ABSTRACT
In this study, we conducted a comprehensive computational investigation of the interaction between α-lactalbumin, a small globular protein, and strong anionic oligoelectrolyte chains with a polymerization degree from 2 to 9. Both the protein and oligoelectrolyte chains are represented using coarse-grained models, and their properties were calculated by the Monte Carlo method under constant pH conditions. We were able to estimate the effects of this interaction on the electrostatic potential around the protein. At acidic pH, the protein had a net positive charge; therefore, the electrostatic potential around it was also positive. To neutralize or reverse this electrostatic potential, oligoelectrolyte chains with a minimum size of six monomers were necessary. Simultaneously, low salt concentrations were required as elevated salt levels led to a significant attenuation of the electrostatic interactions and the corresponding electrostatic potential.
Subject(s)
Lactalbumin , Sodium Chloride , Lactalbumin/chemistry , Static Electricity , Hydrogen-Ion ConcentrationABSTRACT
We present the Python-based Molecule Builder for ESPResSo (pyMBE), an open source software application to design custom coarse-grained (CG) models, as well as pre-defined models of polyelectrolytes, peptides, and globular proteins in the Extensible Simulation Package for Research on Soft Matter (ESPResSo). The Python interface of ESPResSo offers a flexible framework, capable of building custom CG models from scratch. As a downside, building CG models from scratch is prone to mistakes, especially for newcomers in the field of CG modeling, or for molecules with complex architectures. The pyMBE module builds CG models in ESPResSo using a hierarchical bottom-up approach, providing a robust tool to automate the setup of CG models and helping new users prevent common mistakes. ESPResSo features the constant pH (cpH) and grand-reaction (G-RxMC) methods, which have been designed to study chemical reaction equilibria in macromolecular systems with many reactive species. However, setting up these methods for systems, which contain several types of reactive groups, is an error-prone task, especially for beginners. The pyMBE module enables the automatic setup of cpH and G-RxMC simulations in ESPResSo, lowering the barrier for newcomers and opening the door to investigate complex systems not studied with these methods yet. To demonstrate some of the applications of pyMBE, we showcase several case studies where we successfully reproduce previously published simulations of charge-regulating peptides and globular proteins in bulk solution and weak polyelectrolytes in dialysis. The pyMBE module is publicly available as a GitHub repository (https://github.com/pyMBE-dev/pyMBE), which includes its source code and various sample and test scripts, including the ones that we used to generate the data presented in this article.
ABSTRACT
INTRODUCTION: In the treatment of inflammatory bowel disease (IBD), we have biologic therapies administered intravenously and subcutaneously. Recently, some drugs can be administered by either of these routes. The real impact that intravenous administration has on the perception of the disease and the personal and work life of the patient is unknown. METHODS: All IBD patients receiving intravenous infliximab treatment for at least 6 months were anonymously invited to participate. They were provided with a specific structured questionnaire with visual analogue scales (0-10) at two reference centers in the Barcelona area. RESULTS: A total of 90 patients with a median age of 45 years (36-56) and a median infliximab treatment duration of 48 months (24-84) were included. The visit and therapy with infliximab in the day hospital were globally well evaluated (9, IQR 7-10). 78% of patients combined day hospital stays with other activities (26% employment). The personal impact was generally low (4, IQR 0-5.8), but the patient's job was threatened in 43% of patients on intensified treatment. CONCLUSIONS: The intravenous administration of biologic drugs on an outpatient basis is highly satisfactory among IBD patients. The impact on the work sphere appears to be more pronounced than on the personal sphere, an aspect that should be considered in shared decision-making with the patient.
ABSTRACT
The electrostatic potential (EP) generated by the protein α-lactoalbumin in the presence of added salt is computed as a thermal average at a given point in space. With this aim, constant pH Monte Carlo (MC) simulations are performed within the primitive model, namely, the solvent is treated as a continuum dielectric. The study of the thermal and spatial fluctuations of the EP reveals that they are remarkably high inside the protein. The calculations indicate that fluctuations inside the protein are mainly due to the asymmetric distribution of the charge groups, while the charge fluctuations of the titratable groups play a minor role. The computed EP matches very well with the one obtained from the Poisson equation for the average charge density in spherical symmetry. The Tanford-Kirkwood multipole expansion reproduces the simulated angular-averaged potential rather accurately. Surprisingly, two of the simplest mean-field models, the linear Poisson-Boltzmann (PB) equation and Donnan potential, provide good estimations of the average EP in the effective protein surface (surface EP). The linear PB equation predicts a linear relationship between charge and surface EP, which is numerically reproduced only if the small ions within the protein are taken into account. On the other hand, the partition coefficients of the small ions inside and outside the protein predicted by Donnan theory reproduce reasonably well the simulation results.
Subject(s)
Lactalbumin , Transcription Factors , Static Electricity , Membrane Proteins , SolventsABSTRACT
OBJECTIVE: To determine if the evaluation of the fetal ventricular system and hindbrain herniation (HBH) is associated with motor outcome at birth in prenatally repaired open neural tube defect (NTD). METHODS: Retrospective cohort study of 47 patients with NTD who underwent prenatal repair (17 fetoscopic; 30 open-hysterotomy). At referral and 6 weeks postoperatively, the degree of HBH, ventricular atrial widths and ventricular volume were evaluated by MRI. Head circumference and ventricular atrial widths were measured on ultrasound at referral and during the last ultrasound before delivery. Anatomic level of the lesion (LL) was determined based on the upper bony spinal defect detected by ultrasound. We considered the functional level as worse than anatomical level at birth when the motor level was equal or worse than the anatomical LL. RESULTS: 26% (12/47) of the cases showed worse functional level than anatomical level at birth. Having a HBH below C1 at the time of referral was associated with a worse functional level than anatomical level at birth (OR = 9.7, CI95 [2.2-42.8], p < 0.01). None of the other brain parameters showed a significant association with motor outcomes at birth. CONCLUSIONS: HBH below C1 before surgery was associated with a worse functional level than anatomical level at birth.
Subject(s)
Functional Status , Hydrocephalus/complications , Neural Tube Defects/surgery , Rhombencephalon/abnormalities , Adult , Cohort Studies , Female , Humans , Hydrocephalus/epidemiology , Hydrocephalus/surgery , Infant, Newborn , Magnetic Resonance Imaging/methods , Neural Tube Defects/complications , Neural Tube Defects/epidemiology , Neurosurgical Procedures/adverse effects , Neurosurgical Procedures/methods , Neurosurgical Procedures/statistics & numerical data , Pregnancy , Prenatal Care/methods , Retrospective Studies , Rhombencephalon/injuries , Rhombencephalon/surgery , Texas/epidemiologyABSTRACT
BACKGROUND: Trends in breast cancer mortality in the United States are decreasing, but racial disparities persist. Using an implementation science framework to inform evidence-based breast cancer screening and navigation within federally qualified health centers (FQHCs) with community stakeholders can mitigate barriers to screening. METHODS: Using an integrated theoretical framework of the Practical, Robust Implementation and Sustainability Model and the Social Ecological Model, the University of Illinois Cancer Center and Mile Square Health Centers (MSHC) FQHC developed a breast cancer screening and navigation program, known as the Mile Square Accessible Mammogram Outreach and Engagement (Mi-MAMO) program, to tackle breast cancer disparities in Chicago among underresourced communities. To increase access to screening, patient navigators conducted community outreach activities. Partnerships were forged with community-based organizations, health care systems, and insurers. Outcomes were monitored with standardized performance measures. RESULTS: Between January and December 2017, 103 women received a screening mammogram at MSHC. To increase screening rates, Mi-MAMO was started in August 2017. Between January and December 2018, the number of women who received a screening mammogram increased to 567. From August 2017 to December 2018, 779 women received navigation to screening and/or diagnostic services through the Mi-MAMO program. The majority of women were uninsured (63.9%), and 95.5% were racial/ethnic minorities. Twenty-four percent (n = 185) completed diagnostic services, and 10 women received positive breast cancer diagnoses (mean age, 49.7 years); all successfully navigated to treatment. The Mi-MAMO program is ongoing. CONCLUSIONS: Deploying an integrated framework for patient navigation programs can increase breast cancer screening utilization and awareness among underresourced populations at higher risk for breast cancer.
Subject(s)
Breast Neoplasms/diagnostic imaging , Early Detection of Cancer/methods , Medically Underserved Area , Patient Navigation/organization & administration , Breast Neoplasms/ethnology , Chicago/ethnology , Evidence-Based Practice , Female , Health Promotion , Humans , Mammography , Medically Uninsured/ethnology , Medically Uninsured/statistics & numerical data , Middle Aged , Practice Guidelines as TopicABSTRACT
BACKGROUND: Increasing the interval of administration of anti-TNF agents over the duration specified in the data sheet is not common in inflammatory bowel disease (IBD). AIM: To evaluate the outcomes of IBD patients treated with this strategy. METHODS: Patients with IBD who were treated with infliximab or adalimumab at intervals > 8 weeks or > 2 weeks, respectively, because of persistent clinical remission, were identified at local databases of the ENEIDA registry (a nationwide registry promoted by the Spanish Working Group in Crohn's disease and Ulcerative Colitis-GETECCU) of two referral centers. Treatment success was considered if patients remained in clinical remission with the same schedule or without biological therapy at the end of follow-up, and if no return to the conventional schedule, dose-escalation, change in biological agent, or a course of systemic corticosteroids or surgery were required. RESULTS: Eighty-five patients were included, 60 treated with infliximab and 25 with adalimumab. The spaced schedule was initiated after a median of 25 months on anti-TNF treatment (IQR 14-49). Throughout a median follow-up of 34 months (IQR 21-47), fifty patients (59%) fulfilled the success criteria of the spaced strategy. No differences were found regarding type of IBD or anti-TNF agent. Baseline C-reactive protein levels and disease duration at the time of starting anti-TNF treatment were the only factors associated with treatment success. CONCLUSIONS: Anti-TNF administration at longer intervals than those provided in the data sheet may be an efficacious, convenient, and cheaper treatment option, particularly in patients in whom anti-TNF treatment was initiated early.
Subject(s)
Adalimumab/administration & dosage , Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Infliximab/administration & dosage , Tumor Necrosis Factor Inhibitors/administration & dosage , Adult , C-Reactive Protein/immunology , Colitis, Ulcerative/immunology , Colitis, Ulcerative/physiopathology , Crohn Disease/immunology , Crohn Disease/physiopathology , Drug Administration Schedule , Drug Therapy, Combination , Female , Humans , Immunosuppressive Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/immunology , Inflammatory Bowel Diseases/physiopathology , Male , Middle Aged , Prognosis , Registries , Retrospective Studies , Spain , Time Factors , Treatment OutcomeABSTRACT
OBJECTIVES: To describe and compare placental and amniotic histology in women who underwent a fetoscopic myelomeningocele repair to those who underwent an open hysterotomy myelomeningocele repair. Also, we intended to compare findings from both prenatal repair groups to age-matched control pregnant patients. METHODS: Placental and membrane histopathology from 43 prenatally repaired spina bifida cases (17 fetoscopic and 26 open) and 18 healthy controls were retrospectively assessed. Quantitative assessment of histopathology included apoptosis count and maternal and fetal underperfusion scores. Qualitative assessment included the detection of pigmented macrophages and/or signs of placental/amniotic inflammation. Associations between the duration of surgery or the duration of CO2 insufflation and quantitative histological parameters were tested. RESULTS: Fetoscopic surgery cases did not show significant differences in any of the studied parameters when compared against controls. No differences were detected either when compared with open repaired cases, except for lower proportion of pigmented laden macrophages in the fetoscopic group (11.8% vs 61.5%, P < 0.01). No associations between the duration of surgery or the duration of CO2 exposure and any of the quantitative histological parameters were detected. CONCLUSIONS: These preliminary results support the lack of detrimental effects of the use of heated and humidified CO2 gas for uterine insufflation to fetal membranes and placenta.
Subject(s)
Amnion/pathology , Fetoscopy/statistics & numerical data , Neural Tube Defects/surgery , Open Abdomen Techniques/statistics & numerical data , Placenta Diseases/epidemiology , Placenta/pathology , Adult , Amnion/surgery , Case-Control Studies , Female , Fetal Diseases/epidemiology , Fetal Diseases/pathology , Fetal Diseases/surgery , Fetal Therapies/methods , Fetal Therapies/statistics & numerical data , Fetoscopy/methods , Humans , Meningomyelocele/epidemiology , Meningomyelocele/pathology , Meningomyelocele/surgery , Neural Tube Defects/epidemiology , Open Abdomen Techniques/methods , Placenta/surgery , Placenta Diseases/diagnosis , Placenta Diseases/pathology , Pregnancy , Retrospective Studies , Uterus/pathology , Uterus/surgery , Young AdultABSTRACT
OBJECTIVE: To evaluate outcomes with expectant management of preterm prelabor rupture of membranes (PROM) until 35 weeks versus immediate delivery at ≥34 weeks. STUDY DESIGN: This was a multicenter retrospective cohort study of singletons with preterm PROM at >20 weeks from 2011 through 2017. Groups were defined as expectant management until 35 weeks versus immediate delivery at ≥34 weeks. Primary outcome was composite neonatal morbidity: need for respiratory support, culture positive neonatal sepsis, or antibiotic administration for >72 hours. Univariate and general estimating equation models were used with p < 0.05 considered significant. RESULTS: A total of 280 mother-infant dyads were included. There was no difference in composite neonatal outcome in pregnancies managed with expectant management compared with immediate delivery (43.4 vs. 37.5%; p = 0.32). Those with expectant management had shorter length of neonatal intensive care unit (NICU) admission but higher rates of neonatal antibiotics for > 72 hours, endometritis, and histological chorioamnionitis. There were no cases of fetal demise, neonatal death, or maternal sepsis, and only three cases of neonatal sepsis. CONCLUSION: There is no difference in composite neonatal morbidity in pregnancies with preterm PROM managed with expectant management until 35 weeks as compared with immediate delivery at 34 weeks. Expectant management is associated with a decreased length of NICU admission but increased short-term infectious morbidity.
Subject(s)
Delivery, Obstetric , Fetal Membranes, Premature Rupture/therapy , Watchful Waiting , Adult , Analysis of Variance , Anti-Bacterial Agents/administration & dosage , Cesarean Section , Chorioamnionitis/etiology , Endometritis/etiology , Female , Gestational Age , Humans , Infant, Newborn , Infant, Newborn, Diseases/epidemiology , Intensive Care Units, Neonatal , Length of Stay , Pregnancy , Pregnancy Outcome , Retrospective Studies , Sepsis/epidemiology , Time Factors , Watchful Waiting/methodsABSTRACT
PURPOSE: The purpose of this review was to develop recommendations for the management of spinal disorders in low-income communities, with a focus on non-invasive pharmacological and non-pharmacological therapies for non-specific low back and neck pain. METHODS: We synthesized two evidence-based clinical practice guidelines for the management of low back and neck pain. Our recommendations considered benefits, harms, quality of evidence, and costs, with attention to feasibility in medically underserved areas and low- and middle-income countries. RESULTS: Clinicians should provide education and reassurance, advise patients to remain active, and provide information about self-care options. For acute low back and neck pain without serious pathology, primary conservative treatment options are exercise, manual therapy, superficial heat, and nonsteroidal anti-inflammatory drugs (NSAIDs). For patients with chronic low back and neck pain without serious pathology, primary treatment options are exercise, yoga, cognitive behavioral therapies, acupuncture, biofeedback, progressive relaxation, massage, manual therapy, interdisciplinary rehabilitation, NSAIDs, acetaminophen, and antidepressants. For patients with spinal pain with radiculopathy, clinicians may consider exercise, spinal manipulation, or NSAIDs; use of other interventions requires extrapolation from evidence regarding effectiveness for non-radicular spinal pain. Clinicians should not offer treatments that are not effective, including benzodiazepines, botulinum toxin injection, systemic corticosteroids, cervical collar, electrical muscle stimulation, short-wave diathermy, transcutaneous electrical nerve stimulation, and traction. CONCLUSION: Guidelines developed for high-income settings were adapted to inform a care pathway and model of care for medically underserved areas and low- and middle-income countries by considering factors such as costs and feasibility, in addition to benefits, harms, and the quality of underlying evidence. The selection of recommended conservative treatments must be finalized through discussion with the involved community and based on a biopsychosocial approach. Decision determinants for selecting recommended treatments include costs, availability of interventions, and cultural and patient preferences. These slides can be retrieved under Electronic Supplementary Material.
Subject(s)
Low Back Pain/therapy , Neck Pain/therapy , Developing Countries , Humans , Patient Education as Topic , Practice Guidelines as Topic , Self CareABSTRACT
PURPOSE: The purpose of this review was to synthesize literature on the burden of spinal disorders in rural communities to inform the Global Spine Care Initiative care pathway and model of care for their application in medically underserved areas and low- and middle-income countries. METHODS: A systematic review was conducted. Inclusion criteria included all age groups with nonspecific low back pain, neck pain, and associated disorders, nonspecific thoracic spinal pain, musculoskeletal chest pain, radiculopathy, or spinal stenosis. Study designs included observational study design (case-control, cross-sectional, cohort, ecologic, qualitative) or review or meta-analysis. After study selection, studies with low or moderate risk of bias were qualitatively synthesized. RESULTS: Of 1150 potentially relevant articles, 43 were eligible and included in the review. All 10 low and 18 moderate risk of bias studies were cross-sectional, 14 of which included rural residents only. All studies included estimates of low back pain prevalence, one included neck pain and one reported estimates for spinal disorders other than back or neck pain. The prevalence of low back pain appears greater among females and in those with less education, psychological factors (stress, anxiety, depression), and alcohol consumers. The literature is inconsistent as to whether back pain is more common in rural or urban areas. High risk of bias in many studies, lack of data on disability and other burden measures and few studies on conditions other than back and neck pain preclude a more comprehensive assessment of the individual and community-based burden of spinal disorders in less-developed communities. CONCLUSION: We identified few high-quality studies that may inform patients, providers, policymakers, and other stakeholders about spinal disorders and their burden on individuals and communities in most rural places of the developing world. These findings should be a call to action to devote resources for high-quality research to fill these knowledge gaps in medically underserved areas and low and middle-income countries. These slides can be retrieved under Electronic Supplementary Material.
Subject(s)
Low Back Pain/epidemiology , Neck Pain/epidemiology , Spinal Diseases/epidemiology , Developing Countries , Health Behavior , Humans , Occupational Diseases/epidemiology , Rural Population , Stress, Psychological/epidemiologyABSTRACT
PURPOSE: The purpose of this systematic literature review was to develop recommendations for the assessment of spine-related complaints in medically underserved areas with limited resources. METHODS: We conducted a systematic review and best evidence synthesis of guidelines on the assessment of spine-related complaints. Independent reviewers critically appraised eligible guidelines using the Appraisal of Guidelines for Research and Evaluation-II criteria. Low risk of bias clinical practice guidelines was used to develop recommendations. In accordance with the mandate of the Global Spinal Care Initiative (GSCI), recommendations were selected that could be applied to medically underserved areas and low- and middle-income countries by considering the limited access and costs of diagnostic technologies. RESULTS: We screened 3069 citations; 20 guidelines were eligible for critical appraisal. We used 13 that had a low risk of bias that targeted neck and back pain. CONCLUSIONS: When assessing patients with spine-related complaints in medically underserved areas and low- and middle-income countries, we recommend that clinicians should: (1) take a clinical history to determine signs or symptoms suggesting serious pathology (red flags) and psychological factors (yellow flags); (2) perform a physical examination (musculoskeletal and neurological); (3) do not routinely obtain diagnostic imaging; (4) obtain diagnostic imaging and/or laboratory tests when serious pathologies are suspected, and/or presence of progressive neurologic deficits, and/or disabling persistent pain; (5) do not perform electromyography or nerve conduction studies for diagnosis of intervertebral disc disease with radiculopathy; and (6) do not perform discography for the assessment of spinal disorders. This information can be used to inform the GSCI care pathway and model of care. These slides can be retrieved under Electronic Supplementary Material.
Subject(s)
Spinal Diseases/diagnosis , Back Pain/etiology , Developing Countries , Humans , Medical History Taking , Physical Examination , Spinal Diseases/epidemiology , Spine/diagnostic imagingABSTRACT
PURPOSE: The purpose of this report is to describe the development of a list of resources necessary to implement a model of care for the management of spine-related concerns anywhere in the world, but especially in underserved communities and low- and middle-income countries. METHODS: Contents from the Global Spine Care Initiative (GSCI) Classification System and GSCI care pathway papers provided a foundation for the resources list. A seed document was developed that included resources for spine care that could be delivered in primary, secondary and tertiary settings, as well as resources needed for self-care and community-based settings for a wide variety of spine concerns (e.g., back and neck pain, deformity, spine injury, neurological conditions, pathology and spinal diseases). An iterative expert consensus process was used using electronic surveys. RESULTS: Thirty-five experts completed the process. An iterative consensus process was used through an electronic survey. A consensus was reached after two rounds. The checklist of resources included the following categories: healthcare provider knowledge and skills, materials and equipment, human resources, facilities and infrastructure. The list identifies resources needed to implement a spine care program in any community, which are based upon spine care needs. CONCLUSION: To our knowledge, this is the first international and interprofessional attempt to develop a list of resources needed to deliver care in an evidence-based care pathway for the management of people presenting with spine-related concerns. This resource list needs to be field tested in a variety of communities with different resource capacities to verify its utility. These slides can be retrieved under Electronic Supplementary Material.
Subject(s)
Delivery of Health Care/organization & administration , Spinal Diseases/therapy , Delphi Technique , Humans , Self Care , Spinal Diseases/classificationABSTRACT
PURPOSE: The purpose of this report is to describe the development of a classification system that would apply to anyone with a spine-related concern and that can be used in an evidence-based spine care pathway. METHODS: Existing classification systems for spinal disorders were assembled. A seed document was developed through round-table discussions followed by a modified Delphi process. International and interprofessional clinicians and scientists with expertise in spine-related conditions were invited to participate. RESULTS: Thirty-six experts from 15 countries participated. After the second round, there was 95% agreement of the proposed classification system. The six major classifications included: no or minimal symptoms (class 0); mild symptoms (i.e., neck or back pain) but no interference with activities (class I); moderate or severe symptoms with interference of activities (class II); spine-related neurological signs or symptoms (class III); severe bony spine deformity, trauma or pathology (class IV); and spine-related symptoms or destructive lesions associated with systemic pathology (class V). Subclasses for each major class included chronicity and severity when different interventions were anticipated or recommended. CONCLUSIONS: An international and interprofessional group developed a comprehensive classification system for all potential presentations of people who may seek care or advice at a spine care program. This classification can be used in the development of a spine care pathway, in clinical practice, and for research purposes. This classification needs to be tested for validity, reliability, and consistency among clinicians from different specialties and in different communities and cultures. These slides can be retrieved under Electronic Supplementary Material.
Subject(s)
Disability Evaluation , Spinal Diseases/classification , Delphi Technique , HumansABSTRACT
PURPOSE: The purpose of this report is to describe the development of an evidence-based care pathway that can be implemented globally. METHODS: The Global Spine Care Initiative (GSCI) care pathway development team extracted interventions recommended for the management of spinal disorders from six GSCI articles that synthesized the available evidence from guidelines and relevant literature. Sixty-eight international and interprofessional clinicians and scientists with expertise in spine-related conditions were invited to participate. An iterative consensus process was used. RESULTS: After three rounds of review, 46 experts from 16 countries reached consensus for the care pathway that includes five decision steps: awareness, initial triage, provider assessment, interventions (e.g., non-invasive treatment; invasive treatment; psychological and social intervention; prevention and public health; specialty care and interprofessional management), and outcomes. The care pathway can be used to guide the management of patients with any spine-related concern (e.g., back and neck pain, deformity, spinal injury, neurological conditions, pathology, spinal diseases). The pathway is simple and can be incorporated into educational tools, decision-making trees, and electronic medical records. CONCLUSION: A care pathway for the management of individuals presenting with spine-related concerns includes evidence-based recommendations to guide health care providers in the management of common spinal disorders. The proposed pathway is person-centered and evidence-based. The acceptability and utility of this care pathway will need to be evaluated in various communities, especially in low- and middle-income countries, with different cultural background and resources. These slides can be retrieved under Electronic Supplementary Material.
Subject(s)
Critical Pathways , Spinal Diseases/therapy , Delphi Technique , Humans , TriageABSTRACT
In the present work, the adsorption of three-domain antifreeze proteins on ice is studied by combining a statistical thermodynamics based theory and Monte Carlo simulations. The three-domain protein is modeled by a trimer, and the ice surface is represented by a lattice of adsorption sites. The statistical theory, obtained from the exact partition function of non-interacting trimers adsorbed in one dimension and its extension to two dimensions, includes the configuration of the molecule in the adsorbed state, and allows the existence of multiple adsorption states for the protein. We called this theory "lattice-gas model of molecules with multiple adsorption states" (LGMMAS). The main thermodynamics functions (partial and total adsorption isotherms, Helmholtz free energy and configurational entropy) are obtained by solving a non-linear system of j equations, where j is the total number of possible adsorption states of the protein. The theoretical results are contrasted with Monte Carlo simulations, and a modified Langmuir model (MLM) where the arrangement of the adsorption sites in space is immaterial. The formalism introduced here provides exact results in one-dimensional lattices, and offers a very accurate description in two dimensions (2D). In addition, the scheme is capable of predicting the proportion between coverage degrees corresponding to different conformations in the same energetic state. In contrast, the MLM does not distinguish between different adsorption states, and shows severe discrepancies with the 2D simulation results. These findings indicate that the adsorbate structure and the lattice geometry play fundamental roles in determining the statistics of multistate adsorbed molecules, and consequently, must be included in the theory.
ABSTRACT
G(M1)-gangliosidosis is a rare progressive neurodegenerative disorder due to an autosomal recessively inherited deficiency of lysosomal ß-galactosidase. We have identified seven American black bears (Ursus americanus) found in the Northeast United States suffering from G(M1)-gangliosidosis. This report describes the clinical features, brain MRI, and morphologic, biochemical and molecular genetic findings in the affected bears. Brain lipids were compared with those in the brain of a G(M1)-mouse. The bears presented at ages 10-14 months in poor clinical condition, lethargic, tremulous and ataxic. They continued to decline and were humanely euthanized. The T(2)-weighted MR images of the brain of one bear disclosed white matter hyperintensity. Morphological studies of the brain from five of the bears revealed enlarged neurons with foamy cytoplasm containing granules. Axonal spheroids were present in white matter. Electron microscopic examination revealed lamellated membrane structures within neurons. Cytoplasmic vacuoles were found in the liver, kidneys and chondrocytes and foamy macrophages within the lungs. Acid ß-galactosidase activity in cultured skin fibroblasts was only 1-2% of control values. In the brain, ganglioside-bound sialic acid was increased more than 2-fold with G(M1)-ganglioside predominating. G(A1) content was also increased whereas cerebrosides and sulfatides were markedly decreased. The distribution of gangliosides was similar to that in the G(M1)-mouse brain, but the loss of myelin lipids was greater in the brain of the affected bear than in the brain of the G(M1) mouse. Isolated full-length cDNA of the black bear GLB1 gene revealed 86% homology to its human counterpart in nucleotide sequence and 82% in amino acid sequence. GLB1 cDNA from liver tissue of an affected bear contained a homozygous recessive T(1042) to C transition inducing a Tyr348 to His mutation (Y348H) within a highly conserved region of the GLB1 gene. The coincidence of several black bears with G(M1)-gangliosidosis in the same geographic area suggests increased frequency of a founder mutation in this animal population.
Subject(s)
Gangliosidosis, GM1/genetics , Gangliosidosis, GM1/pathology , Ursidae/genetics , Animals , Base Sequence , Cerebellum/pathology , Cerebellum/ultrastructure , Chromatography, Thin Layer , DNA Mutational Analysis , DNA, Complementary/genetics , DNA, Complementary/isolation & purification , Female , Fibroblasts/enzymology , Fibroblasts/pathology , Gangliosides/metabolism , Gangliosidosis, GM1/enzymology , Gene Expression Regulation , Genome/genetics , Humans , Hyaline Cartilage/pathology , Hyaline Cartilage/ultrastructure , Hydrolases/metabolism , Kidney Tubules/pathology , Kidney Tubules/ultrastructure , Magnetic Resonance Imaging , Mice , Molecular Sequence Data , Mutant Proteins/metabolism , Myelin Sheath/metabolism , Retina/pathology , Transfection , United States , beta-Galactosidase/geneticsABSTRACT
BACKGROUND: Proper exercise training modifies intra miocellular energy utilization, glucose transport and mitochondrial biogenesis. AIM: To determine the therapeutic effects of a high intensity intermittent training (HIIT) program on glucose homeostasis, physical fitness and body fat in glucose intolerant patients. PATIENTS AND METHODS: Eighteen patients with overweight or obesity and glucose intolerance were invited to participate in an exercise program consisting in three sessions per week for 3 months. Ten participants aged 35 ± 13 years who attended > 26 of the planned 36 sessions, were considered as adherent to exercise. The other eight participants aged 37 ± 17 years, who attended to a mean of 13 sessions, were considered as non-adherent. Both groups had similar body weight, body mass index, body fat, plasma glucose 2 h after an oral glucose load and maximal oxygen uptake. All these variables were measured at the end of exercise intervention. Each session consisted of 1 min exercise of cycling at maximal intensity until muscle fatigue followed by 2 min rest, repeated 10 times. RESULTS: Among adherent participants, twelve weeks of HIIT improved significantly maximal oxygen uptake (6.1 + 3.6 mL/kg/min or 24.6%), reduced 2 h post load blood glucose (-33.7 + 47.9 mg/dL or -12.5%) and body fat (-4.3 + 5.6 kg). No significant changes were observed in the non-adherent group. CONCLUSIONS: HIIT exercise reduces blood glucose after an oral load in glucose intolerant patients.
Subject(s)
Blood Glucose/analysis , Exercise/physiology , Glucose Intolerance/blood , Obesity/blood , Oxygen Consumption/physiology , Physical Fitness/physiology , Adult , Body Mass Index , Exercise Tolerance , Female , Glucose Intolerance/physiopathology , Humans , Male , Middle Aged , Obesity/physiopathologyABSTRACT
Medical advocacy has continued to significantly impact quality of life and survivorship outcomes among Latina breast cancer survivors in the United States. However, little is known about the unique experiences of Latina survivors, including the perceived value, process, and context in which they practice medical advocacy. To help address this gap, we conducted a qualitative, secondary analysis of semi-structured focus groups with 18 Latina breast cancer survivors from Chicago, Illinois. Eligible women had to self-identify as (1) female, (2) Latina, (3) 18 years or older, and (4) having a breast cancer diagnosis 5 years ago or more. In total, 61% of participants were 50-59 years old, 83% were born in Mexico, and 100% spoke Spanish. The three emergent themes from the focus groups were (1) the cultural need for Latina advocates and support groups; (2) the process and experiences of becoming a community advocate within Latine culture; and (3) the cultural contexts for advocacy by Latina breast cancer survivors. Latina survivor advocates share strengths of receiving ongoing health education, peer support, and access to resources when being linked to a support group furthering their exposure to role models, increasing their awareness of opportunities in medical advocacy, and providing an entry to participate in medical advocacy.
Subject(s)
Breast Neoplasms , Cancer Survivors , Focus Groups , Hispanic or Latino , Humans , Breast Neoplasms/psychology , Breast Neoplasms/ethnology , Female , Hispanic or Latino/psychology , Hispanic or Latino/statistics & numerical data , Middle Aged , Cancer Survivors/psychology , Cancer Survivors/statistics & numerical data , Patient Advocacy , Chicago , Adult , Aged , Quality of LifeABSTRACT
BACKGROUND: Data on ustekinumab and vedolizumab in the elderly inflammatory bowel disease (IBD) population are limited. The aim of the current study was to assess the safety and effectiveness of both in an elderly real-life population. METHODS: A multicentric retrospective study was performed on IBD patients who started vedolizumab or ustekinumab between 2010 and 2020. Clinical and endoscopic remission rates and (serious) adverse events (AE) were assessed. RESULTS: A total of 911 IBD patients were included, with 171 (19%) aged above 60 (111 VDZ, 60 UST). Elderly patients treated with vedolizumab or ustekinumab had an increased risk for non-IBD hospitalization (10.5% vs. 5.7%, p = 0.021) and malignancy (2.3% vs. 0.5%, p = 0.045) compared to the younger population. Corticosteroid-free clinical (50% vs. 44%; p = 0.201) and endoscopic remission rates (47.9% vs. 31%, p = 0.07) at 1 year were similar. Comparing vedolizumab to ustekinumab in the elderly population, corticosteroid-free (47.9% vs. 31%, p = 0.061) and endoscopic remission rates (66.7% vs. 64.4%, p = 0.981) were similar. Vedolizumab- and ustekinumab-treated patients had comparable infection rates (13.5% vs. 10.0%, p = 0.504), IBD flare-ups (4.5% vs. 5%, p = 1.000), the occurrence of new EIMs (13.5% vs. 10%, p = 0.504), a risk of intestinal surgery (5.4% vs. 6.7%, p = 0.742), malignancy (1.8% vs. 3.3%, p = 0.613), hospitalization (9.9% vs. 11.7%, p = 0.721), and mortality (0.9% vs. 1.7%, p = 1.000). AE risk was associated only with corticosteroid use. CONCLUSIONS: Ustekinumab and vedolizumab show comparable effectiveness and safety in the elderly IBD population. Elderly IBD patients have an increased risk for non-IBD hospitalizations and malignancy compared to the younger IBD population, with corticosteroid use as the main risk factor.