An Optimal Integral Controller for Adaptive Optics Systems.

Integral controllers are commonly employed in astronomical adaptive optics. This work presents a novel tuning procedure for integral controllers in adaptive optics systems which relies on information about the measured disturbances. This tuning procedure consists of two main steps. First, it models and identifies measured disturbances as continuous-time-damped oscillators using Whittles´s likelihood and the wavefront sensor output signal. Second, it determines the integral controller gain of the adaptive optics system by minimizing the output variance. The effectiveness of this proposed method is evaluated through theoretical examples and numerical simulations conducted using the Object-Oriented Matlab Adaptive Optics toolbox. The simulation results demonstrate that this approach accurately estimates the disturbance model and can reduce the output variance. Our proposal results in improved performance and better astronomical images even in challenging atmospheric conditions. These findings significantly contribute to adaptive optics system operations in astronomical observatories and establish our procedure as a promising tool for fine-tuning integral controllers in astronomical adaptive optics systems.

TIMEx: tumor-immune microenvironment deconvolution web-portal for bulk transcriptomics using pan-cancer scRNA-seq signatures.

SUMMARY: The heterogeneous cell types of the tumor-immune microenvironment (TIME) play key roles in determining cancer progression, metastasis and response to treatment. We report the development of TIMEx, a novel TIME deconvolution method emphasizing on estimating infiltrating immune cells for bulk transcriptomics using pan-cancer single-cell RNA-seq signatures. We also implemented a comprehensive, user-friendly web-portal for users to evaluate TIMEx and other deconvolution methods with bulk transcriptomic profiles. AVAILABILITY AND IMPLEMENTATION: TIMEx web-portal is freely accessible at http://timex.moffitt.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A multilevel, low literacy dual language intervention to promote colorectal cancer screening in community clinics in Florida: A randomized controlled trial.

One of the largest disparities in cancer mortality in the United States occurs with colorectal cancer (CRC). The objectives of this multilevel two-arm intervention trial were to compare the efficacy of two interventions to promote CRC screening (CRCS) with fecal immunochemical test (FIT) and examine sociodemographic and psychosocial predictors of FIT screening. Individuals ages 50-75 (n = 326) who were not up-to-date with CRCS, could understand English or Spanish, and were at average CRC risk were recruited from two federally qualified health centers (FQHCs) in Florida. Prior to intervention, CRCS rates in the FQHCs were 27.1% and 32.9%, respectively. Study enrollment occurred April 2018-November 2019. System-level intervention components included leveraging electronic medical record (EMR) systems and delivering patient reminders. Participants were randomized to C-CARES (education+FIT) or C-CARES Plus (C-CARES+personalized coaching [for those not completing FIT within 90 days]). Primary outcome was completed FIT returned <1 year. Primary outcome analyses were performed using logistic regression. 225 participants completed FIT (69.0% [95% CI: 64.0-74.0%]), with no significant difference in FIT uptake by intervention arm (67.3% C-CARES Plus vs. 70.8% C-CARES; p = .49). FIT uptake was significantly higher among patients who received intervention materials in Spanish (77.2%) compared to those who received materials in English (63.2%, p < .01). The personalized coaching in the C-CARES Plus arm did not appear to provide added benefit beyond the C-CARES intervention. Multilevel approaches that include EMR prompts, reminders, FIT access, and provision of low-literacy, language-concordant education can support efforts to improved community clinics' CRCS rates. Future efforts should focus on repeat FIT screening. Trial registration: The trial was registered at ClinicalTrials.gov (NCT03906110).

LoRa Based IoT Platform for Remote Monitoring of Large-Scale Agriculture Farms in Chile.

Nowadays, conventional agriculture farms lack high-level automated management due to the limited number of installed sensor nodes and measuring devices. Recent progress of the Internet of Things (IoT) technologies will play an essential role in future smart farming by enabling automated operations with minimum human intervention. The main objective of this work is to design and implement a flexible IoT-based platform for remote monitoring of agriculture farms of different scales, enabling continuous data collection from various IoT devices (sensors, actuators, meteorological masts, and drones). Such data will be available for end-users to improve decision-making and for training and validating advanced prediction algorithms. Unlike related works that concentrate on specific applications or evaluate technical aspects of specific layers of the IoT stack, this work considers a versatile approach and technical aspects at four layers: farm perception layer, sensors and actuators layer, communication layer, and application layer. The proposed solutions have been designed, implemented, and assessed for remote monitoring of plants, soil, and environmental conditions based on LoRaWAN technology. Results collected through both simulation and experimental validation show that the platform can be used to obtain valuable analytics of real-time monitoring that enable decisions and actions such as, for example, controlling the irrigation system or generating alarms. The contribution of this article relies on proposing a flexible hardware and software platform oriented on monitoring agriculture farms of different scales, based on LoRaWAN technology. Even though previous work can be found using similar technologies, they focus on specific applications or evaluate technical aspects of specific layers of the IoT stack.

Metformin Treatment Regulates the Expression of Molecules Involved in Adiponectin and Insulin Signaling Pathways in Endometria from Women with Obesity-Associated Insulin Resistance and PCOS.

Polycystic ovary syndrome (PCOS) is an endocrine/metabolic disorder associated with insulin resistance (IR) and obesity. Endometria from women with PCOS present failures in insulin action, glucose uptake and signaling of insulin-sensitizing molecules, such as adiponectin, with consequences for reproduction. Metformin (MTF) treatment improves insulin signaling in endometrial tissues, but its mechanism is not fully understood. This study addresses the MTF effect, as well as adiponectin agonist action, on levels of molecules associated with insulin and adiponectin signaling pathways in endometrial tissue and cells, as assessed by immunohistochemistry and immunocytochemistry, respectively. Endometrial tissues were obtained from women and divided into five groups: Normal Weight (control); Obesity + IR; Obesity + IR + PCOS; Obesity + IR + MTF; Obesity + IR + PCOS + MTF. Endometrial cells stimulated with TNFα (as obesity-marker) were also used to partially emulate an obesity environment. The results showed low levels of insulin/adiponectin signaling in the endometria from women with obesity, IR and PCOS compared with the control group. MTF re-established these levels, independently of PCOS. TNFα-associated molecules were elevated in pathologic endometria, whereas MTF diminished these levels. The low levels of insulin/adiponectin molecules in endometrial cells treated with TNFα were reverted by MTF, similar to what was observed in the case of the adiponectin agonist. Therefore, independently of PCOS, MTF can re-establish levels of molecules involved in insulin/adiponectin signaling in endometrial cells, suggesting an improvement in insulin action and reproductive failures observed in endometria from women with obesity/PCOS.

Sensor Data Integration: A New Cross-Industry Collaboration to Articulate Value, Define Needs, and Advance a Framework for Best Practices.

Data integration, the processes by which data are aggregated, combined, and made available for use, has been key to the development and growth of many technological solutions. In health care, we are experiencing a revolution in the use of sensors to collect data on patient behaviors and experiences. Yet, the potential of this data to transform health outcomes is being held back. Deficits in standards, lexicons, data rights, permissioning, and security have been well documented, less so the cultural adoption of sensor data integration as a priority for large-scale deployment and impact on patient lives. The use and reuse of trustworthy data to make better and faster decisions across drug development and care delivery will require an understanding of all stakeholder needs and best practices to ensure these needs are met. The Digital Medicine Society is launching a new multistakeholder Sensor Data Integration Tour of Duty to address these challenges and more, providing a clear direction on how sensor data can fulfill its potential to enhance patient lives.

On the Uncertainty Identification for Linear Dynamic Systems Using Stochastic Embedding Approach with Gaussian Mixture Models.

In control and monitoring of manufacturing processes, it is key to understand model uncertainty in order to achieve the required levels of consistency, quality, and economy, among others. In aerospace applications, models need to be very precise and able to describe the entire dynamics of an aircraft. In addition, the complexity of modern real systems has turned deterministic models impractical, since they cannot adequately represent the behavior of disturbances in sensors and actuators, and tool and machine wear, to name a few. Thus, it is necessary to deal with model uncertainties in the dynamics of the plant by incorporating a stochastic behavior. These uncertainties could also affect the effectiveness of fault diagnosis methodologies used to increment the safety and reliability in real-world systems. Determining suitable dynamic system models of real processes is essential to obtain effective process control strategies and accurate fault detection and diagnosis methodologies that deliver good performance. In this paper, a maximum likelihood estimation algorithm for the uncertainty modeling in linear dynamic systems is developed utilizing a stochastic embedding approach. In this approach, system uncertainties are accounted for as a stochastic error term in a transfer function. In this paper, we model the error-model probability density function as a finite Gaussian mixture model. For the estimation of the nominal model and the probability density function of the parameters of the error-model, we develop an iterative algorithm based on the Expectation-Maximization algorithm using the data from independent experiments. The benefits of our proposal are illustrated via numerical simulations.

Disturbance Modelling for Minimum Variance Control in Adaptive Optics Systems Using Wavefront Sensor Sampled-Data.

Modern large telescopes are built based on the effectiveness of adaptive optics systems in mitigating the detrimental effects of wavefront distortions on astronomical images. In astronomical adaptive optics systems, the main sources of wavefront distortions are atmospheric turbulence and mechanical vibrations that are induced by the wind or the instrumentation systems, such as fans and cooling pumps. The mitigation of wavefront distortions is typically attained via a control law that is based on an adequate and accurate model. In this paper, we develop a modelling technique based on continuous-time damped-oscillators and on the Whittle's likelihood method to estimate the parameters of disturbance models from wavefront sensor time-domain sampled-data. On the other hand, when the model is not accurate, the performance of the minimum variance controller is affected. We show that our modelling and identification techniques not only allow for more accurate estimates, but also for better minimum variance control performance. We illustrate the benefits of our proposal via numerical simulations.

A Two-Filter Approach for State Estimation Utilizing Quantized Output Data.

Filtering and smoothing algorithms are key tools to develop decision-making strategies and parameter identification techniques in different areas of research, such as economics, financial data analysis, communications, and control systems. These algorithms are used to obtain an estimation of the system state based on the sequentially available noisy measurements of the system output. In a real-world system, the noisy measurements can suffer a significant loss of information due to (among others): (i) a reduced resolution of cost-effective sensors typically used in practice or (ii) a digitalization process for storing or transmitting the measurements through a communication channel using a minimum amount of resources. Thus, obtaining suitable state estimates in this context is essential. In this paper, Gaussian sum filtering and smoothing algorithms are developed in order to deal with noisy measurements that are also subject to quantization. In this approach, the probability mass function of the quantized output given the state is characterized by an integral equation. This integral was approximated by using a Gauss-Legendre quadrature; hence, a model with a Gaussian mixture structure was obtained. This model was used to develop filtering and smoothing algorithms. The benefits of this proposal, in terms of accuracy of the estimation and computational cost, are illustrated via numerical simulations.

Exogenous Application of Brassinosteroid 24-Norcholane 22(S)-23-Dihydroxy Type Analogs to Enhance Water Deficit Stress Tolerance in Arabidopsis thaliana.

Brassinosteroids (BRs) are plant hormones that play an essential role in plant development and have the ability to protect plants against various environmental stresses, such as low and high temperature, drought, heat, salinity, heavy metal toxicity, and pesticides. Mitigation of stress effects are produced through independent mechanisms or by interaction with other important phytohormones. However, there are few studies in which this property has been reported for BRs analogs. Thus, in this work, the enhancement of drought stress tolerance of A. thaliana was assessed for a series of 2-deoxybrassinosteroid analogs. In addition, the growth-promoting activity in the Rice Lamina Inclination Test (RLIT) was also evaluated. The results show that analog 1 exhibits similar growth activity as brassinolide (BL; used as positive control) in the RLIT bioassay. Interestingly, both compounds increase their activities by a factor of 1.2-1.5 when they are incorporated to polymer micelles formed by Pluronic F-127. On the other hand, tolerance to water deficit stress of Arabidopsis thaliana seedlings was evaluated by determining survival rate and dry weight of seedlings after the recovery period. In both cases, the effect of analog 1 is higher than that exhibited by BL. Additionally, the expression of a subset of drought stress marker genes was evaluated in presence and absence of exogenous applied BRs. Results obtained by qRT-PCR analysis, indicate that transcriptional changes of AtDREBD2A and AtNCED3 genes were more significant in A. thaliana treated with analog 1 in homogeneous solution than in that treated with BL. These changes suggest the activation of alternative pathway in response to water stress deficit. Thus, exogenous application of BRs synthetic analogs could be a potential tool for improvement of crop production under stress conditions.

PDXGEM: patient-derived tumor xenograft-based gene expression model for predicting clinical response to anticancer therapy in cancer patients.

BACKGROUND: Cancer is a highly heterogeneous disease with varying responses to anti-cancer drugs. Although several attempts have been made to predict the anti-cancer therapeutic responses, there remains a great need to develop highly accurate prediction models of response to the anti-cancer drugs for clinical applications toward a personalized medicine. Patient derived xenografts (PDXs) are preclinical cancer models in which the tissue or cells from a patient's tumor are implanted into an immunodeficient or humanized mouse. In the present study, we develop a bioinformatics analysis pipeline to build a predictive gene expression model (GEM) for cancer patients' drug responses based on gene expression and drug activity data from PDX models. RESULTS: Drug sensitivity biomarkers were identified by performing an association analysis between gene expression levels and post-treatment tumor volume changes in PDX models. We built a drug response prediction model (called PDXGEM) in a random-forest algorithm by using a subset of the drug sensitvity biomarkers with concordant co-expression patterns between the PDXs and pretreatment cancer patient tumors. We applied the PDXGEM to several cytotoxic chemotherapies as well as targeted therapy agents that are used to treat breast cancer, pancreatic cancer, colorectal cancer, or non-small cell lung cancer. Significantly accurate predictions of PDXGEM for pathological response or survival outcomes were observed in extensive independent validations on multiple cancer patient datasets obtained from retrospective observational studies and prospective clinical trials. CONCLUSION: Our results demonstrated the strong potential of using molecular profiles and drug activity data of PDX tumors in developing a clinically translatable predictive cancer biomarkers for cancer patients. The PDXGEM web application is publicly available at http://pdxgem.moffitt.org .

Exploring patient and provider perspectives on the intersection between fertility, genetics, and family building.

OBJECTIVE: Adolescent and young adult (AYA) cancer patients have distinct medical and psychosocial needs and fertility is a key concern. Early age of onset is a risk factor for hereditary cancer and AYAs are more likely to experience reduced fertility. This has implications for future family building decisions and fertility preservation (FP) and genetic testing/counseling (GT/GC) education. METHODS: Patients diagnosed with cancer between the ages of 18 and 39 and health care providers (HCPs) who treat AYA cancer patients were recruited from a single institution. Qualitative interviews explored AYA patients' and HCPs' concerns regarding their experiences discussing genetics and FP. RESULTS: The majority of patients (n = 17) were female (59%), and the majority of HCPs (n = 18) were male (67%). Overall, participants had differing perceptions of FP and GT/GC-related information provided during the clinical visit. Patients indicated initiating the conversation about FP and did not recall HCPs discussing GT/GC with them. HCPs indicated patients were often overwhelmed with too much information and comprehension of this discussion is limited. HCPs also felt patients' emotions/beliefs determined their information-seeking behavior specific to FP and GT/GC. Participants felt educational materials should be developed and delivered in a video format depicting a patient-provider interaction or patient testimonial. CONCLUSION: AYA patients are often overwhelmed by a cancer diagnosis; the complexity/volume of information regarding FP and GT/GC may hinder understanding and decision-making about family building. Educational materials that help patients understand what questions to ask HCPs about FP and GT/GC should be developed to improve knowledge, psychosocial well-being, and future family building decisions.

Biological Activities and Molecular Docking of Brassinosteroids 24-Norcholane Type Analogs.

The quest and design of new brassinosteroids analogs is a matter of current interest. Herein, the effect of short alkyl side chains and the configuration at C22 on the growth-promoting activity of a series of new brassinosteroid 24-norcholan-type analogs have been evaluated by the rice leaf inclination test using brassinolide as positive control. The highest activities were found for triol 3 with a C22(S) configuration and monobenzoylated derivatives. A docking study of these compounds into the active site of the Brassinosteroid Insensitive 1(BRI1)-ligand-BRI1-Associated Receptor Kinase 1 (BAK1) complex was performed using AutoDock Vina, and protein-ligand contacts were analyzed using LigPlot+. The results suggest that the hydrophobic interactions of ligands with the receptor BRI1LRR and hydrogen bonding with BAK1 in the complex are important for ligand recognition. For monobenzoylated derivatives, the absence of the hydrophobic end in the alkyl chain seems to be compensated by the benzoyl group. Thus, it would be interesting to determine if this result depends on the nature of the substituent group. Finally, mixtures of S/R triols 3/4 exhibit activities that are comparable or even better than those found for brassinolide. Thus, these compounds are potential candidates for application in agriculture to improve the growth and yield of plants against various types of biotic and abiotic stress.

Synthesis of 2-Deoxybrassinosteroids Analogs with 24-nor, 22(S)-23-Dihydroxy-Type Side Chains from Hyodeoxycholic Acid.

Natural brassinosteroids are widespread in the plant kingdom and it is known that they play an important role in regulating plant growth. In this study, two new brassinosteroid analogs with shorter side chains but keeping the diol function were synthesized. Thus, the synthesis of 2-deoxybrassinosteroids analogs of the 3α-hydroxy-24-nor, 22,23-dihydroxy-5α-cholestane side chain type is described. The starting material is a derivative from hyodeoxycholic acid (4), which was obtained with an overall yield of 59% following a previously reported five step route. The side chain of this intermediate was modified by oxidative decarboxylation to get a terminal olefin at the C22-C23 position (compound 20) and subsequent dihydroxylation of the olefin. The resulting epimeric mixture of 21a, 21b was separated and the absolute configuration at the C22 carbon for the main product 21a was elucidated by single crystal X-ray diffraction analysis of the benzoylated derivative 22. Finally, lactonization of 21a through a Baeyer-Villiger oxidation of triacetylated derivative 23, using CF3CO3H/CHCl3 as oxidant system, leads to lactones 24 and 25 in 35% and 14% yields, respectively. Deacetylation of these compounds leads to 2-deoxybrassinosteroids 18 and 19 in 86% and 81% yields. Full structural characterization of all synthesized compounds was achieved using their 1D, 2D NMR, and HRMS data.

Minimum variance control for mitigation of vibrations in adaptive optics systems.

In this paper, we address the design of a minimum variance controller (MVC) for the mitigation of vibrations in modern telescope adaptive optics (AO) systems. It is widely accepted that a main source of non-turbulent perturbations is the mechanical resonance induced by the wind or the instrumentation systems, such as fans and cooling pumps. To adequately mitigate vibrations, the application of frequency-based controllers has been considered in the past decade. In this work, we express the system model in terms of the tracking of a zero-input signal via the MVC. We show that the MVC is an equivalent representation of the linear quadratic Gaussian (LQG) controller for the AO system. We also show that by developing the MVC, we can obtain different expressions, in terms of transfer functions, that offer insights into the behavior and expected performance of the controller in the frequency domain. In addition, we analyze the impact of the accuracy of the system and perturbations model on the mitigation of vibrations.

Structural Modifications of Deoxycholic Acid to Obtain Three Known Brassinosteroid Analogues and Full NMR Spectroscopic Characterization.

An improved synthesis route for obtaining known brassinosteroid analogues, i.e., methyl 2α,3α-dihydroxy-6-oxo-5α-cholan-24-oate (11), methyl 3α-hydroxy-6-oxo-7-oxa-5α-cholan-24-oate (15) and methyl 3α-hydroxy-6-oxa-7-oxo-5α-cholan-24-oate (16), from hyodeoxycholic acid (4) maintaining the native side chain is described. In the alternative procedure, the di-oxidized product 6, obtained in the oxidation of methyl hyodeoxycholate 5, was converted almost quantitatively into the target monoketone 7 by stereoselective reduction with NaBH4, increasing the overall yield of this synthetic route to 96.8%. The complete ¹H- and (13)C-NMR assignments for all compounds synthesized in this work have been made by 1D and 2D heteronuclear correlation gs-HSQC and gs-HMBC techniques. Thus, it was possible to update the spectroscopic information of ¹H-NMR and to accomplish a complete assignment of all (13)C-NMR signals for analogues 5-16, which were previously reported only in partial form.

Metformin augments the levels of molecules that regulate the expression of the insulin-dependent glucose transporter GLUT4 in the endometria of hyperinsulinemic PCOS patients.

STUDY QUESTION: Does treatment with the insulin sensitizer metformin modify the levels and activation of proteins related to the expression of the insulin-dependent glucose transporter (GLUT4), such as adenosine monophosphate-activated protein kinase (AMPK) and myocyte enhancer factor 2A (MEF2A), in endometria from hyperinsulinemic hyperandrogenemic polycystic ovary syndrome (PCOS h-Ins) patients? SUMMARY ANSWER: In PCOS h-Ins patients, metformin increases endometrial levels of GLUT4 mRNA and protein levels by normalizing the quantity and activation of molecules that regulate GLUT4 expression to healthy values. These changes could improve endometrial metabolic function. WHAT IS ALREADY KNOWN: PCOS is an endocrine-metabolic disorders closely associated with insulin resistance. In particular, the insulin signaling pathway is impaired in endometria from these patients and the concentration of GLUT4, as well as the molecules involved in its translocation to the cell surface, is decreased. However, there are limited data about the mechanisms that regulate the GLUT4 expression in the endometria and the effect of metformin on them. STUDY DESIGN, SIZE AND DURATION: This is a case-control study in the setting of a research unit, approved by the Ethical Committees of our institution. The groups whose endometria were studied were PCOS h-Ins (n = 8); PCOS patients with hyperandrogenemia hyperinsulinemia taking only metformin for at least 3 months (PCOS-MTF, n = 8) and healthy fertile women at the time of hysterectomy because of benign pathology as controls (CE, n = 8). PARTICIPANTS/MATERIALS, SETTING, METHODS: Steroids and sex hormone-binding globulin were measured and glucose and insulin levels were evaluated during an oral glucose tolerance test. Protein levels for αAMPK (catalytic subunit of AMPK), phosphorylated (p)-AMPKαThr(172) (activating phosphorylation site), MEF2A, p-MEF2AThr312 (activating phosphorylation site) and GLUT4 were assessed by western blot and immunohistochemistry. In addition, GLUT4 gene expression was evaluated by RT-PCR. MAIN RESULTS AND THE ROLE OF CHANCE: We found significantly lower levels of MEF2A and p-MEF2AThr312 in PCOS h-Ins compared with CE endometria (P < 0.05). Also, we detected lower levels of p-AMPKαThr(172) in PCOS h-Ins endometria compared with the PCOS-MTF group (P < 0.05). The ratios of phospho-AMPK/total AMPK and phospho-MEF2A/total MEF2A were significantly increased in the PCOS-MTF compared with the PCOS h-Ins group (P < 0.05). The RT-PCR experiments showed lower levels of GLUT4 mRNA transcripts in PCOS h-Ins compared with PCOS-MTF-treated group (P < 0.05), the protein levels of GLUT4 were decreased in a similar way. LIMITATIONS, REASONS FOR CAUTION: The limited number of patients included in this study who presented large clinical variability. Therefore, it would be necessary to recruit a greater number of patients to minimize our data dispersion in order to prove the clinical benefits of metformin described by others. WIDER IMPLICATIONS OF THE FINDINGS: Since the insulin sensitizer metformin increases the expression of the GLUT4, it may improve endometrial physiology in PCOS patients and, therefore, promote better reproductive outcomes. These results suggest that in PCOS patients, metformin may act directly at the endometrial level and decrease insulin resistance condition by increasing the expression of GLUT4 and, in this way, indirectly restore endometrial function. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by Fondo Nacional de Desarrollo Científico y Tecnológico (grant number 1095127 to M.V.). None of the authors has any conflict of interest to declare.

[Streptococcus suis meningitis in pig farmers: report of first two cases in Chile]. / Meningitis bacteriana aguda por Streptococcus suis en criadores de cerdos: comunicación de los primeros dos casos en Chile.

UNLABELLED: Human infection by Streptococcus suis is a zoonosis with a known occupational risk. Meningitis is its most frequent clinical manifestation. We present the first two cases in Chile. FIRST CASE: 54-year-old female patient, pig-farmer. She presented headache, vomiting, confusion and meningismus. She presented septic shock. Second case: 48-year-old male patient, also pig farmer, presented headache, vomiting and meningismus. A Gram's staining of cerebrospinal fluid (CSF) showed gram-positive cocci in both cases. Ceftriaxone and dexamethasone treatment was administered. The CSF cultures were positive for Streptococcus suis serotype 2. The patients experienced a good outcome, without neurological sequelae at the time of discharge. It is considerable to evaluate epidemiologic factors in order to suspect this etiological agent in cases of meningitis. These cases enhance the need of heighten awareness of potential for occupational exposure and infection by this emerging human pathogen. Educating population at risk about simple preventive measures must be considered.

Antimicrobial, Antioxidant, and Anti-Inflammatory Properties of Monofloral Honeys from Chile.

Honey is a mixture of compounds produced by bees that has been appreciated by humanity since the creation of the oldest civilizations. It has multiple uses and can be a highly nutritional and healing substance. It has been used in traditional medicine as a natural alternative for the treatment of diverse clinical conditions. This is due to its reported bioactive properties. The objective of this article is to exhibit and analyze the biological properties of different types of honey originating from Chile based on their antimicrobial, antioxidant, and anti-inflammatory activities, focusing primarily on recompiling experimental studies made on monofloral honey of plant species present in the Chilean territory. The result of this bibliographical review shows that Chilean honey possesses remarkable bioactive properties, mainly antimicrobial and antioxidant activities, with a few studies on its anti-inflammatory activity. Most of these results were attributed to monofloral honey belonging to ulmo (Eucryphia cordifolia) and quillay (Quillaja saponaria Molina) plant species. These properties are related to the presence of several bioactive components, such as phenolic components (mainly flavonoids), hydrogen peroxide (H2O2), enzymes, proteins, and carbohydrates. The biodiversity of the flora and the environmental conditions of the Chilean territory are responsible for the wide range of bioactive compounds and biological properties found in Chilean honey. Further studies must be made to uncover the medicinal potential of these native honeys.

Frequency of diminished ovarian reserve in women with multiple sclerosis in Chile: An exploratory study.

INTRODUCTION: Multiple Sclerosis (MS) is a chronic disease affecting around 2.8 million people worldwide. Two-thirds are women, and the mean age at diagnosis is about 30 years old. Social trends are moving towards older age at first pregnancy, both in women with and without MS. OBJECTIVES: To determine the frequency of diminished ovarian reserve (DOR) through anti-Mullerian Hormone (AMH) measurement in women with MS at fertile age and Healthy Females (HF) in Chile. METHODS: Case-control, multicentric, cross-sectional study including relapsing-remitting people with MS (pwMS) between 18 and 40 years and sex and age-matched HF. We obtained a blood sample to determine AMH levels. We defined DOR as AMH <1.5 ng/mL and very-low AMH levels as <0.5 ng/mL. Also, we performed questions regarding reproductive decision-making. RESULTS: We included 79 sex and age-matched HF and 92 pwMS, median age 32(19-40) years, median disease duration 6 (1-17)years, median EDSS 1.0 (0-6), 95% were receiving disease-modifying therapy (DMT), 70% high-efficacy DMT and 37% with a treatment that contraindicates pregnancy. DOR was observed in 24% (n = 22) of the pwMS, compared to 14% (n = 11) of the HF (p = 0.09), while very-low AMH levels were observed in 7.6% (n = 7) of pwMS and none of the HF (p = 0.0166). We observed an inverse correlation between age and AMH levels. Age was the only significant risk factor for low AMH levels in pwMS (OR 1.14 95%CI(1.00-1-31), p = 0.04), including smoking, body mass index (BMI), hormonal contraception, autoimmune comorbidity, high/low-moderate efficacy DMT, and active disease as covariables. We did not find statistically significant differences in age at diagnosis, BMI, disease duration, EDSS, autoimmune comorbidity, use of hormonal contraception, or percentage of active disease between MS women with normal vs DOR. Over 70% of pwMS desired to become pregnant in the future, while 60% considered that the diagnosis of MS was a limitation for pregnancy planning. CONCLUSIONS: No differences in DOR, measured by levels of AMH, were observed between pwMS MS and HF in Chile. As expected, AMH levels were correlated only with ageing. This information may be evaluated early during the disease course to help patients and neurologists with fertility counselling and family planning considerations regarding DMT use.