that systemic administration of TAT-P4-(DATC5)2, a novel high-affinity peptide inhibitor of the PICK1 PDZ domain, dose-dependently attenuated the reinstatement of cocaine seeking in rats at doses that did not produce operant learning deficits or suppress locomotor activity. We also show that systemic TAT-P4-(DATC5)2 penetrated the brain where it was visualized in the nucleus accumbens shell. Consistent with these effects, infusions of TAT-P4-(DATC5)2 directly into the accumbens shell reduced cocaine, but not sucrose, seeking. The effects of TAT-P4-(DATC5)2 on cocaine seeking are likely due, in part, to inhibition of PICK1 in medium spiny neurons (MSNs) of the accumbens shell as TAT-P4-(DATC5)2 was shown to accumulate in striatal neurons and bind PICK1. Taken together, these findings highlight a novel role for PICK1 in the reinstatement of cocaine seeking and support future studies examining the efficacy of peptide inhibitors of PICK1 in animal and human models of cocaine relapse.

Activation of GLP-1 receptors attenuates oxycodone taking and seeking without compromising the antinociceptive effects of oxycodone in rats.

Despite the effectiveness of current medications to treat opioid use disorder, there is still a high rate of relapse following detoxification. Thus, there is critical need for innovative studies aimed at identifying novel neurobiological mechanisms that could be targeted to treat opioid use disorder. A growing body of preclinical evidence indicates that glucagon-like peptide-1 (GLP-1) receptor agonists reduce drug reinforcement. However, the efficacy of GLP-1 receptor agonists in attenuating opioid-mediated behaviors has not been thoroughly investigated. Using recently established models of opioid-taking and -seeking behaviors, we showed that systemic administration of the GLP-1 receptor agonist exendin-4 reduced oxycodone self-administration and the reinstatement of oxycodone-seeking behavior in rats. We also identified behaviorally selective doses of exendin-4 that reduced opioid-taking and -seeking behaviors and did not produce adverse feeding effects in oxycodone-experienced rats. To identify a central site of action, we showed that systemic exendin-4 penetrated the brain and bound putative GLP-1 receptors on dopamine D1 receptor- and dopamine D2 receptor-expressing medium spiny neurons in the nucleus accumbens shell. Consistent with our systemic studies, infusions of exendin-4 directly into the accumbens shell attenuated oxycodone self-administration and the reinstatement of oxycodone-seeking behavior without affecting ad libitum food intake. Finally, exendin-4 did not alter the analgesic effects of oxycodone, suggesting that activation of GLP-1 receptors attenuated opioid reinforcement without reducing the thermal antinociceptive effects of oxycodone. Taken together, these findings suggest that GLP-1 receptors could serve as potential molecular targets for pharmacotherapies aimed at reducing opioid use disorder.

[Why do not pregnant women want to get vaccinated against the flu? A scoping review]. / ¿Por qué las embarazadas no se vacunan de la gripe? Una scoping review.

BACKGROUND: Pregnant women and newborns are at increased risk of complications from seasonal flu. Vaccination is effective and safe but there is low adherence in pregnant women. Objective: to identify the reasons that lead pregnant women not to be vaccinated against seasonal influenza. METHODS: Scoping Review in which we used as search terms. DeCS "Pregnant Women", "Vaccines against Influenza". MeSH "Pregnant Women", "Influenza Vaccines", united by AND. Databases: Medline, VHL, Scielo, CUIDEN. The PRISMA model and the Joanna Briggs Institute tool were used to sort the search and synthesize the results. Motives were identified in each study and ordered according to frequency of appearance. RESULTS: 16 studies were found that identify 15 reasons for not being vaccinated. The most frequent were: Concern about side effects and / or vaccine safety and lack of information / recommendation from health professionals. CONCLUSIONS: The decision of not to be vaccinated seems to be multifactorial. In some cases, health professionals can play a fundamental role in adherence. These results could be useful for future research.

OBJETIVO: Las mujeres embarazadas, los neonatos y los recién nacidos tienen mayor riesgo de complicaciones por la gripe estacional. La vacunación es efectiva y segura, pero hay baja adherencia en embarazadas. El objetivo de este trabajo fue identificar los motivos que llevan a las embarazadas a no vacunarse contra la gripe estacional. METODOS: Scoping Review, en la que su utilizaron como términos de búsqueda: DeCS "Mujeres Embarazadas", "Vacunas contra la Influenza". MeSH "Pregnant Women", "Influenza Vaccines". Las bases de datos en las que se realizaron las búsquedas fueron: Medline, BVS, Scielo, CUIDEN. Se utilizó el modelo PRISMA y herramienta del Instituto Joanna Briggs para ordenar la búsqueda y sintetizar los resultados. Se identificaron los motivos de no vacunación en cada estudio y se ordenaron según su frecuencia de aparición. RESULTADOS: 16 estudios que identifican 15 motivos para no vacunarse. Los más frecuentes: Preocupación por los efectos secundarios y/o seguridad de la vacuna y falta de información/recomendación por parte del personal sanitario. CONCLUSIONES: La decisión para no vacunarse parece ser multifactorial. En algunos motivos hallados el papel del profesional puede jugar un papel fundamental en la adherencia. Estos resultados podrían ser útiles para futuras investigaciones y pueden servir de ejemplo para discusiones internas entre los profesionales sanitarios con el objetivo de promover la vacunación antigripal en embarazadas.

Activation of glucagon-like peptide-1 receptors in the nucleus accumbens attenuates cocaine seeking in rats.

Recent evidence indicates that activation of glucagon-like peptide-1 (GLP-1) receptors reduces cocaine-mediated behaviors and cocaine-evoked dopamine release in the nucleus accumbens (NAc). However, no studies have examined the role of NAc GLP-1 receptors in the reinstatement of cocaine-seeking behavior, an animal model of relapse. Here, we show that systemic infusion of a behaviorally relevant dose of the GLP-1 receptor agonist exendin-4 penetrated the brain and localized with neurons and astrocytes in the NAc. Administration of exendin-4 directly into the NAc core and shell subregions significantly attenuated cocaine priming-induced reinstatement of drug-seeking behavior. These effects were not due to deficits in operant responding or suppression of locomotor activity as intra-accumbal exendin-4 administration had no effect on sucrose-seeking behavior. To determine the effects of GLP-1 receptor activation on neuronal excitability, exendin-4 was bath applied to ex vivo NAc slices from cocaine-experienced and saline-experienced rats following extinction of cocaine-taking behavior. Exendin-4 increased the frequency of action potential firing of NAc core and shell medium spiny neurons in cocaine-experienced rats while no effect was observed in saline controls. In contrast, exendin-4 did not affect the frequency or amplitude of spontaneous excitatory postsynaptic currents or alter the paired-pulse ratios of evoked excitatory postsynaptic currents. These effects were not associated with altered expression of GLP-1 receptors in the NAc following cocaine self-administration. Taken together, these findings indicate that increased activation of GLP-1 receptors in the NAc during cocaine abstinence increases intrinsic, but not synaptic, excitability of medium spiny neurons and is sufficient to reduce cocaine-seeking behavior.

Computer-Assisted Surgery: Applications in Dentistry and Oral and Maxillofacial Surgery.

Computer-assisted surgery (CAS) has evolved over time from its earliest introduction with utility in the Neurosurgical field. Within the past twenty years, optical navigation systems have emerged and developed into a great tool for the fields of dentistry and craniomaxillofacial surgery (CMF). Currently, CAS is useful for orthognathic and temporomandibular joint surgery, facial trauma, maxillomandibular reconstruction, implantology, and restorative dentistry. This article describes the indications of CAS in dentistry, with large emphasis on CMF. We will review the process, benefits as well as shortcomings, and end with a discussion on the future of CAS.

Parity-Dependent Hemosiderin and Lipofuscin Accumulation in the Reproductively Aged Mouse Ovary.

The progressive decline of the ovarian follicle pool leads to reproductive ageing. The latter is accompanied by age-related disorders, including various types of cancer. In fact, the highest rates of ovarian cancer (OC) occur at postmenopause while OC risk is significantly modulated by parity records during previous fertile life. We approached the age-parity relationship in the C57BL/6 mouse model and herein describe the presence of nonheme iron (hemosiderin) and deposits of the "age pigment" lipofuscin in reproductively aged mouse ovaries by applying conventional histochemical methods and autofluorescence. In addition, the 8-OHdG adduct was evaluated in ovarian genomic DNA. Both hemosiderin and lipofuscin were significantly higher in virgin compared to multiparous ovaries. The same pattern was observed for 8-OHdG. We conclude that nulliparity induces a long-term accumulation of iron and lipofuscin with concomitant oxidative damage to DNA in the mouse ovary. Since lipofuscin is a widely accepted senescence marker and given the recently postulated role of lipofuscin-associated iron as a source of reactive oxygen species (ROS) in senescent cells, these findings suggest a possible pathogenic mechanism by which nulliparity contributes to an increased OC risk in the postmenopausal ovary.

Glucagon-like peptide-1 receptor activation in the ventral tegmental area attenuates cocaine seeking in rats.

Novel molecular targets are needed to develop new medications for the treatment of cocaine addiction. Here we investigated a role for glucagon-like peptide-1 (GLP-1) receptors in the reinstatement of cocaine-seeking behavior, an animal model of relapse. We showed that peripheral administration of the GLP-1 receptor agonist exendin-4 dose dependently reduced cocaine seeking in rats at doses that did not affect ad libitum food intake, meal patterns or body weight. We also demonstrated that systemic exendin-4 penetrated the brain where it putatively bound receptors on both neurons and astrocytes in the ventral tegmental area (VTA). The effects of systemic exendin-4 on cocaine reinstatement were attenuated in rats pretreated with intra-VTA infusions of the GLP-1 receptor antagonist exendin-(9-39), indicating that the suppressive effects of systemic exendin-4 on cocaine seeking were due, in part, to activation of GLP-1 receptors in the VTA. Consistent with these effects, infusions of exendin-4 directly into the VTA reduced cocaine seeking. Finally, extinction following cocaine self-administration was associated with decreased preproglucagon mRNA expression in the caudal brainstem. Thus, our study demonstrated a novel role for GLP-1 receptors in the reinstatement of cocaine-seeking behavior and identified behaviorally relevant doses of a GLP-1 receptor agonist that selectively reduced cocaine seeking and did not produce adverse effects.