Afectación iatrogénica de la motilidad ocular por fármacos antitumorales inhibidores de los puntos de control / Iatrogenic impairment of ocular motility by immune checkpoint inhibitors

Se encontraron 4 revisiones sistemáticas que incluían este tipo de iatrogenia ocular, así como numerosos reportes de casos aislados. Los efectos adversos reportados comprenden: paresias oculomotoras, neuropatía óptica, atrofia óptica, síndromes miasteniformes, pseudo-orbitopatía tiroidea, síndrome del ápex orbitario e hipofisitis. La mayoría se manejaron sin interrupción o con interrupción parcial del tratamiento oncológico. Se requirieron tratamientos sistémicos agresivos para el manejo adecuado de la iatrogenia ocular.Es imprescindible que el oftalmólogo se familiarice con los nuevos tratamientos oncológicos ICI, capaces de provocar iatrogenia sobre la motilidad ocular grave e incapacitante para el paciente. La comunicación de efectos adversos con los tratamientos empleados puede ayudar al manejo más adecuado de estos pacientes. La investigación debe ir orientada al diagnóstico diferencial complejo y a optimizar las decisiones sobre los tratamientos oncológicos. (AU)

Cancer therapy relies on new antitumoral drugs called immune checkpoint inhibitors (ICI), which produce long-lasting anti-tumor responses and lengthen survival, but cause autoimmune-type toxicity. The clinical characteristics induced by ICI are not well characterized to date and careful collection of clinical data is required to accurately define its safety profile.We conducted a literature search in the main clinical search engines to identify pharmacological ocular iatrogenic events of ICIs related to ocular motility. Four systematic reviews were found that included this type of ocular iatrogenesis as well as numerous isolated case reports. Reported adverse effects include: oculomotor paresis, optic neuropathy, optic atrophy, myastheniform syndromes, thyroid pseudo-orbitopathy, orbital apex syndrome, and hypophysitis. Most were managed without interruption or with partial interruption of cancer treatment. Aggressive systemic treatments were required for adequate management of ocular iatrogenic events.It is essential that the ophthalmologist become familiar with the new ICI oncological treatments, capable of causing severe and disabling motilidad ocular iatrogenesis for the patient. The communication of adverse effects and the report of the treatments used can help the most appropriate management of these patients. Research should be oriented towards complex differential diagnosis and to optimize decisions on cancer treatments. (AU)

Iatrogenic affectation of ocular motility by immune checkpoint inhibitors.

Cancer therapy relies on new antitumoral drugs called immune checkpoint inhibitors (ICI), which produce long-lasting anti-tumor responses and lengthen survival, but cause autoimmune-type toxicity. The clinical characteristics induced by ICI are not well characterized to date and careful collection of clinical data is required to accurately define its safety profile. We conducted a literature search in the main clinical search engines to identify pharmacological ocular iatrogenic events of ICIs related to ocular motility. Four systematic reviews were found that included this type of ocular iatrogenesis as well as numerous isolated case reports. Reported adverse effects include: oculomotor paresis, optic neuropathy, optic atrophy, myastheniform syndromes, thyroid pseudo-orbitopathy, orbital apex syndrome, and hypophysitis. Most were managed without interruption or with partial interruption of cancer treatment. Aggressive systemic treatments were required for adequate management of ocular iatrogenic events. It is essential that the ophthalmologist become familiar with the new ICI oncological treatments, capable of causing severe and disabling motilidad ocular iatrogenesis for the patient. The communication of adverse effects and the report of the treatments used can help the most appropriate management of these patients. Research should be oriented towards complex differential diagnosis and to optimize decisions on cancer treatments.

Microplastics ingestion and endocrine disrupting chemicals (EDCs) by breeding seabirds in the east tropical Atlantic: Associations with trophic and foraging proxies (δ15N and δ13C).

In this study we found that endocrine disrupting chemicals (EDCs) were omnipresent in a tropical seabird community comprising diverse ecological guilds and distinct foraging and trophic preferences. Because EDCs tend to bioaccumulate within the food web and microplastics can absorb and release harmful chemical compounds, our findings draw attention to the potential threats to wildlife. Thus, the goal of this study was to investigate the role of plastic ingestion, trophic and foraging patterns (δ15N and δ13C) of five tropical seabird species breeding in sympatry, on the exposure to EDCs, namely Polybrominated diphenyl ethers (PBDEs), methoxylated polybrominated diphenyl ethers (MeO-PBDEs) and personal care products (PCPs, e.g., musk fragrances and UV-filters). Results indicated that microplastics occurrence and EDCs detection frequency varied among species. Microplastics occurrence was higher in species with dual and coastal foraging strategies. Preen oil had higher levels of MeO-PBDEs and PCPs, while serum had higher levels of PBDEs. In brown boobies, the correlation between microplastics and ∑PBDEs levels was significant, suggesting that microplastics ingestion is a key PBDEs route. Trophic position (δ15N) plays a key role in PBDEs accumulation, particularly in Bulwer's petrel, which occupies a high trophic position and had more specialized feeding ecology than the other species. MeO-PBDEs were linked to foraging habitat (δ13C), although the link to foraging locations deserves further investigation. Overall, our findings not only fill key gaps in our understanding of seabirds' exposure to microplastics and EDCs, but also provide an essential baseline for future research and monitoring efforts. These findings have broader implications for the marine wildlife conservation and pollution management in sensitive environments, such as the tropical regions off West Africa.

Cerebrovascular risk factors and their time-dependent effects on stroke survival in the EMMA cohort study.

To investigate the time-dependent effects of traditional risk factors on functional disability in all-cause mortality post-stroke, we evaluated data from a long-term stroke cohort. Baseline cerebrovascular risk factors (CVRF) and functionality at 1 and 6 months were evaluated in survivors from a prospective stroke cohort using the modified Rankin scale (m-RS), which classifies participants as improvement of disability, unchanged disability (at least moderate), and worsening disability. Cox regression models considering baseline risk factors, medication use, and functionality 6 months after stroke were fitted to identify their time-dependent effects up to 12 years of follow-up. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) are presented. Among 632 survivors (median age 68, 54% male, 71% first-ever episode), age and functional disability (unchanged and worsening) 6 months after ischemic stroke had time-dependent effects on all-cause mortality risk up to 12 years of follow-up. The most impacting risk factors were unchanged (at least moderate) (HR, 2.99; 95%CI: 1.98-4.52) and worsening disability (HR, 2.85; 95%CI: 1.26-6.44), particularly in the first two years after a stroke event (Time 1: ≥6 mo to <2.5 y). Worsening disability also impacted mortality in the period from ≥2.5 to <7.5 years (Time 2) of follow-up (HR, 2.43 (95%CI: 1.03-5.73). Other baseline factors had a fixed high-risk effect on mortality during follow-up. Post-stroke and continuous medication use had a fixed protective effect on mortality. Functional disability was the main contributor with differential risks of mortality up to 12 years of follow-up.

Anthropogenic debris ingestion in a tropical seabird community: Insights from taxonomy and foraging distribution.

Oceans have been considered as an unlimited supply of goods and services, but resource extraction and waste disposal became ubiquitous and have been damaging the health of marine ecosystems. Finding suitable sentinel species of the human impacts on the oceans is thus imperative, since they may work as early warnings of disruptive situations. In this study, we investigated how taxonomy and foraging distribution influenced the occurrence of anthropogenic debris among five seabird species inhabiting the tropical Atlantic region. Occurrence of anthropogenic debris was assessed using faeces of breeding individuals as a proxy of ingestion. A total of 268 particles were extracted from all samples. The categories "fragments" and "fibres", as well as the colour "blue", were the most prevalent characteristics across species. There was a high diversity of polymers from cellulosic particles to synthetic plastics (Anthropogenic Cellulosic 26.9 %; Polyester 7.7 %; Varnish 5.8 %; Polypropylene 1.9 %). Species with a more coastal foraging strategy exhibited higher occurrence and number of anthropogenic debris when compared to species foraging comparably more in pelagic areas. This suggests that anthropogenic debris are more prevalent in coastal foraging areas, where human activities occur in higher number and frequency (e.g., fisheries) and sources of freshwater input from inland are at close distance. These results provide more evidence to the growing perception on the ubiquity and diversity of anthropogenic debris in the marine environment, and further support the usefulness of using seabirds as bio-indicators of anthropogenic pollution in both neritic and oceanic regions.

Parental stress and dental caries experience in adolescents: analysis of data from a birth cohort study in Pelotas, Southern Brazil.

PURPOSE: Analyze the association between parental stress and dental caries experience in adolescents in southern Brazil using data from the Pelotas 2004 Birth Cohort. METHODS: Interviews and oral health examinations for the determination of the main exposure and outcome of the study were performed in the homes of the adolescents. The outcome was dental caries experience in the permanent dentition analyzed using the Decayed, Missing and Filling Surfaces (DMFS) index. The main exposure was parental stress measured using the Parenting Stress Index-Short Form administered to the parents of the adolescents. Demographic/socioeconomic characteristics, oral health characteristics and oral health-related quality of life were considered potential confounding factors. Negative binomial regressions estimated mean ratios (MR) and 95% confidence intervals (CI). RESULTS: Nine hundred ninety-six adolescents were evaluated at 12 and 13 years of age. The prevalence of dental caries experience in the adolescents was 36.9% (95% CI: 33.8-40.0) and 15.1% (95% CI: 12.8-17.3) of the parents had parental stress. After adjusting for confounding factors, parental stress was associated with a higher mean number of decayed, missing and filling surfaces in the adolescents (MR = 1.10; 95% CI: 1.01-1.26; p = 0.045). CONCLUSION: Adolescents of parents with parental stress have more dental caries experience compared to those whose parents do not have parental stress.

Association of coronary artery calcium with heart rate variability in the Brazilian Longitudinal Study of Adult Health - ELSA-Brasil.

Current data shows that the autonomic and vascular systems can influence each other. However, only a few studies have addressed this association in the general population. We aimed to investigate whether heart rate variability (HRV) was associated with coronary artery calcium (CAC) in a cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We examined baseline data from 3138 participants (aged 35 to 74 years) without previous cardiovascular disease who underwent CAC score assessment and had validated HRV recordings. Prevalent CAC was defined as a CAC score>0, and HRV analyses were performed over 5-min segments. We detected CAC score>0 in 765 (24.4%) participants. Subgroup analyses in older participants (≥49 years) adjusted for sociodemographic and clinical variables revealed that CAC score>0 was associated with lower values of standard deviation of NN intervals (SDNN) (odds ratio [OR]=1.32; 95%CI: 1.05,1.65), root mean square of successive differences between adjacent NN intervals (RMSSD) (OR=1.28; 95%CI: 1.02,1.61), and low frequency (LF) (OR=1.53, 95%CI: 1.21,1.92). Interaction analysis between HRV indices and sex in age-stratified groups revealed significant effect modification: women showed increased OR for prevalent CAC in the younger group, while for men, the associations were in the older group. In conclusion, participants aged ≥49 years with low SDNN, RMSSD, and LF values were more likely to present prevalent CAC, suggesting a complex interaction between these markers in the pathogenesis of atherosclerosis. Furthermore, our results suggested that the relationship between CAC and HRV might be sex- and age-related.

Eight-year change in carotid intima-media thickness and associated risk factors in adults with and without psoriasis - the ELSA-Brasil cohort study.

The longitudinal association between psoriasis and carotid intima-media thickness (CIMT) has not yet been established. This study aimed do compare CIMT and its change (∆CIMT) after an 8-year follow-up according to psoriasis diagnosis and the association with risk factors in the ELSA-Brasil study. Data from 7564 participants were analyzed (median age of 50.0 [44.0-57.0] years, 56.9% women). CIMT was assessed by ultrasound and ∆CIMT was calculated by subtracting baseline values from follow-up values. Psoriasis participants were identified by self-reported medical diagnosis (n=143) and compared with matched participants without disease (n=572) and with the entire sample without psoriasis (n=7421). Baseline CIMT explained the 8-year CIMT increase only in 36.9% among psoriasis participants and in ∼43.0% in participants without disease. CIMT was associated with age (ß=0.002, P=0.002) and hypertension (ß=0.029, P=0.034) in psoriasis participants. Among participants without psoriasis, CIMT was associated with age, male sex, low educational attainment, past smoking, obesity, diabetes, hypertension, and dyslipidemia (P<0.05). There was an inverse association of CIMT with private health insurance (ß=-0.004, P=0.042) and White ethnicity (ß=-0.006, P=0.004) in the entire sample without psoriasis but not in matched participants. Psoriasis participants showed an inverse association between ∆CIMT and diabetes (ß=-0.214, P=0.011), while the entire sample without psoriasis showed an inverse association between ∆CIMT and age (ß=-0.005, P<0.001), past smoking (ß=-0.048, P=0.009), and hypertension (ß=-0.048, P=0.009). In conclusion, psoriasis was not associated with CIMT after an 8-year follow-up. The inverse association of ∆CIMT with diabetes in psoriasis participants needs further clarification.

Association of coronary artery calcium with heart rate variability in the Brazilian Longitudinal Study of Adult Health - ELSA-Brasil

Current data shows that the autonomic and vascular systems can influence each other. However, only a few studies have addressed this association in the general population. We aimed to investigate whether heart rate variability (HRV) was associated with coronary artery calcium (CAC) in a cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We examined baseline data from 3138 participants (aged 35 to 74 years) without previous cardiovascular disease who underwent CAC score assessment and had validated HRV recordings. Prevalent CAC was defined as a CAC score>0, and HRV analyses were performed over 5-min segments. We detected CAC score>0 in 765 (24.4%) participants. Subgroup analyses in older participants (≥49 years) adjusted for sociodemographic and clinical variables revealed that CAC score>0 was associated with lower values of standard deviation of NN intervals (SDNN) (odds ratio [OR]=1.32; 95%CI: 1.05,1.65), root mean square of successive differences between adjacent NN intervals (RMSSD) (OR=1.28; 95%CI: 1.02,1.61), and low frequency (LF) (OR=1.53, 95%CI: 1.21,1.92). Interaction analysis between HRV indices and sex in age-stratified groups revealed significant effect modification: women showed increased OR for prevalent CAC in the younger group, while for men, the associations were in the older group. In conclusion, participants aged ≥49 years with low SDNN, RMSSD, and LF values were more likely to present prevalent CAC, suggesting a complex interaction between these markers in the pathogenesis of atherosclerosis. Furthermore, our results suggested that the relationship between CAC and HRV might be sex- and age-related.

Eight-year change in carotid intima-media thickness and associated risk factors in adults with and without psoriasis - the ELSA-Brasil cohort study

The longitudinal association between psoriasis and carotid intima-media thickness (CIMT) has not yet been established. This study aimed do compare CIMT and its change (∆CIMT) after an 8-year follow-up according to psoriasis diagnosis and the association with risk factors in the ELSA-Brasil study. Data from 7564 participants were analyzed (median age of 50.0 [44.0-57.0] years, 56.9% women). CIMT was assessed by ultrasound and ∆CIMT was calculated by subtracting baseline values from follow-up values. Psoriasis participants were identified by self-reported medical diagnosis (n=143) and compared with matched participants without disease (n=572) and with the entire sample without psoriasis (n=7421). Baseline CIMT explained the 8-year CIMT increase only in 36.9% among psoriasis participants and in ∼43.0% in participants without disease. CIMT was associated with age (β=0.002, P=0.002) and hypertension (β=0.029, P=0.034) in psoriasis participants. Among participants without psoriasis, CIMT was associated with age, male sex, low educational attainment, past smoking, obesity, diabetes, hypertension, and dyslipidemia (P<0.05). There was an inverse association of CIMT with private health insurance (β=-0.004, P=0.042) and White ethnicity (β=-0.006, P=0.004) in the entire sample without psoriasis but not in matched participants. Psoriasis participants showed an inverse association between ∆CIMT and diabetes (β=-0.214, P=0.011), while the entire sample without psoriasis showed an inverse association between ∆CIMT and age (β=-0.005, P<0.001), past smoking (β=-0.048, P=0.009), and hypertension (β=-0.048, P=0.009). In conclusion, psoriasis was not associated with CIMT after an 8-year follow-up. The inverse association of ∆CIMT with diabetes in psoriasis participants needs further clarification.

Cerebrovascular risk factors and their time-dependent effects on stroke survival in the EMMA cohort study

To investigate the time-dependent effects of traditional risk factors on functional disability in all-cause mortality post-stroke, we evaluated data from a long-term stroke cohort. Baseline cerebrovascular risk factors (CVRF) and functionality at 1 and 6 months were evaluated in survivors from a prospective stroke cohort using the modified Rankin scale (m-RS), which classifies participants as improvement of disability, unchanged disability (at least moderate), and worsening disability. Cox regression models considering baseline risk factors, medication use, and functionality 6 months after stroke were fitted to identify their time-dependent effects up to 12 years of follow-up. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) are presented. Among 632 survivors (median age 68, 54% male, 71% first-ever episode), age and functional disability (unchanged and worsening) 6 months after ischemic stroke had time-dependent effects on all-cause mortality risk up to 12 years of follow-up. The most impacting risk factors were unchanged (at least moderate) (HR, 2.99; 95%CI: 1.98-4.52) and worsening disability (HR, 2.85; 95%CI: 1.26-6.44), particularly in the first two years after a stroke event (Time 1: ≥6 mo to <2.5 y). Worsening disability also impacted mortality in the period from ≥2.5 to <7.5 years (Time 2) of follow-up (HR, 2.43 (95%CI: 1.03-5.73). Other baseline factors had a fixed high-risk effect on mortality during follow-up. Post-stroke and continuous medication use had a fixed protective effect on mortality. Functional disability was the main contributor with differential risks of mortality up to 12 years of follow-up.

Optical mapping compendium of structural variants across global cattle breeds.

Structural variants (SV) have been linked to important bovine disease phenotypes, but due to the difficulty of their accurate detection with standard sequencing approaches, their role in shaping important traits across cattle breeds is largely unexplored. Optical mapping is an alternative approach for mapping SVs that has been shown to have higher sensitivity than DNA sequencing approaches. The aim of this project was to use optical mapping to develop a high-quality database of structural variation across cattle breeds from different geographical regions, to enable further study of SVs in cattle. To do this we generated 100X Bionano optical mapping data for 18 cattle of nine different ancestries, three continents and both cattle sub-species. In total we identified 13,457 SVs, of which 1,200 putatively overlap coding regions. This resource provides a high-quality set of optical mapping-based SV calls that can be used across studies, from validating DNA sequencing-based SV calls to prioritising candidate functional variants in genetic association studies and expanding our understanding of the role of SVs in cattle evolution.

Water dynamics in human cancer and non-cancer tissues.

Normal-to-malignant transformation is a poorly understood process associated with cellular biomechanical properties. These are strongly dependent on the dynamical behaviour of water, known to play a fundamental role in normal cellular activity and in the maintenance of the three-dimensional architecture of the tissue and the functional state of biopolymers. In this study, quasi-elastic neutron scattering was used to probe the dynamical behaviour of water in human cancer specimens and their respective surrounding normal tissue from breast and tongue, as an innovative approach for identifying particular features of malignancy. This methodology has been successfully used by the authors in human cells and was the first study of human tissues by neutron scattering techniques. A larger flexibility was observed for breast versus tongue tissues. Additionally, different dynamics were found for malignant and non-malignant specimens, depending on the tissue: higher plasticity for breast invasive cancer versus the normal, and an opposite effect for tongue. The data were interpreted in the light of two different water populations within the samples: one displaying bulk-like dynamics (extracellular and intracellular/cytoplasmic) and another with constrained flexibility (extracellular/interstitial and intracellular/hydration layers).

No effect of combined tele-exercises and nutritional coaching on anthropometric, body composition or exercise capacity outcomes in overweight and obese women: a randomized clinical trial / Ningún efecto de la combinación de ejercicios a distancia y entrenamiento Nutricional sobre los resultados antropométricos, de composición corporal o de capacidad de ejercicio en mujeres con sobrepeso y obesidad: un ensayo clínico aleatorizado

Background: we aimed to investigate the isolated effect of tele-exercises (TE) and their combined effect with nutritional coaching (NC) on health-related parameters of overweight and obese individuals. Methods: forty-one overweight (body mass index ≥ 25 kg/m2) and obese (body mass index ≥ 30 kg/m2) women were randomly assigned to the experimental groups: TE (n = 20) or TE+NC (n = 21). TE was applied 3 days/week in both groups, while TE+NC also received NC 1 day/week. Anthropometric, body composition, and exercise capacity-related outcomes, quality of life, and eating behavior were assessed before and after 8 weeks of the intervention. Results: a significant main time effect (p < 0.01) was detected for flexibility, isometric muscle strength and dynamic muscle endurance, but no main group effect was noted (p > 0.05). On the other hand, neither a significant main time nor group effect (p > 0.05) was detected in the anthropometric and body composition measures, quality of life, or eating behavior. Similarly, no significant between-group difference was observed in the absolute or relative change analysis (all comparisons, p > 0.05). Conclusions: an 8-week TE program enhanced exercise capacity, but did not impact anthropometric or body composition-related outcomes. The combination of NC+TE did not have a clinical advantage in the management of overweight and obesity (AU)

Introducción: nuestro objetivo fue investigar el efecto aislado de los tele-ejercicios (TE) y su efecto combinado con el coaching Nutricional (CN) sobre los parámetros relacionados con la salud de las personas con sobrepeso y obesidad. Métodos: cuarenta y una mujeres con sobrepeso (índice de masa corporal ≥ 25 kg/m2) y obesas (índice de masa corporal ≥ 30 kg/m2) fueron asignadas aleatoriamente a los grupos experimentales: TE (n = 20) o TE+CN (n = 21). La TE se aplicó 3 días/semana en ambos grupos, mientras que el grupo TE+CN también recibió NC 1 día/semana. Se evaluaron los resultados antropométricos, la composición corporal y la capacidad de ejercicio, la calidad de vida y la conducta alimentaria antes y después de 8 semanas de intervención. Resultados: se detectó un efecto de tiempo principal significativo (p < 0,01) para la flexibilidad, la fuerza muscular isométrica y la resistencia muscular dinámica, pero no se observó ningún efecto de grupo principal (p > 0,05). Por otro lado, no se detectó ningún efecto de tiempo principal ni de grupo significativo (p > 0,05) en las medidas antropométricas y de composición corporal, calidad de vida o conducta alimentaria. De manera similar, no se observaron diferencias significativas entre los grupos en el análisis del cambio absoluto o relativo (todas las comparaciones, p > 0,05). Conclusiones: un programa de TE de 8 semanas mejoró la capacidad de ejercicio pero no afectó los resultados antropométricos o relacionados con la composición corporal. La combinación de CN + TE no obtuvo ninguna ventaja clínica en el manejo del sobrepeso y la obesidad (AU)

Depressive symptomatology, temperament and oxytocin serum levels in a sample of healthy female university students.

BACKGROUND: Depressive symptomatology is prevalent among female university students with adverse effects on their quality of life and academic performance. Previous research suggested associations between depressive symptomatology and oxytocin levels and between depressive symptomatology and Temperament Traits. Despite this evidence, to the best of our knowledge no research has studied the effects fboth oxytocin serum levels and temperament dimensions on depressivesymptoms in a healthy sample. The present study aimed to analyse the effect of oxytocin levels and temperament traits on depressive symptomatology in healthy female university students. METHODS: All participants completed the Beck Depression Inventory and the Adult Temperament Questionnaire. Blood samples were collected between 8 and 8H30 a.m. after 12 h of fasting and between 5 and 8 day of the menstrual cycle and serum oxytocin levels were quantified using a commercial enzyme-linked immunosorbent assay. A hierarchical multiple regression model using a stepwise method was conducted to identify predictors of depression. RESULTS: Forty-five women aged between 18 and 25 years old (19.37 ± 1.32 years) volunteered to participate in this study. Depressive symptomatology was negatively associated with oxytocin serum levels and "Negative affect" and positively associated with "Effortful control" and "Activation Control". In the final regression model, only oxytocin level was a predictor (B = - 0.090, p < 0.0001), the model explaining 65.2% of the depression variation. Oxytocin played a mediation role between "Negative affects" and Depressive symptomatology. CONCLUSIONS: Our results showed that oxytocin level, rather than personality dimensions, was associated with depressive symptomatology. These results highlight the relevance of the discussion on the use of oxytocin as a biological marker of emotional and social symptoms that characterize depression.

Acute stress anticipates and amplifies the luteinizing hormone pre-ovulatory surge in rats: Role of noradrenergic neurons.

The stress experienced during rape seems to facilitate ovulation since the pregnancy rate in raped women is higher than that resulting from consensual intercourse. Adrenal progesterone, as well as central norepinephrine, is released in stressful situations. At adequate estrogenic levels, one of the main actions of progesterone is to anticipate the preovulatory LH surge through noradrenaline release. We aimed to investigate whether acute stresses that mimic those of rape (exposure to predator, restraint and cervix stimulation) applied on the proestrus morning in female rats could release progesterone, activate the noradrenergic neurons and facilitate the occurrence of the LH surge. Female rats were submitted to jugular vein cannulation immediately following acute stress: restraint (R), exposure to cat (P), uterine cervix stimulation (CS) applied individually or in association (SA). Non-stressed rats were used as control. Blood samples were collected from 11:00-18:00 h for LH, progesterone, corticosterone and estradiol measurements. Double labeling for c-Fos and tyrosine hydroxylase (TH) was examined in A1, A2 and A6 noradrenergic neurons after stresses. The SA group showed a greater stress-induced increase in progesterone compared to the other groups and the preovulatory LH surge was anticipated and amplified. This effect of SA seems to be related to the higher number of c-Fos/TH + neurons in the A1 and A2. The effect of anticipating the preovulatory surge of LH could in part elucidate why, in raped women, conception can occur in phases of the menstrual cycle other than the ovulatory phase facilitating the occurrence of pregnancies.

The complementary value of intraoperative fluorescence imaging and Raman spectroscopy for cancer surgery: combining the incompatibles.

A clear margin is an important prognostic factor for most solid tumours treated by surgery. Intraoperative fluorescence imaging using exogenous tumour-specific fluorescent agents has shown particular benefit in improving complete resection of tumour tissue. However, signal processing for fluorescence imaging is complex, and fluorescence signal intensity does not always perfectly correlate with tumour location. Raman spectroscopy has the capacity to accurately differentiate between malignant and healthy tissue based on their molecular composition. In Raman spectroscopy, specificity is uniquely high, but signal intensity is weak and Raman measurements are mainly performed in a point-wise manner on microscopic tissue volumes, making whole-field assessment temporally unfeasible. In this review, we describe the state-of-the-art of both optical techniques, paying special attention to the combined intraoperative application of fluorescence imaging and Raman spectroscopy in current clinical research. We demonstrate how these techniques are complementary and address the technical challenges that have traditionally led them to be considered mutually exclusive for clinical implementation. Finally, we present a novel strategy that exploits the optimal characteristics of both modalities to facilitate resection with clear surgical margins.