Herpesviruses and human papillomaviruses in saliva and biopsies of patients with orofacial tumors.

OBJECTIVES: To determine the prevalence and association of HPV and Herpesviruses in saliva and tissue samples of patients with orofacial tumors. METHODS: Biopsies of tumors were done, and saliva samples were collected from patients with orofacial tumors for the determination of viruses using nested multiplex PCR. Independent variables were sex, age, comorbidities, tumor stage, and length of stay. Outcome variables were the presence or absence of herpesviruses and HPV. Descriptive summaries and inferential statistics were done. RESULTS: A hundred patients were included in the study. Prevalence of herpesviruses and HPV were 17.6 % and 57.0 % in tumors, and 48.3 % and 60.0 % in the saliva of patients respectively. Herpesviruses detected included EBV (21.3 %), HHV-7 (11.2 %), CMV (6.7 %), HSV-1 (5.1 %), HSV-2 (1.1 %), VZV (1.1 %), and Kaposi sarcoma virus (0.6 %). The most prevalent HPV genotypes were HPV-42 (29 %), HPV-43 (22.7 %), HPV-52 (22.2 %), HPV-39 (18.8 %), and HPV-18 (9.1 %). The odds of EBV being detected in malignant orofacial tumors were 2 times that of benign orofacial tumors. HPV DNA in the saliva of patients with orofacial tumors was 69.7 %, compared to 18.2 % of the control sample (p < 0.001). The median length of stay for all participants was 6.5 days, those associated with viruses stayed longer. CONCLUSION: There was a high prevalence of Herpesviruses and HPV in saliva and tumor samples of patients with orofacial tumors, signalling some potential for more work to be done in this area.

Estimating personal exposures to household air pollution and plastic garbage burning among adolescent girls in Jalapa, Guatemala.

Waste collection services are uncommon in rural areas of low-resource countries, causing waste accumulation and subsequent dumping and burning of garbage. Air pollution from household garbage burning, including plastics, has been observed in Jalapa, Guatemala in addition to household air pollution (HAP) from cooking. Adolescent girls often help with these cooking and household tasks, but little is known about their exposures. We characterized 24-h exposures to HAP and household garbage burning in adolescent girls by measuring fine particulate matter (PM2.5), black carbon (BC), urinary biomarkers of polycyclic aromatic hydrocarbons (PAHs), bisphenol A (BPA), and phthalates. We recruited 60 girls between 13 and 17 years of age who helped with cooking activities and lived with participants of the Household Air Pollution Intervention Network (HAPIN) trial. We recruited n = 30 girls each from the control (wood-burning stove) and intervention (liquefied petroleum gas stove) arms. We also measured real-time kitchen concentrations of BC in 20 homes (33%). PM2.5 and BC were measured in n = 21 control and n = 20 intervention participants. Median concentrations of personal PM2.5 and BC and kitchen BC were lower (p < 0.05) in the intervention arm by 87%, 80%, and 85%, respectively. PAH metabolite concentrations were lower (p < 0.001) for all nine metabolites in intervention (n = 26) compared to control participants (n = 29). Urinary BPA concentrations were 66% higher in participants who reported using cosmetics (p = 0.02), and phthalate concentrations were 63% higher in participants who had reported using hair products during the sample period (p = 0.05). Our results suggest that gas stoves can reduce HAP exposures among adolescents who are not primary cooks at home. Biomarkers of plastic exposure were not associated with intervention status, but some were elevated compared to age- and sex-matched participants of the National Health and Nutrition Examination Survey (NHANES).

Herpesviruses and human papillomaviruses in saliva and biopsies of patients with orofacial tumors

Abstract Objectives: To determine the prevalence and association of HPV and Herpesviruses in saliva and tissue samples of patients with orofacial tumors. Methods: Biopsies of tumors were done, and saliva samples were collected from patients with orofacial tumors for the determination of viruses using nested multiplex PCR. Independent variables were sex, age, comorbidities, tumor stage, and length of stay. Outcome variables were the presence or absence of herpesviruses and HPV. Descriptive summaries and inferential statistics were done. Results: A hundred patients were included in the study. Prevalence of herpesviruses and HPV were 17.6 % and 57.0 % in tumors, and 48.3 % and 60.0 % in the saliva of patients respectively. Herpesviruses detected included EBV (21.3 %), HHV-7 (11.2 %), CMV (6.7 %), HSV-1 (5.1 %), HSV-2 (1.1 %), VZV (1.1 %), and Kaposi sarcoma virus (0.6 %). The most prevalent HPV genotypes were HPV-42 (29 %), HPV-43 (22.7 %), HPV-52 (22.2 %), HPV-39 (18.8 %), and HPV-18 (9.1 %). The odds of EBV being detected in malignant orofacial tumors were 2 times that of benign orofacial tumors. HPV DNA in the saliva of patients with orofacial tumors was 69.7 %, compared to 18.2 % of the control sample (p < 0.001). The median length of stay for all participants was 6.5 days, those associated with viruses stayed longer. Conclusion: There was a high prevalence of Herpesviruses and HPV in saliva and tumor samples of patients with orofacial tumors, signalling some potential for more work to be done in this area.

Outcomes of Critically Ill Children With Acute Lymphoblastic Leukemia and Cytokine Release Syndrome Due to Chimeric Antigen Receptor T Cell Therapy: US, Multicenter PICU, Cohort Database Study.

OBJECTIVES: Cytokine release syndrome (CRS) is a potentially lethal toxicity associated with chimeric antigen receptor T cell therapy for pediatric acute lymphoblastic leukemia (ALL). Outcomes after critical illness due to severe CRS are poorly described. Our aim was to characterize critical illness outcomes across a multicenter cohort of PICU patients with ALL and CRS. DESIGN: Multicenter retrospective cohort study. SETTING: Twenty-one PICUs contributing data to Virtual Pediatric Systems, LLC (January 2020-December 2021). PATIENTS: PICU patients with ALL or unclassified leukemia and CRS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 55 patients; 34 (62%) were 12 years or older, 48 (87%) were admitted from a hospital inpatient ward, and 23 (42%) received advanced organ failure support or monitoring. Fifty-one survived to PICU discharge (93%) including 19 of 23 (83%) who received advanced organ failure support or monitoring defined as receipt of noninvasive or invasive ventilation, cardiopulmonary resuscitation, extracorporeal membrane oxygenation, continuous renal replacement therapy, or placement of a tracheostomy, arterial catheter, hemodialysis catheter, or intracranial catheter. Twelve patients (22%) received invasive ventilation, nine of whom survived to PICU discharge. Two of four patients who received continuous renal replacement therapy and one of three patients who required cardiopulmonary resuscitation survived to PICU discharge. Lengths of PICU stay were median 3.0 days (interquartile range, 1.4-7.8 d) among PICU survivors, 7.8 (5.4-11.1) among those receiving advanced organ failure support or monitoring, and 7.2 days (interquartile range, 2.9-14.7 d) among nonsurvivors. Of the 51 patients who survived to PICU discharge, 48 (94%) survived the hospitalization. CONCLUSIONS: PICU patients with CRS frequently received a high level of support, and the majority survived their PICU stay and hospitalization. Additional multicenter investigations of severe CRS are necessary to inform evidence-based practice.

Parenting and Neurobehavioral Outcomes in Children Born Moderate-to-Late Preterm and at Term.

OBJECTIVES: To compare the parenting environment and the relationships between parenting behaviors and concurrent child neurobehavioral outcomes at 2 years of corrected age between children born moderate-to-late preterm (MLP; 32-36 weeks of gestation) and at term (≥37 weeks of gestation). STUDY DESIGN: Participants were 129 children born MLP and 110 children born at term and their mothers. Mothers' parenting behaviors (sensitivity, structuring, nonintrusiveness, nonhostility) were assessed at 2 years of corrected age using the Emotional Availability Scales. Child cognitive and language development were assessed using the Bayley Scales of Infant and Toddler Development, and social-emotional competence using the Infant Toddler Social and Emotional Assessment. RESULTS: Mothers of children born MLP and at term displayed similar parenting behaviors overall, with slightly lower nonintrusiveness in mothers of children born MLP (adjusted mean difference -0.32 [-0.60, -0.04]; P = .03). In both groups of children, greater maternal sensitivity was associated with better cognitive development (P < .001 MLP; P = .02 term), increased maternal structuring was associated with better social-emotional competence (P = .02 MLP; P = .03 term), and higher maternal nonintrusiveness was associated with better cognitive, language, and social-emotional outcomes (all P < .04). Greater maternal sensitivity and structuring were associated with better language development in children born MLP but not in children born at term. CONCLUSIONS: Parenting behaviors are important for neurobehavioral outcomes in children born MLP and at term. Language development may be more strongly influenced by select parenting behaviors in children born MLP compared with children born at term.

An Electronically delivered, Patient-activation tool for Intensification of medications for Chronic Heart Failure with reduced ejection fraction: Rationale and design of the EPIC-HF trial.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) benefits from initiation and intensification of multiple pharmacotherapies. Unfortunately, there are major gaps in the routine use of these drugs. Without novel approaches to improve prescribing, the cumulative benefits of HFrEF treatment will be largely unrealized. Direct-to-consumer marketing and shared decision making reflect a culture where patients are increasingly involved in treatment choices, creating opportunities for prescribing interventions that engage patients. HYPOTHESIS: Encouraging patients to engage providers in HFrEF prescribing decisions will improve the use of guideline-directed medical therapies. DESIGN: The Electronically delivered, Patient-activation tool for Intensification of Chronic medications for Heart Failure with reduced ejection fraction (EPIC-HF) trial randomizes patients with HFrEF to usual care versus patient-activation tools-a 3-minute video and 1-page checklist-delivered prior to cardiology clinic visits that encourage patients to work collaboratively with their clinicians to intensify HFrEF prescribing. The study assesses the effectiveness of the EPIC-HF intervention to improve guideline-directed medical therapy in the month after its delivery while using an implementation design to also understand the reach, adoption, implementation, and maintenance of this approach within the context of real-world care delivery. Study enrollment was completed in January 2020, with a total 305 patients. Baseline data revealed significant opportunities, with <1% of patients on optimal HFrEF medical therapy. SUMMARY: The EPIC-HF trial assesses the implementation, effectiveness, and safety of patient engagement in HFrEF prescribing decisions. If successful, the tool can be easily disseminated and may inform similar interventions for other chronic conditions.

Morphology, histology and histochemistry of the digestive tract of the Banded tilapia, Tilapia sparrmanii (Perciformes: Cichlidae)

This study described anatomical, histological and histochemical features of the mucosal layer of the digestive tract of Tilapia sparrmanii Smith, 1840, an omnivorous freshwater fish endemic to Southern Africa. This species exhibited a short thick oesophagus with long deep longitudinal folds (466.68 ± 16.91 µm), and a thick (173.50 ± 10.92 µm) muscular layer that allow the passage of large food items. The mucosa was lined with stratified secretory epithelium rich in goblet cells that secreted neutral and acid mucins. The stomach was a sac-like structure with simple tubular glands surrounded by connective tissue. The mucosa was lined with simple columnar epithelium and the lamina propria exhibited a well-developed layer of gastric glands that occupied the entire length of the cardio-fundic region. The stomach mucosa consisted of epithelial cells with intense neutral mucin secretion which protects against gastric juice. Neck cells of gastric glands synthesized neutral and acid mucins. The intestine was highly coiled and presented a complex pattern of transversal folds internally (villi). Villi length decreased progressively from the anterior to the posterior intestine (p 0.0001). Tunica muscularis of the mid-intestine had the thinnest thickness among all parts of the intestine (p 0.0001). Goblet cells whose numbers increased towards the rectum secreted both acid and neutral mucins. The results indicate structural similarities of T. sparrmanii GIT with other tilapia species and will be useful for understanding the physiology of the digestive systems as well as functional components of the GIT.

Morphology, histology and histochemistry of the digestive tract of the Banded tilapia, Tilapia sparrmanii (Perciformes: Cichlidae)

This study described anatomical, histological and histochemical features of the mucosal layer of the digestive tract of Tilapia sparrmanii Smith, 1840, an omnivorous freshwater fish endemic to Southern Africa. This species exhibited a short thick oesophagus with long deep longitudinal folds (466.68 ± 16.91 µm), and a thick (173.50 ± 10.92 µm) muscular layer that allow the passage of large food items. The mucosa was lined with stratified secretory epithelium rich in goblet cells that secreted neutral and acid mucins. The stomach was a sac-like structure with simple tubular glands surrounded by connective tissue. The mucosa was lined with simple columnar epithelium and the lamina propria exhibited a well-developed layer of gastric glands that occupied the entire length of the cardio-fundic region. The stomach mucosa consisted of epithelial cells with intense neutral mucin secretion which protects against gastric juice. Neck cells of gastric glands synthesized neutral and acid mucins. The intestine was highly coiled and presented a complex pattern of transversal folds internally (villi). Villi length decreased progressively from the anterior to the posterior intestine (p 0.0001). Tunica muscularis of the mid-intestine had the thinnest thickness among all parts of the intestine (p 0.0001). Goblet cells whose numbers increased towards the rectum secreted both acid and neutral mucins. The results indicate structural similarities of T. sparrmanii GIT with other tilapia species and will be useful for understanding the physiology of the digestive systems as well as functional components of the GIT.(AU)

Influence of Fathers' Early Parenting on the Development of Children Born Very Preterm and Full Term.

OBJECTIVES: To examine factors associated with fathers' early parenting behaviors (including very preterm [VPT] birth, familial social risk, child sex, and child medical risk), and the relationship between fathers' early parenting behaviors and later child development. STUDY DESIGN: Participants were 81 VPT (born <30 weeks of gestation) and 39 full-term father-child dyads. Parenting behaviors (sensitivity, structuring, nonintrusiveness, nonhostility) were assessed at 12 months of corrected age using the Emotional Availability Scales, with scores ranging from 1 (low) to 7 (high). At 24 months of corrected age, child cognitive, language, motor, and social-emotional development were assessed. Results are presented as (regression coefficients; 95% CIs). RESULTS: There was little evidence that VPT birth, familial social risk, or child medical risk were associated with fathers' parenting behaviors. Fathers of girls tended to be more sensitive (0.42; 0.18, 0.65), less intrusive (0.36; 0.04, 0.70), and less hostile (0.26; 0.01, 0.50) compared with fathers of boys. Higher structuring was associated with more optimal cognitive (3.29; 1.25, 5.34), and language development (4.69; 2.26, 7.14). Higher sensitivity was associated with more optimal language development 3.35 (0.95, 5.75), and more intrusive behavior was associated with more externalizing symptoms (-1.68; -3.06, -0.31). CONCLUSIONS: Early parenting did not differ between fathers with VPT and full-term children, but fathers' parenting did vary according to child sex. Fathers' early parenting was associated with future neurodevelopment, reinforcing the need to support fathers' parenting, and include fathers in early intervention programs.

Ancestral origin of ApoE ε4 Alzheimer disease risk in Puerto Rican and African American populations.

The ApoE ε4 allele is the most significant genetic risk factor for late-onset Alzheimer disease. The risk conferred by ε4, however, differs across populations, with populations of African ancestry showing lower ε4 risk compared to those of European or Asian ancestry. The cause of this heterogeneity in risk effect is currently unknown; it may be due to environmental or cultural factors correlated with ancestry, or it may be due to genetic variation local to the ApoE region that differs among populations. Exploring these hypotheses may lead to novel, population-specific therapeutics and risk predictions. To test these hypotheses, we analyzed ApoE genotypes and genome-wide array data in individuals from African American and Puerto Rican populations. A total of 1,766 African American and 220 Puerto Rican individuals with late-onset Alzheimer disease, and 3,730 African American and 169 Puerto Rican cognitively healthy individuals (> 65 years) participated in the study. We first assessed average ancestry across the genome ("global" ancestry) and then tested it for interaction with ApoE genotypes. Next, we assessed the ancestral background of ApoE alleles ("local" ancestry) and tested if ancestry local to ApoE influenced Alzheimer disease risk while controlling for global ancestry. Measures of global ancestry showed no interaction with ApoE risk (Puerto Rican: p-value = 0.49; African American: p-value = 0.65). Conversely, ancestry local to the ApoE region showed an interaction with the ApoE ε4 allele in both populations (Puerto Rican: p-value = 0.019; African American: p-value = 0.005). ApoE ε4 alleles on an African background conferred a lower risk than those with a European ancestral background, regardless of population (Puerto Rican: OR = 1.26 on African background, OR = 4.49 on European; African American: OR = 2.34 on African background, OR = 3.05 on European background). Factors contributing to the lower risk effect in the ApoE gene ε4 allele are likely due to ancestry-specific genetic factors near ApoE rather than non-genetic ethnic, cultural, and environmental factors.

The U.S. military's Neisseria gonorrhoeae resistance surveillance initiatives in selected populations of five countries.

Multi-drug resistant Neisseria gonorrhoeae (GC) threatens the successful treatment of gonorrhea. This report presents preliminary findings with regard to the prevalence of laboratory-confirmed GC and the extent of drug-resistance among sample populations in five countries. Between October 2010 and January 2013, 1,694 subjects (54% male; 45% female; 1% unknown) were enrolled and screened for the presence of laboratory-confirmed GC in the United States, Djibouti, Ghana, Kenya, and Peru. Overall, 108 (6%) of enrolled subjects tested positive for GC. Antimicrobial susceptibility testing results were available for 66 GC isolates. Resistance to at least three antibiotics was observed at each overseas site. All isolates tested in Ghana (n=6) were resistant to ciprofloxacin, penicillin, and tetracycline. In Djibouti, preliminary results suggested resistance to penicillin, tetracycline, ciprofloxacin, cefepime, and ceftriaxone. The small sample size and missing data prevent comparative analysis and limit the generalizability of these preliminary findings.

Association between maximum bite force and craniofacial morphology in an Amazonian population with normal dental occlusion / Associação entre força máxima de mordida e morfologia craniofacial em população Amazonense com oclusão normal

The aim of this study was to determine the maximum bite force (MBF) in Amazonian children and young adolescents with normal dental occlusion, the average craniofacial morphology, and investigate associations between craniofacial morphology and body mass with MBF. Ninety-seven children and young adolescents, 21 with primary dentition and 76 with permanent dentition and normal dental occlusion were included in the study. Subjects were from Amazonian tribes studying at three schools in Leticia, Amazonas, Colombia. MBF was determined by means of a digital hydraulic pressure gauge. Body mass index (BMI), facial morphology index, and dental arches transverse dimensions were computed in each subject. Mann Whitney test, a one-tailed non-parametric statistical analysis, was used to contrast MBF between primary dentition and permanent dentition. The same statistical analysis was used to determine MBF statistical differences between the various facial morphologies. Pearson correlation statistical analysis was used to evaluate associations between MBF with BMI, dental arches transverse dimensions or facial morphology. Statistical significance was determined at 95 percent level of confidence. A significant difference was found for the MBF between subjects in primary dentition (incisors: 116.57 ± 48.30; right molars: 368.38 ± 105.52; left molars: 322.76 ± 83.77) and those in permanent dentition (incisors: 260.88 ± 85.73; right molars: 459.63 ± 167.11; left molars: 645.67 ± 170.60). In addition, an association was observed between MBF and facial morphology index. It was concluded that MBF significantly increases from primary to permanent dentition in subjects with normal dental occlusion. Furthermore, this study agrees with other reports stating that MBF is associated with the morphology of the face, but not with BMI or dental arches transverse dimensions.

O presente estudo teve como objetivo determinar a força máxima de mordida (FMM) e morfologia craniofacial média de crianças e adolescentes da região do Amazonas com oclusão dentária normal, e investigar associações entre índice de massa corpórea (IMC), morfologia craniofacial e FMM. Participaram do estudo 97 crianças e adolescentes, 21 deles com dentição primária e 76 com dentição permanente, todos com oclusão dentária normal. Os indivíduos pertencentes a tribos amazônicas estudavam em três escolas em Leticia, Amazonas e Colombia. A FMM foi determinada utilizando medidor de pressão hidráulica digital. Índice de massa corporal (IMC), índice morfológico, e dimensões transversais dos arcos dentários de cada indivíduo foram registrados. O teste de Mann Whitney, análise unicaudal não paramétrica, foi aplicado na comparação da força máxima de mordida em dentição decídua e permanente. A mesma análise estatística foi utilizada para determinar as diferenças estatísticas acerca da FMM entre as diferentes características da morfologia facial. O coeficiente de correlação de Pearson foi empregado para avaliar as associações entre FMM e IMC, dimensão transversal dos arcos dentários ou morfologia facial. A significância estatística foi determinada com intervalos de 95% de confiança. Diferença significativa foi observada para FMM entre sujeitos com dentição decídua (incisivos: 116.57 ± 48.30; molares direitos: 368.38 ± 105.52; molares esquerdos: 322.76 ± 83.77) e aqueles com dentição permanente (incisivos: 260.88 ± 85.73; molares direitos: 459.63 ± 167.11molares esquerdos: 645.67 ± 170.60).

Condom use during last sexual contact and last 30 days in two samples of Caribbean military personnel.

Condom use during last sexual contact is a survey measure that may be used to inform monitoring and evaluation indicators of recent condom use in populations at risk for HIV infection and other sexually transmitted infections, such as the uniformed services. The authors tested for differences in condom use measures that were fielded within separate Biological and Behavioral Surveillance Surveys conducted in the armed forces of two separate nations: the Dominican Republic and Belize. Both surveys included measures of condom use during last sexual contact with specified partners and both surveys included the Risk Behavior Assessment (RBA), which measures specific sexual acts and condom use frequency during a specified time period. In both samples, more than 40% of respondents who reported condom use during last sexual contact with a regular partner also reported engaging in unprotected sex when screened with the RBA. Furthermore, more than 60% of respondents who reported condom use during last sexual encounter with a commercial sex worker also reported engaging in unprotected sex when screened with the RBA. The results carry implications for monitoring and evaluation indicators of large-scale HIV prevention programs. The authors recommend that, when feasible, more in-depth instruments such as the RBA be considered to measure recent condom use in populations of uniformed services personnel.

Not sold here: limited access to legally available syringes at pharmacies in Tijuana, Mexico.

BACKGROUND: Sterile syringe access is a critical component of HIV prevention programs. Although retail pharmacies provide convenient outlets for syringe access, injection drug users (IDUs) may encounter barriers to syringe purchase even where purchase without a prescription is legal. We sought to obtain an objective measure of syringe access in Tijuana, Mexico, where IDUs report being denied or overcharged for syringes at pharmacies. METHODS: Trained "mystery shoppers" attempted to buy a 1 cc insulin syringe according to a predetermined script at all retail pharmacies in three Tijuana neighborhoods. The same pharmacies were surveyed by telephone regarding their syringe sales policies. Data on purchase attempts were analyzed using basic statistics to obtain an objective measure of syringe access and compared with data on stated sales policies to ascertain consistency. RESULTS: Only 46 (28.4%) of 162 syringe purchase attempts were successful. Leading reasons for unsuccessful attempts were being told that the pharmacy didn't sell syringes (35.3%), there were no syringes in stock (31.0%), or a prescription was required (20.7%). Of 136 pharmacies also surveyed by telephone, a majority (88.2%) reported selling syringes but only one-third (32.5%) had a successful mystery shopper purchase; the majority of unsuccessful purchases were attributed to being told the pharmacy didn't sell syringes. There was similar discordance regarding prescription policies: 74 pharmacies said in the telephone survey that they did not require a prescription for syringes, yet 10 of these pharmacies asked the mystery shopper for a prescription. CONCLUSIONS: IDUs in Tijuana have limited access to syringes through retail pharmacies and policies and practices regarding syringe sales are inconsistent. Reasons for these restrictive and inconsistent practices must be identified and addressed to expand syringe access, reduce syringe sharing and prevent HIV transmission.

Interviewer gender and self-reported sexual behavior and mental health among male military personnel.

OBJECTIVES: To determine whether self-reported sexual behavior and mental health varied by interviewer gender in a population of male military personnel. METHODS: Eight male and six female data collectors verbally administered structured interviews to 474 male Dominican military personnel stationed at border crossing zones in the Dominican Republic. Measurements included sexual behaviors and mental health. RESULTS: Respondents were less likely to report oral and vaginal sex to male interviewers, and were more likely to report sexual coercion and alcohol abuse to male interviewers. Respondents were more likely to report depression and post-traumatic stress disorder to female interviewers. CONCLUSION: Interviewer gender influenced the prevalence of sexual behaviors and mental health, which carries implications for future research in military personnel.

Repeated cocaine exposure decreases dopamine D2-like receptor modulation of Ca(2+) homeostasis in rat nucleus accumbens neurons.

The nucleus accumbens (NAc) is a limbic structure in the forebrain that plays a critical role in cognitive function and addiction. Dopamine modulates activity of medium spiny neurons (MSNs) in the NAc. Both dopamine D1-like and D2-like receptors (including D1R or D(1,5)R and D2R or D(2,3,4)R, respectively) are thought to play critical roles in cocaine addiction. Our previous studies demonstrated that repeated cocaine exposure (which alters dopamine transmission) decreases excitability of NAc MSNs in cocaine-sensitized, withdrawn rats. This decrease is characterized by a reduction in voltage-sensitive Na(+) currents and high voltage-activated Ca(2+) currents, along with increased voltage-gated K(+) currents. These changes are associated with enhanced activity in the D1R/cAMP/PKA/protein phosphatase 1 pathway and diminished calcineurin function. Although D1R-mediated signaling is enhanced by repeated cocaine exposure, little is known whether and how the D2R is implicated in the cocaine-induced NAc dysfunction. Here, we performed a combined electrophysiological, biochemical, and neuroimaging study that reveals the cocaine-induced dysregulation of Ca(2+) homeostasis with involvement of D2R. Our novel findings reveal that D2R stimulation reduced Ca(2+) influx preferentially via the L-type Ca(2+) channels and evoked intracellular Ca(2+) release, likely via inhibiting the cAMP/PKA cascade, in the NAc MSNs of drug-free rats. However, repeated cocaine exposure abolished the D2R effects on modulating Ca(2+) homeostasis with enhanced PKA activity and led to a decrease in whole-cell Ca(2+) influx. These adaptations, which persisted for 21 days during cocaine abstinence, may contribute to the mechanism of cocaine withdrawal.

Bryostatins: biological context and biotechnological prospects.

Bryostatins are a family of protein kinase C modulators that have potential applications in biomedicine. Found in miniscule quantities in a small marine invertebrate, lack of supply has hampered their development. In recent years, bryostatins have been shown to have potent bioactivity in the central nervous system, an uncultivated marine bacterial symbiont has been shown to be the likely natural source of the bryostatins, the bryostatin biosynthetic genes have been identified and characterized, and bryostatin analogues with promising biological activity have been developed and tested. Challenges in the development of bryostatins for biomedical and biotechnological application include the cultivation of the bacterial symbiont and heterologous expression of bryostatin biosynthesis genes. Continued exploration of the biology as well as the symbiotic origin of the bryostatins presents promising opportunities for discovery of additional bryostatins, and new functions for bryostatins.

Actividad antipalúdica de plantas procedentes de la Amazonía peruana / Activity antipalúdica of plants coming from the Peruvian Amazonía

El presente trabajo fue realizado con el objetivo de plantear la búsqueda de nuevos agentes antipalúdicos de origen natural a través de pruebas biológicas. Para la realización del mismo se utilizaron extractos crudos de plantas recolectadas en la Amazonia peruana. La evaluacion fue realizada por un método directo que es el modelo in vitro, en cultivo de Plasmodium falciparum F32 sensible a la Cloroquina y por un modelo indirecto que es el ensayo de la inhibición de la Biomineralización de la Ferriprotoporfina IX (FBIT). Los resultados obtenidos nos permiten clasificar a 7 extractos como activos en la prueba de Evaluación de la Actividad Antipalúdica por el método directo in vitro, y 14 por el método indirecto (FBIT), de todos estos solo a 4 presentan actividad por ambos métodos por lo que podemos afirmar que su mecanismo de acción es similar al de la Cloroquina, y los 3 restantes son los que mas interesan pues su mecanismo de acción es diferente al de la Cloroquina, y pordría ser de gran beneficio en cepas resistentes a esta droga. Todos estos extractos se encuentran actualmente en un proceso de purificación para una nueva evaluación a través de estudios químicos y biológicos.

Neural substrates of anorexia nervosa: a behavioral challenge study with positron emission tomography.

OBJECTIVE: To delineate functional brain abnormalities associated with anorexia nervosa (AN). STUDY DESIGN: Positron emission tomographic measurements of regional cerebral blood flow (rCBF) were performed on 8 female patients with AN and 8 healthy female control subjects during exposure to 3 types of stimuli: high-calorie foods, low-calorie foods, and non-food items. Heart rate and internal state analog scale scores were also obtained. Stereotactic transformation and statistical parametric mapping techniques were used to analyze imaging data. RESULTS: During the high-calorie condition, control subjects reported a significant desire to eat, whereas subjects with AN reported elevated anxiety and exhibited increases in heart rate. Patients with AN had elevated bilateral medial temporal lobe rCBF compared with control subjects. Planned comparisons for group-by-condition interactions demonstrated greater activation within left occipital cortex and right temporo-occipital cortex for the high-calorie versus low-calorie contrast in patients with AN compared with control subjects. CONCLUSIONS: Our finding of elevated rCBF within bilateral medial temporal lobes is similar to published results in patients with psychotic disorders and may be related to the body image distortion common to AN. The high-calorie food phobia exhibited by patients with AN appears to be associated with exaggerated responses in visual association cortex, as has been previously observed in studies of specific phobias.