Somos Esenciales, We are Essential: Our Mental Health is Essential. Research for, by and of the Latinx Community in the Mission District during the Pandemic.

We are Latinx immigrants and children of Latinx immigrants. We provided emergency volunteer services at the Mission Food Bank during the pandemic to provide food assistance to low-income families in the Mission District and the city of San Francisco. In March 2021, we were invited to lead a research project that we call "We are Essential". Here we share our process and a few of our findings on the mental health of San Francisco's Latinx community during the pandemic, with a focus on our children and youth. A full report of our findings will be published in 2024.

Comparison of the Magnetic and Structural Properties of MnFePSi Microwires and MnFePSi Bulk Alloy.

We provide comparative studies of the structural, morphological, microstructural, and magnetic properties of MnFePSi-glass-coated microwires (MnFePSi-GCMWs) and bulk MnFePSi at different temperatures and magnetic fields. The structure of MnFePSi GCMWs prepared by the Taylor-Ulitovsky method consists of the main Fe2P phase and secondary impurities phases of Mn5Si3 and Fe3Si, as confirmed by XRD analysis. Additionally, a notable reduction in the average grain size from 24 µm for the bulk sample to 36 nm for the glass-coated microwire sample is observed. The analysis of magnetic properties of MnFePSi-glass-coated microwires shows different magnetic behavior as compared to the bulk MnFePSi. High coercivity (450 Oe) and remanence (0.32) are observed for MnFePSi-GCMWs compared to low coercivity and remanent magnetization observed for bulk MnFePSi alloy. In addition, large irreversibility at low temperatures is observed in the thermal dependence of magnetization of microwires. Meanwhile, the bulk sample shows regular ferromagnetic behavior, where the field cooling and field heating magnetic curves show a monotonic increase by decreasing the temperature. The notable separation between field cooling and field heating curves of MnFePSi-GCMWs is seen for the applied field at 1 kOe. Also, the M/M5K vs. T for MNFePSi-GCMWs shows a notable sensitivity at a low magnetic field compared to a very noisy magnetic signal for bulk alloy. The common features for both MnFePSi samples are high Curie temperatures above 400 K. From the experimental results, we can deduce the substantial effect of drawing and quenching involved in the preparation of glass-coated MnFePSi microwires in modification of the microstructure and magnetic properties as compared to the same bulk alloy. The provided studies prove the suitability of the Taylor-Ulitovsky method for the preparation of MnFePSi-glass-coated microwires.

El deporte paralímpico en Chile: resultados históricos de las participaciones en los juegos paralímpicos de invierno y verano / Paralympic sport in Chile: historical results of participation in summer and winter paralympic games / O esporte paralímpico no Chile: resultados históricos das participações em jogos paralímpico de inverno e verão

Esta investigación tuvo como objetivo relatar la evolución del movimiento paralímpico y su vínculo con el escenario político nacional e internacional. Los Juegos Paralímpicos de Verano hicieron su debut en 1960, mientras que Chile participó por primera vez en 1992. Por otro lado, los Juegos Paralímpicos de Invierno comenzaron en 1976, y la primera participación chilena en este evento se produjo en 2002. Para el desarrollo del estudio se utilizó un análisis documental, donde se analizaron las convocatorias oficiales de las delegaciones chilenas, junto con las planillas de resultados generales obtenidos en los Juegos Paralímpicos, se extrajo de los documentos: el número de atletas participantes de ambos sexos y deportes, información que posteriormente fue agrupada en presencia o no de medallas y tipo de medalla obtenida y, a partir de aquello, se analizó por tipo de discapacidad y año de participación. A través de los años, Chile vivenció constantes procesos y cambios en los periodos de gestión, a esto se suma la promulgación de leyes, tanto nacionales como internacionales, junto con la constante ayuda recibida de distintas agrupaciones privadas y gubernamentales, resultando en un paulatino incremento de deportistas paralímpicos, situación que colaboró en gran medida con el desarrollo integral del movimiento paralímpico chileno hasta lo que es en la actualidad; este crecimiento facilitó resultados exitosos, como el obtenido en el año 2012 con la conquista de la primera medalla paralímpica de Chile, llegando a un total de siete medallas distribuidas en cuatro deportes en los Juegos Paralímpicos Tokio 2020, quedando situado en el ranking paralímpico en la cuadragésima quinta posición.

The aim of this paper was to describe the evolution of the Paralympic movement and its connection with the national and international political scenario. The Summer Paralympic Games made their debut in 1960, while Chile first participated in 1992. On the other hand, the Winter Paralympic Games began in 1976, and Chile's first participation in this event occurred in 2002. A documentary analysis was conducted for the study, in which the official documents of the Chilean delegations were analyzed, along with the overall results obtained in the Paralympic Games. The documents provided information on the number of participating athletes of both genders, results and sports. This information was later grouped based on the presence or absence of medals and the type of medal obtained. It was further analyzed by type of disability and year of participation. Over the years, Chile experienced constant processes and changes in management, in addition to the enactment of laws, both national and international. The constant support received from various private and governmental organizations contributed to the gradual increase in paralympic athletes, which greatly facilitated the overall development of the Chilean Paralympic movement to its current state. This growth led to successful outcomes, such as Chile's 1st Paralympic medal in 2012, and the country has now achieved a total of 7 medals in 4 disciplines in Paralympic Games Tokyo 2020, placing it in the 45th position in paralympic medal board.

O presente trabalho tem como objetivo relatar a evolução do movimento paralímpico e sua relação com o cenário político nacional e internacional. Os Jogos Paralímpicos de Verão fizeram sua estreia em 1960, enquanto o Chile participou pela primeira vez em 1992. Por outro lado, os Jogos Paralímpicos de Inverno começaram em 1976, e a primeira participação chilena neste evento ocorreu em 2002. O estudo foi realizado através de análise documental, de onde foram extraídas informações sobre as delegações chilenas, juntamente com as planilhas de resultados gerais obtidos dos Jogos Paralímpicos. As variáveis registradas foram número de atletas participantes de ambos os sexos, modalidades e esportes. As informações posteriormente foram agrupadas em quantidade de medalhas e tipo da medalha obtida, sendo analisadas por tipo de deficiência e ano de participação. Ao longo dos anos, o Chile experimentou constantes processos e mudanças nos períodos de gestão, como a promulgação de leis, tanto nacionais como internacionais, juntamente com a ajuda constante recebida de diferentes grupos privados e governamentais, resultando em aumento de atletas paralímpicos, situação que contribuiu com o desenvolvimento integral do movimento paralímpico chileno. Este crescimento facilitou resultados exitosos, como o obtido em 2012 com a conquista da primeira medalha paralímpica do Chile, alcançando hoje um total de 7 medalhas distribuídas em 4 disciplinas em Tóquio 2022, colocando-se na quadragésima quinta posição do quadro de medalhas.

Music in the Operating Room: Comparing the Opinions of Surgeons, Anesthesiologists, and Nurses.

BACKGROUND: Music is part of operating room (OR) culture; however, some personnel may perceive music as a distraction. METHODS: A single institution survey of surgeons (SURG), anesthesia (ANES), and nursing (NURS) regarding attitudes on music in the OR. RESULTS: There were 222 responses (67% response rate) agreeing that music in the OR should be allowed (91%), is calming (75%), and helps with focus (63%). Most did not feel music was distracting (63%) or unsafe (80%). SURG were more likely to state that surgeons should decide (46.7%) if music should be played, whereas ANES and NURS (81%) were more likely to feel decisions should be made collaboratively (P < .001). CONCLUSION: Most OR personnel feel positively towards music. Surgeons were more likely to believe the decision to play music should be the surgeon's choice. The majority of OR staff agreed with collaborative decision-making, aligning with creating a safe OR culture.

Producción neurocientífica en revistas estudiantiles cubanas (2019-2021) / Neuroscientific production in Cuban student journals (2019-2021)

Introducción: La realización de estudios bibliométricos sobre neurociencias en Cuba no ha sido prolífica. Objetivo: Describir la producción neurocientífica en revistas científicas estudiantiles cubanas. Métodos: Estudio descriptivo y transversal. Se trabajó con 71 artículos, publicados entre enero de 2019 y diciembre de 2021. Se realizó un análisis estadístico descriptivo. Resultados: Progaleno alcanzó el mayor número de lecturas; mientras, Universidad Médica Pinareña fue líder en cuanto a número de artículos, citas, citas corregidas y tiempo medio de publicación. HolCien poseyó la mayor antigüedad promedio de artículos. A INMEDSUR correspondió el menor tiempo medio de aceptación y el más elevado índice de Price. UNIMED tuvo el promedio más alto de referencias y de referencias actualizadas. Universidad Médica Pinareña y 2 de Diciembre ostentaron el mayor índice de originalidad científica: 0,6. Predominaron los artículos originales. El número de autores más frecuente fue 3 (26,8 por ciento); y el valor promedio, 3,5 ± 1,6. El índice de colaboración resultó de 0,89. Todos los artículos se publicaron en idioma español. Entre los de procedencia extranjera, España apareció como el país más frecuente. En 2021 vio la luz el 48 por ciento de los artículos. Conclusiones: La producción neurocientífica en revistas estudiantiles cubanas ha sido notable y está en ascenso, pero aún debe mejorarse su visibilidad y citación(AU)

Introduction: The realization of bibliometric studies on neurosciences in Cuba has not been prolific. Objective: To describe the neuroscientific production in Cuban student scientific journals. Methods: A descriptive and cross-sectional study was carried out with 71 articles, published between January 2019 and December 2021. A descriptive statistical analysis was conducted. Results: Progaleno reached the highest number of readings; meanwhile, Universidad Médica Pinareña was the leader in terms of number of articles, citations, corrected citations and mean time of publication. HolCien had the highest average age of articles. INMEDSUR had the lowest average acceptance time and the highest Price index. UNIMED had the highest average number of references and updated references. Universidad Médica Pinareña and 2 de Diciembre had the highest index of scientific originality: 0.6. Original articles predominated. The most frequent number of authors was 3 (26.8 percent), and the average value was 3.5±1.6. The collaboration index was 0.89. All the articles were published in Spanish. Among those of foreign origin, Spain appeared as the most frequent country. The year 2021 marked the appearance of 48 percent of the articles. Conclusions: The neuroscientific production in Cuban student journals has been remarkable and is on the rise, but its visibility and citation still need to be improved(AU)

Electro and magnetoactive printed bi-functional actuators based on alginate hybrid hydrogels.

Soft materials are attracting much attention for the development of biostructures able to mimic the movement of natural systems by remote actuation. Multi-sensitive hydrogels are among the best materials for obtaining dynamic and biocompatible soft structures for soft actuators and related biomedical devices. Nevertheless, bioinks based on naturally occurring and stimuli responsive hydrogels able to be 3D printed continues being a challenge for advanced applications. In this work 3D printable electrically and magnetically responsive, non-cytotoxic, hybrid hydrogels based on alginate and zero monovalent iron nanoparticles (NPs) are presented. The effect of NPs addition on the physico-chemical properties of the hydrogels is addressed, together with its effect on the functional electroactive and magnetoactive response. NPs concentration up to 10 % do not affect the mechanical stability of the gels, while promoting an increase actuation response.

Microfluidic Processing of Piezoelectric and Magnetic Responsive Electroactive Microspheres.

Poly(vinylidene fluoride) (PVDF) combined with cobalt ferrite (CFO) particles is one of the most common and effective polymeric magnetoelectric composites. Processing PVDF into its electroactive phase is a mandatory condition for featuring electroactive behavior and specific (post)processing may be needed to achieve this state, although electroactive phase crystallization is favored at processing temperatures below 60 °C. Different techniques are used to process PVDF-CFO nanocomposite structures into microspheres with high CFO dispersion, with microfluidics adding the advantages of high reproducibility, size tunability, and time and resource efficiency. In this work, magnetoelectric microspheres are produced in a one-step approach. We describe the production of high content electroactive phase PVDF and PVDF-CFO microspheres using microfluidic technology. A flow-focusing polydimethylsiloxane device is fabricated based on a 3D printed polylactic acid master, which enables the production of spherical microspheres with mean diameters ranging from 80 to 330 µm. The microspheres feature internal and external cavernous structures and good CFO distribution with an encapsulation efficacy of 80% and prove to be in the electroactive γ-phase with a mean content of 75%. The microspheres produced using this approach show suitable characteristics as active materials for tissue regeneration strategies and other piezoelectric polymer applications.

Multiple drug resistance in hookworms infecting greyhound dogs in the USA.

Ancylostoma caninum is the most prevalent nematode parasite of dogs. We confirmed multiple-drug resistance (MDR) in several A. caninum isolates to all anthelmintic drug classes approved for the treatment of hookworms in dogs in the USA. Cases of MDR hookworms appear to be highly overrepresented in greyhounds. The aims of this study were to evaluate the drug-resistant phenotypes and genotypes of the A. caninum infecting greyhounds. Fecal samples from greyhounds of the USA were acquired from two greyhound adoption kennels, one active greyhound racing kennel, and three veterinary practices. Fecal egg counts (FECs) were performed on fecal samples from 219 greyhounds, and despite treatment with anthelmintics, the mean FEC was 822.4 eggs per gram (EPG). Resistance to benzimidazoles and macrocyclic lactones were measured using the egg hatch assay (EHA) and the larval development assay (LDA), respectively. We performed 23 EHA and 22 LDA on either individual or pooled feces, representing 54 animals. Mean and median IC50 and IC95 values for the EHA were 5.3 µM, 3.6 µM, and 24.5 µM, 23.4 µM, respectively. For the LDA, the median IC50 value was >1000 nM. These values ranged 62-81 times higher than our susceptible laboratory isolate. Only post-treatment samples were available. For samples collected <10 days post-treatment with albendazole, moxidectin, or a combination of febantel-pyrantel-moxidectin, the mean FEC were 349, 333, and 835 EPG, respectively. We obtained DNA from hookworm eggs isolated from 70 fecal samples, comprised of 60 individual dogs and 10 pools. Deep sequencing of the isotype 1 ß-tubulin gene only revealed the presence of the F167Y (TTC>TAC) resistance polymorphism in 99% of these samples. These clinical, in vitro, and genetic data provide strong evidence that greyhound dogs in the USA are infected with MDR A. caninum at very high levels in prevalence and infection intensity.

Routine Use of Tenecteplase for Thrombolysis in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: In ischemic stroke, intravenous tenecteplase is noninferior to alteplase in selected patients and has some practical advantages. Several stroke centers in New Zealand changed to routine off-label intravenous tenecteplase due to improved early recanalization in large vessel occlusion, inconsistent access to thrombectomy within stroke networks, and for consistency in treatment protocols between patients with and without large vessel occlusion. We report the feasibility and safety outcomes in tenecteplase-treated patients. METHODS: We performed a retrospective analysis of consecutive patients thrombolyzed with intravenous tenecteplase at 1 comprehensive and 2 regional stroke centers from July 14, 2018, to February 29, 2020. We report the baseline clinical characteristics, rates of symptomatic intracranial hemorrhage, and angioedema. These were then compared with patient outcomes with those treated with intravenous alteplase at 2 other comprehensive stroke centers. Multivariable mixed-effects logistic regression models were performed assessing the association of tenecteplase with symptomatic intracranial hemorrhage and independent outcome (modified Rankin Scale score, 0-2) at day 90. RESULTS: There were 165 patients treated with tenecteplase and 254 with alteplase. Age (75 versus 74 years), sex (56% versus 60% male), National Institutes of Health Stroke Scale scores (8 versus 10), median door-to-needle times (47 versus 48 minutes), or onset-to-needle time (129 versus 130 minutes) were similar between the groups. Symptomatic intracranial hemorrhage occurred in 3 (1.8% [95% CI, 0.4-5.3]) tenecteplase patients compared with 7 (2.7% [95% CI, 1.1-5.7]) alteplase patients (P=0.75). There were no differences between tenecteplase and alteplase in the rates of angioedema (4 [2.4%; 95% CI, 0.7-6.2] versus 1 [0.4%; 95% CI, 0.01-2.2], P=0.08) or 90-day functional independence (100 [61%] versus 140 [57%], P=0.47), respectively. In mixed-effects logistic regression models, there was no significant association between thrombolytic choice and symptomatic intracranial hemorrhage (odds ratio tenecteplase, 0.62 [95% CI, 0.14-2.80], P=0.53) or functional independence (odds ratio tenecteplase, 1.20 [95% CI, 0.74-1.95], P=0.46). CONCLUSIONS: Routine use of tenecteplase for stroke thrombolysis was feasible and had comparable safety profile and outcome to alteplase.

APEX: a phase II randomised clinical trial evaluating the safety and preliminary efficacy of oral X-82 to treat exudative age-related macular degeneration.

PURPOSE: The safety and efficacy of X-82, an orally administered inhibitor of vascular endothelial growth factor (VEGF) and platelet-derived growth factor, was investigated for treatment of wet age-related macular degeneration (AMD) in a phase II clinical trial. METHODS: This phase II, randomised, double-masked, placebo-controlled trial enrolled subjects with a prior diagnosis of exudative AMD having received at least two intravitreal injections of anti-VEGF therapy. Subjects were randomised equally into four groups that received either daily 50mg, 100mg or 200mg dosages of X-82 or a placebo tablet. At each 4-week interval visit for 52 weeks, subjects were to be assessed to determine if rescue treatment was needed with anti-VEGF therapy. RESULTS: 157 patients were enrolled. Due to gastrointestinal and hepatobiliary adverse events and the fulfilment of the primary endpoint, the trial was stopped prematurely after a second interim analysis. The primary endpoint of non-inferiority of visual acuity compared with placebo was demonstrated in all groups receiving X-82 (p<0.001). There was a dose-dependent trend in the number of injections over a 52-week period, with the 50 mg (n=40), 100 mg (n=39), 200 mg (n=39) and placebo (n=39) group requiring 6.7, 6.0, 4.7 and 8.1 injections, respectively. CONCLUSIONS: X-82 oral therapy in combination with pro re nata anti-VEGF injections showed non-inferiority in visual acuity outcomes while achieving a dose-dependent decrease in the number of anti-VEGF injections compared with placebo. Given the limited tolerability and safety issues observed, X-82 does not have a sufficient benefit to risk profile in treatment of patients with AMD.

Birth of a Live Cria After Transfer of a Vitrified-Warmed Alpaca (Vicugna pacos) Preimplantation Embryo.

The alpaca (Vicugna pacos) is an important species for the production of fiber and food. Genetic improvement programs for alpacas have been hindered, however, by the lack of field-practical techniques for artificial insemination and embryo transfer. In particular, successful techniques for the cryopreservation of alpaca preimplantation embryos have not been reported previously. The objective of this study was to develop a field-practical and efficacious technique for cryopreservation of alpaca preimplantation embryos using a modification of a vitrification protocol originally devised for horses and adapted for dromedary camels. Four naturally cycling non-superovulated Huacaya females serving as embryo donors were mated to males of proven fertility. Donors received 30 µg of gonadorelin at the time of breeding, and embryos were non-surgically recovered 7 days after mating. Recovered embryos (n = 4) were placed individually through a series of three vitrification solutions at 20°C (VS1: 1.4 M glycerol; VS2: 1.4 M glycerol + 3.6 M ethylene glycol; VS3: 3.4 M glycerol + 4.6 M ethylene glycol) before loading into an open-pulled straw (OPS) and plunging directly into liquid nitrogen for storage. At warming, each individual embryo was sequentially placed through warming solutions (WS1: 0.5 M galactose at 37°C; WS2: 0.25 M galactose at 20°C), and warmed embryos were incubated at 37°C in 5% CO2 in humidified air for 20-22 h in 1 ml Syngro® holding medium supplemented with 10% (v/v) alpaca serum to perform an initial in vitro assessment of post-warming viability. Embryos whose diameter increased during culture (n = 2) were transferred individually into synchronous recipients, whereas embryos that did not grow (n = 2) were transferred together into a single recipient to perform an in vivo assessment of post-warming viability. Initial pregnancy detection was performed ultrasonographically 29 days post-transfer when fetal heartbeat could be detected, and one of three recipients was pregnant (25% embryo survival rate). On November 13, 2019, the one pregnant recipient delivered what is believed to be the world's first cria produced from a vitrified-warmed alpaca embryo.

Golden Age of Fluorenylidene Phosphaalkenes-Synthesis, Structures, and Optical Properties of Heteroaromatic Derivatives and Their Gold Complexes.

The substitution of 2,7-dibromo-9-fluorenyl phosphaalkenes with heteroaromatic substituents (bithiophene, benzothiophene, pyridine) offers access to interesting push-pull dye molecules. Steric shielding due to the bulky P-substituent gives marked different reactivities at the 2- and 7-positions, allowing the synthesis of mixed/asymmetric derivatives. Further functionalization via gold(I) coordination was demonstrated and increased the acceptor character, concomitant with a red-shifted absorption.

Reactivity studies of an imine-functionalised phosphaalkene; unusual electrostatic and supramolecular stabilisation of a σ2λ3-phosphorus motif via hydrogen bonding.

A P[double bond, length as m-dash]C heavy-alkene analogue that is unreactive towards the addition of strong acids on its double-bond is presented; instead, a strategically located imine nitrogen on the periphery forms protonated adducts displaying hydrogen bonding interactions. These materials are significantly more stable than the parent species, demonstrating an unprecedented approach towards the stabilisation of a multiple-bonded heavy main group fragment, in this case, a phosphaalkene. An HCl adduct self-assembles with H2O into a dimeric network displaying a discrete quadrilateral hydrogen-bonded arrangement.

Functional small-molecules & polymers containing P[double bond, length as m-dash]C and As[double bond, length as m-dash]C bonds as hybrid π-conjugated materials.

Stable phospha- and arsaalkenes were used to synthesize polymers containing unsaturated P[double bond, length as m-dash]C and As[double bond, length as m-dash]C moieties. The composition, chemical environment, structure, optical, and electronic properties of the monomers and polymers were elucidated. The incorporation of the heteroatom-carbon double bonded units efficiently perturbs the optoelectronics and solid state features of both monomeric and polymeric scaffolds. Proof-of principle work supports their responsive character through post-functionalisation and electrochromic behaviour. To the best of our knowledge, this is the first example of a polymer containing arsenic-carbon double bonds.

Misoprostol en la conducta activa en el tercer período del parto: dosis mínima efectiva / Misoprostol in the active conduct in the third stage of labor: minimum effective dose

OBJETIVO: Comparar los efectos del uso de misoprostol sublingual en dosis de 200 µg, 400 µg o 600 µg en la conducta activa del tercer período del parto. MÉTODOS: Se incluyeron 350 pacientes con embarazos a término, que presentaron parto vaginal. Fueron distribuidas al azar en 3 grupos (A, B y C) las cuales recibieron dosis respectivamente de 200 µg, 400 µg y 600 µg de misoprostol sublingual como parte de la conducta activa durante el alumbramiento. Se registró el tiempo entre la expulsión del recién nacido y el alumbramiento completo, la pérdida hemática durante este período, y la presencia de efectos adversos hasta el momento de su egreso. RESULTADOS: La media del tiempo del alumbramiento fue de 3 ± 0,9 minutos para el grupo de 200 µg, 2,8 ± 0,7 minutos para el grupo de 400 µg y 2,8 ± 0,6 para el grupo de 600 µg (P=0,172). Se reportaron cuatro casos de hipotonía uterina, 1 en el grupo A, 2 en el B y 1 en el C y tres casos de retención de restos, uno en cada grupo. Se presentaron náuseas, vómitos, temblores, evacuaciones líquidas y fiebre en bajo porcentaje (menos de 5 %) sin relación con la dosis (P>0,05) CONCLUSIONES: El misoprostol en dosis de 200 µg es igual de efectivo que dosis mayores, en la conducta activa del alumbramiento, con una incidencia menor al 1 % de hemorragias posparto y escasos efectos secundarios adversos.

OBJECTIVE: To compare the effects of the use of sublingual misoprostol in doses of 200 µg, 400 µg or 600 µg in the active of the third period of confinement conduct. METHODS: 350 patients with pregnancies to term, showing vaginal birth were included. They were distributed randomly in 3 groups (A, B and C) which received doses 200 µg, 400 µg and 600 µg of sublingual misoprostol respectively as part of conduct active during childbirth. Is recorded time between the expulsion of the newly born and full delivery, lost blood during this period, and the presence of adverse effects until the time of his graduation. RESULTS: The average delivery time was 3 ± 0.9 minutes for the Group of 200 µg, 2.8 ± 0.7 minutes for the Group of 400 µg and 2.8 ± 0.6 for the Group of 600 µg (P = 0, 172). Reported four cases of uterine hypotonia, 1 in group A, 2 in group B and 1 in group C, and three cases of retention of remains, one in each group. Were nausea, vomiting, tremors, liquid evacuations, and fever in low percentage (less than 5 %) unrelated to the dose (P > 0.05). CONCLUSIONS: In doses of 200 µg misoprostol is as effective as doses above, conduct active birth, with one incidence of less than 1 % of postpartum haemorrhage and few adverse side effects.

ANTIFUNGAL ACTIVITY OF NEEM (Azadirachta indica: MELIACEAE) EXTRACTS AGAINST DERMATOPHYTES / Actividad antifúngica de extractos de neem (Azadirachta indica: Meliaceae) sobre hongos dermatofitos

In order to assess the antifungal activity of methanolic extracts from neem tree (Azadirachta indica A. Juss.), several bioassays were conducted following M38-A2 broth microdilution method on 14 isolates of the dermatophytes Trichophytonmentagrophytes, Trichophyton rubrum, Microsporum canis and Epidermophyton floccosum. Neem extracts were obtained through methanol-hexane partitioning of mature green leaves and seed oil. Furthermore, high performance liquid chromatography (HPLC) analyses were carried out to relate the chemical profile with their content of terpenoids, ofwidely known antifungal activity. The antimycotic Terbinafine served as a positive control. Results showed that there was total growth inhibition of the dermatophytes isolates at minimal inhibitory concentrations (MIC) between 50 μg/mL and 200 μg/mL for leaves extract, and between 625 μg/mL and 2500 μg/mL for seed oil extract. The MIC of positive control (Terbinafine) ranged between 0.0019 μg/mL and 0.0313 μg/mL. Both neem leaves and seed oil methanol extracts exhibited different chromatographic profiles by HPLC, which could explain the differences observed in their antifungal activity. This analysis revealed the possible presence of terpenoids in both extracts, which are known to have biological activity. The results of this research are a new report on the therapeutic potential of neem to the control of dermatophytosis.

Se determinó la actividad antifúngica de extractos metanólicos de la especie Azadirachta indica A. Juss. (Meliaceae), conocida comúnmente como neem, empleando el método de microdilución en caldo M38-A2 de referencia para hongos filamentosos y dermatofitos. Se evaluaron 14 aislamientos de los dermatofitos Trichophyton mentagrophytes, Trichophyton rubrum, Microsporum canis y Epidermophyton floccosum. Los extractos de neem fueron obtenidos mediante partición metanol-hexano a partir de aceite de semillas y hojas verdes maduras. Adicionalmente, se analizaron por cromatografía líquida de alta resolución (CLAR) con el fin de relacionar su perfil químico con el contenido de terpenoides, de conocida actividad antifúngica. Se empleó como control positivo el antimicótico Terbinafina. Los resultados mostraron inhibición total del crecimiento de los aislamientos de dermatofitos a concentraciones mínimas inhibitorias (CMI) entre 50 μg/mL y 200 μg/mL para el extracto de hojas y entre 625 μg/mL y 2500 μg/mL para el extracto de aceite de semillas. La CMI encontrada para el control positivo (Terbinafina) fluctuó entre 0,0078 μg/mL y 0,0313 μg/mL. Los extractos metanólicos de hojas y aceite de semillas de neem exhibieron diferentes perfiles cromatográficos en CLAR, lo cual podría explicar las diferencias observadas en su actividad antifúngica. Éste análisis químico reveló la posible presencia de compuestos terpenoides en ambos extractos, los cuales se conocen por su actividad biológica. Los resultados de esta investigación son un nuevo aporte sobre el potencial terapéutico del neem para el control de dermatofitosis.

Actividad antifúngica de extractos de biomasa celular de neem sobre aislamientos de dermatofitos / Antifungal activity of neem cellular biomass extracts on dermatophytes isolates

Las líneas celulares de neem (Azadirachta indica A. Juss.) cultivadas en suspensión líquida han demostrado producir metabolitos secundarios bioactivos, particularmente triterpenoides. En consecuencia, se han realizado estudios para el control de microorganismos de importancia médica, como los hongos dermatofitos. El objetivo principal de este trabajo fue evaluar a través de un método de referencia in vitro la actividad antifúngica de diferentes extractos de cultivos celulares de neem sobre varios aislamientos de Trichophyton mentagrophytes, Trichophyton rubrum y Epidermophyton floccosum. Se realizó un escalado de cultivos de suspensiones celulares de neem, a partir de los cuales se obtuvo un extracto crudo metanólico. Éste extracto fue fraccionado posteriormente por cromatografía en columna de silica gel. Con los extractos obtenidos se determinó la Concentración Mínima Inhibitoria (CMI), siguiendo el método de microdilución en caldo M38-2, con cinco aislamientos de T. mentagrophytes, cinco de T. rubrum y tres de E. floccosum. Se usó como control positivo el antimicótico Terbinafina. Los resultados mostraron que el extracto crudo de biomasa celular de neem inhibe el crecimiento hasta en 100 % de T. mentagrophytes, T. rubrum y E. floccosum. Al evaluar las fracciones por separado, se observó que las de menor polaridad exhibieron en general mayor actividad antifúngica (CMI=109 μg/mL) que el extracto crudo per se (CMI=2500 μg/ mL) y las fracciones más polares (CMI=7000 μg/mL). Lo anterior indica que las células de neem cultivadas en suspensión producen compuestos con actividad antifúngica, siendo más bioactivos los presentes en las fracciones de menor polaridad.

Cell lines of neem (Azadirachta indica A. Juss.) grown in liquid suspension have shown to produce bioactive secondary metabolites, particularly triterpenoids. In consequence, its use as a control of medical microorganisms (like dermatophytes) is proposed. The main goal of this study was to assess the antifungal activity of methanolic extracts from neem cultured cell suspensions on several isolates of Trichophyton mentagrophytes (five isolates), Trichophyton rubrum (five isolates) and Epidermophyton floccosum (three isolates). Neem cell suspension cultures were scaled up, from which a raw methanolic extract was obtained. This extract was fractionated by silica gel column chromatography. The raw methanolic extract and its fractions were used in order to determine the Minimal Inhibitory Concentration (MIC) on the dermatophytes isolates by following M38-A2 broth microdilution method. Antimycotic Terbinafine was used as positive control. The results shown that neem raw cellular biomass extract inhibits the growth of T. mentagrophytes, T. rubrum and E. floccosum in at least 100%. In the evaluations of the separated fractions, it was observed that the low polarity fractions had higher antifungal activity (MIC=109 μg/mL) than the raw extract per se (MIC=2500 μg/mL) and the most polar ones (MIC=7000 μg/mL). The latter suggest that neem cells cultured in liquid suspension produces compounds with antifungal activity, being more active those present in the low polarity fractions.

Model-Supported Development of CS-8635: A Fixed-Dose Combination of Olmesartan, Amlodipine, and Hydrochlorothiazide.

CS-8635, a fixed-dose triple combination of olmesartan, amlodipine, and hydrochlorothiazide, was developed to address the growing need for additional blood pressure (BP) reduction in patients not controlled with dual-combination therapies. Prior to Phase III, modeling and simulation (M&S) was conducted to estimate the additional BP lowering effect of CS-8635 compared to the respective dual combinations. The Phase III study evaluated CS-8635 BP lowering effects only at the highest dose strength among the five dose strengths to be developed. Post-trial M&S was performed using an integrated dataset from three Phase III programs; CS-8635 plus two prior dual combinations. M&S robustly estimated and described the BP lowering effects of CS-8635 evaluated in a clinical setting. Furthermore, M&S evaluated BP lowering effects of the additional four dose strengths not studied. In summary, M&S aided the development of the clinical study and full characterization of the BP lowering effects of CS-8635 across intermediate doses.

Characterisation of exposure versus response of edoxaban in patients undergoing total hip replacement surgery.

Edoxaban is an oral direct factor Xa inhibitor approved for the prevention of venous thromboembolism (VTE) in Japan. The objectives of this analysis were to characterise the population pharmacokinetics (PK) of edoxaban and the relationships between edoxaban exposure and clinical outcomes in a phase IIb study of surgical patients following total hip replacement (THR). A total of 1,795 subjects from a phase IIb study, 10 phase I studies, and three phase IIa studies were included in the PK analysis. The exposure-response analysis included data from surgical patients assigned to edoxaban in the phase IIb study. Edoxaban disposition in healthy and post-surgical patients was well-described with a linear, two-compartment model. Creatinine clearance was significantly correlated with edoxaban clearance and the rate of oral absorption was affected by surgery. The probability of a post-operative VTE was significantly correlated with steady-state metrics of edoxaban exposure estimated for each subject by Bayesian post-hoc methods with age and gender being the significant and expected covariates. The incidence of bleeding was low in these studies and hence no exposure-response relationship could be identified. These analyses suggest that edoxaban has a predictable anticoagulant effect in this patient population leading to dose-proportional reduction in incidence of VTE with low incidence of bleeding.

Pharmacokinetics of olmesartan medoxomil in pediatric patients with hypertension.

BACKGROUND: The prevalence and importance of hypertension in younger patients is becoming increasingly recognized; however, only a limited number of clinical trials have been conducted in the pediatric population. OBJECTIVE: The aim of this study was to characterize the pharmacokinetics and short-term safety of olmesartan medoxomil in children and adolescents with hypertension. METHODS: An open-label, multicenter, single-dose study was conducted in children and adolescents aged 12 months-16 years who were receiving treatment for hypertension or, if not currently treated for hypertension, had either a systolic blood pressure (SBP) or diastolic blood pressure (DBP).≥95th percentile, or SBP or DBP ≥90th percentile if diabetic or with a family history of hypertension. Patients were stratified by age: 12-23 months (Group 1; none enrolled), 2-5 years (Group 2; n = 4), 6-12 years (Group 3; n = 10), and 13-16 years (Group 4; n = 10). All patients received a single oral dose of olmesartan medoxomil based on the individual's age and bodyweight. Patients aged <6 years received an oral suspension of olmesartan medoxomil at a dose of 0.3 mg/kg of bodyweight (not to exceed 20 mg), those aged ≥6 years who weighed ≥35 kg received olmesartan medoxomil 40 mg tablets, and those who weighed <35 kg received olmesartan medoxomil 20 mg tablets. RESULTS: In Groups 2, 3, and 4, the weight-adjusted apparent total body clearance (CL/F) of olmesartan medoxomil was 0.100 ± 0.034, 0.062 ± 0.020, and 0.072 ± 0.022 L/h/kg, respectively, and the weight-adjusted apparent volume of distribution (Vd/F) was 0.32 ± 0.16, 0.33 ± 0.14, and 0.49 ± 0.23 L/kg, respectively. CL/F and Vd/F in Groups 3 and 4 were not significantly different. Statistical comparisons between Groups 3 or 4 and Group 2 were not performed due to the small sample size of Group 2 (n = 4). Plasma elimination half-life and time to maximum plasma concentration were similar across the three groups. In Groups 3 and 4, considerable interindividual variability was seen in maximum plasma concentration (C(max)), area under the curve (AUC) from time zero to the last measurable concentration, and apparent clearance, with AUC and C(max) approximately 30% greater in Group 3. Four of 24 (16.7%) patients experienced treatment-emergent adverse events that were all mild in severity and considered not drug-related. No deaths, serious adverse events, or discontinuations due to adverse events occurred in the study. CONCLUSIONS: Olmesartan medoxomil was well tolerated and demonstrated a pharmacokinetic profile in pediatric patients similar to that of adults when adjusted for body size. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00151814