Enhancing Dynamic Spectral Diffusion in Metal-Organic Frameworks through Defect Engineering.

The crystal packing of organic chromophores has a profound impact on their photophysical properties. Molecular crystal engineering is generally incapable of producing precisely spaced arrays of molecules for use in photovoltaics, light-emitting diodes, and sensors. A promising alternative strategy is the incorporation of chromophores into crystalline metal-organic frameworks (MOFs), leading to matrix coordination-induced emission (MCIE) upon confinement. However, it remains unclear how the precise arrangement of chromophores and defects dictates photophysical properties in these systems, limiting the rational design of well-defined photoluminescent materials. Herein, we report new, robust Zr-based MOFs constructed from the linker tetrakis(4-carboxyphenyl)ethylene (TCPE4-) that exhibit an unexpected structural transition in combination with a prominent shift from green to blue photoluminescence (PL) as a function of the amount of acid modulator (benzoic, formic, or acetic acid) used during synthesis. Time-resolved PL (TRPL) measurements provide full spectral information and reveal that the observed hypsochromic shift arises due to a higher concentration of linker substitution defects at higher modulator concentrations, leading to broader excitation transfer-induced spectral diffusion. Spectral diffusion of this type has not been reported in a MOF to date, and its observation provides structural information that is otherwise unobtainable using traditional crystallographic techniques. Our findings suggest that defects have a profound impact on the photophysical properties of MOFs and that their presence can be readily tuned to modify energy transfer processes within these materials.

Kinetic Trapping of Photoluminescent Frameworks During High-Concentration Synthesis of Non-Emissive Metal-Organic Frameworks.

Metal-organic frameworks (MOFs) are porous, crystalline materials constructed from organic linkers and inorganic nodes with potential utility in gas separations, drug delivery, sensing, and catalysis. Small variations in MOF synthesis conditions can lead to a range of accessible frameworks with divergent chemical or photophysical properties. New methods to controllably access phases with tailored properties would broaden the scope of MOFs that can be reliably prepared for specific applications. Herein, we demonstrate that simply increasing the reaction concentration during the solvothermal synthesis of M2(dobdc) (M = Mg, Mn, Ni; dobdc4- = 2,5-dioxido-1,4-benzenedicarboxylate) MOFs unexpectedly leads to trapping of a new framework termed CORN-MOF-1 (CORN = Cornell University) instead. In-depth spectroscopic, crystallographic, and computational studies support that CORN-MOF-1 has a similar structure to M2(dobdc) but with partially protonated linkers and charge-balancing or coordinated formate groups in the pores. The resultant variation in linker spacings causes CORN-MOF-1 (Mg) to be strongly photoluminescent in the solid state, whereas H4dobdc and Mg2(dobdc) are weakly emissive due to excimer formation. In-depth photophysical studies suggest that CORN-MOF-1 (Mg) is the first MOF based on the H2dobdc2- linker that likely does not emit via an excited state intramolecular proton transfer (ESIPT) pathway. In addition, CORN-MOF-1 variants can be converted into high-quality samples of the thermodynamic M2(dobdc) phases by heating in N,N-dimethylformamide (DMF). Overall, our findings support that high-concentration synthesis provides a straightforward method to identify new MOFs with properties distinct from known materials and to produce highly porous samples of MOFs, paving the way for the discovery and gram-scale synthesis of framework materials.

A Structure-Activity Study of Aromatic Acid Modulators for the Synthesis of Zirconium-Based Metal-Organic Frameworks.

Acid modulation is among the most widely employed methods for preparing metal-organic frameworks (MOFs) that are both stable and highly crystalline, yet there exist few guiding principles for selecting the optimal modulator for a given system. Using the Zr-based MOFs UiO-66 and UiO-68-Me2 (UiO = Universitetet i Oslo) as representative materials, here we present for the first time an in-depth structure-activity study of acid modulators and identify key principles of modulation for the synthesis of highly crystalline Zr-MOFs. By applying whole pattern fitting of powder X-ray diffraction (PXRD) patterns as a technique for evaluating modulator efficacy, complemented by scanning electron microscopy (SEM), 1H NMR, and thermogravimetric analysis (TGA), we demonstrate that the key to effective modulation is competition between the linker and modulator for coordination to the Zr secondary building units (SBUs). Specifically, we illustrate that a close match in pK a and structure between the linker and modulator favors larger and more well-defined crystallites, particularly with sterically unhindered aromatic acid modulators. Based on our findings, we demonstrate that 5-membered heteroaromatic carboxylic acids are among the most efficient acid modulators identified to date for the synthesis of several representative Zr-MOFs with fcu net topologies. In addition, we find that coordination modulation is superior to exogenous acid modulation at higher modulator concentrations. Finally, we compare 1H NMR and TGA as data-driven methods for quantifying linker deficiencies in modulated MOF syntheses. The guiding principles established herein have critical implications for the scalable and controllable synthesis of highly crystalline and stable MOFs relevant to chemical separations, gas storage, and catalysis.

Neuromyelitis optica spectrum disorder in Western Mexico.

BACKGROUND: Neuromyelitis Optica Spectrum Disorders (NMOSD) are a group of inflammatory diseases of the Central Nervous System (CNS) that primarily affect the optic nerve and spinal cord, usually with a severe and relapsing course. Due to the scarce information in non-Caucasian populations, we aimed to describe incidence, prevalence, and main clinical characteristics of NMOSD in a defined region in Mexico. MATERIALS AND METHODS: Descriptive, retrospective analysis of all reported cases of NMOSD attended in the neurology department of the UMAE-HE, CMNO, IMSS, the biggest third level hospital in Western Mexico. We searched the electronic medical records of the hospital for patients with a diagnosis of NMO, and reviewed all cases to confirm if they fulfilled NMOSD 2015 diagnostic criteria. Data were collected through a structured form. We described adjusted incidence and prevalence according to the WHO method, for the IMSS affiliated total population in Jalisco state in 2019. RESULTS: 67 NMOSD patients were included in the analysis of clinical data, with a mean age at onset of symptoms of 36 years ((Rivera et al., 2008-65). Most patients were female (74.6%). 53 patients living in Jalisco by the end of 2019 were included in the analysis of prevalence and incidence. Adjusted prevalence was 0.71/100,000 (95% CI 0.55-0.92), while adjusted incidence was 1.87/1,000,000 person-years (95% CI 1.11-3.16). In the full cohort, the first symptom of NMOSD was optic neuritis in 49.3% of the patients, followed by transverse myelitis (23.9%) and area postrema syndrome (10.4%). 62 patients relapsed in a mean follow-up of 2 years (0-7). 5 patients with less than 6 months of follow up had not relapsed. 55.2% of the patients were AQP4-IgG +, 14.9% AQP4-IgG -, and 29.9% unknown status. CONCLUSIONS: Although NMOSD prevalence is similar to other reports around the world, incidence is higher than in Caucasian populations. We believe that this high incidence is related to an increased awareness of the disease in the era of new NMOSD treatments. Recurrent disease is very frequent in our cohort.

Biocompatible metal-organic frameworks for the storage and therapeutic delivery of hydrogen sulfide.

Hydrogen sulfide (H2S) is an endogenous gasotransmitter with potential therapeutic value for treating a range of disorders, such as ischemia-reperfusion injury resulting from a myocardial infarction or stroke. However, the medicinal delivery of H2S is hindered by its corrosive and toxic nature. In addition, small molecule H2S donors often generate other reactive and sulfur-containing species upon H2S release, leading to unwanted side effects. Here, we demonstrate that H2S release from biocompatible porous solids, namely metal-organic frameworks (MOFs), is a promising alternative strategy for H2S delivery under physiologically relevant conditions. In particular, through gas adsorption measurements and density functional theory calculations we establish that H2S binds strongly and reversibly within the tetrahedral pockets of the fumaric acid-derived framework MOF-801 and the mesaconic acid-derived framework Zr-mes, as well as the new itaconic acid-derived framework CORN-MOF-2. These features make all three frameworks among the best materials identified to date for the capture, storage, and delivery of H2S. In addition, these frameworks are non-toxic to HeLa cells and capable of releasing H2S under aqueous conditions, as confirmed by fluorescence assays. Last, a cellular ischemia-reperfusion injury model using H9c2 rat cardiomyoblast cells corroborates that H2S-loaded MOF-801 is capable of mitigating hypoxia-reoxygenation injury, likely due to the release of H2S. Overall, our findings suggest that H2S-loaded MOFs represent a new family of easily-handled solid sources of H2S that merit further investigation as therapeutic agents. In addition, our findings add Zr-mes and CORN-MOF-2 to the growing lexicon of biocompatible MOFs suitable for drug delivery.

Continuous Visual Focal Status Epilepticus as the Primary Presentation of NMDA-R and GAD65-R Autoimmune Epilepsy.

Epilepsia partialis continua (EPC) has changed in its clinical and pathophysiological definition throughout time. Several etiologies have been described in addition to classic causes of EPC. The following case depicts a young woman who had a peculiar onset of epilepsy with a continuous visual aura becoming a form of chronic recurrent and non-progressive EPC. The patient was initially misdiagnosed as a non-neurological entity (assumed psychiatric in origin), but finally, an immune-mediated epilepsy was diagnosed, and EEG showed focal status epilepticus during evolution. Once the diagnosis was achieved and immune treatment was established, the patient is seizure free. Early identification of an immune basis in patients with epilepsy is important because immunotherapy can reverse the epileptogenic process and reduce the risk of chronic epilepsy. To date, this is the only case reported with EPC manifesting as a continuous visual aura associated with antiglutamic acid decarboxylase 65 (anti-GAD65) and anti-N-methyl-d-aspartate (anti-NMDA) antibodies.

Left ventricular volumes and ejection fraction quantification using an automated three-dimensional adaptive analytic echocardiographic algorithm in pediatric population.

INTRODUCTION: The quantitative measurement of the left ventricle by echocardiography is a fundamental tool in the diagnosis and prognosis of acquired and congenital diseases in the pediatric population. The objective of this study was to validate an automated three-dimensional adaptive analytic echocardiographic algorithm, the so-called Heart Model® (HM) in the pediatric population, using as comparators the left atrial and left ventricular volumes and left ventricular ejection fraction obtained by means of conventional 2D and 3D echocardiography. METHODS: Pilot study, where a population comprised of 75 consecutive patients aged 6-17 years who attended a pediatric cardiology clinic, was evaluated. Every patient underwent a conventional 2D and 3D echocardiography and an analysis using HM. Conventional 3D echo was used as the reference method. RESULTS: Seventy-five patients were analyzed. Mean age was 11.2 (4.0) years (52.2% women). The intraclass correlation coefficient of HM vs 2D echo was poor, but it was good for the agreement between HM and 3D echo for left ventricular end-diastolic volume (ICC: 0.98; 95% CI: 0.97-0.99; P < 0.001), left ventricular end-systolic volume ICC: 0.98; 95% CI: 0.96-0.99; P = 0.001), and left ventricular ejection fraction (ICC: 0.87; 95% CI: 0.78-0.92; P < 0.001). The agreement was also good for the three parameters when the analysis was performed according to body weight. CONCLUSIONS: Heart Model® is a feasible and accurate tool for the evaluation of left atrial and left ventricular volumes and left ventricular ejection fraction in pediatric population aged above 6 years.

Reproducción de Pomacea flagellata (Mollusca: Ampullariidae) en la laguna de Bacalar, Quintana Roo, México / Reproductive aspects of Pomacea flagellata (Mollusca: Ampullariidae) at Bacalar lagoon, Quintana Roo, México

Resumen:Pomacea flagellata es una especie de caracol de agua dulce nativo en el sureste de México. Sobre esta especie existen pocos estudios y en ninguno se han abordado aspectos de su reproducción. Este caracol ha sido explotado durante años en la laguna Bacalar y sus poblaciones han decrecido considerablemente, conllevando a la veda de su captura. Este trabajo se realizó con el objetivo de evaluar las variaciones temporales de la frecuencia de cópulas y la abundancia de masas de huevos de P. flagellata en la laguna de Bacalar, así como sus relaciones con la abundancia de los caracoles y con variables ambientales. Los muestreos fueron realizados durante tres temporadas: Lluvias (julio, agosto y septiembre 2012), Nortes (diciembre 2012, enero y febrero 2013) y Secas (marzo, abril y mayo 2013) en 12 estaciones a lo largo de la laguna de Bacalar. En cada estación, se recorrió un transecto de 100 m paralelo a la orilla y se contó el número de huevas frescas (color rosado) puestas sobre la vegetación, troncos, rocas o estructuras artificiales. En el agua se hicieron tres transectos de 50 x 2 m y en cada uno se contaron los caracoles y se registró el número de cópulas. La densidad de caracoles mostró variaciones significativas entre temporadas, disminuyendo desde la temporada de Lluvias hasta la temporada de Secas. Entre los meses dentro de temporadas no se presentaron diferencias significativas (ANOVA, p>0.05). Durante toda la temporada de Lluvias se registraron cópulas con una frecuencia significativamente mayor que en Nortes, mientras en Secas no se registraron cópulas (Kruskal-Wallis, p˂0.05). La puesta de masas de huevos se extendió de julio a marzo. La densidad de huevas no presentó diferencias entre la temporadas de Lluvias y Nortes (2.72 masas/m y 2.93 masas/m, respectivamente), pero en Secas fue significativamente menor con un valor de 0.1 masas/m (H, p˂0.05). La frecuencia de cópulas se relacionó significativamente con la abundancia de caracoles (rs= 0.26; p<0.05) y con la temperatura del agua (rs= 0.34; p<0.05). La abundancia de masas de huevos se relaciona significativamente con la abundancia de individuos (rs= 0.46; p<0.05). De forma general se observó que la actividad reproductiva de P. flagellata en la laguna de Bacalar, está asociada a los meses más cálidos y con mayor precipitación. Este hallazgo es relevante para apoyar la gestión de este recurso en la región, de tal forma que para implementar alguna medida de manejo para esta especie, es necesario tener en cuenta que al menos se debe mantener una veda temporal durante la etapa reproductiva.

Abstract:The freshwater snail Pomacea flagellata is native from Southeastern Mexico. Studies about this species are scarce and none has treated their reproduction. This snail has been exploited at Bacalar lagoon for many years, leading to a significant decrease in their abundance and currently, a permanent ban was proposed by the government. This work aimed to assess the temporal variations of mating frequency and the abundance of egg clutches of P. flagellata at Bacalar lagoon, as well as their relation with snails density and environmental variables. Sampling was done during the three climatic seasons: Rainy (July, August and September/2012), North or Cold fronts (December/2012 and January and February/2013) and Dry (March, April and May/2013) in 12 sampling stations located along the Bacalar lagoon. On each station a transect of 100 m length was set parallel to the edge, and the number of fresh egg clutches (pink color) laid over vegetation, rocks or manmade structures, were counted. In the water, three 50 x 2 m transects were set and the number of snails were counted as well as the mating frequency. Density of snails varied significantly among seasons, decreasing from the rainy to the dry season. There were no significant differences of snail abundance among months, nested in climatic seasons (ANOVA, p>0.05). During the rainy season the mating frequency was significantly higher than in the Norths, meanwhile in the dry season no mating were registered (Kruskal-Wallis, p˂0.05). Eggs clutches appeared from July to March. Density of egg clutches presented no differences between the Rainy and the North seasons (2.72 and 2.93 clutches/m, respectively), nonetheless during the dry season abundance of egg masses was significantly lower (0.1 clutches/m) (H, p˂0.05). Mating frequency was related with snail abundance (rs= 0.26; p<0.05) and water temperature (rs= 0.34; p<0.05) and the abundance of egg masses is related with snail abundance (rs= 0.46; p<0.05). In general, we observed that reproductive activity of P. flagellata at Bacalar lagoon is related with the warmer months and with higher rainfall. This finding is relevant to support the management of this resource in the region, so that to implement any management arrangement they must be aware that a temporal ban is necessary during the reproductive season at least. Rev. Biol. Trop. 64 (4): 1643-1650. Epub 2016 December 01.

Efectos del disturbio humano sobre la dinámica poblacional de Ocypode quadrata (Decapoda: Ocypodidae) en playas del Caribe mexicano / Effects of human disturbance on the population dynamics of Ocypode quadrata (Decapoda: Ocypodidae) in beaches of the Mexican Caribbean

Resumen:El cangrejo fantasma Ocypode quadrata, tiene una alta relevancia ecológica en las playas del Atlántico occidental y se ha propuesto como un indicador del impacto humano sobre este ecosistema. Sin embargo, no se han evaluado los efectos del disturbio humano sobre su dinámica poblacional. En este trabajo se compara la abundancia, el crecimiento y la mortalidad de O. quadrata en dos playas perturbadas (Aventuras y Majahual) y dos playas conservadas (Xcacel y Puerto Ángel) de las costas del Caribe mexicano. Se realizaron nueve muestreos en cada playa (marzo/2013-noviembre/2014). Durante las primeras horas de la noche se recolectaron cangrejos, de forma manual por tres personas, en un área aproximada de 9 000 m2. Los cangrejos fueron medidos, pesados y separados en tres grupos: jóvenes, hembras y machos. La mayor abundancia de cangrejos se encontró en las playas conservadas pero solo se observaron diferencias significativas entre Puerto Ángel y Majahual (Tukey, p<0.05). La proporción jóvenes- adultos fue 1:1 en Xcacel y Aventuras. En Majahual se recolectó un mayor número de jóvenes que adultos y en Puerto Ángel el número de adultos triplicó el de jóvenes. La talla máxima para Aventuras, Xcacel, Majahual y Puerto Ángel fue de 27, 32, 25 y 30 mm, respectivamente. En las playas se encontraron entre dos y tres grupos de edades diferentes. En las cuatro playas se recolectaron individuos con tallas menores de 10 mm en casi todos los meses de muestreo, indicando que el reclutamiento es continuo durante todo el año. La relación entre la longitud y el peso del cangrejo fantasma fue isométrica en las playas mejor conservadas y alométrica negativa en las playas impactadas. Los cangrejos de Puerto Ángel mostraron mejor condición corporal que en el resto de las playas (Tukey, p<0.05). Los valores de K oscilaron entre 0.6-0.97/año y la L∞ entre 29.0-33.6 mm. Los cangrejos en las dos playas conservadas mostraron mayores parámetros de crecimiento en comparación con las dos playas perturbadas. Los mayores valores de mortalidad se encontraron en Xcacel y Aventuras. En las playas perturbadas, la destrucción de las dunas, la limpieza mecánica y la remoción de materia orgánica, parecen ser las principales causas que conllevan a una baja abundancia de cangrejos, un menor crecimiento y una alta mortalidad. Sin embargo en las playas mejor conservadas, las relaciones biológicas parecen ser más importantes en regular la dinámica poblacional de esta especie. Estos resultados tienen relevancia desde el punto de vista de manejo de las playas arenosas, ya que el cangrejo fantasma es un buen indicador del disturbio humano y sus respuestas poblacionales son medibles y comparables.

Abstract:The ghost crab Ocypode quadrata is a relevant species in the Western Atlantic beaches, and has been proposed as an indicator of human impact in these ecosystems. Eventhough some studies have covered various aspects of its natural history, no evaluations on the effects of human disturbance on its population dynamics have been made. This work compared the abundance, growth, and mortality of O. quadrata in two disturbed beaches (Aventuras and Majahual) and two preserved beaches (Xcacel and Puerto Angel) from the Mexican Caribbean. For this, nine samplings were made on each beach (every two to three months) between March 2013 and November 2014. Crabs were collected manually by three people, during the night first hours and for one hour, and a total area of 9 000 m2 per beach. The crabs were measured, weighed, and separated into three groups: juvenile, male and female; while abundance was estimated by the number of collected crabs, and growth parameters were estimated using length frequencies. A total of 1 047 crabs were sampled in the four beaches; a higher crab abundance was found in the preserved beaches, but significant differences were only found between Puerto Angel and Majahual (Tukey, p<0.05). The adult- juvenile ratio was 1:1 in Xcacel and Aventuras, while in Majahual, more juveniles than adults were collected; and Puerto Angel had more adults than the juveniles. The size structure at Xcacel ranged from 4-32 mm, but in the rest of the beaches the minimum size was 5 mm. The maximum size at Aventuras, Majahual and Puerto Angel were 27 mm, 25 mm and 30 mm, respectively. The modal progression analysis of length's pooled data, revealed the presence of at least two groups of ages in all beaches. For all beaches, individuals smaller than 10 mm length were collected in almost all sampling months, indicating a continuous recruitment throughout the year. The length-weight relationship of the ghost crab was found isometric in the two preserved beaches, and negative allometric at the two impacted beaches. Crabs from Puerto Angel showed the highest body condition (Tukey, p<0.05). K-values ranged from 0.6-0.97/year and L∞ from 29.0 mm to 33.6 mm with higher values for the two preserved beaches. The highest mortality values were found in Xcacel and Aventuras. In the disturbed beaches, the destruction of the dunes, the mechanical cleaning and the removal of organic matter, seem to be the main causes that lead to a low abundance of crabs, their slower growth and higher mortalities. However, in the best preserved beaches, biological interactions appear to be the most important aspects in regulating the population dynamics of this species. These results supported the information that the ghost crab is a good indicator of human disturbance, and its population changes were clearly measurable and comparable among protected and impacted beaches; these results are also relevant for the management of sandy beaches in the Mexican Caribbean. Rev. Biol. Trop. 64 (4): 1625-1641. Epub 2016 December 01.

[Effects of human disturbance on the population dynamics of Ocypode quadrata (Decapoda: Ocypodidae) in beaches of the Mexican Caribbean]. / Efectos del disturbio humano sobre la dinámica poblacional de Ocypode quadrata (Decapoda: Ocypodidae) en playas del Caribe mexicano.

The ghost crab Ocypode quadrata is a relevant species in the Western Atlantic beaches, and has been proposed as an indicator of human impact in these ecosystems. Eventhough some studies have covered various aspects of its natural history, no evaluations on the effects of human disturbance on its population dynamics have been made. This work compared the abundance, growth, and mortality of O. quadrata in two disturbed beaches (Aventuras and Majahual) and two preserved beaches (Xcacel and Puerto Angel) from the Mexican Caribbean. For this, nine samplings were made on each beach (every two to three months) between March 2013 and November 2014. Crabs were collected manually by three people, during the night first hours and for one hour, and a total area of 9 000 m2 per beach. The crabs were measured, weighed, and separated into three groups: juvenile, male and female; while abundance was estimated by the number of collected crabs, and growth parameters were estimated using length frequencies. A total of 1 047 crabs were sampled in the four beaches; a higher crab abundance was found in the preserved beaches, but significant differences were only found between Puerto Angel and Majahual (Tukey, p<0.05). The adult-juvenile ratio was 1:1 in Xcacel and Aventuras, while in Majahual, more juveniles than adults were collected; and Puerto Angel had more adults than the juveniles. The size structure at Xcacel ranged from 4-32 mm, but in the rest of the beaches the minimum size was 5 mm. The maximum size at Aventuras, Majahual and Puerto Angel were 27 mm, 25 mm and 30 mm, respectively. The modal progression analysis of length's pooled data, revealed the presence of at least two groups of ages in all beaches. For all beaches, individuals smaller than 10 mm length were collected in almost all sampling months, indicating a continuous recruitment throughout the year. The length-weight relationship of the ghost crab was found isometric in the two preserved beaches, and negative allometric at the two impacted beaches. Crabs from Puerto Angel showed the highest body condition (Tukey, p<0.05). K-values ranged from 0.6-0.97/year and L∞ from 29.0 mm to 33.6 mm with higher values for the two preserved beaches. The highest mortality values were found in Xcacel and Aventuras. In the disturbed beaches, the destruction of the dunes, the mechanical cleaning and the removal of organic matter, seem to be the main causes that lead to a low abundance of crabs, their slower growth and higher mortalities. However, in the best preserved beaches, biological interactions appear to be the most important aspects in regulating the population dynamics of this species. These results supported the information that the ghost crab is a good indicator of human disturbance, and its population changes were clearly measurable and comparable among protected and impacted beaches; these results are also relevant for the management of sandy beaches in the Mexican Caribbean.

[Reproductive aspects of Pomacea flagellata (Mollusca: Ampullariidae) at Bacalar lagoon, Quintana Roo, México]. / Reproducción de Pomacea flagellate (Mollusca: Ampullariidae) en la laguna de Bacalar, Quintana Roo, México.

The freshwater snail Pomacea flagellata is native from Southeastern Mexico. Studies about this species are scarce and none has treated their reproduction. This snail has been exploited at Bacalar lagoon for many years, leading to a significant decrease in their abundance and currently, a permanent ban was proposed by the government. This work aimed to assess the temporal variations of mating frequency and the abundance of egg clutches of P. flagellata at Bacalar lagoon, as well as their relation with snails density and environmental variables. Sampling was done during the three climatic seasons: Rainy (July, August and September/2012), North or Cold fronts (December/2012 and January and February/2013) and Dry (March, April and May/2013) in 12 sampling stations located along the Bacalar lagoon. On each station a transect of 100 m length was set parallel to the edge, and the number of fresh egg clutches (pink color) laid over vegetation, rocks or manmade structures, were counted. In the water, three 50 x 2 m transects were set and the number of snails were counted as well as the mating frequency. Density of snails varied significantly among seasons, decreasing from the rainy to the dry season. There were no significant differences of snail abundance among months, nested in climatic seasons (ANOVA, p>0.05). During the rainy season the mating frequency was significantly higher than in the Norths, meanwhile in the dry season no mating were registered (Kruskal-Wallis, p˂0.05). Eggs clutches appeared from July to March. Density of egg clutches presented no differences between the Rainy and the North seasons (2.72 and 2.93 clutches/m, respectively), nonetheless during the dry season abundance of egg masses was significantly lower (0.1 clutches/m) (H, p˂0.05). Mating frequency was related with snail abundance (rs= 0.26; p<0.05) and water temperature (rs= 0.34; p<0.05) and the abundance of egg masses is related with snail abundance (rs= 0.46; p<0.05). In general, we observed that reproductive activity of P. flagellata at Bacalar lagoon is related with the warmer months and with higher rainfall. This finding is relevant to support the management of this resource in the region, so that to implement any management arrangement they must be aware that a temporal ban is necessary during the reproductive season at least.

A multifunctional streptococcal collagen-mimetic protein coating prevents bacterial adhesion and promotes osteoid formation on titanium.

The major barriers to the clinical success of orthopedic and dental implants are poor integration of fixtures with bone tissue and biomaterial-associated infections. Although multifunctional device coatings have long been considered a promising strategy, their development is hindered by difficulties in integrating biocompatibility, anti-infective activity and antithrombotic properties within a single grafting agent. In this study, we used cell adhesion assays and confocal microscopy of primary murine osteoblasts and human osteoblast cell lines MG-63 and Saos-2 to demonstrate that a streptococcal collagen-like protein engineered to display the α1 and α2 integrin recognition sequences enhances osteoblast adhesion and spreading on titanium fixtures. By measuring calcium deposition and alkaline phosphatase activity, we also showed that selective activation of α2ß1 integrin induces osteoblast differentiation, osteoid formation and mineralization. Moreover, cell adhesion assays and scanning electron microscopy of clinical isolates Staphylococcus aureus Philips and Staphylococcus epidermidis 9491 indicated that streptococcal collagen-mimetic proteins inhibit bacterial colonization and biofilm formation irrespective of their interaction with integrins. Given that streptococcal collagenous substrates neither interact with platelets nor trigger a strong immune response, this novel bioactive coating appears to have desirable multifaceted properties with promising translational applications.

Augmenting the articular cartilage-implant interface: Functionalizing with a collagen adhesion protein.

The lack of integration between implants and articular cartilage is an unsolved problem that negatively impacts the development of treatments for focal cartilage defects. Many approaches attempt to increase the number of matrix-producing cells that can migrate to the interface, which may help to reinforce the boundary over time but does not address the problems associated with an initially unstable interface. The objective of this study was to develop a bioadhesive implant to create an immediate bond with the extracellular matrix components of articular cartilage. We hypothesized that implant-bound collagen adhesion protein (CNA) would increase the interfacial strength between a poly(vinly alcohol) implant and an articular cartilage immediately after implantation, without preventing cell migration into the implant. By way of a series of in vitro immunohistochemical and mechanical experiments, we demonstrated that (i) free CNA can bind to articular cartilage, (ii) implant-bound CNA can bind to collagen type II and (iii) implants functionalized with CNA result in a fourfold increase in interfacial strength with cartilage relative to untreated implants at day zero. Of note, the interfacial strength significantly decreased after 21 days in culture, which may be an indication that the protein itself has lost its effectiveness. Our data suggest that functionalizing scaffolds with CNA may be a viable approach toward creating an initially stable interface between scaffolds and articular cartilage. Further efforts are required to ensure long-term interface stability.

An engineered alpha1 integrin-binding collagenous sequence.

Collagen is an extracellular matrix structural component that can regulate cellular processes through its interaction with the integrins, α1ß1, α2ß1, α10ß1, and α11ß1. Collagen-like proteins have been identified in a number of bacterial species. Here, we used Scl2 from Streptococcus pyogenes serotype M28 strain MGAS6274 as a backbone for the introduction of discrete integrin-binding sequences. The introduced sequences GLPGER, GFPGER, or GFPGEN did not affect triple helix stability of the Scl (Streptococcal collagen-like) protein. Using ELISA and surface plasmon resonance, we determined that Scl2(GLPGER) and Scl2(GFPGER) bound to recombinant human α1 and α2 I-domains in a metal ion-dependent manner and without a requirement for hydroxyproline. We predicted a novel and selective integrin-binding sequence, GFPGEN, through the use of computer modeling and demonstrated that Scl2(GFPGEN) shows specificity toward the α1 I-domain and does not bind the α2 I-domain. Using C2C12 cells, we determined that intact integrins interact with the modified Scl2 proteins with the same selectivity as recombinant I-domains. These modified Scl2 proteins also acted as cell attachment substrates for fibroblast, endothelial, and smooth muscle cells. However, the modified Scl2 proteins were unable to aggregate platelets. These results indicate that Scl2 is a suitable backbone for the introduction of mammalian integrin-binding sequences, and these sequences may be manipulated to individually target α1ß1 and α2ß1.

A structural model of the Staphylococcus aureus ClfA-fibrinogen interaction opens new avenues for the design of anti-staphylococcal therapeutics.

The fibrinogen (Fg) binding MSCRAMM Clumping factor A (ClfA) from Staphylococcus aureus interacts with the C-terminal region of the fibrinogen (Fg) gamma-chain. ClfA is the major virulence factor responsible for the observed clumping of S. aureus in blood plasma and has been implicated as a virulence factor in a mouse model of septic arthritis and in rabbit and rat models of infective endocarditis. We report here a high-resolution crystal structure of the ClfA ligand binding segment in complex with a synthetic peptide mimicking the binding site in Fg. The residues in Fg required for binding to ClfA are identified from this structure and from complementing biochemical studies. Furthermore, the platelet integrin alpha(IIb)beta(3) and ClfA bind to the same segment in the Fg gamma-chain but the two cellular binding proteins recognize different residues in the common targeted Fg segment. Based on these differences, we have identified peptides that selectively antagonize the ClfA-Fg interaction. The ClfA-Fg binding mechanism is a variant of the "Dock, Lock and Latch" mechanism previously described for the Staphylococcus epidermidis SdrG-Fg interaction. The structural insights gained from analyzing the ClfANFg peptide complex and identifications of peptides that selectively recognize ClfA but not alpha(IIb)beta(3) may allow the design of novel anti-staphylococcal agents. Our results also suggest that different MSCRAMMs with similar structural organization may have originated from a common ancestor but have evolved to accommodate specific ligand structures.

Survey of cardiac rhythm management and device implant patterns in Puerto Rico: analysis of 13,854 cardiac implants.

BACKGROUND: Surveys of cardiac pacing and implantable cardiovertor defibrillators (ICD) have been reported since 1969 and 1993 respectively. Increasing costs of medical technology, budget constraints and emergent new clinical indications prompted our committee to conduct the first survey of cardiac rhythm management and device implant patterns in Puerto Rico. METHOD: Clinical and demographic data were obtained for all cardiac devices sold and implanted from 2000 to 2006, through a joint agreement with official representatives of the 2 largest manufacturers and distributors of cardiac pacemakers and ICD in Puerto Rico. RESULTS: 13,854 cardiac devices were implanted from 2000 to 2006. The number of permanent pacemakers (PP) implanted per million population has varied from 430 in the year 2000 to 482 in the year 2006. A significant greater number of males received PP than females (P < .05). Yearly increases in implant rates for cardiac resynchronization therapy (CRT) and ICD were observed, mainly due to new emergent clinical indications, appropriate insurance coverage and availability of implanting electrophysiologists. CONCLUSIONS: Sales figures from PP and ICD manufacturers are a reliable system to calculate and analyze changes in cardiac device implant patterns. The rate of 482 PP per million population positions Puerto Rico as the third largest implant market in North and South America. This finding should be useful to insurance health providers since 76% of the implants are performed in patients over 65 years old. In the year 2006, Puerto Rico was the 10th largest implant market in the world with 67 CRT implanted per million population. A significant greater number of CRT and ICD were implanted in males than females. This gender difference has increased in spite of strict requirements to include more females in clinical trials and intensive, educational and awareness efforts conducted among physicians and patients. A summary of the current guidelines and clinical indications is provided to assist the physician in the selection of patients referred for cardiac rhythm management and implant procedures.

[ISRCTN 16558617] A randomized, controlled trial of spinal endoscopic adhesiolysis in chronic refractory low back and lower extremity pain.

BACKGROUND: Postoperative epidural fibrosis may contribute to between 5% to 60% of the poor surgical outcomes following decompressive surgery. Correlations have been reported between epidural scarring and radicular pain, poor surgical outcomes, and a lack of any form of surgical treatment. The use of spinal endoscopic adhesiolysis in recent years in the management of chronic refractory low back and lower extremity pain has been described. METHODS: A prospective, randomized, double-blind trial was conducted to determine the outcome of spinal endoscopic adhesiolysis to reduce pain and improve function and psychological status in patients with chronic refractory low back and lower extremity pain. A total of 83 patients were evaluated, with 33 patients in Group I and 50 patients in Group II. Group I served as the control, with endoscopy into the sacral level without adhesiolysis, followed by injection of local anesthetic and steroid. Group II received spinal endoscopic adhesiolysis, followed by injection of local anesthetic and steroid. RESULTS: Among the 50 patients in the treatment group receiving spinal endoscopic adhesiolysis, significant improvement without adverse effects was shown in 80% at 3 months, 56% at 6 months, and 48% at 12 months. The control group showed improvement in 33% of the patients at one month and none thereafter. Based on the definition that less than 6 months of relief is considered short-term and longer than 6 months of relief is considered long-term, a significant number of patients obtained long-term relief with improvement in pain, functional status, and psychological status. CONCLUSION: Spinal endoscopic adhesiolysis with targeted delivery of local anesthetic and steroid is an effective treatment in a significant number of patients with chronic low back and lower extremity pain without major adverse effects.

Reliability of psychological evaluation in chronic pain in an interventional pain management setting.

BACKGROUND: Psychological disorders may be associated with poor pain related treatment outcomes. However, there may be limitations with studies evaluating the relationship between pain and psychopathology. OBJECTIVE: To assess the reliability of psychological evaluations in interventional pain management by MCMI-III(R) and P-3(R). STUDY DESIGN: Prospective evaluation of consecutive patients in an interventional pain management center. METHODS: Patients were evaluated using a DSM-IV-TR(R) questionnaire with a physician interview as an integral part of their comprehensive evaluation. In addition, all the patients participating in this study also underwent psychological evaluation with MCMI-III and P-3. A positive diagnosis of major depression or generalized anxiety disorder based on DSM-IV-TR criteria was considered as the criterion standard. All of the patients presented for treatment of chronic pain. The data based on the criterion standard were compared with results of the diagnostic impression from the MCMI-III and the P-3 evaluation utilizing criteria for average, and above average, patient pain scores. RESULTS: Major depression was diagnosed in a total of 59 of 100 patients using DSM-IV-TR criteria, in 32 patients based on MCMI-III criteria, and in 55 patients based on P-3 evaluations utilizing average pain patient criteria. Generalized anxiety disorder was diagnosed in 55 patients by means of DSM-IV-TR, 45 patients by MCMI-III, and 55 patients by P-3 Profile utilizing average pain patient scores. The specificity of MCMI-III was 100% with a sensitivity of 54% for diagnosis of depression; whereas it was 78% specificity and sensitivity for P-3, with average pain patient scores. For generalized anxiety disorder, specificity of MCMI-III was 89% with a sensitivity of 73% compared to specificity of 80% and sensitivity of 84% for average pain patient scores for P-3. CONCLUSION: MCMI-III and P-3 are highly specific in diagnosing depression and generalized anxiety disorder, with variable sensitivity. A DSM-IV-TR questionnaire evaluation incorporated into the pain management questionnaire, along with a short clinical interview, is a reliable means of assessing depression and anxiety in patients suffering with chronic pain.

Evaluation of the effect of sedation as a confounding factor in the diagnostic validity of lumbar facet joint pain: a prospective, randomized, double-blind, placebo-controlled evaluation.

BACKGROUND: Lumbar facet (zygapophysial) joints have been implicated as the source of chronic pain in 15% to 45% of patients with chronic low back pain. Diagnosis may be confounded by false-positive results with a single diagnostic block and administration of anxiolytics and narcotics prior to or during the diagnostic facet joint blocks. OBJECTIVE: To evaluate the effect of midazolam and fentanyl on the diagnostic validity of of lumbar facet joint pain. STUDY DESIGN: Randomized, prospective, double-blind, placebo-controlled evaluation. METHODS: The design consisted of a placebo group receiving sodium chloride solution and two experimental groups receiving either midazolam or fentanyl. The patients included in the study were diagnosed with facet joint pain with controlled comparative local anesthetic blocks of medial branches or L5 dorsal rami. They had been treated with lumbar facet joint nerve blocks with good pain relief, and were presenting for repeat treatment after a period of symptom relief. The study was undertaken in an interventional pain management practice. OUTCOME MEASURES: Outcomes were assessed at baseline and after the administration of 1 of the 3 solutions (Group I, sodium chloride solution; Group II, midazolam; or Group III, fentanyl). Outcome measures included numeric pain scale, proportion of pain relief, and ability to perform prior painful movements. RESULTS: Pain relief of > or =80% was noted in 2% of the patients in Group I, 5% of the patients in Group II, and 7% in Group III. Pain relief of > or =50% was noted in 7% of the patients in Group I, 5% of the patients in Group II, and 13% of the patients in Group III. There were no significant differences among the groups. CONCLUSION: The administration of sedation with midazolam or fentanyl is a confounding factor in the diagnosis of lumbar facet joint pain in patients with chronic low back pain. However, this study suggests that if strict criteria including pain relief and ability to perform prior painful movements is used as the standard for evaluating the effect of controlled local anesthetic blocks, the diagnostic validity of lumbar facet joint nerve blocks may be preserved.

One day lumbar epidural adhesiolysis and hypertonic saline neurolysis in treatment of chronic low back pain: a randomized, double-blind trial.

BACKGROUND: Chronic, refractory low back pain is a common problem. Percutaneous adhesiolysis with hypertonic saline neurolysis was described in the management of chronic refractory low back pain, non-responsive to conservative modalities of management. OBJECTIVE: To determine the ability of percutaneous adhesiolysis and hypertonic saline administration to reduce pain and improve functional and psychological status in patients with chronic low back pain. DESIGN: Randomized, double-blind, controlled trial. METHODS: A total of 75 patients were studied, with 25 patients in each group. Three types of interventions were included, with Group I serving as control with catheterization without adhesiolysis, followed by injection of local anesthetic, normal saline, and steroid. Group II consisted of catheterization and adhesiolysis, followed by injection of local anesthetic, normal saline, and steroid. Group III consisted of adhesiolysis followed by injection of local anesthetic, hypertonic saline, and steroid. Statistical analysis incorporated intent-to-treat analysis. OUTCOME MEASURES: Visual Analogue Scale pain scores, Oswestry Disability Index, work status, opioid intake, range of motion measurement, and P-3 (R). Significant pain relief was defined as average relief of 50% or greater. RESULTS: Significant improvement was seen in patients in Group II and III, at 3 months, 6 months, and 12 months, compared to baseline measurements, as well as compared to Group I without adhesiolysis. Seventy-two percent of patients in Group III (adhesiolysis and hypertonic neurolysis), 60% of patients in Group II (adhesiolysis only), compared to 0% in Group I (control) showed significant improvement at 12-month follow up. The average number of treatments for one year were 2.76 in Group II and 2.16 in Group III. Duration of significant relief with the first procedure was 2.8 +/- 1.49 months in Group II and 3.8 +/- 3.37 months in Group III. CONCLUSION: Percutaneous adhesiolysis, with or without hypertonic saline neurolysis, is an effective treatment for chronic low back pain.