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PURPOSE: Secondary tethered cord syndrome (TCS) can be diagnosed with signs of progressive deterioration in urological or neuro-orthopedic systems following primary untethering surgery. Though urological deterioration is a common secondary TCS manifestation, a paucity of diagnostic criteria makes diagnoses challenging. A detailed description of urological deterioration may help diagnose secondary TCS. Thus, the clinical and urodynamic features of the current secondary TCS cases were described. MATERIALS AND METHODS: Fifty-one patients who had undergone reuntethering for secondary TCS experienced improvement or stabilization of progressive problems. Moreover, their clinical and videourodynamic changes were longitudinally described. RESULTS: Loss of postoperative spontaneous voiding was the first urological secondary TCS sign for those who could void spontaneously. Urological problems mostly occurred during elementary school (6-12 years). Major urological presentations were recalcitrant urinary tract infection or urinary incontinence. Follow-up videourodynamic studies revealed typical changes, from acontractile bladder to overactive and low-complaint bladders. While detrusor overactivity did not always occur during the progression, detrusor sphincter dyssynergia was always present in all patients with urological deterioration. All patients postoperatively showed significant urodynamic improvement regardless of preoperative bladder dysfunction. This included four cases of restoring spontaneous voiding. Nine patients experienced newly appearing nonprogressive neuro-orthopedic complications despite their urological improvement. CONCLUSIONS: Urological deterioration should prompt secondary TCS suspicion, and changes in clinical patterns and videourodynamic studies helped diagnose it. However, reuntethering can effectively address urological problems at the cost of some neuro-orthopedic functions in some patients.
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Defeitos do Tubo Neural , Incontinência Urinária , Seguimentos , Humanos , Defeitos do Tubo Neural/complicações , Defeitos do Tubo Neural/cirurgia , Bexiga Urinária/cirurgia , UrodinâmicaRESUMO
PURPOSE OF REVIEW: To date it is unclear whether the selectivity of new alpha-blockers to alpha-adrenergic receptor subtypes translates into more clinical benefits and less adverse effects in clinical practice. We performed a systematic review of the two new Abs silodosin and naftopidil. With the availability of numerous alpha-blockers to treat lower urinary tract symptoms secondary to benign prostatic hyperplasia, the findings of this review will be highly relevant to the field of urology. RECENT FINDINGS: Silodosin was found to be more effective than placebo in improving International Prostate Symptom Score (IPSS) and quality of life scores and as effective as other alpha-blockers. Although the incidence of cardiovascular adverse events of silodosin was similar compared with placebo and other alpha-blockers (tamsulosin, naftopidil, alfuzosin), the sexual adverse events were more common with silodosin. No placebo-controlled randomized trial exists investigating the effects of naftopidil in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. Naftopidil had similar efficacy with regards to IPSS and quality of life compared with tamsulosin. The rate of adverse events was similar compared with tamsulosin. SUMMARY: The two new selective alpha-blockers, silodosin, and naftopidil showed similar efficacy in IPSS and quality of life compared with other alpha-blockers. However, silodosin has more sexual adverse events.
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Antagonistas Adrenérgicos alfa/uso terapêutico , Ejaculação/efeitos dos fármacos , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Hiperplasia Prostática/tratamento farmacológico , Agentes Urológicos/uso terapêutico , Humanos , Indóis/uso terapêutico , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/psicologia , Masculino , Naftalenos/uso terapêutico , Piperazinas/uso terapêutico , Hiperplasia Prostática/complicações , Hiperplasia Prostática/psicologia , Qualidade de Vida , Resultado do TratamentoRESUMO
The rearrangement of protein domains is known to have key roles in the evolution of signaling networks and, consequently, is a major tool used to synthetically rewire networks. However, natural mutational events leading to the creation of proteins with novel domain combinations, such as in frame fusions followed by domain loss, retrotranspositions, or translocations, to name a few, often simultaneously replace pre-existing genes. Thus, while proteins with new domain combinations may establish novel network connections, it is not clear how the concomitant deletions are tolerated. We investigated the mechanisms that enable signaling networks to tolerate domain rearrangement-mediated gene replacements. Using as a model system the yeast mitogen activated protein kinase (MAPK)-mediated mating pathway, we analyzed 92 domain-rearrangement events affecting 11 genes. Our results indicate that, while domain rearrangement events that result in the loss of catalytic activities within the signaling complex are not tolerated, domain rearrangements can drastically alter protein interactions without impairing function. This suggests that signaling complexes can maintain function even when some components are recruited to alternative sites within the complex. Furthermore, we also found that the ability of the complex to tolerate changes in interaction partners does not depend on long disordered linkers that often connect domains. Taken together, our results suggest that some signaling complexes are dynamic ensembles with loose spatial constraints that could be easily re-shaped by evolution and, therefore, are ideal targets for cellular engineering.
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Mapas de Interação de Proteínas , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Transdução de Sinais , Evolução Molecular , Rearranjo Gênico , Genes Fúngicos Tipo Acasalamento , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Estrutura Terciária de Proteína , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/genéticaRESUMO
The object of this study is test whether mitochondrial blood-based biomarkers are associated with markers of metabolic syndrome in bipolar disorder, hypothesizing higher lactate but unchanged cell-free circulating mitochondrial DNA levels in bipolar disorder patients with metabolic syndrome. In a cohort study, primary testing from the FondaMental Advanced Centers of Expertise for bipolar disorder (FACE-BD) was conducted, including 837 stable bipolar disorder patients. The I-GIVE validation cohort consists of 237 participants: stable and acute bipolar patients, non-psychiatric controls, and acute schizophrenia patients. Multivariable regression analyses show significant lactate association with triglycerides, fasting glucose and systolic and diastolic blood pressure. Significantly higher levels of lactate were associated with presence of metabolic syndrome after adjusting for potential confounding factors. Mitochondrial-targeted metabolomics identified distinct metabolite profiles in patients with lactate presence and metabolic syndrome, differing from those without lactate changes but with metabolic syndrome. Circulating cell-free mitochondrial DNA was not associated with metabolic syndrome. This thorough analysis mitochondrial biomarkers indicate the associations with lactate and metabolic syndrome, while showing the mitochondrial metabolites can further stratify metabolic profiles in patients with BD. This study is relevant to improve the identification and stratification of bipolar patients with metabolic syndrome and provide potential personalized-therapeutic opportunities.
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Biomarcadores , Transtorno Bipolar , DNA Mitocondrial , Ácido Láctico , Síndrome Metabólica , Humanos , Transtorno Bipolar/sangue , Síndrome Metabólica/sangue , Feminino , Masculino , Biomarcadores/sangue , Adulto , Ácido Láctico/sangue , Pessoa de Meia-Idade , DNA Mitocondrial/genética , Mitocôndrias/metabolismo , Estudos de Coortes , Esquizofrenia/sangue , Esquizofrenia/metabolismo , MetabolômicaRESUMO
BACKGROUND: Nutrition is largely affected in bipolar disorder (BD), however, there is a lack of understanding on the relationship between dietary categories, BD, and the prevalence of metabolic syndrome. The objective of this study is to examine dietary trends in BD and it is hypothesized that diets with increased consumption of seafood and high-fiber carbohydrates will be correlated to improved patient outcomes, and a lower frequency of metabolic syndrome. METHODS: This retrospective cohort study includes two French cohorts. The primary cohort, FACE-BD, includes 268 stable BD patients. The second cohort, I-GIVE, includes healthy controls, both stable and acute BD and schizophrenia patients. Four dietary categories were assessed: meat, seafood, low-fiber and high-fiber carbohydrates. Dietary data from two food frequency questionnaires were normalized using min-max scaling and assessed using various statistical analyses. RESULTS: In our primary cohort, the increased high-fiber carbohydrate consumption was correlated to lower prevalence of metabolic syndrome and improved mood. Low-fiber carbohydrate consumption is associated with higher BMI, while higher seafood consumption was correlated to improved mood and delayed age of onset. Results were not replicated in our secondary cohort. LIMITATIONS: Our populations were small and two different dietary questionnaires were used; thus, results were used to examine similarities in trends. CONCLUSIONS: Overall, various dietary trends were associated with metabolic syndrome, BMI, lactate, mood and age of onset. Improving our understanding of nutrition in BD can provide mechanistic insight, clinically relevant nutritional guidelines for precision medicine and ultimately improve the quality of lives for those with BD.
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Placozoa is a phylum of non-bilaterian marine animals. These small, flat organisms adhere to the substrate via their densely ciliated ventral epithelium, which mediates mucociliary locomotion and nutrient uptake. They have only six morphological cell types, including one, fiber cells, for which functional data is lacking. Fiber cells are non-epithelial cells with multiple processes. We used electron and light microscopic approaches to unravel the roles of fiber cells in Trichoplax adhaerens, a representative member of the phylum. Three-dimensional reconstructions of serial sections of Trichoplax showed that each fiber cell is in contact with several other cells. Examination of fiber cells in thin sections and observations of live dissociated fiber cells demonstrated that they phagocytose cell debris and bacteria. In situ hybridization confirmed that fiber cells express genes involved in phagocytic activity. Fiber cells also are involved in wound healing as evidenced from microsurgery experiments. Based on these observations we conclude that fiber cells are multi-purpose macrophage-like cells. Macrophage-like cells have been described in Porifera, Ctenophora, and Cnidaria and are widespread among Bilateria, but our study is the first to show that Placozoa possesses this cell type. The phylogenetic distribution of macrophage-like cells suggests that they appeared early in metazoan evolution.
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Evolução Biológica , Citofagocitose , Imunidade Inata , Placozoa/imunologia , Rodófitas/imunologia , Cicatrização , Animais , FilogeniaRESUMO
Purpose: To compare the lipid layer thickness (LLT) using the LipiView® ocular surface interferometer (TearScience® Inc, Morrisville, NC) between the eye treated with glaucoma medication and untreated normal eye in the unilateral glaucoma patients, and evaluate the effect of topical glaucoma medication on the LLT parameters in glaucoma eyes. Methods: The participants in this cross-sectional comparative study were unilateral glaucoma patients treated with topical glaucoma medications for more than 12 months. Three LLT parameters (average, minimum, and maximum) obtained by the LipiView® were compared between the glaucomatous eye and normal eye. The factors associated with LLT parameters in the eyes treated with glaucoma medication were investigated with multiple regression analysis. Results: Thirty patients with unilateral normal tension glaucoma were enrolled in the present study. Lipid layer average, minimum, and maximum were 64.83 ± 16.50, 51.63 ± 16.73, and 82.53 ± 20.62 in glaucomatous eyes, 77.26 ± 17.81, 62.83 ± 20.99, and 86.13 ± 15.42 in normal eyes. Lipid layer average and minimum were significantly thinner than those in normal eyes (P < 0.001, P < 0.001, respectively). Longer duration of glaucoma eye drops and a greater number of glaucoma medications were associated with the lower LLT average (ß = -0.456, P < 0.001, ß = -8.517, P = 0.003, respectively), and increasing glaucoma medications have a significant correlation with lower LLT minimum in glaucoma eyes (ß = -8.814, P = 0.026). Conclusion: The present study highlights that patients with long-term glaucoma medications need to be assessed for LLT parameters objectively evaluate their ocular surface health.
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Anti-Hipertensivos/efeitos adversos , Metabolismo dos Lipídeos/efeitos dos fármacos , Glaucoma de Baixa Tensão/tratamento farmacológico , Lágrimas/metabolismo , Administração Oftálmica , Adulto , Idoso , Tartarato de Brimonidina/efeitos adversos , Estudos Transversais , Combinação de Medicamentos , Síndromes do Olho Seco/diagnóstico , Feminino , Gonioscopia , Humanos , Interferometria , Pressão Intraocular/fisiologia , Glaucoma de Baixa Tensão/metabolismo , Masculino , Disfunção da Glândula Tarsal/diagnóstico , Pessoa de Meia-Idade , Soluções Oftálmicas , Sulfonamidas/efeitos adversos , Tiofenos/efeitos adversos , Timolol/efeitos adversos , Tonometria OcularRESUMO
Active zone material is an organelle that is common to active zones along the presynaptic membrane of chemical synapses. Electron tomography on active zones at frog neuromuscular junctions has provided evidence that active zone material directs the docking of synaptic vesicles (SVs) on the presynaptic membrane at this synapse. Certain active zone material macromolecules connect to stereotypically arranged macromolecules in the membrane of undocked SVs, stably orienting a predetermined fusion domain of the vesicle membrane toward the presynaptic membrane while bringing and holding the two membranes together. Docking of the vesicles is required for the impulse-triggered vesicle membrane-presynaptic membrane fusion that releases the vesicles' neurotransmitter into the synaptic cleft. As at other synapses, axon terminals at frog neuromuscular junctions contain, in addition to SVs, vesicles that are larger, are much less frequent and, when viewed by electron microscopy, have a distinctive electron dense core. Dense core vesicles at neuromuscular junctions are likely to contain peptides that are released into the synaptic cleft to regulate formation, maintenance and behavior of cellular apparatus essential for synaptic impulse transmission. We show by electron tomography on axon terminals of frog neuromuscular junctions fixed at rest and during repetitive impulse transmission that dense core vesicles selectively dock on and fuse with the presynaptic membrane alongside SVs at active zones, and that active zone material connects to the dense core vesicles undergoing these processes in the same way it connects to SVs. We conclude that undocked dense core vesicles have a predetermined fusion domain, as do undocked SVs, and that active zone material directs oriented docking and fusion of these different vesicle types at active zones of the presynaptic membrane by similar macromolecular interactions.
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OBJECTIVE: Serum uric acid levels increase in postmenopausal women, but decrease when hormone therapy (HT) is administered. No study has, however, evaluated the effects of different types of HT on serum uric acid levels. We therefore examined whether estrogen therapy (ET), estrogen plus progestogen therapy (EPT), and tibolone use affected serum uric acid levels in this population. METHODS: We performed a retrospective cohort study of postmenopausal women. From 2005 to 2015, postmenopausal women who had undergone blood uric acid-level testing at least twice were enrolled. Participants were grouped according to HT regimen: ET, EPT, or tibolone. The nonhormone therapy group did not receive HT. Differences in serum uric acid levels were examined in each group. Our analysis was adjusted to accommodate different follow-up intervals for individual participants. Multiple variables were adjusted using the Tukey-Kramer method. Age, body mass index, hypertension, diabetes mellitus, dyslipidemia, estimated glomerular filtration rate, alcohol consumption, smoking status, and comedications were also adjusted. RESULTS: After adjusting for multiple variables, the serum uric acid level increased to 0.87â±â0.27âmg/dL (least squares meanâ±âstandard error) in the nonhormone therapy group, and serum uric levels in the EPT group were found to be significantly lower (-0.38â±â0.29âmg/dL, Pâ<â0.001). The serum uric acid levels in the ET and tibolone groups did not, however, differ significantly from the nonhormone therapy group level. CONCLUSIONS: We attribute our findings to the effects of progestogen, rather than estrogen.
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Terapia de Reposição de Estrogênios , Pós-Menopausa , Ácido Úrico/sangue , Estudos de Coortes , Estrogênios/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Progestinas/administração & dosagem , Estudos RetrospectivosAssuntos
Glaucoma de Ângulo Aberto/complicações , Síndromes de Compressão Nervosa/etiologia , Quiasma Óptico/patologia , Doenças do Nervo Óptico/etiologia , Neoplasias Hipofisárias/complicações , Rabdomiossarcoma/complicações , Adulto , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/cirurgia , Humanos , Pressão Intraocular , Imageamento por Ressonância Magnética , Masculino , Mitomicina/administração & dosagem , Síndromes de Compressão Nervosa/diagnóstico , Doenças do Nervo Óptico/diagnóstico , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/cirurgia , Rabdomiossarcoma/diagnóstico , Rabdomiossarcoma/cirurgia , Escotoma/diagnóstico , Escotoma/etiologia , Trabeculectomia , Campos VisuaisRESUMO
OBJECTIVES: To set a population-based cut-off value of normal adult and to determine correlations of testicular volume with body mass index (BMI), seminal profiles, and hormone levels. Testicular volume is an index of male fertility but cut-off values of normal adult has not been reported. METHODS: During 54 months from January 2004, 1139 normal young men, 19-27 years old in military service were enrolled. Testicular volumes were measured by ultrasonometry. Height, body weight, and BMI were measured and semen analysis and hormone assay (follicle-stimulating hormone [FSH], luteinizing hormone [LH], and testosterone) were performed. RESULTS: The mean age was 23.52+/-2.74. The mean testicular volume was 18.37+/-3.62 cm3 in left, and 18.13+/-3.85 cm3 in right. The mean body weight was 67.4+/-7.91 kg, the mean height was 176.2+/-6.64 cm, and mean BMI was 22.49+/-2.02 kg/m2. Testicular volumes had significant but weak correlations with height, body weight, and BMI. The semen analyses showed a mean pH of 7.63+/-0.74, volume of 2.49+/-1.12 mL, count of 68.63+/-13.62x10(6), motility of 69.93%+/-10.28%, and morphology of 68.62%+/-7.48%. Sperm counts and motility had positive correlations with testicular volume. The mean hormonal levels of FSH, LH, and testosterone were 7.31+/-2.42 mIU/mL, 7.81+/-2.49 mIU/mL, and 6.23+/-1.69 ng/mL, respectively. Testicular volume was negatively correlated with FSH and LH and positively with testosterone. CONCLUSIONS: In this population-based study, we conclude that the cut-off testicular volume in normal young adults is around 18 mL and that testicular volume is positively correlated with height, body weight, BMI, semen profile, and testosterone, and negatively correlated with FSH and LH.