Zigzag tenotomy of the extensor hallucis longus through minimally invasive surgery in cadaveric specimens: description of a new technique.

BACKGROUND: Lengthening of the extensor hallucis longus (EHL) is performed to address various forefoot pathologies. The retraction of this tendon is strongly associated with the Hallux Abductus Valgus (HAV) deformity. Minimally Invasive Surgery (MIS) lengthening of the EHL is carried out in combination with other surgical techniques for HAV bone realignment. It is performed without ischemia, using local anesthesia and sedation if required by the patient. One of the advantages of this technique is immediate ambulation with a postoperative shoe without the need for a cast. The objective of the research was to demonstrate the efficacy and safety of the minimally invasive technique for lengthening the tendon in patients with HAV. MATERIALS AND METHODS: The procedures were performed on 11 fresh cryopreserved cadaveric feet. HAV surgery was performed through dorsomedial and dorsolateral portals for Reverdin-Isham, Akin and adductor tenotomy. In addition, EHL tendon elongation was performed using the Beaver 67 MIS scalpel through an incomplete zigzag tenotomy. The specimens used did not present any type of disease nor had they undergone previous surgeries that could affect the technique. First, the plantar flexion of the metatarsophalangeal joint was measured with a goniometer to establish the degrees of this joint before proceeding with the technique, the tenotomy was performed and remeasured and finally the osteotomy was performed. In addition, an anatomical dissection of cadaveric specimens was performed and various anatomical and surgical relationships were analyzed and measured. RESULTS: The data indicate that, after performing zigzag tenotomy, there is an average improvement of 13.91 degrees in plantar flexion. CONCLUSIONS: The study confirms the effectiveness and safety of elongating the extensor hallucis longus tendon of the hallux using minimally invasive surgery. The zigzag technique for tendon elongation may be considered a viable minimally invasive treatment option for addressing tendon hyperextension in patients with HAV.

Parallel prediction of dengue cases with different risks in Mexico using an artificial neural network model considering meteorological data.

In 2022, Mexico registered an increase in dengue cases compared to the previous year. On the other hand, the amount of precipitation reported annually was slightly less than the previous year. Similarly, the minimum-mean-maximum temperatures recorded annually were below the previous year. In the literature, it is possible to find studies focused on the spread of dengue only for some specific regions of Mexico. However, given the increase in the number of cases during 2022 in regions not considered by previously published works, this study covers cases reported in all states of the country. On the other hand, determining a relationship between the dynamics of dengue cases and climatic factors through a computational model can provide relevant information on the transmission of the virus. A multiple-learning computational approach was developed to simulate the number of the different risks of dengue cases according to the classification reported per epidemiological week by considering climatic factors in Mexico. For the development of the model, the data were obtained from the reports published in the Epidemiological Panorama of Dengue in Mexico and in the National Meteorological Service. The classification of non-severe dengue, dengue with warning signs, and severe dengue were modeled in parallel through an artificial neural network model. Five variables were considered to train the model: the monthly average of the minimum, mean, and maximum temperatures, the precipitation, and the number of the epidemiological week. The selection of variables in this work is focused on the spread of the different risks of dengue once the mosquito begins transmitting the virus. Therefore, temperature and precipitation were chosen as climatic factors due to the close relationship between the density of adult mosquitoes and the incidence of the disease. The Levenberg-Marquardt algorithm was applied to fit the coefficients during the learning process. In the results, the ANN model simulated the classification of the different risks of dengue with the following precisions (R2): 0.9684, 0.9721, and 0.8001 for non-severe dengue, with alarm signs and severe, respectively. Applying a correlation matrix and a sensitivity analysis of the ANN model coefficients, both the average minimum temperature and precipitation were relevant to predict the number of dengue cases. Finally, the information discovered in this work can support the decision-making of the Ministry of Health to avoid a syndemic between the increase in dengue cases and other seasonal diseases.

Barriers and facilitators in self-care and management of chronic kidney disease in dialysis patients: A systematic review of qualitative studies.

AIM: To identify and synthesise qualitative studies on barriers and facilitators perceived by dialysis patients in relation to self-care and disease management. DESIGN: Systematic review of qualitative studies. DATA SOURCES: Qualitative study articles were extracted from PUBMED, MEDLINE, COCHRANE, WEB OF SCIENCE (WOS), CINAHL PsycINFO and EMBASE and electronic journals of the Spanish Society of Nephrology and Spanish Society of Nephrological Nursing until May 2022. Studies on barriers and/or facilitators affecting self-care and disease management expressed by people undergoing haemodialysis or peritoneal dialysis were included. REVIEW METHODS: The SPICE (Setting, Perspective, Intervention, Comparison and Evaluation) strategy was used to develop issues and subissues through the thematic synthesis of the qualitative findings. GRADE-CERQual was used to evaluate the articles. RESULTS: From 172 articles, 15 qualitative articles about barriers and facilitators perceived by patients concerning self-care and disease management were finally included. Identified eight facilitators and four barriers. CONCLUSION: Patients perceived a significant number of barriers and facilitators. It is possible to identify which aspects facilitate self-management of their disease and to understand that the processes are individualised. This is why therapeutic strategies should be designed to foster the participation and empowerment of the person in the management of the disease. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Identifying the barriers and facilitators concerning the management of chronic kidney disease furnishes us with knowledge for individualised clinical practice and improved care processes. IMPACT: This review is the first to synthesise barriers and facilitators in haemodialysis patients about the management of their disease and treatment. The results enable the proposal of improvements in the training of healthcare personnel, clinical practice guidelines and action protocols to improve the daily life and management of the disease by patients. No patient or public contribution due to this is a systematic review.

Older forests function as energetic and demographic refugia for a climate-sensitive species.

More frequent and extreme heat waves threaten climate-sensitive species. Structurally complex, older forests can buffer these effects by creating cool microclimates, although the mechanisms by which forest refugia mitigate physiological responses to heat exposure and subsequent population-level consequences remain relatively unexplored. We leveraged fine-scale movement data, doubly labeled water, and two decades of demographic data for the California spotted owl (Strix occidentalis occidentalis) to (1) assess the role of older forest characteristics as potential energetic buffers for individuals and (2) examine the subsequent value of older forests as refugia for a core population in the Sierra Nevada and a periphery population in the San Bernardino Mountains. Individuals spent less energy moving during warmer sampling periods and the presence of tall canopies facilitated energetic conservation during daytime roosting activities. In the core population, where tall-canopied forest was prevalent, temperature anomalies did not affect territory occupancy dynamics as warmer sites were both less likely to go extinct and less likely to become colonized, suggesting a trade-off between foraging opportunities and temperature exposure. In the peripheral population, sites were more likely to become unoccupied following warm summers, presumably because of less prevalent older forest conditions. While individuals avoided elevated energetic expenditure associated with temperature exposure, behavioral strategies to conserve energy may have diverted time and energy from reproduction or territory defense. Conserving older forests, which are threatened due to fire and drought, may benefit individuals from energetic consequences of exposure to stressful thermal conditions.

Bacteria associated with apical periodontitis promotes in vitro the differentiation of macrophages to osteoclasts.

OBJECTIVE: To analyze the possible in vitro effect of the cytokine RANKL and bacteria involved in apical periodontitis on the differentiation of macrophages into osteoclasts. MATERIAL AND METHODS: Bacteria were isolated (mainly E. faecium and E. faecalis) from the root canal of fifty patients with apical periodontitis, the possible effect of these bacteria on the phagocytic activity of the monocyte cell line THP-1 was analyzed by flow cytometry. Furthermore, the effect of these bacteria (alone or in combination with the cytokine RANKL) on the differentiation of THP-1 macrophages into osteoclasts was analyzed through the expression of the receptor RANK and the tartrate-resistant acid phosphatase TRAP. Finally, the release of different cytokines (IL-1ß, TNF-α, IL-6, IL-8, IL-10, and IL-12p70) by THP-1 cells induced to differentiate into osteoclasts was also analyzed. RESULTS: We observed a significant proportion of THP-1 cells were able to internalize E. faecium and E. faecalis. Furthermore, these bacteria were able to induce (alone or in combination with RANKL) a significant expression of RANK by THP-1 macrophages; accordingly, E. faecium and E. faecalis induced very significant levels of TRAP in these cells. Finally, during the differentiation of THP-1 macrophages induced by RANKL or bacteria, a significant release of the pro-inflammatory cytokines IL-6 and TNF-α was observed. CONCLUSIONS AND CLINICAL RELEVANCE: Our data suggest that the causative agents of apical periodontitis can induce the differentiation of osteoclasts as well as the release of pro-inflammatory cytokines, phenomena that may have an important role in the bone damage observed in this condition.

A nanographene disk rotating a single molecule gear on a Cu(111) surface.

On Cu(111) surface and in interaction with a single hexa-tert-butylphenylbenzene molecule-gear, the rotation of a graphene nanodisk was studied using the large-scale atomic/molecular massively parallel simulator molecular dynamics simulator. To ensure a transmission of rotation to the molecule-gear, the graphene nanodisk is functionalized on its circumference bytert-butylphenyl chemical groups. The rotational motion can be categorized underdriving, driving and overdriving regimes calculating the locking coefficient of this mechanical machinery as a function of external torque applied to the nanodisk. The rotational friction with the surface of both the phononic and electronic contributions is investigated. For small size graphene nanodisks, the phononic friction is the main contribution. Electronic friction dominates for the larger disks putting constrains on the experimental way of achieving the transfer of rotation from a graphene nanodisk to a single molecule-gear.

The contribution of intermolecular spin interactions to the London dispersion forces between chiral molecules.

Dispersion interactions are one of the components of van der Waals (vdW) forces that play a key role in the understanding of intermolecular interactions in many physical, chemical, and biological processes. The theory of dispersion forces was developed by London in the early years of quantum mechanics. However, it was only in the 1960s that it was recognized that for molecules lacking an inversion center, such as chiral and helical molecules, there are chirality-sensitive corrections to the dispersion forces proportional to the rotatory power known from the theory of circular dichroism and with the same distance scaling law R-6 as the London energy. The discovery of the chirality-induced spin selectivity effect in recent years has led to an additional twist in the study of chiral molecular systems, showing a close relation between spin and molecular geometry. Motivated by it, we propose in this investigation to describe the mutual induction of charge and spin-density fluctuations in a pair A-B of chiral molecules by a simple physical model. The model assumes that the same fluctuating electric fields responsible for vdW forces can induce a magnetic response via a Rashba-like term so that a spin-orbit field acting on molecule B is generated by the electric field arising from charge density fluctuations in molecule A (and vice versa). Within a second-order perturbative approach, these contributions manifest as an effective intermolecular exchange interaction. Although expected to be weaker than the standard London forces, these interactions display the same R-6 distance scaling.

Plastic energy allocation toward life-history functions in a consumer-resource interaction : Analyzing the temporal patterns of the consumer-resource dynamics.

Various environmental alterations resulting from the current global change compromise the persistence of species in their habitual environment. To cope with the obvious risk of extinction, plastic responses provide organisms with rapid acclimatization to new environments. The premise of plastic rescue has been theoretically studied from mathematical models in both deterministic and stochastic environments, focusing on analyzing the persistence and stability of the populations. Here, we evaluate this premise in the framework of a consumer-resource interaction considering the energy investment towards reproduction vs. maintenance as a plastic trait according to positive/negative variation of the available resource. A basic consumer-resource mathematical model is formulated based on the principle of biomass conversion that incorporates the energy allocation toward vital functions of the life-cycle of consumer individuals. Our mathematical approach is based on the impulsive differential equations at fixed moments considering two impulsive effects associated with the instants at which consumers obtain environmental information and when energy allocation strategy change occurs. From a preliminary analysis of the non-plastic temporal dynamics, namely when the energy allocation is constant over time and without experiencing changes concerning the variation of resources, both the persistence and stability of the consumer-resource dynamic are dependent on the energy allocation strategies belonging to a set termed stability range. We found that the plastic energy allocation can promote a stable dynamical pattern in the consumer-resource interaction depending on both the magnitude of the energy allocation change and the time lag between environmental sensibility instants and when the expression of the plastic trait occurs.

Setting up regional diagnostic reference levels for pediatric interventional cardiology in Latin America and the Caribbean countries: preliminary results and identified challenges.

The goal of the present study was to propose a set of preliminary regional diagnostic reference levels (DRLs) for pediatric interventional cardiology (IC) procedures in Latin America and the Caribbean countries, classified by age and weight groups. The study was conducted in the framework of the Optimization of Protection in Pediatric Interventional Radiology in Latin America and the Caribbean program coordinated by the World Health Organization and the Pan American Health Organization in cooperation with the International Atomic Energy Agency. The first step of the program was focused on pediatric IC. Dose data from diagnostic and therapeutic procedures were collected between December 2020 and December 2021. Regional DRLs were set as the third quartile of patient dose data (kerma area product) collected in 18 hospitals from 10 countries in an initial sample of 968 procedures. DRLs were set for four age bands and five weight ranges. The values obtained for the four age bands (<1 yr, 1 to <5 yr, 5 to <10 yr and 10 to <16 yr) were 2.9, 6.1, 8.8 and 14.4 Gy cm2for diagnostic procedures, and 4.0, 5.0, 10.0 and 38.1 Gy cm2for therapeutic procedures, respectively. The values obtained for the five weight bands (<5 kg, 5 to <15 kg, 15 to <30 kg, 30 to <50 kg and 50 to <80 kg) were 3.0, 4.5, 8.1, 9.2 and 26.8 Gy cm2for diagnostic procedures and 3.7, 4,3, 7.3, 16.1 and 53.4 Gy cm2for therapeutic procedures, respectively. While initial data were collected manually as patient dose management systems (DMSs) were not available in most of the hospitals involved in the program, a centralized automatic DMS for the collection and management of patient dose indicators has now been introduced and is envisaged to increase the sample size. The possibility of alerting on high dose values and introducing corrective actions will help in optimization.

Using the ecological significance of animal vocalizations to improve inference in acoustic monitoring programs.

Recent bioacoustic advances have facilitated large-scale population monitoring for acoustically active species. Animal sounds, however, can of information that is underutilized in typical approaches to passive acoustic monitoring (PAM) that treat sounds simply as detections. We developed 3 methods of extracting additional ecological detail from acoustic data that are applicable to a broad range of acoustically active species. We conducted landscape-scale passive acoustic surveys of a declining owl species and an invasive congeneric competitor in California. We then used sex-specific vocalization frequency to inform multistate occupancy models; call rates at occupied sites to characterize interactions with interspecific competitors and assess habitat quality; and a flexible multivariate approach to differentiate individuals based on vocal characteristics. The multistate occupancy models yielded novel estimates of breeding status occupancy rates that were more robust to false detections and captured known habitat associations more consistently than single-state occupancy models agnostic to sex. Call rate was related to the presence of a competitor but not habitat quality and thus could constitute a useful behavioral metric for interactions that are challenging to detect in an occupancy framework. Quantifying multivariate distance between groups of vocalizations provided a novel quantitative means of discriminating individuals with ≥20 vocalizations and a flexible tool for balancing type I and II errors. Therefore, it appears possible to estimate site turnover and demographic rates, rather than just occupancy metrics, in PAM programs. Our methods can be applied individually or in concert and are likely generalizable to many acoustically active species. As such, they are opportunities to improve inferences from PAM data and thus benefit conservation.

Uso de la Importancia Ecológica de las Vocalizaciones Animales para Mejorar la Inferencia en los Programas de Monitoreo Acústico Resumen Los avances bioacústicos recientes han facilitado el monitoreo a gran escala de poblaciones de especies acústicamente activas. Sin embargo, los sonidos de animales pueden transmitir cantidades sustanciales de información que queda utilizada insuficientemente en las estrategias comunes de monitoreo acústico pasivo (MAP) que tratan a los sonidos como simples detecciones. Desarrollamos tres métodos de extracción de detalles ecológicos adicionales de los datos acústicos que son aplicables a una gama amplia de especies acústicamente activas. Realizamos censos acústicos pasivos a escala de paisaje para una especie de búho en declinación y para un competidor congenérico invasivo en California. Después utilizamos la frecuencia de vocalizaciones específicas por sexo para orientar los modelos multiestado de ocupación; las tasas de llamados en sitios ocupados para caracterizar las interacciones con los competidores interespecíficos y evaluar la calidad de su hábitat; y una estrategia multivariada flexible para diferenciar a los individuos con base en sus características vocales. Los modelos multiestado de ocupación brindaron estimaciones novedosas para las tasas de ocupación por estado reproductivo que fueron más sólidas ante las detecciones falsas y capturaron el número de asociaciones de hábitat más sistemáticamente que los modelos de estado único agnósticos al sexo. La tasa de llamados estuvo relacionada con la presencia de un competidor pero no con la calidad del hábitat y por lo tanto podría constituir una medida conductual útil para las interacciones que son difíciles de detectar en un marco de trabajo de ocupación. La cuantificación de la distancia multivariada entre los grupos de vocalizaciones proporcionó un medio cuantitativo novedoso para discriminar a los individuos con ≥20 vocalizaciones y una herramienta flexible para balancear los errores del tipo I y del tipo II. Por lo tanto, parecer que hay posibilidad de estimar las tasas demográficas y de rotación, en lugar de sólo las medidas de ocupación, en los programas MAP. Nuestros métodos pueden aplicarse individualmente o de manera conjunta y es probable poder generalizarlas para muchas especies acústicamente activas. Dicho así, son oportunidades para mejorar las inferencias de los datos MAP y por lo tanto, beneficiar a la conservación.

Comparison of an artificial neural network and Gompertz model for predicting the dynamics of deaths from COVID-19 in México.

The present work is focused on modeling and predicting the cumulative number of deaths from COVID-19 in México by comparing an artificial neural network (ANN) with a Gompertz model applying multiple optimization algorithms for the estimation of coefficients and parameters, respectively. For the modeling process, the data published by the daily technical report COVID-19 in Mexico from March 19th to September 30th were used. The data published in the month of October were included to carry out the prediction. The results show a satisfactory comparison between the real data and those obtained by both models with a R2 > 0.999. The Levenberg-Marquardt and BFGS quasi-Newton optimization algorithm were favorable for fitting the coefficients during learning in the ANN model due to their fast and precision, respectively. On the other hand, the Nelder-Mead simplex algorithm fitted the parameters of the Gompertz model faster by minimizing the sum of squares. Therefore, the ANN model better fits the real data using ten coefficients. However, the Gompertz model using three parameters converges in less computational time. In the prediction, the inverse ANN model was solved by a genetic algorithm obtaining the best precision with a maximum error of 2.22% per day, as opposed to the 5.48% of the Gompertz model with respect to the real data reported from November 1st to 15th. Finally, according to the coefficients and parameters obtained from both models with recent data, a total of 109,724 cumulative deaths for the inverse ANN model and 100,482 cumulative deaths for the Gompertz model were predicted for the end of 2020.

Building Continuous Time Crystals from Rare Events.

Symmetry-breaking dynamical phase transitions (DPTs) abound in the fluctuations of nonequilibrium systems. Here, we show that the spectral features of a particular class of DPTs exhibit the fingerprints of the recently discovered time-crystal phase of matter. Using Doob's transform as a tool, we provide a mechanism to build classical time-crystal generators from the rare event statistics of some driven diffusive systems. An analysis of the Doob's smart field in terms of the order parameter of the transition then leads to the time-crystal lattice gas (TCLG), a model of driven fluid subject to an external packing field, which presents a clear-cut steady-state phase transition to a time-crystalline phase characterized by a matter density wave, which breaks continuous time-translation symmetry and displays rigidity and long-range spatiotemporal order, as required for a time crystal. A hydrodynamic analysis of the TCLG transition uncovers striking similarities, but also key differences, with the Kuramoto synchronization transition. Possible experimental realizations of the TCLG in colloidal fluids are also discussed.

A systematic review of pharmacological therapies and their effectiveness on health-related quality of life outcomes in patients with juvenile-onset systemic lupus erythematosus.

Juvenile-onset systemic lupus erythematosus (JSLE) presents with an aggressive course and high morbidity associated with disease and treatment. JSLE patients have a poorer health-related quality of life (HRQoL) when compared with age-matched patients with other rheumatologic disorders. We aim to summarize the impact of current pharmacological therapies on the HRQoL of JSLE patients. Search strategies were developed across seven databases. Randomized clinical trials (RCTs) and cohort studies comparing interventions to standard therapy, placebo or pre-post cohort comparisons for more than 4 weeks were included. The outcome included self-reported scales compared at baseline and a therapeutic time point. Risk of bias was evaluated by using the Cochrane risk of bias tool and the Newcastle-Ottawa quality assessment scale. A total of 2812 articles were narrowed down to 309 for full-text screening. Four RCTs and one prospective cohort study, with a total of 634 JSLE patients, met the inclusion criteria. Four of the studies had a controlled intervention plus standard therapy compared with standard therapy alone or placebo. Multiple indices were used to evaluate HRQoL. These included the Pediatric Quality of Life Inventory, Childhood Health Assessment Questionnaire, Simple Measure of Impact of Lupus Erythematosus in Youngsters tool, Kids Fatigue Severity Scale and Child Depression Inventory. A single study reported a significant improvement while remaining studies reported no difference or failed to report the statistical analysis. Although HRQoL is significantly impaired in JSLE, evidence regarding its improvement is limited due to the small number of eligible studies, heterogeneity in scales, and HRQoL domains. A universal HRQoL questionnaire for JSLE needs to be established and used in both the research and clinical setting. All studies should adhere to reporting guidelines.

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors and microvascular outcomes in patients with type 2 diabetes: systematic review and meta-analysis.

PURPOSE: The effect of the sodium-glucose 2 (SGLT-2) inhibitors on microvascular complications remains uncertain. We performed a systematic review to determine the efficacy of the SGLT-2 inhibitors on microvascular outcomes in patients with type 2 diabetes. METHODS: A comprehensive search was performed using Ovid, MEDLINE, EMBASE, Web of Science, and Scopus from inception to May 2019. Randomized trials comparing SGLT-2 inhibitors with placebo or other medication for type 2 diabetes for ≥ 4 weeks were included. Diabetes-related microvascular complications such as nephropathy, retinopathy, neuropathy, and peripheral vascular disease were evaluated. A random-effect model using mean differences for continuous outcomes and risk ratio for dichotomous outcomes was used to synthesize data. PROSPERO (CRD 42017076460). RESULTS: A total of 40 RCTs with overall moderate quality of evidence were included. SGLT-2 inhibitors reduced the risk of renal-replacement therapy (0.65; 95% CI 0.54-0.79), renal death (0.57; 95% CI 0.49-0.65), and progression of albuminuria (0.69; 95% CI 0.66-0.73). Conversely, they appeared ineffective in maintaining eGFR (0.33; 95% CI - 0.74 to 1.41) or reducing serum creatinine (- 0.07; 95% CI - 0.26 to 0.11), whereas urine albumin-creatinine ratio (- 23.4; 95% CI - 44.6 to - 2.2) was reduced. Risk of amputation was non-significant (1.30; 95% CI 0.93-1.83). No available data were found regarding neuropathy and retinopathy to perform a quantitative analysis. CONCLUSION: SGLT-2 inhibitors may reduce the risk of renal patient-important outcomes but fail to improve surrogate outcomes. Apparently, no increased risk of amputations was observed with these medications. No data were available regarding other microvascular complications.

Modeling and prediction of COVID-19 in Mexico applying mathematical and computational models.

This work presents the modeling and prediction of cases of COVID-19 infection in Mexico through mathematical and computational models using only the confirmed cases provided by the daily technical report COVID-19 MEXICO until May 8th. The mathematical models: Gompertz and Logistic, as well as the computational model: Artificial Neural Network were applied to carry out the modeling of the number of cases of COVID-19 infection from February 27th to May 8th. The results show a good fit between the observed data and those obtained by the Gompertz, Logistic and Artificial Neural Networks models with an R2 of 0.9998, 0.9996, 0.9999, respectively. The same mathematical models and inverse Artificial Neural Network were applied to predict the number of cases of COVID-19 infection from May 9th to 16th in order to analyze tendencies and extrapolate the projection until the end of the epidemic. The Gompertz model predicts a total of 47,576 cases, the Logistic model a total of 42,131 cases, and the inverse artificial neural network model a total of 44,245 as of May 16th. Finally, to predict the total number of COVID-19 infected until the end of the epidemic, the Gompertz, Logistic and inverse Artificial Neural Network model were used, predicting 469,917, 59,470 and 70,714 cases, respectively.

Hydrogeochemical baseline in a human-altered landscape of the central Pacific coast of Costa Rica.

Groundwater pollution in tropical and human-altered coastal landscapes is receiving novel attention due to decreasing in annual recharge as a consequence of recurrent droughts and overexploitation, whereby saline intrusion, point and diffuse source contamination, and water conflicts are common denominators. This study presents a detailed groundwater evaluation in a coastal aquifer within the central Pacific coast of Costa Rica. Three sampling campaigns including major ions, heavy metals, and fecal coliform analyses were conducted between July 2013 and March 2014 across 17 wells within the alluvial and fissured units of the Jacó aquifer. The groundwater system is classified as mixed HCO3--Ca2+-Mg2+ type. Coliforms presence was found in two wells, nearby Mona Creek headwaters and near the coastal line. Heavy metal concentrations were below quantification limits in most of the wells; however, chromium concentrations up to 6.56 µg/L were quantified within the coastal line and central portion of the alluvial aquifer in 20 out of the 48 samples. The spatial distribution of major ions (K+, Na+, Ca2+, Mg2+, Cl-, SO42-, and HCO3-) exhibited an increasing trend towards the central portion of the alluvial aquifer, which may be potentially associated with the large unregulated urban expansion, invoking a need of a continuous water quality monitoring program in this touristic hot spot. This study provides useful information for other similar coastal aquifers in Central America, whereby increasing population growth and unregulated touristic, industrial, and agricultural activities are posing a truly challenge to ensure water security and sustainability parallel to the economic development in a changing climate.

Enhancement of gemcitabine cytotoxicity in pancreatic adenocarcinoma through controlled release of nitric oxide.

Gemcitabine (GEM) is the first-line treatment for pancreatic adenocarcinoma (PAC) yet chemoresistance is common. Nitric oxide (NO) is the predominant species responsible for the cytotoxic action of macrophages against cancer cells yet localized delivery is difficult given the short half-life. We sought to study the effect of locally delivered NO on GEM mediated PAC cytotoxicity and the potential role of SMAD4 in this effect. We hypothesized that NO would enhance the cytotoxicity of GEM in a SMAD4 dependent manner. NO-Silica nanoparticles (NO-Si) were synthesized via a co-condensation of tetraethoxysilane with aminoalkoxysilane under high-pressure nitrous oxide. NO release was measured using chemiluminescence. A SMAD4 negative PAC cell line (SMAD4-) was made using retroviral knockdown of Panc1 PAC cells. Panc1 and SMAD4- cells were treated with gemcitabine (100 nm (hi) to 30 µm (lo)), 30 mg NOSi particles, or both (NOSihi or NOSilo) and cell viability assessed. NoSi reduced cell viability by 25.99% in Panc1 and 24.38% in SMAD4-. When combined with gemcitabine, further reductions were seen in a dose dependent manner for both cell lines. We have demonstrated the in-vitro dose dependent cytotoxic effects of NOSi. When combined with GEM there is a synergistic effect resulting in improved cytotoxicity seen in both Panc1 and SMAD4- PAC cells with a differential pattern of cell death seen at high concentrations of NO. These findings suggest not only that NO is useful chemosensitizing agent but that SMAD4- may play a role in its synergism with GEM.

Polypharmacy in a hospitalized psychiatric population: risk estimation and damage quantification.

BACKGROUND: Polypharmacy increases the risk of pharmacological interactions, prevalence of secondary effects and with this the lack of adherence to treatment. It is estimated that between 10 and 40% of patients hospitalized in psychiatric institutions are prescribed more than one antipsychotic. The objective of the present study was to identify the prevalence of polypharmacy, evaluate adverse effects associated to the use of psych drugs and to estimate the risk in specific groups. METHODS: We carried out a longitudinal, retrospective study that included the analysis of all discharged patients (n = 140) in the first trimester of the year in a psychiatric hospital in Mexico. The information was classified into 7 sections: sociodemographic, diagnosis, clinical follow-up information, prescribed drugs, adverse reactions, substance abuse, laboratory and complementary results. Risk estimation was obtained with Odds Ratios, to correlate continuous variables Pearson's correlation was used. Student's T and Mann Whitney's U were used to compare 2 independent samples; multiple and linear regressions were carried out. RESULTS: The mean number of drugs used during hospitalization was 7.8 drugs per patient. The mean prescribed psych drugs was 4.07. The mean antipsychotic dose was the risperidone equivalent of 5.08 mg. 29.2% of patients had at least one secondary effect associated to the use of drugs, 17.8% presented extrapyramidal symptoms. 81.4% of patients were prescribed 6 or more drugs (polypharmacy) and were 5 times more likely to suffer a secondary effects (OR 6.24). 14.2% had polypharmacy while receiving antipsychotics and had more than twice the risk of presenting extrapyramidal symptoms (OR 3.05). For each added psych drug, hospital stay increased by 6.56 days. CONCLUSIONS: Despite international guideline recommendations where reasoned and conciliatory prescription of psych drugs is advised, there is still a high prevalence of polypharmacy in patients hospitalized in psychiatric institutions. In the present study 4 out of 5 patients received polypharmacy decreasing tolerability, treatment adherence and increasing the risk and costs secondary to an increased hospital stay.

Demonstration of Single-Barium-Ion Sensitivity for Neutrinoless Double-Beta Decay Using Single-Molecule Fluorescence Imaging.

A new method to tag the barium daughter in the double-beta decay of ^{136}Xe is reported. Using the technique of single molecule fluorescent imaging (SMFI), individual barium dication (Ba^{++}) resolution at a transparent scanning surface is demonstrated. A single-step photobleach confirms the single ion interpretation. Individual ions are localized with superresolution (∼2 nm), and detected with a statistical significance of 12.9σ over backgrounds. This lays the foundation for a new and potentially background-free neutrinoless double-beta decay technology, based on SMFI coupled to high pressure xenon gas time projection chambers.

Paediatric interventional cardiology in Costa Rica: diagnostic reference levels and estimation of population dose.

The goal of the present study was to propose a set of national diagnostic reference levels (DRLs) in Costa Rica for paediatric interventional cardiology (IC) procedures classified by age and weight and to estimate the collective dose of the paediatric population from these intervention practices. The data collection period was May 2016 to May 2017. The third quartile of patient dose data distributions for kerma-area product (KAP) values was set as the national DRLs. A sample of 154 paediatric IC procedures (collected in the national paediatric hospital with a single x-ray system) was used and divided into four age ranges and five weight ranges. The national DRLs obtained for KAPs by age range were 1.79 Gy cm2 (<1 year) to 23.0 Gy cm2 (10-15 years). The national DRLs obtained for KAPs by weight range were 1.0 Gy cm2 (<10 kg) to 49.6 Gy cm2 (50-79 kg). The contribution to the collective dose of the population of Costa Rica amounted to 0.78 person Sv.