ABSTRACT
OBJECTIVE: The purpose of this study was to investigate possible differences in the filling of the various recesses of the maxillary sinus after the procedure of sinus floor elevation in relation with the initial volume of the same and if the sinus volume can influence long-term graft dimensions, by using cone beam computed tomography (CBCT) as diagnostic analysis device. PATIENTS AND METHODS: This study included 32 sinuses corresponding to 16 patients referred for bilateral maxillary sinus augmentation procedures needing to increase the volume of the surgical site with the porcine cortical bone for dental implant placement in the posterior maxilla. The sinuses were analyzed by preoperative and postoperative (15 days and 6 months after sinus surgery) cone beam computed tomography. RESULTS: No statistically significant relations were observed between initial sinus dimensions and the entity of the contraction of the graft between T1 (15 days after surgery) and T2 (180 days after surgery). The behavior was the same either for the large sinus (> 15.65 cm3) and for the small one (< 15.65 cm3). Instead, about the filling of the various sinus recesses, a linear regression model was used to explain the difference between the mean preoperative and postoperative surgical spaces; in most of the samples, the filling of the anterior recess was ~15% of the total volume of the graft, i.e., the minor one among the main recesses. CONCLUSIONS: Our findings suggest that: (1) in the procedure of sinus floor augmentation by a lateral approach with deproteinized porcine bone there are no relations between the initial dimensions of the sinus and the long-term dimensional changes of the graft, and (2) that, among the main recesses of the sinus, the anterior one is generally the less filled.
Subject(s)
Sinus Floor Augmentation , Animals , Swine , Sinus Floor Augmentation/methods , Maxillary Sinus , Bone Transplantation , Cone-Beam Computed Tomography/methods , Maxilla/surgeryABSTRACT
Background: Hypersensitivity pneumonitis (HP) is a syndrome caused by sensitisation to inhaled antigens that leads to an abnormal immune response in the airways and lung parenchyma. Some patients previously diagnosed with certain types of fibrotic interstitial lung diseases (f-ILDs), including fibrotic HP (f-HP), are susceptible to develop a progressive fibrosing phenotype (PF-ILD), despite initial state-of-the-art management. Objectives: To characterise a cohort of patients with a multidisciplinary diagnosis (MTD) of chronic f-HP, who were followed up in an ILD outpatient clinic of a hospital in Portugal, and to assess the prevalence of PF-ILD criteria in these patients. Methods: Data were collected from all patients with a definite or provisional diagnosis of f-HP after a multidisciplinary team discussion. Patients were followed up between December 2014 and July 2019. Data included clinical characteristics, high-resolution chest tomography (HRCT) disease patterns, lung function tests, bronchoalveolar lavage and further immunological work-up, biopsy reports (conventional transbronchial lung biopsy, transbronchial lung cryobiopsy or surgical video-assisted thoracoscopic lung biopsy), all ILD multidisciplinary team records and diagnostic confidence levels. Patients were assessed according to PF-ILD criteria as defined in the INBUILD trial. Results: We identified 83 patients with an MTD of HP, who had been followed up for at least 12 months. Of these, 63 (75.9%) were diagnosed with f-HP. Of the 63 f-HP patients, 33.3% (n=21) fulfilled the predefined criteria for PF-HP: 66.7% had a relative decline of ≥10% forced vital capacity (FVC); 5% a relative decline of 5 - 9% FVC, with worsening symptoms or increased fibrosis on HRCT; and 23.8% had worsening respiratory symptoms with radiological progression. Conclusion: This single-centre cohort study demonstrated that a third of f-HP patients presented with PF-ILD, as determined by progression during initial standard-of-care treatment. A usual interstitial pneumonia (UIP)/UIP-like pattern was present in >70% of patients with f-HP, and two-thirds of these patients had an FVC decline of ≥10%. PF-HP patients were also more exacerbation prone. According to recent trial data, this segment of patients can be considered possible candidates for antifibrotic treatment, with a reasonable prospect of effectiveness. Further efforts should focus on refining knowledge of longitudinal behaviour of large multicentric cohorts of f-HP patients, establishing a consensual and uniform definition of progression for use in clinical practice, as well as developing prognostic prediction tools to better (and early) inform the disease course.
ABSTRACT
OBJECTIVE: Since no effective therapy exists, we aimed to test existing HIV antivirals for combination treatment of Coronavirus disease 19 (COVID-19). MATERIALS AND METHODS: The crystal structures of SARS-CoV-2 main protein (Mpro) (PDB ID: 6Y2F) and SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) (PDB ID: 7BV2) both available from Protein Data Bank were used in the study. Automated Docking by using blind and standard method both on Mpro and RdRp bound to the modified template-primer RNA was performed with AutoDock 4.2.6 program suite. Lamarckian genetic algorithm (LGA) was used for structures docking. All inhibitors were docked with all bonds completely free to rotate. RESULTS: Our molecular docking findings suggest that lopinavir, ritonavir, darunavir, and atazanavir activated interactions with the key binding sites of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) protease with a better inhibition constant (Ki) for lopinavir, ritonavir, and darunavir. Furthermore, we evidenced the ability of remdesivir, tenofovir, emtricitabine, and lamivudine to be incorporated in SARS-CoV-2 RdRp in the same protein pocket where poses the corresponding natural nucleoside substrates with comparable Ki and activating similar interactions. In principle, the four antiviral nucleotides might be used effectively against SARS-CoV-2. CONCLUSIONS: The combination of a protease inhibitor and two nucleoside analogues, drugs widely used to treat HIV infection, could be evaluated in clinical trials for the treatment of COVID-19.
Subject(s)
Antiviral Agents/pharmacology , COVID-19 Drug Treatment , Drug Therapy, Combination/methods , Nucleosides/therapeutic use , Protease Inhibitors/therapeutic use , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Atazanavir Sulfate , Darunavir , Drug Combinations , Early Medical Intervention , Emtricitabine , Humans , Lamivudine , Lopinavir , Molecular Docking Simulation , Ritonavir , SARS-CoV-2ABSTRACT
Fusion oncogenes (FOs) are common in many cancer types and are powerful drivers of tumor development. Because their expression is exclusive to cancer cells and their elimination induces cell apoptosis in FO-driven cancers, FOs are attractive therapeutic targets. However, specifically targeting the resulting chimeric products is challenging. Based on CRISPR/Cas9 technology, here we devise a simple, efficient and non-patient-specific gene-editing strategy through targeting of two introns of the genes involved in the rearrangement, allowing for robust disruption of the FO specifically in cancer cells. As a proof-of-concept of its potential, we demonstrate the efficacy of intron-based targeting of transcription factors or tyrosine kinase FOs in reducing tumor burden/mortality in in vivo models. The FO targeting approach presented here might open new horizons for the selective elimination of cancer cells.
Subject(s)
CRISPR-Cas Systems/genetics , Neoplasms/genetics , Oncogene Fusion/genetics , Animals , Base Sequence , Cell Line, Tumor , Cell Proliferation/genetics , Doxorubicin/therapeutic use , Fusion Proteins, bcr-abl/genetics , Gene Deletion , Genetic Loci , Genomic Instability , HEK293 Cells , Humans , Introns/genetics , Mice, Nude , Neoplasms/drug therapy , Neoplasms/pathology , Oncogene Proteins, Fusion/genetics , RNA, Guide, Kinetoplastida/metabolism , Reproducibility of Results , Xenograft Model Antitumor AssaysABSTRACT
INTRODUCCIÓN: El marcapasos diafragmático (MD) ha demostrado su utilidad en la sustitución de la ventilación mecánica en pacientes afectos de lesiones medulares crónicas (LMC) y esclerosis lateral amiotrófica (ELA), mejorando la calidad de vida y reduciendo la morbimortalidad y los costes sanitarios asociados. El manejo anestésico de dichos pacientes y las particularidades del procedimiento quirúrgico suponen un reto anestésico. El objetivo de nuestro estudio es el análisis del manejo y las complicaciones intraoperatorias de los pacientes sometidos a MD en nuestra institución. METODOLOGÍA: Se trata de una revisión retrospectiva entre diciembre de 2007 y julio de 2018. Se recogieron datos sobre el estado previo del paciente, el manejo anestésico y las complicaciones intraoperatorias. RESULTADOS: Se incluyen 16 pacientes (5 pediátricos) con indicación de MD por LMC (63%), ELA (25%) y otras enfermedades neurológicas (12%). Se requirió anestesia general para la laparoscopia abdominal utilizando inducción intravenosa (87%) o inhalatoria (13%) y anestesia total intravenosa (50%) o balanceada (50%) para el mantenimiento anestésico. En un caso se administró rocuronio para un óptimo manejo de la vía aérea. Las complicaciones registradas incluyeron: hipotensión arterial (50%), dificultades en la ventilación mecánica durante la laparoscopia (31%), pneumotárax (12,5%) y disreflexia autonómica (6%). CONCLUSIONES: La colocación de MD bajo anestesia general es una intervención segura, tanto en el paciente adulto como en el pediátrico, en la que pueden aparecer complicaciones derivadas tanto de la enfermedad de base como de la técnica quirúrgica, siendo necesaria una rápida identificación y tratamiento de las mismas para el buen desarrollo del procedimiento
BACKGROUND: The diaphragm pacemaker (DP) has proven its utility in replacing mechanical ventilation in patients with chronic spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS). The DP improves patient quality of life and reduces morbidity and mortality and their associated health care costs. The anesthetic management of these patients and the particularities of the surgical procedure are challenging. The aim of our study is to analyze anesthetic management and intraoperative complications in patients undergoing DP placement in our hospital. METHODS: We performed a chart review of patients treated between December 2007 and July 2017, recording the patients' preoperative status, anesthetic management and intraoperative complications. RESULTS: The study included 16 patients (5 pediatric) undergoing DP implantation for chronic SCI (63%), ALS (25%) and other neurologic conditions (12%). Abdominal laparoscopy was performed under general anesthesia, with intravenous (87%) or inhalational (13%) induction and maintenance using total intravenous (50%) or balanced (50%) anesthesia. Rocuronium was administered in one case to permit airway management. Complications included: hypotension (50%), difficulties in mechanical ventilation during laparoscopy (31%), pneumothorax (12.5%) and autonomic dysreflexia (6%). CONCLUSIONS: DP placement under general anesthesia is a safe intervention in both adult and pediatric patients. Complications derived from both the underlying disease and the surgical technique may appear, and must be rapidly identified and treated to obtain a satisfactory surgical outcome
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Amyotrophic Lateral Sclerosis/complications , Anesthesia, General/methods , Diaphragm , Pacemaker, Artificial , Quadriplegia/complications , Respiration Disorders/therapy , Spinal Cord Injuries/complications , Autonomic Dysreflexia/etiology , Chronic Disease , Hypotension/etiology , Implantable Neurostimulators , Intraoperative Complications/etiology , Laparoscopy/adverse effects , Phrenic Nerve/injuries , Pneumothorax/etiology , Respiration Disorders/etiology , Respiration, Artificial/adverse effects , Retrospective Studies , Tracheotomy/statistics & numerical dataABSTRACT
BACKGROUND: The diaphragm pacemaker (DP) has proven its utility in replacing mechanical ventilation in patients with chronic spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS). The DP improves patient quality of life and reduces morbidity and mortality and their associated health care costs. The anesthetic management of these patients and the particularities of the surgical procedure are challenging. The aim of our study is to analyze anesthetic management and intraoperative complications in patients undergoing DP placement in our hospital. METHODS: We performed a chart review of patients treated between December 2007 and July 2017, recording the patients' preoperative status, anesthetic management and intraoperative complications. RESULTS: The study included 16 patients (5 pediatric) undergoing DP implantation for chronic SCI (63%), ALS (25%) and other neurologic conditions (12%). Abdominal laparoscopy was performed under general anesthesia, with intravenous (87%) or inhalational (13%) induction and maintenance using total intravenous (50%) or balanced (50%) anesthesia. Rocuronium was administered in one case to permit airway management. Complications included: hypotension (50%), difficulties in mechanical ventilation during laparoscopy (31%), pneumothorax (12.5%) and autonomic dysreflexia (6%). CONCLUSIONS: DP placement under general anesthesia is a safe intervention in both adult and pediatric patients. Complications derived from both the underlying disease and the surgical technique may appear, and must be rapidly identified and treated to obtain a satisfactory surgical outcome.
Subject(s)
Amyotrophic Lateral Sclerosis/complications , Anesthesia, General/methods , Diaphragm , Pacemaker, Artificial , Quadriplegia/complications , Respiration Disorders/therapy , Spinal Cord Injuries/complications , Adolescent , Adult , Aged , Autonomic Dysreflexia/etiology , Child , Child, Preschool , Chronic Disease , Female , Humans , Hypotension/etiology , Implantable Neurostimulators , Intraoperative Complications/etiology , Laparoscopy/adverse effects , Male , Middle Aged , Phrenic Nerve/injuries , Pneumothorax/etiology , Respiration Disorders/etiology , Respiration, Artificial/adverse effects , Retrospective Studies , Tracheostomy/statistics & numerical dataABSTRACT
Highly sensitive detection of ethanol concentrations in discrete brain regions of rats voluntarily accessing ethanol, with high temporal resolution, would represent a source of greatly desirable data in studies devoted to understanding the kinetics of the neurobiological basis of ethanol's ability to impact behavior. In the present study, we present a series of experiments aiming to validate and apply an original high-tech implantable device, consisting of the coupling, for the first time, of an amperometric biosensor for brain ethanol detection, with a sensor for detecting the microvibrations of the animal. This device allows the real-time comparison between the ethanol intake, its cerebral concentrations, and their effect on the motion when the animal is in the condition of voluntary drinking. To this end, we assessed in vitro the efficiency of three different biosensor designs loading diverse alcohol oxidase enzymes (AOx) obtained from three different AOx-donor strains: Hansenula polymorpha, Candida boidinii, and Pichia pastoris. In vitro data disclosed that the devices loading H. polymorpha and C. boidinii were similarly efficient (respectively, linear region slope [LRS]: 1.98 ± 0.07 and 1.38 ± 0.04 nA/mM) but significantly less than the P. pastoris-loaded one (LRS: 7.57 ± 0.12 nA/mM). The in vivo results indicate that this last biosensor design detected the rise of ethanol in the nucleus accumbens shell (AcbSh) after 15 minutes of voluntary 10% ethanol solution intake. At the same time, the microvibration sensor detected a significant increase in the rat's motion signal. Notably, both the biosensor and microvibration sensor described similar and parallel time-dependent U-shaped curves, thus providing a highly sensitive and time-locked high-resolution detection of the neurochemical and behavioral kinetics upon voluntary ethanol intake. The results overall indicate that such a dual telemetry unit represents a powerful device which, implanted in different brain areas, may boost further investigations on the neurobiological mechanisms that underlie ethanol-induced motor activity and reward.
Subject(s)
Biosensing Techniques/instrumentation , Ethanol/pharmacology , Motor Activity/drug effects , Nucleus Accumbens/drug effects , Administration, Oral , Alcohol Drinking/metabolism , Alcohol Oxidoreductases/chemistry , Animals , Extracellular Space , In Vitro Techniques , Male , Nucleus Accumbens/ultrastructure , Rats , Rats, Sprague-Dawley , TelemetryABSTRACT
BACKGROUND: Translational studies investigating the effects of deep brain stimulation (DBS) on brain function up to now mainly relied on BOLD responses measured with fMRI. However, fMRI studies in rodents face technical and practical limitations (e.g., immobilization, sedation or anesthesia, spatial and temporal resolution of data). Direct measurement of oxygen concentration in the brain using electrochemical sensors is a promising alternative to the use of fMRI. Here, we tested for the first time if such measurements can be combined with DBS. NEW METHOD: We combined bilateral DBS in the internal capsule (IC-DBS) with simultaneous amperometric measurements of oxygen in the medial prefrontal cortex (prelimbic area) and striatum of freely moving mice. Using a two-day within-animal experimental design, we tested the effects of DBS on baseline oxygen concentrations, and on novelty- and restraint-induced increases in oxygen concentration. RESULTS: Basal oxygen levels were stable across the daily sampling periods. Exposure to novelty and immobilization reproducibly increased oxygen concentrations in both areas. IC-DBS did not significantly alter basal oxygen, but reduced the novelty-induced increase in the striatum. COMPARISON WITH EXISTING METHOD(S): Amperometric detection of brain oxygen concentration with high temporal and spatial resolution can be performed in a number of key brain areas to study the effects of DBS in animal models of disease. The method is easily implemented and does not require expensive equipment or complicated data analysis processes. CONCLUSIONS: Direct and simultaneous measurement of brain oxygen concentration in multiple brain areas can be used to study the effects of bilateral DBS neuromodulation on brain activity in freely moving mice.
Subject(s)
Biosensing Techniques/methods , Corpus Striatum/metabolism , Deep Brain Stimulation , Oxygen/analysis , Prefrontal Cortex/metabolism , Animals , Behavior, Animal , Biosensing Techniques/instrumentation , Internal Capsule/physiology , Male , Mice, Inbred C57BL , Oxygen/metabolismABSTRACT
PURPOSE: To investigate the efficacy of metformin (M) plus chemotherapy versus chemotherapy alone in metastatic breast cancer (MBC). METHODS: Non-diabetic women with HER2-negative MBC were randomized to receive non-pegylated liposomal doxorubicin (NPLD) 60 mg/m2 + cyclophosphamide (C) 600 mg/m2 × 8 cycles Q21 days plus M 2000 mg/day (arm A) versus NPLD/C (arm B). The primary endpoint was progression-free survival (PFS). RESULTS: One-hundred-twenty-two patients were evaluable for PFS. At a median follow-up of 39.6 months (interquartile range [IQR] 24.6-50.7 months), 112 PFS events and 71 deaths have been registered. Median PFS was 9.4 months (95% CI 7.8-10.4) in arm A and 9.9 (95% CI 7.4-11.5) in arm B (P = 0.651). In patients with HOMA index < 2.5, median PFS was 10.4 months (95% CI 9.6-11.7) versus 8.5 (95% CI 5.8-9.7) in those with HOMA index ≥ 2.5 (P = 0.034). Grade 3/4 neutropenia was the most common toxicity, occurring in 54.4% of arm A patients and 72.3% of the arm B group (P = 0.019). M induced diarrhea (G2) was observed in 8.8% of patients in Arm A. The effect of M was similar in patients with HOMA index < 2.5 and ≥ 2.5, for PFS and OS. CONCLUSIONS: The MYME trial failed to provide evidence in support of an anticancer activity of M in combination with first line CT in MBC. A significantly shorter PFS was observed in insulin-resistant patients (HOMA ≥ 2.5). Noteworthy, M had a significant effect on CT induced severe neutropenia. Further development of M in combination with CT in the setting of MBC is not warranted.
Subject(s)
Breast Neoplasms/drug therapy , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Metformin/administration & dosage , Receptor, ErbB-2/deficiency , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Cyclophosphamide/adverse effects , Doxorubicin/adverse effects , Drug Administration Schedule , Drug Therapy , Female , Humans , Metformin/adverse effects , Middle Aged , Progression-Free Survival , Survival Analysis , Treatment OutcomeABSTRACT
BACKGROUND: In breast cancer patients, the expression statuses of oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are crucial in the choice of treatment. Receptor expression in metastatic lesions can differ from the primary tumour. The aim of our study was to analyse the utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to obtain samples allowing the identification of ER, PR and HER2 expression in patients with mediastinal metastases of breast cancer. PATIENTS AND METHODS: The clinical files of all patients with a final diagnosis of breast cancer mediastinal metastases diagnosed by EBUS-TBNA in our institution were retrospectively analysed. The ability of EBUS-TBNA to obtain samples that allowed hormone receptor and HER2 expression analysis was calculated. RESULTS: Twenty-four patients were included. ER, PR and HER2 assessments could be performed in 22, 20 and 22 patients, respectively. In 20 of the 24 patients it was possible to investigate all three types of receptor expression. In the remaining four cases, where ER, PR or HER2 expression tests could not be performed, it was due to a lack of tissue. In cases with adequate results for EBUS-TBNA and the primary tumour agreement was greater for ER (16/19) and HER2 (12/14) than PR (8/17). Based on receptor status, there was a change in the choice of treatment for five patients. CONCLUSION: In patients with breast cancer mediastinal metastases, ER, PR and HER2 expression can be assessed in samples obtained by EBUS-TBNA whenever a sufficient tissue sample is collected.
Subject(s)
Biomarkers, Tumor/analysis , Biopsy, Fine-Needle/methods , Breast Neoplasms/pathology , Mediastinal Neoplasms/secondary , Neoplasm Metastasis/pathology , Female , Humans , Mediastinal Neoplasms/pathology , Receptor, ErbB-2/analysis , Receptor, ErbB-2/biosynthesis , Receptors, Estrogen/analysis , Receptors, Estrogen/biosynthesis , Receptors, Progesterone/analysis , Receptors, Progesterone/biosynthesis , Retrospective Studies , Ultrasonography, Interventional/methodsABSTRACT
OBJECTIVE: The purpose of our review is an update about the burden of sexually transmitted infections (STIs) among various types of underserved populations, such as migrants, substance abusers, homeless and incarcerated inmates. First-line test and treatment based on the latest available evidence according to the revised guidelines of Centers for Disease Control and Prevention have also been considered. MATERIALS AND METHODS: We performed a comprehensive research using scientific databases such as Medline and Pubmed, followed by a review of citations and reference list. A consultation with other experts in the management of the various subpopulations was also conducted. RESULTS: Health-care is often influenced by social determinants, which play a vital role in the diffusion of STIs. The consequence is a socio-economical and ethnic disparity in the rate of STIs. Early screening and treatment of STIs should be implemented in clinical practice, starting from marginalized social groups, which are the most affected by this health problem. CONCLUSIONS: In the literature, there are very few papers containing information on STIs prevalence in various types of underserved populations, such as migrants, substance abusers, homeless and incarcerated inmates. The availability of more accurate epidemiological data is needed. In these groups, the most relevant barrier is the lower perception of health-care need, with an underestimation of risk and symptoms of STIs, causing a retard of diagnosis and health-care provision and use. For these populations, targeted interventions are needed, particularly on unaware people, responsible for most STIs transmissions.
Subject(s)
Delivery of Health Care , Sexually Transmitted Diseases/pathology , Anti-Bacterial Agents/therapeutic use , Databases, Factual , Female , Ill-Housed Persons , Humans , Male , Sexual Behavior , Sexually Transmitted Diseases/complications , Sexually Transmitted Diseases/drug therapy , Substance-Related Disorders/complications , Substance-Related Disorders/pathology , Transients and MigrantsABSTRACT
OBJECTIVE: The purpose of the present multidisciplinary review is to give an updated insight into the most recent findings regarding the pathophysiology, diagnosis and therapeutics of HIV-associated neurocognitive disorder (HAND). MATERIALS AND METHODS: We performed a comprehensive search, through electronic databases (Pubmed - MEDLINE) and search engines (Google Scholar), of peer-reviewed publications (articles and reviews) and conferences proceedings on HAND pathophysiology, diagnosis, and therapy, from 1999 to 2016. RESULTS: It seems to be increasingly clear that neurodegeneration in HIV-1 affected patients is a multi-faceted disease involving numerous factors, from chronic inflammation to central nervous system (CNS) compartmentalization of HIV. Diagnosis of HAND may benefit from both laboratory analysis and advanced specific neuroimaging techniques. As regards HAND therapy, modified HAART combinations and simplification strategies have been tested, while novel exciting frontiers seem to involve the use of nanoparticles with the ability to cross the Blood-Brain Barrier (BBB). CONCLUSIONS: Albeit highly active antiretroviral therapy (HAART) allowed a major decrease in morbidity and mortality for AIDS patients, CNS involvement still represents a challenge in HIV patients even today, affecting up to 50% of patients with access to combination antiretroviral therapy (cART). Future studies will have to focus on CNS compartmentalization, drugs' ability to penetrate and suppress viral replication in this compartment, and on new approaches to reduce HIV-associated neuroinflammation.
Subject(s)
AIDS Dementia Complex/drug therapy , Antiretroviral Therapy, Highly Active , AIDS Dementia Complex/diagnosis , AIDS Dementia Complex/etiology , Cost of Illness , HumansABSTRACT
We employ dielectric spectroscopy and molecular dynamic simulations to investigate the dipolar dynamics in the orientationally disordered solid phase of (1,1,2,2)tetrachloroethane. Three distinct orientational dynamics are observed as separate dielectric loss features, all characterized by a simply activated temperature dependence. The slower process, associated to a glassy transition at 156 ± 1 K, corresponds to a cooperative motion by which each molecule rotates by 180° around the molecular symmetry axis through an intermediate state in which the symmetry axis is oriented roughly orthogonally to the initial and final states. Of the other two dipolar relaxations, the intermediate one is the Johari-Goldstein precursor relaxation of the cooperative dynamics, while the fastest process corresponds to an orientational fluctuation of single molecules into a higher-energy orientation. The Kirkwood correlation factor of the cooperative relaxation is of the order of one tenth, indicating that the molecular dipoles maintain on average a strong antiparallel alignment during their collective motion. These findings show that the combination of dielectric spectroscopy and molecular simulations allows studying in great detail the orientational dynamics in molecular solids.
ABSTRACT
In symptomless plants of portulaca a potential new pospiviroid was characterized. Analysis by both double and return PAGE showed the presence of a circular RNA. RT-PCR and sequencing revealed a genome of 351 nt with properties characteristic of members of the genus Pospiviroid and with highest sequence identity (circa 80%) with iresine viroid 1 (IrVd-1). The circular RNA from portulaca was shown to replicate independently in its original host, thus showing that it is indeed a viroid. Based on its molecular characteristics, it should be considered a new species. However, since no biological differences have yet been found with its closest relative IrVd-1, the viroid from portulaca does not fulfil all criteria for species demarcation of the ICTV.
Subject(s)
Plant Diseases/virology , Portulaca/virology , Viroids/isolation & purification , Base Sequence , Molecular Sequence Data , Nucleic Acid Conformation , Phylogeny , RNA, Viral/chemistry , RNA, Viral/genetics , Viroids/classification , Viroids/genetics , Viroids/physiology , Virus LatencyABSTRACT
Citrus are natural hosts of several viroid species. Citrus exocortis viroid (CEVd) and Hop stunt viroid (HSVd) are the causal agents of two well-known diseases of citrus, exocortis and cachexia. Other viroids have been found to induce specific symptoms and different degrees of stunting in trees grafted on trifoliate orange and trifoliate orange hybrids. A field assay was initiated in 1989 to establish the effect of CEVd, HSVd, Citrus bent leaf viroid (CBLVd), Citrus dwarfing viroid (CDVd), and Citrus bark cracking viroid (CBCVd) on Washington navel sweet orange trees grafted on Carrizo citrange rootstock. Here we report the effect of viroid infection on symptom expression, tree size, fruit production and quality evaluated from 2004 to 2007. Vegetative growth was affected by viroid infection with height and canopy volume being reduced. No bark scaling symptoms were observed in CEVd-infected trees albeit they presented lesions and blisters in the roots. Bark cracking symptoms were consistently observed in CBCVd-infected trees that were smaller with enhanced productivity and fruit size. No major effects were found as a result of infection with CBLVd, HSVd, or CDVd. The quality of the fruits was not affected by viroid infection, except for the low diameter of the fruits harvested from HSVd-infected trees. An interesting effect was identified in terms of tree productivity increase (yield/canopy volume) as a result of infection with CEVd, CDVd, and especially CBCVd.
ABSTRACT
Innate lymphoid cells (ILC) are RAG-independent lymphocytes with important roles in innate immunity, and include group-1 (natural killer (NK) cell, ILC1), group-2 (ILC2), and group-3 (lymphoid tissue inducer (LTi), NCR(+) ILC3) subsets. Group-3 ILC express Rorγt, produce interleukin (IL)-22, and are critically important in the normal function of mucosal tissues. Here, we describe a novel model cell line for the study of ILC function and differentiation. The parental MNK cell line, derived from NKR-P1B(+) fetal thymocytes, shows a capacity to differentiate in γc cytokines. One IL-7-responsive subline, designated MNK-3, expresses Rorγt and produces high levels of IL-22 in response to IL-23 and IL-1ß stimulation. MNK-3 cells display surface markers and transcript expression characteristic of group-3 ILC, including IL-7Rα (CD127), c-kit (CD117), CCR6, Thy1 (CD90), RANK, RANKL, and lymphotoxin (LTα1ß2). Using an in vitro assay of LTi cell activity, MNK-3 cells induce ICAM-1 and VCAM-1 expression on stromal cells in a manner dependent upon LTα1ß2 expression. A second IL-2-responsive subline, MNK-1, expresses several NK cell receptors, perforin and granzymes, and shows some cytotoxic activity. Thus, MNK-1 cells serve as a model of ILC1/NK development and differentiation, whereas MNK-3 cells provide an attractive in vitro system to study the function of ILC3/LTi cells.
Subject(s)
Cell Differentiation/immunology , Immunity, Innate , Lymphocytes/cytology , Lymphocytes/immunology , Animals , Antigens, Surface/genetics , Antigens, Surface/metabolism , Cell Lineage , Cluster Analysis , Cytokines/metabolism , Gene Expression Profiling , Gene Expression Regulation , Immunophenotyping , Lymphocyte Subsets/cytology , Lymphocyte Subsets/immunology , Lymphocyte Subsets/metabolism , Lymphocytes/metabolism , Mice , Nuclear Receptor Subfamily 1, Group F, Member 3/genetics , Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism , Phenotype , Receptors, Natural Killer Cell/genetics , Receptors, Natural Killer Cell/metabolismABSTRACT
In this work, a "bio-electronic nose" for vapour phase detection of odorant molecules based on surface acoustic wave (SAW) resonators is presented. The biosensor system is composed of an array of five SAW resonators coated with three types of odorant-binding proteins (OBPs): the wild-type OBP from bovine (wtbOBP), a double-mutant of the OBP from bovine (dmbOBP), and the wild-type OBP from pig (wtpOBP). High resolution deposition of OBPs onto the active area of SAW resonators was implemented through laser-induced forward transfer (LIFT). The resonant frequency shifts of the SAW resonators after the deposition of the biomolecules confirmed the immobilisation of the proteins onto the Al/Au inter-digital transducers (IDTs). In addition, a low increase of insertion losses with a limited degradation of Q-factors is reported. The "bio-electronic nose" fabricated by LIFT is tested in nitrogen upon exposure to separated concentrations of R-(-)-1-octen-3-ol (octenol) and R-(-)-carvone (carvone) vapours. The "bio-electronic nose" showed low detection limits for the tested compounds (i.e. 0.48 ppm for the detection of octenol, and 0.74 ppm for the detection of carvone). In addition, the bio-sensing system was able to discriminate the octenol molecules from the carvone molecules, making it pertinent for the assessment of food contamination by moulds, or for the evaluation of indoor air quality in buildings.
Subject(s)
Biosensing Techniques , Electronic Nose , Odorants/analysis , Receptors, Odorant/chemistry , Animals , Cattle , Limit of Detection , Sound , SwineABSTRACT
Information on hormone receptor and human epidermal growth factor receptor-2 (HER2) expression in breast cancer is acknowledged as mandatory for prognostic stratification and treatment planning. Data on the biological features of African breast cancers are poor. We decided to compare histopathological and biomolecular characteristics (estrogen and progesterone receptorER, PgR, and HER2) of Tanzanian and Italian breast cancers. Differences in proliferating index and androgen receptor (AR) expression in triple-negative patients from the two case series were also assessed. Of the 103 consecutive patients seen at the Bugando Medical Center (Mwanza, Tanzania) from 2003 to 2010, who underwent biopsy or surgical resection of primary breast cancer, 69 patients had tissue samples that were evaluable for estrogen receptor (ER), progesterone receptor (PgR), and HER2. Histopathological assessment and biomolecular determinations were performed at the Cancer Institute of Romagna (IRST IRCCS, Meldola, Italy). Caucasian breast cancers were randomly extracted from an electronic database and matched (1:2 ratio) for year of diagnosis and age at diagnosis. Median age of both populations was 51 years (range 2784). With respect to Caucasian tumors, Tanzanian breast cancers at diagnosis more frequently showed high histological grade (mainly grade 3) (P = 0.03), advanced clinical stage (III or IV) (P\0.001), ER negativity (52.2 %, P\0.001) and high proliferation (P = 0.0002). Triple-negative tumors were over-represented in Tanzanian women. AR was positive in 38.5 and 38 %of triple-negative Tanzanian and Italian breast cancers, respectively. Our results show that histopathological and biomolecular characteristics in Tanzanian and Italian breast cancers differ substantially. The high frequency of poorly differentiated, ER-negative, highly proliferating tumors, together with advanced stage at presentation, could be considered as the main prognostic factors linked to the high mortality rates for breast cancer in the African population.
Subject(s)
Breast Neoplasms/ethnology , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Black People , Case-Control Studies , Female , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Italy , Middle Aged , Tanzania , White PeopleABSTRACT
A simple and rapid method was developed for in vivo simultaneous determination of ascorbic-acid and antioxidant capacity in microdialysates from cladodes of Opuntia ficus-indica (L.) Miller. The method is verified in water-stressed plants, as compared with a well-watered test controls. The microdialysis probe construction and insertion procedure was specifically developed to minimise the tissue trauma of the plant and to obtain optimal dialysis performance. Microdialysis was performed using a flow rate of 3 µL/min and the samples were analysed by HPLC coupled to electrochemical detection of ascorbic-acid and DPPH-determined antioxidant capacity. Our data indicate exponential decay of the concentrations of the analysed compounds as a function of microdialysis sampling time. Water-stressed Opuntia show decreased ascorbic acid levels and increased the others antioxidants.