Long-time discrete particle effects versus kinetic theory in the self-consistent single-wave model

The influence of the finite number N of particles coupled to a monochromatic wave in a collisionless plasma is investigated. For growth as well as damping of the wave, discrete particle numerical simulations show an N-dependent long time behavior resulting from the dynamics of individual particles. This behavior differs from the one due to the numerical errors incurred by Vlasov approaches. Trapping oscillations are crucial to long time dynamics, as the wave oscillations are controlled by the particle distribution inhomogeneities and the pulsating separatrix crossings drive the relaxation towards thermal equilibrium.Comment: 11 pages incl. 13 figs. Phys. Rev. E, in pres

Fortification of wheat and maize flour with folic acid for population health outcomes

ABSTRACT: This is the protocol for a review and there is no abstract. The objectives are as follows: To evaluate the health benefits and safety of folic acid fortification of wheat and maize flour (alone or in combination with other micronutrients) on folate status and health outcomes in the overall population, with emphasis on populations at risk. For the purposes of this review, a fortified wheat product includes any food prepared from fortified wheat flour; a fortified maize flour product includes any food prepared from fortified corn meal or maize flour. We will include composite flours that contain more than 50% wheat or maize within the definition of flour in this review

Prolactinomas, Cushing's disease and acromegaly: debating the role of medical therapy for secretory pituitary adenomas

Pituitary adenomas are associated with a variety of clinical manifestations resulting from excessive hormone secretion and tumor mass effects, and require a multidisciplinary management approach. This article discusses the treatment modalities for the management of patients with a prolactinoma, Cushing's disease and acromegaly, and summarizes the options for medical therapy in these patients

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide

Medical genetics in developing countries in the Asia-Pacific region: challenges and opportunities

Advances in genetic and genomic technology changed health-care services rapidly in low and middle income countries (LMICs) in the Asia-Pacific region. While genetic services were initially focused on population-based disease prevention strategies, they have evolved into clinic-based and therapeutics-oriented service. Many LMICs struggled with these noncommunicable diseases and were unprepared for the needs of a clinical genetic service. The emergence of a middle class population, the lack of regulatory oversight, and weak capacity-building in medical genetics expertise and genetic counseling services led to a range of genetic services of variable quality with minimal ethical oversight. Some of the current shortcomings faced include the lack of awareness of cultural values in genetic health care, the variable stages of socioeconomic development and educational background that led to increased demand and abuse of genetics, the role of women in society and the crisis of gender selection, the lack of preventive and care services for genetic and birth defects, the issues of gene ethics in medicine, and the lack of understanding of some religious controversies. These challenges provide opportunities for both developing and developed nations to work together to reduce the inequalities and to ensure a caring, inclusive, ethical, and cost-effective genetic service in the region

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Análisis de los beneficios y riesgos de la fortificación de harina de trigo con ácido fólico en Chile

La fortificación mandataria de harina de trigo con ácido fólico ha sido implementada en numerosos países con el objetivo de reducir el número de recién nacidos con defectos del tubo neural (DTN). Chile implementó esta intervención nutricional a partir del año 2000. El ácido fólico es la vitamina más utilizada en alimentos fortificados y suplementos vitamínicos y corresponde a una forma más oxidada que la natural. Actúa como cofactor y co-sustrato para la metilación biológica y la síntesis de ácidos nucleicos, transportando unidades activas monocarbonadas necesarias para la síntesis de purinas y timidilato, así como para la síntesis, replicación y reparación del ácido desoxirribonucleico (ADN). La revisión sistemática de estudios no controlados de diferentes países que fortifican harina con ácido fólico muestra una importante reducción de DTN. En Chile esta reducción alcanza a 55% considerando un período de diez años a partir del inicio de la fortificación. Chile monitorea el nivel de ácido fólico en harina de trigo desde el año 2005. El análisis de esta información muestra una importante dispersión del nivel de ácido fólico cuando se compara con lo establecido en la norma chilena (2.2 mg/kg). Entre los años 2005 y 2008 destaca que 50% de las muestras presentaba niveles inferiores a lo establecido por norma, 10% no contenía ácido fólico y 30% presentaba niveles muy elevados. La estimación indirecta de la ingesta de folatos totales alcanza, en algunos grupos de adultos mayores, niveles superiores al Límite Superior Tolerable de Ingesta para adultos (>1000 μg/día) que se refleja en elevados niveles de folato sérico. Estos alcanzan niveles suprafisiológicos (>20 μg/L) en 50% de adultos mayores estudiados, siendo el déficit de folato sérico casi inexistente. Una extensa información se ha publicado durante los últimos años en relación a riesgos en salud derivado de la suplementación con ácido fólico, sugiriendo un aumento del riesgo de algunos tipos de cáncer cuando se consume en altas dosis, por tiempo prolongado y asociado a la existencia de lesiones preneoplásicas previas, entre ellos, un aumento en la recurrencia de adenomas colorrectales y de cáncer de colon, sin embargo la revisión sistemática desarrollada no permite concluir la existencia de mayor riesgo. En relación con el cáncer de mama, no puede concluirse que existan beneficios o riesgos asociados a dicha suplementación, observándose sólo un efecto protector en aquellas bebedoras de alcohol y portadoras de algunos polimorfismos de enzimas del ciclo del folato. El folato y otras vitaminas relacionadas, especialmente vitamina B12, cumplen además una importante función en el crecimiento, diferenciación, desarrollo y reparación cerebral, así como también, en la cognición, encontrándose que la suplementación mejora la función cognitiva cuando los niveles de folato sérico iniciales son bajos. En adultos mayores chilenos, cuando los valores de folato sérico son bajos y los niveles de vitamina B12 elevados, el incremento de una unidad de folato sérico (1 μg/L) disminuye el riesgo de deterioro cognitivo; en cambio, el aumento de una unidad de folato sérico cuando los niveles son elevados y el nivel de vitamina B12 bajo aumenta el riesgo. En resumen, la fortificación universal de harina de trigo con ácido fólico en Chile ha sido una intervención nutricional exitosa cumpliendo con el objetivo de reducir la prevalencia de los defectos del tubo neural, determinando un beneficio para la salud y calidad de vida de los recién nacidos, pero también ha determinado un incremento importante de la ingesta de folatos totales y de folato sérico, especialmente en adultos mayores, sugiriendo revisar los niveles de fortificación que prevengan el mayor riesgo de deterioro de la función cognitiva observado en ambos extremos de la distribución de folato sérico.Mandatory fortification of wheat flour with folic acid has been implemented in many countries in order to reduce the number of newborns with neural tube defects (NTDs). Chile has implemented this nutritional intervention since 2000. Folic acid is the most commonly used in fortified foods and supplements. Folate acts as cofactors and co-substrates for methylation, biological synthesis of nucleic acids being essential for DNA replication and repair. The systematic review of uncontrolled studies from different countries that fortified flour with folic acid shows a significant reduction in NTD. In Chile this reduction was 55 % within period of ten years from the beginning of flour fortification. Chile monitors wheat flour folic acid levels since 2005. Analysis of these data in the flour samples shows an important dispersion level when compared with the established in the Chilean rule (2.2 mg/kg). Between 2005 and 2008, 50% of samples had less folic acid that established by law, 10% did not contain folic acid, and 30 % had very high levels. Indirect estimation of total folate intake reached higher levels than adult folic acid Upper Level (>1000 mg/day) in some elderly people, which is related to the high serum folate level. Fifty percent of older adults reached supraphysiological levels (>20 μg/L) with no serum folate deficiency. An extensive literature has been lately published related to health risks derived from folic acid supplementation, suggesting an increased risk of some cancers when it is consumed in high doses, for prolonged periods and associated with preneoplastic lesions, an increase in the recurrence of colorectal adenomas and colon cancer, but it cannot be established that supplementation with folic acid would have benefits on the recurrence of colorectal adenomas or cancer prevention. It cannot be also concluded that folic acid supplementation would have benefits or risks on breast cancer. Its protective effect is only observed in women who drank alcohol and are carriers of some enzyme polymorphisms of folate cycle. Folate and related vitamins, especially vitamin B12, play an important role in growth, differentiation, brain development and repair, as well as, in cognition, finding that supplementation improves cognitive function when initial serum folate levels are low. In elderly Chileans, when serum folate values are low and vitamin B12 levels are high, each one unit (1 μg/L) increase of serum folate decreases the risk of cognitive impairment; however, the one unit increase when serum folate levels are high and the low level of vitamin B12 increases the risk. In summary, the universal wheat flour folic acid fortification in Chile has been a successful nutritional intervention that has met its goal of reducing the prevalence of NTD determining a benefit to the health and quality of life of newborns, but it has also led to an increase in the intake of total folate and serum folate, especially in older adults, suggesting to reassess folic acid fortification level to prevent the increased risk of impaired cognitive function observed at both extremes of serum folate distribution