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Kagami-Ogata syndrome (KOS) (OMIM #608149) is a genetic imprinting disorder affecting chromosome 14 that results in a characteristic phenotype consisting of typical facial features, skeletal abnormalities including rib abnormalities described as “coat hanger ribs,” respiratory distress, abdominal wall defects, polyhydramnios, and developmental delay. First identified by Wang et al in 1991, over 80 cases of KOS have been reported in the literature. KOS, however, continues to remain a rare and potentially underdiagnosed disorder. In this report, we describe two unrelated male infants with differing initial presentations who were both found to have the characteristic “coat hanger” rib appearance on chest X-ray, raising suspicion for KOS. Molecular testing confirmed KOS in each case. In addition to these new cases, we reviewed the existing cases reported in literature. Presence of polyhydramnios, small thorax, curved ribs, and abdominal wall defects must alert the perinatologist toward the possibility of KOS to facilitate appropriate molecular testing. The overall prognosis of KOS remains poor. Early diagnosis allows for counseling by a multidisciplinary team and enables parents to make informed decisions regarding both pregnancy management and postnatal care.

Autoinducer-2 (AI-2) is unique among quorum-sensing signaling molecules, as it is produced and recognized by a wide variety of bacteria and thus facilitates interspecies communication. To date, two classes of AI-2 receptors have been identified: the LuxP-type, present in the Vibrionales, and the LsrB-type, found in a number of phylogenetically distinct bacterial families. Recently, AI-2 was shown to affect the colonization levels of a variety of bacteria in the microbiome of the mouse gut, including members of the genus Clostridium, but no AI-2 receptor had been identified in this genus. Here, we identify a noncanonical, functional LsrB-type receptor in Clostridium saccharobutylicum. This novel LsrB-like receptor is the first one reported with variations in the binding-site amino acid residues that interact with AI-2. The crystal structure of the C. saccharobutylicum receptor determined at 1.35 Å resolution revealed that it binds the same form of AI-2 as the other known LsrB-type receptors, and isothermal titration calorimetry (ITC) assays showed that binding of AI-2 occurs at a submicromolar concentration. Using phylogenetic analysis, we inferred that the newly identified noncanonical LsrB receptor shares a common ancestor with known LsrB receptors and that noncanonical receptors are present in bacteria from different phyla. This led us to identify putative AI-2 receptors in bacterial species in which no receptors were known, as in bacteria belonging to the Spirochaetes and Actinobacteria phyla. Thus, this work represents a significant step toward understanding how AI-2-mediated quorum sensing influences bacterial interactions in complex biological niches. info:eu-repo/semantics/publishedVersion

Autoinducer-2 (AI-2) is unique among quorum-sensing signaling molecules, as it is produced and recognized by a wide variety of bacteria and thus facilitates interspecies communication. To date, two classes of AI-2 receptors have been identified: the LuxP-type, present in the Vibrionales, and the LsrB-type, found in a number of phylogenetically distinct bacterial families. Recently, AI-2 was shown to affect the colonization levels of a variety of bacteria in the microbiome of the mouse gut, including members of the genus Clostridium, but no AI-2 receptor had been identified in this genus. Here, we identify a noncanonical, functional LsrB-type receptor in Clostridium saccharobutylicum. This novel LsrB-like receptor is the first one reported with variations in the binding-site amino acid residues that interact with AI-2. The crystal structure of the C. saccharobutylicum receptor determined at 1.35 Å resolution revealed that it binds the same form of AI-2 as the other known LsrB-type receptors, and isothermal titration calorimetry (ITC) assays showed that binding of AI-2 occurs at a submicromolar concentration. Using phylogenetic analysis, we inferred that the newly identified noncanonical LsrB receptor shares a common ancestor with known LsrB receptors and that noncanonical receptors are present in bacteria from different phyla. This led us to identify putative AI-2 receptors in bacterial species in which no receptors were known, as in bacteria belonging to the Spirochaetes and Actinobacteria phyla. Thus, this work represents a significant step toward understanding how AI-2–mediated quorum sensing influences bacterial interactions in complex biological niches.

OBJECTIVES: To compare falls and fall-related injuries that a fall evaluator or hospital incident report identified with injuries identified according to discharge International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for the same set of inpatient episodes of care. DESIGN: Prospective, descriptive study. SETTING: Sixteen adult general medical and surgical units in a major urban teaching hospital. PARTICIPANTS: All adults who sustained a fall with injury during a 5-year period (380 falls with injury). MEASUREMENTS: Falls that a fall evaluator or hospital incident report identified were classified according to their injury severity. Discharge abstracts provided diagnosis codes (ICD-9-CM) for the discharge, including fall-related injury codes. RESULTS: Three hundred forty-three inpatient falls with injury (90.2%) resulted in temporary harm to the individual; the remaining 37 falls (9.8%) resulted in more-serious harm. Sixteen of the 37 falls with injury extending hospitalization or resulting in death were identified using Centers for Medicare and Medicaid Services (CMS)-targeted injury code ranges combined with present-on-admission indicators. Of the 21 falls with injury that were not identified, nine (42.9%) lacked documentation of any injury, and seven (33.3%) identified other injuries outside the CMS-targeted injury code ranges. CONCLUSION: The CMS-targeted ICD-9-CM codes used to identify fall-related injuries in claims data do not always detect the most-serious falls. Language: en

N-methyl mesoporphyrin IX (NMM) is exceptionally selective for G-quadruplexes (GQ) relative to duplex DNA and, as such, has found a wide range of applications in biology and chemistry. In addition, NMM is selective for parallel versus antiparallel GQ folds, as was recently demonstrated in our laboratory. Here, we present the X-ray crystal structure of a complex between NMM and human telomeric DNA dAGGG(TTAGGG)(3), Tel22, determined in two space groups, P2(1)2(1)2 and P6, at 1.65 and 2.15 Å resolution, respectively. The former is the highest resolution structure of the human telomeric GQ DNA reported to date. The biological unit contains a Tel22 dimer of 5'-5' stacked parallel-stranded quadruplexes capped on both ends with NMM, supporting the spectroscopically determined 1:1 stoichiometry. NMM is capable of adjusting its macrocycle geometry to closely match that of the terminal G-tetrad required for efficient π-π stacking. The out-of-plane N-methyl group of NMM fits perfectly into the center of the parallel GQ core where it aligns with potassium ions. In contrast, the interaction of the N-methyl group with duplex DNA or antiparallel GQ would lead to steric clashes that prevent NMM from binding to these structures, thus explaining its unique selectivity. On the basis of the biochemical data, binding of NMM to Tel22 does not rely on relatively nonspecific electrostatic interactions, which characterize most canonical GQ ligands, but rather it is hydrophobic in nature. The structural features observed in the NMM-Tel22 complex described here will serve as guidelines for developing new quadruplex ligands that have excellent affinity and precisely defined selectivity.

The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is the precursor of the signal molecule autoinducer-2 (AI-2). AI-2 mediates interspecies communication and facilitates regulation of bacterial behaviors such as biofilm formation and virulence. A variety of bacterial species have the ability to sequester and process the AI-2 present in their environment, thereby interfering with the cell-cell communication of other bacteria. This process involves the AI-2-regulated lsr operon, comprised of the Lsr transport system that facilitates uptake of the signal, a kinase that phosphorylates the signal to phospho-DPD (P-DPD), and enzymes (like LsrG) that are responsible for processing the phosphorylated signal. Because P-DPD is the intracellular inducer of the lsr operon, enzymes involved in P-DPD processing impact the levels of Lsr expression. Here we show that LsrG catalyzes isomerization of P-DPD into 3,4,4-trihydroxy-2-pentanone-5-phosphate. We present the crystal structure of LsrG, identify potential catalytic residues, and determine which of these residues affects P-DPD processing in vivo and in vitro. We also show that an lsrG deletion mutant accumulates at least 10 times more P-DPD than wild type cells. Consistent with this result, we find that the lsrG mutant has increased expression of the lsr operon and an altered profile of AI-2 accumulation and removal. Understanding of the biochemical mechanisms employed by bacteria to quench signaling of other species can be of great utility in the development of therapies to control bacterial behavior.

Mining electronic medical records for data without patients' consent might be viewed as less harmful than performing other types of human subjects research without consent, but to do so is a violation of privacy and, as such, of patients' autonomy. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.

If it is to be ethical, the expenditure of public funds for EHR systems must have a favorable outcome for the public as a whole. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.

Although a variety of bacterial species have been reported to use the interspecies communication signal autoinducer-2 (AI-2) to regulate multiple behaviors, the molecular mechanisms of AI-2 recognition and signal transduction remain poorly understood. To date, two types of AI-2 receptors have been identified: LuxP, present in Vibrio spp., and LsrB, first identified in Salmonella enterica serovar Typhimurium. In S. Typhimurium, LsrB is the ligand binding protein of a transport system that enables the internalization of AI-2. Here, using both sequence analysis and structure prediction, we establish a set of criteria for identifying functional AI-2 receptors. We test our predictions experimentally, assaying key species for their abilities to import AI-2 in vivo, and test their LsrB orthologs for AI-2 binding in vitro. Using these experimental approaches, we were able to identify AI-2 receptors in organisms belonging to phylogenetically distinct families such as the Enterobacteriaceae , Rhizobiaceae , and Bacillaceae . Phylogenetic analysis of LsrB orthologs indicates that this pattern could result from one single origin of the functional LsrB gene in a gammaproteobacterium, suggesting possible posterior independent events of lateral gene transfer to the Alphaproteobacteria and Firmicutes . Finally, we used mutagenesis to show that two AI-2-interacting residues are essential for the AI-2 binding ability. These two residues are conserved in the binding sites of all the functional AI-2 binding proteins but not in the non-AI-2-binding orthologs. Together, these results strongly support our ability to identify functional LsrB-type AI-2 receptors, an important step in investigations of this interspecies signal.

Many bacterial species respond to the quorum-sensing signal autoinducer-2 (AI-2) by regulating different niche-specific genes. Here, we show that Sinorhizobium meliloti, a plant symbiont lacking the gene for the AI-2 synthase, while not capable of producing AI-2 can nonetheless respond to AI-2 produced by other species. We demonstrate that S. meliloti has a periplasmic binding protein that binds AI-2. The crystal structure of this protein (here named SmlsrB) with its ligand reveals that it binds (2R,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran (R-THMF), the identical AI-2 isomer recognized by LsrB of Salmonella typhimurium. The gene encoding SmlsrB is in an operon with orthologues of the lsr genes required for AI-2 internalization in enteric bacteria. Accordingly, S. meliloti internalizes exogenous AI-2, and mutants in this operon are defective in AI-2 internalization. S. meliloti does not gain a metabolic benefit from internalizing AI-2, suggesting that AI-2 functions as a signal in S. meliloti. Furthermore, S. meliloti can completely eliminate the AI-2 secreted by Erwinia carotovora, a plant pathogen shown to use AI-2 to regulate virulence. Our findings suggest that S. meliloti is capable of 'eavesdropping' on the AI-2 signalling of other species and interfering with AI-2-regulated behaviours such as virulence.

Quorum sensing is a process of chemical communication that bacteria use to assess cell population density and synchronize behavior on a community-wide scale. Communication is mediated by signal molecules called autoinducers. The LuxS autoinducer synthase produces 4,5-dihydroxy-2,3-pentanedione (DPD), the precursor to a set of interconverting molecules that are generically called autoinducer-2 (AI-2). In enteric bacteria, AI-2 production induces the assembly of a transport apparatus (called the LuxS regulated (Lsr) transporter) that internalizes endogenously produced AI-2 as well as AI-2 produced by other bacterial species. AI-2 internalization is proposed to be a mechanism enteric bacteria employ to interfere with the signaling capabilities of neighboring species of bacteria. We have previously shown that Salmonella enterica serovar Typhimurium binds a specific cyclic derivative of DPD. Here we show that following internalization, the kinase LsrK phosphorylates carbon-5 of the open form of DPD. Phosphorylated DPD (P-DPD) binds specifically to the repressor of the lsr operon, LsrR, consistent with P-DPD being the inducer of the lsr operon. Subsequently, LsrG catalyzes the cleavage of P-DPD producing 2-phosphoglycolic acid. This series of chemical events is proposed to enable enteric bacteria to respond to the presence of competitor bacteria by sequestering and destroying AI-2, thereby eliminating the competitors' intercellular communication capabilities.

The extracellular signaling molecule autoinducer-2 (AI-2) mediates quorum-sensing communication in diverse bacterial species. In marine vibrios, binding of AI-2 to the periplasmic receptor LuxP modulates the activity of the inner membrane sensor kinase LuxQ, transducing the AI-2 information into the cytoplasm. Here, we show that Vibrio harveyi LuxP associates with LuxQ in both the presence and absence of AI-2. The 1.9 A X-ray crystal structure of apoLuxP, complexed with the periplasmic domain of LuxQ, reveals that the latter contains two tandem Per/ARNT/Simple-minded (PAS) folds. Thus, although many prokaryotic PAS folds themselves bind ligands, the LuxQ periplasmic PAS folds instead bind LuxP, monitoring its AI-2 occupancy. Mutations that disrupt the apoLuxP:LuxQ interface sensitize V. harveyi to AI-2, implying that AI-2 binding causes the replacement of one set of LuxP:LuxQ contacts with another. These conformational changes switch LuxQ between two opposing enzymatic activities, each of which conveys information to the cytoplasm about the cell density of the surrounding environment.

Bacterial populations use cell-cell communication to coordinate community-wide regulation of processes such as biofilm formation, virulence, and bioluminescence. This phenomenon, termed quorum sensing, is mediated by small molecule signals known as autoinducers. While most autoinducers are species specific, autoinducer-2 (AI-2), first identified in the marine bacterium Vibrio harveyi, is produced and detected by many Gram-negative and Gram-positive bacteria. The crystal structure of the V. harveyi AI-2 signaling molecule bound to its receptor protein revealed an unusual furanosyl borate diester. Here, we present the crystal structure of a second AI-2 signal binding protein, LsrB from Salmonella typhimurium. We find that LsrB binds a chemically distinct form of the AI-2 signal, (2R,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran (R-THMF), that lacks boron. Our results demonstrate that two different species of bacteria recognize two different forms of the autoinducer signal, both derived from 4,5-dihydroxy-2,3-pentanedione (DPD), and reveal new sophistication in the chemical lexicon used by bacteria in interspecies signaling.

Interspecific comparisons of protein sequences can reveal regions of evolutionary conservation that are under purifying selection because of functional constraints. Interpreting these constraints requires combining evolutionary information with structural, biochemical, and physiological data to understand the biological function of conserved regions. We take this integrative approach to investigate the evolution and function of the nuclear-encoded subunits of cytochrome c oxidase (COX). We find that the nuclear-encoded subunits evolved subsequent to the origin of mitochondria and the subunit composition of the holoenzyme varies across diverse taxa that include animals, yeasts, and plants. By mapping conserved amino acids onto the crystal structure of bovine COX, we show that conserved residues are structurally organized into functional domains. These domains correspond to some known functional sites as well as to other uncharacterized regions. We find that amino acids that are important for structural stability are conserved at frequencies higher than expected within each taxon, and groups of conserved residues cluster together at distances of less than 5 A more frequently than do randomly selected residues. We, therefore, suggest that selection is acting to maintain the structural foundation of COX across taxa, whereas active sites vary or coevolve within lineages.

The LuxS-dependent autoinducer AI-2 is proposed to function in interspecies cell-cell communication in bacteria. In Salmonella typhimurium, AI-2 is produced and released during exponential growth and is subsequently imported into the bacteria via the Lsr (luxS regulated) ATP binding cassette (ABC) transporter. AI-2 induces transcription of the lsrACDBFGE operon, the first four genes of which encode the Lsr transport apparatus. In this report, we identify and characterize LsrK, a new protein that is required for the regulation of the lsr operon and the AI-2 uptake process. LsrK is a kinase that phosphorylates AI-2 upon entry into the cell. Our data indicate that phosphorylation of AI-2 results in its sequestration in the cytoplasm. We suggest that phospho-AI-2 is the inducer responsible for inactivation of LsrR, the repressor of the lsr operon. We also show that two previously uncharacterized members of the lsr operon, LsrF and LsrG, are necessary for the further processing of phospho-AI-2. Transport and processing of AI-2 could be required for removing the quorum-sensing signal, conveying the signal to an internal detector and/or scavenging boron.

GSY1 is one of the two genes encoding glycogen synthase in Saccharomyces cerevisiae. Both the GSY1 message and the protein levels increased as cells approached stationary phase. A combination of deletion analysis and site-directed mutagenesis revealed a complex promoter containing multiple positive and negative regulatory elements. Expression of GSY1 was dependent upon the presence of a TATA box and two stress response elements (STREs). Expression was repressed by Mig1, which mediates responses to glucose, and Rox1, which mediates responses to oxygen. Characterization of the GSY1 promoter also revealed a novel negative element. This element, N1, can repress expression driven by either an STRE or a heterologous element, the UAS of CYC1. Repression by N1 is dependent on the number of these elements that are present, but is independent of their orientation. N1 repressed expression when placed either upstream or downstream of the UAS, although the latter position is more effective. Gel shift analysis detected a factor that appears to bind to the N1 element. The complexity of the GSY1 promoter, which includes two STREs and three distinct negative elements, was surprising. This complexity may allow GSY1 to respond to a wide range of environmental stresses.

We present a multiweek laboratory exercise that exposes students to the fundamental techniques of bacterial expression and protein purification through the preparation of sperm whale myoglobin. Myoglobin, a robust oxygen-binding protein, contains a single heme that gives the protein a reddish color, making it an ideal subject for the teaching laboratory as students can follow the progress of the protein visually in real time. The purification uses both ion-exchange and size-exclusion chromatography, thus, introducing students to two of the most common separation methods. Students evaluate the quality of the purification via sodium dodecyl sulfate−polyacrylamide gel electrophoresis. In most cases, this procedure produces sufficient quantities of pure protein for further laboratory exercises studying the properties of myoglobin.

Background . Although many primary care patients are inactive, being able to classify even small amounts and intensities of activity and factors associated with these activity levels could be helpful for physicians who are trying to motivate their patients to become more physically active. Methods . Sociodemographics, physical activity, fitness, other cardiovascular risk factors, and psychosocial measures were measured at baseline in the 874 patients in the Activity Counseling Trial. Patients were categorized into three groups: (1) no moderate-to-vigorous physical activity (MVPA), (2) some moderate but no vigorous activity, and (3) some vigorous activity. Multiple logistic regression was used to determine factors cross-sectionally associated with activity intensity. Results . One or more cardiovascular risk factors in addition to physical inactivity were present in 84% of participants. Maximal oxygen uptake averaged 25.2 ml/kg/min; 85% had poor to fair aerobic fitness. Physical activity averaged 32.7 kcal/kg/day, with 13.5 min of MVPA/day; 26% engaged in some vigorous activity, 11% engaged in no MVPA. In unadjusted analyses, gender, age, race, education, income, employment, smoking, alcohol use, and exercise self-efficacy were associated with activity intensity ( P = 0.05–0.001). A greater percentage engaged in moderate than in vigorous activity in all subgroups. In multiple logistic regression analyses, odds ratios (95% confidence intervals) for engaging in vigorous activity were 0.39 (0.28, 0.56) for women, 0.38 (0.19, 0.75) for 65+ compared with 35- to 44-year-olds, and 1.14 (1.06, 1.22) for 10-unit increases in performance self-efficacy score. Conclusions . Most primary care patients who are physically inactive have additional cardiovascular risk factors, particularly overweight and obesity. All subgroups pursue moderate-intensity activity more often than vigorous activity. Women, older persons, and those with lower exercise self-efficacy are less likely to engage in vigorous activity.

The objective of this study was to determine the rate of bacteremia in young women admitted to the hospital with presumed pyelonephritis and compare it with other published rates. The study design was a retrospective, structured chart review and a review of published reports of bacteremic pyelonephritis. An urban county teaching hospital provided the setting for the study. The patients were nonpregnant women (n = 98) 44 years of age or younger who were without bladder dysfunction and who had not been admitted to an intensive care unit. Further criteria for participation included discharge with the diagnosis of acute pyelonephritis. Blood cultures were ordered for 69 women; the results of 64 were noted in the chart. Twenty-three women (35.9% of those cultured; 23.4% of all patients) were diagnosed with bacteremia. In patients for whom blood culture results were obtained, trends developed between those patients with bacteremia and those with complicated pyelonephritis, defined as a known or newly discovered genitourinary abnormality or a risk factor (P = 0.044), those who were black (P = .044), those with higher pulses on admission (P = .050), those with more white blood cells per high-powered field after urinalysis (P = 0.007), and those whose fever lasted longer (P = 0.033). Blood culture results were positive in two patients whose urine cultures were negative. This comparatively high bacteremia rate supports routine ordering of blood cultures for urban women suspected of having pyelonephritis.

Genetic algorithms have been investigated as computational tools for the de novo phasing of low-resolution X-ray diffraction data from crystals of icosahedral viruses. Without advance knowledge of the shape of the virus and only approximate knowledge of its size, the virus can be modeled as the symmetry expansion of a short list of nearly tetrahedrally arranged lattice points which coarsely, but uniformly, sample the icosahedrally unique volume. The number of lattice points depends on an estimate of the non-redundant information content at the working resolution limit. This parameterization permits a simple matrix formulation of the model evaluation calculation, resulting in a highly efficient survey of the space of possible models. Initially, one bit per parameter is sufficient, since the assignment of ones and zeros to the lattice points yields a physically reasonable low-resolution image of the virus. The best candidate solutions identified by the survey are refined to relax the constraints imposed by the coarseness of the modeling, and then trials whose intensity-based statistics are comparatively good in all resolution ranges are chosen. This yields an acceptable starting point for symmetry-based direct phase extension about half the time. Improving efficiency by incorporating the selection criterion directly into the genetic algorithm's fitness function is discussed.

National and international policy-making organizations advocate nonpharmacologic therapies to reduce blood pressure (BP). However, data to support such recommendations in older persons are virtually nonexistent. The Trials of Nonpharmacologic Intervention in the Elderly (TONE) is a randomized, controlled trial that will test whether weight loss or a reduced sodium (Na) intake or both can maintain satisfactory BP control, without unacceptable side effects, after withdrawal of antihypertensive drug therapy. Medication-treated hypertensives (aged 60 to 80 years) with a systolic BP less than 145 mm Hg and a diastolic BP less than 85 mm Hg who are taking one antihypertensive medication are randomly assigned to one of four groups: (1) weight loss alone, (2) reduced Na intake alone, (3) combined weight loss and reduced Na intake, or (4) usual life-style (control group). Overweight participants are randomized to one of these four groups, while nonoverweight individuals are assigned to either the reduced Na intake or the usual life-style group. The interventions, tailored to the needs of older persons, use behavioral approaches to accomplish intervention-specific goals (weight loss > or = 10 lb, daily Na intake < or = 80 mEqa). Three months after the start of intervention, antihypertensive drug therapy is withdrawn. The primary trial end point is a BP of 150/90 mm Hg or higher, resumption of antihypertensive drug therapy, or the occurrence of a BP-related clinical complication during 2 to 3 years of follow-up. It is anticipated that TONE findings may identify an effective and acceptable nonpharmacologic approach to control hypertension in the increasingly large number of older persons treated with antihypertensive drug therapy.

Phase II of the Trials of Hypertension Prevention (TOHP) is a multicenter, randomized trial sponsored by the National Heart, Lung, and Blood Institute designed to test whether weight loss alone, sodium reduction alone, or the combination of weight loss and sodium reduction will decrease diastolic (DBP) and systolic blood pressure (SBP) as well as the incidence of hypertension (DBP > or = 90 mm Hg, SBP > or = 140 mm Hg, and/or use of antihypertensive medications) in subjects with high-normal DBP (83 to 89 mm Hg) and SBP less than 140 mm Hg at entry. These interventions were chosen for longer-term testing with end points including hypertension prevention as well as blood pressure (BP) change based on their demonstrated short-term efficacy in reducing BP in phase I of TOHP. The phase II study population is comprised of 2382 participants (1566 men and 816 women) who are 110 to 165% of desirable body weight, allocated at random to the four treatment arms using a 2 x 2 factorial design. The trial has 80% power to detect an overall treatment effect on DBP of 1.2 mm Hg for weight loss or sodium reduction and a difference of 1.6 mm Hg between the combined intervention and placebo groups. BP observers are blinded to participant treatment assignments. Participants will be followed for 3 to 4 years. This trial may have important public policy implications concerning the ability of life-style modifications to reduce BP and prevent the development of hypertension over the long term, thereby avoiding the need for drug therapy which while effective is costly and may have side effects.

Bed alarm systems intended to prevent hospital falls have not been formally evaluated.To investigate whether an intervention aimed at increasing bed alarm use decreases hospital falls and related events.Pair-matched, cluster randomized trial over 18 months. Nursing units were allocated by computer-generated randomization on the basis of baseline fall rates. Patients and outcome assessors were blinded to unit assignment; outcome assessors may have become unblinded. (ClinicalTrials.gov registration number: NCT00183053)16 nursing units in an urban community hospital.27 672 inpatients in general medical, surgical, and specialty units.Education, training, and technical support to promote use of a standard bed alarm system (intervention units); bed alarms available but not formally promoted or supported (control units).Pre-post difference in change in falls per 1000 patient-days (primary end point); number of patients who fell, fall-related injuries, and number of patients restrained (secondary end points).Prevalence of alarm use was 64.41 days per 1000 patient-days on intervention units and 1.79 days per 1000 patient-days on control units (P = 0.004). There was no difference in change in fall rates per 1000 patient-days (risk ratio, 1.09 [95% CI, 0.85 to 1.53]; difference, 0.41 [CI, -1.05 to 2.47], which corresponds to a greater difference in falls in control vs. intervention units) or in the number of patients who fell, injurious fall rates, or the number of patients physically restrained on intervention units compared with control units.The study was conducted at a single site and was slightly underpowered compared with the initial design.An intervention designed to increase bed alarm use in an urban hospital increased alarm use but had no statistically or clinically significant effect on fall-related events or physical restraint use.National Institute on Aging.

PurposeCentral venous catheters (CVCs) are often placed to resuscitate unstable emergency department (ED) patients. In an observational study, we assessed intraosseous (IO) vascular access in the hospital, and compared results to published experiences with CVC placement.MethodsPatients who would typically receive a CVC were considered for the study. Vascular access was gained using a powered IO device. Data collection included placement success, placement time, ease-of-use, satisfaction with flow rates, complications and subsequent CVC placement.ResultsA total of 105 cases were studied from six centers. Mean age was 48.0±28.0 years and 53% were men; 85% of the patients were medical cases, and 53% were in cardiac/respiratory arrest. Of those, 48% returned to spontaneous circulation. A total of 94% of placements were successful on the first attempt. Mean time to IO access was 103.6±96.2 seconds. There was one serious complication – a lower extremity compartment syndrome. IO access costs $100/patient.ConclusionsThe data revealed faster and more successful IO catheter placement than reported for CVCs, few complications and high user satisfaction. For simple placements, cost savings for IO access vs. CVCs was $195/procedure. If 20% of the 3.5 million CVCs placed annually were replaced with IO catheters, cost savings could approach $650 million/year. We conclude that IO access in place of CVCs delivers high value in terms of being a safe, fast and effective mode of vascular access for patients in the hospital setting, with potentially substantial cost savings. These data indicate that IO access is a cost effective and viable alternative to problematic CVC lines.

Ventricular ectopic activity was recorded at baseline in 5.6% of the 12-lead electrocardiograms and 8.2% of the 2-minute rhythm strips of 4674 subjects with isolated systolic hypertension (systolic blood pressure 160 to 219 mm Hg, diastolic blood pressure 10 VPB on the 2-minute rhythm strip. Correlates of VPB presence on the 12-lead ECG were older-age male sex, presence of Q/QS pattern and higher heart rate. Participants with serum potassium < 3.5 mmol/L had a higher prevalence of VPB. Similarly, the number of VPB on the 2-minute rhythm strip was associated with male sex, increasing age, with lower serum potassium, history of palpitations, and presence of Q/QS patterns.

Bacteria coordinate population-dependent behaviors such as virulence by intra- and inter-species communication (quorum sensing). Autoinducer-2 (AI-2) regulates inter-species quorum sensing. AI-2 derives from the spontaneous cyclisation of linear ( S )-4,5-dihydroxypentanedione (DPD) into two isomeric forms in dynamic equilibrium. Different species of bacteria have different classes of AI-2 receptors (LsrB and LuxP) which bind to different cyclic forms. In the present work, DPD analogs with a new stereocenter at C-5 (4,5-dihydroxyhexanediones (DHDs)) have been synthesized and their biological activity tested in two bacteria. (4 S ,5 R )-DHD is a synergistic agonist in Escherichia coli (which contains the LsrB receptor), while it is an agonist in Vibrio harveyi (LuxP), displaying the strongest agonistic activity reported so far (EC 50 = 0.65 μM) in this organism. Thus, modification at C-5 opens the way to novel methods to manipulate quorum sensing as a method for controlling bacteria.

The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is the precursor of the signal molecule autoinducer-2 (AI-2). AI-2 mediates interspecies communication and facilitates regulation of bacterial behaviors such as biofilm formation and virulence. A variety of bacterial species have the ability to sequester and process the AI-2 present in their environment, thereby interfering with the cell-cell communication of other bacteria. This process involves the AI-2-regulated lsr operon, comprised of the Lsr transport system that facilitates uptake of the signal, a kinase that phosphorylates the signal to phospho-DPD (P-DPD), and enzymes (like LsrG) that are responsible for processing the phosphorylated signal. Because P-DPD is the intracellular inducer of the lsr operon, enzymes involved in P-DPD processing impact the levels of Lsr expression. Here we show that LsrG catalyzes isomerization of P-DPD into 3,4,4-trihydroxy-2-pentanone-5-phosphate. We present the crystal structure of LsrG, identify potential catalytic residues, and determine which of these residues affects P-DPD processing in vivo and in vitro. We also show that an lsrG deletion mutant accumulates at least 10 times more P-DPD than wild type cells. Consistent with this result, we find that the lsrG mutant has increased expression of the lsr operon and an altered profile of AI-2 accumulation and removal. Understanding of the biochemical mechanisms employed by bacteria to quench signaling of other species can be of great utility in the development of therapies to control bacterial behavior.

The transition of quality assurance to continuous quality improvement (CQI) in ambulatory care organizations requires careful planning and consideration of efficiency. Ambulatory care organizations must maintain indicators to measure activities, sample the multiple encounters of ambulatory care, and truly change their internal culture. This article provides practical information that persons involved in quality management can use to plan CQI processes in ambulatory care.

Dynamic circumstances have produced dramatic changes in the requirements of medical education in the 1990s. The present system has failed to keep pace with these changes and is viewed by society as one of the leading causes of high health care costs. It is imperative that academic medical centers assume a leadership role in providing the solutions to the problems in medical education and health care reform if they are to provide for their own long‐term stability.

Agreements between auscultatory blood pressure measurements and recordings of the Suntech Accutracker II ambulatory blood pressure monitor (ABPM) were examined in 103 participants ages 23 through 91 to estimate influence of age on accuracy of automated recordings. Simultaneous auscultation by two technicians and recording by the ABPM were compared. Technicians demonstrated close agreement in auscultation of blood pressure. Mean systolic blood pressure measured by ABPM was 5.6 mm Hg lower and mean ABPM diastolic blood pressure was 6.3 mm Hg lower than average auscultatory blood pressure measured by technicians (P less than .0001). Discrepancies in systolic blood pressure measurements between technicians and ABPM were associated with age and systolic blood pressure. The age effect, controlled for gender and race, was a 0.15 mm Hg increase in systolic blood pressure discrepancy per year of age. Discrepancies in diastolic blood pressure measurements were associated with race but not with age or body size measurements. Automated recordings of blood pressure by this ABPM may have systematic bias compared to auscultation which exceeds current standards for ABPM instrumentation. For systolic blood pressure, this bias increases with age and may affect interpretation of ABPM recordings in elderly persons.

Many bacteria produce and respond to the quorum sensing signal autoinducer-2 (AI-2). Escherichia coli and Salmonella typhimurium are among the species with the lsr operon, an operon containing AI-2 transport and processing genes that are up regulated in response to AI-2. One of the Lsr proteins, LsrF, has been implicated in processing the phosphorylated form of AI-2. Here, we present the structure of LsrF, unliganded and in complex with two phospho-AI-2 analogues, ribose-5-phosphate and ribulose-5-phosphate. The crystal structure shows that LsrF is a decamer of (alphabeta)(8)-barrels that exhibit a previously unseen N-terminal domain swap and have high structural homology with aldolases that process phosphorylated sugars. Ligand binding sites and key catalytic residues are structurally conserved, strongly implicating LsrF as a class I aldolase.

Objective The objective of this study was to examine the prevalence and correlates of postural hypotension (defined as a drop in systolic blood pressure of greater than or equal to 20 mm Hg) in a cohort of elderly persons with isolated systolic hypertension (ISH). Design Baseline cross-sectional analysis of the 4,736 persons randomized in the Systolic Hypertension in the Elderly Program (SHEP). Setting A randomized multi-center double-blind outpatient clinical trial of the impact of treating ISH. Participants Men and women age greater than or equal to 60 years with the systolic blood pressure (SBP) greater than or equal to 160 mm Hg and diastolic blood pressure (DBP) less than 90 mm Hg. Measures Medical histories were obtained using interviewer-administered, standardized clinical history forms. At entry into the study, seated and standing BP was measured by certified BP technicians using a random zero sphygmomanometer. Postural hypotension (PH) was assessed at 1 and 3 minutes after the participant arose from a seated position. Main results PH was found in 10.4% of participants at 1 minute and in 12.0% of participants at 3 minutes. 5.3% of participants demonstrated PH at both time intervals while 17.3% demonstrated PH at either or both of the time intervals. Factors significantly (P less than 0.05) associated with the presence of PH were higher mean SBP and a lower mean body mass index. Conclusions Somewhat different persons were defined as having PH based upon the 1 minute and 3 minute standing measures of BP, and prevalence estimates of PH can vary depending on whether one or more intervals of measurement are used. Cross-sectional data analysis indicated that PH, in healthy community-dwelling older persons with ISH, may not be associated with a history of disorders or problems usually thought to be related to PH. However, prospective data are needed to determine the prognostic significance of PH, and whether one or multiple measurements carry more significance.

BACKGROUND. Important clinical decisions often hinge on patients' functional status. Previous studies have shown disagreement among sources of ratings of patients' functional status. This study compared patient self-ratings, family member ratings, and physician ratings of patient function to performance-based functional testing criteria. METHODS. Five activities of daily living of 73 older patients were studied at admission to a rehabilitation unit following discharge from an acute care community hospital. Data were collected from patients, family members, and physicians and were compared with performance-based function testing. RESULTS. Patient ratings were significantly more accurate than physician ratings for walking, transferring, and telephoning. Patients were significantly more accurate than family members for rating walking and telephoning, but patients were not significantly more accurate than family members or physicians for rating eating or dressing. CONCLUSIONS. We conclude that decisions about patients' functional level should be based on performance testing. If performance testing is unavailable, patients' own ratings are most accurate, followed by family ratings. Physicians' ratings are least accurate.

Simple modifications to a MAR 345 detector which facilitate the collection of very low resolution data are described. With these modifications, the lowest order reflections from a poliovirus crystal (c= 377.1 Å) were observed, and measurement of all reflections in typical protein cells should be routine.

Cardiovascular reactivity is the change in blood pressure, pulse, and other parameters of cardiovascular function in response to a challenging task. During the conduct of cardiovascular reactivity protocols, researchers frequently use automated blood pressure devices to measure blood pressure reactivity. However, the accuracy of automated devices in measuring blood pressure reactivity is unknown. To investigate the accuracy and precision of the Dinamap 1846 SXP and the VitaStat 2600B in the measurement of blood pressure reactivity, we compared blood pressure reactivity recorded by the VitaStat and Dinamap with that obtained by observers using a conventional mercury sphygmomanometer. At three sites, 159 normotensive subjects performed the same task twice, once with blood pressure reactivity measured by the manual observers and once by the VitaStat (n = 79) or Dinamap (n = 80), with the order determined at random. Ratios (VitaStat/Dinamap) of aggregate within-person variance for baseline and task, systolic and diastolic blood pressures ranged from 1.53 to 4.93 (all P < 0.01), suggesting that the Dinamap has better precision than the VitaStat. For both diastolic and systolic blood pressure reactivity and for both types of automated devices, the mean differences in blood pressure reactivity between manual and automated measurements were small (range, -1.8 to 0.8 mm Hg). However, the VitaStat versus manual scatter plot of diastolic blood pressure reactivity showed greater dispersion (correlation coefficient r = 0.16, P = 0.15) than the Dinamap versus manual scatter plot (r = 0.36, P = 0.001). For systolic blood pressure reactivity, the VitaStat versus manual and Dinamap versus manual scatter plots were similar. Our data indicate that the Dinamap is superior to the VitaStat in the measurement of blood pressure reactivity. The substantial performance differences between the VitaStat and Dinamap suggest that other automated blood pressure monitors must be evaluated prior to use in cardiovascular reactivity studies.

We conducted a randomized trial in a community rehabilitation hospital to determine the effect of treatment in a geriatric assessment unit on the physical function, institutionalization rate, and mortality of elderly patients. Functionally impaired elderly patients (mean age, 78.8 years) who were recovering from acute medical or surgical illnesses and were considered at risk for nursing home placement were randomly assigned either to the geriatric assessment unit (n = 78) or to a control group that received usual care (n = 77). The two groups were similar at entry and were stratified according to the perceived risk of an immediate nursing home placement. After six months, the patients treated in the geriatric assessment unit had significantly more functional improvement in three of eight basic self-care activities (P less than 0.05). Those in the lower-risk stratum had significantly more improvement in seven of eight self-care activities. Both six weeks and six months after randomization, significantly more patients treated in the geriatric assessment unit than controls (79 vs. 61 percent after six months) were residing in the community. During the year of follow-up, the control patients had more nursing home stays of six months or longer (10 vs. 3; P less than 0.05). However, there was no difference between the groups in the mean number of days spent in health care facilities (acute care hospital, nursing home, or rehabilitation hospital). Survival analysis showed a trend toward fewer deaths among the patients treated in the geriatric assessment unit, and mortality was significantly reduced in the patients considered to be at lower risk of immediate nursing home placement (P less than 0.05). We conclude that the treatment of selected elderly patients in a specialized geriatric rehabilitation unit improves function, decreases the risk of nursing home placement, and may reduce mortality. The beneficial effects on mortality and function appear greatest for patients at a moderate rather than high risk of nursing home placement.

The LuxS-dependent autoinducer AI-2 is proposed to function in interspecies cell-cell communication in bacteria. In Salmonella typhimurium, AI-2 is produced and released during exponential growth and is subsequently imported into the bacteria via the Lsr (luxS regulated) ATP binding cassette (ABC) transporter. AI-2 induces transcription of the lsrACDBFGE operon, the first four genes of which encode the Lsr transport apparatus. In this report, we identify and characterize LsrK, a new protein that is required for the regulation of the lsr operon and the AI-2 uptake process. LsrK is a kinase that phosphorylates AI-2 upon entry into the cell. Our data indicate that phosphorylation of AI-2 results in its sequestration in the cytoplasm. We suggest that phospho-AI-2 is the inducer responsible for inactivation of LsrR, the repressor of the lsr operon. We also show that two previously uncharacterized members of the lsr operon, LsrF and LsrG, are necessary for the further processing of phospho-AI-2. Transport and processing of AI-2 could be required for removing the quorum-sensing signal, conveying the signal to an internal detector and/or scavenging boron.

Twelve hypertensive black males completed the study, which was conducted to evaluate the effect of metoprolol on 24-h ambulatory blood pressure (ABP). Study participants took 50 mg to 100 mg metoprolol twice daily for a minimum of 3 weeks. Metoprolol had no significant effect on blood pressure (147/90 +/- 11/8 mm Hg v 151/88 +/- 16/8 mm Hg, baseline v treated, respectively) in spite of causing significant reductions in heart rate (87 +/- 9 beats/min v 69 +/- 7 beats/min, P.001). Only one subject had aor = 10 mm Hg decrease in 24-h diastolic blood pressure. The nighttime fall in blood pressure was minimized by metoprolol and clinically significant increases in daytime or nighttime blood pressure were noted in 58% of patients. Metoprolol therapy failed to lower blood pressure and eliminated the normal nighttime decline in blood pressure. Since the nighttime decline in blood pressure is thought to protect against target organ damage, it may be important to identify antihypertensive agents which preserve or enhance the nighttime blood pressure dip.

Article-at-a-Glance Background Patient falls are among the most commonly reported adverse hospital events with more than one million occurring annually in the United States; approximately 10% result in serious injury. A retrospective study was conducted to determine predictors and outcomes of fall injuries among a cohort of adult hospitalized patients. Methods Data were obtained regarding patients who sustained an initial fall in hospital during a 26-month period from 16 adult general medical and surgical units in an urban university-affiliated community hospital. Data on intrinsic (individual) factors, extrinsic (environmental) factors, and situational activities were collected via nurse and patient interviews, patient examinations, and audits of incident reports and electronic health records. Fall injuries were classified as none/any for analyses. Unadjusted odds ratios [ORs] and 95% confidence intervals [CIs] for each of the variables of interest with fall injury were generated using logistic regressions. Results The 784 patients had a median age of 63.5 years (range, 20 to > 90 years), 390 (50%) were women, and 526 (67%) were black. Some 228 (29%) fallers sustained injury; patients who were white (OR: 2.23; 95% CI: 1.62, 3.08), or were administered a selective serotonin reuptake inhibitor (OR: 1.04; 95% CI: 1.04, 2.67), two antipsychotic agents (OR: 3.26; 95% CI: 1.20, 8.90), an opiate (OR: 1.59; 95%; CI: 1.14, 2.20), or a diuretic non-antihypertensive agent (OR: 1.53; 95% CI: 1.03, 2.26) were more likely to sustain an injury. Home-based wheelchair use was protective of fall injury (OR: 0.20; 95% CI: 0.05, 0.84). Seventy-nine percent of the patients had been designated as "high" fall risk within 24hours before the fall. Conclusions Few variables were able to distinguish patients who sustained injury after a hospital fall, further challenging clinicians' efforts to minimize hospital-related fall injury.

Objective: To determine if diagnostic classification is associated with different outcomes from treatment on a geriatric assessment unit (GAU) compared with usual care for elderly patients with acute illnesses. Study Design: Reanalysis after post-hoc diagnostic classification of a randomized clinical trial with one year follow up. Setting: Community hospital with rehabilitation facility. Subjects: A total of 155 subjects, mean age 78 years and 78% female, of whom 58 subjects had a rehabilitation classification of their diagnoses and 97 had a medical or surgical classification. Outcome Measures: Mortality, nursing home use, activities of daily living, and charges for subsequent medical services. Results: Mortality was decreased in persons with a rehabilitation classification who had received the GAU intervention. The GAU increased point-prevalence residence in the community for persons with a rehabilitation classification. For persons with a medical-surgical classification, the GAU intervention was associated with decreased cumulative use of nursing homes. However, GAU intervention was also associated with trends for increased charges in both diagnostic classification groups, even when adjusted for differential survival. Conclusion: Greater benefit from the GAU intervention on mortality and maintenance of residence in the community was observed in a group with a rehabilitation classification when compared with a group with a medical-surgical classification. These improved outcomes in the rehabilitation group were not accompanied by decreased charges for later medical services that could compensate for initial rehabilitation charges. J Am Geriatr Soc 42:11–15, 1994

To test the short-term feasibility and efficacy of seven nonpharmacologic interventions in persons with high normal diastolic blood pressure.Randomized control multicenter trials.Volunteers recruited from the community, treated and followed up at special clinics.Of 16,821 screenees, 2182 men and women, aged 30 through 54 years, with diastolic blood pressure from 80 through 89 mm Hg were selected. Of these, 50 did not return for follow-up blood pressure measurements.Three life-style change groups (weight reduction, sodium reduction, and stress management) were each compared with unmasked nonintervention controls over 18 months. Four nutritional supplement groups (calcium, magnesium, potassium, and fish oil) were each compared singly, in double-blind fashion, with placebo controls over 6 months.Primary: change in diastolic blood pressure from baseline to final follow-up, measured by blinded observers. Secondary: changes in systolic blood pressure and intervention compliance measures.Weight reduction intervention produced weight loss of 3.9 kg (P less than .01), diastolic blood pressure change of -2.3 mm Hg (P less than .01), and systolic blood pressure change of -2.9 mm Hg (P less than .01). Sodium reduction interventions lowered urinary sodium excretion by 44 mmol/24 h (P less than .01), diastolic blood pressure by 0.9 mm Hg (P less than .05), and systolic blood pressure by 1.7 mm Hg (P less than .01). Despite good compliance, neither stress management nor nutritional supplements reduced diastolic blood pressure or systolic blood pressure significantly (P greater than .05).Weight reduction is the most effective of the strategies tested for reducing blood pressure in normotensive persons. Sodium reduction is also effective. The long-term effects of weight reduction and sodium reduction, alone and in combination, require further evaluation.

BACKGROUND. In a recent randomized controlled trial assessing the efficacy of an inpatient geriatric assessment unit (GAU), we demonstrated that patients assigned to the unit were less likely than those in the usual care group to be admitted to a nursing home and more likely to remain living in the community. Despite evidence of benefits of GAU care, questions remain about its cost. We examine the impact of GAU treatment on subsequent health care charges. METHODS. Sequential referrals of elderly disabled patients considered at risk for institutionalization or likely to improve with rehabilitation were randomized to the GAU or to usual care. Charge data were collected on utilization of a wide variety of health care services starting at the point of randomization. RESULTS. The group randomized to the GAU experienced significantly higher rehabilitation charges per participant ($10,583 vs $2066, P = .0001), but lower mean nursing home charges ($1798 vs $3426, P = .004). Total health care charges per participant over the 1 year follow-up were greater for the GAU group ($28,406 vs $16,444, P = .004). When charges were adjusted per year of life survived, the GAU group still showed a substantial (but nonsignificant, P = .10) increase in total charges. However, when charges were adjusted per day subsequently spent residing in the community, adjusted total charges were similar between the two groups. CONCLUSIONS. Our results indicated that improved outcomes from GAU care require an investment in rehabilitation that is not totally offset by decreased institutional charges in the following year.

At their first visits to a clinic, 102 outpatients rated the severity of their presenting complaint, of 12 possible body problems including 6 nonspecific symptoms, of a set of adjustment difficulties, and answered the Welsh A and the Beck Depression inventories. Then, an internist 'blind' to the foregoing answers performed a routine history and physical exam, afterward rating the patient for degree of organic and of psychosomatic involvement. Significant correlations were found between clinician judgments of psychosomatic involvement and patients' self-reported complaints on all assessment measures (smallest r = 0.25, P less than 0.01). Substantial intercorrelations were found among the assessment measures, especially between Welsh A (Anxiety) and Beck Depression scores (r = 0.73).

Patients with cataracts and coincident retinal disease are at increased risk for unsuccessful cataract surgery. We developed a method for estimating probabilities of surgical success for older cataract patients with retinal disease. Using data from a prospective study of cataract surgery outcomes, 36 patients with both cataracts and retinal disease were identified, 13 of whom attained surgical success with 20/40 or better vision 4 months after surgery. Age, presurgical Snellen letter acuity, location of retinal lesions, and presurgical visual function in everyday life (newspaper reading or television viewing) were all reliable correlates of surgical outcome. These data were analyzed using multiple logistic regression to develop a clinical index combining presurgical Snellen letter acuity, location of retinal lesions, and age to predict surgical success. The resulting index demonstrated 83% sensitivity and 85% specificity in sample data, correctly predicting 83% of patients (predictive value positive: 73%; predictive value negative: 90%).

A new nurse practitioner service at a public teaching hospital received patients from internal medicine teaching services. To determine the characteristics of the patients, the ratings by the residents, and the professional team costs, the authors performed a case-series study of the first 248 patients. Transferred patients had conditions that necessitated long hospitalizations, most frequently cerebrovascular accident, dementia, and pneumonia. Housestaff rated the service positively. Estimated professional costs were similar to teaching service costs after 15 months. The nurse practitioner inpatient service effectively cared for internal medicine patients with long lengths of stay and received favorable housestaff ratings.

• Background.—Although nonpharmacologic interventions are widely recommended in the therapy of high blood pressure in older adults, surprisingly little data exist to confirm the efficacy of these interventions in older persons.Methods.—We conducted a randomized, controlled clinical trial in persons aged 60 to 85 years with a diastolic blood pressure of 85 to 100 mm Hg. The experimental arm was a nonpharmacologic intervention combining weight reduction, sodium restriction, and increased physical activity. The nonpharmacologic intervention consisted of eight weekly group and two individual sessions during the intensive phase, followed by four monthly group sessions during the maintenance phase. The control group received no treatment during the study. Blood pressure was assessed by certified technicians (blinded to group assignment) using random zero sphygmomanometers.Results.—Of 56 participants randomized, 47 completed the entire 6-month trial (21 in the intervention group and 26 in the control group). Attendance at the intervention sessions was excellent. The intervention group lost more weight (-2.1 kg) over 6 months than the control group (+0.3 kg). Trends for decreasing 24-hour urine sodium excretion in both the intervention and control groups, with greater trend in the intervention group, were not statistically significant. The intervention group experienced more reduction in systolic and diastolic blood pressure than did the control group (mean differences between groups at 6 months, 4.2/4.9 mm Hg, respectively).Conclusions.—Our data indicate that a nonpharmacologic intervention will lower systolic and diastolic blood pressure levels in older people with borderline or mild elevations of diastolic blood pressure.