Association between intimate partner violence and pregnancy intention: evidence from the Peruvian demographic and health survey.

BACKGROUND: Intimate partner violence (IPV) in Peru represents a significant public health challenge. IPV can influence women's reproductive and social behaviors, undermining fertility control, and exacerbating unintended pregnancies. Our objective was to assess the association between IPV and pregnancy intention among Peruvian women of reproductive age. METHODS: We conducted a secondary analysis of Peru's 2020 Demographic and Family Health Survey data. The independent variable in this study was IPV against women, which includes psychological IPV, sexual IPV, and physical IPV. If a respondent experienced any of these three forms of IPV, the IPV variable was labeled as "yes"; if none were present, it was labeled as "no". The dependent variable was pregnancy intention (no vs. yes). We utilized a generalized linear model (GLM) from the Poisson family with a log link function to assess the relationship between IPV occurrences (total and each IPV type) and pregnancy intention. We report crude and adjusted prevalence ratios (aPR) with 95% confidence intervals (95%CI). RESULTS: We analyzed data from 8466 women aged 15 to 49. The prevalence of any IPV was 49.6% (psychological IPV: 45.8%; physical IPV: 22.2%; and sexual IPV: 4.3%). Exposure to physical IPV (aPR: 1.05; 95% CI: 1.03-1.07), psychological IPV (aPR: 1.04; 95% CI: 1.02-1.06), and sexual IPV (aPR: 1.09; 95% CI: 1.04-1.13), as well as a history of any IPV (aPR: 1.05; 95% CI: 1.02-1.07), were associated with a higher probability of not intending to become pregnant. This association persisted after adjusting for confounders like age, marital status, educational attainment, education level of the child's father, place of residence, wealth, ethnicity, and parity. CONCLUSION: One in two Peruvian women reported experiencing IPV. An association was observed between IPV exposure and a higher probability of not holding an intention to become pregnant.

Efficacy and safety of visnadine in the treatment of symptoms of sexual dysfunction in heterosexual women: a systematic review of randomized clinical trials.

OBJECTIVE: To synthesize the primary evidence on the efficacy and safety of visnadine on symptoms of sexual dysfunction (SD) in heterosexual women. METHODS: We conducted a systematic review of randomized clinical trials (RCTs) with a primary search without language restriction in PubMed/Medline, Scopus, Embase, Web of Science, Cochrane Library, and international clinical trial registries. Trials reporting the use of visnadine by any route in women with SD were eligible. We performed screening, data extraction, and risk of bias assessment in a double-blind approach. The primary outcomes were the Female Sexual Function Index (FSFI) and its domains. Secondary outcomes were safety, arousal, lubrication, pleasure, orgasm, negative sensations, duration, and overall satisfaction. RESULTS: Initially, 242 records were retrieved. We selected nine papers for full-text reading and finally included two RCTs: one with a parallel design and one with a crossover design with a total of 96 patients. One study compared visnadine aerosol with a placebo, while the other compared different frequencies of visnadine aerosol use. Visnadine use showed a statistically significant improvement (p < 0.05) in overall FSFI scores, regardless of the frequency of use. A meta-analysis was not possible due to the high clinical and methodological heterogeneity between available studies. CONCLUSION: RCTs regarding the use of visnadine for the Female SD are scarce and methodologically limited. This preliminary evidence shows visnadine as a potentially effective and safe option to alleviate some of the clinical symptoms of SD in heterosexual women. However, future better-designed randomized studies with larger sample numbers are required.

Surface wave propagation control with locally resonant metasurfaces using topology-optimized resonatorsa).

Locally resonant elastodynamic metasurfaces for suppressing surface waves have gained popularity in recent years, especially because of their potential in low-frequency applications such as seismic barriers. Their design strategy typically involves tailoring geometrical features of local resonators to attain a desired frequency bandgap through extensive dispersion analyses. In this paper, a systematic design methodology is presented to conceive these local resonators using topology optimization, where frequency bandgaps develop by matching multiple antiresonances with predefined target frequencies. The design approach modifies an individual resonator's response to unidirectional harmonic excitations in the in-plane and out-of-plane directions, mimicking the elliptical motion of surface waves. Once an arrangement of optimized resonators composes a locally resonant metasurface, frequency bandgaps appear around the designed antiresonance frequencies. Numerical investigations analyze three case studies, showing that longitudinal-like and flexural-like antiresonances lead to nonoverlapping bandgaps unless both antiresonance modes are combined to generate a single and wider bandgap. Experimental data demonstrate good agreement with the numerical results, validating the proposed design methodology as an effective tool to realize locally resonant metasurfaces by matching multiple antiresonances such that bandgaps generated as a result of in-plane and out-of-plane surface wave motion combine into wider bandgaps.

Factors associated with poor adherence to medication in patients with diabetes and hypertension in Peru: findings from a pooled analysis of six years of population-based surveys.

OBJECTIVE: To evaluate the factors associated with poor medication adherence in patients with DM and HTN in Peru. STUDY DESIGN: A cross-sectional study. METHODS: We analyzed data from the Peruvian Demographic and Family Health Survey from 2014 to 2019. Adjusted prevalence ratios (aPR) and their respective 95% confidence intervals (CI) were estimated to determine the factors associated with poor medication adherence. RESULTS: We included 15,184 participants with a known diagnosis of DM and HTN. The frequency of poor medication adherence was 37.1%, with 36.7% among individuals with HTN and 29.2% among individuals with DM. Those belonging to age groups above 30 years (aPR: 0.77; 95% CI: 0.74-0.80, for the group ≥ 60 years) had a lower frequency of poor medication adherence. Meanwhile, being male (aPR: 1.03; 95% CI: 1.01-1.05), lacking health insurance (aPR: 1.08; 95% CI: 1.05-1.10), belonging to lower wealth quintiles (aPR: 1.12; 95% CI: 1.08-1.17, for the first quintile), and living in the mountain region (aPR: 1.09; 95% CI: 1.06-1.12) were associated with a higher frequency of poor medication adherence. These findings were consistent when stratifying by the type of disease. CONCLUSION: This study showed that poor medication adherence is common in patients with HTN and DM in Peru and is associated with sociodemographic factors, highlighting the importance of public health approaches to improve adherence.

Health science students' preparedness for climate change: a scoping review on knowledge, attitudes, and practices.

INTRODUCTION: Climate change (CC) is a global public health issue, and the role of health professionals in addressing its impact is crucial. However, to what extent health professionals are prepared to deal with CC-related health problems is unclear. We aimed to evaluate the knowledge, attitudes, and practices of health students about the CC. METHODS: We conducted a scoping review through systematic searches in PubMed, Scopus, Web of Science, Proquest, and EBSCO. We included original scientific research with no language or time restrictions. Two authors independently reviewed and decided on the eligibility of the studies, then performed data extraction. RESULTS: 21 studies were included, with a total of 9205 undergraduate nursing, medical, pharmacy, and public health students mainly. Most health science students (> 75%) recognized human activities as the main cause of CC. However, they perceived a lack of knowledge on how to address CC. Moreover, we found inadequate coverage or limited development of CC in related curricula that may contribute to incomplete learning or low confidence in the theoretical and practical concepts of students. CONCLUSION: The findings of our scoping review suggest that while health sciences students possess a general understanding of CC, there is a significant gap in their knowledge regarding its specific health impacts. To address this gap, there is a need for targeted education and training for future health care professionals that emphasizes the health effects of CC.

Retraction of health science articles by researchers in Latin America and the Caribbean: A scoping review.

We aimed to conduct a scoping review to assess the profile of retracted health sciences articles authored by individuals affiliated with academic institutions in Latin America and the Caribbean (LAC). We systematically searched seven databases (PubMed, Scopus, Web of Science, Embase, Medline/Ovid, Scielo, and LILACS). We included articles published in peer-reviewed journals between 2003 and 2022 that had at least one author with an institutional affiliation in LAC. Data were collected on the year of publication, study design, authors' countries of origin, number of authors, subject matter of the manuscript, scientific journals of publication, retraction characteristics, and reasons for retraction. We included 147 articles, the majority being observational studies (41.5%). The LAC countries with the highest number of retractions were Brazil (n = 69), Colombia (n = 16), and Mexico (n = 15). The areas of study with the highest number of retractions were infectology (n = 21) and basic sciences (n = 15). A retraction label was applied to 89.1% of the articles, 70.7% were retracted by journal editors, and 89.1% followed international retraction guidelines. The primary reasons for retraction included errors in procedures or data collection (n = 39), inconsistency in results or conclusions (n = 37), plagiarism (n = 21), and suspected scientific fraud (n = 19). In conclusion, most retractions of scientific publications in health sciences in LAC adhered to international guidelines and were linked to methodological issues in execution and scientific misconduct. Efforts should be directed toward ensuring the integrity of scientific research in the field of health.

Eosinophils Recruited during Pulmonary Vaccination Regulate Mucosal Antibody Production.

Eosinophils have been previously shown to be able to regulate early humoral responses during systemic vaccination. Here we investigated the role of eosinophils during pulmonary vaccination, comparing vaccine-induced responses in eosinophil-deficient (ΔdblGATA) and wild-type mice using a Th2 adjuvant. We observed that eosinophils were needed to induce a complete vaccine response, thereby eliciting specific antibody-secreting plasma cells in the regional lymph nodes and antibody secretion in the BAL at the early stage of the immune response. Reintroduction of eosinophils in the lungs of ΔdblGATA mice during the priming stage enhanced both specific IgM and IgG plasma cells but not specific IgA plasma cells. Upon vaccination, eosinophils migrated to the lungs and secreted cytokines involved in B-cell activation, which might promote antibody production. Importantly, however, the absence of eosinophils did not impair late immune responses in a prime/boost protocol because, in that setup, we uncovered a compensating mechanism involving a Th17 pathway. In conclusion, our data demonstrate for the first time a new role for eosinophils during lung mucosal vaccination, whereby they accelerate early immune responses (IgM and IgG) while regulating IgA production at the late stages.

mtDNA Single-Nucleotide Variants Associated with Type 2 Diabetes.

Type 2 diabetes (T2D) is a chronic systemic disease with a complex etiology, characterized by insulin resistance and mitochondrial dysfunction in various cell tissues. To explore this relationship, we conducted a secondary analysis of complete mtDNA sequences from 1261 T2D patients and 1105 control individuals. Our findings revealed significant associations between certain single-nucleotide polymorphisms (SNPs) and T2D. Notably, the variants m.1438A>G (rs2001030) (controls: 32 [27.6%], T2D: 84 [72.4%]; OR: 2.46; 95%CI: 1.64-3.78; p < 0.001), m.14766C>T (rs193302980) (controls: 498 [36.9%], T2D: 853 [63.1%]; OR: 2.57, 95%CI: 2.18-3.04, p < 0.001), and m.16519T>C (rs3937033) (controls: 363 [43.4%], T2D: 474 [56.6%]; OR: 1.24, 95%CI: 1.05-1.47, p = 0.012) were significantly associated with the likelihood of developing diabetes. The variant m.16189T>C (rs28693675), which has been previously documented in several studies across diverse populations, showed no association with T2D in our analysis (controls: 148 [13.39] T2D: 171 [13.56%]; OR: 1.03; 95%CI: 0.815-1.31; p = 0.83). These results provide evidence suggesting a link between specific mtDNA polymorphisms and T2D, possibly related to association rules, topological patterns, and three-dimensional conformations associated with regions where changes occur, rather than specific point mutations in the sequence.

Factors associated with alcohol abuse in the Peruvian population: analysis of a national health survey 2019.

AIM: To evaluate the factors associated with alcohol abuse in the Peruvian population. METHODS: A secondary analysis was performed using data from the Demographic and Family Health Survey of Peru, 2019. We included 24 264 Peruvians between 18 and 59 years. For the analysis of association, the Poisson regression model with robust standard errors was used. Adjusted Prevalence Ratios (aPR) with their respective 95% confidence intervals (95% CI) were calculated. RESULTS: The prevalence of alcohol abuse was 5.2%. Having higher education (aPR:1.61; 95%CI:1.04-2.48), being widowed, separated or divorced (aPR:1.73; 95%CI:1.18-2.54), belonging to the third (aPR:1.70; 95%CI:1.12-2.60), fourth (aPR:2.08; 95%CI:1.33-3.23) or fifth socioeconomic quintile (aPR:2.16; 95%CI:1.33-3.50), being from the Sierra (aPR:1.45; 95%CI:1.12-1.87) or Selva (aPR:1.48; 95%CI:1.13-1.94), not having health insurance (aPR:1.25; 95%CI:1.04-1.50), being a current smoker (aPR:2.43; 95%CI:2.02-2.93) and having major depression (aPR:1.77; 95%CI:1.32-2.36) were associated with a higher prevalence of alcohol abuse. On the other hand being a middle-aged adult (aPR:0.73; 95%CI:0.60-0.88), female (aPR:0.16; 95%CI:0.12-0.22) and having started drinking alcohol after the age of 18 years (aPR:0.57; 95%CI:0.47-0.69) were associated with a lower prevalence. CONCLUSIONS: One in 20 Peruvians between 18 and 59 years had alcohol abuse. Age, gender, education level, marital status, socioeconomic level, region, age of first drink, smoking and depression were associated with alcohol abuse.

Slope until reaching the plateau: a new predictor of valve response obtained by lumbar infusion test for idiopathic normal pressure hydrocephalus.

BACKGROUND: Diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is based on clinical, radiological, and hydrodynamic data of cerebrospinal fluid (CSF) obtained by invasive methods such as lumbar infusion test, which is used to determine the resistance to CSF outflow (Rout). However, Rout has limitations, and its value as predictor of valve response is questioned. Other variables can be obtained by lumbar infusion test, such as the time to reach the plateau (TRP) and the slope until reaching the plateau (SRP). The objectives were to determine if SRP could be a predictor of response to ventriculoperitoneal shunt (VPS) and what variable (Rout versus SRP) would have greater predictive value. METHOD: Patients with probable iNPH who underwent a lumbar infusion test and were indicated for a VPS were retrospectively studied. Two groups were established, responders and non-responders. Rout, TRP (period between the start of infusion until reaching the plateau measured in seconds) and SRP ((plateau pressure-opening pressure)/TRP) were obtained. For Rout and SRP, the receiver operating curves (ROC) with its areas under the curve (AUC) were calculated. RESULTS: One hundred ten patients were included, being 86 responders (78.20%). Shunt responders had a significantly greater Rout (17.02 (14.45-20.23) versus 13.34 (12.10-16.28) mmHg/ml/min, p = 0.002) and SRP (0.049 (0.043-0.054) versus 0.031 (0.026-0.036) mmHg/sec, p < 0.001) and smaller TRP (641.28 (584.83-697.73) versus 777.65 (654.03-901.27) sec, p = 0.028) than non-responders. The AUC for SRP was greater than the AUC for Rout (0.763 (95 % CI 0.655-0.871, p < 0.001) versus 0.673 (95 % CI 0.595-0.801, p = 0.008), respectively), but the differences were not significant (p = 0.180). CONCLUSIONS: SRP could be considered predictor of response to VPS, and its accuracy tends to be better than Rout. So, this variable may be a useful tool to select shunt candidates among patients with probable iNPH.

Microaerobic degradation of crude oil and long chain alkanes by a new Rhodococcus strain from Gulf of Mexico.

Bacterial degradation of crude oil is a promising strategy for reducing the concentration of hydrocarbons in contaminated environments. In the first part of this study, we report the enrichment of two bacterial consortia from deep sediments of the Gulf of Mexico with crude oil as the sole carbon and energy source. We conducted a comparative analysis of the bacterial community in the original sediment, assessing its diversity, and compared it to the enrichment observed after exposure to crude oil in defined cultures. The consortium exhibiting the highest hydrocarbon degradation was predominantly enriched with Rhodococcus (75%). Bacterial community analysis revealed the presence of other hydrocarbonoclastic members in both consortia. In the second part, we report the isolation of the strain Rhodococcus sp. GOMB7 with crude oil as a unique carbon source under microaerobic conditions and its characterization. This strain demonstrated the ability to degrade long-chain alkanes, including eicosane, tetracosane, and octacosane. We named this new strain Rhodococcus qingshengii GOMB7. Genome analysis revealed the presence of several genes related to aromatic compound degradation, such as benA, benB, benC, catA, catB, and catC; and five alkB genes related to alkane degradation. Although members of the genus Rhodococcus are well known for their great metabolic versatility, including the aerobic degradation of recalcitrant organic compounds such as petroleum hydrocarbons, this is the first report of a novel strain of Rhodococcus capable of degrading long-chain alkanes under microaerobic conditions. The potential of R. qingshengii GOMB7 for applications in bioreactors or controlled systems with low oxygen levels offers an energy-efficient approach for treating crude oil-contaminated water and sediments.

Lithifying and Non-Lithifying Microbial Ecosystems in the Wetlands and Salt Flats of the Central Andes.

The wetlands and salt flats of the Central Andes region are unique extreme environments as they are located in high-altitude saline deserts, largely influenced by volcanic activity. Environmental factors, such as ultraviolet (UV) radiation, arsenic content, high salinity, low dissolved oxygen content, extreme daily temperature fluctuation, and oligotrophic conditions, resemble the early Earth and potentially extraterrestrial conditions. The discovery of modern microbialites and microbial mats in the Central Andes during the past decade has increased the interest in this area as an early Earth analog. In this work, we review the current state of knowledge of Central Andes region environments found within lakes, small ponds or puquios, and salt flats of Argentina, Chile, and Bolivia, many of them harboring a diverse range of microbial communities that we have termed Andean Microbial Ecosystems (AMEs). We have integrated the data recovered from all the known AMEs and compared their biogeochemistry and microbial diversity to achieve a better understanding of them and, consequently, facilitate their protection.

Treatment of melasma with platelet-rich plasma: A self-controlled clinical trial.

Melasma is a common circumscribed hypermelanosis of sun-exposed areas of the skin. Platelet-Rich Plasma therapy has been evidenced to inhibit melanin synthesis in animals and humans. To determine the effectiveness of platelet-rich plasma as a treatment for melasma. Twenty female patient with melasma were involved in this study. The intervention included three Platelet-Rich Plasma application sessions at 15-day intervals. Patients were evaluated before and after treatment. Variables measured included the facial melanin concentration using the melasma area and severity index score, melasma quality of life scale satisfaction grade, and histologic changes. Mean age was 41 ± 7 years. An initial MELASQOL score of 42 ± 14.8 and final score of 16.6 ± 7.2 (p = 0.008) were reported; the initial and final MASI score were 15.5 ± 8.4 and 9.5 ± 7.2 (p = 0.001), respectively. The dermatoscopy examination revealed a decrease in pigmentation after intervention (p = 0.001). Histopathologic improvement was detected in reductions in cutaneous atrophy (14 [70%] vs. 11 [55%]), solar elastosis (15 [75%] vs.11 [55%]), and inflammatory infiltrate (9 [45%] vs. 6 [30%]), before and after treatment, respectively. The intervention was associated with decreased intensity of the melasma patch and improved skin quality, shown by the MELASQOL and MASI scores.

3D-PLA-experimental set up to display the electrical background of the so-called geometric factor of electrokinetic cells.

The so-called geometric factor defined in electrokinetic cells, L/S (L being the length and S the cross-section of the channel), is relevant for providing the surface interaction electrical potential (zeta potential, ζ) of large surfaces, such as those used in the design of biomedical devices or water purification systems. Conversely, recent studies demonstrate that this factor is also employed to determine geometrical parameters, such as porosity in membrane-like systems. This factor, which has been attributed exclusively a geometrical character, can also be obtained from the electrical conductivity and resistance of the electrokinetic channel. In this work, we assess whether these two ways of obtaining the L/S factor are equivalent and how possible deviations can affect the value of the zeta potential. For this purpose, we work with channels of different geometries obtained by 3D printing using PLA (polylactic acid) as a polymer employed in biomedical applications. The discrepancies between the L/S factor obtained by electrical and purely geometrical measurements increase as the geometrical L/S factor becomes larger, reaching differences close to 80%. The results show that the so-called geometrical L/S factor also has an important electrical contribution and would be better denoted as electrogeometric factor. The differences found between the L/S factors are also propagated to the calculation of ζ but an optimum conductivity zone (from about 10 to 40 mS m-1) can be defined to obtain the zeta potential by selecting any of the L/S factors obtained from electrokinetic measurements. The results of this work should be taken into account in those investigations that use the L/S factor to obtain the geometry-porosity of permeable materials.

Microbial prospection of communities that produce biosurfactants from the water column and sediments of the Gulf of Mexico.

Microbial communities capable of hydrocarbon degradation linked to biosurfactant (BS) and bioemulsifier (BE) production are basically unexplored in the Gulf of México (GOM). In this work, the BS and BE production of culturable marine bacterial hydrocarbonoclasts consortia isolated from two sites (the Perdido Fold Belt and Coatzacoalcos area) was investigated. The prospection at different locations and depths led to the screening and isolation of a wide variety of bacterial consortia with BS and BE activities, after culture enrichment with crude oil and glycerol as the carbon sources. At least 55 isolated consortia presented reduction in surface tension (ST) and emulsifying activity (EI24 ). After colony purification, bacteria were submitted to polyphasic analysis assays that resulted in the identification of different strains of cultivable Gammaproteobacteria Gram (-) Citrobacter, Enterobacter, Erwinia, Pseudomonas, Vibrio, Shewanella, Thalassospira, Idiomarina, Pseudoalteromonas, Photobacterium, and Gram (+) Staphylococcus, Bacillus, and Microbacterium. Overall, the best results for ST reduction and EI24 were obtained with consortia. Individually, Pseudomonas, Bacillus, and Enterobacter strains showed the best results for the reduction of ST after 6 days, while Thalassospira and Idiomarina strains showed the best results for EI24 (above 68% after 9 days). Consortia isolates from the GOM had the ability to degrade crude oil by up to 40-80% after 24 and 36 months, respectively. In all cases, biodegradation of crude oil was related to the reduction in ST and bioemulsifying activity and was independent from the depth in the water column.

Factors associated with the consumption of chlorine dioxide to prevent and treat COVID-19 in the Peruvian population: a cross-sectional study.

BACKGROUND: Chlorine dioxide has been promoted as an alternative for the prevention and treatment of COVID-19, especially in Peru, despite the lack of evidence to support its efficacy. This study aimed to evaluate the factors associated with chlorine dioxide consumption in the Peruvian population. METHODS: Analytical cross-sectional study. An adult Peruvian population was evaluated where chlorine dioxide consumption was divided into two groups according to the purpose of use: as prevention (individuals without COVID-19 history) and as treatment (individuals with COVID-19 history). The associated factors in each group were evaluated using Poisson regressions with the bootstrapping resampling method. RESULTS: Of 3610 participants included, 3213 reported no history of COVID-19, and 397 had been infected. The prevalence of chlorine dioxide consumption to prevent or treat COVID-19 was 8 and 16%, respectively. Factors either positively or negatively associated with chlorine dioxide consumption for prevention were male sex (aPR: 1.36; 95% CI: 1.09-1.71), being an adult or older adult (aPR: 0.54; 95% CI: 0.35-0.82), having a health sciences student within the family unit (aPR: 1.38; 95% CI: 1.02-1.87), using medical information as the main source of information of COVID-19 (aPR: 0.57; 95% CI: 0.40-0.80), having comorbidities for COVID-19 (aPR: 1.36; 95% CI: 1.01-1.82), considering COVID-19 dangerous and deadly (aPR: 0.57; 95% CI: 0.45-0.74), using medications (aPR: 1.59; 95% CI: 1.25-2.06) and plants to prevent COVID-19 (aPR: 1.69; 95% CI: 1.21-2.36), considering chlorine dioxide ineffective (aPR: 0.18; 95% CI: 0.18-0.24), and being uninformed of its efficacy (aPR: 0.21; 95% CI: 0.16-0.28). In addition, factors associated with chlorine dioxide consumption for treatment were considering COVID-19 dangerous and deadly (aPR: 0.56; 95% CI: 0.33-0.96), considering chlorine dioxide ineffective (aPR: 0.22; 95% CI: 0.12-0.42), and being uninformed of its efficacy (aPR: 0.15; 95% CI: 0.07-0.32). CONCLUSIONS: The prevalence of chlorine dioxide consumption to treat COVID-19 was higher than prevent. It is important to apply information strategies, prioritizing population groups with certain characteristics that are associated with a higher consumption pattern.

BDNF-TrkB controls cocaine-induced dendritic spines in rodent nucleus accumbens dissociated from increases in addictive behaviors.

Chronic cocaine use is associated with prominent morphological changes in nucleus accumbens shell (NACsh) neurons, including increases in dendritic spine density along with enhanced motivation for cocaine, but a functional relationship between these morphological and behavioral phenomena has not been shown. Here we show that brain-derived neurotrophic factor (BDNF) signaling through tyrosine kinase B (TrkB) receptors in NACsh neurons is necessary for cocaine-induced dendritic spine formation by using either localized TrkB knockout or viral-mediated expression of a dominant negative, kinase-dead TrkB mutant. Interestingly, augmenting wild-type TrkB expression after chronic cocaine self-administration reverses the sustained increase in dendritic spine density, an effect mediated by TrkB signaling pathways that converge on extracellular regulated kinase. Loss of TrkB function after cocaine self-administration, however, leaves spine density intact but markedly enhances the motivation for cocaine, an effect mediated by specific loss of TrkB signaling through phospholipase Cgamma1 (PLCγ1). Conversely, overexpression of PLCγ1 both reduces the motivation for cocaine and reverses dendritic spine density, suggesting a potential target for the treatment of addiction in chronic users. Together, these findings indicate that BDNF-TrkB signaling both mediates and reverses cocaine-induced increases in dendritic spine density in NACsh neurons, and these morphological changes are entirely dissociable from changes in addictive behavior.

Overexpression of the Histone Dimethyltransferase G9a in Nucleus Accumbens Shell Increases Cocaine Self-Administration, Stress-Induced Reinstatement, and Anxiety.

Repeated exposure to cocaine induces lasting epigenetic changes in neurons that promote the development and persistence of addiction. One epigenetic alteration involves reductions in levels of the histone dimethyltransferase G9a in nucleus accumbens (NAc) after chronic cocaine administration. This reduction in G9a may enhance cocaine reward because overexpressing G9a in the NAc decreases cocaine-conditioned place preference. Therefore, we hypothesized that HSV-mediated G9a overexpression in the NAc shell (NAcSh) would attenuate cocaine self-administration (SA) and cocaine-seeking behavior. Instead, we found that G9a overexpression, and the resulting increase in histone 3 lysine 9 dimethylation (H3K9me2), increases sensitivity to cocaine reinforcement and enhances motivation for cocaine in self-administering male rats. Moreover, when G9a overexpression is limited to the initial 15 d of cocaine SA training, it produces an enduring postexpression enhancement in cocaine SA and prolonged (over 5 weeks) increases in reinstatement of cocaine seeking induced by foot-shock stress, but in the absence of continued global elevations in H3K9me2. The increase in stress-induced reinstatement is paralleled by heightened anxiety measures, suggesting that countering the cocaine-induced decreases in endogenous G9a with ectopic G9a overexpression leads to lasting anxiogenic effects. Finally, we found an enduring reduction in phosphorylated cAMP-response element binding protein levels in the NAcSh that could account for the increased anxiety. These data demonstrate a novel role for G9a in promoting comorbid cocaine addiction and anxiety and suggest that increased epigenetic repression of transcription through H3K9 during cocaine use can have long-lasting and unexpected negative consequences on behavior.SIGNIFICANCE STATEMENT Cocaine addiction is a neuropsychiatric disorder that is detrimental to society and currently has no effective treatments. The difficulty in treating drug addiction is compounded by the high comorbidity with other psychiatric illnesses, including anxiety disorders. Here, we demonstrate that G9a, an epigenetic repressor of gene expression, acting in the nucleus accumbens, a brain reward region, is capable of increasing both addiction- and anxiety-like behaviors in rats. These findings are intriguing because repeated cocaine exposure decreases G9a in this region and thereby enhances expression of certain addiction-promoting genes. However, our results suggest that countering this cocaine-induced decrease in G9a activity actually exacerbates addiction and sensitivity to relapse under stressful situations.

Inactivation of NMDA Receptors in the Ventral Tegmental Area during Cocaine Self-Administration Prevents GluA1 Upregulation but with Paradoxical Increases in Cocaine-Seeking Behavior.

Cocaine self-administration increases expression of GluA1 subunits in ventral tegmental area (VTA) dopamine neurons, which subsequently enhance the motivation for cocaine. This increase in GluA1 may be dependent on concomitant NMDA receptor (NMDAR) activation during self-administration, similar to cocaine-induced long-term potentiation in the VTA. In this study, we used viral-mediated expression of a dominant-negative GluN1 subunit (HSV-dnGluN1) in VTA neurons to study the effect of transient NMDAR inactivation on the GluA1 increases induced by chronic cocaine self-administration in male rats. We found that dnGluN1 expression in the VTA limited to the 3 weeks of cocaine self-administration prevents the subsequent increase in tissue GluA1 levels when compared with control infusions of HSV-LacZ. Surprisingly, dnGluN1 expression led to an enhancement in the motivation to self-administer cocaine as measured using a progressive ratio reinforcement schedule and to enhanced cocaine seeking measured in extinction/reinstatement tests following an extended 3 week withdrawal period. Despite blocking tissue GluA1 increases in cocaine self-administering animals, the HSV-dnGluN1 treatment resulted in increased membrane levels of GluA1 and GluN2B, along with markedly higher locomotor responses to intra-VTA infusions of AMPA, suggesting a paradoxical increase in VTA AMPA receptor responsiveness. Together, these data suggest that NMDARs mediate cocaine-induced increases in VTA GluA1 expression, but such transient NMDAR inactivation also leads to compensatory scaling of synaptic AMPA receptors that enhance the motivational for cocaine.SIGNIFICANCE STATEMENT Dopamine neurons in the ventral tegmental area (VTA) are critical substrates of drug rewards. Animal models indicate that chronic cocaine use enhances excitatory glutamatergic input to these neurons, making them more susceptible to environmental stimuli that trigger drug craving and relapse. We previously found that self-administration of cocaine increases AMPA glutamate receptors in the VTA, and this effect enhances motivation for cocaine. Here we report that the mechanism for this upregulation involves NMDA receptor activity during cocaine use. While interference with NMDA receptor function blocks AMPA receptor upregulation, it also produces a paradoxical enhancement in membrane AMPA receptor subunits, AMPA responsiveness, and the motivation for cocaine. Thus, pharmacotherapy targeting NMDA receptors may inadvertently produce substantial adverse consequences for cocaine addiction.

Production and application of a thermostable lipase from Serratia marcescens in detergent formulation and biodiesel production.

In this study, extracellular lipase was produced by Serratia marcescens wild type and three mutant strains. The maximum lipase activity (80 U/mL) was obtained with the SMRG4 mutant strain using soybean oil. Using a 22 factorial design, the lipase production increased 1.55-fold (124 U/mL) with 4% and 0.05% of soybean oil and Triton X-100, respectively. The optimum conditions for maximum lipase activity were 50 °C and pH 8. However, the enzyme was active in a broad range of pH (6-10) and temperatures (5-55 °C). This lipase was stable in organic solvents and in the presence of oxidizing agents. The enzyme also proved to be efficient for the removal of triacylglycerol from olive oil in cotton cloth. A Box-Behnken experimental design was used to evaluate the effects of the interactions between total lipase activity, buffer pH, and wash temperatures on oil removal. The model obtained suggested that all selected factors had a significant impact on oil removal, with optimum conditions of 550 U lipase, 45 °C, pH 9.5, with 79.45% removal. Biotransformation of waste frying oil using the enzyme and in presence of methanol resulted in the synthesis of methyl esters such as methyl oleate, methyl palmitate, and methyl stearate.