Quantification of glycated hemoglobin and glucose in vivo using Raman spectroscopy and artificial neural networks.

Undiagnosed type 2 diabetes (T2D) remains a major public health concern. The global estimation of undiagnosed diabetes is about 46%, being this situation more critical in developing countries. Therefore, we proposed a non-invasive method to quantify glycated hemoglobin (HbA1c) and glucose in vivo. We developed a technique based on Raman spectroscopy, RReliefF as a feature selection method, and regression based on feed-forward artificial neural networks (FFNN). The spectra were obtained from the forearm, wrist, and index finger of 46 individuals. The use of FFNN allowed us to achieve an error in the predictive model of 0.69% for HbA1c and 30.12 mg/dL for glucose. Patients were classified according to HbA1c values into three categories: healthy, prediabetes, and T2D. The proposed method obtained a specificity and sensitivity of 87.50% and 80.77%, respectively. This work demonstrates the benefit of using artificial neural networks and feature selection techniques to enhance Raman spectra processing to determine glycated hemoglobin and glucose in patients with undiagnosed T2D.

Trauma patients who present in a delayed fashion: a unique and challenging population.

BACKGROUND: A proportion of trauma patients present for evaluation in a delayed fashion after injury, likely due to a variety of medical and nonmedical reasons. There has been little investigation into the characteristics and outcomes of trauma patients who present delayed. We hypothesize that trauma patients who present in a delayed fashion are a unique population at risk of increased trauma-related complications. MATERIALS AND METHODS: This was a retrospective review from 2010-2015 at a Level I trauma center. Patients were termed delayed if they presented >24 hours after injury. Patients admitted within 24 hours of their injury were the comparison group. Charts were reviewed for demographics, mechanism, comorbidities, complications and outcomes. A subgroup analysis was done on patients who suffered falls. RESULTS: During the 5-y period, 11,705 patients were admitted. A total of 588 patients (5%) presented >24 h after their injury. Patients in the delayed group were older (65 versus 55 y, P < 0.001) and more likely to have psychiatric comorbidities (33% vs. 24%, P = 0.0001) than the control group. They were also more likely to suffer substance withdrawal (8.9% vs. 4.1%, P < 0.001) but had toxicology testing for drugs and alcohol done at significantly lower rates. Patients that presented delayed after falls were similar in age and injury severity score (ISS) but more likely to suffer substance withdrawal when compared to those with falls that presented within 24 hours. Patients with falls that presented delayed had toxicology testing at significantly lower rates than the comparison group. CONCLUSIONS: Trauma patients that present to the hospital in a delayed fashion have unique characteristics and are more likely to suffer negative outcomes including substance withdrawal. Future goals will include exploring strategies for early intervention, such as automatic withdrawal monitoring and social work referral for all patients who present in a delayed fashion.

Effect of the influence function of deformable mirrors on laser beam shaping.

The continuous membrane stiffness of a deformable mirror propagates the deformation of the actuators beyond their neighbors. When phase-retrieval algorithms are used to determine the desired shape of these mirrors, this cross-coupling-also known as influence function (IF)-is generally disregarded. We study this problem via simulations and bench tests for different target shapes to gain further insight into the phenomenon. Sound modeling of the IF effect is achieved as highlighted by the concurrence between the modeled and experimental results. In addition, we observe that the actuators IF is a key parameter that determines the accuracy of the output light pattern. Finally, it is shown that in some cases it is possible to achieve better shaping by modifying the input irradiance of the phase-retrieval algorithm. The results obtained from this analysis open the door to further improvements in this type of beam-shaping systems.

Bioenergy Development Policy and Practice Must Recognize Potential Hydrologic Impacts: Lessons from the Americas.

Large-scale bioenergy production will affect the hydrologic cycle in multiple ways, including changes in canopy interception, evapotranspiration, infiltration, and the quantity and quality of surface runoff and groundwater recharge. As such, the water footprints of bioenergy sources vary significantly by type of feedstock, soil characteristics, cultivation practices, and hydro-climatic regime. Furthermore, water management implications of bioenergy production depend on existing land use, relative water availability, and competing water uses at a watershed scale. This paper reviews previous research on the water resource impacts of bioenergy production-from plot-scale hydrologic and nutrient cycling impacts to watershed and regional scale hydro-economic systems relationships. Primary gaps in knowledge that hinder policy development for integrated management of water-bioenergy systems are highlighted. Four case studies in the Americas are analyzed to illustrate relevant spatial and temporal scales for impact assessment, along with unique aspects of biofuel production compared to other agroforestry systems, such as energy-related conflicts and tradeoffs. Based on the case studies, the potential benefits of integrated resource management are assessed, as is the need for further case-specific research.

Beam shaping for laser-based adaptive optics in astronomy.

The availability and performance of laser-based adaptive optics (AO) systems are strongly dependent on the power and quality of the laser beam before being projected to the sky. Frequent and time-consuming alignment procedures are usually required in the laser systems with free-space optics to optimize the beam. Despite these procedures, significant distortions of the laser beam have been observed during the first two years of operation of the Gemini South multi-conjugate adaptive optics system (GeMS). A beam shaping concept with two deformable mirrors is investigated in order to provide automated optimization of the laser quality for astronomical AO. This study aims at demonstrating the correction of quasi-static aberrations of the laser, in both amplitude and phase, testing a prototype of this two-deformable mirror concept on GeMS. The paper presents the results of the preparatory study before the experimental phase. An algorithm to control amplitude and phase correction, based on phase retrieval techniques, is presented with a novel unwrapping method. Its performance is assessed via numerical simulations, using aberrations measured at GeMS as reference. The results predict effective amplitude and phase correction of the laser distortions with about 120 actuators per mirror and a separation of 1.4 m between the mirrors. The spot size is estimated to be reduced by up to 15% thanks to the correction. In terms of AO noise level, this has the same benefit as increasing the photon flux by 40%.

Implementation of a bundle to improve HIV testing during hospitalization for people who inject drugs.

Background: Increased HIV testing is essential to ending the HIV epidemic. People who inject drugs (PWID) are among the highest risk for HIV infection. Previous research at Tufts Medical Center identified low HIV testing rates in hospitalized PWID. Our research team aimed to identify and overcome barriers to inpatient HIV screening of PWID using implementation science methods. Methods: Stakeholders were engaged to gather perspectives on barriers and facilitators of HIV testing. A PWID care bundle was developed and implemented, which included (1) HIV screening; (2) hepatitis A, B, and C testing and vaccination; (3) medications for opioid use disorder; and (4) naloxone prescription. Strategies from all nine Expert Recommendations for Implementing Change (ERIC) clusters guided the implementation plan. Stakeholder feedback was gathered throughout implementation, and implementation outcomes of acceptability and feasibility were assessed. Results: PWID overall felt comfortable with HIV testing being offered while hospitalized. Clinicians cited that the main barriers to HIV testing were discomfort and confusion around consenting requirements. Many resident physicians surveyed reported that, at times, they forgot HIV testing for PWID. Overall, though, resident physicians felt that the PWID bundle was useful and did not distract from other patient care responsibilities. Conclusions: Engagement of key stakeholders to increase HIV testing in an inpatient setting led to the implementation of a PWID bundle, which was feasible and acceptable. Bundling evidence-informed care elements for inpatient PWID should be investigated further.

People who inject drugs (PWID) are at an increased risk of contracting HIV. HIV testing is a key strategy to stop the spread of HIV. Our study created a bundle of services and tests to offer to all PWID who were admitted to the hospital. The bundle included HIV testing; hepatitis A, B, and C testing and vaccination; medications for opioid use disorder; and prescription for Narcan, a medication that can reverse opioid overdose. We then asked doctors and patients how they felt about the bundle and any barriers and facilitators that they predicted for expanding HIV testing to PWID while admitted to the hospital. Patients were accepting of expanding HIV testing, and resident physicians felt it was important as well and was a manageable addition to their list of responsibilities. However, the most likely part of the bundle to be forgotten was HIV testing. This study lays the groundwork for bundling services for PWID while they are hospitalized. We also highlight areas for future exploration.

Administration of high doses of copper to capuchin monkeys does not cause liver damage but induces transcriptional activation of hepatic proliferative responses.

Liver cells respond to copper loading upregulating protective mechanisms. However, to date, except for liver content, there are no good indicators that identify individuals with excess liver copper. We hypothesized that administering high doses of copper to young (5.5 mg Cu · kg⁻¹ . d⁻¹) and adult (7.5 mg Cu · kg⁻¹ . d⁻¹) capuchin monkeys would induce detectable liver damage. Study groups included adult monkeys (2 females, 2 males) 3-3.5 y old at enrollment treated with copper for 36 mo (ACu); age-matched controls (1 female, 3 males) that did not receive additional copper (AC); young monkeys (2 female, 2 males) treated from birth with copper for 36 mo (YCu); and young age-matched controls (2 female, 2 males) that did not receive additional copper (YC). We periodically assessed clinical, blood biochemical, and liver histological indicators and at 36 mo the hepatic mRNA abundance of MT2a, APP, DMT1, CTR1, HGF, TGFß, and NFκΒ only in adult monkeys. After 36 mo, the liver copper concentration was 4-5 times greater in treated monkeys relative to controls. All monkeys remained healthy with normal routine serum biochemical indices and there was no evidence of liver tissue damage. Relative mRNA abundance of HGF, TGFß and NFκB was significantly greater in ACu than in AC monkeys. In conclusion, capuchin monkeys exposed to copper at doses up to 50 times the current upper level enhanced expression of genes related to inflammation and injury without clinical, blood biochemical, or histological evidence of liver damage.

Pupil aberrations in Offner spectrometers.

The light path function (LPF) of an Offner spectrometer is presented. The evaluation of the LPF of this spectrometer enables its imaging properties to be studied for arbitrary object and image positions, while avoiding the more complicated analysis of intermediate images generated by the diffraction grating, which is often involved. A power series expansion of the LPF on the grating coordinates directly determines pupil aberrations of the generated spectrum and facilitates the search for configurations with small low-order aberrations. This analysis not only confirms the possibility of reducing low-order aberrations in Rowland-type mounts, namely astigmatism and coma, as predicted in previous studies, but also proves that all third-order terms in the series expansion of the aberration function can be canceled at the image of the design point and for the corresponding design wavelength, when the design point is located on a plane orthogonal to the optical axis. Furthermore, fourth-order terms are computed and shown to represent the most relevant contribution to image blurring. Third- and fourth-order aberrations are also evaluated for Rowland mounts with the design point located outside the aforementioned plane. The study described in this manuscript is not restricted to small angles of incidence, and, therefore, it goes beyond Seidel and Buchdahl aberrations.

Trends in risk behaviors and sexually transmitted infections among youth presenting to a sexually transmitted infection clinic in the United States, 2013-2017.

Background: Sexually transmitted infections (STIs) are increasing among adolescents and young adults (AYA) across the United States. However, data are scarce on trends in condom use, number of partners, and other STI risk factors among AYA. The present study evaluated associations between sexual behaviors and STI diagnoses over time among AYA. Methods: We evaluated linked encounters of AYA aged 13-26 attending an urban Northeast public STI clinic from 2013-2017. Demographics, risk behaviors, self-reported past year and lifetime STI, and STI diagnosis during clinic encounter (positive test for urine, oral, or anal chlamydia; urine, oral, or anal gonorrhea; urine trichomonas; HIV; and syphilis) were extracted from electronic health records. We estimated prevalence and performed trend analyses of the repeated cross-sectional data. Cochran-Armitage and Kruskal-Wallis trend test were conducted for categorical and continuous variables, respectively. Results: Among 3822 encounters, clinical STIs demonstrated statistically significant increases including chlamydia (+9%, p = 0.001), gonorrhea (+5%, p = 0.008), and syphilis (+3%, p = 0.006) all of which significantly increased over time, as did any STI (+10%, p < 0.001). HIV and trichomonas rates remained low and unchanged. Self-reported STI increased as well, both past year (+9%) and lifetime (+14%). Greater proportions of AYA reported multiple partners (+9%, p < 0.001), and condomless oral (+12%, p = 0.001) and vaginal/anal (+7%, p = 0.001) sex. Conclusion: Among AYA presenting to a STI clinic, the proportion who engaged in condomless sex and had multiple partners increased over a 5 year period, which corresponded to increased STI prevalence during this period. Preventions efforts for AYA should continue to emphasize the importance of condoms and partner selection.

Off-plane anastigmatic imaging in Offner spectrometers.

In this paper, the imaging performance of an Offner concentric imaging spectrometer is analyzed when the spectrometer entrance slit is disposed arbitrarily on the plane that is parallel to the grating grooves and contains the common center of curvature. Astigmatism-corrected designs are obtained for off-plane incidence on the grating if one point on the slit is located on the Rowland circle of the primary mirror. In this case, the combined system of primary mirror plus diffraction grating provides two astigmatic line images oriented parallel and orthogonal to the plane of diffraction, with the former located on the same plane as the slit. Consequently, these images can be brought to a single focus on this plane by the tertiary mirror if its radius of curvature is chosen properly. In addition, coma aberration is simultaneously removed. These results can be applied to the design of two-mirror or three-mirror spectrometers, generalizing the concept of the best imaging circle and providing solutions to get anastigmatic imaging for two object points and two wavelengths.

Design of Dyson imaging spectrometers based on the Rowland circle concept.

We aim to show that Dyson imaging spectrometers can be easily designed by applying the concept of the Rowland circle to refracting surfaces. This allows us to conceive an analytical procedure that is based on the removal of astigmatism at two wavelengths. Following this procedure, high-optical-quality spectrometers can be designed even for high speeds. Root-mean-square spot radii less than 2.5 µm are obtained for speeds as high as f/1.5, slit lengths of 15 mm, and wavelength ranges of 0.4-1.7 µm. Design examples are presented for classical Dyson spectrometers in which the detector is glued to the glass plane surface and for spectrometers with an air gap between this surface and the image plane.

Schwarzschild spectrometer.

This is a proposal and description of a new spectrometer based on the Schwarzschild optical system. The proposed design contains two Schwarzschild optical systems. Light diverging from the spectrometer entrance slit is collimated by the first one; the collimated light beam hits a planar diffraction grating and the light dispersed from the grating is focused by the second system, which is concentric with the first. A very simple procedure obtains designs that are anastigmatic for the center of the slit and for a particular wavelength. A specific example shows the performance of this type of spectrometer.

[Hurricane impact on Thalassia testudinum (Hydrocharitaceae) beds in the Mexican Caribbean]. / Impacto por huracanes en las praderas de Thalassia testudinum (Hydrocharitaceae) en el Caribe Mexicano.

Hurricanes have increased in strength and frequency as a result of global climate change. This research was conducted to study the spatio-temporal distribution and changes of Thalassia testudinum, the dominant species in Bahia de la Ascension (Quintana Roo, Mexico), when affected by heavy weather conditions. To complete this objective, a 2001 Landsat ETM+ image and the information from 525 sampling stations on morpho-functional and coverage of T. testudinum were used, and the seeds generated for the classification of eight benthic habitats. To quantify the changes caused by two hurricanes, we used two images, one of 1988 (Gilberto) and another of 1995 (Roxanne); other three data sets (2003, 2005 and 2007) were also used to describe the study area without major weather effects. Six categorial maps were obtained and subjected to analysis by 8 Landscape Ecology indexes, that describe the spatial characteristics, structure, function, change of the elements (matrix-patch-corridor), effects on ecosystems, connectivity, edges, shape and patch habitat fragmentation. Models indicate that T. testudinum may be classified as a continuum (matrix), since the fragments were not observed intermittently, but as a progression from minimum to maximum areas in reference to their coverage (ecological corridors). The fragments do not have a regular shape, indicating that the impacts are recent and may be due to direct effects (high-intensity hurricanes) or indirect (sediment). Fragments of type "bare soils" have a discontinuous distribution, and are considered to be the sites that have remained stable over a long timescale. While more dense coverage areas ("beds", "medium prairie" and "prairie") have low fragmentation and high connection of fragments. Features have an irregular perimeter and radial growth of formal; suggesting that the impact of meteors has no effect on the resilience of T. testudinum in this ecosystem, indicating good environmental quality to grow in this bay.

Pharmacogenomic polygenic risk score for clopidogrel responsiveness among Caribbean Hispanics: A candidate gene approach.

This multicenter clinical study was aimed at conducting a targeted pharmacogenomic association analysis of residual on-clopidogrel platelet reactivity in 474 Caribbean Hispanic patients. Platelet reactivity was measured using the VerifyNow P2Y12 assay and clopidogrel resistance was defined as P2Y12 reaction units (PRUs) greater than or equal to 208. Genotyping was performed using the whole-genome Infinium MEGA BeadChip array. An ancestry-adjusted, weighted polygenic risk score (wPGxRS) was developed to account for the effect of multiple variants on PRU and compared between clopidogrel responders and nonresponders. The mean PRU across the study cohort was 173.8 ± 68.5 and 33.5% of patients were defined as clopidogrel resistant. Multivariate linear regression showed that 19% of PRU variability was attributed to nine independent predictors, with CYP2C19*2 (rs4244285) accounting for ~ 7% of observed PRU variation (p < 0.001). PON1 rs662, ABCB1/MDR1 rs2032582, PEAR1 rs12041331 carrier status, and the interaction between African ancestry and rs12041331 carriers also predicted PRU among the participants (p ≤ 0.05). A clear gene-dose effect was detected between PRU and CYP2C19*2 genotype, consistent with previous studies in European patient populations, as well as rs12777823. Importantly, a significant positive correlation was detected between our novel wPGxRS (4 variants) and PRU among the Hispanic patient population (rp  = 0.35, p < 0.001). Moreover, the wPGxRS discriminated between nonresponders and responders (p = 0.003), indicating that this multigene-based score is a useful predictor of clopidogrel resistance among Caribbean Hispanics. Taken together, these results help close the gap of knowledge on clopidogrel pharmacogenomics and its potential clinical implementation in this under-represented population.

The Offner imaging spectrometer in quadrature.

This is a proposal and description of a new configuration for an Offner imaging spectrometer based on the theory of aberrations of off-plane classical-ruled spherical diffraction gratings. This new spectrometer comprises a concave mirror used in double reflection and a convex reflection grating operating in quadrature, in a concentric layout. A very simple procedure obtains designs that are anastigmatic for a given point on the entrance slit and a given wavelength. Specific examples show that the performance of this type of system improves the performance of analogous conventional in-plane systems, when compactness and/or high spectral resolution is of fundamental importance.

Two-wavelength anastigmatic Dyson imaging spectrometers.

High-quality Dyson imaging spectrometers are designed by applying a telecentric condition for off-axis image points. By imposing this condition for two different wavelengths, designs presenting low aberrations for the whole spectral range of the system are obtained. A UV-TO-NIR fast design (f/1.5) exhibiting excellent optical performance is presented.

Implementing a pharmacogenetic-driven algorithm to guide dual antiplatelet therapy (DAPT) in Caribbean Hispanics: protocol for a non-randomised clinical trial.

INTRODUCTION: Minority populations in the USA are disproportionately affected by cardiovascular conditions. Reduced responsiveness to clopidogrel among carriers of CYP2C19 variants has been reported in patients with either coronary artery disease (CAD) or acute coronary syndrome (ACS) after the percutaneous coronary intervention (PCI). Previous studies have evaluated CYP2C19 genotyping-guided antiplatelet therapy in selected populations; however, this has yet to be tested among Hispanics. Given the paucity of clinical research on CYP2C19 and antiplatelet clinical outcomes in Hispanics, our study will test the safety and efficacy of a genetic-driven treatment algorithm to guide dual antiplatelet therapy (DAPT) in Caribbean Hispanics. METHODS AND ANALYSIS: This is a multicentre, prospective, non-randomised clinical trial that proposes an assessment of pharmacogenomic-guided DAPT in post-PCI Caribbean Hispanic patients with ACS or CAD. We will recruit 250 patients to be compared with a matched non-concurrent cohort of 250 clopidogrel-treated patients (standard-of-care). Major adverse cardiovascular events (MACEs) such as all-cause death, myocardial infarction (MI), stroke, coronary revascularisation, stent thrombosis and bleedings over 6 months will be the study endpoints. Among the recruited, high-risk patients will be escalated to ticagrelor and low-risk patients will remain on clopidogrel. The primary objective is to determine whether genetic-guided therapy is superior to standard of care. The secondary objective will determine if clopidogrel treatment in low-risk patients is not associated with a higher rate of MACEs compared with escalated antiplatelet therapy in high-risk patients. Patients will be enrolled up to the group's completion. ETHICS AND DISSEMINATION: Approval was obtained from the Institutional Review Board of the University of Puerto Rico Medical Sciences Campus (protocol # A4070417). The study will be carried out in compliance with the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice Guidelines. Findings will be published in a peer-reviewed journal and controlled access to experimental data will be available. TRIAL REGISTRATION NUMBER: NCT03419325; Pre-results.

Imaging with classical spherical diffraction gratings: the quadrature configuration.

We review the theory of spherical diffraction gratings with regard to their imaging properties in off-plane arrangements. Our study is restricted to gratings with equally spaced grooves, and it is focused on the quadrature configuration, where the incident and diffraction planes are orthogonal to each other. We identify regions of low astigmatism and propose some monochromator mounts.

Complicaciones de la laringectomía total: experiencia de 7 años en un hospital universitario de Paraguay / Complications of total laryngectomy: a 7-year experience in a university hospital in Paraguay

Introducción: El cáncer de laringe es la neoplasia maligna más común de las vías aerodigestivas superiores. La laringectomía total es el tratamiento de elección en casos avanzados, pero se asocia a una alta tasa de complicaciones. Objetivos: Conocer la prevalencia de las complicaciones posquirúrgicas de la laringectomía total y los factores asociados en pacientes con cáncer de laringe. Materiales y métodos: Estudio observacional, descriptivo, retrospectivo, de corte transversal, revisando el comportamiento de la laringectomía total y sus principales complicaciones en la Cátedra y Servicio de Otorrinolaringología del Hospital de Clínicas de la Facultad de Ciencias Médicas de la Universidad Nacional de Asunción, Paraguay, de 2015 a 2022. Se incluyeron pacientes mayores de 18 años, de ambos sexos, postoperados de laringectomía total, con diagnóstico anatomopatológico de neoplasia de laringe. Se excluyeron pacientes no operados, con fichas incompletas o que abandonaron el tratamiento. Se analizaron variables demográficas, clínicas, quirúrgicas y anatomopatológicas. Resultados: Se incluyeron 10 pacientes, todos varones, con edad media de 56,3 ± 10,2 años. El 90% presentaba hábitos tóxicos. La complicación más frecuente fue la fístula faringocutánea (70%), seguida por infección del sitio quirúrgico (10%) y sangrado posoperatorio (10%). El 71,4% de las fístulas se resolvieron con medidas conservadoras. El 30% tenía afectación supraglótica y el 57,1% de los que presentaron complicaciones recibieron radioterapia previa. Conclusión: Las complicaciones de la laringectomía total son frecuentes, principalmente la fístula faringocutánea. La afectación supraglótica y la radioterapia previa se asociaron a mayor tasa de complicaciones. Se requieren estudios prospectivos con muestras más grandes para confirmar estos hallazgos.

Introduction: Laryngeal cancer is the most common malignant neoplasm of the upper aerodigestive tract. Total laryngectomy is the treatment of choice in advanced cases, but it is associated with a high rate of complications. Objectives: To determine the prevalence of postoperative complications of total laryngectomy and associated factors in patients with laryngeal cancer. Materials and methods: Observational, descriptive, retrospective, cross-sectional study, reviewing the behavior of total laryngectomy and its main complications in the Department of Otorhinolaryngology of the Hospital de Clínicas, Faculty of Medical Sciences, National University of Asunción, Paraguay, from 2015 to 2022. Patients over 18 years of age, of both sexes, who underwent total laryngectomy, with anatomopathological diagnosis of laryngeal neoplasm were included. Non-operated patients, those with incomplete records or who abandoned treatment were excluded. Demographic, clinical, surgical and anatomopathological variables were analyzed. Results: Ten patients were included, all male, with a mean age of 56.3 ± 10.2 years. Ninety percent had toxic habits. The most frequent complication was pharyngocutaneous fistula (70%), followed by surgical site infection (10%) and postoperative bleeding (10%). Conservative measures resolved 71.4% of the fistulas. Thirty percent had supraglottic involvement and 57.1% of those who presented complications received previous radiotherapy. Conclusion: Complications of total laryngectomy are frequent, mainly pharyngocutaneous fistula. Supraglottic involvement and previous radiotherapy were associated with a higher rate of complications. Prospective studies with larger samples are required to confirm these findings.

Fetal undernutrition induces overexpression of CRH mRNA and CRH protein in hypothalamus and increases CRH and corticosterone in plasma during postnatal life in the rat.

Prenatal undernutrition induces a variety of cardiovascular alterations in mammals when adults, including hypertension and hypercortisolism, which are thought to be caused by decreased glucocorticoid feedback control of the hypothalamus-pituitary-adrenal (HPA) axis programmed during fetal life. Hypothalamic CRH seems to be involved in blood pressure elevation of spontaneously hypertensive rats and in primary hypertension of humans, but the influence of prenatal undernutrition on CRH expression has deserved little attention. Here, we studied the expression of both CRH mRNA and CRH protein in the hypothalamus of neonatal and juvenile offspring of rats undernourished during fetal life, as well as the plasma levels of CRH and corticosterone. Prenatal undernutrition of pups was induced by submitting pregnant rats to diet restriction (10g daily of 21% protein standard laboratory diet). Pups born from dams with free access to the standard laboratory diet served as controls. At day 2 of postnatal age, undernourished pups showed lower body and brain weights, but higher plasma CRH and corticosterone than normal pups. At day 40 of age, brain weight was significantly decreased in the undernourished rats, while plasma corticosterone, plasma CRH and systolic pressure were significantly increased in these animals. At days 2 and 40 of postnatal age, increased CRH mRNA expression and CRH concentration were found in the hypothalamus of undernourished rats. Results indicate that, in the rat, prenatal undernutrition led to fetal programming of CRH overexpression, a neuropeptide serving as activating signal to the HPA axis and/or to extrahypothalamic brain regions concerned with cardiovascular regulation.