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BACKGROUND: Telemedicine helps to provide the safe management of stroke patients in the emergency department (ED) and has been used worldwide. However, we had limited experience of telestroke in Taiwan. We aimed to identify the quality of telestroke and compare it with the original face-to-face consultation model. METHODS: Among 178 consecutive acute ischemic stroke patients treated with intravenous tissue plasminogen activator (IVtPA) from January 1, 2018, to December 31, 2019, we compared two different consultation methods: face-to-face consultation and telestroke consultation. We collected data on demographics, the National Institutes of Health Stroke Scale (NIHSS) scores, Modified Rankin Scale (mRS) scores, time measurements (onset-to-arrival time, onset-to-telestroke activation time, and time of IVtPA administration (Door-to-Needle; DTN)). RESULTS: The mean age to receive a telestroke consultation was 66.6 years, 36% were female, and the median NIHSS score was 9. The median time from patient arrival to telestroke consult activation was 40 min, and the median DTN time was 11 min longer than for face-to-face consults (62 min versus 51 min, p = .01). Telestroke consultation, similar to a face-to-face consultation, resulted in safe IVtPA eligibility assessments and administration with post-thrombolysis ICH in 4% overall (4% telestroke, 3% face-to-face consultation; p = .851). The 90-day outcomes were not different for mRS score, dichotomized 0-2 (60% telestroke 59% face-to-face consultation; p = .961), or for mortality (16% telestroke, 9% face-to-face consultation; p = .292). CONCLUSION: In the ED, consultation via the telestroke program provides equal quality to the original face-to-face consultation model to manage ischemic stroke.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Telemedicina , Isquemia Encefálica/tratamiento farmacológico , Femenino , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Taiwán , Activador de Tejido Plasminógeno/uso terapéutico , Estados UnidosRESUMEN
BACKGROUND: Right ventricular (RV) function is the major determinant for both functional capacity and survival in patients with pulmonary arterial hypertension (PAH). Despite the recognized clinical importance of preserving RV function, the subcellular mechanisms that govern the transition from a compensated to a decompensated state remain poorly understood and as a consequence there are no clinically established treatments for RV failure and a paucity of clinically useful biomarkers. Accumulating evidence indicates that long noncoding RNAs are powerful regulators of cardiac development and disease. Nonetheless, their implication in adverse RV remodeling in PAH is unknown. METHODS: Expression of the long noncoding RNA H19 was assessed by quantitative PCR in plasma and RV from patients categorized as control RV, compensated RV or decompensated RV based on clinical history and cardiac index. The impact of H19 suppression using GapmeR was explored in 2 rat models mimicking RV failure, namely the monocrotaline and pulmonary artery banding. Echocardiographic, hemodynamic, histological, and biochemical analyses were conducted. In vitro gain- and loss-of-function experiments were performed in rat cardiomyocytes. RESULTS: We demonstrated that H19 is upregulated in decompensated RV from PAH patients and correlates with RV hypertrophy and fibrosis. Similar findings were observed in monocrotaline and pulmonary artery banding rats. We found that silencing H19 limits pathological RV hypertrophy, fibrosis and capillary rarefaction, thus preserving RV function in monocrotaline and pulmonary artery banding rats without affecting pulmonary vascular remodeling. This cardioprotective effect was accompanied by E2F transcription factor 1-mediated upregulation of enhancer of zeste homolog 2. In vitro, knockdown of H19 suppressed cardiomyocyte hypertrophy induced by phenylephrine, while its overexpression has the opposite effect. Finally, we demonstrated that circulating H19 levels in plasma discriminate PAH patients from controls, correlate with RV function and predict long-term survival in 2 independent idiopathic PAH cohorts. Moreover, H19 levels delineate subgroups of patients with differentiated prognosis when combined with the NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels or the risk score proposed by both REVEAL (Registry to Evaluate Early and Long-Term PAH Disease Management) and the 2015 European Pulmonary Hypertension Guidelines. CONCLUSIONS: Our findings identify H19 as a new therapeutic target to impede the development of maladaptive RV remodeling and a promising biomarker of PAH severity and prognosis.
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Insuficiencia Cardíaca/metabolismo , Hipertensión Arterial Pulmonar/metabolismo , ARN Largo no Codificante/metabolismo , Remodelación Vascular , Disfunción Ventricular Derecha/metabolismo , Animales , Biomarcadores/metabolismo , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/patología , Humanos , Péptido Natriurético Encefálico/metabolismo , Fragmentos de Péptidos/metabolismo , Hipertensión Arterial Pulmonar/mortalidad , Hipertensión Arterial Pulmonar/patología , Ratas , Disfunción Ventricular Derecha/mortalidad , Disfunción Ventricular Derecha/patologíaRESUMEN
In this study, we investigated the effect of mTOR inhibitor (mTORi) drug-eluting biodegradable stent (DE stent), a putative restenosis-inhibiting device for coronary artery, on thermal-injury-related ureteral stricture in rabbits. In vitro evaluation confirmed the dose-dependent effect of mTORi, i.e., rapamycin, on fibrotic markers in ureteral component cell lines. Upper ureteral fibrosis was induced by ureteral thermal injury in open surgery, which was followed by insertion of biodegradable stents, with or without rapamycin drug-eluting. Immunohistochemistry and Western blotting were performed 4 weeks after the operation to determine gross anatomy changes, collagen deposition, expression of epithelial-mesenchymal transition markers, including Smad, α-SMA, and SNAI 1. Ureteral thermal injury resulted in severe ipsilateral hydronephrosis. The levels of type III collagen, Smad, α-SMA, and SNAI 1 were increased 28 days after ureteral thermal injury. Treatment with mTORi-eluting biodegradable stents significantly attenuated thermal injury-induced urinary tract obstruction and reduced the level of fibrosis proteins, i.e., type III collagen. TGF-ß and EMT signaling pathway markers, Smad and SNAI 1, were significantly modified in DE stent-treated thermal-injury-related ureteral stricture rabbits. These results suggested that intra-ureteral administration of rapamycin by DE stent provides modification of fibrosis signaling pathway, and inhibiting mTOR may result in fibrotic process change.
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Implantes Absorbibles , Stents Liberadores de Fármacos , Sirolimus , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Obstrucción Ureteral , Animales , Fibrosis , Conejos , Sirolimus/química , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/metabolismo , Obstrucción Ureteral/metabolismo , Obstrucción Ureteral/patología , Obstrucción Ureteral/terapiaRESUMEN
Abscisic acid-insensitive 5 (ABI5) is a basic leucine zipper (bZIP) transcription factor that is abundantly expressed in seeds. It plays a central role in regulating the abscisic acid (ABA) signal of seed germination and early seedling growth. Brassinosteroid (BR) is a new type of plant endogenous hormone, which has many physiological functions such as regulating plant growth and development and response to adversity stress. It has recently been discovered that under brassinolide stress, BIN2 (BRASSINOSTEROID INSENSITIVE2) and BES1 (BRI1-EMS-SUPPRESSOR 1) in the BR signaling pathway can inhibit the expression of ABI5 and promote Arabidopsis thaliana seed germination. In order to further explore the function of ABI5 under BR stress, this study analyzed the ABI5 expression characteristics during seed germination, identified Arabidopsis ABI5 gene deletion mutant abi5-1 and analyzed its function under BR stress, the results of which indicated that ABI5 was abundantly expressed in Arabidopsis dry seeds and responded to BR stress during germination. Under normal conditions, there was no significant difference between the hypocotyls of abi5-1 and wild-type seedlings; but under BR stress, the hypocotyls of abi5-1 seedlings were significantly longer than those of wild-type seedlings. These results reveal that ABI5 regulates the growth of Arabidopsis hypocotyls under BR stress, thereby providing a basis for in-depth understanding of the molecular mechanism of ABI5 regulation on plant development.
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Proteínas de Arabidopsis , Arabidopsis , Ácido Abscísico , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Brasinoesteroides , Regulación de la Expresión Génica de las Plantas , Germinación , Hipocótilo/genética , Hipocótilo/metabolismo , Proteínas Quinasas , Plantones/genética , SemillasRESUMEN
Non-bacterial prostatitis is an inflammatory disease that is difficult to treat. Oligonucleotide aptamers are well known for their stability and flexibility in conjugating various inflammatory molecules. In this study, we investigated the effects of inflammatory cytokine-targeting aptamers (ICTA), putative neutralizers of TNF-alpha and IL-1 beta activation, on local carrageenan-induced prostate inflammation, allodynia, and hyperalgesia in rats. In vitro evaluation confirmed the binding capability of ICTA. Intraprostatic injection of carrageenan or control vehicle was performed in six-week-old rats, and ICTA (150 µg) or vehicle was administered in the prostate along with carrageenan injection. The von Frey filament test was performed to determine mechanical allodynia, and prostate inflammation was examined seven days after drug administration. Local carrageenan administration resulted in a reduction of the tactile threshold. The levels of mononuclear cell infiltration, pro-inflammatory cytokine interleukin-1 beta (b), caspase-1 (casp-1), and Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing proteins 1 and 3 (NALP1 and NALP3) in the prostate of rats were increased seven days after carrageenan injection. Treatment with ICTA significantly attenuated the carrageenan-induced hyperalgesia and reduced the elevated levels of proteins including TNF-a and IL-1b in the rats. Apoptosis markers, B-cell lymphoma 2-associated X protein (Bax) and caspase-3, were elevated in ICTA-treated Chronic pelvic pain syndrome (CPPS) rats. These results suggest that ICTA provides protection against local carrageenan-induced enhanced pain sensitivity, and that the neutralization of proinflammatory cytokines may result in inflammatory cell apoptosis.
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Aptámeros de Nucleótidos/farmacología , Citocinas/metabolismo , Prostatitis/tratamiento farmacológico , Animales , Apoptosis , Carragenina/farmacología , Caspasa 1/metabolismo , Caspasa 3/metabolismo , Dolor Crónico/tratamiento farmacológico , Modelos Animales de Enfermedad , Humanos , Hiperalgesia/metabolismo , Inflamación , Interleucina-1beta/metabolismo , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Umbral del Dolor , Dolor Pélvico/tratamiento farmacológico , Próstata/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Proteína X Asociada a bcl-2/metabolismoRESUMEN
BACKGROUND: Diet is associated with self-reported indices of sexual health. The mechanisms responsible for these changes remain poorly understood. AIM: To investigate the hemodynamic and histological impact of dietary change in a rat model of hyperlipidemia-associated erectile dysfunction. METHODS: 40 2-month old male Sprague-Dawley rats were divided into 4 groups. 10 rats were fed a diet of standard chow and served as negative controls (N group). The remaining 30 age-matched rats were divided at random into 3 groups: (i) high-fat diet for 5 months starting at age 5 months (H group); (ii) high-fat diet for 5 months starting at age 4 months followed by 1 month of standard chow (H+N1M group); and (iii) high-fat diet for 5 months starting at age 2 months followed by 3 months of standard chow (H+N3M group). All rats underwent erectile function testing and sacrifice at age 10 months. OUTCOMES: Intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured to evaluate erectile function. Blood samples were collected to measure serum testosterone and lipid levels, and penile tissue specimens were obtained for histological examination. RESULTS: Total body weight, low-density lipoprotein, and serum glucose were significantly higher in the H group compared with the N and H+N3M groups. Serum high-density lipoprotein level was significantly lower in the H group compared with the N and H+N3M groups. The mean ICP/MAP ratio was significantly lower in the H group compared with the N and H+N3M groups (0.33 ± 0.05 vs 0.79 ± 0.07 vs 0.73 ± 0.13; P < .05 for both). Markers for intracorporal neuronal nitric oxide synthase and endothelial cells were more weakly expressed in the H group compared with the N and H+N3M groups. There was no significant difference in smooth muscle content among the groups. Mean cavernosal oxidative stress and the apoptotic index were significantly higher in the H group compared with the N and H+N3M groups. No significant between-group differences were noted with respect to serum testosterone; the H group had significantly higher serum glucose and low-density lipoprotein levels, effects that were partially mitigated in the H +N1M and H+N3M groups. CLINICAL TRANSLATION: Administration of a healthy diet is associated with normalization of functional and histological penile defects associated with a high-fat diet. STRENGTHS & LIMITATIONS: Metabolic changes were clearly linked to functional improvements in penile blood flow. Differences between rat and human lipoprotein metabolism are a limitation of this study. CONCLUSION: Dietary changes may have positive effects on penile hemodynamics in a rat model of hyperlipidemia-associated erectile dysfunction. Huang Y-C, Ho D-R, Lin J-H, et al. Dietary Modification Is Associated with Normalization of Penile Hemodynamics in Rats Fed a High-Fat Diet. J Sex Med 2019;16:791-802.
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Dieta Alta en Grasa , Hemodinámica/fisiología , Pene/irrigación sanguínea , Animales , Peso Corporal , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Disfunción Eréctil/fisiopatología , Hiperlipidemias/fisiopatología , Lipoproteínas LDL/metabolismo , Masculino , Músculo Liso/metabolismo , Óxido Nítrico Sintasa de Tipo I/metabolismo , Estrés Oxidativo/fisiología , Erección Peniana/fisiología , Distribución Aleatoria , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Complete urinary tract extirpation (CUTE) is a complex procedure with substantial risk for perioperative complications. The association between clinical characteristics and the risk of major postoperative complications has not been systematically investigated. OBJECTIVE: The aim of this study was to analyze the incidence and risks for major perioperative complications after CUTE. METHODS: Respective chart review of 81 patients with urothelial carcinoma (UC) who were treated with one-stage CUTE between January 2004 and December 2015. Fisher's exact test with Chi square and two-tailed t test were used in categorical and continuous variables, respectively. Univariable and multivariable logistic regression models were used to evaluate the probability of major complications. RESULTS: In this population, 53 (65.4%) patients had Clavien grade 0-2 complications ('no major complications') and 28 (34.6%) patients had Clavien grade 3-5 complications ('major complications'). Compared with the major complications group, patients in the no major complications group were younger, had lower Charlson Comorbidity Index (CCI), higher preoperative serum albumin, and shorter duration of hospitalization (p < 0.05 for all). Major complications were more common in low-volume surgeons (p = 0.002). On multivariate logistic regression analyses, CCI ≥ 5 (odds ratio [OR] 6.25, 95% confidence interval [CI] 1.42-27.47; p = 0.015) and surgery by a provider who performed three or fewer cases during the study interval (OR 13.4, 95% CI 2.20-80.89; p = 0.005) were independent predictors for major complications. CONCLUSIONS: High CCI should alert providers to increased probability of major complications, and warrant vigilant management after CUTE. Surgeon volume was inversely related to major postoperative complications.
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Fallo Renal Crónico/mortalidad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/mortalidad , Sistema Urinario/cirugía , Neoplasias Urológicas/mortalidad , Procedimientos Quirúrgicos Urológicos/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Fallo Renal Crónico/patología , Fallo Renal Crónico/cirugía , Masculino , Persona de Mediana Edad , Atención Perioperativa , Pronóstico , Factores de Riesgo , Tasa de Supervivencia , Taiwán/epidemiología , Factores de Tiempo , Sistema Urinario/patología , Neoplasias Urológicas/patología , Neoplasias Urológicas/cirugía , Adulto JovenRESUMEN
Diabetes is usually asymptomatic in its early stage. Early diagnosis may improve outcomes by enabling initiation of treatment before end organ damage has progressed. The aim of this study was to determine whether the clinical sign of phimosis with preputial fissures is predictive of type 2 diabetes in patients not previously diagnosed with diabetes. Twenty-eight patients with acquired phimosis and preputial fissures were collected prospectively. Twenty-eight controls with acquired phimosis without preputial fissures were selected. Statistically significant differences were found in body mass index, random plasma glucose, glucosuria and glycosylated haemoglobin levels, but not in age, family history of diabetes, hypertension and classical hyperglycaemic symptoms. Diabetes was confirmed in all 28 patients in the preputial fissures group, but only 2 (7.1%) patients in the non-preputial fissures group (p < 0.0001). In conclusion, phimosis with preputial fissures may be a specific sign of undiagnosed diabetes mellitus.
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Diabetes Mellitus Tipo 2/complicaciones , Prepucio/patología , Fimosis/etiología , Adulto , Anciano , Biomarcadores/sangre , Glucemia/análisis , Estudios de Casos y Controles , Circuncisión Masculina , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Prepucio/cirugía , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Fimosis/diagnóstico , Fimosis/cirugía , Valor Predictivo de las Pruebas , Estudios Prospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
The rare N-unsubstituted glucosamine (GlcNH(3)(+)) residues in heparan sulfate (HS) have important biological and pathophysiological roles. Because of their low natural abundance, the use of chemically generated, structurally defined, N-unsubstituted heparin/HS oligosaccharides can greatly contribute to the investigation of their natural role in HS. However, the sequencing of mixtures of chemically generated oligosaccharides presents major challenges due to the difficulties in separating isomers and the available detection methods. In this study, we developed and validated a simple and sensitive method for the sequence analysis of N-unsubstituted heparin/HS oligosaccharides. This protocol involves pH 4 nitrous acid (HNO(2)) degradation, size-exclusion HPLC and ion-pair reversed-phase liquid chromatography-ion trap/time-of-flight mass spectrometry (IPRP-LC-ITTOF MS). We unexpectedly found that absorbance at 232 nm (normally used for specific detection of C4-C5 unsaturated oligosaccharides) was, in most cases, still sufficiently sensitive to also simultaneously detect saturated oligosaccharides during HPLC, thus simplifying the positional analysis of GlcNH(3)(+)) residues. The IPRP-LC-ITTOF MS system can supply further structural information leading to full sequence determination of the original oligosaccharide. This new methodology has been used to separate and sequence a variety of chemically generated, N-unsubstituted dp6 species containing between 1 and 3 GlcNH(3)(+)) residues per oligosaccharide in different positional combinations. This strategy offers possibilities for the sequencing of natural N-unsubstituted oligosaccharides from HS and should also be applicable, with minor modification, for sequencing at N-sulfated residues using alternative pH 1.5 HNO(2) scission.
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Heparina/química , Heparitina Sulfato/química , Oligosacáridos/química , Secuencia de Carbohidratos , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Espectrometría de Masas , Datos de Secuencia MolecularRESUMEN
Bladder cancer is a urothelial malignancy. Bladder cancer starts in the urothelial cells lining the inside of the bladder. The 5-year recurrence rate for bladder cancer ranges from 31% to 78%, and the progression rate is approximately 45%. To treat bladder cancer, intravesical drug therapy is often used. Leonurus artemisia extract (LaE) was obtained from medicinal samples of Chinese motherwort Scientific Chinese Medicine; L. artemisia has various biological effects. This study investigated the impact of LaE on human bladder cancer cells (the BFTC-905 cell line) and the molecular mechanism underlying apoptosis resulting from the activation of cell signal transduction pathways in bladder cancer cells. A cell counting kit-8 (CCK-8) assay was used to determine the effect of LaE on cell growth. The effect of LaE on migration ability was observed using a wound healing assay. The effects of LaE on the cell cycle, reactive oxygen species production, and apoptosis were investigated. Western blot analysis detected apoptosis-related and mitogen-activated protein kinase signaling pathway-related protein concentrations. At non-toxic concentrations, LaE inhibited the proliferation of BFTC-905 cells in a concentration-dependent manner, and the half-maximal inhibitory concentration (IC50) was 24.08172 µg/µL. LaE impaired the migration ability of BFTC-905 cells. LaE arrested the cell cycle in the G1 and G0 phases, increased reactive oxygen species production, and induced apoptosis. LaE increased Bax and p-ERK concentrations and decreased Bcl-2, cleaved caspase-3, and p-p38 concentrations. No differences in PARP, C-PARP, vimentin, e-cadherin, p-JNK, or TNF-alpha concentrations were observed. These results suggest that LaE inhibits the proliferation of human bladder cancer cells. Moreover, the mitogen-activated protein kinase signaling pathway is involved in the inhibition of the proliferation of BFTC-905 cells.
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BACKGROUND: The majority of kidney recipients are a subset of chronic kidney disease. Our previous study demonstrated that the combination of Lactobacillus plantarum and Lactobacillus paracasei (Lm) had the highest clearance ability of uremic toxins and improved kidney function in a mouse model. This study aimed to evaluate Lm in improving graft function, effects on immunosuppressants, and safety in transplant recipients. METHODS: We retrospectively reviewed 24 patients. Twelve of them take Lm regularly; we compared the creatinine measurements and estimated glomerular filtration rate 3 months before and after Lm using a 2-tailed Wilcoxon matched-pairs signed-rank test while also evaluating the drug level of immunosuppressants and infection events. Other 12 patients who do not have Lm for evaluation of laboratory calibration and compared the proportion of improving creatinine using Fisher's exact test. RESULTS: The creatinine decreased by 0.06 mg/dL (P = .02), and the estimated glomerular filtration rate increased by 3.1 mL/min/1.73 m2 (P = .03) after Lm supplementation. This pilot study revealed the association of higher incidence (odds ratio 13.3, 95% CI 1.64-77.2, P = .01) of decreasing creatinine in transplant recipients using Lm. Furthermore, results showed a trend of higher trough levels of tacrolimus and sirolimus, which might provide a potential strategy for reducing the dosages of immunosuppressants. CONCLUSION: Our findings revealed an association between a higher incidence of decreasing creatinine in kidney transplant recipients using Lm, which may also provide a potential strategy for reducing the acquired dosages of immunosuppressants.
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Trasplante de Riñón , Animales , Ratones , Humanos , Trasplante de Riñón/efectos adversos , Proyectos Piloto , Estudios Retrospectivos , Creatinina , Inmunosupresores/efectos adversos , Tacrolimus , Tasa de Filtración Glomerular , Rechazo de Injerto/epidemiologíaRESUMEN
Currently, the coronavirus disease 2019 (COVID-19) pandemic is still an ongoing and constant medical issue, and with upcoming new variants, vaccinations and boosters remain important. The safety of vaccines in patients after kidney transplantation is an essential problem, with thrombosis being one of the severe side effects and vaccine-induced immune thrombotic thrombocytopenia (VITT) revealed as the most commonly reported syndrome for thromboembolic events following COVID-19 vaccination. Here, we present two cases of kidney transplantation developing pulmonary embolism post-Moderna vaccination within 30 days without thrombocytopenia. The first case was a 52-year-old man with history of type II diabetes, hypertension and hyperlipidemia who had had cadaveric kidney transplantation in September 2008, where right leg swelling with claudication occurred 23 days after the second Moderna vaccination. The second case was a 57-year-old man with history of type II diabetes and glaucoma who had had living-related kidney transplantation in April 2013 and then complained of exertional dyspnea 26 days after administration of the third Moderna vaccine. The advantages of vaccination even in immunocompromised patients far outweigh the disadvantages, although clinicians must understand the risks of deep-vein thrombosis or even pulmonary embolism for such patients, which might not occur after just the first vaccination.
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BACKGROUND: While epidemiological studies have clearly documented that smoking cessation significantly enhances sexual health, the underlying mechanism remains largely unknown. Thus, we wished to explore possible mechanisms by using a rat model of smoking-associated erectile dysfunction (ED). METHODS: Forty 8-week old male Sprague-Dawley rats were divided into 4 groups. Ten rats were exposed only to room air (N group). The remaining 30 rats were passively exposed to cigarette smoke over a 12-week period. At the end of 12 weeks, the smoking (S, n=10) group underwent immediate erectile function testing and were sacrificed. The remaining 20 rats were exposed to room air only for 4 (Q4W, n=10) or 8 (Q8W, n=10) weeks and then underwent erectile function testing and sacrifice. Erectile function was evaluated by measuring intracavernous pressure (ICP) and mean arterial pressure (MAP). After blood collection for serum testosterone determination, rats were sacrificed to obtain corporal tissue for immunohistochemistry. RESULTS: Mean ICP/MAP ratio was significantly lower in the S group compared to the N and Q8W groups (0.52±0.11, 0.94±0.05, and 0.94±0.12, respectively, P=0.0189). Smooth muscle/collagen ratio was also significantly lower in the S group compared to the N and Q8W groups (11.8±0.94, 17.5±1.82, and 16.4±0.60, respectively, P=0.0008). Oxidative stress and apoptotic indices were significantly higher in the S group compared to the N and Q8W groups. Neuronal and endothelial nitric oxide synthases were significantly less expressed in the S group compared to the N and Q8W groups. CONCLUSIONS: Smoking cessation is associated with partial recovery of penile hemodynamics in a rat model of smoking associated ED.
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BACKGROUND: Mutations in the gene encoding bone morphogenetic protein receptor type 2 (BMPR2) are the most common genetic risk factors underlying pulmonary arterial hypertension (PAH). However, the features of PAH-related BMPR2 rare variants remain unclear. We propose that the discrepancy of BMPR2 rare variants landscape between patients with PAH and reference population would be important to address the genetic background of PAH-related variants. METHODS: We genotyped BMPR2 rare variants in 670 Chinese patients with pulmonary arterial hypertension. The BMPR2 rare variants were screened in 10,508 reference people from two exome databases. RESULTS: The prevalence of rare BMPR2 variants in patients with PAH was significantly higher compared to the reference population (21.5%, 144/670 vs 0.87%, 91/10508, p = 1.3 × 10-118). In patients with PAH, 49% of identified BMPR2 rare variants were loss-of-function or splicing. These BMPR2 rare variants were only observed in 1% of the reference population (p = 9.0 × 10-12). Arg491, which is absent in the reference population, represented as hot-spot site (14.6%, 21/144) in PAH patients. BMPR2 missense mutations in PAH patients were more likely distributed in extracellular ligand-binding domain (ECD, 29.7% vs 11.1%, p < 0.001). Compared with Non-PAH-related variations, PAH-related missense variants tend to alter the amino acid electric status (51.4% vs 23.3%, p < 0.001). CONCLUSIONS: BMPR2 variants located in extracellular ligand-binding domain or altered the amino acid electric status are more pathogenic.
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Hipertensión Arterial Pulmonar , Pueblo Asiatico , Receptores de Proteínas Morfogenéticas Óseas de Tipo II/genética , Exoma , Hipertensión Pulmonar Primaria Familiar/diagnóstico , Hipertensión Pulmonar Primaria Familiar/epidemiología , Hipertensión Pulmonar Primaria Familiar/genética , Humanos , MutaciónRESUMEN
BACKGROUND: Pulmonary arterial hypertension (PAH) is a severe progressive disease with systemic metabolic dysregulation. Monocrotaline (MCT)-induced and hypoxia-induced pulmonary hypertension (PH) rodent models are the most widely used preclinical models, however, whether or not these preclinical models recapitulate metabolomic profiles of PAH patients remain unclear. METHODS: In this study, a targeted metabolomics panel of 126 small molecule metabolites was conducted. We applied it to the plasma of the 2 preclinical rodent models of PH and 30 idiopathic pulmonary arterial hypertension (IPAH) patients as well as 30 healthy controls to comparatively assess the metabolomic profiles of PAH patients and rodent models. RESULTS: Significantly different metabolomics profiling and pathways were shown among the 2 classical rodent models and IPAH patients. Pathway analysis demonstrated that methionine metabolism and urea cycle metabolism were the most significant pathway involved in the pathogenesis of hypoxia-induced PH model and MCT-induced model, respectively, and both of them were also observed in the dysregulated pathways in IPAH patients. CONCLUSIONS: These 2 models may develop PAH through different metabolomic pathways and each of the 2 classical PH model resembles IPAH patients in certain aspects.
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Hipertensión Pulmonar Primaria Familiar/sangre , Hipertensión Pulmonar/sangre , Metabolómica , Metionina/sangre , Urea/sangre , Adulto , Animales , Biomarcadores/sangre , Estudios de Casos y Controles , Modelos Animales de Enfermedad , Hipertensión Pulmonar Primaria Familiar/diagnóstico , Hipertensión Pulmonar Primaria Familiar/etiología , Femenino , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/etiología , Hipoxia/complicaciones , Masculino , Monocrotalina , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: Comprehensively analysis the correlation and the law of variation between the height of a person and the length of his/her footprint. METHODS: Collecting footprint samples of those people of different age and sex from different area all of our country, and adopt the regressive analysis method to study these samples. RESULTS: A sum of useful data and regressive equation were obtained. CONCLUSION: The correlation between the height of a person and the length of his/her footprint is obviously, the approximate height of a person can be reckoned according to thelength of his/her footprints.
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Estatura , Pie/anatomía & histología , Adolescente , Adulto , Factores de Edad , Femenino , Medicina Legal/métodos , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Factores Sexuales , Zapatos/clasificaciónRESUMEN
OBJECTIVE: Comprehensively analysis the correlation and the law of variation between the height of a person and the length of his/her handprint. METHODS: Collecting handprint samples of those people of different age and sex from different area all of our country, and adopt the regressive analysis method to study these samples. RESULTS: A sum of useful data and regressive equation were obtained. CONCLUSION: The correlation between the height of a person and the length of his/her handprint is obviously, the approximate height of a person can be reckoned according to the length of his/her handprints.
Asunto(s)
Estatura , Mano/anatomía & histología , Adolescente , Adulto , Factores de Edad , Femenino , Dedos/anatomía & histología , Medicina Legal/métodos , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Factores SexualesRESUMEN
In-situ annealing at a high temperature of 640°C was performed for a low temperature grown Si capping layer, which was grown at 300°C on SiGe self-assembled quantum dots with a thickness of 50 nm. Square nanopits, with a depth of about 8 nm and boundaries along ã110ã, are formed in the Si capping layer after annealing. Cross-sectional transmission electron microscopy observation shows that each nanopit is located right over one dot with one to one correspondence. The detailed migration of Si atoms for the nanopit formation is revealed by in-situ annealing at a low temperature of 540°C. The final well-defined profiles of the nanopits indicate that both strain energy and surface energy play roles during the nanopit formation, and the nanopits are stable at 640°C. A subsequent growth of Ge on the nanopit-patterned surface results in the formation of SiGe quantum dot molecules around the nanopits.