The Rise and Current Status of Polaritonic Photochemistry and Photophysics.

The interaction between molecular electronic transitions and electromagnetic fields can be enlarged to the point where distinct hybrid light-matter states, polaritons, emerge. The photonic contribution to these states results in increased complexity as well as an opening to modify the photophysics and photochemistry beyond what normally can be seen in organic molecules. It is today evident that polaritons offer opportunities for molecular photochemistry and photophysics, which has caused an ever-rising interest in the field. Focusing on the experimental landmarks, this review takes its reader from the advent of the field of polaritonic chemistry, over the split into polariton chemistry and photochemistry, to present day status within polaritonic photochemistry and photophysics. To introduce the field, the review starts with a general description of light-matter interactions, how to enhance these, and what characterizes the coupling strength. Then the photochemistry and photophysics of strongly coupled systems using Fabry-Perot and plasmonic cavities are described. This is followed by a description of room-temperature Bose-Einstein condensation/polariton lasing in polaritonic systems. The review ends with a discussion on the benefits, limitations, and future developments of strong exciton-photon coupling using organic molecules.

Room Temperature Exciton-Polariton Condensation in Silicon Metasurfaces Emerging from Bound States in the Continuum.

We show the first experimental demonstration of room-temperature exciton-polariton (EP) condensation from a bound state in the continuum (BIC). This demonstration is achieved by strongly coupling stable excitons in an organic perylene dye with the extremely long-lived BIC in a dielectric metasurface of silicon nanoparticles. The long lifetime of the BIC, mainly due to the suppression of radiation leakage, allows for EP thermalization to the ground state before decaying. This property results in a condensation threshold of less than 5 µJ cm-2, 1 order of magnitude lower than the lasing threshold reported in similar systems in the weak coupling limit.

Automatic Segmentation and Quantification of Nigrosome-1 Neuromelanin and Iron in MRI: A Candidate Biomarker for Parkinson's Disease.

BACKGROUND: There is a lack of automated tools for the segmentation and quantification of neuromelanin (NM) and iron in the nigrosome-1 (N1). Existing tools evaluate the N1 sign, i.e., the presence or absence of the "swallow-tail" in iron-sensitive MRI, or globally analyze the MRI signal in an area containing the N1, without providing a volumetric delineation. PURPOSE: Present an automated method to segment the N1 and quantify differences in N1's NM and iron content between Parkinson's disease (PD) patients and healthy controls (HCs). Study whether N1 degeneration is clinically related to PD and could be used as a biomarker of the disease. STUDY TYPE: Prospective. SUBJECTS: Seventy-one PD (65.3 ± 10.3 years old, 34 female/37 male); 30 HC (62.7 ± 7.8 years old, 17 female/13 male). FIELD STRENGTH/SEQUENCE: 3 T Anatomical T1-weighted MPRAGE, NM-MRI T1-weighted gradient with magnetization transfer, susceptibility-weighted imaging (SWI). ASSESSMENT: N1 was automatically segmented in SWI images using a multi-image atlas, populated with healthy N1 structures manually annotated by a neurologist. Relative NM and iron content were quantified and their diagnostic performance assessed and compared with the substantia nigra pars compacta (SNc). The association between image parameters and clinically relevant variables was studied. STATISTICAL TESTS: Nonparametric tests were used (Mann-Whitney's U, chi-square, and Friedman tests) at P = 0.05. RESULTS: N1's relative NM content decreased and relative iron content increased in PD patients compared with HCs (NM-CRHC = 22.55 ± 1.49; NM-CRPD = 19.79 ± 1.92; NM-nVolHC = 2.69 × 10-5 ± 1.02 × 10-5 ; NM-nVolPD = 1.18 × 10-5 ± 0.96 × 10-5 ; Iron-CRHC = 10.51 ± 2.64; Iron-CRPD = 19.35 ± 7.88; Iron-nVolHC = 0.72 × 10-5 ± 0.81 × 10-5 ; Iron-nVolPD = 2.82 × 10-5 ± 2.04 × 10-5 ). Binary logistic regression analyses combining N1 and SNc image parameters yielded a top AUC = 0.955. Significant correlation was found between most N1 parameters and both disease duration (ρNM-CR = -0.31; ρiron-CR = 0.43; ρiron-nVol = 0.46) and the motor status (ρNM-nVol = -0.27; ρiron-CR = 0.33; ρiron-nVol = 0.28), suggesting NM reduction along with iron accumulation in N1 as the disease progresses. DATA CONCLUSION: This method provides a fully automatic N1 segmentation, and the analyses performed reveal that N1 relative NM and iron quantification improves diagnostic performance and suggest a relative NM reduction along with a relative iron accumulation in N1 as the disease progresses. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Perinatal outcomes in young women with breast cancer and pregnancy.

INTRODUCTION: Breast cancer associated with pregnancy is defined as a malignant neoplasm of the breast that is diagnosed during pregnancy, breastfeeding or one year after delivery. OBJECTIVE: To analyze perinatal outcomes in a series of young patients with breast cancer and pregnancy in a tertiary care hospital. METHODS: Retrospective, analytical study of 26 women younger than 40 years of age with breast cancer who resolved their pregnancy at the National Institute of Perinatology between 2013 and 2018. Clinical-pathological characteristics, perinatal outcomes and family planning methods were studied. Percentages and central tendency measures were obtained, and comparisons were made with the chi-square test or Fisher's exact test. RESULTS: Association of breast cancer with pregnancy was observed in 0.26% of all births; mean age of presentation was 34 years, 38.4% of cases had cancer at advanced clinical stages and 57.1% of the women were treated with modified radical mastectomy; no trend towards higher perinatal complications was observed. CONCLUSIONS: Breast cancer associated with pregnancy implies an oncological challenge and does not appear to be a risk factor for adverse perinatal outcomes.

INTRODUCCIÓN: El cáncer de mama asociado a embarazo se define como la neoplasia maligna de mama que se diagnostica durante el embarazo, la lactancia o un año después del parto. OBJETIVO: Analizar los resultados perinatales en una serie de pacientes jóvenes con cáncer de mama y embarazo en un hospital de tercer nivel. MÉTODOS: Estudio analítico retrospectivo de 26 mujeres menores de 40 años con cáncer de mama que resolvieron su embarazo en el Instituto Nacional de Perinatología entre 2013 y 2018. Se estudiaron las características clínico-patológicas, resultados perinatales y métodos de planificación familiar. Se obtuvieron porcentajes y medidas de tendencia central y se realizaron comparaciones con pruebas de chi cuadrada o exacta de Fisher. RESULTADOS: La asociación de cáncer de mama y embarazo se observó en 0.26 % de todos los nacimientos, la edad media de presentación fue de 34 años, 38.4 % de los casos cursaba con cáncer en estadio clínico avanzado y 57.1 % de las mujeres fueron tratadas con mastectomía radical modificada; no se apreció tendencia a mayores complicaciones perinatales. CONCLUSIONES: El cáncer de mama asociado a embarazo implica un reto oncológico y no parece ser un factor de riesgo para desenlaces perinatales adversos.

Trade-off between frequency and precision during stepping movements: Kinematic and BOLD brain activation patterns.

The central nervous system has the ability to adapt our locomotor pattern to produce a wide range of gait modalities and velocities. In reacting to external pacing stimuli, deviations from an individual preferred cadence provoke a concurrent decrease in accuracy that suggests the existence of a trade-off between frequency and precision; a compromise that could result from the specialization within the control centers of locomotion to ensure a stable transition and optimal adaptation to changing environment. Here, we explore the neural correlates of such adaptive mechanisms by visually guiding a group of healthy subjects to follow three comfortable stepping frequencies while simultaneously recording their BOLD responses and lower limb kinematics with the use of a custom-built treadmill device. In following the visual stimuli, subjects adopt a common pattern of symmetric and anti-phase movements across pace conditions. However, when increasing the stimulus frequency, an improvement in motor performance (precision and stability) was found, which suggests a change in the control mode from reactive to predictive schemes. Brain activity patterns showed similar BOLD responses across pace conditions though significant differences were observed in parietal and cerebellar regions. Neural correlates of stepping precision were found in the insula, cerebellum, dorsolateral pons and inferior olivary nucleus, whereas neural correlates of stepping stability were found in a distributed network, suggesting a transition in the control strategy across the stimulated range of frequencies: from unstable/reactive at lower paces (i.e., stepping stability managed by subcortical regions) to stable/predictive at higher paces (i.e., stability managed by cortical regions). Hum Brain Mapp 37:1722-1737, 2016. © 2016 Wiley Periodicals, Inc.

Resting state functional connectivity of the subthalamic nucleus in Parkinson's disease assessed using arterial spin-labeled perfusion fMRI.

Neurophysiological changes within the cortico-basal ganglia-thalamocortical circuits appear to be a characteristic of Parkinson's disease (PD) pathophysiology. The subthalamic nucleus (STN) is one of the basal ganglia components showing pathological neural activity patterns in PD. In this study, perfusion imaging data, acquired noninvasively using arterial spin-labeled (ASL) perfusion MRI, were used to assess the resting state functional connectivity (FC) of the STN in 24 early-to-moderate PD patients and 34 age-matched healthy controls, to determine whether altered FC in the very low frequency range of the perfusion time signal occurs as a result of the disease. Our results showed that the healthy STN was functionally connected with other nuclei of the basal ganglia and the thalamus, as well as with discrete cortical areas including the insular cortex and the hippocampus. In PD patients, connectivity of the STN was increased with two cortical areas involved in motor and cognitive processes. These findings suggest that hyperconnectivity of the STN could underlie some of the motor and cognitive deficits often present even at early stages of the disease. The FC measures provided good discrimination between controls and patients, suggesting that ASL-derived FC metrics could be a putative PD biomarker.

Automated neuromelanin imaging as a diagnostic biomarker for Parkinson's disease.

BACKGROUND: We aimed to analyze the diagnostic accuracy of an automated segmentation and quantification method of the SNc and locus coeruleus (LC) volumes based on neuromelanin (NM)-sensitive MRI (NM-MRI) in patients with idiopathic (iPD) and monogenic (iPD) Parkinson's disease (PD). METHODS: Thirty-six patients (23 idiopathic and 13 monogenic PARKIN or LRRK2 mutations) and 37 age-matched healthy controls underwent 3T-NM-MRI. SNc and LC volumetry were performed using fully automated multi-image atlas segmentation. The diagnostic performance to differentiate PD from controls was measured using the area under the curve (AUC) and likelihood ratios based on receiver operating characteristic (ROC) analyses. RESULTS: We found a significant reduction of SNc and LC volumes in patients, when compared to controls. ROC analysis showed better diagnostic accuracy when using SNc volume than LC volume. Significant differences between ipsilateral and contralateral SNc volumes, in relation to the more clinically affected side, were found in patients with iPD (P = 0.007). Contralateral atrophy in the SNc showed the highest power to discriminate PD subjects from controls (AUC, 0.93-0.94; sensitivity, 91%-92%; specificity, 89%; positive likelihood ratio: 8.4-8.5; negative likelihood ratio: 0.09-0.1 at a single cut-off point). Interval likelihood ratios for contralateral SNc volume improved the diagnostic accuracy of volumetric measurements. CONCLUSION: SNc and LC volumetry based on NM-MRI resulting from the automated segmentation and quantification technique can yield high diagnostic accuracy for differentiating PD from health and might be an unbiased disease biomarker. © 2015 International Parkinson and Movement Disorder Society.

Brainstem neuromelanin and iron MRI reveals a precise signature for idiopathic and LRRK2 Parkinson's disease.

Neuromelanin (NM) loss in substantia nigra pars compacta (SNc) and locus coeruleus (LC) reflects neuronal death in Parkinson's disease (PD). Since genetically-determined PD shows varied clinical expressivity, we wanted to accurately quantify and locate brainstem NM and iron, to discover whether specific MRI patterns are linked to Leucine-rich repeat kinase 2 G2019S PD (LRRK2-PD) or idiopathic Parkinson's disease (iPD). A 3D automated MRI atlas-based segmentation pipeline (3D-ABSP) for NM/iron-sensitive MRI images topographically characterized the SNc, LC, and red nucleus (RN) neuronal loss and calculated NM/iron contrast ratio (CR) and normalized volume (nVol). Left-side NM nVol was larger in all groups. PD had lower NM CR and nVol in ventral-caudal SNc, whereas iron increased in lateral, medial-rostral, and caudal SNc. The SNc NM CR reduction was associated with psychiatric symptoms. LC CR and nVol discriminated better among subgroups: LRRK2-PD had similar LC NM CR and nVol as that of controls, and larger LC NM nVol and RN iron CR than iPD. PD showed higher iron SNc nVol than controls, especially among LRRK2-PD. ROC analyses showed an AUC > 0.92 for most pairwise subgroup comparisons, with SNc NM being the best discriminator between HC and PD. NM measures maintained their discriminator power considering the subgroup of PD patients with less than 5 years of disease duration. The SNc iron CR and nVol increase was associated with longer disease duration in PD patients. The 3D-ABSP sensitively identified NM and iron MRI patterns strongly correlated with phenotypic PD features.

Inverse designed plasmonic metasurface with parts per billion optical hydrogen detection.

Plasmonic sensors rely on optical resonances in metal nanoparticles and are typically limited by their broad spectral features. This constraint is particularly taxing for optical hydrogen sensors, in which hydrogen is absorbed inside optically-lossy Pd nanostructures and for which state-of-the-art detection limits are only at the low parts-per-million (ppm) range. Here, we overcome this limitation by inversely designing a plasmonic metasurface based on a periodic array of Pd nanoparticles. Guided by a particle swarm optimization algorithm, we numerically identify and experimentally demonstrate a sensor with an optimal balance between a narrow spectral linewidth and a large field enhancement inside the nanoparticles, enabling a measured hydrogen detection limit of 250 parts-per-billion (ppb). Our work significantly improves current plasmonic hydrogen sensor capabilities and, in a broader context, highlights the power of inverse design of plasmonic metasurfaces for ultrasensitive optical (gas) detection.

Time-Delay Latency of Resting-State Blood Oxygen Level-Dependent Signal Related to the Level of Consciousness in Patients with Severe Consciousness Impairment.

Recent evidence on resting-state functional magnetic resonance imaging (rs-fMRI) suggests that healthy human brains have a temporal organization represented in a widely complex time-delay structure. This structure seems to underlie brain communication flow, integration/propagation of brain activity, as well as information processing. Therefore, it is probably linked to the emergence of highly coordinated complex brain phenomena, such as consciousness. Nevertheless, possible changes in this structure during an altered state of consciousness remain poorly investigated. In this work, we hypothesized that due to a disruption in high-order functions and alterations of the brain communication flow, patients with disorders of consciousness (DOC) might exhibit changes in their time-delay structure of spontaneous brain activity. We explored this hypothesis by comparing the time-delay projections from fMRI resting-state data acquired in resting state from 48 patients with DOC and 27 healthy controls (HC) subjects. Results suggest that time-delay structure modifies for patients with DOC conditions when compared with HC. Specifically, the average value and the directionality of latency inside the midcingulate cortex (mCC) shift with the level of consciousness. In particular, positive values of latency inside the mCC relate to preserved states of consciousness, whereas negative values change proportionally with the level of consciousness in patients with DOC. These results suggest that the mCC may play a critical role as an integrator of brain activity in HC subjects, but this role vanishes in an altered state of consciousness.

Super-resolution Mapping of Enhanced Emission by Collective Plasmonic Resonances.

Plasmonic particle arrays have remarkable optical properties originating from their collective behavior, which results in resonances with narrow line widths and enhanced electric fields extending far into the surrounding medium. Such resonances can be exploited for applications in strong light-matter coupling, sensing, light harvesting, nonlinear nanophotonics, lasing, and solid-state lighting. However, as the lattice constants associated with plasmonic particle arrays are on the order of their resonance wavelengths, mapping the interaction between point dipoles and plasmonic particle arrays cannot be done with diffraction-limited methods. Here, we map the enhanced emission of single fluorescent molecules coupled to a plasmonic particle array with ∼20 nm in-plane resolution by using stochastic super-resolution microscopy. We find that extended lattice resonances have minimal influence on the spontaneous decay rate of an emitter but instead can be exploited to enhance the outcoupling and directivity of the emission. Our results can guide the rational design of future optical devices based on plasmonic particle arrays.

Dynamic Atlas-Based Segmentation and Quantification of Neuromelanin-Rich Brainstem Structures in Parkinson Disease.

We present a dynamic atlas composed of neuromelanin-enhanced magnetic resonance brain images of 40 healthy subjects. The performance of this atlas is evaluated on the fully automated segmentation of two paired neuromelanin-rich brainstem healthy structures: the substantia nigra pars compacta and the locus coeruleus. We show that our dynamic atlas requires in average 60% less images and, therefore, 60% less computation time than a static multi-image atlas while achieving a similar segmentation performance. Then, we show that by applying our dynamic atlas, composed of healthy subjects, to the segmentation and neuromelanin quantification of a set of brain images of 39 Parkinson disease patients, we are able to find significant quantitative differences in the level of neuromelanin between healthy subjects and Parkinson disease patients, thus opening the door to the use of these structures as image biomarkers in future computer aided diagnosis systems for the diagnosis of Parkinson disease.

Quantifying Photothermal and Hot Charge Carrier Effects in Plasmon-Driven Nanoparticle Syntheses.

The excitation of localized surface plasmon resonances in Au and Ag colloids can be used to drive the synthesis of complex nanostructures, such as anisotropic prisms, bipyramids, and core@shell nanoparticles. Yet, after two decades of research, it is challenging to paint a complete picture of the mechanisms driving such light-induced chemical transformations. In particular, whereas the injection of hot charge carriers from the metal nanoparticles is usually proposed as the dominant mechanism, the contribution of plasmon-induced heating can often not be neglected. Here, we tackle this uncertainty and quantify the contribution of different activation mechanisms using a temperature-sensitive synthesis of Au@Ag core@shell nanoparticles. We compare the rate of Ag shell growth in the dark at different temperatures with the one under plasmon excitation with varying laser intensities. Our controlled illumination geometry, coupled to numerical modeling of light propagation and heat diffusion in the reaction volume, allows us to quantify both localized and collective heating effects and determine their contribution to the total growth rate of the nanoparticles. We find that nonthermal effects can be dominant, and their relative contribution depends on the fraction of nanoparticle suspension under irradiation. Understanding the mechanism of plasmon-activated chemistry at the surface of metal nanoparticles is of paramount importance for a wide range of applications, from the rational design of novel light-assisted nanoparticle syntheses to the development of plasmonic nanostructures for catalytic and therapeutic purposes.

Guillain-Barré syndrome in patients with a recent history of Zika in Cúcuta, Colombia: A descriptive case series of 19 patients from December 2015 to March 2016.

PURPOSE: Zika virus (ZIKV) infection is an emerging global threat and a public health problem in the Americas. Guillain-Barré syndrome (GBS) has been recently associated to ZIKV. This report presents a case series of GBS possibly associated to ZIKV. METHODS: Clinical and demographic data from patients with GBS treated in 5 intensive care units and with recent history of ZIKV in Cúcuta, Colombia were collected from December 1 2015 to April 30 2016. Electrophysiological examination, lumbar puncture, and reverse transcriptase-polymerase chain reaction for ZIKV were performed in 14, 10, and 1 patients, respectively. RESULTS: Nineteen patients with GBS and a recent history of acute viral syndrome compatible with ZIKV infection were studied (mean age, 44 years; range, 17-78). Neurologic symptoms developed at a median of 10 days after the onset of the viral symptoms. Albuminocytological dissociation was found in 8 cases. Electrophysiological criteria for acute motor axonal neuropathy were found in all patients tested. Five patients met level 1, 8 patients level 2, and 6 patients level 3 of diagnostic certainty for GBS in the Brighton classification. Fifteen patients required respiratory assistance, 16 received intravenous immunoglobulins, and 3 had plasmapheresis. Seventy-nine percent of patients were in Hughes GBS disability scale 4 to 5 at discharge and no patients died during the observation period. Acute ZIKV infection, confirmed by reverse transcriptase-polymerase chain reaction, was observed for 1 patient. CONCLUSIONS: All cases of this GBS outbreak had a recent history ZIKV infection, reinforcing existing evidence for the association between GBS and ZIKV. Future genetic and immunologic studies are warranted to further investigate the cause of the outbreak in detail.

Dominio y aplicación del método clínico por los estudiantes del tercer año de la carrera de Medicina de la Universidad de Ciencias Médicas de Holguín / Mastery and application of the clinical method by third-year students of Medicine Career at Health Sciences University of Holguín

Introducción: la crisis del método clínico es una preocupación constante para los profesionales de la salud porque esta comprende aspectos muy sensibles de la práctica médica y la preparación para su empleo se produce tempranamente en la formación de los estudiantes. Objetivo: determinar el desempeño en la aplicación del método clínico de los estudiantes de tercer año de la carrera de Medicina en la provincia Holguín. Métodos: se realizó un estudio descriptivo con los estudiantes del tercer año de la carrera de Medicina de la Universidad de Ciencias Médicas de Holguín en el curso escolar 2009-2010. La muestra estuvo integrada por 439 estudiantes, el 66,6% de la población estudiada. Se consideraron los resultados obtenidos por los estudiantes en los exámenes prácticos de la asignatura de Medicina Interna. Resultados: el 95% de los alumnos presentaron dificultades en el interrogatorio del paciente, el 92% en el examen físico y el 93,6% no pudieron realizar el diagnóstico correcto. En cuanto a los criterios de los profesores sobre la interrelación interrogatorio-examen físico, análisis complementarios, diagnóstico y conducta, el 46,7% lo consideró regular y el 23,3%, malo. Conclusiones: Los estudiantes del tercer año de la carrera de Medicina carecieron del dominio y aplicaron de manera deficiente el método clínico durante los exámenes prácticos de Medicina Interna.

Introduction: the crisis of the clinical method is a constant concern for all the health professionals as it turns around many sensitive aspects of the medical practice and takes place at an early stage in their formation as doctors. Objective: to determine the role of clinical method application by third-year students of Medicine Career of Holguín province. Methods: A descriptive study in the third-year medical students from the University of Medical Sciences in Holguín was conducted during the school year 2009-2010. The sample comprised 439 students representing 66.6% of the studied population. The results obtained in the practical examinations of Internal Medicine Subject were considered. Results: Ninety-five percent of the students had difficulties in interviewing the patients; 92% had problems in the physical examination and 93.6% had troubles in making the accurate diagnosis. As for the professors' assessment of the interrelation between interview-physical examinations, routine tests, diagnosis and treatment: 46.7% considered it fair and 23.3%, bad. Conclusions: the mastery and the application of the clinical method during the practical examinations of Internal Medicine are deficient, since the students were unable, through the interview and the physical exam, to make a correct diagnosis or develop a logical reasoning of diagnosis-treatment.

Valoraciones sobre la crisis del método clínico en el nuevo milenio / Aassessments on the Crisis of the Clinical Method in the New Millennium

Se valora el deterioro acelerado que experimenta la aplicación del método clínico en la actualidad. Se identifican los aspectos en relación con la aplicación del método clínico en el ejercicio de la práctica médica. Se tratan de manera crítica los aspectos humanos y éticos de la profesión, asociados con la relación médico-paciente, las nuevas tecnologías y su uso. Se expone la crisis actual del método clínico y sus implicaciones para el futuro de la Medicina.

An assessment of the implementation of the clinical method it was performed. The aspects related to its implementation in the medical practice, considering human and ethical aspects of medicine profession that involucrate the doctor-patient relationship and new technology use were identifies. The authors also considered the current crisis of the clinical method and its implications for the future of Medicine.