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The objective of the work was to determine the antioxidant potential in vitro of freeze-dried peel extracts of 20 fruits from the northern region of Peru through five tests (Folin-Ciocalteu, DPPH., ABTS+., FRAP and CUPRAC). According to multivariate statistical analyzes, five groups were found: (i.) peel extracts with the highest values of antioxidant capacity (AC) from custard apple, and star fruit; (ii.) rind extracts with high AC values from quince, sweet granadilla, guava, and black grape; (iii.) husk extracts with middle values of AC from passion fruit, and red mombin; (iv.) shell extracts with low AC values from tangerine, mandarine, and bitter orange; and, (v.) coating extracts with the lowest AC values from pawpaw, red pawpaw, muskmelon, dragon fruit, yellow and red indian figs, pear, apple, and green grape. To conclude, the fruit lyophilized-husk extracts of custard apple, star fruit, quince, sweet granadilla, guava, and black grape obtained the best AC.

INTRODUCTION: The leishmaniases represent a group of parasitic diseases caused by infection with one of several species of Leishmania parasites. Disease presentation varies because of differences in parasite and host genetics and may be influenced by additional factors such as host nutritional status or co-infection. Studies in experimental models of Leishmania infection, vaccination of companion animals and human epidemiological data suggest that many forms of leishmaniasis could be prevented by vaccination, but no vaccines are currently available for human use. AREAS COVERED: We describe some of the existing roadblocks to the development and implementation of an effective leishmaniasis vaccine, based on a review of recent literature found on PubMed, BioRxiv and MedRxiv. In addition to discussing scientific unknowns that hinder vaccine candidate identification and selection, we explore gaps in knowledge regarding the commercial and public health value propositions underpinning vaccine development and provide a route map for future research and advocacy. EXPERT OPINION: Despite significant progress, leishmaniasis vaccine development remains hindered by significant gaps in understanding that span the vaccine development pipeline. Increased coordination and adoption of a more holistic view to vaccine development will be required to ensure more rapid progress in the years ahead.

Societal Impact Statement Rapidly growing global populations mandate greater crop productivity despite increasingly scarce natural resources, including freshwater. The adoption of sustainable agricultural practices seek to address such issues, but an unintended consequence is the exposure of agricultural soils and associated biota to emerging contaminants including azole pharmaceutical antifungals. We show that environmentally relevant exposure to three commonly prescribed azole antifungals can reduce mycorrhizal 33P transfer from the soil into the host plant. This suggests that exposure to azoles may have a significant impact on mycorrhizal‐mediated transfer of nutrients in soil‐plant systems. Understanding the unintended consequences of sustainable agricultural practices is needed to ensure the security and safety of future food production systems. Summary Sustainable farming practices are increasingly necessary to meet the demands of a growing population under constraints imposed by climate change. These practices, in particular the reuse of wastewater and amending soil with wastewater derived biosolids, provide a pathway for man‐made chemicals to enter the agricultural environment. Among the chemicals commonly detected in wastewater and biosolids are pharmaceutical azole antifungals. Fungi, in particular mycorrhiza‐forming fungal symbionts of plant roots, are key drivers of nutrient cycling in the soil–plant system. As such, greater understanding of the impacts of azole antifungal exposure in agricultural systems is urgently needed. We exposed wheat (Triticum aestivum L. cv. ‘Skyfall’) and arbuscular mycorrhizal fungi to environmentally relevant concentrations of three azole antifungals (clotrimazole, miconazole nitrate and fluconazole). We traced the mycorrhizal‐acquired 33P from the soil into the host plant in contaminated versus non‐contaminated soils and found 33P transfer from mycorrhizal fungi to host plants was reduced in soils containing antifungals. This represents a potentially major disruption to soil nutrient flows as a result of soil contamination. Our work raises the major issue of exposure of soil biota to pharmaceuticals such as azole antifungals, introduced via sustainable agricultural practices, as a potentially globally important disruptive influence on soil nutrient cycles. The impacts of these compounds on non‐target organisms, beneficial mycorrhizal fungi in particular, could have major implications on security and sustainability of future food systems.

Introducción: Ni el legislador, ni los diferentes estudios previos han establecido una clasificación exhaustiva de los medicamentos de elaboración o preparación no industrial en el territorio regulatorio español. Métodos: Revisión bibliográfica sobre la normativa (nacional y comunitaria) y estudios doctrinales relativos al marco jurídico de los medicamentos de uso humano, y el análisis de la misma. Resultados: En la literatura no se encuentra una clasificación adecuada de los medicamentos de elaboración o preparación no industrial. Conclusiones: Se ha propuesto una clasificación doctrinal de los medicamentos de elaboración o preparación no industrial basada en cuatro categorías principales., Introduction: Neither the legislator nor the different previous studies have established an exhaustive classification of non-industrially elaborated or prepared drugs in the Spanish regulatory territory. Method: Bibliographic review on the regulations (national and community) and doctrinal studies related to the legal framework of medicines for human use, and their analysis. Results: There is no adequate classification of non-industrially elaborated or prepared drugs in the literature. Conclusions: A doctrinal classification of non-industrially elaborated or prepared drugs has been proposed based on four main categories.

espanolEl objetivo de este trabajo fue evaluar la calidad del agua de 11 manantiales del humedal natural “Cienega Tamasopo”, los cuales son la principal fuente de agua disponible para uso humano entre la poblacion alrededor de este humedal. Actualmente no existe informacion suficiente de los parametros fisicoquimicos y biologicos de tales manantiales. El analisis microbiologico y los parametros in situ como temperatura, pH, solidos totales disueltos y turbidez se midieron en los 11 manantiales en dos temporadas de muestreo. Los resultados obtenidos se compararon con las legislaciones nacionales (Criterios Ecologicos de Calidad del Agua, 1989, Norma Oficial Mexicana Modificada NOM-127-SSA1-1994) e internacionales (Agencia de Proteccion Ambiental y Organizacion Mundial de la Salud) para determinar si la calidad del agua de los manantiales es adecuada para el consumo humano. La problematica que enfrentan los manantiales es variada debido a las actividades antropicas y de agricultura. Por ello es necesario emprender actividades y proyectos para su proteccion y un buen aprovechamiento, a fin de evitar su deterioro. EnglishThe aim of this work was to evaluate the water quality of 11 springs of the natural wetland “Cienega Tamasopo”, which are the main source of water available for human use among the population around this wetland. Currently, there is insufficient information about the physicochemical and biological parameters of these springs. The microbiological analysis and in situ parameters such as temperature, pH, total dissolved solids, and turbidity were measured in the 11 springs in two sampling seasons. The results obtained were compared with national (Ecological Criteria for Water Quality, 1989, Official Mexican Standard Modified NOM-127-SSA1-1994) and international legislations (Environmental Protection Agency and World Health Organization) to determine whether the quality of spring water is adequate for human consumption. The problems faced by these springs are varied due to anthropogenic and agricultural activities. Therefore, it is necessary to undertake activities and projects for their protection and good use to avoid their deterioration.

It is a problem that the environment is often seen and treated as a reservoir of resources awaiting human use. How did this outlook arise? This essay analyzes a formative moment in the constitution of the environment as a buffet of goods to be consumed: seventeenth-century efforts by agricultural improvers, including John Locke, to eradicate waste. Locke’s theory of property prohibits the wasteful spoilage of food and charges mankind with a responsibility to cultivate, incorporate, and thereby appropriate earth’s nonhuman eatables—what I call his “partition of the digestible.” But eating both underwrites and unhinges Lockean property rights, for all food contains materials that cannot be used by the body and must be excreted from it. Poop and pee serve as visible (and smelly) reminders that consumption is inhabited by, and thus cannot resolve, waste. Even the improvers’ ostensible solution of repurposing excrement as manure to produce more food just creates more waste: this “peristaltic circle,” as I describe it, is voracious and expansive. Circular waste-eradication projects are best understood as enabling preconditions for the wastefulness of linear, take-make-waste political economies, not their antidote.

Human use of land has been transforming Earth's ecology for millennia. From hunting and foraging to burning the land to farming to industrial agriculture, increasingly intensive human use of land has reshaped global patterns of biodiversity, ecosystems, landscapes, and climate. This review examines recent evidence from archaeology, paleoecology, environmental history, and model-based reconstructions that reveal a planet largely transformed by land use over more than 10,000 years. Although land use has always sustained human societies, its ecological consequences are diverse and sometimes opposing, both degrading and enriching soils, shrinking wild habitats and shaping novel ones, causing extinctions of some species while propagating and domesticating others, and both emitting and absorbing the greenhouse gases that cause global climate change. By transforming Earth's ecology, land use has literally paved the way for the Anthropocene. Now, a better future depends on land use strategies that can effectively sustain people together with the rest of terrestrial nature on Earth's limited land.

Plants have been use for the treatment, mitigation and cure of the disease since time immemorial. The natural recourses are considered as safe for human use. Ayurveda advocates the Jatamansi in various human ailments. In the present review article we tried to establish the morphological, ehno-pharmacological and therapeutic aspect of the Jatamansi. The various search engines like, Google scholar, EMBASE, pub med, pub med central are used to search the literary information and published article. We tried to put the facts that are demand of this article and explore the proficiency of the Jatamansi as panacea for various ailments.

Current archaeological research on cultigens emphasizes the protracted and intimate human interactions with wild species that defined paths to domestication and, with certain plants, profoundly impacted humanity. Tobacco arguably has had more impact on global patterns in history than any other psychoactive substance, but how deep its cultural ties extend has been widely debated. Excavations at the Wishbone site, directed at the hearth-side activities of the early inhabitants of North America’s desert west, have uncovered evidence for human tobacco use approximately 12,300 years ago, 9,000 years earlier than previously documented. Here we detail the preservation context of the site, discuss its cultural affiliation and suggest ways that the tobacco may have been used. The find has implications for our understanding of deep-time human use of intoxicants and its sociocultural intersection with food crop domestication. The finding of tobacco seeds in a Pleistocene-age fire hearth suggests people learned of this plant’s intoxicant value shortly after their arrival in the Americas, initiating a long heritage of use with global societal impact.

Vaccines by different manufacturers are available for most of the vaccine-preventable infections covered by the National Immunisation Schedule of the Russian Federation. Determination of the possibility of replacing a vaccine in the case of routine or emergency vaccination still remains a challenging issue. The aim of the study was to substantiate the problem of vaccine interchangeability, outline specific challenges and ways of solving them, analyse criteria underlying evaluation of vaccine interchangeability in Russia, and international experience in this area. The procedure for determining the interchangeability of biological products, including vaccines, was established in the Decree of the Government of the Russian Federation of 5 September 2020, No. 1360 “On the procedure for determination of interchangeability of medicinal products for human use”. The paper analyses the applicability of the official criteria for interchangeability of biological products, including vaccines. It outlines the main problems of performing evaluation of vaccine interchangeability in accordance with the established criteria. It is concluded that the vaccine interchangeability criteria need to be clarified in order to allow for assessment of comparability of active substances, and comparison of efficacy, safety, and immunogenicity of vaccines, taking into account vaccination schedules for different age groups. The possibility of evaluating interchangeability based on the results of post-authorisation studies also needs clarification. It is also necessary to align patient information leaflets for interchangeable vaccines.

Fermented foods are an important part of the human diet. While the types of fermented foods consumed as well as the processes used to create them vary regionally, the majority of human populations ...

Current equipment and methods for preparation of radiopharmaceuticals for positron emission tomography (PET) are expensive and best suited for large-scale multi-doses batches. Microfluidic radiosynthesizers have been shown to provide an economic approach to synthesize these compounds in smaller quantities, but can also be scaled to clinically-relevant levels. Batch microfluidic approaches, in particular, offer significant reduction in system size and reagent consumption. Here we show a simple and rapid technique to concentrate the radioisotope, prior to synthesis in a droplet-based radiosynthesizer, enabling production of clinically-relevant batches of [18F]FET and [18F]FBB. The synthesis was carried out with an automated synthesizer platform based on a disposable Teflon-silicon surface-tension trap chip. Up to 0.1 mL (4 GBq) of radioactivity was used per synthesis by drying cyclotron-produced aqueous [18F]fluoride in small increments directly inside the reaction site. Precursor solution (10 µL) was added to the dried [18F]fluoride, the reaction chip was heated for 5 min to perform radiofluorination, and then a deprotection step was performed with addition of acid solution and heating. The product was recovered in 80 µL volume and transferred to analytical HPLC for purification. Purified product was formulated via evaporation and resuspension or a micro-SPE formulation system. Quality control testing was performed on 3 sequential batches of each tracer. The method afforded production of up to 0.8 GBq of [18F]FET and [18F]FBB. Each production was completed within an hour. All batches passed quality control testing, confirming suitability for human use. In summary, we present a simple and efficient synthesis of clinically-relevant batches of [18F]FET and [18F]FBB using a microfluidic radiosynthesizer. This work demonstrates that the droplet-based micro-radiosynthesizer has a potential for batch-on-demand synthesis of 18F-labeled radiopharmaceuticals for human use.

Objetivo: identificar os principais aspetos inovadores do Regulamento relativo aos ensaios clínicos de medicamentos para uso humano, em termos de oportunidades para a investigação e desenvolvimento e refletir sobre os desafios éticos deste novo quadro legal. Metodologia: estudo documental, descritivo, comparativo, do Regulamento face à Diretiva 2001/20/CE, e leitura de bibliografia publicada no PubMed, usando termos de pesquisa combinados ou simples como clinical, trials, European, Regulation, Directive, opportunities, challenges e innovation. Resultados: os principais aspetos inovadores identificados foram o Portal da União Europeia para submissão do dossiê do ensaio clínico e avaliação conjunta entre os Estados-Membros envolvidos num ensaio clínico; disponibilização pública de informação, resultados dos ensaios e um sumário de resultados para leigos; foram criadas a figura do copromotor, categorias de ensaios em função do risco; estabelecidos novos procedimentos para obtenção de consentimento informado e requisitos para uma maior proteção para os indivíduos mais vulneráveis; e definido o quadro normativo para a realização de ensaios clínicos em situação de emergência. Discussão: estão previstos procedimentos que visam contrariar a perda de competitividade da Europa, promovendo a inovação, alguns dos quais não estão isentos de questionamento ético. Conclusão: a simplificação, harmonização e maior transparência em todo o processo de submissão e condução dos ensaios clínicos tem o potencial de promover a investigação, mas traz alguns aspetos inquietantes em matéria de proteção dos participantes nos ensaios clínicos.

Mollusk and ostracode assemblages from the distal Old River Bed delta (ORBD) contribute to our understanding of the Lake Bonneville basin Pleistocene-Holocene transition (PHT) wetland and human presence on the ORBD (ca. 13,000–7500 cal yr BP). Located on U.S. Air Force-managed lands of the Great Salt Lake Desert (GSLD) in western Utah, USA, the area provided 30 samples from 12 localities. The biological assemblages and the potential water sources using 87Sr/86Sr analyses showed wetland expansion and contraction across the PHT, including the Younger-Dryas Chronozone (YDC). The record reflects cold, freshwater conditions, which is uncharacteristic of the Great Salt Lake Desert, after recession of Lake Bonneville. Lymnaea stagnalis jugularis, Cytherissa lacustris, and possibly Candona sp. cf. C. adunca, an endemic and extinct species only reported from Lake Bonneville, suggest cold-water environments. Between 13,000–12,400 cal yr BP, a shallow lake formed, referred to as the Old River Bed delta lake, fed by Lake Gunnison, as shown by 87Sr/86Sr ratios of 0.71024–0.71063 in mollusk fossils collected at the ORBD, characteristic of the Sevier basin. These findings add paleoenvironmental context to the long-term use of the ORBD by humans in constantly changing wetland habitats between 13,000–9500 cal yr BP.

Introdução:O teste de toxicidade in vivo, conhecido como Teste de Toxicidade Inespecífica (TTI), é sugerido para avaliar a segurança de produtos biológicos e derivados de biotecnologia. O princípio do teste é a administração do produto em animais, seguido por um período de observação. O Instituto Nacional de Controle de Qualidade em Saúde (INCQS) é o laboratório de controle nacional brasileiro (LCN) que controla os produtos biológicos, especialmente vacinas e soros hiperimunes, para o Programa Nacional de Imunização (PNI) antes da liberação para o mercado. São preconizados ensaios químicos, microbiológicos e toxicológicos, inclusive o TTI. Objetivo:Analisar retrospectivamente o TTI realizado no INCQS e verificar as monografias da Farmacopeia Brasileiraonde ainda é preconizado o teste. Método:Foi realizado um levantamento no sistema de dados Harpya do INCQS, para verificar os resultados satisfatórios e insatisfatórios do TTI. Resultados:No período de 1999 a 2012, foram realizados 3.453 TTI nos produtos biológicos, resultando em 100% de resultados satisfatórios. Com base nestes resultados e seguindo a tendência mundial, o INCQS vem desde 2002 reduzindo gradualmente a quantidade de produtos biológicos submetidos ao TTI. Atualmente, o risco de contaminação de produtos farmacêuticos com substâncias não específicas é significativamente baixo, pois as indústrias são reguladas para o cumprimento das boas práticas de fabricação (BPF). Embora o TTI ainda permaneça nos Testes Gerais da Farmacopeia Brasileira, ele não é requerido nas monografias específicas de soros hiperimunes e vacinas para uso humano. Conclusões: O TTI não parece ser eficiente para detectar toxicidade inespecífica em biológicos e o Brasil deve seguir a tendência mundial de interromper a sua execução.

Human health is plagued by several challenges throughout life. Different endogenous and exogenous factors influence the well-being of humans. The endogenous factors may be the enzymes and hormonal functions that alter the normal human physiological status and cause diseases like metabolic disorders, organ dysfunctions (liver diseases, heart diseases), and several others. Also, the human immune system and the cells involved in the immune responses may be disturbed causing autoimmune disorders, and tumors/cancers/malignancies. The exogenous reasons for human illnesses may be infectious diseases caused by microbes, chemicals, toxins, and others to those humans get exposed during their lifetime. The management of such illnesses and diseases is generally carried out by qualified physicians, and surgeons, and respective clinical experts in healthcare institutions that include hospitals. The drugs, devices, and other agents used to manage human diseases are synthesized and tested exhaustively before being approved and marketed for human use for their safety and efficacy by performing clinical research. In this review, we attempt to delineate the different types of clinical research and their implications.

Background In 2016, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use updated its efficacy guideline for good clinical practice and introduced quality tolerance limits (QTLs) as a quality control in clinical trials. Previously, TransCelerate proposed a framework for QTL implementation and parameters. Historical data can be important in helping to determine QTL thresholds in new clinical trials. Methods This article presents results of historical data analyses for the previously proposed parameters based on data from 294 clinical trials from seven TransCelerate member companies. The differences across therapeutic areas were assessed by comparing Alzheimer’s disease (AD) and oncology trials using a separate dataset provided by Medidata. Results TransCelerate member companies provided historical data on 11 QTL parameters with data sufficient for analysis for parameters. The distribution of values was similar for most parameters with a relatively small number of outlying trials with high parameter values. Medidata provided values for three parameters in a total of 45 AD and oncology trials with no obvious differences between the therapeutic areas. Conclusion Historical parameter values can provide helpful benchmark information for quality control activities in future trials.

The concept of going 'green' and 'cold' has led to utilizing renewable resources for the synthesis of microbial biosurfactants that are both patient and eco-friendly. In this review, we shed light on the potential and regulatory aspects of biosurfactants in pharmaceutical applications and how they can significantly contribute to novel concepts for the Coronavirus 2019 (COVID-19) vaccine and future treatment. We emphasize that more specific guidelines should be formulated to regulate the approval of biosurfactants for human use. It is also crucial to implement a risk-based approach from the early research and development (R&D) phase in addition to establishing more robust standardized techniques and assays to evaluate the characteristics of biosurfactants.

The pandemic coronavirus disease 2019 (COVID-19) is instigated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is mainly transmitted via the inhalation route and characterized by fever, coughing and shortness of breath. COVID-19 affects all age groups with no single cure. The drug discovery, manufacturing, and safety studies require extensive time and sources and, therefore, struggled to match the exponential spread of COVID-19. Yet, various repurposed drugs (antivirals, immune-modulators, nucleotide analogues), and convalescent plasma therapy have been authorized for emergency use against COVID-19 by Food and Drug Administration under certain limits and conditions. The discovery of vaccine is the biggest milestone achieved during the current pandemic era. About nine vaccines were developed for human use with varying claims of efficacy. The rapid emergence of mutations in SARS-CoV-2, suspected adverse drug reactions of current therapies in special population groups and limited availability of drugs in developing countries necessitate the development of more efficacious, safe and cheap drugs/vaccines for treatment and prevention of COVID-19. Keeping in view these limitations, the current review provides an update on the efficacy and safety of the repurposed, and natural drugs to treat COVID-19 as well as the vaccines used for its prophylaxis.

Providing suitable drinking water for human use is a major goal in all countries, and contamination of drinking water with microorganisms represents a great danger to human health. Free-living amoebae (FLAs, Pathogenic) are found in all natural and manufactured environments, including aquatic environments. Several FLAs such as Acanthamoeba spp. infect humans, causing dangerous diseases. The purpose of this investigation was to search about FLAs in tap water in Nasr City, Cairo. FLAs were detected in 59 (53.63 %) out of 110 tap water samples which were morphologically identified as two Acanthamoeba spp. The molecular identification to the species level was carried out, using a simple PCR technique and DNA sequencing. Acanthamoeba spp. were recorded in the gene bank under accession numbers Acanthamoeba MT944118 and Acanthamoeba MT944119.

Introduction: Continuous positive airway pressure (CPAP) therapy remains the standard treatment for obstructive sleep apnea. However, its proven effect is useless if the patient does not tolerate the treatment. The electrical stimulation approach has been investigated for several decades now and it seems that the implantable devices for invasive electrical stimulation of hypoglossal nerve are viewed as effective with some of them already approved for human use. Areas covered: in this review, we intent to summarize the existing records of noninvasive stimulation in sleep apnea to make the scientific community aware of the details before deciding on its future. We believe that this is a battle still to fight and more could be done bearing in mind the safety of this method. Expertopinion: noninvasive electrical stimulation has been left behind based on few, small and inconsistent studies using different stimulation parameters. These studies are difficult to compare and to draw conclusions. Electrical stimulation is a field for research in the treatment of obstructive sleep apnea, with many aspects still to be discovered, and which may become a therapeutic alternative to the use of CPAP in certain patients.

This « Magnum Opus » emphasizes that serendipity is a corner stone in research. The paths of discovery and innovation often result from the interdisciplinarity of scientific areas that are a priori disconnected from each other. In the 1970s, fundamental discoveries in cell biology led to unexpected advances in galenic pharmacy with the emergence of nanotechnologies for the intracellular delivery of non diffusing molecules. As well, fluorescein-loaded polyacrylamide nanocapsules were shown to deliver this fluorescent agent precisely into cellular lysosomes which represented a seminal observation. However, due to the lack of biodegradability of this carrier polymer, this approach was still far from therapeutic application. The use of cyanoacrylates as surgical glue inspired us to use this material in the design of the first biodegradable nanoparticles for human use. Capable of transporting compounds with anti-tumor activity, these polyalkylcyanoacrylate nanoparticles demonstrated the unexpected property of overcoming multi-drug resistance. This discovery led to the development of a nanomedicine that has completed phase III clinical trials for the treatment of resistant hepatocarcinoma. Going beyond the state-of-the art, a step ahead in the nanomedicine field was the drug « squalenoylation » technology, which represents a shift from the « physical » to the « chemical » encapsulation paradigm. The bioconjugation of anticancer and other drugs to squalene, a natural and biocompatible lipid, enabled a dramatic increase in drug payload, and eliminated the so-called « burst release » of drug: Two major drawbacks commonly associated with drug nanoencapsulation. The drug « squalenoylation » approach resulted in a generic nanomedicine platform with broad pharmacological applications.

Inert and stable radiolabeling of monoclonal antibodies (mAb), antibody fragments, or antibody mimetics with radiometals is a prerequisite for immuno-PET. While radiolabeling is preferably fast, mild, efficient, and reproducible, especially when applied for human use in a current Good Manufacturing Practice compliant way, it is crucial that the obtained radioimmunoconjugate is stable and shows preserved immunoreactivity and in vivo behavior. Radiometals and chelators have extensively been evaluated to come to the most ideal radiometal-chelator pair for each type of antibody derivative. Although PET imaging of antibodies is a relatively recent tool, applications with 89Zr, 64Cu, and 68Ga have greatly increased in recent years, especially in the clinical setting, while other less common radionuclides such as 52Mn, 86Y, 66Ga, and 44Sc, but also 18F as in [18F]AlF are emerging promising candidates for the radiolabeling of antibodies. This review presents a state of the art overview of the practical aspects of radiolabeling of antibodies, ranging from fast kinetic affibodies and nanobodies to slow kinetic intact mAbs. Herein, we focus on the most common approach which consists of first modification of the antibody with a chelator, and after eventual storage of the premodified molecule, radiolabeling as a second step. Other approaches are possible but have been excluded from this review. The review includes recent and representative examples from the literature highlighting which radiometal-chelator-antibody combinations are the most successful for in vivo application.

The first patient with coronavirus disease (COVID-19) was reported in December 2019 in Wuhan, Hubei province, China. Since then, more than 149.471 million COVID-19 cases have been reported worldwide, with over 3.15 million deaths. The rapid spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection or COVID-19 has made researchers focus on developing an effective vaccine to prevent the disease. One hundred and eighty-four vaccine candidates in pre-clinical development have been tested on different animal models of SARS-CoV-2 infection (Source WHO; Draft landscape and tracker of COVID-19 candidate vaccines (who.int)). An additional 63 vaccines are currently in clinical development. Thus, more than 200 vaccine candidates have been developed within almost a year of the first reported case of COVID-19, and of these, 10 vaccines have been approved for human use (Table 1). The first human trial of a COVID-19 vaccine started on 6 March 2020, and the rapid pace of vaccine development would not have been feasible without a combined proteomics and genomics approach against SARS-CoV-2. Table 1. Different vaccines approved for human use to prevent COVID-19

Utilization of crude extracts separated from herbal medicine is getting more worthy and ideal, conceivably because of the expense of production, accessibility and availability to bring down harmful effects as much as possible. Various researches have shown that the regular use of particular soil products like fruits and vegetables can minimize the risk of a number of infections. Ginger is among the most commonly and regularly devoured dietary sauces on the planet. One of the major impactful components of ginger, 6-gingerol is suggested for the avoidance of malignancy and different maladies. As a spice and home grown medicine, the rhizome of Zingiber officinale (ginger) is devoured worldwide and it contains sharp phenolic compounds known as gingerols aggregately. The main pharmacologically-dynamic segment of ginger is 6-Gingerol. It is recognized to show a variety of organic actions including anti-cancer, anti-inflammation, and anti-oxidation. 6-Gingerol has been found to have anticancer effects by means of its impact on an assortment of natural pathways associated with apoptosis, control of cell cycle, cytotoxic action and restraint of angiogenesis. Consequently, because of its adequacy and control of different targets, just as its security for human use, 6-gingerol has gained impressive enthusiasm as an expected helpful operator for the anticipation and additionally treatment for different maladies. Taken together, this review sums up the different in vitro and in vivo pharmacological aspects of 6-gingerol and their underlying mechanisms.

The global number of deaths due to COVID-19 is almost at the two million mark, with over 35 000 deaths in South Africa. Although there are hopes of a safe and effective vaccination programme, the increasing number of COVID-19 cases in the country is putting a significant strain on the healthcare system. Ivermectin, an antiparasitic drug, has been widely published on social media platforms and news outlets as a so-called miracle drug for the treatment of COVID-19. Ivermectin is not registered in SA as a drug for human use, but rather as a veterinary and agricultural product. Currently, from a small number of randomised controlled trials (RCTs), there does seem to be a signal of evidence for the use of ivermectin in the management of COVID-19. Pharmacists must, however, remain cognisant of their ethical responsibilities as well as the applicable regulations that prohibit the procurement and dispensing of any unregistered medicine.

Sob o viés arqueológico denominado archaeogaming (Reinhard, 2018), este artigo tem por objetivo central colaborar com a metodologia de análise de jogos eletrônicos em ambientes digitais a partir do produto Detroit: Become Human, lançado em 2018 pela desenvolvedora francesa Quantic Dream. Serão objetos de análise as paisagens arqueológicas extra e intra-jogo, buscando os tecnofósseis que corroboram a inserção do jogo, enquanto mídia física, no debate sobre o Antropoceno; e, enquanto mídia digital, na recente hipótese de datação geológica, elencada pelo químico e ambientalista James Lovelock denominada Novaceno (Novacene). Pretende-se, assim, apresentar não uma Arqueologia Digital, mas, sim, uma Arqueologia do Digital, escavando e trazendo à luz vestígios que permitam, ao mesmo tempo, o entendimento do uso humano de máquinas cibernéticas, bem como a representação dessas máquinas a partir de códigos de programação intra-jogo escritos por humanos.

[89 Zr]Oxinate4 is a Positron Emission Tomography (PET) tracer for cell radiolabeling that can enable imaging techniques to help better understand cell trafficking in various diseases. Although several groups have synthetized this compound for use in preclinical studies, there is no available data regarding the production of [89 Zr]Oxinate4 for human use. In this report, we describe the detailed production of [89 Zr]Oxinate4 under USP and autologous leukocyte radiolabeling under USP . The final product presented high radiochemical purity and stability at 24 h post synthesis (>99%) and passed in all quality control assays required for clinical use. [89 Zr]Oxinate4 did not compromise the white blood cells viability and did not show considerable cellular efflux up to 3 h post labeling. The translation of this technique into human use can provide insight into several disease mechanisms since [89 Zr]Oxinate4 has the potential to label any cell subset of interest.

Botanical drugs are plant-derived, complex mixtures which may have synergistic effects. In order to understand this disparity between human use and drugs approved by regulatory agencies, we analyzed botanical drug clinical trials registered at ClinicalTrial.gov to detect trends in current trials and guide future trials. A total of 195 botanical drug clinical trials were registered from 2016 to 2019, of which 81 are phase II or phase II/III. 95% of all phase II and II/III studies were designed with 100 or less participants per arm, indicating a more observational nature due to the limited power to detect differences in outcomes between treatment and control groups. Due to the limited number of participants, efficacy outcome from results may be highly subjective. 14% of the total trials were phase I studies. For botanical drugs with well-documented or extensive history of human use, phase I may not provide significant additional information, and may, therefore, not be necessary. For the trial design, we suggest added-on studies when botanical drugs are used as part of a combination treatment. Additionally, we believe standardized data collection methods and criteria are critical to utilizing the vast collection of human experience as quality evidence to support regulatory approval.

O municipio de Minacu, na regiao norte do estado de Goias, difere de muitos municipios brasileiros pelas intensas alteracoes ocorridas em seu territorio. O municipio e conhecido como a capital brasileira do amianto, minerio que deu origem a ocupacao da regiao, cuja extracao ja dura seis decadas. Alem das grandes cavas abertas pela atividade mineratoria, o municipio ainda conta com duas usinas hidreletricas, bem como parte de seus respectivos reservatorios, que cobrem boa parte de suas terras. O objetivo desse estudo foi analisar o uso e cobertura do solo entre os anos de 1988 e 2018 de Minacu. Para tanto, foram empregados os dados de uso do solo do projeto MapBiomas, utilizados tambem para analise da conversao entre as classes do mapeamento do ano inicial para o final do periodo de analise. As classes menos expressivas para o periodo em analise foram area nao vegetada, mineracao, infraestrutura urbana e floresta plantada. As areas de vegetacao natural, como florestas e savana, foram convertidas para areas de uso antropico, principalmente pastagem, alem de terem tambem as maiores areas inundadas pelos dois reservatorios de usinas hidreletricas presentes no municipio. Os dados utilizados possibilitaram um estudo eficiente e de baixo custo, que serve de base para uma maior compreensao da dinâmica do uso e cobertura, servindo ainda como base ao planejamento da ocupacao sustentavel do solo. Temporal analysis of land use and land cover in the Brazilian capital of asbestos: Minacu, state of Goias A B S T R A C T The municipality of Minacu, in the northern region of the state of Goias, differs from many Brazilian municipalities due to the intense changes that have occurred in its territory. The municipality is known as the Brazilian capital of asbestos, an ore that gave rise to the occupation of the region, whose extraction has lasted six decades. In addition to the large pits opened by mining, the municipality also has two hydroelectric plants, in addition to part of their respective reservoirs, which occupy a large part of their land. The objective of this study was to analyze the land use and cover between the years 1988 and 2018 of Minacu. For that, the data of land use of the MapBiomas project were used, also used for analysis of the conversion between the classes of the mapping from the initial year to the end of the period of analysis. The least significant classes for the period under analysis were non-vegetated area, mining, urban infrastructure and planted forest. The areas of natural vegetation, such as forests and savanna, were converted to areas for human use, mainly pasture, also had the largest areas flooded by the two reservoirs of hydroelectric plants present in the municipality. The data used enabled an efficient and low-cost study, which serves as a basis for a greater understanding of the dynamics of use and coverage, also serving as a basis for planning sustainable land occupation. Keywords: Remote sensing, Geoprocessing, Geographic information systems, QGIS.

Elimination of fluoride from water sample is an imperative stimulus for the betterment of society. Based on WHO policy, the fluoride level superior than 1.5 miligram/litre causes dental and bone scarcity to living entities. In order to prevent these issues, the proper deflouridation technique was chosen. In the present investigations highlighted the elimination percentage of Fluoride from water with the aid of low-cost material, rice husk. Various physical and chemical deflouridation methods were developed to treat high concentrations of fluoride in ground water. Those deflouridation methods need to be built which this will be cost-efficient, and biodegradable. Rice husk is used to detoxify fluoride-rich water and making it safe for human use. 0.5 g/100 mL of adsorbent accomplished 87% of fluoride removal.

Review paper DOI: https://doi.org/10.37458/ssj.1.2.1 Security is in general closely linked to any activity of individuals and societyas a whole, and bound to social relations, which are always decisive inshaping the security strategies of individual states. Security is one of the mostimportant values of society and culture. Security and conflict resolutionshould be an object of the interdisciplinary approach. Socio-culturalanthropology applied in security studies is a valuable and effective source ofknowledge protecting all actors. Only with a proper understanding of theoperational environment with its variables and elements, it is possible toassure effective and human use of power and military decision-making toolsand methods. While this paper brings the ideas of many authors, socioculturalanthropology is not that widely used in the military.

Introduction: The main purpose of this study was comparing median time (TTR, time to reimbursement) between the first Agenzia Italiana del Farmaco (AIFA) pricing and reimbursement (P&R) dossier’s evaluation and patient access in Italy and to observe the key P&R negotiation results for all new active substances approved by the European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use between January 2014 and December 2019. We analysed the different factors influencing TTR. Methods: A panel of medicines for human use approved by the EMA in the period 2014-2019 was considered. All information about authorisation and reimbursement in Italy, including timelines and results from the negotiation, were gathered through EMA and Italian Official Journal databases. Results: Of 213 new active substances approved from January 2014 to December 2019, 137 obtained reimbursement in Italy, with a median TTR of 7.6 months (228 days). Even if orphan designation, oncology indication, application of Managed Entry Agreements (MEAs; both outcome and financial based) or a discount did not show an impact on TTR, recognition of full innovativeness (n = 27; 20%) was associated with a reduction of 1 month in median TTR. Interestingly, drugs reimbursed with a lower price/daily defined dose showed a reduced TTR (−22%). Conclusions: Even if the lack of impact of some negotiation conditions was predictable (e.g. oncology indication or orphan status) or the application of a MEA helped to manage possible uncertainties, it did not lead to a quicker completion of the negotiation procedure. Likewise, full innovative drugs showed a shorter TTR underlying the AIFA commitment in recognising, promoting and rewarding innovation.