Novel multiferroic state and ME enhancement by breaking the AFM frustration in LuMn1-xO3.

This study provides a comprehensive insight into the effects of controlled off-stoichiometry on the structural and multiferroic properties of the hexagonal manganite LuMn1-xO3+δ (x = 0.02; δ ∼ 0), supported by neutron powder diffraction measurements confirming single phase P63cm symmetry and evidencing a relevant ferromagnetic component, below TN ∼ 90 K, which breaks the archetypal geometrically frustrated antiferromagnetic state typically ascribed to LuMnO3. The perturbations in the triangular disposition of spins prompt an additional electric polarization contribution and a clear enhancement of the magnetoelectric coupling which are in good agreement with the results of first principles calculations. In addition, Raman spectroscopy, dielectric permittivity, pyroelectric current and magnetic measurements as a function of temperature point out the precursor effects of the magnetic phase transitions involving a strong coupling between spins, lattice and electric order, even above the Néel temperature.

The microtubular cytoskeleton of olfactory neurons derived from patients with schizophrenia or with bipolar disorder: Implications for biomarker characterization, neuronal physiology and pharmacological screening.

Schizophrenia (SZ) and Bipolar Disorder (BD) are highly inheritable chronic mental disorders with a worldwide prevalence of around 1%. Despite that many efforts had been made to characterize biomarkers in order to allow for biological testing for their diagnoses, these disorders are currently detected and classified only by clinical appraisal based on the Diagnostic and Statistical Manual of Mental Disorders. Olfactory neuroepithelium-derived neuronal precursors have been recently proposed as a model for biomarker characterization. Because of their peripheral localization, they are amenable to collection and suitable for being cultured and propagated in vitro. Olfactory neuroepithelial cells can be obtained by a non-invasive brush-exfoliation technique from neuropsychiatric patients and healthy subjects. Neuronal precursors isolated from these samples undergo in vitro the cytoskeletal reorganization inherent to the neurodevelopment process which has been described as one important feature in the etiology of both diseases. In this paper, we will review the current knowledge on microtubular organization in olfactory neurons of patients with SZ and with BD that may constitute specific cytoskeletal endophenotypes and their relation with alterations in L-type voltage-activated Ca(2+) currents. Finally, the potential usefulness of neuronal precursors for pharmacological screening will be discussed.

Insecticidal Activity of a Destruxin-Containing Extract of Metarhizium brunneum Against Ceratitis capitata (Diptera: Tephritidae).

Tephritid fruit flies are major pests that limit fruit production around the world; they cause important damages, increasing directly and indirectly annual costs, and their management is predominately based on the use of chemical insecticides. This research investigated the insecticidal activity of the crude extract obtained of Metarhizium brunneum Petch EAMb 09/01-Su strain and its capacity to secrete secondary metabolites including destruxins (dtx). Dtx A and A2 had insecticidal activity against Ceratitis capitata (Wiedemann) when administered per os. The crude extract of seven Metarhizium and one Beauveria isolates were evaluated per os against medfly adults. The crude extracts of the isolate EAMb 09/01-Su resulted in mortality ranging between 95 and 100% at 48 h. The high-pressure liquid chromatography profile showed two active peaks (F5B and F6 subfractions) related with dtx A2 and dtx A, which caused 70 and 100% mortality on C. capitata at 48 h postfeeding, respectively. The LC50 was 104.92 ppm of dtx A, contained in the F6 subfraction, and the LT50 was 4.16 h at a concentration of 400 ppm of dtx A contained in the F6 subfraction. Moreover, the average survival time of adults exposed to this subfraction was 12.6 h with only 1 h of exposure. The insecticide metabolites of the F6 subfraction of the EAMb 09/01-Su isolate retained >90% of its insecticidal activity after exposure to 60°C for 2 h and 120°C for 20 min. These results highlight the potential of this strain as a source of new insecticidal compounds of natural origin for fruit fly control.

Interplay of lattice-spin-orbital coupling and Jahn-Teller effect in noncollinear spinel TixMn1-x(FeyCo1-y)2O4: a neutron diffraction study.

Local magnetostructural changes and dynamical spin fluctuations in doubly diluted spinel TixMn1‒x(FeyCo1‒y)2O4has been reported by means of neutron diffraction and magnetization studies. Two distinct sets of compositions (i)x(Ti) = 0.20 andy(Fe) = 0.18; (ii)x(Ti) = 0.40 andy(Fe) = 0.435 have been considered for this study. The first compound of equivalent stoichiometry Ti0.20Mn0.80Fe0.36Co1.64O4exhibits enhanced tetragonal distortion across the ferrimagnetic transition temperatureTC= 258 K in comparison to the end compound MnCo2O4(TC∼ 180 K) with a characteristic ratioct/√2atof 0.99795(8) demonstrating robust lattice-spin-orbital coupling. However, in the second case Ti0.40Mn0.60Fe0.87Co1.13O4with higherB-site compositions, the presence of Jahn-Teller ions with distinct behavior appears to counterbalance the strong tetragonal distortion thereby ceasing the lattice-spin-orbital coupling. Both the investigated systems show the coexistence of noncollinear antiferromagnetic and ferrimagnetic components in cubic and tetragonal settings. On the other hand, the dynamical ac-susceptibility,χac(T) reveals a cluster spin-glass state with Gabay-Toulouse (GT) like mixed phases behaviour belowTC. Such dispersive behaviour appears to be sensitive to the level of octahedral substitution. Further, the field dependence ofχac(T) follows the weak anisotropic GT-line behaviour with crossover exponent Φ lies in the range 1.38-1.52 on theH-Tplane which is in contrast to theB-site Ti substituted MnCo2O4spinel that appears to follow irreversible non-mean-field AT-line behaviour (Φ âˆ¼ 3 +δ). Finally, the Arrott plots analysis indicates the presence of a pseudo first-order like transition (T< 20 K) which is in consonance with and zero crossover of the magnetic entropy change within the frozen spin-glass regime.

Biocontrol of Bactrocera oleae (Diptera: Tephritidae) with Metarhizium brunneum and its extracts.

The susceptibility of preimaginal and adult olive fruit fly, Bactrocera oleae (Gmelin) (Diptera: Tephritidae), to a strain of the mitosporic ascomycete Metarhizium brunneum (Petch) (Hypocreales: Clavicipitaceae) and the insecticidal activity of its crude extract to olive fruit fly adults were investigated. Strain EAMb 09/01-Su caused 60% mortality to B. oleae adults, with average survival time (AST) of 8.8 d. In soil treatments against pupariating third-instar larvae, preimaginal B. oleae mortality reached 82.3%, whereas preimaginal mortality targeting puparia was 33.3%. The crude extract of EAMb 09/01-Su strain caused 80.0% adult mortality when administered per os, with AST of 27.7 h. The crude extract was demonstrated to be quite thermostable and photoresistant. These results indicate that M. brunneum EAMb 09/01-Su strain and its crude extract show potential to be used in an integrated pest management olive fruit fly management strategy targeting both adults and preimaginals.

Addressing mechanism bias in model-based impact forecasts of new tuberculosis vaccines.

In tuberculosis (TB) vaccine development, multiple factors hinder the design and interpretation of the clinical trials used to estimate vaccine efficacy. The complex transmission chain of TB includes multiple routes to disease, making it hard to link the vaccine efficacy observed in a trial to specific protective mechanisms. Here, we present a Bayesian framework to evaluate the compatibility of different vaccine descriptions with clinical trial outcomes, unlocking impact forecasting from vaccines whose specific mechanisms of action are unknown. Applying our method to the analysis of the M72/AS01E vaccine trial -conducted on IGRA+ individuals- as a case study, we found that most plausible models for this vaccine needed to include protection against, at least, two over the three possible routes to active TB classically considered in the literature: namely, primary TB, latent TB reactivation and TB upon re-infection. Gathering new data regarding the impact of TB vaccines in various epidemiological settings would be instrumental to improve our model estimates of the underlying mechanisms.

Clinical standards for drug-susceptible TB in children and adolescents.

BACKGROUND: These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.METHODS: Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.RESULTS: Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.CONCLUSION: These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.

Health professions and risk of sporadic Creutzfeldt-Jakob disease, 1965 to 2010.

In 2009, a pathologist with sporadic Creutzfeldt-Jakob Disease (sCJD) was reported to the Spanish registry. This case prompted a request for information on health-related occupation in sCJD cases from countries participating in the European Creutzfeldt Jakob Disease Surveillance network (EuroCJD). Responses from registries in 21 countries revealed that of 8,321 registered cases, 65 physicians or dentists, two of whom were pathologists, and another 137 healthcare workers had been identified with sCJD. Five countries reported 15 physicians and 68 other health professionals among 2,968 controls or non-cases, suggesting no relative excess of sCJD among healthcare professionals. A literature review revealed: (i) 12 case or small case-series reports of 66 health professionals with sCJD, and (ii) five analytical studies on health-related occupation and sCJD, where statistically significant findings were solely observed for persons working at physicians' offices (odds ratio: 4.6 (95 CI: 1.2-17.6)). We conclude that a wide spectrum of medical specialities and health professions are represented in sCJD cases and that the data analysed do not support any overall increased occupational risk for health professionals. Nevertheless, there may be a specific risk in some professions associated with direct contact with high human-infectivity tissue.

Integrated screening and testing for TB and COVID-19 in Peru.

We describe the experience of integrating COVID-19 screening and testing into a mobile TB screening unit in Lima, Peru. All attendees received chest radiographs, which were analysed using CAD4TB and CAD4COVID; Xpert MTB/RIF Ultra was used to test for TB, and antibody and polymerase chain reaction (PCR) for SARS-CoV-2. One Xpert-positive TB case was diagnosed per 168 people screened, one person with SARS-CoV-2 antibodies per 3 people screened, and one PCR-confirmed SARS-CoV-2 infection per 8 people screened. Integrated screening can help to avoid delays in the diagnosis of both TB and COVID-19.

Nous décrivons l'expérience de l'intégration du dépistage et du test COVID-19 dans une unité mobile de dépistage de la TB à Lima, au Pérou. Toutes les personnes présentes ont reçu des radiographies pulmonaires, qui ont été analysées à l'aide de CAD4TB et CAD4COVID ; Xpert® MTB/RIF Ultra a été utilisé pour le dépistage de la TB, et les anticorps et la réaction en chaîne par polymérase (PCR) pour le SARS-CoV-2. Un cas de TB Xpert-positif a été diagnostiqué pour 168 personnes dépistées, une personne présentant des anticorps du SARS-CoV-2 pour 3 personnes dépistées et une infection du SARS-CoV-2 confirmée par PCR pour 8 personnes dépistées. Le dépistage intégré peut contribuer à éviter les retards dans le diagnostic de la TB et du COVID-19.

Using digital chatbots to close gaps in healthcare access during the COVID-19 pandemic.

INTRODUCTION: Chatbots have emerged as a first link to care in recent years. The COVID-19 pandemic, and consequent health system disruptions, expanded their use. Socios En Salud (SES) introduced chatbots in Peru, which experienced one of the highest excess COVID mortalities in the world. METHODS: SES and the government identified unmet population health needs, which could be amenable to virtual interventions. Chatbots were developed to screen individuals for these conditions; we describe the period of deployment, number of screenings, and number of people who received services. RESULTS: Between April 2020 and May 2021, SES deployed nine ChatBots: four for mental health, two for maternal and child health, and three for chronic diseases: breast cancer, hypertension, diabetes mellitus, and obesity. Mental health services were provided to 42,932 people, 99.99% of those offered services. The other ChatBots reached fewer people. Overall, more than 50% of eligible people accepted chatbot-based services. DISCUSSION: ChatBot use was highest for mental health. Chatbots may increase connections between a vulnerable population and health services; this is likely dependent on several factors, including condition, population, and penetration of smart phones. Future research will be critical to understand user experience and preferences and to ensure that chatbots link vulnerable populations to appropriate, high-quality care.

INTRODUCTION: Les chatbots se sont imposés comme un premier lien aux soins ces dernières années. La pandémie de COVID-19, et les perturbations du système de santé qui en ont résultées, ont élargi leur champ d'application. Socios En Salud (SES) a introduit les chatbots au Pérou, qui a connu l'une des surmortalités dues au COVID les plus élevées au monde. MÉTHODES: SES et le gouvernement ont identifié des besoins non satisfaits en matière de santé de la population, qui pourraient faire l'objet d'interventions virtuelles. Des chatbots ont été développés pour dépister des individus pour ces conditions ; nous décrivons la période de leur déploiement, le nombre de dépistages et le nombre de personnes qui ont reçu ces services. RÉSULTATS: Entre avril 2020 et mai 2021, SES a déployé neuf ChatBots : quatre pour la santé mentale, deux pour la santé maternelle et infantile et trois pour les maladies chroniques, comme le cancer du sein, l'hypertension, le diabète et l'obésité. Des services de santé mentale ont été fournis à 42 932 personnes, soit 99,99% des personnes proposées. Les autres ChatBots ont touché moins de personnes. Dans l'ensemble, plus de 50% des personnes éligibles ont accepté les services proposés par les chatbots. DISCUSSION: L'utilisation des ChatBots était la plus élevée pour la santé mentale. Les chatbots peuvent augmenter les connexions entre une population vulnérable et les services de santé, mais cela dépende de plusieurs facteurs, dont la condition, la type de population et la pénétration des smartphones. Les recherches futures seront essentielles pour comprendre l'expérience et les préférences des utilisateurs et pour s'assurer que les chatbots relient les populations vulnérables vulnérables aux soins appropriés et de qualité.

Mental and physical health in service member and veteran students who identify as American Indians and Alaskan natives.

OBJECTIVE: The purpose of this study was to explore (a) current utilization rates of university mental health services among American Indian/Alaskan Native/Native Hawaiian (AI/AN/NH) student veterans and (b) predictors of mental health service utilization among AI/AN student veterans. Participants: Data for this cross-sectional study were obtained from the American College Health Association (ACHA)'s 2011-2014 National College Health Assessment II (n = 103). Methods: University mental health service utilization rates were calculated as a percentage for AI/AN/NH student veterans. Multivariable logistic regression was used to determine predictors of mental health service utilization. Results: Results showed that 14% of AI/AN/NH student veterans have used university mental health services. Predictors of mental health service utilization in this population included financial stress, lack of deployment during service, suicidal ideation, and a diagnosis of depression, model χ2 (13) = 162. 128, p < 0.001, Nagelkerke R2 = 0.130. Conclusion: This research identified gaps in service provision for AI/AN service member and veteran students on college campuses and provided possible models for intervention development.

Presence of the most abundant ionic species and their contribution to PM2.5 mass, in the city of Guadalajara, Jalisco (Mexico).

Ambient PM2.5 samples were taken at 24 h intervals at two sites (Centro and Miravalle) in the city of Guadalajara from January to June 2008. The Centro site is located in the downtown, while the Miravalle site is located in an industrial zone south of the downtown. For both sites the higher concentrations of PM2.5 were between January and May. High correlation coefficients between sulfate, nitrate and ammonium of 0.95, 0.92 and 0.91, respectively, showed low variations in the concentrations of these species in the city. It was estimated that sulfate, nitrate and ammonium represented almost 47% of the PM2.5 mass in June at the Centro site, but in general the contributions in the other months were less than 21%, while at Miravalle this percentage was between 7.7% and 27.6%.

Uncovering reasons for treatment initiation delays among children with TB in Lima, Peru.

BACKGROUND: Timely diagnosis and treatment of pediatric tuberculosis (TB) is critical to reducing mortality but remains challenging in the absence of adequate diagnostic tools. Even once a TB diagnosis is made, delays in treatment initiation are common, but for reasons that are not well understood.METHODS: To examine reasons for delay post-diagnosis, we conducted semi-structured interviews with Ministry of Health (MoH) physicians and field workers affiliated with a pediatric TB diagnostic study, and caregivers of children aged 0-14 years who were diagnosed with pulmonary TB in Lima, Peru. Interviews were analyzed using systematic comparative and descriptive content analysis.RESULTS: We interviewed five physicians, five field workers and 26 caregivers with children who initiated TB treatment < 7 days after diagnosis (n = 15) or who experienced a delay of ≥7 days (n = 11). Median time in delay from diagnosis to treatment initiation was 26 days (range 7-117). Reasons for delay included: health systems challenges (administrative hurdles, medication stock, clinic hours), burden of care on families and caregiver perceptions of disease severity.CONCLUSION: Reasons for delay in treatment initiation are complex. Interventions to streamline administrative processes and tools to identify and support families at risk for delays in treatment initiation are urgently needed.

Optofluidic detection setup for multi-parametric analysis of microbiological samples in droplets.

High-throughput microbiological experimentation using droplet microfluidics is limited due to the complexity and restricted versatility of the available detection techniques. Current detection setups are bulky, complicated, expensive, and require tedious optical alignment procedures while still mostly limited to fluorescence. In this work, we demonstrate an optofluidic detection setup for multi-parametric analyses of droplet samples by easily integrating micro-lenses and embedding optical fibers for guiding light in and out of the microfluidic chip. The optofluidic setup was validated for detection of absorbance, fluorescence, and scattered light. The developed platform was used for simultaneous detection of multiple parameters in different microbiological applications like cell density determination, growth kinetics, and antibiotic inhibition assays. Combining the high-throughput potential of droplet microfluidics with the ease, flexibility, and simplicity of optical fibers results in a powerful platform for microbiological experiments.

High MMP-9 activity characterises pleural tuberculosis correlating with granuloma formation.

Tuberculosis (TB) pleural disease is complicated by extensive tissue destruction. Matrix metalloproteinase (MMP)-1 and -9 are implicated in immunopathology of pulmonary and central nervous system TB. There are few data on MMP activity in TB pleurisy. The present study investigated MMP-1, -2 and -9 and their specific inhibitors (tissue inhibitor of metalloproteinase (TIMP)-1 and -2) in tuberculous effusions, and correlated these with clinical and histopathological features. Clinical data, routine blood tests, and pleural fluid/biopsy material were obtained from 89 patients presenting with pleural effusions in a TB-endemic area. MMP-1, -2 and -9 were measured by zymography or western blot, and TIMP-1 and -2 by ELISA. Pleural biopsies were examined microscopically, cultured for acid-alcohol fast bacilli and immunostained for MMP-9. Tuberculous pleural effusions contained the highest concentrations of MMP-9 compared with malignant effusions or heart failure transudates. MMP-9 concentrations were highest in effusions from patients with granulomatous biopsies: median (interquartile range) 108 (61-218) pg x mL(-1) versus 43 (12-83) pg x mL(-1) in those with nongranulomatous pleural biopsies. MMP-1 and -2 were not upregulated in tuberculous pleural fluid. The ratio of MMP-9:TIMP-1 was significantly higher in TB effusions. Tuberculous pleurisy is characterised by a specific pattern of matrix metalloproteinase-9 upregulation, correlating with the presence of granulomas and suggesting a specific role for matrix metalloproteinase-9 in inflammatory responses in tuberculous pleural disease.

The final destiny of acantholytic cells in pemphigus is Fas mediated.

BACKGROUND: Pemphigus is an autoimmune disease characterized by the formation of intra-epidermal blisters. Patients develop auto-antibodies against desmoglein 1 and 3 proteins and induce acantholysis. OBJECTIVE: This work addresses the issue of whether the Fas pathway mediates acantholysis. Furthermore, the possible suppliers of the Fas pathway were investigated. METHODS: Seventeen biopsies of pemphigus patients were studied by haematoxylin and eosin staining, and apoptosis was defined by TUNEL. The expression of Fas, FasL and caspase 3 was studied by in situ hybridization and immunohistochemistry. Cell infiltrates were studied by immunofluorescence with monoclonal anti-CD3, CD4, CD8, CD19 and CD69. RESULTS: All of the biopsies showed intra-epidermal blisters, acantholytic cells and inflammatory infiltrates. The blisters expressed Fas, FasL and caspase 3. Cell infiltrates were composed of CD8 and a few CD4(+)CD69(+) cells. Additionally, CD19(+) cells were detected. Interestingly, the Fas expression was increased in acantholytic cells and perilesional keratinocytes. Incidentally, these cells exhibited apoptotic features. Interestingly, the CD8 cells expressed FasL. CONCLUSION: This paper presents the morphological evidence that apoptosis and acantholysis are linked. Therefore, the Fas pathway is associated with CD8 cells in pemphigus lesions.

A dermatomyositis and scleroderma overlap syndrome with a remarkable high titer of anti-exosome antibodies.

An overlap syndrome of dermatomyositis and scleroderma is reported. The case corresponded to a 27-year-old female with a clinical picture of 14 months evolution, characterized by proximal muscles weakness, erythematous rash in wrists, knees, ankles, Gottron sign, heliotrope periorbital rash and dysphagia. A muscle biopsy was compatible with dermatomyositis; meanwhile the skin biopsy was compatible with scleroderma. Muscle enzymes were increased. Interestingly, the antinuclear antibody determination in HEp-2 cells was positive with a remarkable titer of 81,920 exhibiting a nucleolar pattern. Anti-Jo1 antibody was negative, but anti-PM/Scl-100 positive. The patient received methylprednisolone and cyclophosphamide pulses, with gradual improvement. Present report constitutes a case of overlap dermatomyositis-scleroderma syndrome, with anti-PM/Scl autoantibodies (anti-exosome). The remarkable of this case was the exceptional high antinucleolar antibody titer.

Efficacy and Cost of Trap-Bait Combinations for Capturing Rhynchophorus palmarum L. (Coleoptera: Curculionidae) in Ornamental Palm Polycultures.

Ornamental palms are an economically important component of international trade yet have recently experienced yield losses in Mexico due to red ring and bud rot diseases, which are spread by Rhynchophorus palmarum L. Considering that massive capture is a common strategy to control this pest and the cost of commercial traps and baits could be inaccessible for small farmers, an inexpensive trap-bait combination is desired. In this study, 16 trap-bait combinations for capturing R. palmarum were assessed in ornamental palm polycultures over the course of 1 year. An expensive yellow bucket trap combined with aggregation pheromone + insecticide + banana was compared with inexpensive, handmade trap-bait combinations. A total of 4712 weevils were collected in all traps, of which 52.7% were male and 47.3% female. The efficacy of the handmade trap made from a colorless polyethylene bottle and baited with banana + pineapple + sugarcane + sugarcane molasses was similar to that of the yellow bucket trap baited with aggregation pheromone + insecticide + banana. These two trap-bait combinations remained effective even when the R. palmarum population significantly decreased during the dry, warm season. The affordable handmade trap baited with food attractants and without insecticides was highly efficient in capturing R. palmarum and therefore represents an effective tool for monitoring weevil populations. As ornamental crops have recently gained greater economic importance in the studied region, the use of a novel and cheap trap-bait combination could offer great benefits to producers and form part of the integrated management of R. palmarum.

Rat brain opioid peptides-circadian rhythm is under control of melatonin.

Several experiments have revealed an Endogenous Opioid System (EOS)-circadian rhythm. The brain-borne hormone, melatonin (MEL) has been shown to regulate the organism photoperiodic activity and may be implicated in the EOS-circadian rhythm. To explore this hypothesis, we studied the effect of functional pinealectomy on the EOS-circadian rhythm by measuring the immunoreactive content of Met-Enkephalin, Leu-Enkephalin and Synenkephalin in both hypothalamus and hippocampus of the rat brain, using standard radioimmunoassay procedures. Experimental animals exposed to white fluorescent light (WFL) for 15days (<50lux), displayed a disruption of the EOS-circadian rhythm, showing that absence of MEL induced a significant decrease of tissue content of enkephalin peptides at 01:00h during the dark-phase of the 24-h circadian rhythm, when compared to control rats. Functional pinealectomized rats exposed to 4 or 6h period of darkness (used to revert the effects induced by the absence of melatonin) significantly increased the tissue content of ME-IR and LE-IR, when compared to both controls and non-exposed WFL-treated rats. In addition, subcutaneous administration of exogenous melatonin (10, 100, 150, 300, 600microg/kg), in WFL-treated animals produced significant dose-dependent increases of ME-IR in both brain regions tested. Finally, luzindole (melatonin receptor antagonist) administration, was not able to prevent the enkephalin tissue increase, induced with the MEL administration (150microg/kg). This data suggest that MEL not only regulates the EOS-circadian rhythm, but also appears to modulate their synthesis in the rat brain from their respective neurons.