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BACKGROUND: Despite the frequent diagnostic delays of rare neurologic diseases (RND), it remains difficult to study RNDs and their comorbidities due to their rarity and hence the statistical underpowering. Affecting one to two in a million annually, stiff person syndrome (SPS) is an RND characterized by painful muscle spasms and rigidity. Leveraging underutilized electronic health records (EHR), this study showcased a machine-learning-based framework to identify clinical features that optimally characterize the diagnosis of SPS. METHODS: A machine-learning-based feature selection approach was employed on 319 items from the past medical histories of 48 individuals (23 with a diagnosis of SPS and 25 controls) with elevated serum autoantibodies against glutamic-acid-decarboxylase-65 (anti-GAD65) in Dartmouth Health's EHR to determine features with the highest discriminatory power. Each iteration of the algorithm implemented a Support Vector Machine (SVM) model, generating importance scores-SHapley Additive exPlanation (SHAP) values-for each feature and removing one with the least salient. Evaluation metrics were calculated through repeated stratified cross-validation. RESULTS: Depression, hypothyroidism, GERD, and joint pain were the most characteristic features of SPS. Utilizing these features, the SVM model attained precision of 0.817 (95% CI 0.795-0.840), sensitivity of 0.766 (95% CI 0.743-0.790), F-score of 0.761 (95% CI 0.744-0.778), AUC of 0.808 (95% CI 0.791-0.825), and accuracy of 0.775 (95% CI 0.759-0.790). CONCLUSIONS: This framework discerned features that, with further research, may help fully characterize the pathologic mechanism of SPS: depression, hypothyroidism, and GERD may respectively represent comorbidities through common inflammatory, genetic, and dysautonomic links. This methodology could address diagnostic challenges in neurology by uncovering latent associations and generating hypotheses for RNDs.
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Registros Electrónicos de Salud , Aprendizaje Automático , Síndrome de la Persona Rígida , Humanos , Síndrome de la Persona Rígida/diagnóstico , Síndrome de la Persona Rígida/inmunología , Síndrome de la Persona Rígida/epidemiología , Registros Electrónicos de Salud/estadística & datos numéricos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Máquina de Vectores de Soporte , Prueba de Estudio Conceptual , Glutamato Descarboxilasa/inmunología , Enfermedades Raras/diagnóstico , Autoanticuerpos/sangreRESUMEN
BACKGROUND AND HYPOTHESIS: Up to 43% of people with schizophrenia have a lifetime cannabis use disorder (CUD). Tetrahydrocannabinol (THC) has been shown to exacerbate psychosis in a dose-dependent manner, but little research has assessed its effects on schizophrenia and co-occurring CUD (SCZ-CUD). In this double-dummy, placebo-controlled trial (total nâ =â 130), we hypothesized that a modest dose of THC would worsen cognitive function but not psychosis. STUDY DESIGN: Effects of single-dose oral THC (15 mg dronabinol) or smoked 3.5% THC cigarettes vs placebo in SCZ-CUD or CUD-only on positive and negative symptoms of schizophrenia (only for SCZ-CUD), cognition, and drug experiences assessed several hours after drug administration. SCZ-only and healthy control participants were also assessed. STUDY RESULTS: Drug liking was higher in THC groups vs placebo. Neither smoked THC nor oral dronabinol predicted positive or negative symptom subscale scores 2 and 5 h, respectively, after drug exposure in SCZ-CUD participants. The oral dronabinol SCZ-CUD group, but not smoked THC SCZ-CUD group, performed worse than placebo on verbal learning (Bâ =â -9.89; 95% CI: -16.06, -3.18; Pâ =â .004) and attention (Bâ =â -0.61; 95% CI: -1.00, -0.23; Pâ =â .002). Every 10-point increment in serum THCâ +â THCC ng/ml was associated with increased negative symptoms (0.40 points; 95% CI: 0.15, 0.65; Pâ =â .001; subscale ranges 7-49) and trends were observed for worse positive symptoms and performance in verbal learning, delayed recall, and working memory. CONCLUSIONS: In people with SCZ-CUD, a modest single dose of oral THC was associated with worse cognitive functioning without symptom exacerbation several hours after administration, and a THC dose-response effect was seen for negative symptoms.
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Artificial intelligence (AI) is rapidly being introduced into the clinical workflow of many specialties. Despite the need to train physicians who understand the utility and implications of AI and mitigate a growing skills gap, no established consensus exists on how to best introduce AI concepts to medical students during preclinical training. This study examined the effectiveness of a pilot Digital Health Scholars (DHS) non-credit enrichment elective that paralleled the Dartmouth Geisel School of Medicine's first-year preclinical curriculum with a focus on introducing AI algorithms and their applications in the concurrently occurring systems-blocks. From September 2022 to March 2023, ten self-selected first-year students enrolled in the elective curriculum run in parallel with four existing curricular blocks (Immunology, Hematology, Cardiology, and Pulmonology). Each DHS block consisted of a journal club, a live-coding demonstration, and an integration session led by a researcher in that field. Students' confidence in explaining the content objectives (high-level knowledge, implications, and limitations of AI) was measured before and after each block and compared using Mann-Whitney U tests. Students reported significant increases in confidence in describing the content objectives after all four blocks (Immunology: U = 4.5, p = 0.030; Hematology: U = 1.0, p = 0.009; Cardiology: U = 4.0, p = 0.019; Pulmonology: U = 4.0, p = 0.030) as well as an average overall satisfaction level of 4.29/5 in rating the curriculum content. Our study demonstrates that a digital health enrichment elective that runs in parallel to an institution's preclinical curriculum and embeds AI concepts into relevant clinical topics can enhance students' confidence in describing the content objectives that pertain to high-level algorithmic understanding, implications, and limitations of the studied models. Building on this elective curricular design, further studies with a larger enrollment can help determine the most effective approach in preparing future physicians for the AI-enhanced clinical workflow.
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Inteligencia Artificial , Estudiantes de Medicina , Humanos , Proyectos Piloto , Curriculum , Atención a la SaludRESUMEN
Apples are widely cultivated in the Republic of Korea and are preferred by consumers for their sweetness. Soluble solid content (SSC) is measured non-destructively using near-infrared (NIR) spectroscopy; however, the SSC measurement error increases with the change in apple size since the distance between the light source and the near-infrared sensor is fixed. In this study, spectral characteristics caused by the differences in apple size were investigated. An optimal SSC prediction model applying partial least squares regression (PLSR) to three measurement conditions based on apple size was developed. The three optimal measurement conditions under which the Vis/NIR spectrum is less affected by six apple size levels (Levels I-VI) were selected. The distance from the apple center to the light source and that to the sensor were 125 and 75 mm (Distance 1), 123 and 75 mm (Distance 2), and 135 and 80 mm (Distance 3). The PLSR model applying multiplicative scatter correction pretreatment under Distance 3 measurement conditions showed the best performance for Level IV-sized apples (Rpre2 = 0.91, RMSEP = 0.508 °Brix). This study shows the possibility of improving the SSC prediction performance of apples by adjusting the distance between the light source and the NIR sensor according to fruit size.
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Evidence indicating abnormal functional connectivity (FC) among the cortex, thalamus, and cerebellum in schizophrenia patients has increased. However, the role of the thalamus and cerebellum when integrated into intrinsic networks and how those integrated networks interact in schizophrenia patients are largely unknown. We generated an integrative network map by merging thalamic and cerebellar network maps, which were parcellated using a winner-take-all approach, onto a cortical network map. Using cognitive networks, the default mode network (DMN), the dorsal attention network (DAN), the salience network (SAL), and the central executive network (CEN) as regions of interest, the FC of 48 schizophrenia patients was compared with that of 57 healthy controls (HCs). The association between abnormal FC and cognitive impairment was also investigated in patients. FC was lower between the SAL-CEN, SAL-DMN, and DMN-CEN and within-CEN in schizophrenia patients than in HCs. Hypoconnectivity between the DMN-CEN was correlated with impaired cognition in schizophrenia patients. Our findings broadly suggest the plausible role of the thalamus and cerebellum in integrative intrinsic networks in patients, which may contribute to the disrupted triple network and cognitive dysmetria in schizophrenia.
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Background: While online reviews from physician rating websites are increasingly utilized by healthcare providers to better understand patient needs, it remains difficult to objectively identify areas for improvement in providing psychiatric care. Objectives: To quantitatively characterize the sentiment of online written reviews of psychiatrists to determine clinical attributes that can be strengthened to improve psychiatrists' therapeutic alliance with their patients. Materials and methods: Sentiment scores of 6,400 written reviews of 400 US-based psychiatrists on a US-based online physician rating website were obtained through a natural-language-processing-based sentiment analysis. Relationships among sentiment scores, average star ratings, and demographics were examined. Linguistic analyses determined words and bigrams that were highly associated with reviews with the most positive and negative sentiment. Findings: Sentiment scores were significantly correlated with average star ratings of the psychiatrists (R = 0.737, p < 0.001). Psychiatrists who were younger (< 56 years old) and/or practiced in the Northeast had significantly higher average star ratings than those older and/or practicing in the Southwest. Frequency analysis showed that positive reviews most frequently contained "time" (N = 1,138) and "caring" (N = 784) while negative reviews most frequently contained "medication" (N = 495) and "time" (N = 379). Logistic regression analysis revealed that reviews were more likely to be considered positive when they included "great listener" (OR = 16.89) and "comfortable" (OR = 10.72) and more likely to be negative when they included "meds" (OR = 0.55) and "side effect" (OR = 0.59). Conclusion: Psychiatrists who are younger and located in the Northeast receive more positive reviews; there may be potential for demographic bias among patient reviewers. Patients positively rate psychiatrists who make them feel heard and comfortable but negatively rate encounters centered around medications and their side effects. Our study lends quantitative evidence to support the importance of thorough and empathetic communication of psychiatrists in building a strong therapeutic alliance.
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Due to climate change, soil moisture may increase, and outflows could become more frequent, which will have a considerable impact on crop growth. Crops are affected by soil moisture; thus, soil moisture prediction is necessary for irrigating at an appropriate time according to weather changes. Therefore, the aim of this study is to develop a future soil moisture (SM) prediction model to determine whether to conduct irrigation according to changes in soil moisture due to weather conditions. Sensors were used to measure soil moisture and soil temperature at a depth of 10 cm, 20 cm, and 30 cm from the topsoil. The combination of optimal variables was investigated using soil moisture and soil temperature at depths between 10 cm and 30 cm and weather data as input variables. The recurrent neural network long short-term memory (RNN-LSTM) models for predicting SM was developed using time series data. The loss and the coefficient of determination (R2) values were used as indicators for evaluating the model performance and two verification datasets were used to test various conditions. The best model performance for 10 cm depth was an R2 of 0.999, a loss of 0.022, and a validation loss of 0.105, and the best results for 20 cm and 30 cm depths were an R2 of 0.999, a loss of 0.016, and a validation loss of 0.098 and an R2 of 0.956, a loss of 0.057, and a validation loss of 2.883, respectively. The RNN-LSTM model was used to confirm the SM predictability in soybean arable land and could be applied to supply the appropriate moisture needed for crop growth. The results of this study show that a soil moisture prediction model based on time-series weather data can help determine the appropriate amount of irrigation required for crop cultivation.
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Glycine max , Memoria a Corto Plazo , Cambio Climático , Redes Neurales de la Computación , SueloRESUMEN
Neuroimaging studies have revealed how intrinsic dysconnectivity among cortical regions of the mentalizing network (MENT) and the mirror neuron system (MNS) could explain the theory of mind (ToM) deficit in schizophrenia patients. However, despite the concurrent involvement of the cerebellum with the cortex in social cognition, the dysfunction in intrinsic interplay between the cerebellar nodes of MENT/MNS and the cortex in schizophrenia patients remains unknown. Thus, we aimed to investigate whether resting-state cerebello-cortical dysconnectivity exists in first-episode psychosis (FEP) patients in relationship with their ToM deficit. A total of 37 FEP patients and 80 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. Using a priori-defined cerebellar seeds that functionally connect to the MENT (right crus II) and MNS (right crus I), we compared cerebello-cortical functional connectivities (FCs) in FEP patients and HCs. Correlations between cerebello-parietal connectivities and ToM performance were investigated in FEP patients. FEP patients showed hyperconnectivity between the right crus II and anterior cingulate gyrus and between the right crus I and supplementary motor area, bilateral postcentral gyrus, and right central/parietal operculum (CO/PO). Hypoconnectivity was found between the right crus II and left supramarginal gyrus (SMG) in FEP patients. FCs between the right crus II and left SMG and between the right crus I and right CO/PO were significantly correlated with ToM scores in FEP patients. In accordance with the "cognitive dysmetria" hypothesis, our results highlight the importance of cerbello-cortical dysconnectivities in understanding social cognitive deficits in schizophrenia patients.
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BACKGROUND: Extracellular vesicle (EV)-mimetic nanovesicles (NVs) from embryonic stem cells have been observed to stimulate neurovascular regeneration in the streptozotocin-induced diabetic mouse. Pericytes play important roles in maintaining penile erection, yet no previous studies have explored the effects of pericyte-derived NVs (PC-NVs) in neurovascular regeneration in the context of erectile dysfunction. AIM: To investigate the potential effect of PC-NVs in neurovascular regeneration. METHODS: PC-NVs were isolated from mouse cavernous pericytes, and neurovascular regeneration was evaluated in an in vitro study. Twelve-week-old C57BL/6J mice were used to prepare cavernous nerve injury model. Erectile function evaluation, histologic examination of the penis, and Western blots were assessed 2 weeks after model creation and PC-NVs treatment. OUTCOMES: The main outcomes of this study are PC-NVs characterization, intracavernous pressure, neurovascular regeneration in the penis, and in vitro functional evaluation. RESULTS: The PC-NVs were extracted and characterized by cryotransmission electron microscopy and EV-positive (Alix, TSG101, CD81) and EV-negative (GM130) markers. In the in vivo studies, PC-NVs successfully improved erectile function in cavernous nerve injury mice (â¼82% of control values). Immunofluorescence staining showed significant increases in pericytes, endothelial cell, and neuronal contents. In the in vitro studies, PC-NVs significantly increased mouse cavernous endothelial cells tube formation, Schwann cell migration, and dorsal root ganglion and major pelvic ganglion neurite sprouting. Finally, Western blot analysis revealed that PC-NVs upregulated cell survival signaling (Akt and eNOS) and induced the expression of neurotrophic factors (brain-derived neurotrophic factor, neurotrophin-3, and nerve growth factor). CLINICAL IMPLICATIONS: PC-NVs may be used as a strategy to treat erectile dysfunction after radical prostatectomy or in men with neurovascular diseases. STRENGTHS & LIMITATIONS: We evaluated the effect of PC-NVs in vitro and in a mouse nerve injury model, cavernous nerve injury. Additional studies are necessary to determine the detailed mechanisms of neurovascular improvement. Further study is needed to test whether PC-NVs are also effective when given weeks or months after nerve injury. CONCLUSION: PC-NVs significantly improved erectile function by enhancing neurovascular regeneration. Local treatment with PC-NVs may represent a promising therapeutic strategy for the treatment of neurovascular diseases. Yin GN, Park S-H, Ock J, et al. Pericyte-Derived Extracellular Vesicle-Mimetic Nanovesicles Restore Erectile Function by Enhancing Neurovascular Regeneration in a Mouse Model of Cavernous Nerve Injury. J Sex Med 2020;17:2118-2128.
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Disfunción Eréctil , Vesículas Extracelulares , Animales , Modelos Animales de Enfermedad , Células Endoteliales , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Regeneración Nerviosa , Erección Peniana , Pene , Pericitos , RegeneraciónRESUMEN
INTRODUCTION: Diabetic erectile dysfunction is a disease mostly of vascular origin and men with diabetic erectile dysfunction respond poorly to oral phosphodiesterase-5 inhibitors. Hepatocyte growth factor (HGF) is a pleiotropic factor that plays an essential role in the regulation of cell proliferation, survival, and angiogenesis. AIM: To determine the effectiveness of recombinant human (rh)-HGF in restoring erectile function in diabetic mice. METHODS: Four groups of mice were used: control non-diabetic mice and streptozotocin-induced diabetic mice receiving two successive intracavernous injections of phosphate buffered saline (days -3 and 0), a single intracavernous injection of rh-HGF (day 0), or two successive intracavernous injections of rh-HGF (days -3 and 0). We also examined the effect of rh-HGF in primary cultured mouse cavernous endothelial cells and in major pelvic ganglion culture in vitro, which was incubated under a normal-glucose (5 mmol/L) or a high-glucose (30 mmol/L) condition. MAIN OUTCOME MEASURES: Two weeks after treatment, we measured erectile function by electrical stimulation of the cavernous nerve and the penis was harvested for histologic studies. RESULTS: Repeated intracavernous injections of rh-HGF protein induced significant restoration of erectile function in diabetic mice (89-100% of control values), whereas a single intracavernous injection of rh-HGF protein elicited modest improvement. Rh-HGF significantly induced phosphorylation of its receptor c-Met, increased the content of endothelial cells and smooth muscle cells, and decreased the generation of reactive oxygen species (superoxide anion and peroxynitrite) and extravasation of oxidized low-density lipoprotein in diabetic mice. Under the high-glucose condition, rh-HGF protein also promoted tube formation in mouse cavernous endothelial cells and enhanced neurite sprouting in major pelvic ganglion culture in vitro. CONCLUSION: The dual angiogenic and neurotrophic effects of HGF could open a new avenue through which diabetic erectile dysfunction can be treated.
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Disfunción Eréctil/tratamiento farmacológico , Factor de Crecimiento de Hepatocito/farmacología , Erección Peniana/efectos de los fármacos , Animales , Proliferación Celular/fisiología , Diabetes Mellitus Experimental/fisiopatología , Células Endoteliales/citología , Células Endoteliales/fisiología , Endotelio/metabolismo , Disfunción Eréctil/fisiopatología , Humanos , Inyecciones Intralesiones , Lipoproteínas LDL/metabolismo , Masculino , Ratones Endogámicos C57BL , Óxido Nítrico Sintasa de Tipo III/metabolismo , Pene/irrigación sanguínea , Inhibidores de Fosfodiesterasa 5/farmacología , Fosforilación/fisiología , Ratas Sprague-Dawley , Proteínas Recombinantes/farmacología , Regeneración/fisiologíaRESUMEN
BACKGROUND: Acute myocardial infarction (AMI) is a risk factor for contrast-induced nephropathy (CIN). We investigated whether pretreatment with statin, N-acetylcysteine (NAC) and sodium bicarbonate (NaHCO3) reduces the risk of CIN. METHODS: We conducted a prospective trial and enrolled a total of 334 ST-segment elevation myocardial infarction (STEMI) patients. Patients were divided into four groups: Group I (statin 40mg), Group II (statin 80mg), Group III (statin 80mg plus NAC 1200mg) and Group IV (regimen of group III plus NaHCO3 154mEq/L). CIN was defined as ≥25% or ≥0.5mg/dL increase in serum creatinine from the baseline within the 72h after PCI. RESULTS: CIN occurred in 72 (21.6%) patients. The incidence of CIN was the lowest in the group III (14.3%), and multivariate analysis showed the lower incidence of CIN in group III compared to Group I [odds ratio (OR) 0.29, 95% confidence interval (CI) 0.13-0.64, p=0.002]. Admission hyperglycemia [(AHG)>198mg/dL] (OR 2.20, 95% Cl 1.20-3.68, p=0.011) and the use of intra-aortic balloon pump (IABP) (OR 4.20, 95% CI 1.38-12.78, p=0.016) were independent predictors for CIN. The CIN (OR 9.00, 95% CI 1.30-62.06, p=0.026) was an independent predictor for in-hospital mortality. CONCLUSIONS: Combination of high-dose statin plus NAC was associated with lower incidence of CIN in patients with STEMI who underwent primary PCI compared to statin only.
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Acetilcisteína/administración & dosificación , Lesión Renal Aguda/prevención & control , Medios de Contraste/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Intervención Coronaria Percutánea/efectos adversos , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/diagnóstico por imagen , Anciano , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/cirugía , Resultado del TratamientoRESUMEN
OBJECTIVES: To determine the molecular events related to penile erection in the corpus cavernosum tissue of mice after electrical stimulation of the cavernous nerve. METHODS: Twelve-week-old male C57BL/6 mice were used in this study. Electrical stimulation of the cavernous nerve was carried out to induce penile erection. Corpus cavernosum tissues were then harvested to determine the effect of nerve-induced penile erection on signaling pathway involved in angiogenesis (vascular endothelial growth factor, hepatocyte growth factor, angiopoietin-1, matrix metalloproteinase 2, and matrix metalloproteinase 9), cell survival and proliferation (phosphatidylinositol 3-kinase, phospho-Akt/Akt, and phospho-ERK/ERK), and tissue fibrosis (phospho-Smad2/Smad2, phospho-Smad3/Smad3, and plasminogen activator inhibitor-1). RESULTS: Cavernous nerve stimulation enhanced the expression of factors involved in angiogenesis (vascular endothelial growth factor, hepatocyte growth factor, angiopoietin-1, matrix metalloproteinase 2, and metalloproteinase 9), and activated intracellular signaling mediators related to cell survival and proliferation (phosphatidylinositol 3-kinase, phospho-Akt/Akt, and phospho-ERK/ERK), while suppressing the pathways involved in tissue fibrosis (phospho-Smad2/Smad2, phospho-Smad3/Smad3, and plasminogen activator inhibitor-1). CONCLUSIONS: Penile erection in mice is accompanied by the activation of a cascade of signaling pathways involved in angiogenesis, cell survival and proliferation, and antifibrosis. The present results might provide a theoretical and molecular basis for understanding the importance of penile rehabilitation and subsequent restoration of nocturnal or sexually-mediated penile erections.
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Neovascularización Fisiológica , Erección Peniana/fisiología , Pene/metabolismo , Animales , Disfunción Eréctil , Humanos , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
PURPOSE: We examined whether and how Sac-1004, a vascular leakage blocker, would restore erectile function in an animal model of diabetic erectile dysfunction. MATERIALS AND METHODS: Eight-week-old C57BL/6J mice were used. Diabetes was induced by intraperitoneal injection of streptozotocin. Eight weeks after diabetes induction the animals were divided into 6 groups, including controls, diabetic mice that received repeat intracavernous injections of phosphate buffered saline (20 µl) on days -3 and 0, and diabetic mice that received repeat intracavernous injections of Sac-1004 on days -3 and 0 (1, 2, 5 and 10 µg, respectively, in 20 µl phosphate buffered saline). One week after injection erectile function was measured by cavernous nerve stimulation. The penis was then harvested for histological examinations and Western blot analysis. RESULTS: Local delivery of Sac-1004 in the corpus cavernosum restored erectile function in diabetic mice. The highest erectile response was noted at a dose of 5 µg with a response comparable to that in the control group. Sac-1004 significantly increased cavernous endothelial and smooth muscle contents, and induced endothelial nitric oxide synthase phosphorylation (Ser1177). Sac-1004 decreased extravasation of oxidized low density lipoprotein by restoring endothelial cell-cell junction proteins and pericyte content. Sac-1004 also promoted tube formation in primary cultured mouse cavernous endothelial cells in vitro. Sac-1004 mediated cavernous angiogenesis and erectile function recovery was abolished by inhibiting angiopoietin-1-Tie2 signaling with soluble Tie2 antibody. CONCLUSIONS: With the effects of angiogenesis and antipermeability Sac-1004 reestablishes structural and functional cavernous sinusoids. This is highly promising for future treatment of erectile dysfunction from vascular causes.
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Inductores de la Angiogénesis/uso terapéutico , Diabetes Mellitus Experimental/complicaciones , Disfunción Eréctil/tratamiento farmacológico , Saponinas/uso terapéutico , Inductores de la Angiogénesis/farmacología , Animales , Diabetes Mellitus Experimental/inducido químicamente , Disfunción Eréctil/etiología , Masculino , Ratones , Ratones Endogámicos C57BL , Neovascularización Fisiológica/efectos de los fármacos , Saponinas/farmacología , Estreptozocina , Resultado del TratamientoRESUMEN
CASE: An 88-year-old woman visited us with a complaint of total urinary leak, and was diagnosed as having vesicovaginal fistula after pessary insertion. A part of pessary was seen in the bladder and it was removed by cutting pessary in the vagina. And then she was managed by antibiotics, local estrogen cream and Foley catheter indwelling. OUTCOME: Vesicovaginal fistula was healed completely. This is the first successful case of conservative treatment of vesicovaginal fistula caused by vaginal pessary without surgical repair. CONCLUSION: The conservative approach could be an option of treatments of vesicovaginal fistula caused by neglected vaginal pessary.
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Pesarios/efectos adversos , Fístula Vesicovaginal/etiología , Fístula Vesicovaginal/terapia , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Terapia Combinada , Quimioterapia Combinada , Estrógenos/uso terapéutico , Femenino , Humanos , Cateterismo Urinario , Fístula Vesicovaginal/diagnósticoRESUMEN
PURPOSE: Electroporation is known to enhance the efficiency of gene transfer through a transient increase in cell membrane permeability. The aim of this study was to determine the optimal conditions for in vivo electroporation-mediated gene delivery into mouse corpus cavernosum. MATERIALS AND METHODS: Diabetes was induced in C57BL/6 mice by intraperitoneal injections of streptozotocin. After intracavernous injection of pCMV-Luc (100 µg/40 µL), different electroporation settings (5-50 V, 8-16 pulses with a duration of 40-100 ms) were applied to the penis to establish the optimal conditions for electroporation. Gene expression was evaluated by luciferase assay. We also assessed the undesired consequences of electroporation by visual inspection and hematoxylin-eosin staining of penile tissue. RESULTS: Electroporation profoundly induced gene expression in the corpus cavernosum tissue of normal mice in a voltage-dependent manner. We observed electrical burn scars in the penis of normal mice who received electroporation with eight 40-ms pulses at a voltage of 50 V and sixteen 40-ms pulses, eight 100-ms pulses, and sixteen 100-ms pulses at a voltage of 30 V. No detectable burn scars were noted in normal mice stimulated with eight 40-ms pulses at a voltage of 30 V. Electroporation also significantly induced gene expression in diabetic mice stimulated with 40-ms pulse at a voltage of 30 V without injury to the penis. CONCLUSIONS: We have established the optimal electroporation conditions for maximizing gene transfer into the corpus cavernosum of mice while avoiding damage to the erectile tissue. The electroporation-mediated gene delivery technique will be a valuable tool for gene therapy in the field of erectile dysfunction.
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Electroporación/métodos , Disfunción Eréctil/terapia , Terapia Genética/métodos , Pene/fisiopatología , Animales , Diabetes Mellitus Experimental/complicaciones , Expresión Génica , Técnicas de Transferencia de Gen , Genes Reporteros , Luciferasas/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Erección Peniana/fisiología , TransfecciónRESUMEN
OBJECTIVES: To investigate bacterial infection in the seminal vesicles by bacteriological examination and radionuclide imaging in men with chronic prostatitis. METHODS: The study included 50 patients with chronic prostatitis who showed hot uptake in seminal vesicles on Tc-99m ciprofloxacin imaging and eight patients who did not show hot uptake. The evaluation included the National Institutes of Health Chronic Prostatitis Symptom Index and four-glass test. In all participants, transperineal aspiration of seminal vesicle fluid under the guidance of transrectal ultrasonography and bacteriological examination was carried out. RESULTS: Of the 50 patients who showed hot uptake in the seminal vesicles on the isotope study, microorganisms were isolated from the seminal vesicle fluid in 17 patients (positive predictive value, 34%). The most common causative organisms were Escherichia coli in 13 patients (26%), followed by coagulase-negative Staphylococcus species in two patients (4%), Enterococcus faecalis in one patient (2%) and Chlamydia trachomatis in one patient (2%). No microorganisms were isolated in the eight patients who did not show hot uptake in the seminal vesicles (negative predictive value, 100%). However, there were no significant differences in National Institutes of Health Chronic Prostatitis Symptom Index total scores and subscores between the study groups. CONCLUSIONS: Chronic bacterial seminal vesiculitis might simultaneously affect a considerable portion of patients with chronic prostatitis, although the clinical implication of the disease remains to be further investigated.
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Infecciones Bacterianas/diagnóstico por imagen , Prostatitis/diagnóstico por imagen , Vesículas Seminales/diagnóstico por imagen , Adulto , Enfermedad Crónica , Ciprofloxacina/análogos & derivados , Humanos , Masculino , Persona de Mediana Edad , Compuestos de Organotecnecio , Prostatitis/microbiología , Vesículas Seminales/microbiología , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Transforming growth factor-ß1 (TGF-ß1) has been identified as one of the most important fibrogenic cytokines associated with Peyronie's disease (PD). The mothers against decapentaplegic homolog 7 (SMAD7) is an inhibitory Smad protein that blocks TGF-ß signaling pathway. The aim of this study was to examine the anti-fibrotic effect of the SMAD7 gene in primary fibroblasts derived from human PD plaques. PD fibroblasts were pretreated with the SMAD7 gene and then stimulated with TGF-ß1. Treated fibroblasts were used for Western blotting, fluorescent immunocytochemistry, hydroxyproline determination, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assays. Overexpression of the SMAD7 gene inhibited TGF-ß1-induced phosphorylation and nuclear translocation of SMAD2 and SMAD3, transdifferentiation of fibroblasts into myofibroblasts, and quashed TGF-ß1-induced production of extracellular matrix protein and hydroxyproline. Overexpression of the SMAD7 gene decreased the expression of cyclin D1 (a positive cell cycle regulator) and induced the expression of poly (ADP-ribose) polymerase 1, which is known to terminate Smad-mediated transcription, in PD fibroblasts. These findings suggest that the blocking of the TGF-ß pathway by use of SMAD7 may be a promising therapeutic strategy for the treatment of PD.
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Fibroblastos/efectos de los fármacos , Fibroblastos/patología , Induración Peniana/patología , Proteína smad7/fisiología , Factor de Crecimiento Transformador beta1/farmacología , Regulación hacia Arriba/fisiología , Células Cultivadas , Ciclina D1/efectos de los fármacos , Ciclina D1/metabolismo , Proteínas de la Matriz Extracelular/antagonistas & inhibidores , Proteínas de la Matriz Extracelular/efectos de los fármacos , Proteínas de la Matriz Extracelular/metabolismo , Fibrosis/inducido químicamente , Humanos , Hidroxiprolina/antagonistas & inhibidores , Hidroxiprolina/efectos de los fármacos , Hidroxiprolina/metabolismo , Masculino , Induración Peniana/tratamiento farmacológico , Induración Peniana/fisiopatología , Poli(ADP-Ribosa) Polimerasas/efectos de los fármacos , Poli(ADP-Ribosa) Polimerasas/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Proteína smad7/genética , Proteína smad7/uso terapéutico , Transfección , Factor de Crecimiento Transformador beta1/efectos adversos , Factor de Crecimiento Transformador beta1/antagonistas & inhibidores , Regulación hacia Arriba/genéticaRESUMEN
Interstitial cystitis/painful bladder syndrome (IC) is a chronic syndrome of unknown etiology that presents with bladder pain, urinary frequency, and urgency. The lack of specific biomarkers and a poor understanding of underlying molecular mechanisms present challenges for disease diagnosis and therapy. The goals of this study were to identify noninvasive biomarker candidates for IC from urine specimens and to potentially gain new insight into disease mechanisms using a nuclear magnetic resonance (NMR)-based global metabolomics analysis of urine from female IC patients and controls. Principal component analysis (PCA) suggested that the urinary metabolome of IC and controls was clearly different, with 140 NMR peaks significantly altered in IC patients (FDR < 0.05) compared to that in controls. On the basis of strong correlation scores, fifteen metabolite peaks were nominated as the strongest signature of IC. Among those signals that were higher in the IC group, three peaks were annotated as tyramine, the pain-related neuromodulator. Two peaks were annotated as 2-oxoglutarate. Levels of tyramine and 2-oxoglutarate were significantly elevated in urine specimens of IC subjects. An independent analysis using mass spectrometry also showed significantly increased levels of tyramine and 2-oxoglutarate in IC patients compared to controls. Functional studies showed that 2-oxoglutarate, but not tyramine, retarded growth of normal bladder epithelial cells. These preliminary findings suggest that analysis of urine metabolites has promise in biomarker development in the context of IC.
Asunto(s)
Biomarcadores/orina , Cistitis Intersticial/metabolismo , Metaboloma , Cromatografía Líquida de Alta Presión , Estudios de Cohortes , Biología Computacional/métodos , Cistitis Intersticial/orina , Femenino , Humanos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Metabolómica/métodos , Análisis de Componente Principal , República de CoreaRESUMEN
Sparganosis is a parasitic infestation of human by plerocercoid larvae. Sparganum is usually reported to be found in the subcutaneous tissues as well as other organs, including scrotum. However, testicular sparganosis is extremely rare, because of strong capsule of tunica albuginea. An urban-living 54-yr-old Korean man presented with left scrotal pain for 6 yr. Both testes look normal physically. Ultrasonography revealed poorly defined, heterogeneous mass with increased echogenicity in the left testis. This case was misdiagnosed as testicular tumor and underwent orchiectomy, but was diagnosed as testicular sparganosis by histopathology. Sparganosis should be included for differential diagnosis of testis tumor in countries where sparganosis is prevalent.