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1.
World Neurosurg ; 188: 68-75, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38692567

ABSTRACT

OBJECTIVE: To describe a simple variation of burr hole craniostomy for the management of chronic subdural hematoma (CSDH) that uses a frontal drainage system to facilitate timely decompression in the event of tension pneumocephalus and spares the need for additional surgery. METHODS: We conducted a retrospective analysis of 20 patients with CSDH who underwent burr hole craniostomy and 20 patients who underwent the same procedure alongside the placement of a 5 Fr neonatal feeding tube as a backup drainage for the anterior craniostomy. Depending on the situation, the secondary drain stayed for a maximum of 72 hours to be opened and used in emergency settings for drainage, aspiration, or as a 1-way valve with a water seal. RESULTS: The outcomes of 20 patients who underwent this procedure and 20 controls are described. One patient from each group presented tension pneumocephalus. One was promptly resolved by opening the backup drain under a water seal to evacuate pneumocephalus and the other patient had to undergo a reopening of the craniostomy. CONCLUSIONS: The described variation of burr hole craniostomy represents a low-cost and easy-to-implement technique that can be used for emergency decompression of tension pneumocephalus. It also has the potential to reduce reoperation rates and CSDH recurrence. Prospective controlled research is needed to validate this approach further.


Subject(s)
Drainage , Hematoma, Subdural, Chronic , Pneumocephalus , Postoperative Complications , Humans , Hematoma, Subdural, Chronic/surgery , Pneumocephalus/etiology , Pneumocephalus/surgery , Pneumocephalus/diagnostic imaging , Drainage/methods , Male , Retrospective Studies , Female , Aged , Middle Aged , Aged, 80 and over , Postoperative Complications/surgery , Postoperative Complications/etiology , Cohort Studies , Craniotomy/methods , Treatment Outcome , Decompression, Surgical/methods , Adult
2.
Osteoporos Int ; 34(11): 1881-1891, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37418151

ABSTRACT

Realising the benefits of systematic secondary fracture prevention requires supporting local sites to get started and becoming effective. We here describe the development, implementation and impact of a regional fracture liaison service (FLS) mentorship programme in Latin America that led to 64 FLS getting started and coverage of 17,205 patients. INTRODUCTION: Despite treatments and service models to deliver effective secondary fracture prevention, most patients are left untreated after a fragility fracture. To improve the capability to get FLS started and more effective, we describe the development, implementation and evaluation of an international programme to develop national communities of FLS mentors as part of the Capture the Fracture Partnership in Latin America. METHODS: The IOF regional team and the University of Oxford developed the curriculum and associated resources for training mentors in setting up FLS, service improvement and mentorship. Mentors were selected during a preparatory meeting, trained using live online sessions followed by regular mentor-led post-training meetings. The programme was evaluated using a pre-training needs assessment and post-training evaluation based on Moore's outcomes. RESULTS: The mentorship programme was initiated in Mexico, Brazil, Colombia and Argentina. The mentors were multidisciplinary, including orthopaedic surgery, rehabilitation, rheumatology, endocrinology, geriatrics, gynaecology and internal medicine. There was 100% participation in training sessions and reported satisfaction with the training. Since the initiation of the training programme, 22 FLS have been set up in Mexico, 30 in Brazil, 3 in Colombia and 9 in Argentina, in comparison with two in Chile and none in any other LATAM countries that were not involved in the mentorship programme. This equates to approximately 17,025 additional patients identified from 2019 to 2021 after initiation of mentorship. The mentors have engaged with 58 FLS for service development. Post-training activities include two published national best practice guidelines and other country-specific resources for FLS in the local language. CONCLUSION: Despite the COVID pandemic, the mentorship pillar of the Capture the Fracture Partnership has developed a community of FLS mentors with measurable improvement in national FLS provision. The programme is a potentially scalable platform to develop communities of mentors in other countries.


Subject(s)
COVID-19 , Osteoporotic Fractures , Humans , Osteoporotic Fractures/prevention & control , Mentors , Latin America , Mexico , Secondary Prevention
3.
PLoS Negl Trop Dis ; 17(1): e0011040, 2023 01.
Article in English | MEDLINE | ID: mdl-36630476

ABSTRACT

People are infected with Leishmania donovani when the parasite is deposited in the dermis during the blood meal of the sand fly vector. Most infected people develop a subclinical latent infection, but some develop progressive visceral leishmaniasis. Malnutrition is a risk factor for the development of active VL. We previously demonstrated increased parasite dissemination from the skin to visceral organs in a murine model of malnutrition. Here we investigated the mechanism of early parasite dissemination. After delivery of L. donovani to the skin, we found enhanced capture of parasites by inflammatory monocytes and neutrophils in the skin of malnourished mice. However, parasite dissemination in malnourished mice was driven primarily by infected inflammatory monocytes, which showed increased CCR7 expression, greater intrinsic migratory capacity, and increased trafficking from skin to spleen. PGE2 production, which was increased at the site of skin infection, increased monocyte CCR7 expression and promoted CCR7-related monocyte-mediated early parasite dissemination in malnourished mice. Parasite dissemination in monocytes was reduced by inhibition of PGE2, knockdown or silencing of CCR7 in monocytes, and depletion of inflammatory monocytes through administration of diphtheria toxin to CSFR1-DTR transgenic mice that have monocyte-specific DT receptor expression. CCR7-driven trafficking of infected inflammatory monocytes through the lymph node was accompanied by increased expression of its ligands CCL19 and CCL21. These results show that the CCR7/PGE2 axis is responsible for the increased trafficking of L. donovani-infected inflammatory monocytes from the skin to the spleen in the malnourished host. Undernutrition and production of PGE2 are potential targets to reduce the risk of people developing VL. Nutritional interventions that target improved immune function and reduced PGE2 synthesis should be studied in people at risk of developing VL.


Subject(s)
Leishmania donovani , Leishmaniasis, Visceral , Malnutrition , Parasites , Mice , Animals , Leishmaniasis, Visceral/parasitology , Monocytes , Receptors, CCR7 , Dinoprostone , Malnutrition/complications
4.
Front Immunol ; 13: 846246, 2022.
Article in English | MEDLINE | ID: mdl-35983045

ABSTRACT

Inflammation has a role in the pathogenesis of childhood malnutrition. We investigated the effect of malnutrition and inflammatory challenge on bone marrow composition and bone health. We studied an established murine model of moderate acute malnutrition at baseline and after acute inflammatory challenge with bacterial lipopolysaccharide (LPS), a surrogate of Gram-negative bacterial sepsis, or Leishmania donovani, the cause of visceral leishmaniasis. Both of these infections cause significant morbidity and mortality in malnourished children. Of the 2 stimuli, LPS caused more pronounced bone marrow changes that were amplified in malnourished mice. LPS challenge led to increased inflammatory cytokine expression (Il1b, Il6, and Tnf), inflammasome activation, and inflammatory monocyte accumulation in the bone marrow of malnourished mice. Depletion of inflammatory monocytes in Csfr1-LysMcre-DT malnourished mice significantly reduced the inflammasome activation and IL1-ß production after LPS challenge. The inflammatory challenge also led to increased expansion of mesenchymal stem cells (MSCs), bone marrow adiposity, and expression of genes (Pparg, Adipoq, and Srbp1) associated with adipogenesis in malnourished mice. This suggests that inflammatory challenge promotes differentiation of BM MSCs toward the adipocyte lineage rather than toward bone-forming osteoblasts in the malnourished host. Concurrent with this reduced osteoblastic potential there was an increase in bone-resorbing osteoclasts, enhanced osteoclast activity, upregulation of inflammatory genes, and IL-1B involved in osteoclast differentiation and activation. The resulting weakened bone formation and increased bone resorption would contribute to the bone fragility associated with malnutrition. Lastly, we evaluated the effect of replacing lipid rich in omega-6 fatty acids (corn oil) with lipid-rich in omega-3 fatty acids (fish oil) in the nutrient-deficient diet. LPS-challenged malnourished mice that received dietary fish oil showed decreased expression of inflammatory cytokines and Rankl and reduced osteoclast differentiation and activation in the bone marrow. This work demonstrates that the negative effect of inflammatory challenge on bone marrow is amplified in the malnourished host. Increasing dietary intake of omega-3 fatty acids may be a means to reduce inflammation and improve bone health in malnourished children.


Subject(s)
Fatty Acids, Omega-3 , Malnutrition , Animals , Bone Density , Bone Marrow/metabolism , Cytokines/metabolism , Fish Oils , Inflammasomes , Inflammation , Lipopolysaccharides , Mice
5.
PLoS One ; 17(7): e0264566, 2022.
Article in English | MEDLINE | ID: mdl-35901034

ABSTRACT

Current medical guidelines consider pregnant women with COVID-19 to be a high-risk group. Since physiological gestation downregulates the immunological response to maintain "maternal-fetal tolerance", SARS-CoV-2 infection may constitute a potentially threatening condition to both the mother and the fetus. To establish the immune profile in pregnant COVID-19+ patients, a cross-sectional study was conducted. Pregnant women with COVID-19 (P-COVID-19+; n = 15) were analyzed and compared with nonpregnant women with COVID-19 (NP-COVID-19+; n = 15) or those with physiological pregnancy (P-COVID-19-; n = 13). Serological cytokine and chemokine concentrations, leucocyte immunophenotypes, and mononuclear leucocyte responses to polyclonal stimuli were analyzed in all groups. Higher concentrations of serological TNF-α, IL-6, MIP1b and IL-4 were observed within the P-COVID-19+ group, while cytokines and chemokines secreted by peripheral leucocytes in response to LPS, IL-6 or PMA-ionomicin were similar among the groups. Immunophenotype analysis showed a lower percentage of HLA-DR+ monocytes in P-COVID-19+ than in P-COVID-19- and a higher percentage of CD39+ monocytes in P-COVID-19+ than in NP-COVID-19+. After whole blood polyclonal stimulation, similar percentages of T cells and TNF+ monocytes between groups were observed. Our results suggest that P-COVID-19+ elicits a strong inflammatory response similar to NP-COVID19+ but also displays an anti-inflammatory response that controls the ATP/adenosine balance and prevents hyperinflammatory damage in COVID-19.


Subject(s)
COVID-19 , Monocytes , Apyrase/immunology , Cross-Sectional Studies , Cytokines , Female , Humans , Interleukin-6 , Pregnancy , SARS-CoV-2
6.
Cancer Treat Res Commun ; 31: 100540, 2022.
Article in English | MEDLINE | ID: mdl-35231874

ABSTRACT

PURPOSE: Prediction of clinical complete response in rectal cancer before neoadjuvant chemo-radiotherapy treatment enables treatment selection. Patients predicted to have complete response could have chemo-radiotherapy, and others could have additional doublet chemotherapy at this stage of their treatment to improve their overall outcome. This work investigates the role of clinical variables in predicting clinical complete response. METHOD: Using the UK-based OnCoRe database (2008 to 2019), we performed a propensity-score matched study of 322 patients who received neoadjuvant chemoradiotherapy. We collected pre-treatment clinic-pathological, inflammatory and radiotherapy-related characteristics. We determined the odds for the occurrence of cCR using conditional logistic regression models. We derived the post-model Area under the Curve (AUC) as an indicator of discrimination performance and stated a priori that an AUC of 0.75 or greater was required for potential clinical utility. RESULTS: Pre-treatment tumour diameter, mrT-stage, haemoglobin, alkaline phosphate and total radiotherapy depths were associated with cCR on univariable and multivariable analysis. Additionally, neutrophil to lymphocyte ratio (NLR), neutrophil-monocyte to lymphocyte ratio (NMLR), lymphocyte count and albumin were all significantly associated with cCR on multivariable analysis. A nomogram using the above parameters was developed with a resulting ROC AUC of 0.75. CONCLUSION: We identified routine clinic-pathological, inflammatory and radiotherapy-related variables which are independently associated with cCR. A nomogram was developed to predict cCR. The performance characteristics from this model were on the prior clinical utility threshold. Additional research is required to develop more associated variables to better select patients with rectal cancer undergoing chemoradiotherapy who may benefit from pursuing a W&W strategy.


Subject(s)
Rectal Neoplasms , Chemoradiotherapy , Humans , Neoadjuvant Therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Treatment Outcome
8.
Rev. clín. esp. (Ed. impr.) ; 221(10): 592-595, dic. 2021. tab
Article in Spanish | IBECS | ID: ibc-227039

ABSTRACT

Introducción El efecto de la dexametasona en la fase inicial de la infección por SARS-CoV-2 y su influencia sobre la COVID-19 no está bien definido. Describimos las características clínico-radiológicas, los parámetros de tormenta de citoquinas y la evolución clínica de una serie de pacientes tratados con dexametasona en la fase inicial de la enfermedad. Método Estudio de 8 pacientes que recibieron dexametasona previo al desarrollo de la COVID-19. Evaluamos variables clínicas, pruebas de imagen, parámetros de liberación de citoquinas, tratamiento empleado y su evolución. Resultados Todos los pacientes recibieron una dosis de 6mg/día con una duración media de 4,5 días previos al ingreso. La mayoría de los pacientes presentaron una extensión grave en la tomografía computarizada de alta resolución (TCAR) y una elevación leve de los parámetros de liberación de citoquinas; 3 pacientes requirieron oxigenoterpia nasal de alto flujo (ONAF) por insuficiencia respiratoria, y ningún paciente requirió intubación orotraqueal ni falleció. Conclusión La dexametasona en las fases iniciales de la infección por SARS-CoV-2 parece asociarse con una COVID-19 grave (AU)


Introduction The effect of dexamethasone in the initial phase of infection by SARS-CoV-2 and its influence on COVID-19 is not well defined. We describe clinical-radiological characteristics, the cytokine storm parameters, and the clinical evolution of a series of patients treated with dexamethasone in the disease's initial phase. Method A study of 8 patients who received dexamethasone before the development of COVID-19. We evaluate clinical variables, imaging tests, cytokine release parameters, treatment used and patient evolution. Results All patients received a 6mg/day dose with a mean duration of 4.5 days before admission. High resolution computed tomography (HRCT) revealed that most of them presented a severe extension; most patients had a slightly elevated level of cytokine release parameters. Three patients required high-flow oxygen therapy due to respiratory failure; none required orotracheal intubation or died. Conclusion Dexamethasone in the early stages of SARS-CoV-2 infection appears to be associated with severe COVID-19 (AU)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Dexamethasone/administration & dosage , Anti-Inflammatory Agents/administration & dosage , /drug therapy , Severity of Illness Index , Retrospective Studies
9.
Rev Clin Esp (Barc) ; 221(10): 592-595, 2021 12.
Article in English | MEDLINE | ID: mdl-34563488

ABSTRACT

INTRODUCTION: The effect of dexamethasone in the initial phase of infection by SARS-CoV-2 and its influence on COVID-19 is not well defined. We describe clinical-radiological characteristics, the cytokine storm parameters, and the clinical evolution of a series of patients treated with dexamethasone in the disease's initial phase. METHOD: A study of 8 patients who received dexamethasone before the development of COVID-19. We evaluate clinical variables, imaging tests, cytokine release parameters, treatment used and patient evolution. RESULTS: All patients received a 6 mg/day dose with a mean duration of 4.5 days before admission. High resolution computed tomography (HRCT) revealed that most of them presented a severe extension; most patients had a slightly elevated level of cytokine release parameters. Three patients required high-flow oxygen therapy due to respiratory failure; none required orotracheal intubation or died. CONCLUSION: Dexamethasone in the early stages of SARS-CoV-2 infection appears to be associated with severe COVID-19.


Subject(s)
COVID-19 Drug Treatment , Cytokine Release Syndrome , Dexamethasone , Humans , SARS-CoV-2
10.
Rev Sci Instrum ; 92(6): 063518, 2021 Jun 01.
Article in English | MEDLINE | ID: mdl-34243512

ABSTRACT

A simple and selective new technique for atomic hydrogen flux measurements in a hydrogen plasma environment is introduced and demonstrated in this work. This technique works by measuring the etching rate of an amorphous carbon film and translating this to an incoming hydrogen radical flux through a well-defined carbon etch yield per radical. Ions present in the plasma environment have a much higher etch yield than radicals do. For that reason, suppression of the ion flux toward the carbon film is crucial to ensure that the observed carbon etch rate is dominated by atomic hydrogen etching. It is demonstrated that this can be achieved using a simple cylindrical pipe (hereinafter "chimney") in which a bend is introduced to enforce ion-wall collisions, neutralizing the ions. The chimney is made out of Macor, a material with low catalytic surface activity, to preserve the incoming atomic hydrogen flux while effectively suppressing ions. Ultimately, the etching sensor is deployed in a radio frequency inductively coupled hydrogen plasma operated at low pressure (1-10 Pa). Atomic hydrogen fluxes are measured and compared with heat flux sensor and vacuum ultraviolet absorption spectroscopy measurements in the same setup. All sensors agreed within a factor 4 in the atomic hydrogen flux range 1019 to 1021 m-2 s-1.

11.
Clin Oncol (R Coll Radiol) ; 33(10): e433-e441, 2021 10.
Article in English | MEDLINE | ID: mdl-34090753

ABSTRACT

AIMS: Careful management of a patient's nutritional status during and after treatment for head and neck squamous cell cancers (HNSCC) is crucial for optimal outcomes. The aim of this study was to develop a model for stratifying a patient's risk of requiring reactive enteral feeding through a nasogastric tube during radiotherapy for HNSCC, based on clinical and treatment-related factors. MATERIALS AND METHODS: A cohort of consecutive patients treated with definitive (chemo)radiotherapy for HNSCC between January 2016 and January 2018 was identified in the institutional electronic database for retrospective analysis. Patients requiring enteral feeding pretreatment were excluded. Clinical and treatment data were obtained from prospectively recorded electronic clinical notes and planning software. RESULTS: Baseline patient characteristics and tumour-related parameters were captured for 225 patients. Based on the results of the univariate analysis and using a stepwise backwards selection process, clinical and dosimetric variables were selected to optimise a clinically predictive multivariate model, fitted using logistic regression. The parameters found to affect the probability, P, of requiring a nasogastric feeding tube for >4 weeks in our clinical multivariate model were: tumour site, tumour stage (early T0/1/2 stage versus advanced T3/T4 stage), chemotherapy drug (none versus any drug) and mean dose to the contralateral parotid gland. A scoring model using the regression coefficients of the selected variables in the clinical multivariate model achieved an area under the curve (AUC) of 0.745 (95% confidence interval 0.678-0.812), indicating good discriminative performance. Internal validation of the model involved splitting the dataset 80:20 into training and test datasets 10 times and assessing differences in AUC of the model fitted to these. CONCLUSIONS: We developed an easy-to-use prediction model based on both clinical and dosimetric parameters, which, once externally validated, can lead to more personalised treatment planning and inform clinical decision-making on the appropriateness of prophylactic versus reactive enteral feeding.


Subject(s)
Enteral Nutrition , Head and Neck Neoplasms , Chemoradiotherapy , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Humans , Intubation, Gastrointestinal , Retrospective Studies
12.
Rev Clin Esp ; 221(10): 592-595, 2021 Dec.
Article in Spanish | MEDLINE | ID: mdl-33716310

ABSTRACT

INTRODUCTION: The effect of dexamethasone in the initial phase of infection by SARS-CoV-2 and its influence on COVID-19 is not well defined. We describe clinical-radiological characteristics, the cytokine storm parameters, and the clinical evolution of a series of patients treated with dexamethasone in the disease's initial phase. METHOD: A study of 8 patients who received dexamethasone before the development of COVID-19. We evaluate clinical variables, imaging tests, cytokine release parameters, treatment used and patient evolution. RESULTS: All patients received a 6 mg/day dose with a mean duration of 4.5 days before admission. High resolution computed tomography (HRCT) revealed that most of them presented a severe extension; most patients had a slightly elevated level of cytokine release parameters. Three patients required high-flow oxygen therapy due to respiratory failure; none required orotracheal intubation or died. CONCLUSION: Dexamethasone in the early stages of SARS-CoV-2 infection appears to be associated with severe COVID-19.

13.
Med Phys ; 48(1): 414-426, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33164217

ABSTRACT

PURPOSE: Due to the electron return effect (ERE) during magnetic resonance imaging guided radiotherapy (MRIgRT), rectal gas during pelvic treatments can result in hot spots of over-dosage in the rectal wall. Determining the clinical impact of this effect on rectal toxicity requires estimation of the amount and mobility (and stability) of rectal gas during treatment. We therefore investigated the amount of rectal gas and local inter- and intra-fractional changes of rectal gas in pelvic cancer patients. METHODS: To estimate the volume of gas present at treatment planning, the rectal gas contents in the planning computed tomography (CT) scans of 124 bladder, 70 cervical and 2180 prostate cancer patients were calculated. To estimate inter- and intra-fractional variations in rectal gas, 174 and 131 T2-w MRIs for six cervical and eleven bladder cancer patients were used. These scans were acquired during four scan-sessions (~20-25 min each) at various time-points. Additionally, 258 T2-w MRIs of the first five prostate cancer patients treated using MRIgRT at our center, acquired during each fraction, were analyzed. Rectums were delineated on all scans. The area of gas within the rectum delineations was identified on each MRI slice using thresholding techniques. The area of gas on each slice of the rectum was used to calculate the inter- and intra-fractional group mean, systematic and random variations along the length of the rectum. The cumulative dose perturbation as a result of the gas was estimated. Two approaches were explored: accounting or not accounting for the gas at the start of the scan-session. RESULTS: Intra-fractional variations in rectal gas are small compared to the absolute volume of rectal gas detected for all patient groups. That is, rectal gas is likely to remain stable for periods of 20-25 min. Larger volumes of gas and larger variations in gas volume were observed in bladder cancer patients compared with cervical and prostate cancer patients. For all patients, local cumulative dose perturbations per beam over an entire treatment in the order of 60 % were estimated when gas had not been accounted for in the daily adaption. The calculated dose perturbation over the whole treatment was dramatically reduced in all patients when accounting for the gas in the daily set-up image. CONCLUSION: Rectal gas in pelvic cancer patients is likely to remain stable over the course of an MRIgRT fraction, and also likely to reappear in the same location in multiple fractions, and can therefore result in clinically relevant over-dosage in the rectal wall. The over-dosage is reduced when accounting for gas in the daily adaption.


Subject(s)
Pelvic Neoplasms , Prostatic Neoplasms , Radiotherapy, Image-Guided , Humans , Male , Pelvic Neoplasms/diagnostic imaging , Pelvic Neoplasms/radiotherapy , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/radiotherapy , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Rectum/diagnostic imaging
14.
PLoS One ; 15(11): e0242337, 2020.
Article in English | MEDLINE | ID: mdl-33180876

ABSTRACT

Visceral leishmaniasis (VL) is characterized by expansion of myeloid cells in the liver and spleen, which leads to a severe splenomegaly associated with higher risk of mortality. This increased cellularity is thought to be a consequence of recruitment of cells to the viscera. We studied whether the local proliferation of splenic myeloid cells contributes to increased splenic cellularity. We found that a monocyte-like population of adherent splenic cells from Leishmania donovani-infected hamsters had enhanced replicative capacity ex vivo and in vivo (BrdU incorporation, p<0.0001). In vitro assays demonstrated that proliferation was more pronounced in the proinflammatory M1 environment and that intracellular infection prevented proliferation. Secondary analysis of the published splenic transcriptome in the hamster model of progressive VL revealed a gene expression signature that included division of tumoral cells (Z = 2.0), cell cycle progression (Z = 2.3), hematopoiesis (Z = 2.8), proliferation of stem cells (Z = 2.5) and overexpression of proto-oncogenes. Regulators of myeloid cell proliferation were predicted in-silico (CSF2, TLR4, IFNG, IL-6, IL-4, RTK signaling, and STAT3). The in-silico prediction was confirmed with chemical inhibitors of PI3K/AKT, MAPK and STAT3 which decreased splenic myeloid cell division ex vivo. Hamsters infected with L. donovani treated with a STAT3 inhibitor had reduced in situ splenic myeloid proliferation (p = 0.03) and parasite burden. We conclude that monocyte-like myeloid cells have increased STAT3-dependent proliferation in the spleen of hamsters with visceral leishmaniasis and that inhibition of STAT3 reduces myeloid cell proliferation and parasite burden.


Subject(s)
Leishmaniasis, Visceral/immunology , Myeloid Cells/metabolism , Spleen/metabolism , Animals , Cell Proliferation/physiology , Cytokines/metabolism , Disease Models, Animal , Female , Leishmania donovani/metabolism , Leishmania donovani/pathogenicity , Leishmaniasis, Visceral/physiopathology , Liver/immunology , Liver/metabolism , Macrophages/metabolism , Mesocricetus , Myeloid Cells/physiology , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction , Spleen/immunology , Transcriptome
15.
PLoS Negl Trop Dis ; 14(8): e0008482, 2020 08.
Article in English | MEDLINE | ID: mdl-32776923

ABSTRACT

Current drug therapies for cutaneous leishmaniasis are often difficult to administer and treatment failure is an increasingly common occurrence. The efficacy of anti-leishmanial therapy relies on a combination of anti-parasite activity of drugs and the patient's immune response. Previous studies have reported in vitro antimicrobial activity of histamine 1-receptor antagonists (H1RAs) against different pathogens. We used an ex vivo explant culture of lymph nodes from mice infected with Leishmania major to screen H1RAs compounds. Azelastine (AZ) and Fexofenadine (FX) showed remarkable ex vivo efficacy (EC50 = 0.05 and 1.50 µM respectively) and low in vitro cytotoxicity yielding a high therapeutic index. AZ significantly decreased the expression of H1R and the proinflammatory cytokine IL-1ẞ in the ex vivo system, which were shown to be augmented by histamine addition. The anti-leishmanial efficacy of AZ was enhanced in the presence of T cells from infected mice suggesting an immune-modulatory mechanism of parasite suppression. L. major infected BALB/c mice treated per os with FX or intralesionally with AZ showed a significant reduction of lesion size (FX = 69%; AZ = 52%). Furthermore, there was significant parasite suppression in the lesion (FX = 82%; AZ = 87%) and lymph nodes (FX = 81%; AZ = 36%) with no observable side effects. AZ and FX and potentially other H1RAs are good candidates for assessing efficacy in larger studies as monotherapies or in combination with current anti-leishmanial drugs to treat cutaneous leishmaniasis.


Subject(s)
Histamine H1 Antagonists, Non-Sedating/therapeutic use , Leishmaniasis, Cutaneous/drug therapy , Phthalazines/therapeutic use , Terfenadine/analogs & derivatives , Animals , Leishmania major , Lymph Nodes/parasitology , Male , Mice , Mice, Inbred BALB C , Molecular Structure , Phthalazines/chemistry , Terfenadine/chemistry , Terfenadine/therapeutic use , Tissue Culture Techniques
16.
Med Phys ; 47(6): 2506-2515, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32145087

ABSTRACT

PURPOSE: Dose deposition around unplanned air cavities during magnetic resonance-guided radiotherapy (MRgRT) is influenced by the electron return effect (ERE). This is clinically relevant for gas forming close to or inside organs at risk (OARs) that lie in the path of a single beam, for example, intestinal track during pelvic treatment. This work aims to verify Monte Carlo calculations that predict the dosimetric effects of ERE around air cavities. For this, we use GafChromic EBT3 film inside poly-methyl methacrylate (PMMA) -air phantoms. METHOD: Four PMMA phantoms were produced. Three of the phantoms contained centrally located spherical air cavities (0.5, 3.5, 7.5 cm diameter), and one phantom contained no air. The phantoms were split to sandwich GafChromic EBT3 film in the center. The phantoms were irradiated on an Elekta Unity system using a single 10 × 10 cm2 7-MV photon beam under the influence of a 1.5-T transverse magnetic field. The measurements were replicated using the Elekta Monaco treatment planning system (TPS). Gamma analysis with pass criteria 3%/3 mm was used to compare the measured and calculated dose distributions. We also consider 3%/2 mm, 2%/3 mm, and 2%/2 mm pass criteria for interest. RESULTS: The gamma analysis showed that >95% of the points agreed between the TPS-calculated and measured dose distributions, using 3%/3 mm criteria. The phantom containing the largest air cavity had the lowest agreement, with most of the disagreeing points lying inside the air cavity (dose to air region). CONCLUSIONS: The dose effects due to ERE around spherical air cavities are being calculated in the TPS with sufficient accuracy for clinical use.


Subject(s)
Electrons , Radiotherapy Planning, Computer-Assisted , Monte Carlo Method , Particle Accelerators , Phantoms, Imaging , Radiotherapy Dosage
17.
Med Oral Patol Oral Cir Bucal ; 24(2): e156-e164, 2019 Mar 01.
Article in English | MEDLINE | ID: mdl-30818307

ABSTRACT

BACKGROUND: The aim was to evaluate the effect of silver loaded nanoparticles (NPs) application on the triboscopic, crystallographic and viscoelastic properties of demineralized dentin. Polymethylmetacrylate-based NPs and Ag loaded NPs were applied on demineralized dentin. MATERIAL AND METHODS: Treated and untreated surfaces were probed by a nanoindenter to test viscoelasticity, and by atomic force microscopy to test nanoroughness and collagen fibril diameter. X-ray diffraction and transmission electron microscopy through selected area diffraction and bright-field imaging were also used. RESULTS: Dentin treated with Ag-NPs attained the lowest complex modulus, and the highest tan delta values after 7 days of storage. Dentin treated with undoped-NPs achieved the lowest nanoroughness and the greatest collagen bandwidths among groups. Crystals were identified as hydroxyapatite with the highest crystallographic maturity and crystallite size in dentin treated with undoped-NPs. Texture increased in all samples from 24 h to 7 d, except in dentin surfaces treated with Ag-NPs at 310 plane. Polyhedral, block-like, hexagonal or plate-like shaped apatite crystals constituted the bulk of minerals in dentin treated with Ag-NPs, after 7 d. Polyhedral or rounded/drop-like, and polymorphic in strata crystal apatite characterized the minerals when undoped-NPs were used, with more crystalline characteristics after 7 d than that found when Ag-NPs were applied. Ag-NPs application did not improve the mechanical performance of dentin and did not produce dentin remineralization. However, energy was dissipated through the dentin without showing stress concentration; contrary was occurring at dentin treated with undoped-NPs, that provoked bridge-like mineral deposits at the dentin surface. CONCLUSIONS: Ag-NPs application did not enhance the mechanical properties of cervical dentin, though the energy dissipation did not damage the dentin structure. Remineralization at dentin was not produced after Ag-NPs application, though improved crystallinity may lead to increase stability of the apatite that was generated at the dentin surface.


Subject(s)
Dentin/drug effects , Metal Nanoparticles/chemistry , Silver/pharmacology , Tooth Remineralization , Collagen , Humans , Materials Testing , Microscopy, Atomic Force , Microscopy, Electron, Transmission , Polymethyl Methacrylate/pharmacology , Surface Properties , Time Factors , Viscoelastic Substances , X-Ray Diffraction
18.
Med Oral Patol Oral Cir Bucal ; 23(6): e646-e655, 2018 Nov 01.
Article in English | MEDLINE | ID: mdl-30341273

ABSTRACT

BACKGROUND: The purpose of this study was to evaluate nanohardness and viscoelastic behavior of dentin surfaces treated with two canal sealer cements for dentin remineralization. MATERIAL AND METHODS: Dentin surfaces were subjected to: i) 37% phosphoric acid (PA) or ii) 0.5 M ethylenediaminetetraacetic acid (EDTA) conditioning prior to the application of two experimental hydroxyapatite-based cements, containing sodium hydroxide (calcypatite) or zinc oxide (oxipatite), respectively. Samples were stored in simulated body fluid during 24 h or 21 d. The intertubular and peritubular dentin were evaluated using a nanoindenter to assess nanohardness (Hi). The load/displacement responses were used for the nano-dynamic mechanical analysis to estimate complex modulus (E*) and tan delta (δ). The modulus mapping was obtained by imposing a quasistatic force setpoint to which a sinusoidal force was superimposed. AFM imaging and FESEM analysis were performed. RESULTS: After 21 d of storage, dentin surfaces treated with EDTA+calcypatite, PA+calcypatite and EDTA+oxipatite showed viscoelastic discrepancies between peritubular and intertubular dentin, meaning a risk for cracking and breakdown of the surface. At both 24 h and 21 d, tan δ values at intertubular dentin treated with the four treatments performed similar. At 21 d time point, intertubular dentin treated with PA+oxipatite achieved the highest complex modulus and nanohardness, i.e., highest resistance to deformation and functional mineralization, among groups. CONCLUSIONS: Intertubular and peritubular dentin treated with PA+oxipatite showed similar values of tan δ after 21 d of storage. This produced a favorable dissipation of energy with minimal energy concentration, preserving the structural integrity at the dentin surface.


Subject(s)
Dental Cements/pharmacology , Dentin/drug effects , Sodium Hydroxide/pharmacology , Tooth Remineralization/methods , Zinc Oxide/pharmacology , Humans , In Vitro Techniques , Materials Testing , Surface Properties
19.
Med. U.P.B ; 37(2): 97-106, 22 de agosto de 2018.
Article in Spanish | LILACS, COLNAL | ID: biblio-912071

ABSTRACT

Objetivo: la reserva cognitiva (RC) se define como la capacidad cerebral de tolerar y soportar las neuropatologías antes de alcanzar el umbral que da inicio a las manifestaciones clínicas. Debido al aumento de la esperanza de vida, este concepto surge con el propósito de identificar factores que mantengan la funcionalidad e independencia de los adultos mayores, favoreciendo así la calidad de vida en este grupo poblacional. El objetivo de este estudio fue analizar la relación entre el tiempo de exposición a práctica musical dirigida y el rendimiento cognitivo de adultos mayores sanos. Metodología: estudio observacional descriptivo de 11 adultos mayores sanos con historia de práctica musical dirigida. Se aplicó el cuestionario de Reserva Cognitiva, y se evaluó el rendimiento neurocognitivo con el test de capacidad intelectual K-BIT y la batería NEURONORMA COLOMBIA. Resultados: en personas con entrenamiento musical, la reserva cognitiva está relacionada con mejor desempeño en tareas de denominación, memoria de trabajo visoespacial y verbal, atención focalizada y alternante, fluidez verbal fonológica y rendimiento semántico. Por otra parte, el tiempo de exposición a práctica musical dirigida se asoció a mejor desempeño en lenguaje semántico y favorece la memoria de trabajo y a largo plazo. Conclusiones: el tiempo de exposición a la práctica musical dirigida, la edad y el nivel educativo, favorecen la reserva cognitiva en los dominios lingüísticos y mnémicos.


Objective: cognitive reserve (CR) is defined as the brain's ability to tolerate and support neuropathologies before reaching the threshold that gives rise to clinical manifestations. Due to the increase in life expectancy, this concept arises with the purpose of identifying factors that maintain the functionality and independence of the elderly, thus favoring the quality of life in this population group. The objective of this study was to analyze the relationship between the time of exposure to directed musical practice and the cognitive performance of healthy older adults. Methodology: Observational, descriptive study including 11 healthy, older adults with a history of guided musical practice. The Cognitive Reserve questionnaire was applied and neurocognitive performance was evaluated using the K-BIT intellectual capacity test and the NEURONORMA COLOMBIA battery. Results: in people with musical training, cognitive reserve was associated to better performance in tasks of denomination, visuospatial and verbal working memory, focused and alternating attention, phonological verbal fluency and semantic performance. On the other hand, the time of exposure to directed musical practice was associated to better performance in semantic language and favored working memory and in the long term. Conclusions: time of exposure to directed musical practice, age, and educational level favor cognitive reserve in the linguistic and mnemonic domains.


Objetivo: a reserva cognitiva (RC) se define como a capacidade cerebral de tolerar e suportar as neuropatologias antes de alcançar o umbral que dá início às manifestações clínicas. Devido ao aumento da esperança de vida, este conceito surge com o propósito de identificar fatores que mantenham a funcionalidade e independência dos adultos maiores, favorecendo assim a qualidade de vida neste grupo populacional. O objetivo deste estudo foi analisar a relação entre o tempo de exposição a prática musical dirigida e o rendimento cognitivo de adultos maiores saudáveis. Metodologia: estudo observacional descritivo de 11 adultos maiores saudáveis com história de prática musical dirigida. Se aplicou o questionário de Reserva Cognitiva, e se avaliou o rendimento neurocognitivo com o teste de capacidade intelectual K-BIT e a bateria NEURONORMA COLÔMBIA. Resultados: em pessoas com treinamento musical, a reserva cognitiva está relacionada com melhor desempenho em tarefas de denominação, memória de trabalho visoespacial e verbal, atenção focalizada e alternante, fluidez verbal fonológica e rendimento semântico. Por outra parte, o tempo de exposição a prática musical dirigida se associou a melhor desempenho em linguagem semântico e favorece a memória de trabalho e a longo prazo. Conclusões: o tempo de exposição à prática musical dirigida, a idade e o nível educativo, favorecem a reserva cognitiva nos domínios linguísticos e mnêmicos.


Subject(s)
Humans , Middle Aged , Aged , Aged, 80 and over , Cognitive Reserve , Aging , Cognitive Aging , Memory, Short-Term
20.
Chem Commun (Camb) ; 53(89): 12112-12115, 2017 Nov 07.
Article in English | MEDLINE | ID: mdl-29072722

ABSTRACT

A new approach to stabilize compounds containing a planar tetracoordinate carbon (ptC), embedded in aromatic hydrocarbons, is presented herein. This is achieved by using ligands that promote the formation of a 3c-2e σ-bond with the ptC under two conditions: without altering the sp2 hybridization of the aromatic carbons; and containing empty orbitals perpendicular to the aromatic ring to participate in the aromatic π-electronic delocalization.

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