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PURPOSE: Laser interstitial thermal therapy (LITT) is an effective minimally invasive treatment option for intracranial tumors. Our group produced plasmonics-active gold nanostars (GNS) designed to preferentially accumulate within intracranial tumors and amplify the ablative capacity of LITT. EXPERIMENTAL DESIGN: The impact of GNS on LITT coverage capacity was tested in ex vivo models using clinical LITT equipment and agarose gel-based phantoms of control and GNS-infused central "tumors." In vivo accumulation of GNS and amplification of ablation were tested in murine intracranial and extracranial tumor models followed by intravenous GNS injection, PET/CT, two-photon photoluminescence, inductively coupled plasma mass spectrometry (ICP-MS), histopathology, and laser ablation. RESULTS: Monte Carlo simulations demonstrated the potential of GNS to accelerate and specify thermal distributions. In ex vivo cuboid tumor phantoms, the GNS-infused phantom heated 5.5× faster than the control. In a split-cylinder tumor phantom, the GNS-infused border heated 2× faster and the surrounding area was exposed to 30% lower temperatures, with margin conformation observed in a model of irregular GNS distribution. In vivo, GNS preferentially accumulated within intracranial tumors on PET/CT, two-photon photoluminescence, and ICP-MS at 24 and 72 hours and significantly expedited and increased the maximal temperature achieved in laser ablation compared with control. CONCLUSIONS: Our results provide evidence for use of GNS to improve the efficiency and potentially safety of LITT. The in vivo data support selective accumulation within intracranial tumors and amplification of laser ablation, and the GNS-infused phantom experiments demonstrate increased rates of heating, heat contouring to tumor borders, and decreased heating of surrounding regions representing normal structures.
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Neoplasias Encefálicas , Hipertermia Inducida , Humanos , Animales , Ratones , Oro , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias Encefálicas/cirugía , Hipertermia Inducida/métodos , Rayos LáserRESUMEN
This study aimed to assess the effects of dietary supplementation of inosine-5'-monophosphate (5'-IMP) on energy efficiency, growth performance, carcass characteristics, meat quality, oxidative status, and biochemical profile of blood plasma in finishing pigs. Fifty-four crossbred castrated male pigs were distributed in a randomized block design consisting of nine blocks, with six treatments per block and one animal per treatment per block. Experimental diets were as follows: positive control diet (PC, 3300 kcal ME/kg), negative control diet (NC, 3200 kcal ME/kg), and four diets prepared by supplementing the NC diet with 0.050%, 0.100%, 0.150%, or 0.200% 5'-IMP. Based on regression analysis, supplementation with 0.129% 5'-IMP increased average daily weight gain (1.30 kg). Backfat thickness, pH45minutes and redness of m. Longissimus Lumborum (LL) increased linearly with 5'-IMP supplementation level. Drip loss and pH at 24 h post-slaughter had a quadratic response to 5'-IMP supplementation. It is concluded that 5'-IMP supplementation positively influenced growth performance, carcass characteristics and LL meat quality in finishing barrows.
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Alimentación Animal , Inosina Monofosfato , Animales , Masculino , Alimentación Animal/análisis , Composición Corporal , Dieta/veterinaria , Suplementos Dietéticos , Inosina/farmacología , Carne/análisis , Porcinos , Aumento de PesoRESUMEN
Background: Though evidence demonstrating benefits of local anesthetic continues to compound, a consensus among surgeons regarding optimal anesthetic modality has not been reached. General and regional anesthetic may still be preferred for patient anxiety, concomitant procedures, increased complexity, or poor patient pain tolerance. Therefore, the primary purpose of this study was to analyze trends in anesthetic utilization using a large-scale state healthcare database for common outpatient hand procedures. We hypothesize that over the 10 years between 2010-2019, local anesthetic [including Wide-Awake Local Anesthesia with no Tourniquet (WALANT)] utilization use for common hand procedures has increased, while the use of general and regional anesthesia has decreased. Methods: A cross-sectional analysis was performed using the Texas Healthcare Information Collection Outpatient Database between 2010-2019. The de-identified data was queried for reported Current Procedure Terminology (CPT) anesthetic and associated procedure codes for the following ambulatory techniques: open carpal tunnel release, endoscopic carpal tunnel release, trigger finger release, De Quervain's release, partial palmar fasciectomy, and hand mass excision. Anesthetic options included: regional anesthesia (RA), local or WALANT anesthesia (LA), and general anesthesia (GA). Results: There were 340,117 procedures performed during the study period. 98.14% of patient records reported LA application, while GA and RA only accounted for 0.41% and 1.45%, respectively. No significant growth was found for each form of anesthetic individually [LA: -0.12%, RA: 0.09%, and GA: 0.03%]. However, a significant difference in proportional growth is present when comparing all anesthetics (Figure 1, p<0.001). Commercial/ private insurance was the most common payer regardless of anesthesia type, though Medicaid payment source covered a larger proportion of procedures performed under GA [Medicaid: 2.48%, Medicare: 0.37%, worker's compensation: 0.12%, commercial/private insurance: 0.20%]. Conclusion: LA was the most utilized modality over the study period, though a significant proportion of usage has shifted back towards RA and GA over time. Commercial/private insurance was the most frequent reimbursement source for all procedures, though Medicaid covered disproportionately more procedures utilizing GA. RA use was noted to be disproportionately higher in mid-sized population centers (2-4 million in population). Level of Evidence: IV.
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Anestésicos Locales , Síndrome del Túnel Carpiano , Anciano , Humanos , Estados Unidos , Estudios Transversales , Medicare , Anestesia Local/métodos , Extremidad Superior , Síndrome del Túnel Carpiano/cirugía , Anestesia GeneralRESUMEN
Objective was evaluated the therapeutic effect of Juglans regia (J) and Zingiber officinale (Z) extracts, alone or associated (Z75% + J25%, Z50% + J50% and Z25% + J75%) applied on planktonic cultures and biofilms of Propionibacterium acnes, Staphylococcus epidermidis and Staphylococcus aureus, as well as analyzing the cytotoxic effects of plant extracts on mouse macrophages (Raw 264-7). Broth microdilution assay was performed (M7-A6 - CLSI). Anti-biofilm activities and cytotoxicity on Raw 264-7 were studied using MTT assay and scanning electron microscopy. ANOVA with post-hoc Tukey HSD applied for parametric data and Kruskal-Wallis with Conover-Iman test, for non-parametric (p<0.05). On P. acnes biofilm, Z50% + J50% reduced 46.9% in 5 min and Z25% + J75% reduced 74.1% in 24hs. On S. aureus, Z75% + J25% reduced 23.1% in 5 min Z25% +J75% reduced 79.4% in 24hs. On S. epidermidis, Z75% + J25% reduced 74.6% in 5 min and 82.05% in 24 h. The treatments on macrophages for 24 h promoted a maximum reduction by 14,5% for groups of extracts associations. On multispecies biofilm, Z75%+J25% reduced 84.3% in 24 h. In conclusion association of glycolic extracts provided therapeutic effect, demonstrated antimicrobial activity and low cytotoxicity.
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Juglans , Infecciones Estafilocócicas , Zingiber officinale , Animales , Ratones , Staphylococcus epidermidis , Staphylococcus aureus , Propionibacterium acnes , Infecciones Estafilocócicas/tratamiento farmacológico , BiopelículasRESUMEN
Purpose: The aim of this study was to investigate the reported persistent or new symptoms 1 year after a single dose of 200,000 IU of vitamin D3 and hospitalization in patients with moderate to severe COVID-19. Methods: This is a post-hoc, exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial from two hospitals in São Paulo, Brazil, registered in ClinicalTrials.gov, NCT04449718. Discharged patients were followed for up to 1 year and evaluated by telephone interviews at 6 and 12 months. The primary and secondary outcomes were previously published. These post-hoc exploratory secondary outcomes are the persistent or new symptoms and quality of life (QoL) at the post-viral stage of COVID-19. Generalized estimating equations (GEE) for repeated measures with Bonferroni's adjustment were used for testing outcomes. Results: Between 2 June and 27 August 2020, we randomized 240 patients of which 144 were included in this study [the vitamin D3 (n = 71) or placebo (n = 73) group]. The mean (SD) age was 54.3 (13.1) years, and body mass index (BMI) was 32.4 (6.5) kg/m2. Fever demonstrated a significant main effect of time (P < 0.001) with a reduction from baseline to 6 (52-0) and 12 months (52-0). No significant differences between groups were observed for fever, cough, fatigue, fever, myalgia, joint pain, runny nose, nasal congestion, sore throat, hypertension, diabetes, cardiovascular disease, rheumatic disease, asthma, chronic obstructive pulmonary, chronic kidney disease, QoL, and new or persistent symptoms up to 1-year of follow-up. Conclusion: The findings do not support the use of 200,000 IU of vitamin D3 compared to placebo for the management of persistence or new symptoms, and QoL reported by moderate to severe patients after hospitalization for COVID-19.
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Inosine 5'-monophosphate (5'-IMP) is an essential nucleotide for de novo nucleotide biosynthesis and metabolism of energy, proteins, and antioxidants. Nucleotides are conditionally essential, as they cannot be produced sufficiently rapidly to meet the needs of the body in situations of oxidative stress or rapid muscle growth. A deficient intake of nucleotides can result in decreased ATP and GTP synthesis and impaired metabolism. We demonstrated that supplementation of finishing pig diets with 5'-IMP reduces the relative weight of the liver, and increases oxygen consumption during mitochondrial respiration without changing the ADP/O ratio, indicating an increase in the respiratory efficiency of liver mitochondria. We also observed a reduction in liver lipid peroxidation and an increase in muscle creatine. Moreover, 5'IMP supplementation increases slaughter weight, lean meat yield, sarcomere length, and backfat thickness in finishing barrows, demonstrating influence on protein metabolism. We suggest that 5'-IMP supplementation increase the mitochondrial respiratory capacity when the liver metabolic activity is stimulated, enhances antioxidant defense, and promotes muscle growth in finishing barrows.
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Fenómenos Fisiológicos Nutricionales de los Animales , Antioxidantes/metabolismo , Suplementos Dietéticos , Metabolismo Energético , Inosina Monofosfato/administración & dosificación , Hígado/metabolismo , Músculo Esquelético/metabolismo , Sus scrofa/metabolismo , Alimentación Animal , Animales , Peroxidación de Lípido , Hígado/crecimiento & desarrollo , Mitocondrias Hepáticas/metabolismo , Músculo Esquelético/crecimiento & desarrollo , Consumo de Oxígeno , Sus scrofa/crecimiento & desarrollo , Aumento de PesoRESUMEN
BACKGROUND: The modulating effect of vitamin D on cytokine concentrations in severe coronavirus disease 2019 (COVID-19) remains unknown. OBJECTIVES: We aimed to investigate the effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19. METHODS: This is a post hoc, ancillary, and exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients with moderate to severe COVID-19 were recruited from 2 hospitals in São Paulo, Brazil. Of 240 randomly assigned patients, 200 were assessed in this study and randomly assigned to receive a single oral dose of 200,000 IU vitamin D3 (n = 101) or placebo (n = 99). The primary outcome was hospital length of stay, which has been published in our previous study. The prespecified secondary outcomes were serum concentrations of IL-1ß, IL-6, IL-10, TNF-α, and 25-hydroxyvitamin D. The post hoc exploratory secondary outcomes were IL-4, IL-12p70, IL-17A, IFN-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, IFN-inducible protein-10 (IP-10), macrophage inflammatory protein-1ß (MIP-1ß), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and leukocyte count. Generalized estimating equations for repeated measures, with Bonferroni's adjustment, were used for testing all outcomes. RESULTS: The study included 200 patients with a mean ± SD age of 55.5 ± 14.3 y and BMI of 32.2 ± 7.1 kg/m2, of which 109 (54.5%) were male. GM-CSF concentrations showed a significant group-by-time interaction effect (P = 0.04), although the between-group difference at postintervention after Bonferroni's adjustment was not significant. No significant effects were observed for the other outcomes. CONCLUSIONS: The findings do not support the use of a single dose of 200,000 IU vitamin D3, compared with placebo, for the improvement of cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19.This trial was registered at clinicaltrials.gov as NCT04449718.
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Tratamiento Farmacológico de COVID-19 , Quimiocinas/efectos de los fármacos , Colecalciferol/administración & dosificación , Citocinas/efectos de los fármacos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacos , Vitaminas/administración & dosificación , Adulto , Anciano , Brasil , COVID-19/inmunología , Método Doble Ciego , Femenino , Humanos , Péptidos y Proteínas de Señalización Intercelular/sangre , Masculino , Persona de Mediana Edad , SARS-CoV-2/inmunologíaRESUMEN
Cardiovascular diseases are associated with high morbidity and mortality worldwide and have several risk factors, including dyslipidemia, smoking, and hypertension. Studies have evaluated isolated risk factors in experimental models of cardiovascular disease, but few preclinical studies have assessed associations between multiple risk factors. In the present study, hypertensive Wistar rats (Goldblatt 2K1C model) received a 0.5% cholesterol diet and were exposed to tobacco smoke for 8 weeks. During the last 4 weeks, the animals were treated with vehicle, an ethanol-soluble fraction of B. trimera (30, 100, and 300 mg/kg), or simvastatin + enalapril. A group of normotensive, non-dyslipidemic, and non-smoking rats was treated with vehicle. The levels of aspartate aminotransferase, alanine aminotransferase, urea, creatinine, and hepatic and fecal lipids, blood pressure, and mesenteric arterial bed reactivity were evaluated. Cardiac, hepatic, and renal histopathology and tecidual redox state were also investigated. Untreated animals exhibited significant changes in blood pressure, lipid profile, and biomarkers of heart, liver, and kidney damage. Treatment with B. trimera reversed these changes, with effects that were similar to simvastatin + enalapril. These findings suggest that B. trimera may be promising for the treatment of cardiovascular and hepatic disorders, especially disorders that are associated with multiple risk factors.
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Baccharis , Enfermedades no Transmisibles , Animales , Extractos Vegetales , Ratas , Ratas Wistar , Factores de RiesgoRESUMEN
Importance: The efficacy of vitamin D3 supplementation in coronavirus disease 2019 (COVID-19) remains unclear. Objective: To investigate the effect of a single high dose of vitamin D3 on hospital length of stay in patients with COVID-19. Design, Setting, and Participants: This was a multicenter, double-blind, randomized, placebo-controlled trial conducted in 2 sites in Sao Paulo, Brazil. The study included 240 hospitalized patients with COVID-19 who were moderately to severely ill at the time of enrollment from June 2, 2020, to August 27, 2020. The final follow-up was on October 7, 2020. Interventions: Patients were randomly assigned to receive a single oral dose of 200â¯000 IU of vitamin D3 (n = 120) or placebo (n = 120). Main Outcomes and Measures: The primary outcome was length of stay, defined as the time from the date of randomization to hospital discharge. Prespecified secondary outcomes included mortality during hospitalization; the number of patients admitted to the intensive care unit; the number of patients who required mechanical ventilation and the duration of mechanical ventilation; and serum levels of 25-hydroxyvitamin D, total calcium, creatinine, and C-reactive protein. Results: Of 240 randomized patients, 237 were included in the primary analysis (mean [SD] age, 56.2 [14.4] years; 104 [43.9%] women; mean [SD] baseline 25-hydroxyvitamin D level, 20.9 [9.2] ng/mL). Median (interquartile range) length of stay was not significantly different between the vitamin D3 (7.0 [4.0-10.0] days) and placebo groups (7.0 [5.0-13.0] days) (log-rank P = .59; unadjusted hazard ratio for hospital discharge, 1.07 [95% CI, 0.82-1.39]; P = .62). The difference between the vitamin D3 group and the placebo group was not significant for in-hospital mortality (7.6% vs 5.1%; difference, 2.5% [95% CI, -4.1% to 9.2%]; P = .43), admission to the intensive care unit (16.0% vs 21.2%; difference, -5.2% [95% CI, -15.1% to 4.7%]; P = .30), or need for mechanical ventilation (7.6% vs 14.4%; difference, -6.8% [95% CI, -15.1% to 1.2%]; P = .09). Mean serum levels of 25-hydroxyvitamin D significantly increased after a single dose of vitamin D3 vs placebo (44.4 ng/mL vs 19.8 ng/mL; difference, 24.1 ng/mL [95% CI, 19.5-28.7]; P < .001). There were no adverse events, but an episode of vomiting was associated with the intervention. Conclusions and Relevance: Among hospitalized patients with COVID-19, a single high dose of vitamin D3, compared with placebo, did not significantly reduce hospital length of stay. The findings do not support the use of a high dose of vitamin D3 for treatment of moderate to severe COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04449718.
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Tratamiento Farmacológico de COVID-19 , Colecalciferol/administración & dosificación , Tiempo de Internación , Vitaminas/administración & dosificación , Adulto , Brasil , COVID-19/mortalidad , COVID-19/terapia , Método Doble Ciego , Femenino , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Respiración Artificial , Insuficiencia del Tratamiento , Vitamina D/análogos & derivados , Vitamina D/sangre , Deficiencia de Vitamina D/tratamiento farmacológicoRESUMEN
BACKGROUND: Dermatophytes belonging to the Trichophyton genus are important human pathogens, but they have developed resistance to griseofulvin, the most common antifungal drug used to treat dermatophytosis. OBJECTIVE: This study was aimed to evaluate the antidermatophytic activity of synthetic peptides, as well as mechanisms of action and synergistic effect with griseofulvin. METHODS: Scanning electron microscopy (SEM), atomic force microscopy (AFM) and fluorescence microscopy (FM) were employed to understand the activity and the mechanism of action of peptides. RESULTS: Here we report that synthetic peptides at 50 µg/mL, a concentration 20-fold lower than griseofulvin, reduced the microconidia viability of T. mentagrophytes and T. rubrum by 100%, whereas griseofulvin decreased their viability by only 50% and 0%, respectively. The action mechanism of peptides involved cell wall damage, membrane pore formation and loss of cytoplasmic content. Peptides also induced overproduction of reactive oxygen species (ROS) and enhanced the activity of griseofulvin 10-fold against both fungi, suggesting synergistic effects, and eliminated the toxicity of this drug to human erythrocytes. Docking analysis revealed ionic and hydrophobic interactions between peptides and griseofulvin, which may explain the decline of griseofulvin toxicity when mixed with peptides. CONCLUSION: Therefore, our results strongly suggest six peptides with high potential to be employed alone as new drugs or as adjuvants to enhance the activity and decrease the toxicity of griseofulvin.
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Antifúngicos/farmacología , Griseofulvina/farmacología , Péptidos/síntesis química , Péptidos/farmacología , Esporas Fúngicas/efectos de los fármacos , Trichophyton/efectos de los fármacos , Descubrimiento de Drogas , Farmacorresistencia Fúngica , Sinergismo Farmacológico , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
Plant seeds can exudate active molecules with inhibitory effects against several soil pathogens, including nematodes. This study aimed to characterize and evaluate the nematicidal properties against Meloidogyne incognita of exuded proteins from Moringa oleifera seeds. M. oleifera seeds were soaked in distilled water, and exudates were harvested and analyzed for the presence of defense proteins and anthelmintic activity. Enzymatic assays revealed the existence of PR-proteins such as ß-1,3-glucanases (0.18 ± 0.003 nkatal mg-1 of protein), chitinases (0.22 ± 0.004 nkatal mg-1 of protein), proteases (261.30 ± 6.405 AU mg-1 of protein min-1), serine (190.30 ± 5.574 IA mg-1 of protein) and cysteine (231.70 ± 0.923 IA mg-1 of protein), protease inhibitors. The exuded proteins presented ovicidal activity and caused 100% mortality of second-stage juveniles (J2s). Scanning electron microscopy (SEM) revealed deleterious effects on M. incognita eggs, such as invaginations, cracks, scratched surface, and loss of internal content. These findings confirm the presence of anthelmintic proteins in M. oleifera seed exudate, possibly involved in plant defense during seed germination. Besides this, the exuded proteins exhibited strong biotechnological potential for use in the biocontrol of M. incognita infections, which are responsible for millions of dollars in staple crop losses every year.
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Antinematodos/farmacología , Moringa oleifera/química , Enfermedades de las Plantas/prevención & control , Proteínas de Plantas/farmacología , Semillas/química , Tylenchoidea/efectos de los fármacos , Animales , Óvulo/efectos de los fármacos , Extractos Vegetales/farmacologíaRESUMEN
BACKGROUND: Major depressive disorder (MDD) is one of the leading causes of disability in the world. However, treatment options are still limited, and marked by high refractoriness rates, new approaches are needed to optimize clinical improvement. Trigeminal nerve stimulation (TNS) is an innovative neuromodulation strategy consisting on the application of an electric current over the trigeminal nerve that propagates stimuli towards brain areas involved in mood control. OBJECTIVE: We examined the effects of TNS in MDD after a 10-day experimental protocol. METHODS: This was a randomized, double blind, and sham-controlled phase II study with 24 patients with severe MDD. Patients underwent a 10-day intervention protocol and were assessed with the 17-item Hamilton Depression Rating Scale (HDRS-17) at following three observation points: baseline (T1), after 10â¯days (T2), and after one month of the last stimulation session (T3). Main clinical outcome analysis of variance (ANOVA) was performed. RESULTS: Patients in the active group presented a mean reduction of 36.15% in depressive symptoms after the stimulation protocol. There was a significant interaction between group and time regarding HDRS-17 scores (Fâ¯=â¯3.18; dfâ¯=â¯2; pâ¯=â¯0.0456). Post hoc analyses exhibited a statistically significant difference between active and sham group symptoms at T2 (pâ¯=â¯0.040) and T3 (pâ¯=â¯0.026), which highlights the sustained amelioration of depressive symptoms. CONCLUSION: The present study found amelioration of depressive symptoms for patients undergoing a 10-day stimulation protocol of TNS, and this was sustained after one month of follow-up.
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Trastorno Depresivo Mayor/terapia , Estimulación Eléctrica Transcutánea del Nervio/métodos , Nervio Trigémino , Adolescente , Adulto , Anciano , Trastorno Depresivo Mayor/diagnóstico , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
This study aimed to evaluate whether dietary supplementation with diphenyl diselenide (Ph2Se2) would prevent the impaired immune and inflammatory responses elicited by methylmercury chloride (CH3HgCl) via protective effects on purinergic signaling in fish immune organs. Tissue and lymphocytic nucleoside triphosphate diphosphohydrolase (NTPDase) activity for adenosine triphosphate (ATP) and adenosine diphosphate (ADP) was downregulated in the head kidney and spleen of grass carp (Ctenopharyngodon idella) exposed to CH3HgCl. Concomitantly, adenosine deaminase (ADA) activity was upregulated. Further, nucleotide-binding oligomerization domain-like receptor (NLRP3) inflammasome gene expression was upregulated in the spleen and head kidney of CH3HgCl-exposed grass carp. Dietary supplementation with Ph2Se2 ameliorated these CH3HgCl-mediated alterations on purinergic enzymes, and their activities returned to baseline levels (except NTPDase activity for ADP). Based on these results, purinergic signaling in immune organs and lymphocytes can be considered a pathway linked to pro-inflammatory effects during exposure to environmental CH3HgCl concentrations, which may contribute to mortality of the affected fish. Since dietary supplementation with 3â¯mg Ph2Se2/kg in the feed prevented the CH3HgCl-induced alterations, it can be considered a potential suitable treatment to prevent impaired immune and inflammatory responses caused by Hg.
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Derivados del Benceno/farmacología , Carpas , Enfermedades de los Peces/inducido químicamente , Riñón Cefálico/efectos de los fármacos , Compuestos de Metilmercurio/toxicidad , Compuestos de Organoselenio/farmacología , Bazo/efectos de los fármacos , Alimentación Animal/análisis , Animales , Dieta/veterinaria , Suplementos Dietéticos , Enfermedades de los Peces/prevención & control , Regulación de la Expresión Génica/efectos de los fármacos , Inflamasomas/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Sustancias Protectoras/farmacología , Transducción de SeñalRESUMEN
BACKGROUND: More than 30% of major depressive disorder patients fail to respond to adequate trials of medications and psychotherapy. While modern neuromodulation approaches (ie, vagal nerve stimulation, deep brain stimulation) are yet to prove their efficacy for such cases in large randomized controlled trials, trigeminal nerve stimulation (TNS) has emerged as an alternative with promising effects on mood disorders. OBJECTIVE: To assess efficacy, safety, tolerability, and placebo effect duration of continuous subcutaneous TNS (sTNS) in treatment-resistant depression (TRD). METHODS: The TREND study is a single-center, double-blind, randomized, controlled, phase II clinical trial. Twenty unipolar TRD patients will receive V1 sTNS as adjuvant to medical therapy and randomized to active vs sham stimulation throughout a 24-wk period. An additional 24-wk open-label phase will follow. Data concerning efficacy, placebo response, relapse, and side effects related to surgery or electrical stimulation will be recorded. We will use the HDRS-17, BDI-SR, IDS_SR30, and UKU scales. EXPECTED OUTCOMES: The main outcome measure is improvement in depression scores using HAM-17 under continuous sTNS as adjuvant to antidepressants. Active stimulation is expected to significantly impact response and remission rates. Minor side effects are expected due to the surgical procedure and electrical stimulation. The open-label phase should further confirm efficacy and tolerability. DISCUSSION: This study protocol is designed to define efficacy of a novel adjuvant therapy for TRD. We must strive to develop safe, reproducible, predictable, and well-tolerated neuromodulation approaches for TRD patients impaired to manage their lives and contribute with society.
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Trastorno Depresivo Mayor/terapia , Trastorno Depresivo Resistente al Tratamiento/terapia , Terapia por Estimulación Eléctrica/métodos , Nervio Trigémino , Adulto , Enfermedad Crónica/terapia , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos de Investigación , Resultado del TratamientoRESUMEN
Endothelial cells are thought to play a central role in the pathogenesis of antiphospholipid syndrome (APS). Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been shown to improve endothelial function in a number of diseases; thus, it could be of high clinical relevance in APS. The aim of this study was to evaluate the efficacy of n-3 PUFA supplementation on endothelial function (primary outcome) of patients with primary APS (PAPS). A 16-week randomized clinical trial was conducted with 22 adult women with PAPS. Patients were randomly assigned (1:1) to receive placebo (PL, n = 11) or n-3 PUFA (ω-3, n = 11) supplementation. Before (pre) and after (post) 16 weeks of the intervention, patients were assessed for endothelial function (peripheral artery tonometry) (primary outcome). Patients were also assessed for systemic markers of endothelial cell activation, inflammatory markers, dietary intake, international normalized ratio (INR), and adverse effects. At post, ω-3 group presented significant increases in endothelial function estimates reactive hyperemia index (RHI) and logarithmic transformation of RHI (LnRHI) when compared with PL (+13 vs. -12%, p = 0.06, ES = 0.9; and +23 vs. -22%, p = 0.02, ES = 1.0). No changes were observed for e-selectin, vascular adhesion molecule-1, and fibrinogen levels (p > 0.05). In addition, ω-3 group showed decreased circulating levels of interleukin-10 (-4 vs. +45%, p = 0.04, ES = -0.9) and tumor necrosis factor (-13 vs. +0.3%, p = 0.04, ES = -0.95) and a tendency toward a lower intercellular adhesion molecule-1 response (+3 vs. +48%, p = 0.1, ES = -0.7) at post when compared with PL. No changes in dietary intake, INR, or self-reported adverse effects were observed. In conclusion, 16 weeks of n-3 PUFA supplementation improved endothelial function in patients with well-controlled PAPS. These results support a role of n-3 PUFA supplementation as an adjuvant therapy in APS. Registered at http://ClinicalTrials.gov as NCT01956188.
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Síndrome Antifosfolípido/tratamiento farmacológico , Proteínas Sanguíneas/inmunología , Suplementos Dietéticos , Endotelio Vascular/inmunología , Ácidos Grasos Omega-3/administración & dosificación , Adulto , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/patología , Biomarcadores/sangre , Proteínas Sanguíneas/metabolismo , Método Doble Ciego , Endotelio Vascular/metabolismo , Endotelio Vascular/patología , Femenino , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND: Infertility is one of many complications of spinal cord injury (SCI) in male patients, who are often at the peak of their reproductive life. This study evaluated effects of hyperbaric therapy (HT) on quality of sperm of rats with SCI and correlated the findings with histologic analysis of the testicles. METHODS: This experimental study comprised 18 rats that were submitted to SCI with a MASCIS Impactor and randomly allocated to either a HT or a control group. Testicular biopsies were performed on the first and 28th day of the study; 4 parameters were evaluated: concentration of sperm per mL, number of round cells per field, number of inflammatory cells per field (peroxidase [Endtz] test), and sperm viability (hypo-osmotic swelling test). RESULTS: There was no difference in sperm concentration between the HT group (P = 0.41) and control group (P = 0.74) during 28 days. From day 1 to day 28, sperm viability decreased twice as much in the control group (P = 0.001) compared with the HT group (P = 0.017). There was no difference between the groups in mean sperm concentration and number of round and inflammatory cells. On the first day, there was no difference in sperm viability between groups. There was a significantly higher (P = 0.001) percentage of viable sperm in the HT group (86.8 ± 5.6) compared with the control group (48.8 ± 21.8) on day 28. CONCLUSIONS: SCI increased the number of round and inflammatory cells and diminished sperm viability in both groups. HT promoted greater sperm viability in rats with SCI.
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Oxigenoterapia Hiperbárica , Infertilidad Masculina/terapia , Espermatozoides/citología , Traumatismos de la Médula Espinal/complicaciones , Animales , Biopsia , Supervivencia Celular , Infertilidad Masculina/etiología , Infertilidad Masculina/patología , Inflamación , Masculino , Estrés Oxidativo , Distribución Aleatoria , Ratas , Ratas Wistar , Análisis de Semen , Recuento de Espermatozoides , Testículo/patologíaRESUMEN
Terrestrial laser scanning (TLS) provides fast collection of high-definition structural information, making it a valuable field instrument to many monitoring applications. A weakness of TLS collections, especially in vegetation, is the occurrence of unsampled regions in point clouds where the sensor's line-of-sight is blocked by intervening material. This problem, referred to as occlusion, may be mitigated by scanning target areas from several positions, increasing the chance that any given area will fall within the scanner's line-of-sight from at least one position. Because TLS collections are often employed in remote regions where the scope of sampling is limited by logistical factors such as time and battery power, it is important to design field protocols which maximize efficiency and support increased quantity and quality of the data collected. This study informs researchers and practitioners seeking to optimize TLS sampling methods for vegetation monitoring in dryland ecosystems through three analyses. First, we quantify the 2D extent of occluded regions based on the range from single scan positions. Second, we measure the efficacy of additional scan positions on the reduction of 2D occluded regions (area) using progressive configurations of scan positions in 1 ha plots. Third, we test the reproducibility of 3D sampling yielded by a 5-scan/ha sampling methodology using redundant sets of scans. Analyses were performed using measurements at analysis scales of 5 to 50 cm across the 1-ha plots, and we considered plots in grass and shrub-dominated communities separately. In grass-dominated plots, a center-scan configuration and 5 cm pixel size sampled at least 90% of the area up to 18 m away from the scanner. In shrub-dominated plots, sampling at least 90% of the area was only achieved within a distance of 12 m. We found that 3 and 5 scans/ha are needed to sample at least ~ 70% of the total area (1 ha) in the grass and shrub-dominated plots, respectively, using 5 cm pixels to measure sampling presence-absence. The reproducibility of 3D sampling provided by a 5 position scan layout across 1-ha plots was 50% (shrub) and 70% (grass) using a 5-cm voxel size, whereas at the 50-cm voxel scale, reproducibility of sampling was nearly 100% for all plot types. Future studies applying TLS in similar dryland environments for vegetation monitoring may use our results as a guide to efficiently achieve sampling coverage and reproducibility in datasets.
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Artemisia/crecimiento & desarrollo , Ecosistema , Monitoreo del Ambiente/métodos , Rayos Láser , Clima , Monitoreo del Ambiente/instrumentación , Idaho , Reproducibilidad de los Resultados , Estaciones del AñoRESUMEN
Tai Chi mind-body exercise is widely believed to improve mindfulness through incorporating meditative states into physical movements. A growing number of studies indicate that Tai Chi may improve health in knee osteoarthritis (OA), a chronic pain disease and a primary cause of global disability. However, little is known about the contribution of mindfulness to treatment effect of Tai Chi practice. Therefore, our purpose was to investigate the effect of Tai Chi mind-body practice compared to physical therapy (PT) on mindfulness in knee OA. Adults with radiographic-confirmed, symptomatic knee OA were randomized to either 12 weeks (twice weekly) of Tai Chi or PT. Participants completed the Five Facet Mindfulness Questionnaire (FFMQ) before and after intervention along with commonly-used patient-reported outcomes for pain, physical function, and other health-related outcomes. Among 86 participants (74% female, 48% white, mean age 60 years, 85% at least college educated), mean total FFMQ was 142±17. Despite substantial improvements in pain, function, and other health-related outcomes, each treatment group's total FFMQ did not significantly change from baseline (Tai Chi= 0.76, 95% CI: -2.93, 4.45; PT= 1.80, 95% CI: -2.33, 5.93). The difference in total FFMQ between Tai Chi and PT was not significant (-1.04 points, 95% CI: -6.48, 4.39). Mindfulness did not change after Tai Chi or PT intervention in knee OA, which suggests that Tai Chi may not improve health in knee OA through cultivating mindfulness. Further study is needed to identify underlying mechanisms of effective mind-body interventions among people with knee OA.
RESUMEN
La disfunción muscular de pacientes con enfermedad pulmonar obstructiva crónica (EPOC) constituye una de las comorbilidades más importantes, con repercusiones negativas en su capacidad de ejercicio y calidad de vida. En la presente normativa se ha resumido la literatura publicada más recientemente sobre los diferentes aspectos del tema y se ha utilizado también la escala Grading of Recommendations Assessment, Development, and Evaluation (GRADE) de recomendaciones sobre el grado de evidencia de las diferentes propuestas de la normativa. Respecto a una población control, se estima que en un tercio de los pacientes EPOC la fuerza del cuádriceps es un 25% inferior incluso en estadios precoces de su enfermedad. Aunque tanto los músculos respiratorios como los de las extremidades están alterados, estos últimos suelen verse mayormente afectados. Diversos factores y mecanismos biológicos están involucrados en la disfunción muscular de los pacientes. Se proponen diversas pruebas para evaluar y diagnosticar el grado de afectación de los músculos respiratorios y de las extremidades (periféricos), así como identificar la capacidad de esfuerzo de los pacientes (prueba de marcha de 6min y cicloergometría). Se describen también las posibles estrategias terapéuticas vigentes que incluyen las diversas modalidades de entrenamiento y de soporte farmacológico y nutricional.(AU)
In patients with chronic obstructive pulmonary disease (COPD), skeletal muscle dysfunction is a major comorbidity that negatively impacts their exercise capacity and quality of life. In the current guidelines, the most recent literature on the various aspects of COPD muscle dysfunction has been included. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) scale has been used to make evidence-based recommendations on the different features. Compared to a control population, one third of COPD patients exhibited a 25% decline in quadriceps muscle strength, even at early stages of their disease. Although both respiratory and limb muscles are altered, the latter are usually more severely affected. Numerous factors and biological mechanisms are involved in the etiology of COPD muscle dysfunction. Several tests are proposed in order to diagnose and evaluate the degree of muscle dysfunction of both respiratory and limb muscles (peripheral), as well as to identify the patients' exercise capacity (six-minute walking test and cycloergometry). Currently available therapeutic strategies including the different training modalities and pharmacological and nutritional support are also described.(AU)
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Humanos , Debilidad Muscular/terapia , Enfermedad Pulmonar Obstructiva Crónica , Oxígeno/uso terapéutico , Espirometría , Esteroides/uso terapéutico , Ejercicios Respiratorios , Hormona Liberadora de Hormona del Crecimiento/uso terapéutico , Apoyo Nutricional , Electrodiagnóstico , Terapia por Ejercicio , Ghrelina/uso terapéutico , Helio/uso terapéuticoRESUMEN
We report two occurrences of high-grade tears of the lateral collateral ligament complex (LCLC), consisting of the anterolateral ligament (ALL) and fibular collateral ligament (FCL). One injury occurred in a rock climber and the other in a martial artist. Increasing awareness of isolated injuries of the LCLC will allow for appropriate diagnosis and management. We review and discuss the anatomy of the LCLC, the unique mechanism of isolated injury, as well as physical and imaging examination findings.