Showing papers by "University of Texas Medical Branch published in 2009"

A Multicenter, Randomized Trial of Treatment for Mild Gestational Diabetes

Abstract: Background It is uncertain whether treatment of mild gestational diabetes mellitus improves pregnancy outcomes. Methods Women who were in the 24th to 31st week of gestation and who met the criteria for mild gestational diabetes mellitus (i.e., an abnormal result on an oral glucose-tolerance test but a fasting glucose level below 95 mg per deciliter [5.3 mmol per liter]) were randomly assigned to usual prenatal care (control group) or dietary intervention, self-monitoring of blood glucose, and insulin therapy, if necessary (treatment group). The primary outcome was a composite of stillbirth or perinatal death and neonatal complications, including hyperbilirubinemia, hypoglycemia, hyperinsulinemia, and birth trauma. Results A total of 958 women were randomly assigned to a study group — 485 to the treatment group and 473 to the control group. We observed no significant difference between groups in the frequency of the composite outcome (32.4% and 37.0% in the treatment and control groups, respectively; P=0.1...

Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline

Abstract: Objective: The aim was to formulate practice guidelines for endocrine treatment oftranssexual persons. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence, which was low or very low. Consensus Process: Committees and members of The Endocrine Society, European Society of Endocrinology, European Society for Paediatric Endocrinology, Lawson Wilkins Pediatric Endocrine Society, and World Professional Association for Transgender Health commented on preliminary drafts of these guidelines. Conclusions: Transsexual persons seeking to develop the physical characteristics of the desired gender require a safe, effective hormone regimen that will 1) suppress endogenous hormone secretion determined by the person’s genetic/biologic sex and 2) maintain sex hormone levels within the normal range for the person’s desired gender. A mental health professional ...

Hydrogen sulfide is an endogenous stimulator of angiogenesis

Abstract: The goal of the current study was to investigate the role of exogenous and endogenous hydrogen sulfide (H2S) on neovascularization and wound healing in vitro and in vivo Incubation of endothelial cells (ECs) with H2S enhanced their angiogenic potential, evidenced by accelerated cell growth, migration, and capillary morphogenesis on Matrigel Treatment of chicken chorioallantoic membranes (CAMS) with H2S increased vascular length Exposure of ECs to H2S resulted in increased phosphorylation of Akt, ERK, and p38 The KATP channel blocker glibenclamide or the p38 inhibitor SB203580 abolished H2S-induced EC motility Since glibenclamide inhibited H2S-triggered p38 phosphorylation, we propose that KATP channels lay upstream of p38 in this process When CAMs were treated with H2S biosynthesis inhibitors dl-propylargylglycine or beta-cyano-L-alanine, a reduction in vessel length and branching was observed, indicating that H2S serves as an endogenous stimulator of the angiogenic response Stimulation of ECs with vascular endothelial growth factor (VEGF) increased H2S release, while pharmacological inhibition of H2S production or KATP channels or silencing of cystathionine gamma-lyase (CSE) attenuated VEGF signaling and migration of ECs These results implicate endothelial H2S synthesis in the pro-angiogenic action of VEGF Aortic rings isolated from CSE knockout mice exhibited markedly reduced microvessel formation in response to VEGF when compared to wild-type littermates Finally, in vivo, topical administration of H2S enhanced wound healing in a rat model, while wound healing was delayed in CSE−/− mice We conclude that endogenous and exogenous H2S stimulates EC-related angiogenic properties through a KATP channel/MAPK pathway

Dietary protein recommendations and the prevention of sarcopenia.

Abstract: Purpose of review Summary On the basis of recent work, we propose a novel and specific dietary approach to prevent or slow-muscle loss with ageing. Rather than recommending a large, global increase in the recommended dietary allowance (RDA) for protein for all elderly individuals, clinicians should stress the importance of ingesting a sufficient amount of protein with each meal. To maximize muscle protein synthesis while being cognizant of total energy intake, we propose a dietary plan that includes 25-30g of high quality protein per meal.

Theory, Practice, and Applications of Paramagnetic Relaxation Enhancement for the Characterization of Transient Low-Population States of Biological Macromolecules and Their Complexes

Abstract: Understanding the function of biological macromolecules and their complexes at the physicochemical level requires knowledge of both their structure and dynamics. Conventional biophysical techniques, such as crystallography and NMR, have yielded incredibly detailed structural information at the atomic level on highly populated static states.1 In the context of the energy landscape representation of macromolecules, highly populated states are located within the global free energy minimum region of a relatively rough free energy hypersurface.2-5 Much less is known, however, about lowly populated, higher free energy states which cannot be * E-mail: G.M.C., mariusc@mail.nih.gov; J.I., j.iwahara@utmb.edu. † National Institutes of Health. ‡ University of Texas Medical Branch. Chem. Rev. 2009, 109, 4108–4139 4108

Laser optoacoustic imaging system for detection of breast cancer

Abstract: We designed, fabricated and tested the laser optoacoustic imaging system for breast cancer detection LOIS-64, which fuses optical and acoustic imaging techniques in one modality by utilizing pulsed optical illumination and ultrawide-band ultrasonic detection of resulting optoacoustic OA signals. The system was designed to im- age a single breast slice in craniocaudal or mediolateral projection with an arc-shaped array of 64 ultrawide-band acoustic transducers. The system resolution on breast phantoms was at least 0.5 mm. The single-channel sensitivity of 1.66 mV/Pa was estimated to be suffi- cient for single-pulse imaging of 6t o 11 mm tumors through the whole imaging slice of the breast. The implemented signal processing using the wavelet transform allowed significant reduction of the low- frequency LF acoustic noise, allowed localization of the optoacous- tic signals from tumors, and enhanced the contrast and sharpened the boundaries of the optoacoustic images of the tumors. During the pre- liminary clinical studies on 27 patients, the LOIS-64 was able to visu- alize 18 out of 20 malignant lesions suspected from mammography and ultrasound images and confirmed by the biopsy performed after the optoacoustic tomography OAT procedure. © 2009 Society of Photo-

County-Level Estimates of Mental Health Professional Shortage in the United States

Abstract: Objective: This study examined shortages of mental health professionals at the county level across the United States. A goal was to motivate discussion of the data improvements and practice standards required to develop an adequate mental health professional workforce. Methods: Shortage of mental health professionals was conceptualized as the percentage of need for mental health visits that is unmet within a county. County-level need was measured by estimating the prevalence of serious mental illness, then combining separate estimates of provider time needed by individuals with and without serious mental illness derived from National Comorbidity Survey Replication, U.S. Census, and Medical Panel Expenditure Survey data. County-level supply data were compiled from professional associations, state licensure boards, and national certification boards. Shortage was measured for prescribers, nonprescribers, and a combination of both groups in the nation’s 3,140 counties. Ordinary least-squares regression identified county characteristics associated with shortage. Results: Nearly one in five counties (18%) in the nation had unmet need for nonprescribers. Nearly every county (96%) had unmet need for prescribers and therefore some level of unmet need overall. Rural counties and those with low per capita income had higher levels of unmet need. Conclusions: These findings identified widespread prescriber shortage and poor distribution of nonprescribers. A caveat is that these estimates of need were extrapolated from current provider treatment patterns rather than from a normative standard of how much care should be provided and by whom. Better data would improve these estimates, but future work needs to move beyond simply describing shortages to resolving them. (Psychiatric Services 60:1323–1328, 2009)

Rapamycin administration in humans blocks the contraction-induced increase in skeletal muscle protein synthesis

Abstract: Muscle protein synthesis and mTORC1 signalling are concurrently stimulated following muscle contraction in humans. In an effort to determine whether mTORC1 signalling is essential for regulating muscle protein synthesis in humans, we treated subjects with a potent mTORC1 inhibitor (rapamycin) prior to performing a series of high-intensity muscle contractions. Here we show that rapamycin treatment blocks the early (1–2 h) acute contraction-induced increase (∼40%) in human muscle protein synthesis. In addition, several downstream components of the mTORC1 signalling pathway were also blunted or blocked by rapamycin. For instance, S6K1 phosphorylation (Thr421/Ser424) was increased post-exercise 6-fold in the control group while being unchanged with rapamycin treatment. Furthermore, eEF2 phosphorylation (Thr56) was reduced by ∼25% post-exercise in the control group but phosphorylation following rapamycin treatment was unaltered, indicating that translation elongation was inhibited. Rapamycin administration prior to exercise also reduced the ability of raptor to associate with mTORC1 during post-exercise recovery. Surprisingly, rapamycin treatment prior to resistance exercise completely blocked the contraction-induced increase in the phosphorylation of ERK1/2 (Thr202/Tyr204) and blunted the increase in MNK1 (Thr197/202) phosphorylation. However, the phosphorylation of a known target of MNK1, eIF4E (Ser208), was similar in both groups (P > 0.05) which is consistent with the notion that rapamycin does not directly inhibit MAPK signalling. We conclude that mTORC1 signalling is, in part, playing a key role in regulating the contraction-induced stimulation of muscle protein synthesis in humans, while dual activation of mTORC1 and ERK1/2 stimulation may be required for full stimulation of human skeletal muscle protein synthesis.

Impact of climate change and other factors on emerging arbovirus diseases

Abstract: While some sceptics remain unconvinced that global climate change is a reality, there is no doubt that during the past 50 years or so, patterns of emerging arbovirus diseases have changed significantly. Can this be attributed to climate change? Climate is a major factor in determining: (1) the geographic and temporal distribution of arthropods; (2) characteristics of arthropod life cycles; (3) dispersal patterns of associated arboviruses; (4) the evolution of arboviruses; and (5) the efficiency with which they are transmitted from arthropods to vertebrate hosts. Thus, under the influence of increasing temperatures and rainfall through warming of the oceans, and alteration of the natural cycles that stabilise climate, one is inevitably drawn to the conclusion that arboviruses will continue to emerge in new regions. For example, we cannot ignore the unexpected but successful establishment of chikungunya fever in northern Italy, the sudden appearance of West Nile virus in North America, the increasing frequency of Rift Valley fever epidemics in the Arabian Peninsula, and very recently, the emergence of Bluetongue virus in northern Europe. In this brief review we ask the question, are these diseases emerging because of climate change or do other factors play an equal or even more important role in their emergence?

Rift Valley fever virus

Abstract: Vet Med Today: Zoonosis Update 883 R Valley fever virus is a mosquito-borne pathogen of livestock and humans that historically has been responsible for widespread and devastating outbreaks of severe disease throughout Africa and, more recently, the Arabian Peninsula. The virus was first isolated and RVF disease was initially characterized following the sudden deaths (over a 4-week period) of approximately 4,700 lambs and ewes on a single farm along the shores of Lake Naivasha in the Great Rift Valley of Kenya in 1931. Since that time, RVF virus has caused numerous economically devastating epizootics that were characterized by sweeping abortion storms and mortality ratios of approximately 100% among neonatal animals and of 10% to 20% among adult ruminant livestock (especially sheep and cattle). Infections in humans are typically associated with selflimiting febrile illnesses. However, in 1% to 2% of affected individuals, RVF infections can progress to more severe disease including fulminant hepatitis, encephalitis, retinitis, blindness, or a hemorrhagic syndrome; among severely affected persons who are hospitalized, the case fatality ratio is approximately 10% to 20%. Rift Valley fever epizootics and epidemics can rapidly overwhelm the capacities of the public health and veterinary medical communities to provide rapid diagnostic testing and adequate medical care for affected humans and other animals, which can number in the tens if not hundreds of thousands. Veterinarians, other health personnel, farmers, and abattoir workers also are at high risk of infection from direct contact with infected animals and patients; indeed, many historical outbreaks of RVF disease in Africa were initially detected because of illnesses among veterinarians and their assistants after they performed necropsies on infected animals. In 2008, several veterinarians, staff, and veterinary students at a South African veterinary college were infected after handling and performing necropsies Rift Valley fever virus

A two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein

Abstract: Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression, including type I interferon production, by promoting host mRNA degradation and inhibiting host translation, in infected cells. We present evidence that nsp1 uses a novel, two-pronged strategy to inhibit host translation and gene expression. Nsp1 bound to the 40S ribosomal subunit and inactivated the translational activity of the 40S subunits. Furthermore, the nsp1-40S ribosome complex induced the modification of the 5' region of capped mRNA template and rendered the template RNA translationally incompetent. Nsp1 also induced RNA cleavage in templates carrying the internal ribosome entry site (IRES) from encephalomyocarditis virus, but not in those carrying IRES elements from hepatitis C or cricket paralysis viruses, demonstrating that the nsp1-induced RNA modification was template-dependent. We speculate that the mRNAs that underwent the nsp1-mediated modification are marked for rapid turnover by the host RNA degradation machinery.

Role of superoxide, nitric oxide, and peroxynitrite in doxorubicin-induced cell death in vivo and in vitro

Abstract: Doxorubicin (DOX) is a potent available antitumor agent; however, its clinical use is limited because of its cardiotoxicity. Cell death is a key component in DOX-induced cardiotoxicity, but its mec...

Nutritional and contractile regulation of human skeletal muscle protein synthesis and mTORC1 signaling

Abstract: In this review we discuss current findings in the human skeletal muscle literature describing the acute influence of nutrients (leucine-enriched essential amino acids in particular) and resistance exercise on muscle protein synthesis and mammalian target of rapamycin complex 1 (mTORC1) signaling. We show that essential amino acids and an acute bout of resistance exercise independently stimulate human skeletal muscle protein synthesis. It also appears that ingestion of essential amino acids following resistance exercise leads to an even larger increase in the rate of muscle protein synthesis compared with the independent effects of nutrients or muscle contraction. Until recently the cellular mechanisms responsible for controlling the rate of muscle protein synthesis in humans were unknown. In this review, we highlight new studies in humans that have clearly shown the mTORC1 signaling pathway is playing an important regulatory role in controlling muscle protein synthesis in response to nutrients and/or muscle contraction. We propose that essential amino acid ingestion shortly following a bout of resistance exercise is beneficial in promoting skeletal muscle growth and may be useful in counteracting muscle wasting in a variety of conditions such as aging, cancer cachexia, physical inactivity, and perhaps during rehabilitation following trauma or surgery.

Emerging infections in burns.

Abstract: Background: Patients who suffer severe burns are at higher risk for local and systemic infections. In recent years, emerging resistant pathogens have forced burn care providers world wide to search for alternative forms of treatment. Multidrug-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter spp., and various fungal strains have been the major contributors to the increase in morbidity and mortality rates. Multi-drug-resistant S. aureus remains the major cause of gram-positive burn wound infections world wide. Treatment strategies include rigorous isolation protocols and new types of antibiotics where necessary. Methods: We reviewed 398 severely burned patients (burns >40% total body surface area [TBSA]) admitted to our hospital between 2000 and 2006. Patients who did not contract multi-drug-resistant gram-negative organisms during their hospital course and received our standard antibiotic regimen—vancomycin and piperacillin/tazobactam—served as controls (piperacillin/tazobac...

The leading causes of death after burn injury in a single pediatric burn center.

Abstract: Severe thermal injury is characterized by profound morbidity and mortality. Advances in burn and critical care, including early excision and grafting, aggressive resuscitation and advances in antimicrobial therapy have made substantial contributions to decrease morbidity and mortality. Despite these advances, death still occurs. Our aim was to determine the predominant causes of death in burned pediatric patients in order to develop new treatment avenues and future trajectories associated with increased survival. Primary causes of death were reviewed from 144 pediatric autopsy reports. Percentages of patients that died from anoxic brain injuries, sepsis, or multi-organ failure were calculated by comparing to the total number of deaths. Data was stratified by time (from 1989 to 1999, and 1999 to 2009), and gender. Statistical analysis was done by chi-squared, Student's t-test and Kaplan-Meier for survival where applicable. Significance was accepted as P < 0.05. Five-thousand two-hundred-sixty patients were admitted after burn injury from July 1989 to June 2009, and of those, 145 patients died after burn injury. Of these patients, 144 patients had an autopsy. The leading causes of death over 20 years were sepsis (47%), respiratory failure (29%), anoxic brain injury (16%), and shock (8%). From 1989 to 1999, sepsis accounted for 35% of deaths but increased to 54% from 1999 to 2009, with a significant increase in the proportion due to antibiotic resistant organisms (P < 0.05). Sepsis is the leading cause of death after burn injury. Multiple antibiotic resistant bacteria now account for the bulk of deaths due to sepsis. Further improvement in survival may require improved strategies to deal with this problem.

Accessing antiretroviral therapy following release from prison.

Abstract: Context Interruption of antiretroviral therapy (ART) during the first weeks after release from prison may increase risk for adverse clinical outcomes, transmission of human immunodeficiency virus (HIV), and drug-resistant HIV reservoirs in the community. The extent to which HIV-infected inmates experience ART interruption following release from prison is unknown. Objectives To determine the proportion of inmates who filled an ART prescription within 60 days after release from prison and to examine predictors of this outcome. Design, Setting, and Participants Retrospective cohort study of all 2115 HIV-infected inmates released from the Texas Department of Criminal Justice prison system between January 2004 and December 2007 and who were receiving ART before release. Main Outcome Measure Proportion of inmates who filled an ART prescription within 10, 30, and 60 days of release from prison. Results Among the entire study cohort (N = 2115), an initial prescription for ART was filled by 115 (5.4%) inmates within 10 days of release (95% confidence interval [CI], 4.5%-6.5%), by 375 (17.7%) within 30 days (95% CI, 16.2%-19.4%), and by 634 (30.0%) within 60 days (95% CI, 28.1%-32.0%). In a multivariate analysis of predictors (including sex, age, race/ethnicity, viral load, duration of ART, year of discharge, duration of incarceration, parole, and AIDS Drug Assistance Program application assistance), Hispanic and African American inmates were less likely to fill a prescription within 10 days (adjusted estimated risk ratio [RR], 0.4 [95% CI, 0.2-0.8] and 0.4 [95% CI, 0.3-0.7], respectively) and 30 days (adjusted estimated RR, 0.7 [95% CI, 0.5-0.9] and 0.7 [95% CI, 0.5-0.9]). Inmates with an undetectable viral load were more likely to fill a prescription within 10 days (adjusted estimated RR, 1.8 [95% CI, 1.2-2.7]), 30 days (1.5 [95% CI, 1.2-1.8]), and 60 days (1.3 [95% CI, 1.1-1.5]). Inmates released on parole were more likely to fill a prescription within 30 days (adjusted estimated RR, 1.3 [95% CI, 1.1-1.6]) and 60 days (1.5 [95% CI, 1.4-1.7]). Inmates who received assistance completing a Texas AIDS Drug Assistance Program application were more likely to fill a prescription within 10 days (adjusted estimated RR, 3.1 [95% CI, 2.0-4.9]), 30 days (1.8 [95% CI, 1.4-2.2]), and 60 days (1.3 [95% CI, 1.1-1.4]). Conclusion Only a small percentage of Texas prison inmates receiving ART while incarcerated filled an initial ART prescription within 60 days of their release.

Why Public Health Agencies Cannot Depend on Good Laboratory Practices as a Criterion for Selecting Data: The Case of Bisphenol A

Abstract: BackgroundIn their safety evaluations of bisphenol A (BPA), the U.S. Food and Drug Administration (FDA) and a counterpart in Europe, the European Food Safety Authority (EFSA), have given special pr...

Management of blood glucose in type 2 diabetes mellitus.

Abstract: Evidence-based guidelines for the treatment of type 2 diabetes mellitus focus on three areas: intensive lifestyle intervention that includes at least 150 minutes per week of physical activity, weight loss with an initial goal of 7 percent of baseline weight, and a low-fat, reduced-calorie diet; aggressive management of cardiovascular risk factors (i.e., hypertension, dyslipidemia, and microalbuminuria) with the use of aspirin, statins, and angiotensin-converting enzyme inhibitors; and normalization of blood glucose levels (hemoglobin A1C level less than 7 percent). Insulin resistance, decreased insulin secretion, and increased hepatic glucose output are the hallmarks of type 2 diabetes, and each class of medication targets one or more of these defects. Metformin, which decreases hepatic glucose output and sensitizes peripheral tissues to insulin, has been shown to decrease mortality rates in patients with type 2 diabetes and is considered a first-line agent. Other medications include sulfonylureas and nonsulfonylurea secretagogues, alpha glucosidase inhibitors, and thiazolidinediones. Insulin can be used acutely in patients newly diagnosed with type 2 diabetes to normalize blood glucose, or it can be added to a regimen of oral medication to improve glycemic control. Except in patients taking multiple insulin injections, home monitoring of blood glucose levels has questionable utility, especially in relatively well-controlled patients. Its use should be tailored to the needs of the individual patient.

Synaptotagmin-1 functions as a Ca2+ sensor for spontaneous release.

Abstract: Spontaneous 'mini' release occurs at all synapses, but its nature remains enigmatic. We found that >95% of spontaneous release in murine cortical neurons was induced by Ca2+-binding to synaptotagmin-1 (Syt1), the Ca2+ sensor for fast synchronous neurotransmitter release. Thus, spontaneous and evoked release used the same Ca2+-dependent release mechanism. As a consequence, Syt1 mutations that altered its Ca2+ affinity altered spontaneous and evoked release correspondingly. Paradoxically, Syt1 deletions (as opposed to point mutations) massively increased spontaneous release. This increased spontaneous release remained Ca2+ dependent but was activated at lower Ca2+ concentrations and with a lower Ca2+ cooperativity than synaptotagmin-driven spontaneous release. Thus, in addition to serving as a Ca2+ sensor for spontaneous and evoked release, Syt1 clamped a second, more sensitive Ca2+ sensor for spontaneous release that resembles the Ca2+ sensor for evoked asynchronous release. These data suggest that Syt1 controls both evoked and spontaneous release at a synapse as a simultaneous Ca2+-dependent activator and clamp of exocytosis.

Amino Acid Supplementation Increases Lean Body Mass, Basal Muscle Protein Synthesis, and Insulin-Like Growth Factor-I Expression in Older Women

Abstract: Context: Inadequate dietary protein intake has been implicated in sarcopenia. Objective and Design: The objectives of this study were to determine whether: 1) chronic essential amino acid (EAA) supplementation improves postabsorptive muscle protein fractional synthesis rate (FSR), lean body mass (LBM), and one-repetition maximum muscle strength, and androgen receptor and IGF-I muscle protein expression; and 2) the acute anabolic response to EAA ingestion is preserved after a 3-month supplementation period. Using a randomized, double-blinded, placebo-controlled design, older women (68 ± 2 yr) were assigned to receive either placebo (n = 7), or 15 g EAA/d [supplemented treatment group (SUP)] (n = 7) for 3 months. Metabolic outcomes were assessed in association with stable isotope studies conducted at 0 and 3 months. Setting: The study was performed at The University of Texas Medical Branch General Clinical Research Center. Results: Ingestion of 7.5 g EAA acutely stimulated FSR in both groups at 0 months (P < 0.05). Basal FSR at 3 months was increased in SUP only. The magnitude of the acute response to EAA was unaltered after 3 months in SUP. LBM increased in SUP only (P < 0.05). One-repetition maximum strength remained unchanged in both groups. Basal IGF-I protein expression increased in SUP after 3 months (P = 0.05), with no changes in androgen receptor or total and phosphorylated Akt, mammalian target of rapamycin, S6 kinase, and 4E-binding protein. Conclusions: EAA improved LBM and basal muscle protein synthesis in older individuals. The acute anabolic response to EAA supplementation is maintained over time and can improve LBM, possibly offsetting the debilitating effects of sarcopenia.

Intraclonal competition limits the fate determination of regulatory T cells in the thymus

Abstract: Because the deletion of self-reactive T cells is incomplete, thymic development of natural Foxp3+CD4+ regulatory T cells (Treg cells) is required for preventing autoimmunity. However, the function of T cell antigen receptor (TCR) specificity in thymic Treg cell development remains controversial. To address this issue, we generated a transgenic line expressing a naturally occurring Treg cell-derived TCR. Unexpectedly, we found that efficient thymic Treg cell development occurred only when the antigen-specific Treg cell precursors were present at low clonal frequency (o1%) in a normal thymus. Using retroviral vectors and bone marrow chimeras, we observed similar activity with two other Treg cell-derived TCRs. Our data demonstrate that thymic Treg cell development is a 'TCR-instructive' process involving a niche that can be saturable at much lower clonal frequencies than is the niche for positive selection.

Molecular aspects of human cellular zinc homeostasis: redox control of zinc potentials and zinc signals.

Abstract: Zinc(II) ions are essential for all forms of life. In humans, they have catalytic and structural functions in an estimated 3,000 zinc proteins. In addition, they interact with proteins transiently when they regulate proteins or when proteins regulate cellular zinc re-distribution. As yet, these types of zinc proteins have been explored poorly. Therefore the number of zinc/protein interactions is potentially larger than that given by the above estimate. Confronted with such a wide range of functions, which affect virtually all aspects of cellular physiology, investigators have begun to elucidate the molecular mechanisms of cellular homeostatic control of zinc, especially the functions of transporter, sensor, and trafficking proteins, such as metallothioneins, in providing the correct amounts of zinc ions for the synthesis of zinc metalloproteins. The sulfur-containing amino acid cysteine in proteins has an important role in the cellular mobility of zinc ions. Sulfur-coordination environments provide sufficiently strong interactions with zinc ions; they can undergo fast ligand-exchange; and they can serve as molecular redox switches for zinc binding and release. For the cellular functions of zinc, the free zinc ion concentrations (zinc potentials, pZn = −log[Zn2+]) and the zinc buffering capacity are critically important parameters that need to be defined quantitatively. In the cytoplasm, free zinc ions are kept at picomolar concentrations as a minute fraction of the few hundred micromolar concentrations of total cellular zinc. However, zinc ion concentrations can fluctuate under various conditions. Zinc ions released intracellularly from the zinc/thiolate clusters of metallothioneins or secreted from specialized organelles are potent effectors of proteins and are considered zinc signals. The cellular zinc buffering capacity determines the threshold between physiological and pathophysiological actions of zinc ions. When drugs, toxins, other transition metal ions or reactive compounds compromise zinc buffering, large zinc ion fluctuations can injure cells through effects on redox biology and interactions of zinc ions with proteins that are normally not targeted.

Growth in the care of older patients by hospitalists in the United States.

Abstract: BACKGROUND National and population-based information on the increase in patient care by hospitalists in the United States is lacking. METHODS Using a 5% sample of Medicare beneficiaries in 1995, 1997, 1999, and the period from 2001 through 2006, we identified 120,226 physicians in general internal medicine who were providing care to older patients in 5800 U.S. hospitals. We defined hospitalists as general internists who derived 90% or more of their Medicare claims for evaluation-and-management services from the care of hospitalized patients. We then calculated the percentage of all inpatient Medicare services provided by hospitalists and identified patient and hospital characteristics associated with the receipt of hospitalist services. RESULTS The percentage of physicians in general internal medicine who were identified as hospitalists increased from 5.9% in 1995 to 19.0% in 2006, and the percentage of all claims for inpatient evaluation-and-management services by general internists that were attributed to hospitalists increased from 9.1% to 37.1% during this same period. Accompanying the increase in care by hospitalists was an increase in the percentage of all hospitalized Medicare patients who were treated by general internists (both hospitalists and traditional, non-hospital-based general internists), from 46.4% in 1995 to 61.0% in 2006. In a multilevel, multivariable analysis controlling for patient and hospital characteristics, the odds of receiving care from a hospitalist increased by 29.2% per year from 1997 through 2006. In 2006, there was marked geographic variation in the rates of care provided by hospitalists, with rates of more than 70% in some hospital-referral regions. CONCLUSIONS These analyses of data from Medicare claims showed a substantial increase in the care of hospitalized patients by hospitalist physicians from 1995 to 2006.