In Brazil, the snail Biomphalaria glabrata is the most important vector of schistosomiasis due to its wide geographical distribution, high infection rate and efficient disease transmission. Among the ...methods of schistosomiasis control, the World Health Organization recommends the use of synthetic molluscicides, such as niclosamide. However, different substances of natural origin have been tested as alternatives for the control or eradication of mollusks. The literature describes the antitumor, antimicrobial and antiviral properties of usnic acid as well as other important activities of common interest between medicine and the environment. However, usnic acid has a low degree of water solubility, which can be a limiting factor for its use, especially in aquatic environments, since the organic solvents commonly used to solubilize this substance can have toxic effects on aquatic biota. Thus, the aim of the present study was to test the potassium salt of usnic acid (potassium usnate) with regard to molluscicidal activity and toxicity to brine shrimp (Artemia salina). To obtain potassium usnate, usnic acid was extracted with diethyl ether isolated and purified from the lichen Cladonia substellata. Biological assays were performed with embryos and adult snails of B. glabrata exposed for 24 h to the usnate solution solubilized in dechlorinated water at 2.5; 5 and 10 µg/ml for embryos, 0.5; 0.9; 1;5 and 10 µg/ml for mollusks and 0.5; 1; 5; 10 µg/ml for A. salina. The lowest lethal concentration for the embryos and adult snails was 10 and 1 µg/ml, respectively. No toxicity to A. salina was found. The results show that modified usnic acid has increased solubility (100%) without losing its biological activity and may be a viable alternative for the control of B. glabrata.
The Amazon Basin plays key roles in the carbon and water cycles, climate change, atmospheric chemistry, and biodiversity. It has already been changed significantly by human activities, and more ...pervasive change is expected to occur in the coming decades. It is therefore essential to establish long-term measurement sites that provide a baseline record of present-day climatic, biogeochemical, and atmospheric conditions and that will be operated over coming decades to monitor change in the Amazon region, as human perturbations increase in the future. The Amazon Tall Tower Observatory (ATTO) has been set up in a pristine rain forest region in the central Amazon Basin, about 150 km northeast of the city of Manaus. Two 80 m towers have been operated at the site since 2012, and a 325 m tower is nearing completion in mid-2015. An ecological survey including a biodiversity assessment has been conducted in the forest region surrounding the site. Measurements of micrometeorological and atmospheric chemical variables were initiated in 2012, and their range has continued to broaden over the last few years. The meteorological and micrometeorological measurements include temperature and wind profiles, precipitation, water and energy fluxes, turbulence components, soil temperature profiles and soil heat fluxes, radiation fluxes, and visibility. A tree has been instrumented to measure stem profiles of temperature, light intensity, and water content in cryptogamic covers. The trace gas measurements comprise continuous monitoring of carbon dioxide, carbon monoxide, methane, and ozone at five to eight different heights, complemented by a variety of additional species measured during intensive campaigns (e.g., VOC, NO, NO2, and OH reactivity). Aerosol optical, microphysical, and chemical measurements are being made above the canopy as well as in the canopy space. They include aerosol light scattering and absorption, fluorescence, number and volume size distributions, chemical composition, cloud condensation nuclei (CCN) concentrations, and hygroscopicity. In this paper, we discuss the scientific context of the ATTO observatory and present an overview of results from ecological, meteorological, and chemical pilot studies at the ATTO site.
Objectives
There is a growing incidence of cognitive decline and dementia associated with the ageing population. Lifestyle factors such as diet, physical activity, and cognitive activities may ...individually or collectively be undertaken to increase one’s odds of preventing cognitive decline and future dementia. This study will examine whether clinical trials using multidomain lifestyle intervention can significantly decrease the risk of cognitive decline and therefore dementia.
Design, Setting and Participants
This systematic literature review of multidomain lifestyle interventions for the prevention of cognitive decline and dementia followed the PRISMA guidelines. Clinical trials involving multidomain intervention (i.e., diet and physical activity, or without cognitive training) in older adults (≥ 49 years old) at higher risk of dementia were identified through 5 electronic databases (EMBASE, MEDLINE, CINAHL, Cochrane, and Scopus). A comprehensive search was performed to identify and retrieve publications until 15 November 2022. Trials were published in English.
Results
The included studies (n=15) assessed change in cognition in response to a multidomain lifestyle intervention. However, the cognitive outcome measures used in these studies were heterogeneous. Despite this heterogeneity, two thirds of the studies showed improvement in cognition following a multidomain intervention (n=10 with a total of 9,439 participants). However, five studies reported no improvement in cognition following the multidomain intervention. The most common form of dietary intervention included higher amount of fruit and vegetable intake; whole-grain cereal products instead of refined; low fat options in milk and meat products; and limiting sucrose intake to less than 50 g/day. Most clinical trial studies were powered to examining the effects of multidomain interventions in cognition but were not designed to test the contribution of individual domains (i.e., dietary changes, increased physical activity, or increased cognitive stimulation alone).
Conclusion
This systematic review aimed to determine the effect of multimodal lifestyle interventions on cognitive outcomes in older adults at risk of dementia. We found that participants with conditions that may increase the risk of dementia, (e.g., hypertension, cardiovascular fragility) do benefit from multi-modal lifestyle changes including diet, physical activity, and cognitive training. Two thirds of studies using multidomain lifestyle interventions showed improvements in cognitive function. Trials with a focus on cognitive training, dietary improvement, and physical activity may prevent or delay cognitive decline in older adults including those at risk of developing dementia. Future studies should consider longer follow-up periods and adequate power to be able to examine the effects of each lifestyle component in the context of multimodal interventions.
BACKGROUND AND PURPOSE—The increasing demand and shortage of experts to evaluate and treat acute stroke patients has led to the development of remote communication tools to aid stroke management. We ...aimed to evaluate the JOIN App smartphone system—a low-cost tool for rapid clinical and neuroimaging data sharing to expedite decision-making in stroke.
METHODS—Consecutive acute ischemic stroke patients treated at a University Hospital in Brazil from December 2014 to December 2015 were evaluated. The analysis included all patients presenting with acute ischemic stroke who underwent initial evaluation by neurology residents followed by JOIN teleconsultation with a stroke neurologist on call for management decisions. An expert panel of stroke neurologists and neuroradiologists revised all cases using a standard Picture Archiving and Communication System imaging workstation within 24 hours and analyzed the decision made with remote assistance during the emergency setting.
RESULTS—A total of 720 stroke codes were evaluated with 442 acute ischemic stroke qualifying. Seventy-eight (18%) patients were treated with intravenous thrombolysis. The main reasons for tPA (tissue-type plasminogen activator) exclusion were symptom onset >4.5 hours (n=295; 67%) and hypodense middle cerebral artery territory area >1/3 (n=31; 7%). The agreement rates between Picture Archiving and Communication System versus JOIN-based thrombolysis decisions were 100% for the stroke (unblinded) and 99.3% for the neuroradiologist (blinded) experts. The use of the application resulted in a significant reduction in the door-to-needle times across the pre- versus postimplementation periods (median, 90 interquartile range, 75–106 versus 63 interquartile range, 61–117 minutes; P=0.03). The rates of 90-day excellent outcomes (modified Rankin Scale, 0–1) were 51.3%; 90-day mortality, 2.6%; and symptomatic intracranial hemorrhage, 3.8%.
CONCLUSIONS—The JOIN smartphone system allows rapid sharing of clinical and imaging data to facilitate decisions for stroke treatment. The remote application-based decisions seem to be as accurate as the physical presence of stroke experts and might lead to faster times to treatment. This system represents an easily implementable low-cost telemedicine solution for centers that cannot afford the full-time presence of stroke specialists.
Normal-to-cancer (NTC) transition is known to be closely associated to cell´s biomechanical properties which are dependent on the dynamics of the intracellular medium. This study probes different ...human cancer cells (breast, prostate and lung), concomitantly to their healthy counterparts, aiming at characterising the dynamical profile of water in distinct cellular locations, for each type of cell, and how it changes between normal and cancer states. An increased plasticity of the cytomatrix is observed upon normal-to-malignant transformation, the lung carcinoma cells displaying the highest flexibility followed by prostate and breast cancers. Also, lung cells show a distinct behaviour relative to breast and prostate, with a higher influence from hydration water motions and localised fast rotations upon NTC transformation. Quasielastic neutron scattering techniques allowed to accurately distinguish the different dynamical processes taking place within these highly heterogeneous cellular systems. The results thus obtained suggest that intracellular water dynamics may be regarded as a specific reporter of the cellular conditions-either healthy or malignant.
Objectives
In a short approach, we want to present the improvements that have recently been done in the world of new solid forms of known active pharmaceutical ingredients (APIs). The different ...strategies will be addressed, and successful examples will be given.
Key findings
This overview presents a possible step to overcome the 10–15 years of hard work involved in launching a new drug in the market: the use of new forms of well‐known APIs, and improve their efficiency by enhancing their bioavailability and pharmacokinetics. It discusses some of the latest progresses.
Summary
We want to present, in a brief overview, what recently has been done to improve the discovery of innovative methods of using well‐known APIs, and improve their efficiency. Multicomponent crystal forms have shown to be the most promising achievements to accomplish these aims, by altering API physico‐chemical properties, such as solubility, thermal stability, shelf life, dissolution rate and compressibility. API‐ionic liquids (ILs) and their advantages will be briefly referred. An outline of what has recently been achieved in metal drug coordination and in drug storage and delivery using bio‐inspired metal‐organic frameworks (BioMOFs) will also be addressed.
This study tested the usability of a home-based self-administration transcranial direct current stimulation (tDCS) device designed specifically for women's health needs. This is a single center ...triple blinded clinical usability study for a new wireless, Bluetooth-controlled wearable tDCS device for women's health. The study aims to evaluate the usability and effective blinding of a home-based tDCS system. A total of forty-nine women of reproductive age were randomly allocated (1:1) to receive one session of active tDCS (n = 24) or sham tDCS (n = 25) over the motor and dorsolateral prefrontal cortex. Each participant self-administered one 20-minute session without supervision following guidance on a software application alone. The System Usability Scale (SUS) and the Patient Global Impression of Change (PGIC) were used to evaluate the usability of the system. Regardless of sham or active conditions, all users found the system easy to use without the support of researchers. Usability scores were considered to be "excellent" in both groups and no significant difference was found between sham and active groups showing effective blinding of the device (Active group: 93.7 (83.1-97.5); Sham group 90 (86.2-95) p = 0.79) and PGIC (Active group: 2 (1-2.75); Sham group 2 (1-2) p = 0.99) using an unpaired t-test or non-parametric statistical tests accordingly. The new Bluetooth-controlled wearable tDCS device is easy, safe to use and completely controlled by a smartphone app. This device is focused on women's health and will be tested as an alternative treatment for chronic pelvic pain and mood disturbance associated with menstrual cycles in further research.
Polyamorphism has been a controversial and highly debated solid-state phenomenon in both material and pharmaceutical communities. Although some evidence of this fascinating phenomenon has been ...reported for several inorganic systems, and more recently also for a few organic compounds, the occurrence of polyamorphism is poorly understood and the molecular-level organization of polyamorphic forms is still unknown. Here we have investigated the occurrence of polyamorphism and polyamorphic interconversions in hydrochlorothiazide (HCT), using both experimental and computational methods. Three distinct HCT polyamorphs, presenting distinct physical and thermal stabilities as well as distinct relaxation properties, were systematically prepared using spray-drying (SD), quench-cooling (QC) and ball milling (BM) methods. HCT polyamorph II (obtained by QC) was found to be more physically stable than polyamorphs I and III (obtained by SD and BM, respectively). Furthermore, polyamorphs I and III could be converted into polyamorph II after QC, while polyamorph II did not convert to any other polyamorph after SD or BM. Molecular dynamics simulations show that HCT dihedral angle distributions are significantly different for polyamorphs I and II, which is postulated as a possible explanation for their different physicochemical properties.
Three polyamorphs of hydrochlorothiazide with distinct physicochemical properties were discovered. MD simulations show different dihedral angle distributions in polyamorphs I and II. Polyamorphs I and III were converted into polyamorph II.
The reaction of the Schiff base (3,5-di-tert-butyl-2-hydroxybenzylidene)-2-hydroxybenzohydrazide (H3L) with a copper(II) salt of a base of a strong acid, i.e., nitrate, chloride or sulphate, yielded ...the mononuclear complexes Cu(H2L)(NO3)(H2O) (1), Cu(H2L)Cl·2MeOH (2) and the binuclear complex {Cu(H2L)}2(µ-SO4)·2MeOH (3), respectively, with H2L(-) in the keto form. Compounds 1-3 were characterized by elemental analysis, Infrared (IR) spectroscopy, Electrospray Ionisation Mass Spectrometry (ESI-MS) and single crystal X-ray crystallography. All compounds act as efficient catalysts towards the peroxidative oxidation of cyclohexane to cyclohexyl hydroperoxide, cyclohexanol and cyclohexanone, under mild conditions. In the presence of an acid promoter, overall yields (based on the alkane) up to 25% and a turnover number (TON) of 250 (TOF of 42 h(-1)) after 6 h, were achieved.
An alternative, efficient, and green synthetic strategy for the preparation of pharmaceutical ionic liquids using mechanochemistry (MechanoAPI‐ILs) is reported. Six new API‐ILs based on gabapentin ...and l‐glutamic acid were successfully synthesized and characterized, demonstrating that mechanochemistry is a very promising synthetic strategy. Results compare both the new and the classical approach and clearly show the advantages of the new method. This new technique is faster, solvent free, reproducible, selective, and leads to higher yields.
A solid state strategy: For the first time, mechanochemistry is used in the preparation of pharmaceutical ionic liquids (MechanoAPI‐ILs). Six new API‐ILs are successfully synthesized and characterized, demonstrating this to be a very promising synthetic strategy. The technique is faster, solvent free, reproducible, selective, and leads to higher yields compared to conventional processes
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