The Dynamics of Histone Modifications during Mammalian Zygotic Genome Activation.

Mammalian fertilization initiates the reprogramming of oocytes and sperm, forming a totipotent zygote. During this intricate process, the zygotic genome undergoes a maternal-to-zygotic transition (MZT) and subsequent zygotic genome activation (ZGA), marking the initiation of transcriptional control and gene expression post-fertilization. Histone modifications are pivotal in shaping cellular identity and gene expression in many mammals. Recent advances in chromatin analysis have enabled detailed explorations of histone modifications during ZGA. This review delves into conserved and unique regulatory strategies, providing essential insights into the dynamic changes in histone modifications and their variants during ZGA in mammals. The objective is to explore recent advancements in leading mechanisms related to histone modifications governing this embryonic development phase in depth. These considerations will be useful for informing future therapeutic approaches that target epigenetic regulation in diverse biological contexts. It will also contribute to the extensive areas of evolutionary and developmental biology and possibly lay the foundation for future research and discussion on this seminal topic.

Application of mass cytometry to characterize hematopoietic stem cells in apheresis products of patients with hematological malignancies.

INTRODUCTION: Hematopoietic stem cell transplantation (HSCT) is a widely used therapy, but its success largely depends on the number and quality of stem cells collected. Current evidence shows the complexity of the hematopoietic system, which implies that, in the quality assurance of the apheresis product, the hematopoietic stem cells are adequately characterized and quantified, in which mass cytometry (MC) can provide its advantages in high-dimensional analysis. OBJECTIVE: This research aimed to characterize and enumerate CD45dim/CD34+ stem cells using the MC in apheresis product yields from patients with chronic lymphoid malignant diseases undergoing autologous transplantation at the Abu Dhabi Stem Cells Center. METHODS: An analytical and cross-sectional study was performed on 31 apheresis products from 15 patients diagnosed with multiple myeloma (n = 9) and non-Hodgkin lymphomas (n = 6) eligible for HSCT. The MC was employed using the MaxPar Kit for stem cell immunophenotyping. The analysis was performed manually in the Kaluza and unsupervised by machine learning in Cytobank Premium. RESULTS: An excellent agreement was found between mass and flow cytometry for the relative and absolute counts of CD45dim/CD34+ cells (Bland-Altman bias: -0.029 and -64, respectively), seven subpopulations were phenotyped and no lineage bias was detected for any of the methods used in the pool of collected cells. A CD34+/CD38+/CD138+ population was seen in the analyses performed on four patients with multiple myeloma. CONCLUSIONS: The MC helps to characterize subpopulations of stem cells in apheresis products. It also allows cell quantification by double platform. Unsupervised analysis allows results completion and validation of the manual strategy. The proposed methodology can be extended to apheresis products for purposes other than HSCT.

Las donaciones de sangre en Cuba desde una perspectiva histórica / Blood donations in Cuba from a historical perspective

Introducción: Las donaciones de sangre constituyen una actividad sanitaria de importancia estratégica, su historia ha evolucionado junto a la del sistema de salud cubano. Objetivo: Describir el comportamiento de las donaciones de sangre desde una perspectiva histórica, según las etapas del desarrollo del sistema sanitario cubano. Métodos: Se realizó una investigación por el método histórico-lógico sobre los antecedentes históricos y la actualidad de las donaciones de sangre. La información se obtuvo mediante la entrevista y las revisiones bibliográfica y documental. Resultados: Durante la seudorepública se fundaron las primeras instituciones de salud para las donaciones y transfusiones de sangre, su administración se fundamentaba en las recolecciones provenientes de los donantes remunerados y familiares. En el período revolucionario se logró un programa de sangre organizado e integrado al sistema de salud, por primera vez unificado y de alcance nacional, con la participación coordinada entre el personal del nivel primario de atención y las organizaciones sociales. Esto permitió el creciente y considerable incremento de la disponibilidad de sangre y el desarrollo de la medicina transfusional, las especialidades médico-quirúrgicas y la industria médico-farmacéutica cubanas. Además, se consolidó la práctica de donar sangre como un acto voluntario. Conclusiones: La donación de sangre en Cuba constituye una actividad trazadora que muestra el desarrollo del sistema sanitario cubano en sus diferentes etapas y es reflejo de la voluntad política del gobierno, el pueblo y sus instituciones(AU)

Introduction: Blood donations are health care activity of a strategic importance. Their history has evolved together with the Cuban health system. Objective: To describe the behaviour of blood donations from a historical perspective according to the development stages of the Cuban health system. Method: It was carried out a research by the logic-historical method on the historical background and the current data on blood donations. The information was collected through interviews and the bibliographic and documentary reviews. Results: During the pseudo-republic times, the first institutions for blood donations and transfusions were created, and their managements was supported with the collections of paid donors and relatives. In the Revolution period, it was achieved an organized blood donation program which was integrated to the health system and for the fist time unified and of national scope, with coordinated participation between the staff of the first level of care and the social organizations. This allowed the significant increase of the availability of blood and the development of the Cuban transfusion medicine, medical-surgical specialties and medical-pharmaceutical industry. In addition, it was strengthen the practice of blood donation as a voluntary act. Conclusions: Blood donation in Cuba is a trace activity that shows the development of the Cuban health system in its different stages and it is a reflection of the political will of the Government, the people and the institutions(AU)

Refractory pemphigus vulgaris and high-intensity extracorporeal photopheresis: A case report.

A 41-year-old man with oral pemphigus vulgaris (PV) presented to our clinic with a history of no response to numerous immunosuppressant agents and was referred for extracorporeal photopheresis (ECP) therapy. Although the patient underwent a high-intensity ECP regimen for five months, which included two different photopheresis systems, his oral dysesthesia continued to interfere with oral intake, leading to continued weight loss and other adverse events. The intervention was associated with changes in several immune cell subpopulations without modifying the anti-epidermal antibody titers, aligned with his poor clinical outcome. To the best of the authors' knowledge, this is the first report to examine immunophenotyping of a PV patient who was refractory to previous immunosuppression and recalcitrant to high-intensity ECP therapy.

Wide Range Applications of Spirulina: From Earth to Space Missions.

Spirulina is the most studied cyanobacterium species for both pharmacological applications and the food industry. The aim of the present review is to summarize the potential benefits of the use of Spirulina for improving healthcare both in space and on Earth. Regarding the first field of application, Spirulina could represent a new technology for the sustainment of long-duration manned missions to planets beyond the Lower Earth Orbit (e.g., Mars); furthermore, it could help astronauts stay healthy while exposed to a variety of stress factors that can have negative consequences even after years. As far as the second field of application, Spirulina could have an active role in various aspects of medicine, such as metabolism, oncology, ophthalmology, central and peripheral nervous systems, and nephrology. The recent findings of the capacity of Spirulina to improve stem cells mobility and to increase immune response have opened new intriguing scenarios in oncological and infectious diseases, respectively.

Producción de insumos biológicos - REDAPRODARE / Production of biological inputs - REDAPRODARE

Cuatro cooperativas productoras de hortalizas, frutas y café de los municipios La Palma y San Ignacio en el departamento de Chalatenango, El Salvador, han creado la REDAPRODARE y promueven el desarrollo de prácticas agrícolas sostenibles que contribuyen a la recuperación y conservación de los agroecosistemas de la Reserva Biológica de la Fraternidad, ubicada en la Región Trifinio (El Salvador, Guatemala y Honduras). La red incide a nivel nacional con la producción y distribución de biofertilizantes e insumos orgánicos innovadores, para el desarrollo de la agricultura sostenible. Con el acompañamiento del Plan Trifinio, la REDAPRODARE desarrolló el establecimiento de una planta y laboratorio de bioinsumos y creó la marca Bioamigo para fortalecer el desarrollo de la productividad, la reducción de la vulnerabilidad ambiental, el desarrollo económico y la seguridad alimentaria. La producción, diseminación y comercialización de los insumos biológicos de calidad representan una innovación social y sostenible de una empresa asociativa social sin fines de lucro.

Pharmacists and COVID-19 vaccination - Considering mobile phone caller tunes as a novel approach to promote vaccine uptake in low- and middle-income countries.

As several low- and middle-income countries roll out their COVID-19 vaccination programmes, COVID-19 vaccines hesitancy could threaten the success of such programmes. But pharmacists can play a leading role in addressing COVID-19 vaccine hesitancy by using a critical mobile phone-based technology. This technology, known as caller tunes or ringback tones, is flourishing in low- and middle-income countries such as those in Africa and Asia where it is used to promote popular songs and religious messages. With this technology, callers to mobile phones hear a message or a song instead of the typical ringing sound. There is a need for pharmacists associations to collaborate with the creative arts industry and telecommunication companies to have caller tunes on COVID-19 vaccines. As pharmacists and others download COVID-19 vaccine caller tunes onto their mobile phones, their callers will hear COVID-19 vaccines messages or songs. This could help combat disinformation and hesitancy, and promote widespread vaccination as availability increases.

Molecular study of a large cohort of 109 haemophilia patients from Cuba using a gene panel with next generation sequencing-based technology.

INTRODUCTION: In several countries, molecular diagnosis of haemophilia A (HA) and B (HB) is hampered by a lack of resources for DNA analysis. The advent of next-generation sequencing (NGS) has enabled gene analysis at a reasonable cost. AIM: Describe a collaboration between Cuban and Spanish researchers to identify candidate variants and investigate the molecular epidemiology of 106 Cuban haemophilia patients using NGS. PATIENTS/METHODS: The molecular analysis protocol included well-established LR-PCR procedures to detect F8 inversions, NGS with a 30-gene panel to sequence F8 and F9, and multiplex ligation-dependent probe amplification to identify large structural variants. RESULTS: One-hundred and thirty-one candidate variants were identified along F8, F9, and VWF; 72 were unique and 28 (39%) had not been previously recorded. Putative variants were identified in 105/106 patients. Molecular characterization enabled confirmation and reclassification of: 90 HA (85%), 15 HB (14%), and one type 2N VWD (1%). Null variants leading to non-production of FVIII or FIX were common in severe HA (64%), moderate HA (74%), and severe HB (60%), whereas missense variants were frequent in mild HA (57%) and moderate or mild HB (83%). Additional variants in VWF were identified in 16 patients. CONCLUSION: This is the first description of the molecular epidemiology of HA and HB in Cuba. Variants identified in index cases will be of value for local implementation of familial studies and prenatal diagnosis using the molecular approaches available in Cuba. The results of this protocolled genetic study improved the accuracy of the clinical diagnosis and will facilitate management of these patients.

Viability assessment of human peripheral blood-derived stem cells after three methods of nebulization.

BACKGROUND AND OBJECTIVES: Drug delivery by nebulization has become a crucial strategy for treating different respiratory and lung diseases. Emerging evidence implicates stem cell therapy as a promising tool in treating such conditions, not only by alleviating the related symptoms but by improving the prognosis. However, delivery of human peripheral blood-derived stem cells (hPBSCs) to the respiratory airways remains an innovative approach yet to be realized. This study is an analytic, translational, and in vitro research to assess the viability and morphological changes of identified cell populations in hPBSCs cocktail derived from COVID-19 patients. METHODS AND RESULTS: Peripheral blood (PB) samples were obtained from patients enrolled in the SENTAD-COVID Study (ClinicalTrials.gov Reference: NCT04473170). hPBSCs cocktails (n=15) were provided by the Cells Processing Laboratory of Abu Dhabi Stem Cells Center, and were nebulized by three different methods of nebulization: compressor (jet), ultrasonic, and mesh. Our results reported that nucleated CD45dim cell count was significantly lower after the three nebulization methods, but nucleated CD45- cells show a significant decrease only after mesh nebulization. Mesh-nebulized samples had a significant reduction in viability of both CD45dim and CD45- cells. CONCLUSIONS: This study provides evidence that stem cells derived from PB of COVID-19 patients can be nebulized without substantial loss of cell viability, cell count, and morphological changes using the compressor nebulization. Therefore, we recommend compressor nebulizers as the preferable procedure for hPBSCs delivery to the respiratory airways in further clinical settings.

Safety and efficacy of autologous non-hematopoietic enriched stem cell nebulization in COVID-19 patients: a randomized clinical trial, Abu Dhabi 2020.

BACKGROUND: The novel SARS-CoV-2 has caused the coronavirus disease 2019 (COVID-19) pandemic. Currently, with insufficient worldwide vaccination rates, identifying treatment solutions to reduce the impact of the virus is urgently needed. METHOD: An adaptive, multicentric, open-label, and randomized controlled phase I/II clinical trial entitled the "SENTAD-COVID Study" was conducted by the Abu Dhabi Stem Cells Center under exceptional conditional approval by the Emirates Institutional Review Board (IRB) for COVID-19 Research Committee from April 4th to July 31st, 2020, using an autologous peripheral blood non-hematopoietic enriched stem cell cocktail (PB-NHESC-C) administered by compressor (jet) nebulization as a complement to standard care therapy. The primary endpoints include safety and efficacy assessments, adverse events, the mortality rate within 28 days, and the time to clinical improvement as measured by a 2-point reduction on a seven-category ordinal scale or discharge from the hospital whichever occurred first. RESULTS: The study included a total of 139 randomized COVID-19 patients, with 69 in the experimental group and 70 in the control group (standard care). Overall survival was 94.20% for the cocktail-treated group vs. 90.27% for the control group. Adverse events were reported in 50 (72.46%) patients receiving PB-NHESC-C and 51 (72.85%) in the control group (p = 0.9590), with signs and symptoms commonly found in COVID-19. After the first 9 days of the intervention, 67.3% of cocktail-treated patients recovered and were released from hospitals compared to 53.1% (RR = 0.84; 95% CI, 0.56-1.28) in the control group. Improvement, i.e., at least a 2-point reduction in the severity scale, was more frequently observed in cocktail-treated patients (42.0%) than in controls (17.0%) (RR = 0.69; 95% CI, 0.56-0.88). CONCLUSIONS: Cocktail treatment improved clinical outcomes without increasing adverse events. Thus, the nebulization of PB-NHESC-C was safe and effective for treatment in most of these patients. TRIAL REGISTRATION: ClinicalTrials.gov. NCT04473170. It was retrospectively registered on July 16th, 2020.

Children against antibiotics misuse and antimicrobial resistance: assessing effectiveness of storytelling and picture drawing as public engagement approaches.

Background: Interventions delivered in schools have been found to be effective in improving knowledge of antibiotics and antimicrobial resistance (AMR) among school-aged children, particularly those in high-income countries, but the evidence is largely lacking in low- and middle-income countries. This study aimed to design, implement and assess storytelling and picture drawing as engagement approaches for improving knowledge, attitudes and beliefs about antibiotics and AMR among schoolchildren in Ghana. Methods: Two schools with a total population of 375 schoolchildren ages 11-15 years in Tema, a city in Ghana, participated in public engagement interventions involving storytelling in one school and picture drawing in another school. The interventions included eight weeks of engagement led by science teachers and a competition held in each school. For quantitative outcome-based evaluation, some schoolchildren were randomly sampled in each school. Purposive sampling was also used to select some schoolchildren in each school for qualitative outcome-based evaluation. Respondents completed identical knowledge, attitudes and beliefs questionnaires and were interviewed at two time points (before and at most a week) after key interventions to assess changes in antibiotics and AMR knowledge, attitudes and beliefs. Results: Picture drawing had more significant effects (both positive and negative) on schoolchildren's AMR knowledge, attitudes and beliefs, whereas storytelling had a negative effect on children's AMR knowledge and no significant impact on beliefs and attitudes. Conclusions: Our project's findings suggest that public engagement interventions that use picture drawing and storytelling may influence the knowledge, attitudes and beliefs of schoolchildren regarding antibiotic misuse and AMR. However, modifications are required to make them more effective. These include making the storytelling effective by turning it into drama or plays.

Lipoma arborescente bilateral de hombro: manejo de un caso en consulta de rehabilitación y revisión de la literatura / Bilateral lipoma arborescens of the shoulder: rehabilitation management inoutpatient clinic and literature review

La lipomatosis arborescente, también conocida como 'proliferación de vellosidades de la membrana sinovial', es una entidad que se caracteriza por la proliferación difusa de vellosidades con reemplazo del tejido sinovial por adipocitos maduros. La presentación típica es una enfermedad monoarticular que afecta a la rodilla, con predilección por la bolsa suprapatelar, aunque también se describe afectación mono o biarticular de articulaciones grandes como las caderas, los tobillos, los codos y los hombros. La resonancia magnética nuclear (RMN) es el método de imagen de elección para hacer el diagnóstico. El tratamiento consiste en practicar sinovectomía, ya sea abierta o artroscópica. En este estudio se presenta un caso de lipoma arborescente con afectación simultánea de la bursa subacromial-subdeltoidea, vaina del tendón de la porción larga del bíceps y articulación glenohumeral, que se asoció a lesión del manguito de los rotadores valorado en la Unidad de Alta Resolución de Hombro de nuestro servicio de rehabilitación

Arborescent lipomatosis, also known as 'synovial membrane villous proliferation', is an entity characterized by diffuse proliferation of villi with replacement of synovial tissue by mature adipocytes. The typical presentation is a monoarticular disease affecting the knee, with a predilection for the suprapatellar bursa, although mono- or biarticular involvement of large joints such as the hips, ankles, elbows and shoulders is also described. Magnetic resonance imaging (MRI) is the imaging method of choice for diagnosis. Treatment consists of synovectomy, either open or arthroscopic. This study presents a case of arborescent lipoma with simultaneous involvement of the subacromial-subdeltoid bursa, tendon sheath of the long portion of the biceps and glenohumeral joint, which was associated with rotator cuff lesion assessed in the High Resolution Shoulder Unit of our rehabilitation service.

Renal Involvement in Patients with COVID-19 Pneumonia and Outcomes After Stem Cell Nebulization.

BackgroundThe COVID-19 pandemic presented an unprecedented challenge to identify effective drugs for prevention and treatment. ObjectiveTo characterize acute renal injury (AKI) in patients with COVID-19 and their relation with clinical outcomes within the framework of the SENTAD COVID clinical trial at the Abu Dhabi Stem Cells Center. MethodsAbu Dhabi Stem Cell Center (ADSCC) proposed a prospective clinical trial nebulization treatment with autologous stem cells (Non-Hematopoietic Peripheral Blood Stem Cells (NHPBSC)), at Abu Dhabi hospitals. Participants20 treated patients were compared with 23 not treated patients. Both groups received COVID 19 standard treatment. OutcomesAfter the results were collected, this study was created to determine the impact of the disease on the renal function and the efficacy of the therapy on patients outcomes. ResultsOne third of the critical patients studied suffered kidney failure. Patients in the treated group showed a favorable tendency to improve in contrast to those in the control group. Less patients from group A suffered from sepsis in comparison with the group B (25% vs 65%), HR=0.38, (95% Confidence Interval: 0.16 - 0.86), *p=0.0212. These results suggested a NNT=2.5. An improvement in lymphocyte count, CRP, and shorter hospital stay after treatment was evidenced, which led to less superinfection and sepsis in the treated group. ConclusionsThe proposed anti-inflammatory effect of the stem cells, offers a great promise for managing the illness, emerging as a crucial adjuvant tool in promoting healing and early recovery in severe COVID-19 infections and other supportive treatments. ARTICLE SUMMARYOur study had several strengths and limitation: O_LIIt was a randomized trial. C_LIO_LIThe treatment showed a positive result, providing evidence that this intervention is effective in routine practice. C_LIO_LIWe found fewer complications related to prolonged hospital stay in the treated group. C_LIO_LIThe is the small number of participants. C_LIO_LIIt was carried out in 4 different hospitals, each with different criteria for the selection of the initial empirical antimicrobials, which can cause multiple resistant germs. C_LI

Features and outcomes of secondary sepsis and urinary tract infections in COVID-19 patients treated with stem cell nebulization

BackgroundCOVID-19 is the defining global crisis of our time. Secondary complication such as urinary tract infections and sepsis, worsen the already established problem, creating a new challenge. ObjectiveTo characterize the features and outcomes in COVID-19 patients with sepsis and urinary tract infection. MethodsAn observational and analytical study was conducted within the framework of the SENTAD COVID clinical trial at the Abu Dhabi Stem Cells Center, were the patients received a nebulization therapy with the use of autologous stem cells (group A). Those patients were compared with a not stem cells treated control arm (group B), and both received the UAE COVID 19 standard management. An analysis of the culture samples, antimicrobial agents and the efficacy of the therapy on patients outcomes was done. ResultsA significant difference between the groups was found in the UTI incidence (p=*0.0206). Patients in group A showed a lower tendency to sepsis in comparison with group B (7% vs 21%), HR=0.35, (95% Confidence Interval: 0.13 - 0.91), p=0.0175. It was calculated a NNT=7.3. Candida albicans was the most frequently agent causing sepsis and UTI. The massive use of broad-spectrum antimicrobials was striking. ConclusionsWe found a protective factor of stem cells against secondary infection in COVID 19 cases, in terms of sepsis and UTI. The suggested immunomodulatory effect of stem cells offers a therapeutic strategy to manage the disease and avoid several complications. Antimicrobial agents can lead to increased opportunistic infections, so a rational approach to these treatments must be considered.

Exosomas: terapia celular regenerativa libre de células / Exosomes: "cell-free" regenerative cell therapy

La terapia celular basada en células mesenquimales/estromales se aplica ampliamente en la medicina moderna, aun cuando no todos los mecanismos de supervivencia y diferenciación están identificados. Sin embargo, hace pocos años se comenzaron a encontrar elementos extracelulares que generan nuevos paradigmas. En el presente trabajo se explican las principales características y funciones atribuidas a los exosomas, nanopartículas constituidas por microvesículas secretadas por las células con efecto en la matriz extracelular, y su repercusión como alternativa hacia una medicina regenerativa libre de células. Estas estructuras participan de forma notoria y crucial en la comunicación intercelular, lo que ha supuesto un cambio en el concepto de las funciones y el papel que desempeñan estas vesículas en los organismos vivos, en particular en la restauración de tejidos dañados y la respuesta inflamatoria e inmunológica. Se comentan algunos ejemplos de la repercusión biotecnológica de los exosomas en empresas y el mercado biofarmaceútico(AU)

Mesenchymal/stromal cell ;based therapy is widely applied in modern medicine, even though not all survival and differentiation mechanisms are identified. However, a few years ago, extracellular elements began to be found that generate new paradigms. The present work explains the main characteristics and functions attributed to exosomes, nanoparticles made up of microvesicles secreted by with an effect on the extracellular matrix, and their impact as an alternative towards cell-free regenerative medicine. These structures participate, notoriously and critically, in intercellular communication, which has led to a change in the concept of the functions and role that these vesicles play within living organisms, particularly in the restoration of damaged tissues and the inflammatory and immunological response. Some examples of the exosomes' biotechnological impact on companies and the biopharmaceutical market are discussed(AU)

Corrigendum: Urinary Luteinizing Hormone Tests: Which Concentration Threshold Best Predicts Ovulation?

[This corrects the article DOI: 10.3389/fpubh.2017.00320.].

Urinary Luteinizing Hormone Tests: Which Concentration Threshold Best Predicts Ovulation?

OBJECTIVE: To study the best possible luteinizing hormone (LH) threshold to predict ovulation within the 24, 48, and 72 h. DESIGN: Observational study. SETTING: Multicenter collaborative study. PATIENTS: A total of 107 women. INTERVENTIONS: Women collected daily first morning urine for hormonal assessment and underwent serial ovarian ultrasound. This is a secondary analysis of 283 cycles. MAIN OUTCOME MEASURES: The sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were estimated for varying ranges of LH thresholds. Receiver operating characteristic curves and cost-benefit ratios were used to estimate the best thresholds to predict ovulation. RESULTS: The best scenario to predict ovulation at random was within 24 h after the first single positive test. The false-positive rate was found to increase as (1) the cycle progressed or (2) two or three consecutive tests were used, or (3) ovulation was predicted within 48 or 72 h. Testing earlier in the cycle increases the predictive value of the test. The ideal thresholds to predict ovulation ranged between 25 and 30 mIU/ml with a PPV (50-60%), NPV (98%), LR+ (20-30), and LR- (0.5). At least, one day with LH ≥25 mIU/ml followed by three negatives (LH <25) occurred before ovulation in 31% of all cycles. When used throughout the cycle and evaluated together, peak-fertility type mucus with a positive LH test ≥25 mIU/ml provides a higher specificity than either mucus or LH testing alone (97-99 vs. 77-95 vs. 91%, respectively). CONCLUSION: We identified that beginning LH testing earlier in the cycle (day 7) with a threshold of 25-30 mIU/ml may present the best predictive value for ovulation within 24 h. However, prediction by LH testing alone may be affected negatively by several confounding factors so LH testing alone should not be used to define the end of the fertile window. Complementary markers should be further investigated to predict ovulation and identify the fertile window. The use of the peak cervical mucus along with an LH test may provide a higher specificity and predictive value than either of them alone. We recommend that manufacturers disclose their tests' threshold to the public.

Evaluation of exposure to fluoride in child population of North Argentina.

Fluoride is an important element for humans. It inhibits initiation and progression of dental caries and stimulates bone formation. However, excessive intake may lead to the appearance of dental and/or skeletal fluorosis and a decrease in intellectual coefficient in child populations. This study evaluates exposure to fluoride in the child population of Chaco province (Argentina) by analysis of drinking water, food and its bioaccessible fraction (quantity of fluoride solubilised by gastrointestinal digestion and available for intestinal absorption) and urine as a biomarker of internal dose. The concentration of fluoride in drinking water varied between 0.050 and 4.6 mg L-1, and 80% of the samples exceeded the WHO drinking-water guideline value (1.5 mg L-1). Fluoride concentrations in food ranged between 0.80 and 3.0 mg kg-1 fresh weight (fw), being lower in bioaccessible fraction (0.43-1.9 mg kg-1, fw). On the basis of the consumption data declared for the young child population, fluoride intake varies between 4.1 and 6.5 mg day-1, greater than the level recommended for this age group. Moreover, in some cases, concentrations of fluoride found in urine (0.62-8.9 mg L-1) exceeded those reported in areas with declared fluorosis. All data obtained show the worrying situation of child population in this area of Argentina.

Effects of sodium fluoride on immune response in murine macrophages.

Excessive fluoride intake may be harmful for health, producing dental and skeletal fluorosis, and effects upon neurobehavioral development. Studies in animals have revealed effects upon the gastrointestinal, renal and reproductive systems. Some of the disorders may be a consequence of immune system alterations. In this study, an in vitro evaluation is made of fluoride immunotoxicity using the RAW 264.7 murine macrophage line over a broad range of concentrations (2.5-75mg/L). The results show that the highest fluoride concentrations used (50-75mg/L) reduce the macrophage population in part as a consequence of the generation of reactive oxygen and/or nitrogen species and consequent redox imbalance, which in turn is accompanied by lipid peroxidation. A decrease in the expression of the antiinflammatory cytokine Il10 is observed from the lowest concentrations (5mg/L). High concentrations (50mg/L) in turn produce a significant increase in the proinflammatory cytokines Il6 and Mip2 from 4h of exposure. In addition, cell phagocytic capacity is seen to decrease at concentrations of ≥20mg/L. These data indicate that fluoride, at high concentrations, may affect macrophages and thus immune system function - particularly with regard to the inflammation autoregulatory processes, in which macrophages play a key role.