Rehospitalization risk factors for psychiatric treatment among elderly Medicaid beneficiaries following hospitalization for a physical health condition.

OBJECTIVES: Hospitalizations for physical health problems can cause great mental health challenges. We examined risk factors and expenditures for early readmission for inpatient psychiatric treatment following a hospitalization for a non-psychiatric condition. METHOD: We used eight years of Florida Medicaid enrollment and claims data for (FY 2003-2011) as well as data obtained from the Florida Center for Health Information and Policy Analysis, Inpatient Hospital Database, to identify episodes of hospitalization for all Medicaid-enrolled older adults. There were a total of 781,660 index hospitalizations for non-behavioral health-related hospitalizations, 2690 (0.3%) of which resulted in a behavioral health-related rehospitalization within 30 days after discharge. We estimated the relative risk of early rehospitalization using Cox proportional hazards regression. RESULTS: Participants (n = 276,254) were 76.8 ± 8.3 years old; 68.4% female and 43.5% White. As expected, we found that having a preexisting behavioral health disorder (including severe mental illness, substance use disorder, or dementia) greatly increased the risk of readmission. We also found that male gender increased the risk of early readmission. Older age, being Black and having one or more comorbid medical conditions as identified by the Charlson Index were associated with substantially reduced risk. CONCLUSION: Identifying hospitalized patients with psychiatric conditions, as well as those who are relatively young within this age group, male, White rather than Black or of other race, alcohol abusers, and those without comorbid conditions, and providing them with care to address their behavioral needs may help in efforts to reduce early rehospitalizations for psychiatric conditions.

Risk of Early Rehospitalization for Non-Behavioral Health Conditions Among Adult Medicaid Beneficiaries with Severe Mental Illness or Substance Use Disorders.

The goal was to examine risk factors and expenditures for early rehospitalization (within 30 days of discharge) for non-behavioral health conditions among Medicaid-enrolled Floridians over 8 years. There were 1,689,797 hospitalization episodes with 19% (N = 314,742) resulting in early rehospitalization. Total gross charges for early rehospitalization were over 13 billion dollars. In Cox proportional hazards regression adjusted for demographic and health covariates, drug use disorder was associated with 50% increased risk of early rehospitalization. Having major depressive disorder increased risk by 17%; psychotic disorder, bipolar disorder, and alcohol use disorder increased risk of early rehospitalization slightly by 10, 6, and 6% respectively. The effect of dementia on risk was minimal at 2%. Risk of early rehospitalization decreased by 3.5% per year over the 8 years of the study. Attention to mental health problems, especially drug use disorder, may help further reduce rates of early readmission for non-behavioral health conditions.

Predictors of behavioural health service use and associated expenditures: Individuals with TBI in Pinellas County.

OBJECTIVE: Traumatic brain injury (TBI) is a major public health concern. Such injuries often result in dramatic changes in the individual's life-course due to the associated complex co-morbidities. Limited research exists on the use and expenditures incurred for behavioural healthcare services post-TBI. This study examined predictors of behavioural service use, incarceration and associated expenditures for individuals with TBI. METHODS: Emergency Medical Services and Medicaid Claims data were used to identify individuals diagnosed with a TBI in Pinellas County, Florida, in FY 2005. Ten statewide and local administrative data sets from 2005-2008 were employed to determine subject's demographic characteristics, criminal justice encounters, behavioural health services use and associated expenditures. Average annual expenditures and use of mental health, substance abuse and criminal justice services over a 3-year period were determined. RESULTS: A total of 1005 individuals diagnosed with TBI were identified and, of these, 910 survived the 3-year period. Study participants were grouped into high and low behavioural health expenditure groups. Those in the high expenditure group were more likely to be male, white and to have received behavioural health services. CONCLUSIONS: This study provides new information about predictors of behavioural health service use and Medicaid expenditures for Floridians with TBI.

Risk factors for early readmission to acute care for persons with schizophrenia taking antipsychotic medications.

OBJECTIVE The study examined risk factors for readmission to acute care among Florida Medicaid enrollees with schizophrenia treated with antipsychotics. METHODS Medicaid and service use data for 2004 to 2008 were used to identify adults with schizophrenia discharged from hospitals and crisis units who were taking antipsychotics. Data were extracted on demographic characteristics, service use before admission, psychopharmacologic treatment after discharge, and readmission to acute behavioral health care. Cox proportional hazards regression estimated readmission risk in the 30 days after discharge and in the period after 30 days for participants not readmitted in the first 30 days. RESULTS The mean±SD age of the 3,563 participants was 43.4±11.1; 61% were male, and 38% were white. Participants had 6,633 inpatient episodes; duration of hospitalization was 10.6±7.0 days. Readmission occurred for 84% of episodes, 23% within 30 days. Variables associated with an increased readmission risk in the first 30 days were shorter hospitalization (hazard ratio [HR]=1.18, 95% confidence interval [CI]=1.10-1.27, p<.001), shorter time on medication before discharge (HR=1.19, CI=1.06-1.35, p=.003), greater prehospitalization use of acute care (HR=2.64, CI=2.29-3.05, p<.001), serious general medical comorbidity (HR=1.21, CI=1.06-1.38, p=.005), and prior substance abuse treatment (HR=1.58, CI=1.37-1.83, p<.001). After 30 days, hospitalization duration and time on medication were not significant risk factors. CONCLUSIONS Short hospital stays for persons with schizophrenia may be associated with risk of early readmission, possibly because the person is insufficiently stabilized. More chronic risk factors include prior acute care, general medical comorbidity, and substance abuse.

Predictors of emergency commitment for nursing home residents: the role of resident and facility characteristics.

OBJECTIVES: The ability of nursing homes to manage the mental health needs of their residents is crucial to providing high quality care. An important element is preventing exacerbations of psychiatric conditions that trigger discharge from the nursing home (NH) because of an emergency commitment (EC) for an involuntary psychiatric examination. The objective of this study was to examine the relationship between resident and facility characteristics and the risk of EC for involuntary psychiatric examination among Medicaid-enrolled NH residents in Florida. DESIGN: This retrospective cohort study employed 2.5 years (31 December 2002 through 30 June 2005) of Medicaid enrollment and fee-for-service, pharmacy, and involuntary commitment data to examine resident characteristics. NH characteristics were obtained from the Online Survey Certification and Reporting database. SETTING: Medicaid-certified NHs in Florida (N= 584). PARTICIPANTS: Medicaid-enrolled NH residents (N= 32,604). RESULTS: Younger age, male gender, having dementia, having a serious mental illness (SMI), and residing in a for-profit facility were all independently associated with the greater risk of EC. Although most residents with EC were prescribed psychotropic medication, less than half received non-pharmacological behavioral health outpatient services before or after their involuntary psychiatric examination. CONCLUSION: Our findings highlight the salience of resident and facility characteristics to prevalence rates of EC for involuntary psychiatric examinations among NH residents and underscore a need for increased education, communication, and future research on the predictive factors as well as the consequences of these adverse events.

The 70S ribosome modulates the ATPase activity of Escherichia coli YchF.

YchF is one of two universally conserved GTPases with unknown cellular function. As a first step toward elucidating YchF's cellular role, we performed a detailed biochemical characterization of the protein from Escherichia coli. Our data from fluorescence titrations not only confirmed the surprising finding that YchFE.coli binds adenine nucleotides more efficiently than guanine nucleotides, but also provides the first evidence suggesting that YchF assumes two distinct conformational states (ATP- and ADP-bound) consistent with the functional cycle of a typical GTPase. Based on an in vivo pull-down experiment using a His-tagged variant of YchF from E. coli (YchFE.coli), we were able to isolate a megadalton complex containing the 70S ribosome. Based on this finding, we report the successful reconstitution of a YchF•70S complex in vitro, revealing an affinity (KD) of the YchFE.coli•ADPNP complex for 70S ribosomes of 3 µM. The in vitro reconstitution data also suggests that the identity of the nucleotide-bound state of YchF (ADP or ATP) modulates its affinity for 70S ribosomes. A detailed Michaelis-Menten analysis of YchF's catalytic activity in the presence and the absence of the 70S ribosome and its subunits revealed for the first time that the 70S ribosome is able to stimulate YchF's ATPase activity (~10-fold), confirming the ribosome as part of the functional cycle of YchF. Our findings taken together with previously reported data for the human homolog of YchF (hOLA1) indicate a high level of evolutionary conservation in the enzymatic properties of YchF and suggest that the ribosome is the main functional partner of YchF not only in bacteria.

Path tortuosity in everyday movements of elderly persons increases fall prediction beyond knowledge of fall history, medication use, and standardized gait and balance assessments.

OBJECTIVES: We hypothesized that variability in voluntary movement paths of assisted living facility (ALF) residents would be greater in the week preceding a fall compared with residents who did not fall. DESIGN: Prospective, observational study using telesurveillance technology. SETTING: Two ALFs. PARTICIPANTS: The sample consisted of 69 older ALF residents (53 female) aged 76.9 (SD ± 11.9 years). MEASUREMENT: Daytime movement in ALF common use areas was automatically tracked using a commercially available ultra-wideband radio real-time location sensor network with a spatial resolution of approximately 20 cm. Movement path variability (tortuosity) was gauged using fractal dimension (fractal D). A logistic regression was performed predicting movement related falls from fractal D, presence of a fall in the prior year, psychoactive medication use, and movement path length. Fallers and non-fallers were also compared on activities of daily living requiring supervision or assistance, performance on standardized static and dynamic balance, and stride velocity assessments gathered at the start of a 1-year fall observation period. Fall risk due to cognitive deficit was assessed by the Mini Mental Status Examination (MMSE), and by clinical dementia diagnoses from participant's activities of daily living health record. RESULTS: Logistic regression analysis revealed odds of falling increased 2.548 (P = .021) for every 0.1 increase in fractal D, and having a fall in the prior year increased odds of falling by 7.36 (P = .006). There was a trend for longer movement paths to reduce the odds of falling (OR .976 P = .08) but it was not significant. Number of psychoactive medications did not contribute significantly to fall prediction in the model. Fallers had more variable stride-to-stride velocities and required more activities of daily living assistance. CONCLUSIONS: High fractal D levels can be detected using commercially available telesurveillance technologies and offers a new tool for health services administrators seeking to reduce falls at their facilities.

The role of race and ethnicity in predicting length of hospice care among older adults.

BACKGROUND: The purpose of the study was to examine both direct and interactive roles of race/ethnicity with patients' characteristics (age, gender, relationship with caregiver, diagnosis, referral source, and payment type) in predicting length of hospice care. METHOD: This study included a total of 16,323 patients 65 years of age and older (M(age)=81.4, SD=8.3) who were served by a hospice in central Florida during a four-year period, 2002-2006. Survival analyses were conducted using the Cox proportional hazards model to predict the length of hospice care and test the interaction effects of race/ethnicity. RESULTS: The majority of subjects (83.5%) were white, 7.6% were African-American, and 8.9% were Hispanic. During the study period, 58.5% died. All patient characteristics were significantly associated with the length of hospice care (p < .05). Overall, Hispanics had the longest hospice stay (M=98.84 days), followed by African-Americans (M=90.29) and whites (M=88.20). With the exception of African-American women who were no more likely to stay longer under hospice care than African-American men, the women in this study stayed longer under hospice care than men did. Patients referred from long-term care (LTC) settings had shorter stays in hospice care compared to those referred by physicians in other settings. Additionally, African-Americans and Hispanics referred from LTC had significantly shorter hospice stays than those referred by primary physicians. CONCLUSION: In this limited sample of hospice patients, length of stay was longer for minority patients than white patients.

Predictors of avoidable hospitalizations among assisted living residents.

OBJECTIVES: Hospitalizations for long term care residents, including those from assisted living facilities (ALFs), are very costly, often traumatic, and increase risk for iatrogenic disorders for those involved. Currently, hospital expenditures account for approximately one-third of total national health care spending. Hospitalizations for ambulatory care-sensitive (ACS) conditions are considered potentially avoidable, as these are physical health conditions that can often be treated safely at a lower level of care or occur as a result of lack of timely, adequate treatment at a lower level of care. The goal was to examine risk factors for hospitalization for an ACS condition of Medicaid-enrolled younger and older ALF residents during 2003-2008. DESIGN: This is a retrospective cohort study that used 5 years of Medicaid enrollment and fee-for-service claims data. PARTICIPANTS: The study sample included 16,208 Medicaid-enrolled ALF residents in Florida, 7991 (49%) of whom were 65 years of age or older. RESULTS: In total, study participants had 22,114 hospitalizations, 3759 (17%) of which were for an ACS condition. Sixteen percent of all ALF residents (n = 2587), about 12% of the younger residents and 20% of the older residents, had at least one ACS hospitalization. ACS hospitalizations constitute 13% of all hospitalizations for the younger residents and 22% of all hospitalizations for the older residents. Using Cox proportional hazard regression, we found that for both age groups, increased age, being Hispanic or of other race/ethnicity, and having comorbid physical health conditions were associated with a higher risk of ACS hospitalization. For older residents, having a dementia diagnosis and being African American reduced the risk of ACS hospitalization, whereas for younger residents having a major psychotic disorder reduced the risk of ACS hospitalization. CONCLUSION: The results highlight the need for increased education, communication, and future research on these predictive factors. The increased frequency of hospitalization for ACS conditions among ALF residents with minority status and older age may well indicate that their more complex health care needs are not being adequately addressed. The role of serious mental illness and dementia in risk for ACS hospitalization also deserves further attention.

Do Latino and non-Latino White Medicaid-enrolled adults differ in utilization of evidence-based treatment for major depressive disorder?

Although evidence-based practice guidelines have been developed to achieve greater consistency and quality in mental health care, insufficient research exists on implementing these guidelines among different racial/ethnic groups and the impact of guideline adherence on treatment outcomes. This study compared mental health care received by community dwelling Latino and non-Latino White Medicaid enrollees in Florida with a diagnosis of major depressive disorder (MDD) and examined predictors of adherence to American Psychiatric Association (APA) guidelines for the treatment of MDD. Latinos were more likely than Whites to receive guideline adherent treatment (OR = 1.21, P < .0001). Enrollees receiving combination drug therapy were most likely to receive treatment consistent with APA guidelines (OR = 4.25, P < .0001). Despite research demonstrating the efficacy of evidence-based practices, many study participants did not receive guideline adherent treatment. Policies and practices targeted at increasing adherence to approved guidelines and improving treatment outcomes are recommended.

Risk of arrest in persons with schizophrenia and bipolar disorder in a Florida Medicaid program: the role of atypical antipsychotics, conventional neuroleptics, and routine outpatient behavioral health services.

OBJECTIVE: To examine (1) arrest outcomes for adults with schizophrenia and bipolar disorder who were treated with first-generation antipsychotics (FGAs) or second-generation atypical antipsychotics (SGAs) and (2) the interaction between medication class and outpatient services in a Florida Medicaid program. METHOD: In a secondary data analysis, Florida Medicaid data covering the period from July 1, 2002, to March 31, 2008, were used to identify persons diagnosed with schizophrenia, schizoaffective disorder, and bipolar disorder and to examine antipsychotic medication episodes lasting at least 60 days. There were 93,999 medication episodes in the population examined (N = 36,519). Medication episodes were coded as (1) SGA-aripiprazole, clozapine, olanzapine, paliperidone, quetiapine, risperidone, risperidone long-acting therapy, or ziprasidone; or (2) FGA-any other antipsychotic medication. Outpatient services were defined as the proportion of 30-day periods of each medication episode with at least 1 behavioral health visit. Survival analyses were used to analyze the data, and they were adjusted for the baseline propensity for receiving an SGA. RESULTS: Second-generation antipsychotic episodes were not associated with reduced arrests compared to FGA episodes; however, the interaction between outpatient services and SGA episodes was significant (hazard ratio [HR] = 0.68; 95% CI, 0.50-0.93; P = .02) such that an SGA episode with an outpatient visit during at least 80% of every 30-day period of the episode was associated with reduced arrests compared to SGA episodes with fewer outpatient services. There was no significant effect for concurrent FGA episodes and outpatient treatment (HR = 0.81; 95% CI, 0.60-1.10; P = .18). Substance use, poor refill compliance, and prior arrest increased risk of subsequent arrest. CONCLUSIONS: The interaction between outpatient visits and treatment with SGAs was significantly associated with reduced arrests. These findings indicate the importance of concurrent antipsychotic medications and outpatient services to affect arrest outcomes for adults with schizophrenia and bipolar disorder.

Cloning of the repertoire of individual Plasmodium falciparum var genes using transformation associated recombination (TAR).

One of the major virulence factors of the malaria causing parasite is the Plasmodium falciparum encoded erythrocyte membrane protein 1 (PfEMP1). It is translocated to It the membrane of infected erythrocytes and expressed from approximately 60 var genes in a mutually exclusive manner. Switching of var genes allows the parasite to alter functional and antigenic properties of infected erythrocytes, to escape the immune defense and to establish chronic infections. We have developed an efficient method for isolating VAR genes from telomeric and other genome locations by adapting transformation-associated recombination (TAR) cloning, which can then be analyzed and sequenced. For this purpose, three plasmids each containing a homologous sequence representing the upstream regions of the group A, B, and C var genes and a sequence homologous to the conserved acidic terminal segment (ATS) of var genes were generated. Co-transfection with P. falciparum strain ITG2F6 genomic DNA in yeast cells yielded 200 TAR clones. The relative frequencies of clones from each group were not biased. Clones were screened by PCR, as well as Southern blotting, which revealed clones missed by PCR due to sequence mismatches with the primers. Selected clones were transformed into E. coli and further analyzed by RFLP and end sequencing. Physical analysis of 36 clones revealed 27 distinct types potentially representing 50% of the var gene repertoire. Three clones were selected for sequencing and assembled into single var gene containing contigs. This study demonstrates that it is possible to rapidly obtain the repertoire of var genes from P. falciparum within a single set of cloning experiments. This technique can be applied to individual isolates which will provide a detailed picture of the diversity of var genes in the field. This is a powerful tool to overcome the obstacles with cloning and assembly of multi-gene families by simultaneously cloning each member.

Gender differences and risk of arrest among offenders with serious mental illness.

Despite the increasing number of men and women with serious mental illness (SMI) incarcerated in America's jails, little research exists on the role gender may play in arrest among persons with SMI. This study examined correlates of arrests among offenders with SMI, specifically the role of gender. County criminal justice records, as well as county and statewide social service archival databases, were used to identify jail inmates with SMI in a large urban county in Florida. Of the 3,769 inmates identified, 41% were female. This study identified three distinct classes of male and female offenders within which persons had similar trajectories of arrests over the 4-year study period representing those with minimal, low, and high arrest rates. Findings suggest some important differences between women and men in risk factors for re-arrests. Attention to these factors may improve the ability to prevent future recidivism among men and women with SMI.

Risperidone long-acting therapy prescribing patterns and their impact on early discontinuation of treatment in a large Medicaid population.

OBJECTIVE: Medicaid claims were examined to determine whether utilization of risperidone long-acting therapy (LAT) was consistent with manufacturer's prescribing information recommendations and what factors were associated with early discontinuation. METHOD: Florida Medicaid claims between July 1, 2003, and June 30, 2007, were used. Recipient demographics and diagnoses, provision of oral antipsychotic supplementation during the first 21 days, number of injections received, medication possession ratio, and augmentation/polypharmacy after the first 21 days were assessed. Logistic regression was used to identify factors associated with early discontinuation of risperidone LAT. RESULTS: There were 3,364 individuals who received 4,546 episodes of risperidone LAT. Most recipients were between 18 and 64 years and had schizophrenia or schizoaffective disorder. Median episode length was 106 days. Median number of injections was 5. Supplementation with oral antipsychotic during the first 21 days was provided in 48% of episodes. Mean dosages were 25 mg or less for 28% of episodes and greater than 75 mg for 7% of episodes. Augmentation/polypharmacy after the first 21 days occurred in 43% of episodes. Early risperidone LAT discontinuation was associated with absence of oral supplementation during the first 21 days (P < .001), low (P = .045) or high (P < .001) initial doses of risperidone LAT, prior inpatient treatment (P < .001), having a substance use disorder (P = .001), and being male (P = .036). CONCLUSIONS: Prescribing practices for risperidone LAT were compared with the recommended protocol. Risperidone LAT was typically used with recommended age and diagnostic groups. However, important discrepancies were identified that could have reduced perceived effectiveness and tolerability of risperidone LAT. Early discontinuation was less likely when the recommendations in the manufacturer's prescribing information regarding dosage and supplementation with oral antipsychotics were followed.

Short-term impact of preferred drug list changes on health care use and Medicaid costs: injectable risperidone.

OBJECTIVE: This study assessed short-term effects of the removal of injectable risperidone long-acting therapy from the Florida Medicaid preferred drug list (PDL) in April 2006. METHODS: A difference-in-difference approach was used to contrast changes (60 days pre and post) in health care utilization and costs of Medicaid recipients who were receiving risperidone long-acting therapy when the policy was changed (N=247) and of a matched sample who received risperidone long-acting therapy in April 2005 (non-PDL, N=247). RESULTS: The policy change was associated with increased acute care events. Whereas acute care events declined for the non-PDL group, involuntary commitments and total acute care events increased for the PDL group, as did expenditures for crisis-related events. Medicaid pharmacy costs fell for both groups, but total expenditures did not decline significantly for the PDL group. CONCLUSIONS: The PDL restriction was associated with increased acute care events and did not reduce short-term Medicaid program expenditures.

Characteristics and experiences of adults with a serious mental illness who were involved in the criminal justice system.

OBJECTIVE: This study identified characteristics and experiences of arrestees and jail inmates with a serious mental illness that were associated with misdemeanor and felony arrests and additional days in jail. METHODS: County and statewide criminal justice records and health and social service archival data sets were used to identify inmates with serious mental illness who were in the Pinellas County, Florida, jail between July 1, 2003, and June 30, 2004, and their health and social service contacts from July 1, 2002, to June 10, 2006. Criminal justice and mental health services were recorded longitudinally across 16 quarters, or 90-day periods. Generalized estimating equations for count data were used to describe the associations between individual characteristics and experiences and the risks of misdemeanor and felony arrests and additional days in jail. RESULTS: A total of 3,769 jail inmates (10.1% of all jail inmates) were diagnosed as having a serious mental illness. Participants experienced a mean+/-SD of .90+/-.60 arrest for every three quarters and 10.9+/-23.6 days in jail per quarter that they resided in the county. Being male, being homeless, not having outpatient mental health treatment, and having an involuntary psychiatric evaluation in the previous quarter were independently associated with significantly increased odds of misdemeanor arrests and additional days in jail. On the other hand, being black, being younger than 21 years, having a nonpsychotic diagnosis, and a co-occurring substance use disorder diagnosis were all independently associated with significantly increased odds of felony arrests, and with the exception of having a nonpsychotic diagnosis, they were also significantly associated with additional days in jail. CONCLUSIONS: Findings suggest that there are subgroups of individuals with a serious mental illness in the criminal justice system that may require different policy and programmatic responses.

Predictors of preventable nursing home hospitalizations: the role of mental disorders and dementia.

OBJECTIVES: Nursing home (NH) hospitalizations place an enormous economic burden on an already overtaxed American healthcare system. Hospitalizations for "ambulatory care-sensitive" (ACS) conditions are considered preventable, as these are physical health conditions that can potentially be treated safely in a NH. The authors examined risk factors, including mental disorders and dementia, for hospitalization of Medicaid-enrolled NH residents with ACS conditions during fiscal year 2003-2006. METHODS: The authors merged Medicaid claims and enrollment data and Online Survey Certification and Reporting information for 72,251 Medicaid-enrolled NH residents in 647 NHs in Florida. The authors identified at least one ACS hospitalization in 8,382 residents for a total of 10,091 hospital admissions (18.5% of all hospitalizations). The authors used Cox proportional hazard regression to assess time to the first ACS hospitalization. RESULTS: In a fully adjusted model, younger age, non-white race, dementia, and serious mental disorder were associated with greater risk of ACS hospitalization. In addition, residents with a diagnosed mental disorder and no dementia incurred relatively high expenditures for ACS hospitalizations. Among facility characteristics, participants from for-profit facilities, facilities that were not a member of a chain, had more Medicaid recipients, and fewer than 120 beds had greater risk of ACS hospitalizations. CONCLUSIONS: Attention to the identified predictors of hospitalization for ACS conditions, which are potentially preventable, could reduce the risk and cost of these hospitalizations among Medicaid-enrolled NH residents. The need to reduce unnecessary hospitalization will become only more urgent as the population ages and healthcare expenses continue to escalate.

The association of yKu with subtelomeric core X sequences prevents recombination involving telomeric sequences.

The yKu protein of Saccharomyces cerevisiae is important for genome stability by repressing recombination involving telomeric sequences. The mechanism of this repression is not known, but silent heterochromatin such as HML, HMR, and telomeres are compartmentalized at the nuclear periphery and yKu is proposed to interact with these regions and to play a role in telomeric silencing and tethering. We have utilized ChIP on chip, quantitative PCR, and quantitative recombination assays to analyze yKu binding and its effect on genome stability in wild-type and mutant backgrounds. Our data suggest that, although yKu binds to the TG1-3 repeats and other parts of the genome when needed, such as during nonhomologous end-joining, it specifically binds to core X sequences in addition to the mating-type loci, HML and HMR. Association with core X occurred in the absence of Sir proteins, and enhanced binding was observed at silenced ends compared to nonsilenced ends. In contrast, binding to HML and HMR was totally dependent on Sir2-4p and partially dependent on Sir1p with a stronger association at HML in both MATa and MATalpha strains. Using yku80 separation-of-function mutants, we show a direct correlation between core X binding and recombination rate. We believe our findings support our hypothesis that yKu and core X play a pivotal role in maintaining genome stability through nuclear architecture by mediating a defensive fold-back structure at yeast chromosome ends.

Risk for suicide among medicaid beneficiaries.

Demographic, diagnostic, and service expenditure characteristics of Florida Medicaid enrollees who died by suicide were investigated. Among persons receiving Medicaid and Supplemental Security Income (SSI), findings indicate the most powerful predictors of suicide were involuntary psychiatric examination, mental health hospitalization, and high mental health service use. Among Medicaid enrollees not receiving SSI, strongest suicide predictors were mental health hospitalization, high expenditures for physical health medications, and involuntary psychiatric examination. Findings suggest reducing involuntary psychiatric examinations and mental health hospitalizations while improving physical health may reduce suicide in the Medicaid population. Comprehensive hospital discharge planning, adherence monitoring with follow-up care, training mental health providers in assessing suicide lethality, and providing adequate assessment time are all crucial to achieve these objectives.

Invivo folding efficiencies for mutants of the P22 tailspike beta-helix protein correlate with predicted stability changes.

Parallel beta-helices are among the simplest repetitive structural elements in proteins. The folding behavior of beta-helix proteins has been studied intensively, also to gain insight on the formation of amyloid fibrils, which share the parallel beta-helix as a central structural motif. An important system for investigating beta-helix folding is the tailspike protein from the Salmonella bacteriophage P22. The central domain of this protein is a right-handed parallel beta-helix with 13 windings. Extensive mutational analyses of the P22 tailspike protein have revealed two main phenotypes: temperature-sensitive-folding (tsf) mutations that reduce the folding efficiency at elevated temperatures, and global suppressor (su) mutations that increase the tailspike folding efficiency. A central question is whether these phenotypes can be understood from changes in the protein stability induced by the mutations. Experimental determination of the protein stability is complicated by the nearly irreversible trimerization of the folded tailspike protein. Here, we present calculations of stability changes with the program FoldX, focusing on a recently published extensive data set of 145 singe-residue alanine mutants. We find that the calculated stability changes are correlated with the experimentally measured invivo folding efficiencies. In addition, we determine the free-energy landscape of the P22 tailspike protein in a nucleation-propagation model to explore the folding mechanism of this protein, and obtain a processive folding route on which the protein nucleates in the N-terminal region of the helix.