Fotopic and scotopic retinal sensitivity and foveal fixation normal values using microperimetry in healthy population.

PURPOSE: To determine normal values of fotopic and scotopic retinal sensitivity and foveal fixation obtained by microperimetry, using MP3-S microperimeter (Nidek, Gamagori, Japan), in a healthy population. METHODS: Observational, crossectional, single centre study. Fotopic and scotopic microperimetry was performed using with a customized 13-point fovea-centered pattern in healthy volunteers without ocular pathology. A intraclass correlation coefficient (ICC) was performed to evaluate fotopic and scotopic microperimetry reliability. RESULTS: We analyzed 102 eyes of 54 patients with a mean age of 49.8 +/- 15 years old. The fotopic and scotopic mean retinal sensitivity (MRS) was 28.55±3.3dB (95% CI=[27.87-29.23]) and 15.72±1.9dB (95% CI=[15.35-16.09]) respectively, showing a significant statistical difference (p<0.05). No differences were found when comparing SRM by gender group. However, when analyzing the SRM by age groups, statistically significant differences were found in both modalities of the test; SRM being higher in the group of subjects under 35 years of age with 30.3±1.7dB in the photopic and 16.3±1.3dB in the scotopic; and lower in the group of older than 65 years with 26.7±2.2dB in the photopic and 13.8±1.8dB in the scotopic with p=0.0001. The reliability analysis of both tests, revealed an excellent reliability of the fotopic microperimetry with a Crombach alpha of 0.958 and a good reliability of 0.841 in scotopic microperimetry. CONCLUSIONS: Microperimetry is a test with good reliability both under photopic and scotopic conditions. SRM and fixation stability under photopic and scotopic conditions do not differ according to sex, but it does decrease with age. There is a positive correlation between photopic and scotopic SRM.

Early-life stress elicits peripheral and brain immune activation differently in wild type and 5xFAD mice in a sex-specific manner.

BACKGROUND: The risk of developing Alzheimer's disease (AD) is modulated by genetic and environmental factors. Early-life stress (ELS) exposure during critical periods of brain development can impact later brain function and health, including increasing the risk of developing AD. Microglial dysfunction and neuroinflammation have been implicated as playing a role in AD pathology and may be modulated by ELS. To complicate matters further, sex-specific effects have been noted in response to ELS and in the incidence and progression of AD. METHODS: Here, we subjected male and female mice with either a wild type or 5xFAD familial AD-model background to maternal separation (MS) from postnatal day 2 to 14 to induce ELS. RESULTS: We detected hippocampal neuroinflammatory alterations already at postnatal day 15. By 4 months of age, MS mice presented increased immobility time in the forced swim test and a lower discrimination index in the novel object recognition memory test compared to controls. We found altered Bdnf and Arc expression in the hippocampus and increased microglial activation in the prefrontal cortex due to MS in a sex-dependent manner. In 5xFAD mice specifically, MS exacerbated amyloid-beta deposition, particularly in females. In the periphery, the immune cell population was altered by MS exposure. CONCLUSION: Overall, our results demonstrate that MS has both short- and long-term effects on brain regions related to memory and on the inflammatory system, both in the brain and periphery. These ELS-related effects that are detectable even in adulthood may exacerbate pathology and increase the risk of developing AD via sex-specific mechanisms.

Continuous thoracic paravertebral analgesia after minimally invasive atrial septal defect closure surgery in pediatric population: Effectiveness and safety analysis.

INTRODUCTION: Lateral thoracotomy is replacing traditional median sternotomy for atrial septal defect (ASD) closure in children in order to improve cosmetic outcomes. Continuous paravertebral block has been described as an effective and safe analgesic technique in children. The aim of this study is to assess pain management by continuous perfusion of local anesthetic through a thoracic paravertebral catheter (PVC) in a pediatric population after thoracotomy closure of ASD, and its effectiveness in a fast-track program. METHODS: Descriptive cross-sectional study. Analgesic effectiveness, perioperative and safety-related data were analyzed in 21 patients who underwent thoracotomy closure of ASD with PVC. In the postoperative period, patients received continuous perfusion of bupivacaine 0.125% and fentanyl (1 mcg.ml-1) at 0.2 ml.kg-1.h-1 through the PVC. RESULTS: The median of mean pain scale score for each patient was 1.5. All patients were extubated in the operating theatre. No patient with PVC required opioid rescue. The median length of stay in the Pediatric Intensive Care Unit was 48 hours. There were 3 adverse events related to PVC: 1 due to malposition and 2 due to accidental removal. No other complications or cases of local anesthetic toxicity were recorded. CONCLUSIONS: PVC provides effective, safe, opioid-saving analgesia in the postoperative period of ASD closure by thoracotomy in the context of a fast-track protocol.

Patients with initial nodal involvement due to breast cancer who have received neoadjuvant chemotherapy: Combined sentinel node-radioguided surgery of the pathological node.

OBJECTIVE: To study the feasibility and usefulness of ultrasound-guided pre-chemotherapy marking of pathologic lymph node followed by sentinel lymph node biopsy (SLNB)-pathologic node radioguided biopsy (ROLL) combined technique, in axillary involvement breast cancer patients undergoing neoadjuvant chemotherapy (NACT). MATERIAL AND METHODS: Prospective diagnostic study of 30 patients with breast cancer and cN1 axillary staging with NACT indication. Before NACT, the biopsied node was marked with a clip (MBN). After NACT an ultrasound was performed and in case of good response a SLNB (99mTc-nanocolloids) plus targeted axillary dissection MBN ROLL biopsy (99mTc-albumin macroaggregates) was performed. Axillary lymph node dissection (ALND) was performed if SLNB and/or MBN were positive for tumor cells. The localization-removal rate of the sentinel lymph node (SLN) and MBN were evaluated. False-negative rate (FNR) and positive predictive value (PPV) of SLNB alone were also evaluated. RESULTS: Thirty patients were included in the study. SLN could be detected in all patients while MBN was successfully removed in 27 (90%). The SLN coincided with MBN in 15 patients (50%). In 12 patients SLNB was negative while MBN positive, leading to a FNR of 44.4% for SLNB alone. We found a PPV of 37% for the SLNB. In 5 patients (18.5%) both SLNB and MBN were negative, avoiding ALND. CONCLUSIONS: SLNB-MBN radioguided biopsy ROLL combined technique is a useful and accessible procedure for accurate axillary restaging after NACT, avoiding the high rate of FNR of SLNB alone in this group of patients and avoiding a great number of ALND.

Anesthetic planning and management for a caesarian section in a pregnant woman affected by SARS-COV-2 pneumonía. / Planificación y manejo anestésico para cesárea en gestante con neumonía por SARS-CoV-2.

Pregnant women experience physiological and immunological changes which make them more prone to all kind of viral and bacterial infections, this is because they have been considered as vulnerable group if infected by SARS-CoV-2. They could even deploy a severe form of this disease which may require to end pregnancy to improve oxygenation and to safeguard foetal wellbeing the in case the mother situation gets worse. In this scenario, any intervention would require a detailed planning by the whole surgical team, and, specifically, by the anaesthesiologists, in order to guarantee both mother and child wellbeing and to prevent from infections all the healthcare team. We describe the case of 37week pregnant woman, admitted in our Critical Care Unit with respiratory high flows device support, due to severe respiratory failure due to COVID-19 which needed an urgent caesarean section.

Endotracheal intubation through laryngeal Ambu® Auragain™ mask airway mask in paediatric patients affected by congenital infiltrating lipomatosis. / Intubación orotraqueal a través de mascarilla laríngea Ambu® Auragain™ en paciente pediátrico con lipomatosis infiltrante congénita.

Congenital defects that affect paediatric airway could lead to several difficulties for effective ventilation, intubation, or even both, increasing the risk of hypoxaemia. It is essential for the paediatric anaesthesiologist to have accurate knowledge of the anatomy of patient́s airway, as well as judicious preoperative planning. Increasingly, more devices have been designed for the control of difficult airway in the paediatric patient. This case report describes the application of a third-generation laryngeal mask (- Ambu® Auragain ™) for endotracheal intubation of a child with anticipated difficult airway, secondary to congenital diffuse infiltrating facial lipomatosis.

Biomechanical Description of Phonation in Children Affected by Williams Syndrome.

The voice of persons with Williams syndrome (WS) is described as hoarse with a deep and unstable fundamental frequency (f0). These observations may be justified by the deficit of elastin due to a haplo-insufficiency in the ELN gene characteristic of the syndrome. In view of the possible relationship between elastin deficit and dysphonia, a study of the dynamic function of WS phonation was conducted by means of biomechanical analysis. In order to assess the presence of dysphonic symptoms and their degree of severity, the biomechanical description of WS phonation has been evaluated in terms of dynamic mass and viscoelasticity estimates. Glottal biomechanical features such as vocal fold dynamic mass, stiffness, unbalances, and laryngeal tremor of 12 children with WS aged 3 to 8 years (five girls and seven boys) have been estimated and compared with the normative phonation of 97 children with typical development (53 girls and 44 boys). The results show that WS children show differences in f0, vocal fold mass and stiffness, phonation stability, glottal contact defects, and laryngeal tremor. The conclusions may help to make a more complete view of the connection between WS and dysphonia based on objective assessments.

Results and functional outcomes of acute ischemic stroke patients who underwent mechanical thrombectomy admitted to intensive care unit. / Resultados y evolución funcional de pacientes críticos con ictus isquémico sometidos a trombectomía mecánica.

PURPOSE: To study the results and complications of endovascular treatment (EVT) in acute ischemic stroke patients admitted to Intensive Care Unit (ICU). To analyse the possible factors related to mortality and level of disability at ICU discharge and one year after stroke. DESIGN: Observational prospective study. SETTING: Mixed ICU. Third level hospital. PATIENTS: Sixty adult patients. Consecutive sample. INTERVENTIONS: None. VARIABLES OF INTEREST: Epidemiological data, time from symptom onset to EVT, angiographic result, length of stay, days on mechanical ventilation, neurological complications, National Institutes of Health Stroke Scale (NIHSS) at ICU admission and discharge, modified Rankin scale score (mRS) at one year. RESULTS: Mean age 68,90±8,84years. Median time from symptom onset to EVT: 180minutes. Median NIHSS at admission: 17,5; at discharge: 3. Distal flow was achieved in 90% of cases. Median ICU stay: 3 days. Mechanical ventilation: 81,7.%. Functional independence (mRS≤2) 50% at one year. Deaths: 22 (36,6%) of which 8 (13,3%) died during UCI stay and the rest during the first year. CONCLUSIONS: The factors relating to a worse functional outcome were symptomatic hemorrhage transformation, lack of recanalization and complications during EVT. The factors relating to mortality were symptomatic hemorrhage and hydrocephalus. Distal flow was achieve in most cases with a low complication rate. Half of the patients presented functional independence one year after the stroke.

Dissolution/permeation: The importance of the experimental setup for the prediction of formulation effects on fenofibrate in vivo performance.

The evaluation of formulation strategies in early drug development requires in vitro methods that correctly predict oral drug absorption. The present study aimed to define key parameters for the predictability of dissolution/permeation experiments. Dissolution/permeation experiments were performed in various setups. The IDAS1 chamber, Ussing chamber, and transwells were used as Caco-2 cell based dissolution/permeation models to study the impact of chamber volumes and vertical or horizontal membrane orientation. Dissolution/permeation experiments in Ussing chambers with excised rat intestine were performed to depict the impact of the permeation membrane. Fenofibrate served as model compound in formulations of different particle size. Caco-2 cell based dissolution/permeation experiments with a vertical membrane orientation correctly depicted the formulation effect seen in vivo. The chamber volumes did not affect the outcome. A horizontal membrane orientation achieved no distinction. Experiments using excised rat intestinal sheets did not distinguish between the formulations, and the permeation was much lower than across Caco-2 cells. Mucus might present an artificially enhanced barrier for fenofibrate. Factors that greatly affected the predictivity of the dissolution/permeation experiments were thus the type and orientation of the permeation membrane, whereas chamber volumes only had a minor influence. Vertically mounted Caco-2 cells resulted in the best formulation distinction.

Bmi1 limits dilated cardiomyopathy and heart failure by inhibiting cardiac senescence.

Dilated cardiomyopathy (DCM) is the most frequent cause of heart failure and the leading indication for heart transplantation. Here we show that epigenetic regulator and central transcriptional instructor in adult stem cells, Bmi1, protects against DCM by repressing cardiac senescence. Cardiac-specific Bmi1 deletion induces the development of DCM, which progresses to lung congestion and heart failure. In contrast, Bmi1 overexpression in the heart protects from hypertrophic stimuli. Transcriptome analysis of mouse and human DCM samples indicates that p16(INK4a) derepression, accompanied by a senescence-associated secretory phenotype (SASP), is linked to severely impaired ventricular dimensions and contractility. Genetic reduction of p16(INK4a) levels reverses the pathology of Bmi1-deficient hearts. In parabiosis assays, the paracrine senescence response underlying the DCM phenotype does not transmit to healthy mice. As senescence is implicated in tissue repair and the loss of regenerative potential in aging tissues, these findings suggest a source for cardiac rejuvenation.

[Immunohistochemical markers in the diagnosis of pigmented conjunctival lesions]. / Utilidad de marcadores inmunohistoquímicos para el diagnóstico de lesiones pigmentadas conjuntivales.

OBJECTIVE/METHOD: The aim of this study was to assess the importance of immunohistochemical markers in the diagnosis of pigmented conjunctival lesions. Due to the difficulty of making an exact clinical diagnosis, the suspicion of malignancy requires the removal of the lesion and performing a histopathology study in which immunohistochemical markers may help to determine the nature of the lesion. CASES REPORT/DISCUSSION: A case is presented of a 25 year-old woman with a pigmented lesion in the caruncle. It appeared recently and was growing fast with increasing pigmentation. Due to a suspicion of malignancy, the total lesion was removed. The microscopic study revealed cellular alterations which suggested malignancy. However, after carrying out immunohistochemical markers the diagnosis was conjunctival compound nevus.

[Effects of contrast, eccentricity and position in the detection of visual stimuli in humans]. / Efectos del contraste, excentricidad y posicion en la deteccion de estimulos visuales en humanos.

INTRODUCTION: Contrast, eccentricity and position of stimuli used on research of attention in human vision strongly vary among studies. AIM. To study how contrast, eccentricity and position affects detection of stimuli in humans. SUBJECTS AND METHODS: In adults with normal vision, we measured response times to stimuli (gray circles of 0.5 masculine of diameter) presented at random at eight polar coordinates, in three eccentricities with respect of fixation point (2.15, 3.83 and 5.53 masculine) and with three levels of contrast (6, 16 and 78%). RESULTS: Stimuli with eccentricity of 5.38 masculine and 6% of contrast showed the longest response times. In all eccentricities studied, longer response times were found with stimuli of 6% of contrast. Response times of stimuli of 16% and 78% of contrast showed similar response times in all eccentricities studied. Response times founded at eight polar coordinates were heterogeneous at eccentricities of 2.15 and 5.53 masculine, but not at 3.83 masculine. CONCLUSIONS: Contrast is the factor that most influence detection of visual stimuli used in this study, particularly at the biggest eccentricity employed. Response times among polar coordinates are also affected by eccentricities of 2.15 and 5.53 masculine, suggesting that distance of stimuli to fixation point is critical for visual detection of stimuli.

Evaluación de los efectos antioxidante, antibacteriano y antifúngico de Calophyllum Brasilense Cambes (Lagarto Caspi) / Evaluation of antioxidant effects, antibacterial and antifungal Brasilense Calophyllum Cambes (Caspi Lizard)

Objetivo: Evaluar el efecto antibacteriano, antifúngico y antioxidante de diferentes extractos del Calophyllum brasiliense Cambess. Material y Métodos: El efecto antioxidante fue determinado por captación de radicales libres, midiendo la decoloración de una solución de 2,2-difenil-1-picril hidrazilo (DPPH); La actividad antibacteriana y antifúngica, in Vitro, se determinó mediante la prueba de dilución. El efecto antibacteriano se evaluó en cepas de E. coli ATCC25922 y Staphylococcus aureus ATCC25923, utilizando medios de cultivo: Caldo y Agar Mueller Hinton. Para evaluar el efecto antifúngico, se utilizó cepas de Cándida albicans en medio de Agar Sabouraud. Resultados: La actividad antioxidante de los extractos acuoso, metanólico y etanólico fue muy satisfactoria, siendo de 110.56 por ciento, 99.17 por ciento y 99.57 por ciento, respectivamente, a una concentración de 100 ug/mL, en comparación con la Vitamina C que presentó 86,5 por ciento. Asimismo, observamos un buen efecto antifúngico para los extractos acuoso y etanólico al 20 por ciento p/v a los volúmenes de 3, 3.5 y 4mL. y en el caso del extracto etanólico también presentó un buen efecto a una concentración del 10 por ciento a un volumen de 1.6mL. Conclusiones: Los extractos: acuoso, metanólico y etanólico, presentaron un buen efecto antioxidante y antifúngico, en las cepas estudiadas.

Objetive: To evaluate, in vitro, the antibacterial, antifungal andantioxidant effects of different extracts of Calophyllum brasiliense Cambess. Material and Methods: The antioxidant effect was tested by free radicals capture, measuring discoloration of the 2,2-diphenyl-1-pycryl hydrazyle solution (DPPH). We used a dilution to measure antibacterial and antifungal in vitro activity. Strains of E. coli ATCC25922 and Staphylococcus aureus ATCC25923 were used to evaluate antibacterial effect; using Broth and Mueller Hinton Agar as culture medium. Strains of Candida albicans and Agar Sabouraud as culture medium were usedto evaluate antifungal effect. Results: Aqueous, methanolic and ethanolic extracts, showed good antioxidant activity having 110.56 per cent, 99.17 per cent and 99.57 per cent of antioxidant activity at 100 ug/mL concentration, respectively. This is superior to the vitamin C referencepattern that showed 86,5 per cent activity. Good antifungal effect for aqueous and ethanol extracts at a 20 per cent concentration for 3, 3.5 and 4 ml of volume was determined. Ethanol extracts had the same antifungal effect at a 10 per cent concentration for 1.6mL. of volume. Conclusions: The aqueous, methanolic and ethanolic extracts showed a good antioxidant and antifungal activity on the strains studied.

Assessing the absorption of new pharmaceuticals.

The advent of more efficient methods to synthesize and screen new chemical compounds is increasing the number of chemical leads identified in the drug discovery phase. Compounds with good biological activity may fail to become drugs due to insufficient oral absorption. Selection of drug development candidates with adequate absorption characteristics should increase the probability of success in the development phase. To assess the absorption potential of new chemical entities numerous in vitro and in vivo model systems have been used. Many laboratories rely on cell culture models of intestinal permeability such as, Caco-2, HT-29 and MDCK. To attempt to increase the throughput of permeability measurements, several physicochemical methods such as, immobilized artificial membrane (IAM) columns and parallel artificial membrane permeation assay (PAMPA) have been used. More recently, much attention has been given to the development of computational methods to predict drug absorption. However, it is clear that no single method will sufficient for studying drug absorption, but most likely a combination of systems will be needed. Higher throughput, less reliable methods could be used to discover 'loser' compounds, whereas lower throughput, more accurate methods could be used to optimize the absorption properties of lead compounds. Finally, accurate methods are needed to understand absorption mechanisms (efflux-limited absorption, carrier-mediated, intestinal metabolism) that may limit intestinal drug absorption. This information could be extremely valuable to medicinal chemists in the selection of favorable chemo-types. This review describes different techniques used for evaluating drug absorption and indicates their advantages and disadvantages.