104 research outputs found
Comparative study between two recombinant human insulins NPH in the treatment of type 2 diabetes mellitus
No full textBackground: The number of patients with Type 2 Diabetes Mellitus (T2DM) in Brazil
has, in recent decades, increased substantially and insulin therapy is often necessary
in a large portion of this population in order to achieve appropriate glycemic control.
Objective: To evaluate glycemic control achieved with recombinant human insulin
NPH - Gansulin and compares it with human NPH insulin - Humulin N® in patients
with Type 2 Diabetes Mellitus. Subjects and methods: A prospective, double-blind,
randomized, parallel, single center with 37 individuals with type 2 diabetes using
insulin NPH insulin. For statistical analyzes were used: the multiple comparison test
of Tukey-Kramer test, Wilcoxon paired comparison test and Chi- Square. It was
regarded level of significance value lower than 5% (p<0.05). Results: Insulins NPH
and Humulin Gansulin showed similar reductions in HbA1c at the end of the study
compared to baseline. Initial HbA1c 7.91% in the Humulin group was reduced to
6.56% (p<0.001) at the end of the study whereas in the Gansulin the glycated
hemoglobin was reduced from 8.18% to 6.65% (p<0.001). At the end of the study
there was no significant difference between the glycated hemoglobin levels
(p=0.2410), fasting blood glucose (p=0.9257) and glucose at bedtime (p=0.3906)
between the two types of insulin. Regarding the number of hypoglycemic events,
there was no significant difference between the two insulins and no severe
hypoglycemic episodes were recorded. Conclusion: The NPH Gansulin (Insuneo
N®) presented glycemic control similar to that presented by human insulin Humulin
N® in patients with DM2. It was considered level of significance value less than 5%.Fundamento: O número de pacientes com Diabetes Mellitus Tipo 2 (DM2) no Brasil
tem, nas últimas décadas, aumentado substancialmente e a terapia insulínica é
necessária em uma grande parcela desta população com a finalidade de adquirir
controle glicêmico adequado. Objetivo: Avaliar o controle glicêmico obtido com a
insulina humana recombinante NPH – Gansulin e compará-la com o da insulina
humana NPH – Humulin N® em pacientes com Diabetes Mellitus Tipo 2 (DM2).
Sujeitos e métodos: Estudo prospectivo, duplo cego, randomizado, paralelo e
monocêntrico com 37 indivíduos portadores de diabetes tipo 2, em uso de insulina
NPH. Para as análises estatísticas foram utilizados: o teste de comparações
múltiplas de Tukey-Kramer, o teste de comparação pareada de Wilcoxon e o teste
Chi-Square. Foi considerado como nível de significância o valor inferior a 5%
(p<0,05). Resultados: As insulinas NPH Humulin e Gansulin apresentaram
reduções semelhantes da HbA1c ao final do estudo, quando comparadas aos
valores iniciais. A HbA1c inicial de 7,91% do grupo Humulin foi reduzida para 6,56%
(p<0,001), enquanto que na do Gansulin, a redução foi de 8,18% para 6,65%
(p<0,001). Ao final do estudo não houve diferença significativa entre os valores de
hemoglobina glicada (p=0,2410), glicemia jejum (p=0,9257) e glicemia ao deitar
(p=0,3906) entre os dois tipos de insulina. Em relação ao número de eventos
hipoglicêmicos, não se observou diferença significativa entre as duas insulinas e não
foram registrados episódios hipoglicêmicos graves. Conclusão: A insulina NPH
Gansulin apresentou controle glicêmico semelhante ao apresentado pela insulina
humana Humulin N® em pacientes com DM2
Beta Band Rhythms Influence Reaction Times
No full textDespite their involvement in many cognitive functions, s oscillations are among the least understood brain rhythms. Reports on whether the functional role of s is primarily inhibitory or excitatory have been contradictory. Our framework attempts to reconcile these findings and proposes that several s rhythms co-exist at different frequencies. s Frequency shifts and their potential influence on behavior have thus far received little attention. In this human magnetoencephalography (MEG) experiment, we asked whether changes in s power or frequency in auditory cortex and motor cortex influence behavior (reaction times) during an auditory sweep discrimination task. We found that in motor cortex, increased s power slowed down responses, while in auditory cortex, increased s frequency slowed down responses. We further characterized s as transient burst events with distinct spectro-temporal profiles influencing reaction times. Finally, we found that increased motor-to-auditory s connectivity also slowed down responses. In sum, s power, frequency, bursting properties, cortical focus, and connectivity profile all influenced behavioral outcomes. Our results imply that the study of s oscillations requires caution as s dynamics are multifaceted phenomena, and that several dynamics must be taken into account to reconcile mixed findings in the literature.This research was funded in whole, or in part, by the Austrian Science Fund (FWF) Erwin Schrödinger Fellowship J4580 to ER. For the purpose of open access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. SH is supported by NWO Vidi 016.Vidi.185.137 and NIH R01 MH123679
La justicia constitucional desde la perspectiva de la filosofía de Jeremy Waldron y la experiencia venezolana reciente
No full textThe article reviews Jeremy Waldron’s theory about the legitimacy and moral authority of the various forms of constitutional justice. According to this theory, it is always illegitimate insofar as it violates the principle of majority decision, the only moral principle of legitimate legal authority.The author explains the conditions that, according to Waldron, a political community must gather so that his theory is applicable. He also ventures into forwarding some criticisms to the author regarding these conditions.Specially, the problem of the regressivity of Waldron’s argument and the problem of stability of his conditions are explored. However, it is assumed that Waldron’s theory off ers important contributions and a reflection is made in the face of the Venezuelan constitutional reality. Finally, a theoretical outline is used to combine the institution of constitutional justice with the most relevant criticisms of Waldron.El artículo repasa la teoría de Jeremy Waldron en torno a la legitimidad y autoridad moral de las diversas formas de justicia constitucional. Según esta teoría, la justicia constitucional siempre es ilegítima en la medida en que vulnera el principio de decisión mayoritaria, único de autoridad jurídica legítima. El autor expone las condiciones que, bajo el criterio de Waldron, debe reunir una comunidad política para que su teoría sea aplicable y ensaya algunas críticas al autor respecto de dichas condiciones.Especialmente, se contempla el problema de la regresividad del argumento de Waldron y el problema de la estabilidad que de las condiciones que el propio autor sugiere. Sin embargo, se asume que esta teoría ofrece aportes importantes y se hace una refl exión de ellos de cara a la realidad constitucional venezolana. Finalmente, se ensaya un bosquejo teórico que permita conjugar la institución de la justicia constitucional con las críticas más pertinentes de Waldron
Alchemy in an Age of Disclosure: The Case of an Arabic Pseudo-Aristotelian Treatise and its Syriac Christian “Translator”
No full textThis article examines a little-known and unstudied alchemical treatise, The Epistle on Alchemy (al-Risāla fī l-ṣināʿa) attributed to Aristotle, purportedly translated from Syriac into Arabic by the Nestorian bishop ʿAbdīshōʿ bar Brīkhā (d. 1318). In particular, I investigate the Epistle’s discourse on the concealment and revelation of alchemical knowledge. Like other occult sciences, alchemy was characterised by a marked concern for secrecy and frequently employed codes, or Decknamen, when discussing the “Noble Art.” Yet the author of the Epistle consciously avoids such conventions, choosing instead to disclose its mysteries in an open and accessible manner, while making clear that secrecy would otherwise be necessary were the reader deemed unworthy. By engaging with scholarship in Islamic and Jewish occult science and esotericism, I show that the author of the Epistle navigates the boundaries between concealment and disclosure by framing his treatise as a private exchange between two foundational figures of philosophy and kingship: Aristotle and Alexander the Great. Based on a study of the Epistle’s sources and genre, I consider it possible that the work was not a translation of any Syriac original but a composition by ʿAbdīshōʿ himself and a product of the Arabicspeaking, Islamicate environment in which he lived
Avaliação da ansiedade e depressão no período pré-operatório em pacientes submetidos a procedimentos cardíacos invasivos Evaluación de la ansiedad y depresión en el período preoperatorio en pacientes sometidos a procedimientos cardíacos Evaluation of preoperative anxiety and depression in patients undergoing invasive cardiac procedures
No full textJUSTIFICATIVA E OBJETIVOS: A avaliação específica da ansiedade e da depressão não está incluída na rotina de avaliação pré-operatória, o que faz com que em situações como as doenças cardíacas, em que o estado emocional dos pacientes pode estar modificado pela própria doença, possam não ser diagnosticadas. O objetivo do estudo foi comparar o nível e a prevalência de ansiedade e depressão em pacientes com doença cardíaca a serem submetidos a procedimentos invasivos e/ou cirúrgicos, utilizando a Escala Hospitalar de Ansiedade e Depressão (Hospital Anxiety and Depression Scale - HAD). MÉTODO: Após a aprovação pelos Comitês de Ética, foram incluídos 96 pacientes, estado físico ASA II e III, que constituíram três grupos: estudo eletrofisiológico (EEF), implante de marcapasso (MP) e revascularização do miocárdio (RM). Os escores considerados "ponto de corte" foram: escala HAD-ansiedade (HAD-A) com ansiedade > 9; escala HAD-depressão (HAD-D) com depressão > 9. RESULTADOS: Os grupos foram homogêneos quanto às variáveis sociodemográficas. Observou-se diferença estatística significativa entre os três grupos (p = 0,006; p = 0,034) quanto ao nível e prevalência de ansiedade (HAD-A) e na comparação do nível de ansiedade grupo a grupo verificou-se diferença significativa entre os grupos EEF × RM e EEF × MP (p JUSTIFICATIVA Y OBJETIVOS: La evaluación específica de la ansiedad y de la depresión no está incluida en la rutina de evaluación preoperatoria, lo que hace con que en algunas situaciones como las enfermedades cardiacas, en que el estado emocional de los pacientes puede estar modificado por la propia enfermedad, puedan no quedar diagnosticadas. El objetivo del estudio fue comparar el nivel y la prevalencia de ansiedad y depresión en pacientes con enfermedad cardiaca a ser sometidos a procedimientos invasivos y/o quirúrgicos, utilizando la Escala Hospitalaria de Ansiedad y Depresión (Hospital Anxiety and Depression Scale - HAD). MÉTODO: Después de la aprobación por parte de los Comités de Ética, se incluyeron 96 pacientes, estado físico ASA II y III, que constituyeron tres grupos: estudio electrofisiológico (EEF), implante de marcapaso (MP) y revascularización del miocardio (RM). Las puntuaciones consideradas "punto de corte" fueron las siguientes: escala HAD-ansiedad (HAD-A): con ansiedad > 9; escala HAD-depresión (HAD-D): con depresión > 9. RESULTADOS: Los grupos fueron homogéneos en cuanto a las variables sociodemográficas. Se observó una diferencia estadística significativa entre los tres grupos (p = 0,006; p = 0,034) en lo concerniente al nivel y a la prevalencia de ansiedad (HAD-A) y en la comparación del nivel de ansiedad grupo a grupo, se verificó la diferencia significativa entre los grupos EEF x RM y EEF x MP (p BACKGROUND AND OBJECTIVES: Specific assessment of anxiety and depression is not included in routine preoperative evaluation; therefore, in cases of cardiac diseases in which the emotional status of the patient may be modified by the disease those disorders may not be diagnosed. The objective of the present study was to compare the level and prevalence of anxiety and depression in patients with cardiac disease undergoing invasive and/or surgical procedures using the Hospital Anxiety and Depression Scale - HAD. METHODS: After approval by the Ethics Committee, 96 patients, physical status ASA II and III, were divided in three groups: electrophysiological study (EPS), pacemaker (PM) placement, and myocardial revascularization (MR). "Cutting points" were as follows: HAD-anxiety scale (HAD-A) with anxiety > 9; HAD-depression scale (HAD-D) with depression > 9. RESULTS: All three groups were homogenous regarding sociodemographic parameters. Statistically significant differences were observed among the three groups (p = 0.006; p = 0.034) in the level and prevalence of anxiety (HAD-A); and in the intergroup comparison of the anxiety level significant differences were observed between the EPS x MR and EPS x PM groups (p < 0.05). Significant differences in the level and prevalence of depression (HAD-D) among the study groups were not observed. CONCLUSIONS: Patients with cardiac diseases undergoing electrophysiological studies, pacemaker implantation, and myocardial revascularization have different levels and prevalence of anxiety, but they do not show differences in the level and prevalence of depression
Justifying Christianity in the Islamic middle ages: the apologetic theology of ʿAbdīshōʿ bar Brīkhā (d. 1318)
No full textThe subject of this thesis is the theology of the late 13th- early 14th century churchman 'Abdīshō' bar Brīkhā. Better known by modern scholars for his poetry and canon law, he is far less recognised as a religious controversialist who composed works in Arabic as well as Syriac to answer Muslim criticisms. My overall argument contends that 'Abdīshō''s hitherto neglected theological works are critical to our understanding of how anti-Muslim apologetics had by his time become central to his Church's articulation of a distinct Christian identity in a largely non-Christian environment. 'Abdīshō' wrote his apologetic theology at a time when Christians experienced increasing hardship under the rule of the Mongol Ilkhans, who had officially converted to Islam in 1295. While the gradual hardening of attitudes towards Christians may well have informed 'Abdīshō''s defensive stance, this thesis also demonstrates that his theology is built on a genre of apologetics that emerged as early as the mid-8th century. Our author compiles and systematises earlier debates and authorities from this tradition while updating them for a current authorship. In doing so, he contributes to the formation of a theological canon that would remain authoritative for centuries to come. My analysis of 'Abdīshō''s oeuvre extends to three doctrinal themes: the Trinity, the Incarnation, and devotional practices (viz. the veneration of the Cross and the striking of the church clapper). I situate his discussion of these topics in a period when Syriac Christian scholarship was marked by a familiarity with Arabo-Islamic theological and philosophical models. While our author does not engage with these models as closely as his better-known Syriac Christian contemporary Bar Hebraeus (d. 1286), he nevertheless appeals to a literary and theological idiom common to both Muslims and Christians in order to convince his coreligionists of their faith’s reasonableness against centuries-long polemical attacks
Synthesis methods for heterocyclic drug compounds
No full textThe first part of this work involved the synthesis of small molecules as potential inhibitors of the bacterioferritin B-bacterioferritin-associated ferredoxin (BfrB-Bfd) protein-protein interaction in Pseudomonas aeruginosa. BfrB is the main iron storage protein, which is central to bacterial iron homeostasis. The mobilization of iron from BfrB requires binding by a cognate ferredoxin (Bfd), thus BfrB-Bfd interaction is essential to the regulation of cytosolic iron levels in P. aeruginosa. The aim of this project was to develop small molecules which could inhibit this protein-protein interaction and elicit perturbations in iron homeostasis consequently leading to bacterial cell death. Previous work from our research group involved the synthesis of 4-(alkylamino)isoindoline-1,3-diones which demonstrated promising inhibition of the BfrB-Bfd interaction. The current project focused on the synthesis of analogs that could be effective in a relatively low micromolar range. Consequently, 1- and 3-carbon linker analogs of the 4-(alkylamino)isoindoline-1,3-diones and other heterocyclic derivatives were synthesized and characterized. Based on molecular modeling, the following modifications below led to the synthesis of new series of compounds. • Incorporation of new substituted benzaldehydes and altering the 3-carbon linker unit into a 1-carbon linker with similar substitution pattern: It was envisioned that, the incorporation of these functionalities in the analogs of the 4-aminoisoindoline-1,3-dione would possibly increase the inhibitory effect. We subsequently designed and synthesized a series of new compounds incorporating various substituents on the benzaldehyde component. • Replacing the benzaldehyde component with other heterocycles. • Replacing the 4-aminoisoindoline-1,3-dione component with different heterocycles.The second part of this work involved the design of new methods for the synthesis of bioactive heterocyclic scaffolds. A summary of these methods follows:• A domino Aza-Michael-SNAr-heteroaromatization route to C5-substituted1-alkyl-1H-indole-3-carboxylic esters was developed and optimized. • Naphthalenes and quinolines were prepared by domino reactions of Morita-Baylis-Hillman acetates. • Synthesis and elimination pathways of 1-methanesulfonyl-1,2-dihydroquinoline sulfonamides was developed. • A one-pot route to quinolin-2(1H)-ones and 1,8-naphthyridin -2(1H)-ones was accomplished using domino Knoevenagel-SNAr reactions
Design, synthesis and characterization of organic semiconductors: From eumelanin-inspired organic materials to novel electron acceptors
No full textEumelanin, the black-brown variety of natural pigment melanin, is a fascinating material owing to its multifunctional physicochemical properties, such as broad-band absorption spectrum, antioxidant and free radical scavenging behavior, strong nonradiative relaxation of photoexcited electronic states and metal chelating properties. Further, biocompatible and biodegradable nature, peculiar physicochemical properties and intrinsic antimicrobial activities make eumelanin a promising material in bioelectronic and biomedical fields. Here, the Eumelanin-inspired indole core has been utilized to synthesize bio-inspired organic semiconductors (OSCs), sensors, and antimicrobials.In the field of organic semiconductors, both p-type and n-type materials are equally important. While p-type OSCs have seen a dramatic rise in performance over the last decade, n-type OSCs, in general, still lag behind p-type OSCs. This lack of high performance n-type OSCs is mainly related to lower stability, difficulties in synthesis and less availability of electron deficient building blocks that can be used for making n-type OSCs. Both types of OSCs with high performance are required in order to fabricate high-performance complementary circuits or p-n junction devices. Thus, there is a critical need for exploration of new building blocks for making novel n-type OSCs with improved electron mobility, material stability both under processing and operational conditions, and ease of synthesis. Benzo[1,2-b:4,5-b0 ]dithiophene-1,1,5,5-tetraoxide (BDTT) has seen less utility as a building block to make n-type OSCs despite it being an electron poor heterocycle with promise for development of n-type materials. Difficulties in functionalizing BDTT via carbon-carbon cross coupling reactions and often in low yield is one likely reason for the lack of utilization of BDTT in OSCs. This dissertation will report the successful functionalization and utilization of BDTT for the synthesis of n-type OSCsIn past few years, organic conductive fibers have emerged as an attractive as well as promising class of materials for realizing non-metallic electrodes for different clinical applications. This is because these materials are biocompatible, better integrated, easier to fabricate, lightweight and have limited magnetic resonance imaging problems compared to the metallic electrodes. This dissertation will highlight novel organic conductive fibers that have been fabricated by a facile, economical, and scalable method by using conductive ink prepared from the two intrinsically conductive materials - poly(3-hexylthiophene) and single walled carbon nanotubes - and these conductive fibers have been utilized as non-metallic electrodes for recording skin surface biological signals
Electrochemical and surface plasmon bioassays for circulating biomarkers
No full textTo address analytical detection needs, sensitive and selective assay methodologies are of great importance. Compared to simple buffer medium, a great challenge exists in detecting ultra-low levels of biomarkers in clinical matrices due to their inherent complexity and interferences posed by non-specific molecules. In addition, small molecules do not yield measurable assay signal changes compared to large biomolecules. My thesis research is focused on designing nano-biological interfaces to detect small and large molecules at low parts-per-billion and femto/picomolar concentrations in complex biofluids (serum and urine samples). Compared to harsh and tedious chemical carboxylation, non-covalent carboxylation of multiwalled carbon nanotubes by π-π stacking 1-pyrenebutyric acid retains the innate sp2 structure and electronic properties of the nanotubes and offers surface carboxyl groups for stable covalent amine coupling of a large amount of enzymes, thus improving the sensitivity of the assay. Chapter 2 demonstrates the first pyrenyl carbon nanostructure modified enzymatic bioelectrode for amperometric detection of urine formaldehyde at clinically relevant parts-per-billion levels with selectivity and wide dynamic range. Subsequently, we explored the low dielectric permittivity and intrinsic plasmonics of graphene for the detection of serum glutamic acid decarboxylase autoantibody (GADA). Graphene-based electrochemical immunosensing approach is advantageous due to its additional applicability for surface plasmon based validation and binding strength analysis with surface immobilized GAD-65 antigens (Chapter 3). My thesis focused on the third class of biomarkers, microRNAs, which are small oligonucleotides with 21-25 bases. To develop the microRNA assay with quantitative characterization, surface plasmon resonance imaging (SPRi) coupled with quartz crystal microbalance (QCM) was designed (Chapter 4). Gold nanoparticles (Au NPs) were linked to the oligonucleotides to increase the detection sensitivity upon hybridization with the selective capture oligonucleotide immobilized on the sensor surface with minimal non-specific signals. Often, cancer and other similar health disorders have been shown to be related to various types of biomarkers. Hence, in Chapter 5, we designed a multiplex assay platform for combined measurement of proteins and microRNAs. For this multiplex assay, we synthesized iron-gold bimetallic core/shell nanoparticles (Fe3O4@Au NPs) that displayed a greater plasmonic signal amplification than either Fe3O4 or Au NPs.Chemistr
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