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BACKGROUND: Literature on the safety of remdesivir in hospitalized COVID-19 patients with severe renal impairment is limited. We aimed to investigate the safety and effectiveness of remdesivir in this population. METHODS: We conducted a retrospective cohort study of adult hospitalized COVID-19 patients who received remdesivir between April 2022 and October 2022. Outcomes were compared between estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and ≥30 mL/min/1.73 m2 groups. The primary safety outcomes were acute kidney injury (AKI) and bradycardia, while the primary effectiveness outcomes included mortality in COVID-19-dedicated wards and hospital mortality. Secondary outcomes included laboratory changes, disease progression, and recovery time. RESULTS: A total of 1,343 patients were recruited, with 307 (22.9%) in the eGFR <30 group and 1,036 (77.1%) in the eGFR ≥30 group. Patients with an eGFR <30 had higher risks of AKI (adjusted hazard ratio [aHR] 2.92, 95% CI 1.93-4.44) and hospital mortality (aHR 1.47, 95% CI 1.06-2.05) but had comparable risks of bradycardia (aHR 1.15, 95% CI 0.85-1.56) and mortality in dedicated wards (aHR 1.43, 95% CI 0.90-2.28) than patients with an eGFR ≥30. Risk of disease progression was higher in the eGFR <30 group (adjusted odds ratio 1.62, 95% CI 1.16-2.26). No difference between the two groups in laboratory changes and recovery time. CONCLUSIONS: Hospitalized COVID-19 patients receiving remdesivir with severe renal impairment had an increased risk of AKI, hospital mortality, and COVID-19 disease progression compared to patients without severe renal impairment.
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Lesión Renal Aguda , Adenosina Monofosfato , Alanina , Antivirales , Tratamiento Farmacológico de COVID-19 , Tasa de Filtración Glomerular , Mortalidad Hospitalaria , Hospitalización , SARS-CoV-2 , Humanos , Alanina/análogos & derivados , Alanina/uso terapéutico , Alanina/efectos adversos , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Adenosina Monofosfato/efectos adversos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Antivirales/uso terapéutico , Antivirales/efectos adversos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiología , Hospitalización/estadística & datos numéricos , COVID-19/complicaciones , COVID-19/mortalidad , Resultado del Tratamiento , Insuficiencia Renal/epidemiología , Bradicardia/inducido químicamente , Bradicardia/epidemiología , AdultoRESUMEN
Escherichia coli (E. coli) plays an important ecological role, and is a useful bioindicator to recognize the evolution of resistance in human, animal and environment. Recently, extended-spectrum ß-lactamases (ESBL) producing E.coli has posed a threat to public health. Generally, captive healthy giant pandas are not exposed to antibiotics; however, they still acquire antimicrobial resistant bacteria. In order to understand whether there is an exchange of resistance genes within the ecosystems of captive giant pandas, this study explored resistance characteristics of 330 commensal E. coli isolates from feces of giant pandas, the surroundings, and breeders. Isolates from different sources showed similar resistance phenotype, and ESBL/AmpC-producing isolates showed more profound resistance to antibiotics than non-ESBL/AmpC-producing isolates (P<0.05). Furthermore, the occurrence of broad-spectrum ß-lactamase related resistance genes and colistin resistance genes was detected, and isolates phylogenetic typing and multilocus sequence typing (MLST) were applied in this study. Seven different ß-lactamase resistance genes (blaCTX-M-55, blaCTX-M-15, blaCTX-M-27, blaCTX-M-65, blaTEM-1, blaOXA-1 and blaCMY) and mcr-1 were found in 68 ESBL/AmpC-producing isolates. blaCTX-M-55 (48.53 %) was found the most predominant resistance genes, followed by blaTEM-1 (19.12 %) and blaCTX-M-27 (16.18 %). Nonetheless, blaCTX-M-55 was commonly detected in the isolates from giant pandas (63.16 %), the surroundings (43.48 %), and breeders (33.33 %). However, there were no carbapenemase genes detected in this study. mcr-1 was harbored in only one isolate from giant panda. Forty-five tansconjugants were successfully obtained in the conjugation experiments. The presence of antimicrobial resistance and related resistance genes tested were observed in the transconjugants. The results indicated that 52.63 % of the isolates from giant panda 73.91 % of the isolates from surroundings, and 100 % of the isolates from breeders were phylogroup A. Total of 27 sequence types (ST) were recognized from the isolate by MLST and found that ST48 (19/68; 27.94 %) was the predominant ST type, especially in the isolates from giant pandas and the surroundings. In conclusion, commensal ESBL/AmpC-producing E. coli becomes a reservoir of ESBL resistance genes, which is a potential threaten to health of giant pandas. The interaction between giant pandas, surroundings and breeders contribute to development of resistant phenotypes and genotypes which might transfer across species or the surroundings easily; hence, strict monitoring based on a "One Health" approach is recommended.
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Antibacterianos , Proteínas Bacterianas , Escherichia coli , Heces , Tipificación de Secuencias Multilocus , Ursidae , beta-Lactamasas , Animales , Escherichia coli/genética , Escherichia coli/efectos de los fármacos , beta-Lactamasas/genética , Ursidae/microbiología , China , Antibacterianos/farmacología , Heces/microbiología , Proteínas Bacterianas/genética , Ecosistema , Filogenia , Pruebas de Sensibilidad Microbiana , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/veterinaria , Farmacorresistencia Bacteriana Múltiple/genética , Farmacorresistencia Bacteriana/genéticaRESUMEN
Formosan serows are endemic to the mountainous regions of Taiwan. This crossover study aimed to assess and compare the anesthetic induction and recovery using either dexmedetomidine-tiletamine-zolazepam (DZ) or dexmedetomidine-ketamine (DK) by intramuscular injection from a blow-dart in a zoo environment. Ten anesthetic procedures were performed with five adult Formosan serows. Each participant was anesthetized with both combinations at least once with a minimal 12-month washout. The average dosages were 22.6 ± 8.3 µg/kg and 35.8 ± 2.5 µg/kg for dexmedetomidine and 185.6 ± 123.6 and 357.8 ± 25.2 µg/kg for atipamezole for the DZ and DK groups, respectively. The doses of tiletamine-zolazepam and ketamine were 2.1 ± 0.25 mg/kg and 3.6 ± 0.3 mg/kg, respectively, in the DZ and DK groups. All participants were induced within 10 min (median: 8 min for both groups), except one serow in the DK group with an induction time of 22 min. Serows in the DZ group had a lower respiratory rate (p = 0.016) and lower rectal temperature (p = 0.008) than those in the DK group. The quality of recovery was poor for DZ because of paddling, prolonged recovery, and ataxia after antagonism of dexmedetomidine with atipamezole. The induction of anesthesia with dexmedetomidine-tiletamine-zolazepam was uneventful and rapid. However, recovery from this combination was not smooth.
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BACKGROUND: Catharanthus roseus, a Madagascar native flowering plant, is known for its glossy leaves and vibrant flowers, and its medicinal significance due to its alkaloid compounds. As a source of vinblastine and vincristine used in chemotherapy, Catharanthus roseus is also employed in traditional medicine with its flower and stalks in dried form. Its toxicity can lead to various adverse effects. We report a case of Catharanthus roseus juice toxicity presenting as acute cholangitis, emphasizing the importance of healthcare providers obtaining detailed herbal supplement histories. CASE PRESENTATION: A 65-year-old woman presented with abdominal pain, fever, anorexia, and lower limb numbness. Initial diagnosis of acute cholangitis was considered, but imaging excluded common bile duct stones. Further investigation revealed a history of ingesting Catharanthus roseus juice for neck pain. Laboratory findings showed leukocytosis, elevated liver enzymes, and hyperbilirubinemia. The patient developed gastric ulcers, possibly due to alkaloids in Catharanthus roseus. No bacterial growth was noted in blood cultures. The patient recovered after discontinuing the herbal extract. CONCLUSIONS: Catharanthus roseus toxicity can manifest as fever, hepatotoxicity with cholestatic jaundice, and gastric ulcers, mimicking acute cholangitis. Awareness of herbal supplement use and potential toxicities is crucial for healthcare providers to ensure prompt diagnosis and appropriate management. This case emphasizes the need for public awareness regarding the possible toxicity of therapeutic herbs and the importance of comprehensive patient histories in healthcare settings.
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Alcaloides , Catharanthus , Colangitis , Úlcera Gástrica , Anciano , Humanos , Hojas de la Planta , FemeninoRESUMEN
Background and objective: Hemorheology and blood glucose are commonly used to estimate the risks of thrombosis and stress hyperglycemia after anaesthesia. The sequence of acupoint stimulation might influence the therapeutic effects of acupuncture. In the current study, we aimed at investigating the effect of different acupuncture sequences of "Huiyangjiuzhen" acupoints on the blood glucose and hemorheology in anesthetized rabbits. Methods: Twenty-five rabbits were randomly divided into five groups, including the control group (CG), the positive-sequence group (PSG), the reverse-sequence group (RSG), the disorder-sequence group (DSG), and the random group (RG). Except for the CG and RG, the rabbits in other groups were acupunctured with different sequences of "Huiyangjiuzhen"acupoints when the rabbits were anesthetized. The acupoints in rabbits of the RG were chosen randomly. The levels of blood glucose and hemorheology indexes before and after anaesthesia was detected. Results: In the PSG, Hηb 200/s, Mηb 30/s, Hηr 200/s, ERI, hematocrit and plasma viscosity levels were decreased, and the blood glucose level was not changed. In the DSG, the levels of Mηb 30/s and hematocrit were decreased, and the blood glucose was increased. In the CG, RSG and RG, no hemorheology indexes were changed and the blood glucose was increased. Conclusion: "Huiyangjiuzhen" acupuncture could decrease the risks of post-operative thrombosis and stress hyperglycemia in anesthetized rabbits. This effectiveness depends on both acupuncture and acupuncture sequence at the "Huiyangjiuzhen" acupoints.
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The aim of this study was to investigate the effects of adding tea tree oil (TTO) in the basal diet on growth performance, immune function, and intestinal function in broilers. This study utilized 1,650 one-day-old broilers with good health and similar body weight. Subjects were randomized into 5 groups with 6 replicates each: the control group (CON, basal diet), positive control group (PCG, basal diet + 100 mg/kg oregano oil in diet), low-dose TTO group (TTO-L, 50 mg/kg TTO added in the basal diet), medium-dose TTO group (TTO-M, 100 mg/kg TTO added in the basal diet), and high-dose TTO group (TTO-H, 200 mg/kg TTO added in the basal diet). The whole test period lasted 28 d. The results showed that the broilers fed with TTO supplemented diet had significantly higher body weight and average daily gain (ADG) (P = 0.013), and had a lower feed conversion ratio (F/G) (P = 0.010) throughout the trial period. The index of thymus in TTO-M increased significantly compared to CON (P = 0.015) on d 28. On d 14 and 28, C3, IFN-γ, TNF-α, and IL-2 levels in TTO-L serum were significantly increased (P < 0.001); the 3 test groups supplemented with TTO had significantly higher titers of avian influenza H9 subtype in their serum (P < 0.05). Tea tree oil supplement in the diet also had a positive and significant effect on the intestinal morphology of broilers throughout the experiment (P < 0.05). These results indicate that TTO has the ability to promote broiler growth, regulate immunity, and improve intestinal morphology. The proposed dosage of adding 50 mg/kg in broiler basal diets provides a theoretical basis for its subsequent use in livestock feeds.
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Aceite de Árbol de Té , Animales , Aceite de Árbol de Té/farmacología , Pollos/fisiología , Suplementos Dietéticos , Dieta/veterinaria , Peso Corporal , Inmunidad , Alimentación Animal/análisisRESUMEN
The excessive intake of fluoride, one of the trace elements required to maintain health, leads to liver injury. Tetramethylpyrazine (TMP) is a kind of traditional Chinese medicine monomer with a good antioxidant and hepatoprotective function. The aim of this study was to investigate the effect of TMP on liver injury induced by acute fluorosis. A total of 60 1-month-old male ICR mice were selected. All mice were randomly divided into five groups: a control (K) group, a model (F) group, a low-dose (LT) group, a medium-dose (MT) group, and a high-dose (HT) group. The control and model groups were given distilled water, while 40 mg/kg (LT), 80 mg/kg (MT), or 160 mg/kg (HT) of TMP was fed by gavage for two weeks, with a maximum gavage volume for the mice of 0.2 mL/10 g/d. Except for the control group, all groups were given fluoride (35 mg/kg) by an intraperitoneal injection on the last day of the experiment. The results of this study showed that, compared with the model group, TMP alleviated the pathological changes in the liver induced by the fluoride and improved the ultrastructure of liver cells; TMP significantly decreased the levels of ALT, AST, and MDA (p < 0.05) and increased the levels of T-AOC, T-SOD, and GSH (p < 0.05). The results of mRNA detection showed that TMP significantly increased the mRNA expression levels of Nrf2, HO-1, CAT, GSH-Px, and SOD in the liver compared with the model group (p < 0.05). In conclusion, TMP can inhibit oxidative stress by activating the Nrf2 pathway and alleviate the liver injury induced by fluoride.
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Fluoruros , Hepatopatías , Masculino , Ratones , Animales , Fluoruros/efectos adversos , Ratones Endogámicos ICR , Factor 2 Relacionado con NF-E2/metabolismo , Hepatopatías/metabolismo , Hígado , Estrés Oxidativo , ARN Mensajero/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
Lipopolysaccharide (LPS) has been considered the primary agent to establish animal models of inflammation, immunological stress, and organ injury. Previous studies have demonstrated that LPS impaired gastrointestinal development and disrupted intestinal microbial composition and metabolism. Ferulic acid (FA) isolated from multiple plants exhibits multiple biological activities. This study investigated whether FA ameliorated intestinal function and microflora in LPS-challenged Tianfu broilers. The results showed that LPS challenge impaired intestinal function, as evidenced by decreased antioxidant functions (p < 0.05), disrupted morphological structure (p < 0.05), and increased intestinal permeability (p < 0.05); however, these adverse effects were improved by FA supplementation. Additionally, FA supplementation preserved sIgA levels (p < 0.05), increased mRNA expression levels of CLDN and ZO-1 (p < 0.05), and enhanced epithelial proliferation (p < 0.05) in the ileal mucosa in LPS-challenged chickens. Moreover, FA supplementation rectified the ileal microflora disturbances in the LPS-challenged broilers. The results demonstrate that dietary FA supplementation decreased LPS-induced intestinal damage by enhancing antioxidant capacity and maintaining intestinal integrity. Furthermore, FA supplementation protects intestinal tight junctions (TJs), elevates secretory immunoglobulin A (sIgA) levels, and modulates ileal microflora composition in LPS-challenged broilers.
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Lipopolisacáridos , Microbiota , Animales , Lipopolisacáridos/farmacología , Pollos/metabolismo , Antioxidantes/metabolismo , Suplementos Dietéticos/análisis , Dieta/veterinaria , Inmunoglobulina A Secretora , Alimentación Animal/análisisRESUMEN
OBJECTIVE: To compare 5% lidocaine ointment applied for 10 minutes before intravenous (IV) catheterization to a eutectic mixture of local anesthetics (2.5% lidocaine and 2.5% prilocaine; EMLA) cream applied for 10 or 60 minutes prior and a water-based placebo for 60 minutes for successful marginal ear IV catheterization in rabbits. STUDY DESIGN: Randomized, blinded, complete crossover, controlled trial. ANIMALS: A total of 10 intact male, New Zealand White rabbits aged 4 months. METHODS: After application of one of the treatments on the marginal ear vein, an operator unaware of the treatment attempted IV catheter placement. Successful IV catheterization was considered as a catheter inserted at the first attempt, safely secured, with appropriate patency. Generalized linear mixed models were developed to identify relevant predictors of successful catheter placement. RESULTS: Ears that had EMLA cream applied 60 minutes before the catheterization attempt had more than 10 times the odds of successful catheter placement [odds ratio (OR)=10.75; 95% confidence interval (CI), 1.92-60.16; p < 0.008] compared with placebo. Both the application of EMLA cream or lidocaine ointment 10 minutes before the catheterization attempt resulted in approximately three times the odds of successful catheter placement compared with placebo, but were not statistically significant. CONCLUSIONS AND CLINICAL RELEVANCE: Application of EMLA cream on the marginal ear vein 60 minutes before catheterization increases the chance of successful IV catheter placement in conscious rabbits.
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Cateterismo Periférico , Prilocaína , Anestésicos Locales , Animales , Cateterismo Periférico/veterinaria , Método Doble Ciego , Lidocaína , Combinación Lidocaína y Prilocaína , Masculino , Pomadas , Conejos , AguaRESUMEN
Background and Objectives: Direct-acting antiviral agents (DAA) are a safe and highly effective treatment for hepatitis C virus (HCV) infection. However, the uptake of DAA treatment remains a challenge. This study aims to examine the reasons for DAA refusal among HCV patients covered by the Taiwan National Health Insurance system. Materials and Methods: This retrospective observational study covered the period from January 2009 to December 2019 and was conducted at a single hepatitis treatment center in Taiwan. This study involved chart reviews and phone-based surveys to confirm treatment status and refusal causes. To confirm treatment status, subjects with HCV without treatment records were phone-contacted to confirm treatment status. Patients who did not receive treatment were invited back for treatment. If the patient refused, the reason for refusal was discussed. Results: A total of 3566 patients were confirmed with DAA treatment; 418 patients (179 patients who were lost to contact or refused the survey and 239 patients who completed the survey of DAA refusal) were included in the no-DAA-therapy group. Factors associated with receiving DAAs were hemoglobin levels, hepatitis B virus co-infection, and regular gastroenterology visits. Meanwhile, male sex, platelet levels, and primary care physician visits were associated with DAA refusal. The leading causes of treatment refusal were multiple comorbidities, low health literacy, restricted access to hospitals, nursing home residence, and old age. The rate of DAA refusal remains high (10%). Conclusions: The reasons for treatment refusal are multifactorial, and addressing them requires complex interventions.
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Hepatitis C Crónica , Hepatitis C , Antivirales/uso terapéutico , Hepacivirus , Virus de la Hepatitis B , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Masculino , TaiwánRESUMEN
BACKGROUND: The emergence of antibiotic resistance over the past decade has made the treatment of Staphylococcus aureus infection difficult. Burn wounds infected with methicillin-resistant S. aureus (MRSA) can cause mortality in animals. Shikonin (SH) has been reported to possess antimicrobial and anti-inflammatory properties, and is also responsible for the process of wound healing. However, the pharmacological mechanism of its wound healing process remains poorly comprehended, hence the probable mechanism deserves further investigation. PURPOSE: The current study was designed to develop a novel SH-liposome with improved anti-MRSA effect and to detect its beneficial wound healing effects. STUDY DESIGN: In vitro antibacterial tests and in vivo infected wound healing test were conducted. METHODS: SH-liposome was produced by the film formation method, and the characteristics were measured using a laser particle size analyzer, transmission electron microscopy, and the dialysis method. Additionally, in vitro antibacterial tests were conducted to investigate the antibacterial effects and the relative mechanism of SH-liposome. Furthermore, the therapeutic effects and bioactivity of SH-liposome in MRSA infected burn wounds were investigated in rats. Sixty-four male Sprague Dawley rats (250 ± 10 g) were randomly divided into four groups, including Group I (control group); Group II (model group); Group III (SH-liposome group) and Group IV (Arnebia oil® group), and the drug treatments were applied topically twice daily for 21 days. Further, full thickness skin biopsies at different periods were collected aseptically to evaluate tissue cytokines, recognize flora, observe histopathological changes, and determine the mechanism underlying the wound healing effects of SH-liposome. The data were analyzed via one-way analysis of variance (ANOVA) and Duncan's multiple range test. RESULTS: The results showed that SH-liposome was successful with a drug load of 4.6 ± 0.17%. Moreover, SH-liposome showed a sustained-release behavior and improved antibacterial ability in a dose-dependent manner. For the possible antibacterial mechanism, we observed that SH-liposome achieved antibacterial activity by damaging the integrity of bacterial cell wall and membrane to further disturb the physiological activities of S. aureus. In addition, SH-liposome facilitated wound healing by inhibiting bacterial activities to control infection, regulating the I-κBα/NFκB-p65 pathway to alleviate inflammation, and directly promoting repair in burn wounds. CONCLUSION: In conclusion, SH-liposome showed an antibacterial effect against S. aureus, promoted effective healing of infected burn wounds; hence, it could be used as an alternative therapy for drug-resistant infections.
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Post-radiofrequency ablation (RFA) fever is a self-limited complication of RFA. The correlation between post-RFA fever and bacteremia and the risk factors associated with post-RFA fever have not been evaluated. Patients with newly diagnosed or recurrent hepatocellular carcinoma who underwent ultrasonography-guided RFA between April 2014 and February 2019 were retrospectively enrolled. Post-RFA fever was defined as any episode of body temperature >38.0 °C after RFA during hospitalization. A total of 272 patients were enrolled, and there were 452 applications of RFA. The frequency of post-RFA fever was 18.4% (83/452), and 65.1% (54/83) of post-RFA fevers occurred on the first day after ablation. Patients with post-RFA fever had a longer hospital stay than those without (9.06 days vs. 5.50 days, p < 0.001). Only four (4.8%) patients with post-RFA fever had bacteremia. The independent factors associated with post-RFA fever were younger age (adjusted odds ratio (OR) = 0.96, 95% CI, 0.94-0.99, p = 0.019), low serum albumin level (adjusted OR = 0.49, 95% CI, 0.25-0.95, p = 0.036), general anesthesia (adjusted OR = 2.06, 95% CI, 1.15-3.69, p = 0.015), tumor size (adjusted OR = 1.52, 95% CI, 1.04-2.02, p = 0.032), and tumor number (adjusted OR = 1.71, 95% CI, 1.20-2.45, p = 0.003).
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Several life-threatening viruses have recently appeared, including the coronavirus, infecting a variety of human and animal hosts and causing a range of diseases like human upper respiratory tract infections. They not only cause serious human and animal deaths, but also cause serious public health problems worldwide. Currently, seven species are known to infect humans, namely SARS-CoV-2, MERS-CoV, SARS-CoV, HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1. The coronavirus nonstructural protein 16 (NSP16) structure is similar to the 5'-end capping system of mRNA used by eukaryotic hosts and plays a vital role in evading host immunity response and protects the nascent viral mRNA from degradation. NSP16 is also well-conserved among related coronaviruses and requires its binding partner NSP10 to activate its enzymatic activity. With the continued threat of viral emergence highlighted by human coronaviruses and SARS-CoV-2, mutant strains continue to appear, affecting the highly conserved NSP16: this provides a possible therapeutic approach applicable to any novel coronavirus. To this end, current information on the 2'-O-MTase activity mechanism, the differences between NSP16 and NSP10 in human coronaviruses, and the current potential prevention and treatment strategies related to NSP16 are summarized in this review.
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Infecciones por Coronavirus/virología , Coronavirus/metabolismo , Metiltransferasas/metabolismo , Proteínas no Estructurales Virales/metabolismo , Animales , COVID-19/virología , Coronavirus/enzimología , Coronavirus/genética , Humanos , Metiltransferasas/genética , SARS-CoV-2/enzimología , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Proteínas no Estructurales Virales/genéticaRESUMEN
OBJECTIVE: To evaluate and compare the anesthetic, analgesic, and cardiorespiratory effects of tiletamine-zolazepam-detomidine-butorphanol (TZDB), tiletamine-zolazepam-xylazine-butorphanol (TZXB), and ketamine-detomidine-butorphanol (KDB) in pigs and to assess anesthetic recovery duration and quality following administration of tolazoline as a reversal agent. ANIMALS: 11 healthy 2.5-month-old castrated male Landrace mixed-breed pigs. PROCEDURES: In a randomized, blinded crossover study design, pigs received the following anesthetic combinations, IM: TZDB (tiletamine-zolazepam [3 mg/kg {1.36 mg/lb}], detomidine [0.18 mg/kg {0.08 mg/lb}], and butorphanol [0.12 mg/kg {0.05 mg/lb}]); TZXB (tiletamine-zolazepam [4 mg/kg {1.8 mg/lb}], xylazine [4 mg/kg], and butorphanol [0.2 mg/kg {0.09 mg/lb}]); and KDB (ketamine [8 mg/kg {3.63 mg/lb}], detomidine [0.18 mg/kg], and butorphanol [0.3 mg/kg {0.14 mg/lb}]). A 7-day washout period was provided between treatments. At 45 minutes of anesthesia, pigs received tolazoline (2 mg/kg [0.9 mg/lb], IM; n = 6) treatment or control (5) treatment with saline (0.9% NaCl) solution. RESULTS: All anesthetic combinations induced anesthesia. Endotracheal intubation was completed within 5 minutes after anesthetic administration in all pigs, except in 2 pigs following administration of KDB. Durations (mean ± SD) of endotracheal intubation and lateral recumbency in pigs that did not receive tolazoline were 55.3 ± 4.8 minutes, 83.8 ± 15.8 minutes, and 28.2 ± 4.5 minutes and 112.4 ± 18.7 minutes, 117.2 ± 16.7 minutes, and 79.7 ± 6.0 minutes, respectively, for the TZDB, TZXB, and KDB anesthetic treatments. Tolazoline significantly shortened the duration of anesthetic recovery for all anesthetic treatments without affecting the recovery quality. CONCLUSIONS AND CLINICAL RELEVANCE: All 3 anesthetic combinations were suitable for providing anesthesia in pigs. Tolazoline administration shortened the duration of anesthetic recovery without affecting the quality of recovery.
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Anestésicos , Ketamina , Anestésicos/farmacología , Animales , Butorfanol , Estudios Cruzados , Combinación de Medicamentos , Frecuencia Cardíaca , Imidazoles , Ketamina/farmacología , Masculino , Porcinos , Tiletamina/farmacología , Xilazina/farmacología , Zolazepam/farmacologíaRESUMEN
BACKGROUND: Some studies showed patients with chronic urticaria have a higher rate of peptic ulcer disease (PUD). Whether PUD is a risk factor for chronic urticaria is unclear. OBJECTIVE: The objective of this study was to evaluate the incidence of and risk factors for chronic urticaria in patients with PUD using the Taiwan National Health Insurance Research Database. METHODS: We conducted a retrospective nationwide cohort study of the period 2000-2012 and involving 11,901 patients with PUD who underwent Helicobacter pylori (HP) therapy (PUD + HP group) and an equal number of matched patients without HP infection (PUD - HP group). Furthermore, we enrolled 23,802 patients without PUD for comparison (non-PUD group). The Cox proportional hazards regression model was used to analyze chronic urticaria risk after adjusting for potential confounding factors. RESULTS: The mean ages of the three groups were around 50 years. Approximately 42.6% were female. Chronic urticaria incidences in the PUD + HP and PUD - HP groups were both significantly higher than that in the non-PUD group. The hazard ratios of chronic urticaria in the PUD + HP group and the PUD - HP group were 1.34 (95% confidence interval 1.09-1.64) and 1.45 (95% confidence interval 1.19-1.79), respectively. The risk difference became significant 2 years after patients with PUD had the HP infection tests and persisted till the end of follow-up. The risk increase was significant in patients with PUD who were female or aged 40-64 years. There was no difference in the risk comparison between PUD + HP and PUD - HP groups. CONCLUSIONS: Peptic ulcer disease, independent of HP infection, is associated with an increased chronic urticaria risk. Patients with PUD who were female or aged 40-64 years are more likely to have chronic urticaria.
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Urticaria Crónica/epidemiología , Infecciones por Helicobacter/epidemiología , Úlcera Péptica/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Urticaria Crónica/inmunología , Femenino , Estudios de Seguimiento , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/inmunología , Helicobacter pylori/inmunología , Helicobacter pylori/aislamiento & purificación , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Úlcera Péptica/diagnóstico , Úlcera Péptica/tratamiento farmacológico , Úlcera Péptica/inmunología , Estudios Retrospectivos , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , Factores Sexuales , Taiwán/epidemiología , Adulto JovenRESUMEN
Scanning moiré fringe (SMF) is a widely utilized technique for the precise measurement of the strain field in semiconductor transistors and heterointerfaces. With the growing challenges of traditional chip scaling, two-dimensional (2D) materials turn out to be ideal candidates for incorporation into semiconductor devices. Therefore, a method to efficiently locate defects and grain boundaries in 2D materials is highly essential. Here, we present a demonstration of using the SMF method to locate the domain boundaries at the nearly coherent interfaces with sub-angstrom spatial resolution under submicron fields of views. The strain field of small angle grain boundary and lateral heterojunction are instantaneously found and precisely determined by a quick SMF method without any atomic resolution images.
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This study was to investigate the fracture risk of irritable bowel syndrome (IBS) in comparison with non-IBS group. Our results found that IBS group has increased risk for fracture, in particular of the spine, forearm, hip, and hand. INTRODUCTION: Patients with IBS might also be at increased risk of osteoporosis and osteoporotic fractures. Up to now, the association between IBS and the risk of fractures at different anatomic sites occurrences is not completely clear. We conducted a population-based cohort analysis to investigate the fracture risk of IBS in comparison with non-IBS group. METHODS: We identified 29,505 adults aged ≥ 20 years with newly diagnosed IBS using the Taiwan National Health Insurance Research Database in 2000-2012. A comparison group was constructed of patients without IBS who were matched according to gender and age. The occurrence of fracture was monitored until the end of 2013. We analyzed the risk of fracture events to occur in IBS by using Cox proportional hazards regression models. RESULTS: Patients with IBS had a higher incidence of osteoporotic fractures compared with the non-IBS group (12.34 versus 9.45 per 1000 person-years) and an increased risk of osteoporotic fractures (adjusted hazard ratio [aHR] = 1.27, 95% confidence interval [CI] = 1.20-1.35). Site-specific analysis showed that the IBS group had a higher risk of fractures for spine, forearm, hip, and hand than did the non-IBS group. With further stratification for gender and age, a higher aHR value for osteoporotic fractures in the IBS group was seen across all age groups in males, but seen in elderly females. In addition, female, elderly, low income, hypertension, coronary artery disease, cerebrovascular disease, and depressive disorders as independent osteoporotic fracture risk factors in IBS patients. CONCLUSIONS: The IBS is considered as a risk factor for osteoporotic fractures, particularly in female individuals and fracture sites located at the spine, forearm, hip, and hand.
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Síndrome del Colon Irritable/complicaciones , Fracturas Osteoporóticas/epidemiología , Adulto , Anciano , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Traumatismos del Antebrazo/etiología , Traumatismos de la Mano/etiología , Fracturas de Cadera/etiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Fracturas Osteoporóticas/etiología , Modelos de Riesgos Proporcionales , Factores de Riesgo , Traumatismos Vertebrales/etiología , Taiwán/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Computational drug design approaches are important for shortening the time and reducing the cost for drug discovery and development. Among these methods, molecular docking and quantitative structure activity relationship (QSAR) play key roles for lead discovery and optimization. Here, we propose an integrated approach with core strategies to identify the protein-ligand hot spots for QSAR models and lead optimization. These core strategies are: 1) to generate both residue-based and atom-based interactions as the features; 2) to identify compound common and specific skeletons; and 3) to infer consensus features for QSAR models. RESULTS: We evaluated our methods and new strategies on building QSAR models of human acetylcholinesterase (huAChE). The leave-one-out cross validation values q 2 and r 2 of our huAChE QSAR model are 0.82 and 0.78, respectively. The experimental results show that the selected features (resides/atoms) are important for enzymatic functions and stabling the protein structure by forming key interactions (e.g., stack forces and hydrogen bonds) between huAChE and its inhibitors. Finally, we applied our methods to arthrobacter globiformis histamine oxidase (AGHO) which is correlated to heart failure and diabetic. CONCLUSIONS: Based on our AGHO QSAR model, we identified a new substrate verified by bioassay experiments for AGHO. These results show that our methods and new strategies can yield stable and high accuracy QSAR models. We believe that our methods and strategies are useful for discovering new leads and guiding lead optimization in drug discovery.
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Acetilcolinesterasa/química , Aminoácidos/química , Proteínas Bacterianas/química , Diseño de Fármacos , Inhibidores Enzimáticos/química , Oxidorreductasas/química , Arthrobacter/química , Arthrobacter/enzimología , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Ligadas a GPI/antagonistas & inhibidores , Proteínas Ligadas a GPI/química , Histamina/química , Humanos , Enlace de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Ligandos , Simulación del Acoplamiento Molecular , Oxidorreductasas/antagonistas & inhibidores , Relación Estructura-Actividad Cuantitativa , Electricidad Estática , Especificidad por SustratoRESUMEN
An ~21-year-old female Barbary sheep (Ammotragus lervia) died spontaneously following a lengthy episode of difficulty in walking. An ~6 × 3 × 3 cm, unilocular cystic growth was found in the cranioventral thorax. The fibrotic cystic wall, lined by a single layer of flattened to cuboidal epithelial cells, was invaginated and partially encircled solid masses of fusiform neoplastic cells with multiple intratumoral cystic structures. The fusiform neoplastic cells were intensely positive for cytokeratin (CK) and partially positive for α-smooth muscle actin and vimentin, but negative for thyroid transcription factor-1 (TTF-1) and neuron-specific enolase (NSE). The intratumoral cysts were lined by CK-positive but TTF-1- negative, NSE-negative, flattened, cuboidal to columnar epithelial cells, suggestive of cystically dilated medullary duct epithelium-derived structures. Based on the location and histopathologic findings of the growth, concurrent spindle-cell thymoma and thymic cysts was diagnosed. We also discuss the correlation between thymic cysts and thymoma and review the literature of thymomas in ovine and wildlife species.
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Quiste Mediastínico/veterinaria , Rumiantes , Timoma/veterinaria , Neoplasias del Timo/veterinaria , Animales , Diagnóstico Diferencial , Femenino , Quiste Mediastínico/complicaciones , Quiste Mediastínico/diagnóstico , Timoma/complicaciones , Timoma/diagnóstico , Neoplasias del Timo/complicaciones , Neoplasias del Timo/diagnósticoRESUMEN
This study investigated the effect of body position on the electroencephalogram (EEG) and autonomic nervous modulation, and the relationship between them using spectral analysis of EEG and heart rate variability (HRV). All healthy volunteers recruited had their electrocardiogram and EEG recorded for power spectral analysis. We found that when changing position from supine to upright, the EEG spectral components below the α band, such as δ and θ bands, were significantly decreased while the EEG spectral components above the α band, such as ß, γ and ω bands, were significantly increased in both scalps. Correlation analysis showed that the θ rhythm of both scalps might be associated with the control of HR, the α and ß rhythms of right scalp might be associated with vagal modulation, and the γ rhythm of left scalp might be associated with sympathetic modulation of the subject. Thus, some EEG components might be associated with the autonomic nervous modulation of the subject during positional change. There might be a mechanism located in the brain-stem which jointly controls both autonomic influences on heart rate and EEG activation.