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1.
BMC Psychiatry ; 24(1): 208, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38500095

ABSTRACT

BACKGROUND: Using the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework, we outline steps taken to implement an evidence-based cognitive training program, Club Connect, in older adults with major depressive disorder in an Older People's Mental Health Service in Sydney, Australia. The primary aim was to explore feasibility (or 'reach'), tolerability (or 'implementation'), and acceptability (or 'adoption'). The secondary aim was to explore the most sensitive clinical outcomes and measurement tools (i.e. 'effectiveness') to inform a formal randomised controlled trial, and to explore the healthcare resources used (i.e. costs) to assist decision-making by health care managers and policy-makers in relation to future resource allocation. METHODS: Using a single blinded feasibility design, 40 participants (mean age: 76.13 years, SD: 7.45, range: 65-95 years) were randomised to either (a) Club Connect, a 10-week group-based multifaceted program, comprising psychoeducation and computer-based cognitive training, or (b) a waitlist control group. RESULTS: Implementing group-based cognitive training within a clinical setting was feasible, well tolerated and accepted by participants. Further, cognitive training, in comparison to the waiting list control, was associated with moderate to very large effect size improvements in depression, stress and inhibition (ηp2 = 0.115-0.209). We also found moderate effect size improvements on measures of daily functioning, wellbeing and cognitive flexibility. Small effect size improvements for other cognitive and psychosocial outcomes were also observed. The average cost per person participating in in the intervention was AU$607.50. CONCLUSIONS: Our findings support the feasibility of implementing group-based cognitive training into a specialised clinical (public health) setting. This trial was registered on the Australian and New Zealand Clinical Trial Registry (ACTRN12619000195156, 12/02/2019).


Subject(s)
Depressive Disorder, Major , Mental Health Services , Humans , Aged , Depressive Disorder, Major/therapy , Depression , Feasibility Studies , Cognitive Training , Australia , Brain , Aging
2.
Calcif Tissue Int ; 114(3): 222-227, 2024 03.
Article in English | MEDLINE | ID: mdl-38030713

ABSTRACT

This combined retrospective and prospective study aimed to investigate the relationship between scoliosis, spinal bone mineral density (BMD), and truncal muscle strength in patients with familial dysautonomia (FD). A total of 79 FD patients (40 male, 39 female) aged 5-44 years were included. The severity of scoliosis, lumbar spine BMD (Z-score), and truncal muscle strength were assessed. Correlations were analyzed using Pearson's correlation coefficient. Inverse correlations were observed between scoliosis severity and BMD (r = - 0.328, p = 0.001), as indicated by increasingly negative Z-score values with worsening osteoporosis. There were also inverse correlations between scoliosis and truncal muscle strength (r = - 0.595, p < 0.001). The correlation between scoliosis and age was notable up to 22 years (r = 0.421, p = 0.01), but not in the older age group (22-44 years). Our study identified inverse correlations between osteoporosis and scoliosis, as well as between scoliosis and truncal muscle strength, in FD patients. These findings suggest that there may be a relationship between bone density, muscle strength, and the severity of spinal curvature in this population. While our results highlight the potential importance of early diagnosis and management of osteoporosis, and possibly the benefits of physical therapy to strengthen truncal muscles, further research is needed to determine the direct impact of these interventions on preventing the progression of scoliosis and its associated complications in FD patients. A long-term longitudinal study could provide more insights into these relationships and inform treatment strategies for FD patients.


Subject(s)
Dysautonomia, Familial , Osteoporosis , Scoliosis , Humans , Male , Female , Aged , Bone Density/physiology , Dysautonomia, Familial/complications , Retrospective Studies , Prospective Studies , Longitudinal Studies , Osteoporosis/complications , Lumbar Vertebrae , Muscle Strength , Absorptiometry, Photon/methods
3.
Ecotoxicology ; 28(9): 1038-1045, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31489593

ABSTRACT

Endocrine-disrupting chemicals have been known to alter important animal behaviors by modulating serotonin (5-hydroxytryptamine, 5-HT) and dopamine. F. heteroclitus (mummichog) brain serotonin and dopamine levels were quantified by enzyme-linked immunosorbent assay (ELISA) following a 28-day exposure regimen involving daily doses of either 0.1 mg l-1 benzyl butyl phthalate (BBP) dissolved in acetone or acetone alone (0.1 mg l-1). No differences in mean brain mass or total protein homogenate were induced by exposure to the acetone vehicle or BBP in acetone. The acetone vehicle had no effect on dopamine, serotonin, or tyrosine hydroxylase levels, but acetone did decrease tryptophan hydroxylase levels (p = 0.011). Exposure to BBP in acetone decreased dopamine (p = 0.024), increased serotonin (p < 0.001), reduced tryptophan hydroxylase as compared to the acetone vehicle alone (p < 0.001), and had no significant effect on tyrosine hydroxylase levels. This study is the first to report modulation of F. heteroclitus brain serotonin and its enzyme tryptophan hydroxylase following sub-lethal exposure to BBP in an acetone vehicle. In addition, modulation of brain dopamine in F. heteroclitus, sans simultaneous modulation of tyrosine hydroxylase, was also observed. These findings support the use of F. heteroclitus for assessing sub-lethal BBP exposure.


Subject(s)
Brain/drug effects , Endocrine Disruptors/adverse effects , Phthalic Acids/adverse effects , Plasticizers/adverse effects , Serotonin/metabolism , Water Pollutants, Chemical/adverse effects , Animals , Female , Fundulidae , Random Allocation
4.
Archiv. med. fam. gen. (En línea) ; 16(1): 4-9, mayo 2019.
Article in Spanish | LILACS, InstitutionalDB, BINACIS, UNISALUD | ID: biblio-1343906

ABSTRACT

Con el objetivo de analizar la percepción acerca del colectivo LGBTIQ por parte del personal de salud, administrativos y usuarios del siste-ma de salud en CeMAP CABA (Ciudad Autónoma de Buenos Aires) OsPeCon, así como identificar la discriminación, sus causas y consecuencias, se realizó un estudio cualitativo, de caso, etnográfico.Se realizaron cinco grupos focales y se analizó la información siguiendo los pasos de la teoría fundamentada. En los grupos focales surgieron dudas acerca de la definición de orientación sexual y las siglas I-Q. Se reconocieron prejuicios relacionados al VIH/SIDA, ETS y adicciones como base de la discriminación y la estigmatización. Se evidenció la persistencia de creencias populares como origen de la orientación sexual. Se vio reflejada la heteronormatividad como característica social y la diferencia generacional como postura negativa. Se identificó como forma de discriminación a la violencia verbal y el rechazo al contacto, teniendo como consecuencia depresión, consumo de sustancias y suicidio. Las cuestiones de géneros son temas en continua evolución en la sociedad, por lo que creemos importante estar informados, con una visión empática y de respeto para brindar una atención adecuada a las personas LGBTIQ, teniendo un rol que nos permite deconstruir los estereotipos (AU)


This qualitative ethnographic case study analyzes perceptions of the LGBTIQ community held biomedical professionals, administrative staff and patients in the Health center of OSPeCon, CABA.The purpose of this analysis is to identify discrimination, its causes and consequencesFive focus groups were carried out and the information was analyzed according to the grounded theory.Major themes that emerged from focus groups included confusion regarding the definition of sexual orientation and the acronym I-Q Beliefs related to HIV/AIDS, STD and addiction were noted to be the foundation for discrimination and stigmatization. Other beliefs identified included heteronormativity, which was more prevalent in older generations. The use of popular beliefs to explain the origin of sexual orientation was often justification for discrimination Means of discrimination included verbal violence and rejecting personal contact. Consequences of discrimination identified included depression, substance abuse and suicide. Gender issues continue to evolve and we hope to analyze our own beliefs, deconstruct stereotypes, and educate ourselves in the development of an empathic and respectful attitude to this vulnerable population (AU)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Sexism , Sexual and Gender Minorities , Social Construction of Gender , Gender Studies , Ambulatory Care Facilities , Interpersonal Relations
5.
Archiv. med. fam. gen. (En línea) ; 16(1): 15-21, mayo 2019. tab
Article in Spanish | LILACS, InstitutionalDB, BINACIS, UNISALUD | ID: biblio-1343921

ABSTRACT

Se realizó un estudio cualitativo, etnográfico para conocer y analizar la percepción de los pacientes extranjeros respecto de su vínculo con el sistema de salud en Argentina, considerando la cultura de origen y proceso migratorio mediante trece entrevistas semiestructuradas. Se incluyeron pacientes extranjeros mayores de 18 años que consultaron a un Centro de Atención Primaria de la Salud (CeMAP) de un agente del subsitema sanitario de la seguridad social argentina. Los mismos fueron seleccionados de manera intencional y por conveniencia. Las transcripciones se analizaron según la teoría fundamentada. En las entrevistas se destacó una relación médico-paciente más estrecha en comparación con la del país de origen, destacándose la calidez, compromiso y mayor comunicación con el binomio paciente-familia, siendo notables estas diferencias en la etapa del embarazo y en el ámbito de la salud sexual y reproductiva. Se han hallado diferencias sustanciales con el país de origen en temáticas como control prenatal y acompañamiento del parto, alimentación, medicinas tradicionales, accesibilidad al sistema sanitario, siendo influyente el tiempo de residencia en Argentina para lograr el empoderamiento en relación con el sistema de salud. Esto nos estimula a seguir trabajando en la cultura y proceso migratorio de los pacientes, explorar su cosmovisión, para propiciar un enfoque intercultural que permita adquirir herramientas para la atención de dicha población (AU)


A qualitative, ethnographic study was carried out to identify and analyze the perception and beliefs of foreign patients, regarding their experiences in Argentina ́s healthcare system, taking into consideration their culture of origin and migratory process through semi-structured interviews. It're included foreign patients over 18 years of age who consulted at a Primary Health Care Center (CeMAP) of an agent of the Argentine social security health system. They were selected intentionally and for convenience. Thirteen semi-structured in-depth interviews were recorded and the transcripts were analyzed according to the Fundamental Theory. In the interviews, a closer patient-physician relationship stood out when compared with the country of origin, highlighting the warmth, commitment and greater communication with the patient and its family, these differences were more notable during prenatal, reproductive and sexual care. Substantial differences have been found with the country of origin in topics such as prenatal post-partum care, nutrition, traditional medicines, and accessibility to the health system. There was a positive impact of length of residency in Argentina on patient empowerment within the healthcare system. This is an estimate to continue working on the culture and the migration process of patients, to explore their worldview, to propose an intercultural approach that allows us to acquire tools for the care of this population (AU)


Subject(s)
Humans , Adult , Physician-Patient Relations , Primary Health Care , Human Migration , Culturally Competent Care/ethnology , Health Services Accessibility , Paraguay , Peru , Social Security , Bolivia , Chile , Colombia , Dominican Republic , Mexico
6.
Phys Med Biol ; 62(14): 5612-5622, 2017 Jun 14.
Article in English | MEDLINE | ID: mdl-28467323

ABSTRACT

New treatment modalities in radiotherapy (RT) enable delivery of highly conformal dose distributions in patients. This creates a need for precise dose verification in three dimensions (3D). A radiochromic silicone-based 3D dosimetry system has recently been developed. Such a dosimeter can be used for dose verification in deformed geometries, which requires knowledge of the dosimeter's mechanical properties. In this study we have characterized the dosimeter's elastic behaviour under tensile and compressive stress. In addition, the dose response under strain was determined. It was found that the dosimeter behaved as an incompressible hyperelastic material with a non-linear stress/strain curve and with no observable hysteresis or plastic deformation even at high strains. The volume was found to be constant within a 2% margin at deformations up to 60%. Furthermore, it was observed that the dosimeter returned to its original geometry within a 2% margin when irradiated under stress, and that the change in optical density per centimeter was constant regardless of the strain during irradiation. In conclusion, we have shown that this radiochromic silicone-based dosimeter's mechanical properties make it a viable candidate for dose verification in deformable 3D geometries.


Subject(s)
Materials Testing , Mechanical Phenomena , Radiometry/instrumentation , Silicones , Humans , Stress, Mechanical
7.
Osteoarthritis Cartilage ; 23(11): 2036-44, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26521750

ABSTRACT

OBJECTIVE: The purpose of this controlled laboratory study was to determine the efficacy of Interleukin-1 Receptor Antagonist Protein (IRAP) treatment as an early intervention strategy by examining the changes in microRNA and mRNA expression in cartilage in an ex-vivo porcine knee joint impact model. METHODS: Custom impact device was used to create replicable injury ex-vivo to intact porcine knee joint. Injury was caused by dropping a 10 kg weight one time from 1 m directly above the knee in extension. One hour after impact 20 µg/ml IRAP solution was intra-articularly injected. At 8 h post-injury, cartilage samples were harvested for cell viability and genetic expression analysis. Genetic expression of miR-27b, miR-140, miR-125b, ADAMTS-4, ADAMTS-5, MMP-3, IL-1ß, and TNF-α were analyzed by RT-PCR. Cell viability image analysis was performed using ImageJ software. Groups were compared by analysis of variance (ANOVA) followed by Tukey's post-hoc test. A P-value <0.05 was considered significant. RESULTS: At 8 h after IRAP treatment, expressions of ADAMTS-4, ADAMTS-5, MMP-3, IL-1ß, and TNF-α in cartilage were significantly down-regulated from injury group (all P < 0.001). MiR-140, miR-125b, and miR-27b expressions were significantly up-regulated after treatment as compared to control and injury groups (all P < 0.001). CONCLUSION: This study demonstrates that IRAP treatment administered during acute phase of cartilage impact injury increases expression levels of miR-140, miR-125b, and miR-27b in cartilage, indicating increased inhibition of their respective matrix-degrading enzymes. Clinically, these findings support the potential of IRAP treatment as an early intervention strategy for the prevention of cartilage degeneration after impact injury.


Subject(s)
Cartilage, Articular/metabolism , Cystinyl Aminopeptidase/pharmacology , Gene Expression Regulation , MicroRNAs/genetics , Osteoarthritis/genetics , RNA, Messenger/genetics , Animals , Cartilage, Articular/pathology , Chondrocytes/metabolism , Chondrocytes/pathology , Disease Models, Animal , MicroRNAs/biosynthesis , Osteoarthritis/metabolism , Osteoarthritis/pathology , RNA, Messenger/biosynthesis , Swine
8.
J Med Entomol ; 52(4): 705-12, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26335478

ABSTRACT

When possible, oviparous females should deposit eggs in sites that maximize the future performance of their offspring. Therefore, studies of oviposition behavior may uncover parameters important to offspring fitness. Gravid female Aedes albopictus (Skuse) were given a choice of containers with leaf infusion or plain water, either open or with a cover with a small opening, and their behavior was compared under summer (long day, higher temperature) or fall (short day, lower temperature) regimes. Open containers with leaf infusion were always preferred, but over time, summer females expanded their choices to oviposit in all containers and follow-up experiments indicated that the number of eggs laid was inversely correlated to the number of eggs present. In contrast, fall females laying diapausing eggs that do not hatch until the spring, accumulated eggs in open containers with food resulting in high egg densities. Combined, these results demonstrate a seasonal shift that suggests either high winter egg mortality or safety in numbers. It also demonstrates that female Ae. albopictus change their behavior based on cues associated with expected added risk, which varies across time and space. The wide distribution of summer eggs across container types may contribute to the fast expansion of Ae. albopictus across its invasive range, but egg accumulation in the fall may be exploited for control.


Subject(s)
Aedes/physiology , Larva/physiology , Oviposition/physiology , Animals , Behavior, Animal/physiology , Female , Male , Seasons , Temperature
9.
Ann Oncol ; 26(5): 958-966, 2015 May.
Article in English | MEDLINE | ID: mdl-25632071

ABSTRACT

BACKGROUND: We undertook the present analysis to examine the shifting influence of prognostic factors in HIV-positive patients diagnosed with aggressive non-Hodgkin lymphoma (NHL) over the last two decades. PATIENTS AND METHODS: We carried out a pooled analysis from an existing database of patients with AIDS-related lymphoma. Individual patient data had been obtained prior from prospective phase II or III clinical trials carried out between 1990 until 2010 in North America and Europe that studied chemo(immuno)therapy in HIV-positive patients diagnosed with AIDS-related lymphomas. Studies had been identified by a systematic review. We analyzed patient-level data for 1546 patients with AIDS-related lymphomas using logistic regression and Cox proportional hazard models to identify the association of patient-, lymphoma-, and HIV-specific variables with the outcomes complete response (CR), progression-free survival, and overall survival (OS) in different eras: pre-cART (1989-1995), early cART (1996-2000), recent cART (2001-2004), and contemporary cART era (2005-2010). RESULTS: Outcomes for patients with AIDS-related diffuse large B-cell lymphoma and Burkitt lymphoma improved significantly over time, irrespective of baseline CD4 count or age-adjusted International Prognostic Index (IPI) risk category. Two-year OS was best in the contemporary era: 67% and 75% compared with 24% and 37% in the pre-cART era (P < 0.001). While the age-adjusted IPI was a significant predictor of outcome in all time periods, the influence of other factors waxed and waned. Individual HIV-related factors such as low CD4 counts (<50/mm(3)) and prior history of AIDS were no longer associated with poor outcomes in the contemporary era. CONCLUSIONS: Our results demonstrate a significant improvement of CR rate and survival for all patients with AIDS-related lymphomas. Effective HIV-directed therapies reduce the impact of HIV-related prognostic factors on outcomes and allow curative antilymphoma therapy for the majority of patients with aggressive NHL.


Subject(s)
Anti-HIV Agents/therapeutic use , Antineoplastic Agents/therapeutic use , HIV Infections/therapy , Immunotherapy/methods , Lymphoma, AIDS-Related/therapy , Lymphoma, Non-Hodgkin/therapy , Adolescent , Adult , Aged , Anti-HIV Agents/adverse effects , Antineoplastic Agents/adverse effects , Chi-Square Distribution , Clinical Trials, Phase II as Topic , Clinical Trials, Phase III as Topic , Databases, Factual , Disease Progression , Disease-Free Survival , Europe , Female , HIV Infections/diagnosis , HIV Infections/immunology , HIV Infections/mortality , Humans , Immunotherapy/adverse effects , Kaplan-Meier Estimate , Logistic Models , Lymphoma, AIDS-Related/diagnosis , Lymphoma, AIDS-Related/immunology , Lymphoma, AIDS-Related/mortality , Lymphoma, Non-Hodgkin/diagnosis , Lymphoma, Non-Hodgkin/immunology , Lymphoma, Non-Hodgkin/mortality , Male , Middle Aged , Multivariate Analysis , North America , Proportional Hazards Models , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Young Adult
10.
AIDS Behav ; 19(8): 1388-97, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25234251

ABSTRACT

Most studies of psychosocial predictors of disease progression in HIV have not considered norepinephrine (NE), a neurohormone related to emotion and stress, even though NE has been related to accelerated viral replication in vitro and impaired response to antiretroviral therapy (ART). We therefore examined NE, cortisol, depression, hopelessness, coping, and life event stress as predictors of HIV progression in a diverse sample. Participants (n = 177) completed psychological assessment, blood draws [CD4, viral load (VL)], and a 15 h urine sample (NE, cortisol) every 6 months over 4 years. Hierarchical linear modeling (HLM) was used to model slope in CD4 and VL controlling for ART at every time point, gender, age, race, SES, and initial disease status. NE (as well as depression, hopelessness, and avoidant coping) significantly predicted a greater rate of decrease in CD4 and increase in VL. Cortisol was not significantly related to CD4, but predicted VL increase. To our knowledge, this is the first study relating NE, in vivo, to accelerated disease progression over an extended time. It also extends our previous 2 year study by relating depressed mood and coping to accelerated disease progression over 4 years.


Subject(s)
Adaptation, Psychological , CD4 Lymphocyte Count , HIV Infections/psychology , Hydrocortisone/urine , Norepinephrine/urine , Social Support , Stress, Psychological/blood , Stress, Psychological/urine , Viral Load , Adult , Anti-Retroviral Agents/pharmacology , Anti-Retroviral Agents/therapeutic use , Avoidance Learning , Biomarkers/blood , Depression/psychology , Depressive Disorder/diagnosis , Depressive Disorder/psychology , Disease Progression , Female , Follow-Up Studies , HIV Infections/blood , HIV Infections/drug therapy , HIV Infections/urine , HIV Infections/virology , Humans , Life Change Events , Male , Medication Adherence , Middle Aged , Prospective Studies , Stress, Psychological/psychology
11.
Bone Marrow Transplant ; 50(1): 40-4, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25243620

ABSTRACT

A potential link between arsenic (ATO)-based therapy and delayed hematopoietic recovery after autologous hematopoietic SCT (HSCT) for acute promyelocytic leukemia (APL) has previously been reported. We retrospectively reviewed the clinical histories of 58 patients undergoing autologous HSCT for APL at 21 institutions in the United States and Japan. Thirty-three (56%) of the patients received ATO-based therapy prior to stem cell collection. Delayed neutrophil engraftment occurred in 10 patients (17%): 9 of the 10 patients (90%) received prior ATO (representing 27% of all ATO-treated patients), compared with 1 of the 10 patients (10%) not previously treated with ATO (representing 4% of all ATO-naïve patients; P<0.001). Compared with ATO-naïve patients, ATO-treated patients experienced significantly longer times to ANC recovery (median 12 days vs 9 days, P<0.001). In multivariate analysis, the only significant independent predictor of delayed neutrophil engraftment was prior treatment with ATO (hazard ratio 4.87; P<0.001). Of the available stem cell aliquots from APL patients, the median viable post-thaw CD34+ cell recovery was significantly lower than that of cryopreserved autologous stem cell products from patients with non-APL AML. Our findings suggest that ATO exposure prior to CD34+ cell harvest has deleterious effects on hematopoietic recovery after autologous HSCT.


Subject(s)
Antineoplastic Agents , Arsenicals , Graft Survival/drug effects , Leukemia, Promyelocytic, Acute/therapy , Oxides , Peripheral Blood Stem Cell Transplantation , Adolescent , Adult , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Arsenic Trioxide , Arsenicals/administration & dosage , Arsenicals/adverse effects , Autografts , Female , Humans , Leukemia, Promyelocytic, Acute/blood , Male , Middle Aged , Oxides/administration & dosage , Oxides/adverse effects
12.
Eur Spine J ; 23(4): 745-53, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24469887

ABSTRACT

PURPOSE: Platelet-rich plasma (PRP) contains growth factors and creates a 3D structure upon clotting; PRP or platelet lysate (PL) might be considered for annulus fibrosus (AF) repair. METHODS: Bovine AF cells were cultured with 25% PRP, 50% PRP, 25% PL, 50% PL, or 10% FBS. After 2 and 4 days, DNA, glycosaminoglycan (GAG), and mRNA levels were analyzed. Histology was performed after injection of PRP into an AF defect in a whole disc ex vivo. RESULTS: By day 4, significant increases in DNA content were observed in all treatment groups. All groups also showed elevated GAG synthesis, with highest amounts at 50% PL. Collagen I and II expression was similar between groups; aggrecan, decorin, and versican expression was highest at 25% PL. Injection of PRP into the AF defect resulted in an increased matrix synthesis. CONCLUSIONS: Platelet-rich preparations increased the matrix production and cell number and may therefore be considered to promote AF repair.


Subject(s)
Cell Proliferation/physiology , Extracellular Matrix/physiology , Guided Tissue Regeneration/methods , Intervertebral Disc/physiology , Platelet-Rich Plasma , Regeneration , Animals , Biomarkers/metabolism , Cattle , Cells, Cultured , Collagen/metabolism , Feasibility Studies , Glycosaminoglycans/metabolism , Intervertebral Disc/metabolism , Organ Culture Techniques
13.
Minerva Anestesiol ; 80(1): 89-95, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23857437

ABSTRACT

Coagulation is a complex cascade whose intact functioning is essential in helping control hemorrhage after injury. While traditionally ascribed to the combined effects of acidosis, hypothermia, factor consumption and factor dilution, coagulopathy is also directly related to injury as well as hypofibrinogenemia and hyperfibrinolysis. Low fibrinogen concentration is readily determined with standard laboratory profiling, but direct analysis of hyperfibrinolysis relies on either thromboelastography or rotational thromboelastometry. Both conditions offer opportunities for therapeutic intervention, and inhibition or abrogation of hyperfibrinolysis in particular may significantly improve survival in patients with injury and massive hemorrhage. Herein, we explore the underpinnings of trauma associated coagulopathy, the basic science behind the role of fibrinogen in acute traumatic coagulopathy, and the rationale behind and the data derived from management of hypofibrinogenemia as well as hyperfibrinolysis.


Subject(s)
Fibrinogen/physiology , Hemorrhage/blood , Hemostasis/physiology , Wounds and Injuries/physiopathology , Afibrinogenemia/blood , Afibrinogenemia/congenital , Afibrinogenemia/etiology , Animals , Antifibrinolytic Agents/pharmacology , Antifibrinolytic Agents/therapeutic use , Blood Component Transfusion , Fibrin/biosynthesis , Fibrinogen/therapeutic use , Fibrinolysis/drug effects , Hemorrhage/etiology , Hemorrhage/therapy , Hemostatic Techniques , Humans , Multicenter Studies as Topic , Plasma , Randomized Controlled Trials as Topic , Tranexamic Acid/therapeutic use , Wounds and Injuries/blood , Wounds and Injuries/complications
14.
Article in English | MEDLINE | ID: mdl-23767517

ABSTRACT

We investigate nonequilibrium stationary distributions induced by stochastic dichotomous noise in double-well and multiwell models of ion channel gating kinetics. The channel kinetics is analyzed using both overdamped Langevin equations and master equations. With the Langevin equation approach we show a nontrivial focusing effect due to the external stochastic noise, namely, the concentration of the probability distribution in one of the two wells of a double-well system or in one or more of the wells of the multiwell model. In the multiwell system, focusing in the outer wells is shown to be achievable under physiological conditions, while focusing in the central wells has proved possible so far only at very low temperatures. We also discuss the strength of the focusing effect and obtain the conditions necessary for maximal focusing to appear. These conditions cannot be predicted by a simple master equation approach.


Subject(s)
Ion Channel Gating/physiology , Ion Channels/chemistry , Ion Channels/physiology , Models, Biological , Models, Chemical , Models, Statistical , Stochastic Processes , Computer Simulation , Kinetics , Models, Molecular
15.
Int J Obes (Lond) ; 37(12): 1553-9, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23567924

ABSTRACT

BACKGROUND: Bile acids (BAs) are nutrient-responsive hormones that modulate energy balance through cell surface and nuclear receptors. Postprandial plasma BAs have been found to be decreased in obesity. OBJECTIVE: We aimed to determine whether meal-stimulated circulating BA levels are altered by Roux-en-Y gastric bypass (RYGB), an operation that modifies the neurohumoral determinants of food intake and energy expenditure to cause significant and durable weight loss. DESIGN: Longitudinal study measuring fasting and postprandial plasma BAs before and after RYGB. SUBJECTS: Five obese surgical patients and eight lean controls underwent frequent blood sampling after a standard liquid meal. Obese subjects were also tested at 1, 4 and 40 weeks after RYGB. Primary and secondary circulating BAs, as well as their glycine and taurine conjugates, were measured via reverse-phase high-performance liquid chromatography/mass spectroscopy. RESULTS: We found that postprandial excursion of conjugated BAs was 52.4% lower in obese than in lean individuals by area-under-the-curve (AUC) analysis (378 vs 793 µmol min l(-1), respectively, P<0.05). By 40 weeks after RYGB, the meal-induced rise in conjugated BAs increased by 55.5% to the level of healthy lean controls (378 pre-op vs 850 µmol min l(-) post-op by AUC analyses, P<0.05). In contrast, postprandial concentrations of unconjugated BAs were similar in lean and obese individuals and were not affected by surgery. CONCLUSION: In light of the growing evidence that BAs have key roles in glucose, lipid and energy homeostasis, the observation that RYGB normalizes the blunted postprandial circulating BA response in obesity suggests that BAs may contribute to the improvement in meal-related physiology seen after RYGB. Further studies are warranted to examine this hypothesis and to determine the degree to which an augmented BA response to nutrient ingestion may mediate the increased incretin response, brown adipose tissue activation and thermic effect of feeding that has been observed after this operation.


Subject(s)
Bile Acids and Salts/metabolism , Gastric Bypass , Obesity, Morbid/metabolism , Obesity, Morbid/surgery , Postprandial Period , Weight Loss , Adult , Area Under Curve , Body Mass Index , Eating , Female , Humans , Longitudinal Studies , Male , Middle Aged , Pilot Projects , Postoperative Period , Preoperative Period , Prospective Studies , Satiety Response , Time Factors
16.
Curr Opin Crit Care ; 17(4): 362-9, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21734490

ABSTRACT

PURPOSE OF REVIEW: This article reviews current concepts in perioperative pulmonary management. RECENT FINDINGS: Preoperative risk assessment tools for perioperative pulmonary complications (POPCs) are evolving for both children and adults. Intraoperative management strategies have a demonstrable effect on outcomes. Late POPCs may be preceded by clinical signs. SUMMARY: POPCs are common and lead to significant resource utilization. Optimal POPC risk mitigation must span all phases of surgical care. Preoperative assessment may identify patients at risk and effectively lower their risk by identifying targeted interventions. Intra-operative strategies impact postoperative outcome. POPCs continue to be a concern for several days postoperatively. We review the current literature on this broad subject with a focus on implementable interventions for the clinician.


Subject(s)
Intraoperative Complications/prevention & control , Perioperative Care , Surgical Procedures, Operative/adverse effects , Airway Management , Humans , Preoperative Care , Respiration, Artificial , Resuscitation , Risk Assessment , Risk Reduction Behavior
17.
Obes Rev ; 12(11): 984-94, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21729236

ABSTRACT

Bariatric surgery is the most effective method for promoting dramatic and durable weight loss in morbidly obese subjects. Furthermore, type 2 diabetes is resolved in over 80% of patients. The mechanisms behind the amelioration in metabolic abnormalities are largely unknown but may be due to changes in energy metabolism, gut peptides and food preference. The goal of this meeting was to review the latest research to better understand the mechanisms behind the 'magic' of bariatric surgery. Replication of these effects in a non-surgical manner remains one of the ultimate challenges for the treatment of obesity and diabetes. Promising data on energy metabolism, gastrointestinal physiology, hedonic response and food intake were reviewed and discussed.


Subject(s)
Bariatric Surgery/methods , Energy Metabolism/physiology , Obesity, Morbid/surgery , Weight Loss , Ghrelin/metabolism , Glucagon-Like Peptide 1/metabolism , Humans , Obesity, Morbid/metabolism , Peptide YY/metabolism , Weight Loss/physiology
18.
Phys Rev Lett ; 104(9): 093901, 2010 Mar 05.
Article in English | MEDLINE | ID: mdl-20366984

ABSTRACT

Microwave transport experiments have been performed in a quasi-two-dimensional resonator with randomly distributed conical scatterers. At high frequencies, the flow shows branching structures similar to those observed in stationary imaging of electron flow. Semiclassical simulations confirm that caustics in the ray dynamics are responsible for these structures. At lower frequencies, large deviations from Rayleigh's law for the wave height distribution are observed, which can only partially be described by existing multiple-scattering theories. In particular, there are "hot spots" with intensities far beyond those expected in a random wave field. The results are analogous to flow patterns observed in the ocean in the presence of spatially varying currents or depth variations in the sea floor, where branches and hot spots lead to an enhanced frequency of freak or rogue wave formation.

19.
Transpl Infect Dis ; 12(1): 45-50, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19793068

ABSTRACT

Seventy-two patients undergoing allogeneic transplantation were treated with voriconazole (VOR) as antifungal prophylaxis starting from day -2 of transplantation and continuing until withdrawal of immunosuppression. Patients were assessed for safety and the incidence of definite, probable, or possible fungal infection throughout transplantation was evaluated. VOR was well tolerated. Only 14% of patients required interruption of VOR therapy because of toxicity: liver toxicity (8%), cardiac Q-T interval prolongation (1%), or other side effects (5%). In the early post-transplant period (<120 days), only 2 patients developed invasive fungal infection: 1 mucormycosis infection and 1 disseminated Aspergillus infection. In the late post-transplant period (>120 days), no patients developed probable or definite fungal infection while receiving VOR. No Candida infections were seen in either period. These data suggest that fungal prophylaxis with VOR following allogeneic transplantation is safe and effective.


Subject(s)
Antifungal Agents/therapeutic use , Hematopoietic Stem Cell Transplantation/adverse effects , Mycoses/prevention & control , Pyrimidines/therapeutic use , Transplantation, Homologous/adverse effects , Triazoles/therapeutic use , Adolescent , Adult , Aged , Antifungal Agents/adverse effects , Aspergillosis/drug therapy , Aspergillosis/epidemiology , Aspergillosis/etiology , Aspergillosis/prevention & control , Candidiasis/drug therapy , Candidiasis/epidemiology , Candidiasis/etiology , Candidiasis/prevention & control , Chemoprevention , Female , Humans , Incidence , Male , Middle Aged , Mycoses/drug therapy , Mycoses/epidemiology , Mycoses/etiology , Pyrimidines/adverse effects , Time Factors , Triazoles/adverse effects , Voriconazole , Young Adult
20.
AIDS Care ; 21(3): 368-77, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19280412

ABSTRACT

We interviewed 147 HIV-positive people regarding their key life-changing experiences - involving profound changes in attitudes, behaviors, beliefs (including spiritual beliefs), or self-views - to determine the prominence of HIV as the key positive/negative turning point. HIV was the key turning point, for 37% (26% positive, 11% negative), whereas for 63% of our sample it was not. Characteristics associated with perceiving HIV as the most positive turning point included having a near-death experience from HIV, increasing spirituality after HIV diagnosis, and feeling chosen by a Higher Powerto have HIV. Notably, perceived antecedents of viewing HIV as the key positive turning point were hitting rock bottom and calling on a Higher Power. Conversely, viewing HIV as the most negative turning point was associated with declining spirituality after diagnosis. Spirituality can both negatively and positively affect coping with HIV. Promoting positive spiritual coping may offer new counseling approaches. Further, for the majority of the participants, HIV is not the key turning point, which may be an indicator of the normalization of HIV with the advent of effective treatment.


Subject(s)
Adaptation, Psychological , Attitude to Health , HIV Infections/psychology , Life Change Events , Spirituality , Adult , Female , Humans , Male , Quality of Life , Stress, Psychological
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