Utilization of dapsone and hemoglobin in the epithelial skin regeneration therapy of cutaneous loxoscelism: A case report and integrative literature review.

BACKGROUND: Loxosceles spp are arthropods found worldwide. Its bite may produce cutaneous loxoscelism (necrotic or edematous) or cutaneous-visceral loxoscelism. Depending on their severity and location, cutaneous forms are managed with local cold application and systemic administration of antihistamines, corticosteroids, antibiotics, polymorphonuclear inhibitors, and analgesics. OBJECTIVE: This study aimed to report a case of cutaneous loxoscelism and to identify the main dermatological manifestations associated with the Loxosceles spp bite. DESIGN AND SETTING: This case report and literature review was conducted in a Mexican university. METHODS: A detailed report on the medical management of a patient with cutaneous loxoscelism treated at the emergency department of a public hospital was published. Scopus, PubMed, Web of Science, and Google Scholar databases were searched to identify articles reporting cutaneous loxoscelism. The following keywords were used during the database search: "loxoscelism" OR "spider bite," OR "loxosceles" OR "loxosceles species" OR "loxosceles venom" OR "loxoscelism case report" AND "cutaneous" OR "dermonecrotic arachnidism." RESULTS: A 62-year-old female patient with cutaneous loxoscelism was treated with systemic dapsone and local heparin spray. Eighteen studies with 22 clinical cases were included in this systematic review. Of the 22 patients, 12 (54.5%) were men. L. rufescens was the predominant spider species. CONCLUSIONS: The administration of dapsone and heparin for the management of cutaneous loxoscelism demonstrated success in this case, with no sequelae observed. In general, the literature review indicated favorable outcomes in patients treated with antimicrobials and corticosteroids, with continuous healing of skin lesions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ID CRD42023422424 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023422424).

Time course of hepatic gluconeogenesis during hindlimb suspension unloading.

The goal of this work was to determine the time-dependent changes in fractional hepatic gluconeogenesis (GNG) during conditions of hindlimb suspension unloading (HSU), a 'ground-based' method for inducing muscular atrophy to simulate space flight. We hypothesized that GNG would increase in HSU conditions as a result of metabolic shifts in the liver and skeletal muscle. A significant and progressive atrophy was observed in the soleus (30, 47 and 55%) and gastrocnemius muscles (0, 15 and 17%) after 3, 7 and 14 days of HSU, respectively. Fractional hepatic GNG was determined following the incorporation of deuterium from deuterated water ((2)H(2)O) into C-H bonds of newly synthesized glucose after an 8 h fast. Enrichment of plasma glucose with (2)H was measured using the classic method of Landau et al. (the 'hexamethylenetetramine (HMT) method'), based on specific (2)H labelling of glucose carbons, and the novel method of Chacko et al. ('average method'), based on the assumption of equal (2)H enrichment on all glucose carbons (except C2). After 3 days of HSU, fractional GNG was significantly elevated in the HSU group, as determined by either method (∼13%, P < 0.05). After 7 and 14 days of HSU, gluconeogenesis was not significantly different. Both analytical methods yielded similar time-dependent trends in gluconeogenic rates, but GNG values determined using the average method were consistently lower (∼30%) than those found by the HMT method. To compare and validate the average method against the HMT method further, we starved animals for 13 h to allow for hepatic GNG to contribute 100% to endogenous glucose production. The HMT method yielded 100% GNG, while the average method yielded GNG of ∼70%. As both methods used the same values of precursor enrichment, we postulated that the underestimation of gluconeogenic rate was as a result of differences in the measurements of product enrichment ((2)H labelling of plasma glucose). This could be explained by the following factors: (i) loss of deuterium via exchange between acetate and glucose; (ii) interference caused by fragment m/z 169, representing multiple isobaric species; and (iii) interference from other sugars at m/z 169. In conclusion, HSU caused a time-dependent increase in hepatic gluconeogenesis, irrespective of the analytical methods used.

One-step simultaneous liquid phase exfoliation-induced chirality in graphene and their chirality-mediated microRNA delivery.

Graphene (G) has established itself as an exciting prospect for a broad range of applications owing to its remarkable properties. Recent innovations in chiral nanosystems have led to sensors, drug delivery, catalysis, etc. owing to the stereospecific interactions between various nanosystems and enantiomers. As the molecular structure of G itself is achiral introducing chirality in G by simple attachment of a functional group (a chiral ligand) on the G nanosheet may result in more diverse applications. Herein, we demonstrate direct liquid phase exfoliation and chiral induction in G nanosheets abbreviated as l-graphene and d-graphene in the presence of chiral l-tyrosine and d-tyrosine and by applying high-temperature sonication. The obtained exfoliated nanosheets demonstrated stable chirality confirmed by circular dichroism. Fourier transform infrared (FTIR) spectra, Raman spectroscopy, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and differential scanning calorimetry (DSC) showed functional, structural, morphological, surface, and thermal characteristics of l-graphene and d-graphene. The hemo-compatibility of these chiral graphenes was evaluated for the very first time utilizing human red blood cells. Lastly, for the very first time, an attempt was made to explore enantiomeric binding between chiral l-graphene and d-graphene with microRNA (miR-205) and their possibility towards chirality-mediated gene delivery in prostate cancerous cells.

Indocyanine Green-based Glow Nanoparticles Probe for Cancer Imaging.

Indocyanine green (ICG) is one of the FDA-approved near infra-red fluorescent (NIRF) probes for cancer imaging and image-guided surgery in the clinical setting. However, the limitations of ICG include poor photostability, high concentration toxicity, short circulation time, and poor cancer cell specificity. To overcome these hurdles, we engineered a nanoconstruct composed of poly (vinyl pyrrolidone) (PVP)-indocyanine green that is cloaked self-assembled with tannic acid (termed as indocyanine green-based glow nanoparticles probe, ICG-Glow NPs) for the cancer cell/tissue-specific targeting. The self-assembled ICG-Glow NPs were confirmed by spherical nanoparticles formation (DLS and TEM) and spectral analyses. The NIRF imaging characteristic of ICG-Glow NPs was established by superior fluorescence counts on filter paper and chicken tissue. The ICG-Glow NPs exhibited excellent hemo and cellular compatibility with human red blood cells, kidney normal, pancreatic normal, and other cancer cell lines. An enhanced cancer-specific NIRF binding and imaging capability of ICG-Glow NPs was confirmed using different human cancer cell lines and human tumor tissues. Additionally, tumor-specific binding/accumulation of ICG-Glow NPs was confirmed in MDA-MB-231 xenograft mouse model. Collectively, these findings suggest that ICG-Glow NPs have great potential as a novel and safe NIRF imaging probe for cancer cell/tumor imaging. This can lead to a quicker cancer diagnosis facilitating precise disease detection and management.

Exercise intensity and oxygen uptake kinetics in African-American and Caucasian women.

The effect of exercise intensity on the on- and off-transient kinetics of oxygen uptake (VO(2)) was investigated in African American (AA) and Caucasian (C) women. African American (n = 7) and Caucasian (n = 6) women of similar age, body mass index and weight, performed an incremental test and bouts of square-wave exercise at moderate, heavy and very heavy intensities on a cycle ergometer. Gas exchange threshold (LT(GE)) was lower in AA (13.6 ± 2.3 mL kg(-1) min(-1)) than C (18.6 ± 5.6 mL kg(-1) min(-1)). The dynamic exercise and recovery VO(2) responses were characterized by mathematical models. There were no significant differences in (1) peak oxygen uptake (VO(2peak)) between AA (28.5 ± 5 mL kg(-1) min(-1)) and C (31.1 ± 6.6 mL kg(-1) min(-1)) and (2) VO(2) kinetics at any exercise intensity. At moderate exercise, the on- and off- VO(2) kinetics was described by a monoexponential function with similar time constants τ (1,on) (39.4 ± 12.5; 38.8 ± 15 s) and τ (1,off) (52.7 ± 10.1; 40.7 ± 4.4 s) for AA and C, respectively. At heavy and very heavy exercise, the VO(2) kinetics was described by a double-exponential function. The parameter values for heavy and very heavy exercise in the AA group were, respectively: τ (1,on) (47.0 ± 10.8; 44.3 ± 10 s), τ (2,on) (289 ± 63; 219 ± 90 s), τ (1,off) (45.9 ± 6.2; 50.7 ± 10 s), τ (2,off) (259 ± 120; 243 ± 93 s) while in the C group were, respectively: τ (1,on) (41 ± 12; 43.2 ± 15 s); τ (2, on) (277 ± 81; 215 ± 36 s), τ (1,off) (40.2 ± 3.4; 42.3 ± 7.2 s), τ (2,off) (215 ± 133; 228 ± 64 s). The on- and off-transients were symmetrical with respect to model order and dependent on exercise intensity regardless of race. Despite similar VO(2) kinetics, LT(GE) and gain of the VO(2) on-kinetics at moderate intensity were lower in AA than C. However, generalization to the African American and Caucasian populations is constrained by the small subject numbers.

Health resource allocation among indigenous peoples from the right to health and health capability approaches: The case of P'urhépecha people.

The right to health under the human rights-based approach and health capability paradigm can be used to identify whether health-related resources are allocated in a way that health inequities are being reduced among indigenous peoples taking into account what they value. Elements for these approaches were identified and assessed for the P'urhépecha people in Mexico through developed indicators based on the available statistics and qualitative data. Compared with the national level, there is a lag for most of the indicators related to the availability and use of public health systems, health determinants, health-related information, and traditional healing. People are worried because diseases such as diabetes and substance abuse are high and rising; however, they continue lifestyles that support them. Through the health capability paradigm and the right to health approach, it is found that health and health capabilities for the P'urhépecha must comprise their idea of good living (Buen Vivir) or sési irékani, which in turn requires the right to development. In this sense, current P'urhépecha demands converge with those of other indigenous peoples in which autonomy, as a right to self-determination, is a necessary condition to design their health policy and allocate health-related resources in a globalised world.

Cardiopulmonary Imaging Utilization and Findings among Hospitalized COVID-19 Patients in Latin America: (From "RIMAC: Registry IMAging Cardiopulmonary among Hospitalized COVID-19 Patients in LATAM").

Objectives: Describe the use and findings of cardiopulmonary imaging-chest X-ray (cX-ray), echocardiography (cEcho), chest CT (cCT), lung ultrasound (LUS), and/or cardiac magnetic resonance imaging (cMRI)-in COVID-19 hospitalizations in Latin America (LATAM). Background: There is a lack of information on the images used and their findings during the SARS-CoV-2 pandemic in LATAM. Methods: Multicenter, prospective, observational study of COVID-19 inpatients, conducted from March to December 2020, from 12 high-complexity centers, in nine LATAM countries. Adults (>18 years) with at least one imaging modality performed, followed from admission until discharge and/or in-hospital death, were included. Results: We studied 1,435 hospitalized patients (64% males) with a median age of 58 years classified into three regions: Mexico (Mx), 262; Central America and Caribbean (CAC), 428; and South America (SAm), 745. More frequent comorbidities were overweight/obesity, hypertension, and diabetes. During hospitalization, 58% were admitted to the ICU. The in-hospital mortality was 28%, and it was highest in Mx (37%).The most frequent images performed were cCT (61%), mostly in Mx and SAm, and cX-ray (46%), significant in CAC. The cEcho was carried out in 18%, similarly among regions, and LUS was carried out in 7%, with a higher frequently in Mx. Abnormal findings on the cX-ray were peripheral or basal infiltrates, and in cCT abnormal findings were the ground glass infiltrates, more commonly in Mx. In LUS, interstitial syndrome was the most abnormal finding, predominantly in Mx and CAC.Renal failure was the most prevalent complication (20%), predominant in Mx and SAm. Heart failure developed in 13%, predominant in Mx and CAC. Lung thromboembolism was higher in Mx while myocardial infarction was in CAC.Logistic regression showed associations of abnormal imaging findings and their severity, with comorbidities, complications, and evolution. Conclusions: The use and findings of cardiopulmonary imaging in LATAM varied between regions and had a great impact on diagnosis and prognosis.

Computational model of cellular metabolic dynamics: effect of insulin on glucose disposal in human skeletal muscle.

Identifying the mechanisms by which insulin regulates glucose metabolism in skeletal muscle is critical to understanding the etiology of insulin resistance and type 2 diabetes. Our knowledge of these mechanisms is limited by the difficulty of obtaining in vivo intracellular data. To quantitatively distinguish significant transport and metabolic mechanisms from limited experimental data, we developed a physiologically based, multiscale mathematical model of cellular metabolic dynamics in skeletal muscle. The model describes mass transport and metabolic processes including distinctive processes of the cytosol and mitochondria. The model simulated skeletal muscle metabolic responses to insulin corresponding to human hyperinsulinemic-euglycemic clamp studies. Insulin-mediated rate of glucose disposal was the primary model input. For model validation, simulations were compared with experimental data: intracellular metabolite concentrations and patterns of glucose disposal. Model variations were simulated to investigate three alternative mechanisms to explain insulin enhancements: Model 1 (M.1), simple mass action; M.2, insulin-mediated activation of key metabolic enzymes (i.e., hexokinase, glycogen synthase, pyruvate dehydrogenase); or M.3, parallel activation by a phenomenological insulin-mediated intracellular signal that modifies reaction rate coefficients. These simulations indicated that models M.1 and M.2 were not sufficient to explain the experimentally measured metabolic responses. However, by application of mechanism M.3, the model predicts metabolite concentration changes and glucose partitioning patterns consistent with experimental data. The reaction rate fluxes quantified by this detailed model of insulin/glucose metabolism provide information that can be used to evaluate the development of type 2 diabetes.

Modeling oxygenation in venous blood and skeletal muscle in response to exercise using near-infrared spectroscopy.

Noninvasive, continuous measurements in vivo are commonly used to make inferences about mechanisms controlling internal and external respiration during exercise. In particular, the dynamic response of muscle oxygenation (Sm(O(2))) measured by near-infrared spectroscopy (NIRS) is assumed to be correlated to that of venous oxygen saturation (Sv(O(2))) measured invasively. However, there are situations where the dynamics of Sm(O(2)) and Sv(O(2)) do not follow the same pattern. A quantitative analysis of venous and muscle oxygenation dynamics during exercise is necessary to explain the links between different patterns observed experimentally. For this purpose, a mathematical model of oxygen transport and utilization that accounts for the relative contribution of hemoglobin (Hb) and myoglobin (Mb) to the NIRS signal was developed. This model includes changes in microvascular composition within skeletal muscle during exercise and integrates experimental data in a consistent and mechanistic manner. Three subjects (age 25.6 +/- 0.6 yr) performed square-wave moderate exercise on a cycle ergometer under normoxic and hypoxic conditions while muscle oxygenation (C(oxy)) and deoxygenation (C(deoxy)) were measured by NIRS. Under normoxia, the oxygenated Hb/Mb concentration (C(oxy)) drops rapidly at the onset of exercise and then increases monotonically. Under hypoxia, C(oxy) decreases exponentially to a steady state within approximately 2 min. In contrast, model simulations of venous oxygen concentration show an exponential decrease under both conditions due to the imbalance between oxygen delivery and consumption at the onset of exercise. Also, model simulations that distinguish the dynamic responses of oxy-and deoxygenated Hb (HbO(2), HHb) and Mb (MbO(2), HMb) concentrations (C(oxy) = HbO(2) + MbO(2); C(deoxy) = HHb + HMb) show that Hb and Mb contributions to the NIRS signal are comparable. Analysis of NIRS signal components during exercise with a mechanistic model of oxygen transport and metabolism indicates that changes in oxygenated Hb and Mb are responsible for different patterns of Sm(O(2)) and Sv(O(2)) dynamics observed under normoxia and hypoxia.

Non-invasive estimation of metabolic flux and blood flow in working muscle: effect of blood-tissue distribution.

Muscle oxygenation measurements by near infrared spectroscopy (NIRS) are frequently obtained in humans to make inferences about mechanisms of metabolic control of respiration in working skeletal muscle. However, these measurements have technical limitations that can mislead the evaluation of tissue processes. In particular, NIRS measurements of working muscle represent oxygenation of a mix of fibers with heterogeneous activation, perfusion and architecture. Specifically, the relative volume distribution of capillaries, small arteries, and venules may affect NIRS data. To determine the effect of spatial volume distribution of components of working muscle on oxygen utilization dynamics and blood flow changes, a mathematical model of oxygen transport and utilization was developed. The model includes blood volume distribution within skeletal muscle and accounts for convective, diffusive, and reactive processes of oxygen transport and metabolism in working muscle. Inputs to the model are arterial O2 concentration, cardiac output and ATP demand. Model simulations were compared to exercise data from human subjects during a rest-to-work transition. Relationships between muscle oxygen consumption, blood flow, and the rate coefficient of capillary-tissue transport are analyzed. Blood volume distribution in muscle has noticeable effects on the optimal estimates of metabolic flux and blood flow in response to an exercise stimulus.

Utilization of dapsone and hemoglobin in the epithelial skin regeneration therapy of cutaneous loxoscelism: A case report and integrative literature review

ABSTRACT BACKGROUND: Loxosceles spp are arthropods found worldwide. Its bite may produce cutaneous loxoscelism (necrotic or edematous) or cutaneous-visceral loxoscelism. Depending on their severity and location, cutaneous forms are managed with local cold application and systemic administration of antihistamines, corticosteroids, antibiotics, polymorphonuclear inhibitors, and analgesics. OBJECTIVE: This study aimed to report a case of cutaneous loxoscelism and to identify the main dermatological manifestations associated with the Loxosceles spp bite. DESIGN AND SETTING: This case report and literature review was conducted in a Mexican university. METHODS: A detailed report on the medical management of a patient with cutaneous loxoscelism treated at the emergency department of a public hospital was published. Scopus, PubMed, Web of Science, and Google Scholar databases were searched to identify articles reporting cutaneous loxoscelism. The following keywords were used during the database search: "loxoscelism" OR "spider bite," OR "loxosceles" OR "loxosceles species" OR "loxosceles venom" OR "loxoscelism case report" AND "cutaneous" OR "dermonecrotic arachnidism." RESULTS: A 62-year-old female patient with cutaneous loxoscelism was treated with systemic dapsone and local heparin spray. Eighteen studies with 22 clinical cases were included in this systematic review. Of the 22 patients, 12 (54.5%) were men. L. rufescens was the predominant spider species. CONCLUSIONS: The administration of dapsone and heparin for the management of cutaneous loxoscelism demonstrated success in this case, with no sequelae observed. In general, the literature review indicated favorable outcomes in patients treated with antimicrobials and corticosteroids, with continuous healing of skin lesions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ID CRD42023422424 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023422424).

Modeling of cellular metabolism and microcirculatory transport.

Oxygen and other substrates, waste products, hormone messengers, and cells and other particles of the immune system are all transported in a closed-loop circulatory system in vertebrates, within which pumped blood travels to within diffusion distances of practically every cell in the body. Exchange of oxygen and carbon dioxide in the pulmonary capillaries and absorption of nutrients in the gut provide the circulating blood with biochemical reactants to sustain bioenergetic processes throughout the body. Inputs and outputs transported by the microcirculation are necessary to drive the open-system nonequilibrium chemical reactions of metabolism that are essential for cellular function. In turn, metabolically derived signals influence microcirculatory dynamics. Indeed, the microcirculation is the key system that ties processes at the whole-body level of the cardiovascular system to subcellular phenomena. This tight integration between cellular metabolism and microcirculatory transport begs for integrative simulations that span the cell, tissue, and organ scales.

Multi-scale model of O2 transport and metabolism: response to exercise.

Regulation of pulmonary oxygen uptake (VO2p) during exercise depends on cellular energy demand, blood flow, ventilation, oxygen exchange across membranes, and oxygen utilization in the contracting skeletal muscle. In human and animal studies of metabolic processes that control cellular respiration in working skeletal muscle, pulmonary VO2 dynamics is measured at the mouth using indirect calorimetry. To provide information on the dynamic balance between oxygen delivery and oxygen consumption at the microvascular level, muscle oxygenation is measured using near-infrared spectroscopy. A multi-scale computational model that links O2 transport and cellular metabolism in the skeletal muscle was developed to relate the measurements and gain quantitative understanding of the regulation of VO2 at the cellular, tissue, and whole-body level. The model incorporates mechanisms of oxygen transport from the airway openings to the cell, as well as the phosphagenic and oxidative pathways of ATP synthesis in the muscle cells.

The role of Ca2+ in coupling cardiac metabolism with regulation of contraction: in silico modeling.

The heart adapts the rate of mitochondrial ATP production to energy demand without noticeable changes in the concentration of ATP, ADP and Pi, even for large transitions between different workloads. We suggest that the changes in demand modulate the cytosolic Ca2+ concentration that changes mitochondrial Ca2+ to regulate ATP production. Thus, the rate of ATP production by the mitochondria is coupled to the rate of ATP consumption by the sarcomere cross-bridges (XBs). An integrated model was developed to couple cardiac metabolism and mitochondrial ATP production with the regulation of Ca2+ transient and ATP consumption by the sarcomere. The model includes two interrelated systems that run simultaneously utilizing two different integration steps: (1) The faster system describes the control of excitation contraction coupling with fast cytosolic Ca2+ transients, twitch mechanical contractions, and associated fluctuations in the mitochondrial Ca2+. (2) A slower system simulates the metabolic system, which consists of three different compartments: blood, cytosol, and mitochondria. The basic elements of the model are dynamic mass balances in the different compartments. Cytosolic Ca2+ handling is determined by four organelles: sarcolemmal Ca2+ influx and efflux; sarcoplasmic reticulum (SR) Ca2+ release and sequestration (SR); binding and dissociation from sarcomeric regulatory troponin complexes; and mitochondrial Ca2+ flows. Mitochondrial Ca2+ flows are determined by the Ca2+ uniporter and the mitochondrial Na+Ca2+ exchanger. The cytosolic Ca2+ determines the rate of ATP consumption by the sarcomere. Ca2+ binding to troponin regulates the rate of XBs recruitment and force development. The mitochondrial Ca2+ concentration determines the pyruvate dehydrogenase activity and the rate of ATP production by the F(1)-F(0) ATPase. The workload modulates the cytosolic Ca2+ concentration through feedback loops. The preload and afterload affect the number of strong XBs. The number of strong XBs determines the affinity of troponin for Ca2+, which alters the cytosolic Ca2+ transient. Model simulations quantify the role of Ca2+ in simultaneously controlling the power of contraction and the rate of ATP production. It explains the established empirical observation that significant changes in the metabolic fluxes can occur without significant changes in the key nucleotide (ATP and ADP) concentrations. Quantitative investigations of the mechanisms underlying the cardiac control of biochemical to mechanical energy conversion may lead to novel therapeutic modalities for the ischemic and failing myocardium.

Role of the malate-aspartate shuttle on the metabolic response to myocardial ischemia.

The malate-aspartate (M-A) shuttle provides an important mechanism to regulate glycolysis and lactate metabolism in the heart by transferring reducing equivalents from cytosol into mitochondria. However, experimental characterization of the M-A shuttle has been incomplete because of limitations in quantifying cytosolic and mitochondrial metabolites. In this study, we developed a multi-compartment model of cardiac metabolism with detailed presentation of the M-A shuttle to quantitatively predict non-observable fluxes and metabolite concentrations under normal and ischemic conditions in vivo. Model simulations predicted that the M-A shuttle is functionally localized to a subdomain that spans the mitochondrial and cytosolic spaces. With the onset of ischemia, the M-A shuttle flux rapidly decreased to a new steady state in proportion to the reduction in blood flow. Simulation results suggest that the reduced M-A shuttle flux during ischemia was not due to changes in shuttle-associated enzymes and transporters. However, there was a redistribution of shuttle-associated metabolites in both cytosol and mitochondria. Therefore, the dramatic acceleration in glycolysis and the switch to lactate production that occur immediately after the onset of ischemia is mediated by reduced M-A shuttle flux through metabolite redistribution of shuttle associated species across the mitochondrial membrane.

Modeling cellular metabolism and energetics in skeletal muscle: large-scale parameter estimation and sensitivity analysis.

Skeletal muscle plays a major role in the regulation of whole-body energy metabolism during physiological stresses such as ischemia, hypoxia, and exercise. Current experimental techniques provide relatively little in vivo data on dynamic responses of metabolite concentrations and metabolic fluxes in skeletal muscle to such physiological stimuli. As a complementary approach to experimental measurements and as a framework for quantitatively analyzing available in vivo data, a physiologically based model of skeletal muscle cellular metabolism and energetics is developed. This model, which incorporates key transport and reaction processes, is based on dynamic mass balances of 30 chemical species in capillary (blood) and tissue (cell) domains. The reaction fluxes in the cellular domain are expressed in terms of a generalized Michaelis?Menten equation involving energy controller ratios ATP/ADP and ATP/ADP and NADH/NAD+ . This formalism introduces a large number of unknown parameters ( approximately 90). Estimating these parameters from in vivo sparse data and evaluating dynamic sensitivities of the model outputs with respect to these parameters is a challenging problem. Parameter estimation is accomplished using an efficient, nonlinear, constraint-based, optimization algorithm that minimizes differences between available experimental data and corresponding model outputs by explicitly utilizing equality constraints on resting fluxes and concentrations. With the estimated parameter values, the model is able to simulate dynamic responses to reduced blood flow (ischemia) of key metabolite concentrations and metabolic fluxes, both measured and nonmeasured. A general parameter sensitivity analysis is carried out to determine and characterize the parameters having the most and least effects on the measured outputs.

Muscle oxygen uptake differs from consumption dynamics during transients in exercise.

Relating external to internal respiration during exercise requires quantitative modeling analysis for reliable inferences with respect to metabolic rate. Often, oxygen transport and metabolism based on steady-state mass balances (Fick principle) and passive diffusion between blood and tissue are applied to link pulmonary to cellular respiration. Indeed, when the work rate does not change rapidly, a quasi-steady-state analysis based on the Fick principle is sufficient to estimate the rate of O2 consumption in working muscle. During exercise when the work rate changes quickly, however, non-invasive in vivo measurements to estimate muscle O2 consumption are not sufficient to characterize cellular respiration of working muscle. To interpret transient changes of venous O2 concentration, blood flow, and O2 consumption in working muscle, a mathematical model of O2 transport and consumption based on dynamic mass balances is required. In this study, a comparison is made of the differences between simulations of O2 uptake and O2 consumption within working skeletal muscle based on a dynamic model and quasi-steady-state approximations. The conditions are specified under which the quasi-steady-state approximation becomes invalid.

Models of muscle contraction and energetics.

How does skeletal muscle manage to regulate the pathways of ATP synthesis during large-scale changes in work rate while maintaining metabolic homeostasis remains unknown. The classic model of metabolic regulation during muscle contraction states that accelerating ATP utilization leads to increasing concentrations of ADP and Pi, which serve as substrates for oxidative phosphorylation and thus accelerate ATP synthesis. An alternative model states that both the ATP demand and ATP supply pathways are simultaneously activated. Here, we review experimental and computational models of muscle contraction and energetics at various organizational levels and compare them with respect to their pros and cons in facilitating understanding of the regulation of energy metabolism during exercise in the intact organism.

Control de historias clínicas clasificadas por patologías a través de una aplicación web

Introducción: Las aplicaciones web actualmente son indispensables para el manejo de los datos en toda organización, permite al usuario acceder y utilizar la información desde cualquier parte del mundo. El uso de las aplicaciones web ha propiciado la agilización de varios procesos. Objetivo: Emplear una aplicación web desarrollada mediante software libre para el control y clasificación de historias clínicas por diferentes patologías del Centro Médico Salud y Vida de Ibarra, Ecuador. Método: Se aplicó una investigación de modalidad mixta cualitativa-cuantitativa la misma que permitió identificar necesidades reales de los pacientes y de los profesionales de esta casa de salud. El uso de la investigación histórica ayudó a conocer cada uno de los procesos que fueron tomados en cuenta en la generación de la historia clínica y cómo poder clasificarlas por patologías. Con ayuda de la investigación bibliográfica se logró recopilar definiciones necesarias para argumentar la base teórica del artículo; a través de la encuesta y entrevista se identificó la disconformidad de los pacientes por factores como el tiempo de espera, la deficiencia de búsqueda y peor aún no encontrarse registrados. Resultados: La agilidad en los procesos de registro de los pacientes y cada uno con su respectiva historia clínica permite que en las próximas citas los especialistas continúen con su diagnóstico. Conclusiones: La aplicación web agiliza de manera efectiva los procesos relacionados a las historias clínicas, lo que contribuye al control y clasificación de dicha documentación.

Introduction: Web applications are currently essential for data management in any organization, they allow the user to access and use information from anywhere in the world. The use of web applications has led to the streamlining of several processes. Objective: To use a web application developed using free software for the control and classification of medical records for different pathologies in the Health and Life Medical Center of Ibarra, Ecuador. Method: A qualitative-quantitative mixed modality research was applied, which allowed us to identify the real needs of the patients and professionals of this health home. The use of historical research helped to know each of the processes that were taken into account in the generation of the clinical history and how to classify them by pathologies. With the help of bibliographic research, it was possible to compile the necessary definitions to argue the theoretical basis of the article; Through the survey and interview, patient dissatisfaction was identified due to factors such as waiting time, search deficiency and, even worse, not being registered. Results: The agility in the patient registration processes and each one with their respective medical history allows the specialists to continue with their diagnosis in the next appointments. Conclusions: The web application effectively streamlines the processes related to medical records, which contributes to the control and classification of said documentation.

Introdução: As aplicações web são atualmente essenciais para a gestão de dados em qualquer organização, pois permitem ao usuário acessar e utilizar informações de qualquer lugar do mundo. A utilização de aplicações web tem levado à agilização de diversos processos. Objetivo: Utilizar uma aplicação web desenvolvida em software livre para o controle e classificação de prontuários de diferentes patologias no Centro Médico Saúde e Vida de Ibarra, Equador. Método: Foi aplicada uma pesquisa quali-quantitativa de modalidade mista, que permitiu identificar as reais necessidades dos pacientes e profissionais desta casa de saúde. A utilização da pesquisa histórica ajudou a conhecer cada um dos processos que foram levados em consideração na geração da história clínica e como classificá-los por patologias. Com o auxílio da pesquisa bibliográfica foi possível compilar as definições necessárias para argumentar a base teórica do artigo; Por meio da pesquisa e entrevista, foi identificada a insatisfação dos pacientes devido a fatores como tempo de espera, deficiência na busca e, pior ainda, não estar cadastrado. Resultados: A agilidade nos processos de cadastramento de pacientes e cada um com seu respectivo histórico permite que os especialistas continuem com seu diagnóstico nas próximas consultas. Conclusões: A aplicação web agiliza eficazmente os processos relacionados com os registos médicos, o que contribui para o controlo e classificação da referida documentação.