Lessons Learned Through Time: An Examination of the 1918 Influenza Pandemic and the COVID-19 Crisis

The purpose of the present study is to compare the United States’ federal and state response to the 1918 Influenza Pandemic and the 2020 COVID-19 Crisis and the role of bureaucracy. Utilizing Qualitative Content Analysis, I examined 300 newspaper articles from The New York Times, The Clarion-Ledger, and The Daily Clarion-Ledger from July 1, 1918, to December 31, 1918, and March 1, 2020, to August 31, 2020. Through this analysis, I found that federal and state governments reacted to the 1918 flu very quickly, whereas the response to COVID-19 was hindered due to political in-fighting that impeded the bureaucracy and interfered with proper procedures to combat the outbreak. Charismatic rule did infringe to some extent on how the bureaucracy responded to COVID-19. This study shows that, while the response to the 1918 flu was much more efficient than the coronavirus pandemic response, the approaches of the federal and state governments to both pandemics were flawed in some way. Based on the findings of this piece, the United States needs an organization or agency on the federal, state, and regional levels to streamline pandemic response so that, in the event of a future epidemic or pandemic, the United States can respond promptly and focus on preserving lives

More than Altruism: An Examination of Dr. Martin Luther King Jr.'s Involvement in the Chicago Campaign and Protest of the Vietnam War

This mix-method study examines whether Dr. Martin Luther King Jr.’s writing reflects altruism. Utilizing content analysis, I examined 60 of King’s sermons, speeches, letters, newspaper statements, and telegrams about the Chicago Campaign and the Vietnam War over two separate two-year periods starting from January 1, 1965 to December 31, 1967. King’s documents were scored based on the Altruistic Personality Scale for Leaders and Protest, which was created based on the characteristics of both passive and active bystanders derived from studies written by scholars of psychology. After analyzing the range, complexity, and density of King’s altruism, this study shows that all but seven of King’s writings expressed altruism with his writings concerning his involvement in the Chicago Campaign and protest of the Vietnam War being moderately altruistic. A pattern emerged within the documents indicating that King envisioned the formation of an entirely new social movement that sought to change the social structure of the northern cities by addressing three major social problems that he saw as paralyzing progress: education, employment, and housing. The effects of such a movement when considered within the range of events such as the Poor People’s Campaign portend change for people of color and for the country as a whole

Evaluation du potentiel de lectines végétales dans le ciblage de médicaments anticancéreux : application à la photochimiothérapie

La photochimiothérapie (ou PCT) peut être utilisée pour le traitement de tumeurs solides (thérapie photodynamique ou PDT) ou pour le traitement ex vivo de différentes pathologies hématologiques (photochimiothérapie extracorporelle ou ECP), comme par exemple le lymphome de Sézary. Le développement de la PCT en oncologie demeure limité en raison de la faible sélectivité des photosensibilisants pour les cellules tumorales. Afin d'augmenter la biodisponibilité des photosensibilisants vis-à-vis des cellules cancéreuses, nous proposons d'utiliser des lectines végétales comme molécule vectrice. A côté des anticorps ou des peptides ciblant les cellules tumorales, les lectines peuvent être une approche complémentaire. En effet, certaines lectines reconnaissent des épitopes glycaniques préférentiellement exprimés par les cellules tumorales. De plus, certaines d'entre elles présentent des effets immunomodulateurs et/ou toxiques, induisant des effets anticancéreux directs (toxicité) ou indirects (immuno-modulation). Deux lectines extraites de l'écorce du mûrier noir Morus nigra semblent être particulièrement intéressantes. Il s'agit de Morniga G (MorG) et de Morniga M (MorM). Ces deux lectines présentent des spécificités glycaniques différentes. Alors que MorM est spécifique du mannose, MorG est spécifique du galactose. Cependant, des lectines présentant une spécificité de reconnaissance monosaccharidique identique peuvent interagir avec des oligosaccharides très différents et induire des effets biologiques distincts. Ainsi, la reconnaissance glycanique médiée par MorM pourrait être sensible à des altérations fines de la N-glycosylation. De même, MorG présente une forte affinité pour certains antigènes O-glycaniques associés aux tumeurs, tels que les antigènes T (CD176; Gal1-3GalNAc1-O-Ser/Thr) et Tn (CD175; GalNAc1-O-Ser/Thr). Dans un premier temps, les effets biologiques de ces deux lectines ont été évalués sur des lymphocytes sains et leucémiques. Elles présentent des effets immunomodulateurs sur les lymphocytes sains et induisent un effet toxique à plus forte dose sur les cellules leucémiques Jurkat. MorM pourrait interagir, en partie, avec la N-glycosylation de certains récepteurs de mort tels que Fas, tandis que MorG pourrait interagir avec la O-glycosylation d'autres récepteurs de mort comme TRAIL-R. Ainsi, ces deux lectines induiraient une mort cellulaire caspase-dépendante en activant des récepteurs de mort différents. De plus, après interaction avec les glycoconjugués membranaires, elles sont rapidement endocytées, ce qui peut, à des concentrations non toxiques, en faire des vecteurs intéressants pour faciliter la pénétration intracellulaire de médicaments. Dans un second temps, un conjugué covalent de la lectine Morniga G et de la porphyrine [5-(4-(5-carboxy-1-butoxy)-phényl)-10,15,20-tris(4-N-méthyl)-pyridiniumyl)] (TrMPyP) a été préparé et caractérisé. La phototoxicité du conjugué TrMPyP-MorG a été évaluée contre la lignée leucémique lymphoïde Jurkat exprimant fortement l'antigène Tn. Le conjugué (1) est internalisé rapidement (5 min) par les cellules Jurkat, (2) augmente très fortement l'activité phototoxique de TrMPyP (DL50 de TrMPyP-MorG = 5 nM ; DL50 de TrMPyP = 15 µM), par l'intermédiaire d'un processus dépendant de la O-glycosylation, (3) induit une mort cellulaire majoritairement caspase indépendante, (4) est capable d'éliminer spécifiquement les cellules leucémiques T Jurkat (Tn-positives) mélangées à des lymphocytes T sains (Tn-négatifs), en préservant le potentiel fonctionnel des lymphocytes sains. De façon intéressante, après irradiation, le conjugué TrMPyP-MorG est capable d'entraîner un effet phototoxique sur différentes lignées cellulaires leucémiques d'origine myéloïde ou lymphoïde et sur des cellules tumorales fraîches provenant de patients atteints de leucémies lymphoïdes aigues ou chroniques. Enfin, des photosensibilisants (activables dans le rouge) plus adaptés au traitement PDT de tumeurs solides ont été greffés sur la lectine MorG. Leur phototoxicité a été étudiée in vitro sur le modèle de cellules leucémiques Jurkat. Les présentes observations démontrent la capacité des lectines végétales à cibler des altérations de la glycosylation à la surface de cellules tumorales et à augmenter l'activité phototoxiques des photosensibilisants dans le cadre de la photochimiothérapie, et en particulier de la photochimiothérapie extracorporelle des leucémies.Photochemotherapy is used both for solid tumors and in extracorporeal treatment of various hematologic disorders, such as Sezary lymphoma. Nevertheless, its development in oncology remains limited, because of the low selectivity of photosensitizers. To enhance photosensitizer selectivity towards human tumor cells, a plant lectin was used as a carrier to target tumor O-glycosylation alterations. Beside monoclonal antibodies or targeting peptides, plant lectins might be a complementary approach. Some lectins have the capability to specifically interact with tumor-associated carbohydrate antigens (TACAs). Morevover, some of them induce immunomodulatory and anticancer effects. Anticancer effects can be resume to indirect effects (such as anticancer immune activation) or direct effects (such cytotoxicity on tumor cells). Two Jacalin-Related Lectins (JRL) extracted from Morus nigra seem to be interesting for biomedical applications. Morniga G (MorG) is a galactose-specific lectin, and Morniga M (MorM) is mannose-specific. Although, MorM could interact with N-linked glycans, MorG could interact with O-linked glycans. Thus, MorG seems to be highly specific for TACAs T (CD176; Gal1-3GalNAc1-O-Ser/Thr) and Tn (CD175; GalNAc1-O-Ser/Thr). These differential monosaccharidic-binding properties could induce different biological effects. First, we have investigated biological effects of the two JRLs on healthy and leukemic lymphocytes. MorG and MorM induce immunomodulatory effects on healthy lymphocytes and cytotoxic effects at higher doses on Jurkat leukemic cells. MorM could interact with N-linked death receptors, such as Fas, and MorG could bind to O-linked death receptors, such as TRAIL-R. So, these lectins might induce caspase-dependent apoptotic process by activating different death receptors-mediated signaling. Thus, after membrane interaction, these lectins are rapidly endocytosed by cells, which at low doses, make them interesting targeting molecules to improve medicines efficacy. On the other hand, a white-light activatable porphyrin, [5-(4-(5-carboxy-1-butoxy)-phenyl)-10,15,20-tris(4N-methyl)-pyridiniumyl)-porphyrin] (TrMPyP), was covalently linked to MorG. The conjugate was molecularly and biologically characterized. Its cytotoxicity was evaluated after photochemotherapy, using human lymphoid leukemia cells as a tumor cell model. Using Tn-positive (Jurkat lymphoid leukemia) cells, the conjugate (with a 1:1 photosensitizer:lectin ratio) (i) was quickly (5 min) taken-up; (ii) dramatically increased cytotoxicity upon irradiation (LD50 = 5 nM) as compared to free photosensitizer (LD50 = 15 µM), through an O-glycan-dependent process; (iii) induced caspase-independent cell death; (iv) specifically purged tumor cells from a 1:1 mixture of Jurkat leukemia (Tn-positive) and healthy (Tn-negative) lymphocytes, preserving the activation potential of healthy lymphocytes. Finally, the effectiveness of the conjugate-mediated killing on various leukemic cell lines as well as human primary acute and chronic lymphoid leukemia cells correlates with the ability of the lectin to bind the cell surface antigens. Lastly, different PS that are more adapted to solid tumors PDT treatment, i.e. activatable in the red wavelengths, were covalently linked to MorG. Their phototoxic activities were tested in vitro against Jurkat cell line. These conjugates were able to kill Jurkat cells when irradiated by red light. The present observations demonstrate the potential of plant lectins to target glycan alterations on tumor cells and their ability to improve PS endocytosis and effectiveness in the field of extracorporeal photochemotherapy of leukemias

Cancer targeting with biomolecules: a comparative study of photodynamic therapy efficacy using antibody or lectin conjugated phthalocyanine-PEG gold nanoparticles

The functionalisation of therapeutic nanoparticle constructs with cancer-specific biomolecules can enable selective tumour accumulation and targeted treatment. Water soluble gold nanoparticles (ca. 4 nm) stabilised by a mixed monolayer of a hydrophobic zinc phthalocyanine photosensitiser (C11Pc) and hydrophilic polyethylene glycol (PEG) have been prepared. The C11Pc-PEG gold nanoparticle constructs were further functionalised with jacalin, a lectin specific for the cancer-associated Thomsen–Friedenreich (T) carbohydrate antigen, or with monoclonal antibodies specific for the human epidermal growth factor receptor-2 (HER-2). The two biofunctionalised nanoparticle conjugates produced similar levels of singlet oxygen upon irradiation at 633 nm. Importantly, both nanoparticle conjugates demonstrated extensive, yet comparable, phototoxicity in HT-29 colorectal adenocarcinoma cells (80–90%) and in SK-BR-3 breast adenocarcinoma cells (>99%). Non-conjugated C11Pc-PEG gold nanoparticles were only minimally phototoxic. Lysosomal colocalisation studies performed with the HT-29 colon cancer cells and the SK-BR-3 breast cancer cells revealed that both nanoparticle conjugates were partially localised within acidic organelles, which is typical of receptor-mediated endocytosis. The similarity of the targeted PDT efficacy of the two biofunctionalised C11Pc-PEG gold nanoparticles is discussed with respect to targeting ligand binding affinity and cell surface antigen density as key determinants of targeting efficiency. This study highlights how targeting small cell-surface molecules, such as the T antigen, can mediate a selective photodynamic treatment response which is similar to that achieved when targeting overexpressed protein receptors, such as HER-2. The high prevalence of the T antigen present on the cellular surface of primary tumours emphasises the broad potential applications for lectin-targeted therapies

Electron-Shading Characterization in a HDP Contact Etching Process Using a Patterned CHARM Wafer

In this work, a CHARM-2 wafer with high aspect ratio resist patterns has been used to quantitatively I. Introduction To understand the origin of plasma-induced damage, useful plasma parameters such as floating potentials and J-V characteristics can be measured using the non-invasive CHARM method To study this effect, we have designed different resist patterns on a 200 mm CHARM™-2 wafer with an e-beam lithography. This allows to obtain realistic variable aspect ratio as high as 4, contrary to previous studie

Le personnel soignant et l'hygiène des mains en réanimation : une analyse sociologique

Introduction/objectif du travail : Depuis quelques années, l’intérêt de l’analyse du comportement du personnel hospitalier vis-à-vis de règles d’hygiène des mains (HM) a été beaucoup étudié, ce qui a permis de mieux comprendre l’échec ou le caractère transitoire du succès de nombreux programmes d’amélioration de son observance. Cependant, peu d’études de ce type ont été réalisées en France. Notre objectif était d’étudier les aspects sociologiques des pratiques d’HM en réanimation. Matériel et Méthodes : L’étude a été réalisée par l\u27Institut de Psychologie et de Sociologie Appliquées de l\u27Université Catholique de l\u27Ouest (UCO, Angers), en collaboration avec l\u27équipe opérationnelle d\u27hygiène et deux services de réanimation du CHU d\u27Angers. Elle a comporté une phase d\u27observation participante menée par une étudiante en sociologie (Master-1), infirmière (IDE) de formation initiale, et une phase d\u27entretiens semi directifs réalisés par deux enseignants chercheurs de l\u27UCO. Résultats : Une constatation importante a été l\u27existence d\u27un conflit pour les soignants entre la règle ontextualisée telle qu\u27elle est pratiquée avec l\u27influence des antériorités du service, de la socialisation par les pairs (périodes de doublage) ou des situations d\u27urgence d\u27une part, et la règle institutionnalisée (recommandations) telle qu\u27elle est définie par les experts et transmise par les IDE hygiénistes. Les professionnels de l\u27hygiène et les soignants ont souvent une conception différente des soins : les premiers les décomposent en séquences de plusieurs tâches avec un acte d\u27HM à pratiquer entre chacune d\u27elles, alors que les seconds perçoivent un soin comme un tout, et effacent mentalement certaines interruptions pour assurer l\u27enchaînement des tâches. Il est apparu que d\u27après les entretiens, l\u27"asepsie" était la règle absolue pour les IDE, constituant un "plus" par rapport à l\u27"hygiène". Ainsi, une pratique comme l\u27HM ne serait "que" de l\u27hygiène par rapport à d\u27autres pratiques considérées comme garantes de l\u27"asepsie", ce qui pourrait constituer un facteur de mauvaise observance de l\u27HM. Enfin, il a été observé le fréquent ressenti d\u27un risque plus important de contamination du patient vers le soignant que du soignant vers un autre patient, ce qui génère des comportements auto protecteurs. Conclusion : Il paraît important que dans leurs relations avec les soignants, les professionnels de l\u27hygiène hospitalière aient conscience que le non suivi des règles d\u27hygiène ne doit pas être interprété comme un dysfonctionnement ou un acte non rationnel, mais qu\u27il correspond à l\u27application d\u27autres logiques d\u27action à caractère prioritaire pour les soignants

Comparative characterization of phenolic and other polar compounds in Spanish melon cultivars by using high-performance liquid chromatography coupled to electrospray ionization quadrupole-time of flight mass spectrometry

Melon (Cucumis melo L.), belonging to the Cucurbitaceae family, is a significant source of phytochemicals which provide human health benefits. High-performance liquid chromatography coupled to electrospray ionization mass spectrometry quadropole-time of flight (HPLC-ESIQTOF-MS) was used for the comprehensive characterization of 14 extracts from 3 Spanish varieties of melon (Galia, Cantaloupe, and Piel de Sapo). A total of 56 different compounds were tentatively identified, including: amino acids and derivatives, nucleosides, organic acids, phenolic acids and derivatives, esters, flavonoids, lignans, and other polar compounds. Of these, 25 were tentatively characterized for the first time in C. melo varieties. Principalcomponent analysis (PCA) was applied to gain an overview of the distribution of the melon varieties and to clearly separate the different varieties. The result of the PCA for the negative mode was evaluated. The variables most decisive to discriminate among varieties included 12 of the metabolites tentatively identified.CIDAF (Centro de Investigación y desarrollo del Alimento Funcional), Departamento de química analítica. Grupo FQM-297

Targeting of T/Tn Antigens with a Plant Lectin to Kill Human Leukemia Cells by Photochemotherapy

Photochemotherapy is used both for solid tumors and in extracorporeal treatment of various hematologic disorders. Nevertheless, its development in oncology remains limited, because of the low selectivity of photosensitizers (PS) towards human tumor cells. To enhance PS efficiency, we recently covalently linked a porphyrin (TrMPyP) to a plant lectin (Morniga G), known to recognize with high affinity tumor-associated T and Tn antigens. The conjugation allowed a quick uptake of PS by Tn-positive Jurkat leukemia cells and efficient PS-induced phototoxicity. The present study was performed: (i) to evaluate the targeting potential of the conjugate towards tumor and normal cells and its phototoxicity on various leukemia cells, (ii) to investigate the mechanism of conjugate-mediated cell death. The conjugate: (i) strongly increased (×1000) the PS phototoxicity towards leukemic Jurkat T cells through an O-glycan-dependent process; (ii) specifically purged tumor cells from a 1∶1 mixture of Jurkat leukemia (Tn-positive) and healthy (Tn-negative) lymphocytes, preserving the activation potential of healthy lymphocytes; (iii) was effective against various leukemic cell lines with distinct phenotypes, as well as fresh human primary acute and chronic lymphoid leukemia cells; (iv) induced mostly a caspase-independent cell death, which might be an advantage as tumor cells often resist caspase-dependent cell death. Altogether, the present observations suggest that conjugation with plant lectins can allow targeting of photosensitizers towards aberrant glycosylation of tumor cells, e.g. to purge leukemia cells from blood and to preserve the normal leukocytes in extracorporeal photochemotherapy

Effect on comfort of administering bubble-humidified or dry oxygen: the Oxyrea non-inferiority randomized study.

The clinical interest of using bubble humidification of oxygen remains controversial. This study was designed to further explore whether delivering dry oxygen instead of bubble-moistened oxygen had an impact on discomfort of ICU patients. This randomized multicenter non-inferiority open trial included patients admitted in intensive care unit and receiving oxygen. Any patient receiving non-humidified oxygen (between 0 and 15 L/min) for less than 2 h could participate in the study. Randomization was stratified based on the flow rate at inclusion (less or more than 4 L/min). Discomfort was assessed 6-8 and 24 h after inclusion using a dedicated 15-item scale (quoted from 0 to 150). Three hundred and fifty-four ICU patients receiving non-humidified oxygen were randomized either in the humidified (HO) (n = 172), using bubble humidifiers, or in the non-humidified (NHO) (n = 182) arms. In modified intention-to-treat analysis at H6-H8, the 15-item score was 26.6 ± 19.4 and 29.8 ± 23.4 in the HO and NHO groups, respectively. The absolute difference between scores in both groups was 3.2 [90% CI 0.0; + 6.5] for a non-inferiority margin of 5.3, meaning that the non-inferiority analysis was not conclusive. This was also true for the subgroups of patients receiving either less or more than 4 L/min of oxygen. At H24, using NHO was not inferior compared to HO in the general population and in the subgroup of patients receiving 4 L/min or less of oxygen. However, for patients receiving more than 4 L/min, a post hoc superiority analysis suggested that patients receiving dry oxygen were less comfortable. Oxygen therapy-related discomfort was low. Dry oxygen could not be demonstrated as non-inferior compared to bubble-moistened oxygen after 6-8 h of oxygen administration. At 24 h, dry oxygen was non-inferior compared to bubble-humidified oxygen for flows below 4 L/min