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J Med Internet Res ; 23(9): e27098, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491204


BACKGROUND: Hemodialysis (HD) therapy is an indispensable tool used in critical care management. Patients undergoing HD are at risk for intradialytic adverse events, ranging from muscle cramps to cardiac arrest. So far, there is no effective HD device-integrated algorithm to assist medical staff in response to these adverse events a step earlier during HD. OBJECTIVE: We aimed to develop machine learning algorithms to predict intradialytic adverse events in an unbiased manner. METHODS: Three-month dialysis and physiological time-series data were collected from all patients who underwent maintenance HD therapy at a tertiary care referral center. Dialysis data were collected automatically by HD devices, and physiological data were recorded by medical staff. Intradialytic adverse events were documented by medical staff according to patient complaints. Features extracted from the time series data sets by linear and differential analyses were used for machine learning to predict adverse events during HD. RESULTS: Time series dialysis data were collected during the 4-hour HD session in 108 patients who underwent maintenance HD therapy. There were a total of 4221 HD sessions, 406 of which involved at least one intradialytic adverse event. Models were built by classification algorithms and evaluated by four-fold cross-validation. The developed algorithm predicted overall intradialytic adverse events, with an area under the curve (AUC) of 0.83, sensitivity of 0.53, and specificity of 0.96. The algorithm also predicted muscle cramps, with an AUC of 0.85, and blood pressure elevation, with an AUC of 0.93. In addition, the model built based on ultrafiltration-unrelated features predicted all types of adverse events, with an AUC of 0.81, indicating that ultrafiltration-unrelated factors also contribute to the onset of adverse events. CONCLUSIONS: Our results demonstrated that algorithms combining linear and differential analyses with two-class classification machine learning can predict intradialytic adverse events in quasi-real time with high AUCs. Such a methodology implemented with local cloud computation and real-time optimization by personalized HD data could warn clinicians to take timely actions in advance.

Free Radic Biol Med ; 168: 234-246, 2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-33781894


Osteoporosis is characterized by reductions in bone mass, which could be attributed to the dysregulation of bone homeostasis, such as the loss of balance between bone-resorbing osteoclasts and bone-forming osteoblasts. Elevated levels of oxidative stress increase bone resorption by promoting osteoclastogenesis and inhibiting the osteogenesis. Ginkgolide B (GB), a small natural molecule from Ginkgo biloba, has been reported to possess pharmacological activities by regulating reactive oxygen species (ROS) in aging-related degenerative diseases. Herein, we assessed the therapeutic effects of GB on the bone phenotypes of mice with osteoporosis induced by (I) aging, (II) ovariectomy, and (III) glucocorticoids. In all three animal models, oral gavage of GB significantly improved bone mass consistent with the increase in the OPG-to-RANKL ratio. In the in vitro experiments, GB promoted osteogenesis in aged mesenchymal stem cells (MSCs) and repressed osteoclastogenesis in aged macrophages by reducing ROS. The serum protein profile in GB-treated aged mice revealed moderate rejuvenating effects; signaling pathways associated with ROS were also regulated. The anabolic and anti-catabolic effects of GB were illustrated by the reduction in ROS. Our results indicate that GB is effective in treating osteoporosis. The use of GB in patients with osteoporosis is worthy of further clinical investigation.

Reabsorção Óssea , Osteoporose , Animais , Diferenciação Celular , Feminino , Ginkgolídeos , Homeostase , Humanos , Lactonas , Camundongos , Osteoclastos/metabolismo , Osteogênese , Osteoporose/tratamento farmacológico , Estresse Oxidativo , Ligante RANK
J Am Vet Med Assoc ; 225(4): 560-6, 2004 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-15344364


OBJECTIVE: To evaluate the cardiopulmonary and clinicopathologic effects of rapid IV administration of dimethyl sulfoxide (DMSO) in awake and halothane-anesthetized horses. DESIGN: Prospective study. ANIMALS: 6 adult horses. PROCEDURES: Horses received IV infusion of 5 L of a balanced electrolyte solution with and without 1 g/kg (0.45 g/lb) of 10% DMSO solution when they were awake and anesthetized with halothane (4 treatments/horse). Arterial and venous blood samples were collected immediately before and at intervals during or after fluid administration and analyzed for blood gases and hematologic and serum biochemical variables, respectively. Heart rate, respiratory rate, and arterial blood pressure variables were recorded prior to, during, and after fluid administration. RESULTS: After administration of fluid with or without DMSO, changes in measured variables were detected immediately, but most variables returned to baseline values within 4 hours. One awake control horse had signs of anxiety; agitation and tachycardia were detected in 2 awake horses administered DMSO. These clinical signs disappeared when the rate of infusion was reduced. In anesthetized horses, increased concentrations of WBCs and plasma fibrinogen and serum creatine kinase activity persisted for 24 hours, which was related to the stress of anesthesia more than the effects of fluid administration. CONCLUSIONS AND CLINICAL RELEVANCE: Infusion of 5 L of balanced electrolyte solution with or without 10% DMSO induced minimal changes in cardiopulmonary function and clinicopathologic variables in either awake or halothane-anesthetized horses. Stress associated with anesthesia and recovery had a greater influence on measured variables in anesthetized horses than fluid administration.

Analgésicos não Narcóticos/administração & dosagem , Dimetil Sulfóxido/administração & dosagem , Cavalos/fisiologia , Anestésicos Inalatórios , Animais , Gasometria/veterinária , Pressão Sanguínea/efeitos dos fármacos , Estudos Cross-Over , Relação Dose-Resposta a Droga , Halotano , Frequência Cardíaca/efeitos dos fármacos , Infusões Intravenosas/veterinária , Estudos Prospectivos , Distribuição Aleatória , Respiração/efeitos dos fármacos
Vet Ther ; 4(3): 285-91, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-15136990


The sedative effect induced by administering xylazine hydrochloride or detomidine hydrochloride with or without butorphanol tartrate to standing dairy cattle was compared in two groups of six adult, healthy Holstein cows. One group received xylazine (0.02 mg/kg i.v.) followed by xylazine (0.02 mg/kg) and butorphanol (0.05 mg/kg i.v.) 1 week later. Cows in Group B received detomidine (0.01 mg/kg i.v.) followed by detomidine (0.01 mg/kg i.v.) and butorphanol (0.05 mg/kg i.v.) 1 week later. Heart rate, respiratory rate, and arterial blood pressure were monitored and recorded before drugs were administered and every 10 minutes for 1 hour after drug administration. The degree of sedation was evaluated and graded. Cows in each treatment group had significant decreases in heart rate and respiratory rate after test drugs were given. Durations of sedation were 49.0 +/- 12.7 minutes (xylazine), 36.0 +/- 14.1 (xylazine with butorphanol), 47.0 +/- 8.1 minutes (detomidine), and 43.0 +/- 14.0 minutes (detomidine with butorphanol). Ptosis and salivation were observed in cows of all groups following drug administration. Slow horizontal nystagmus was observed from three cows following administration of detomidine and butorphanol. All cows remained standing while sedated. The degree of sedation seemed to be most profound in cows receiving detomidine and least profound in cows receiving xylazine.

Bovinos/fisiologia , Hipnóticos e Sedativos/administração & dosagem , Animais , Pressão Sanguínea/efeitos dos fármacos , Butorfanol/administração & dosagem , Combinação de Medicamentos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Imidazóis/administração & dosagem , Infusões Intravenosas , Relaxamento Muscular/efeitos dos fármacos , Respiração/efeitos dos fármacos , Xilazina/administração & dosagem