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New York State was the epicenter for COVID-19 in Spring 2020 when little was known about the pandemic. Dire circumstances necessitated New York State’s (NYS) public mental health system to rapidly pivot, adapt, and innovate its policies and procedures to ensure continuous high-level care to individuals with serious mental illness (SMI), a population especially vulnerable to both the physical and psychosocial sequelae of COVID-19. NYS rapidly adopted emergency measures to support community providers, expanded the capacity of its State-Operated facilities, created policies to promote improved infection control access, collaborated to enhance the public–private continuum of service to support people with SMI, and broadened the use of new technologies to ensure continued engagement of care.

Photochemical reactions that produce a detectable change in the spectroscopic properties of organic chromophores can be exploited to harness the principles of Boolean algebra and design molecule-based logic circuits. Moreover, the logic processing capabilities of these photoactive molecules can be directed to protect, encode, and conceal information at the molecular level. We have designed a photochemical strategy to read, write and encrypt data in the form of optical signals. We have synthesized a supramolecular system based on the known dye resazurin, and investigated a series of photochemical transformations that can be used to regulate its absorption and emission properties upon illumination with ultraviolet or visible light. We have then examined the logic behaviour of the photochemistry involved, and illustrated its potential application in data encryption.

The novel coronavirus pandemic and the resulting expanded use of telemedicine have temporarily transformed community-based care for individuals with serious mental illness (SMI), challenging traditional treatment paradigms. We review the rapid regulatory and practice shifts that facilitated broad use of telemedicine, the literature on the use of telehealth and telemedicine for individuals with SMI supporting the feasibility/acceptability of mobile interventions, and the more limited evidence-based telemedicine practices for this population. We provide anecdotal reflections on the opportunities and challenges for telemedicine drawn from our daily experiences providing services and overseeing systems for this population during the pandemic. We conclude by proposing that a continued, more prominent role for telemedicine in the care of individuals with SMI be sustained in the post-coronavirus landscape, offering future directions for policy, technical assistance, training, and research to bring about this change.

Aim.To identify specific risk factors and features of the course of myocardial infarction (MI) in young patients.Material and methods.The study design is based on a comparison of observation data for patients of different ages from the Russian RECORD-3 registry (n=2359) and the registry of acute coronary syndrome of the Kemerovo city in 2015 (n=1343). The clinical and anamnestic portrait was determined, the frequency of hospital complications and the “hard” endpoints were evaluated.Results.Young patients with myocardial infarction (MI) according to RECORD-3 are more often male smokers (p=0.001) with a heredity in cardiovascular pathology (p=0.034), who have an uncomplicated STEMI upon admission to the hospital, and are sent for coronary angiography with stenting (p=0.001), without prescribing statins in the primary and secondary prevention (p=0.050 and p=0.016, respectively). There were no differences with other age groups by endpoints a year later; during the current hospitalization, young patients less often died (p=0.001) or had a relapse of MI (p=0.011). Young patients with MI from Kemerovo were also mostly male smokers (p=0.001), who more often had a history of chronic kidney disease, chronic heart failure, and lipid metabolism disorders (p=0.001), who admitted to the hospital with uncomplicated STEMI, actively undergoing thrombolytic therapy and endovascular diagnosis and treatment (p=0.001). However, it should be noted that these patients were less likely to receive aspirin (p=0.015), dual antiplatelet therapy (p=0.003), angiotensin converting enzyme (ACE) inhibitors (p=0.040) and statins (p=0.001). Moreover, in young patients with MI, deficiency of high density lipoproteins (p=0.005) was more often found in the absence of very high values of low density lipoproteins (p=0.001). Among the complications of inpatient treatment, it should be noted a tendency to bleeding (p=0.001). One year after referent MI a high proportion of repeated non-fatal MI (p=0.005) and deaths (p=0.001) were observed. A comparison of the registries showed that young patients from Kemerovo were more likely to have STEMI (p=0.032), they were more likely to have stenting (p=0.004), they were more often diagnosed with chronic renal and heart failure (p=0.001), and more often ACE inhibitors was prescribed (p=0.017), and MI during hospitalization was more often complicated by bleeding (p=0.003).Conclusion.From 1.7 to 2.4% of all MI occurs in young patients. The most frequent version of the debut is STEMI. The leading factors of cardiovascular risk in such patients are the male gender, active smoking, a hereditary history of cardiovascular diseases, low cholesterol of high density lipoproteins with insufficient statins prevention. In young patients of the Kemerovo registry, chronic heart failure and chronic kidney disease were more often observed, and ACE inhibitors were prescribed, hospitalization was often accompanied by bleeding. In a young age differences in the frequency and structure of outcomes in one year after referent MI were not found when comparing registries.

Structural racism has received renewed focus over the past year, fueled by the convergence of major political and social events. Psychiatry as a field has been forced to confront a legacy of systemic inequities. Here, we use examples from our clinical and supervisory work to highlight the urgent need to integrate techniques addressing racial identity and racism into psychiatric practice and teaching. This urgency is underlined by extensive evidence of psychiatry's long-standing systemic inequities. We argue that our field suffers not from a lack of available techniques, but rather a lack of sustained commitment to understand and integrate those techniques into our work; indeed, there are multiple published examples of strategies to address racism and racial identity in psychiatric clinical practice. We conclude with recommendations geared toward more firmly institutionalizing a focus on racism and racial identity in psychiatry, and suggest applications of existing techniques to our initial clinical examples.

Synopsis Numerous reports describe how individual hospitals responded to the COVID-19 pandemic, but few describe how these changes occurred across a large public health system of care. As the early epicenter of the pandemic, New York State’s response, particularly the New York City metropolitan area, included a range of coordinated planning and regulatory efforts to preserve and create medical and intensive care unit capacity where needed; maintain access to acute psychiatric services; and redefine inpatient psychiatric care through strict infection control, easing of regulatory requirements, and use of telehealth. These strategies reflected similar efforts across the United States. Integration of public and not-for-profit hospital systems with each other and the residential and outpatient community remain key challenges.

The novel coronavirus pandemic and the resulting expanded use of telemedicine have temporarily transformed community-based care for individuals with serious mental illness (SMI), challenging traditional treatment paradigms. We review the rapid regulatory and practice shifts that facilitated broad use of telemedicine, the literature on the use of telehealth and telemedicine for individuals with SMI supporting the feasibility/acceptability of mobile interventions, and the more limited evidence-based telemedicine practices for this population. We provide anecdotal reflections on the opportunities and challenges for telemedicine drawn from our daily experiences providing services and overseeing systems for this population during the pandemic. We conclude by proposing that a continued, more prominent role for telemedicine in the care of individuals with SMI be sustained in the post-coronavirus landscape, offering future directions for policy, technical assistance, training, and research to bring about this change.

The Internet has fundamentally altered mental health clinicians' "public selves," challenging previous models of self-disclosure and maintenance of boundaries within treatment. The conception of a public self altered by the digital age presents both opportunities and pitfalls in clinical practice. Information about clinicians available online may be professional or personal; accurate or inaccurate; and publicly accessible, purchased, or hacked. Clinicians must consider how to manage their public selves in work with patients and the community. This Open Forum outlines a set of recommendations for managing the public self in the digital age as a routine part of therapeutic work.

Suicide prevention efforts are increasing to enhance capabilities and better understand risk factors and etiologies. Postvention, or how clinicians manage the postsuicide aftermath, strengthens suicide prevention, destigmatizes the tragedy, operationalizes the confusing aftermath, and promotes caregiver recovery. However, studies regarding its efficacy are minimal. The Psychopathology Committee of the Group for the Advancement for Psychiatry surveyed a convenience sample of psychiatrists to better understand postvention activities. Ninety psychiatrists completed the survey; they were predominantly men (72%) with an average of 24.6 years of experience (SD, 16.7 years). Most had contact with the patient’s family within 6 months of the suicide, and most psychiatrists sought some form of support. Few psychiatrists used a suicide postvention procedure or toolkit (9%). No psychiatrists stopped clinical practice after a patient suicide, although 10% stopped accepting patients they deemed at risk of suicide. Postvention efforts, therefore, should be improved to better address survivor care.

The number of people with opioid use disorder and the number of overdose deaths in the United States have increased dramatically over the past 20 years. U.S. Congress passed the SUPPORT for Patients and Communities Act, which was signed into law in 2018, authorizing almost $8 billion to address the crisis. As experts in the treatment of central nervous systems disorders, psychiatrists can play a leading role in expanding treatment for people with opioid use disorder and in advocating for policy changes to support community treatment for this group.

Despite widespread use, how clinicians use the DSM in psychiatric practice is not well understood. Recognizing public and professional attitudes toward the DSM are integral to future DSM development, to assess a commonly held assumption such as that the DSM is used primarily for coding, and to assess its clinical utility. A convenience sample of Psychiatric Times readers was surveyed to assess the DSM's use in clinical practice. A total of 394 behavioral health care practitioners fully completed the online survey. Results suggest that the DSM, beyond administrative and billing use, is used for communication with health care providers, for teaching diagnoses to trainees, and, importantly, as an educational tool to inform patients and caregivers alike.

Cognitive remediation (CR) research typically addresses internal validity, and few studies consider CR in a real-world context. This study evaluated the fit between the program conditions and treatment model in research and clinical settings, with the goal of informing future research on the contextual challenges associated with the implementation of CR. Data was drawn from an initiative by New York State's Office of Mental Health (OMH), to implement CR programs for adults with Serious Mental Illness (SMI) in 16 state operated outpatient clinics. One of these clinics first became a research site for a CR randomized clinical trial, which allowed for a comparison of the feasibility and acceptability of CR in a research as compared to a clinical setting. RESULTS: The research site averaged almost triple the number of referrals as the clinical sites. Over nine months 46.51% of clinic referrals were enrolled in the CR program whereas 64.29% of research referrals were enrolled. Clinical site utilization averaged 70.53% while research site utilization averaged 90.47%. At the clinical sites, 97% of respondents reported CR was an excellent or good experience. There was high treatment fidelity for program structure and content across sites. CONCLUSIONS: This comparison of CR in clinical and research sites highlights the decrease in referrals, enrollment and utilization that occurs when a program moves from a highly controlled setting to the real world. Still, the acceptability, fill rates and utilization indicated that CR can be successfully implemented in large scale, geographically diverse, publically funded clinic settings.

At the start, there was Marshall Tymn founding his series with Greenwood Press, Contributions to the Study of Science Fiction and Fantasy, in which the first volume was The Mechanical God: Machines in Science Fiction (1982). This volume was edited by Thomas P. Dunn and Richard D. Erlich, with an Introduction by Brian W. Aldiss and collected eighteen essays by eighteen scholars on the subtitle's topic. Mechanical God was followed in 1983 by Number 7 in the Contributions series, Erlich and Dunn's Clockwork Worlds: Mechanized Environments in SF.Mechanical God and Clockwork Worlds got decent reviews and a somewhat surprising number of positive informal comments on the Dunn/ Erlich contribution of a "List of Works Useful for the Study of Machines in Science Fiction" and a "List of Works Useful for the Study of Mechanized Environments in SF": a biblio-, filmo-, video-, discographical effort to provide a briefly annotated list of basic works for the study of each theme. So Dunn and I decided that our most immediately useful project for the academic study of sf might be to join the scholars putting together the basic tools for research. We "got professional help" in areas outside our expertise, and produced a combined and expanded volume with the ungainly title Clockworks: A Multimedia Bibliography of Works Useful for the Study of the Human/ Machine Interface in SF. The formal credits list Erlich and Dunn as compilers, "Assisted by Edward K. Montgomery, Catherine Mills Royer, and D. Scott DeLoach," though others helped with the project, including Chad Dresbach (who supplemented Dunn's extensive knowledge of pinball machines with his own expertise in that area and in the developing medium of video games and their early successors), and Jeffrey R. Wilson and Vincent Moore, who compiled the core of the section on music."Multimedia Bibliography" was a necessary phrase for us to use because Clockworks appeared in the Greenwood series "Bibliographies and Indexes in World Literature" (Number 37), and the word "Bibliography" had to appear in the title. The multimedia part, though, was crucial, or at least our most original contribution.In our Introduction, Dunn and I-I've moved the "voice" here to just Rich Erlich-described Clockworks as "an analytical, selected list, with comments, of works useful for the study of the human/machine interface in SF, stressing English-language works produced 1895-1990," and expanded upon "analytical" by noting the sections into which the List had been divided, "with works arranged alphabetically within each section":(1) Reference Works(2) Anthologies and Collections(3) Fiction(4) Literary Criticism(5) Stage, Screen, and Television Drama(6) Stage, Screen, and Television Drama Criticism(7) Graphic and Plastic Arts(8) Music(9) Background ReadingClockworks was published in 1993, and Dunn and I mostly moved on to other things, including, in my case, film studies and occasional consulting on movie scripts. Now and then, though, friends would recommend books relevant to "the human/machine interface," and I saw on my own a number of relevant movies. As cyberpunk and its successors rolled on, human relationships with our machines-in a widening sense of "machine"-became still more pronounced, intimate, and unavoidable. And, significantly for the usefulness of the Clockworks project, those relationships continued to be expressed in a number of different artistic media, which reflected ways of life that, for good and for ill, were becoming increasingly science fictional. Somewhat to my snobbish and/or philistine expectations, even graphic novels and video games evolved into sophisticated art forms that often addressed the human/machine interface.So I found myself fitfully preparing a Supplement to the List, a "Clockworks 2," and eventually had a significant number of entries. For my convenience, and that of my students, I put the supplement online. …

Clinical practice is assumed to be informed and supported by evidence-based clinical research. Nonetheless, clinical practice often deviates from the research evidence base, sometimes leading and sometimes lagging. Two examples from integrated care in mental health care (care for serious mental illness and collaborative mental health care in primary care settings) illustrate the natural space and therefore tension between evidence and implementation that needs to be better understood. Using the tools and perspectives of both examples, the authors present a framework for the connected relationship between practice and research that is founded on measurement and uses iterative adaptation guided by oversight of and feedback from the stakeholders in this process.

IntroductionWith the increasing enthusiasm to provide cognitive remediation (CR) as an evidence-based practice, questions arise as to what is involved in implementing CR in a large system of care. This article describes the first statewide implementation of CR in the USA, with the goal of documenting the implementation issues that care providers are likely to face when bringing CR services to their patients.MethodsIn 2014, the New York State Office of Mental Health set up a Cognitive Health Service that could be implemented throughout the state-operated system of care. This service was intended to broadly address cognitive health, to assure that the cognitive deficits commonly associated with psychiatric illnesses are recognized and addressed, and that cognitive health is embedded in the vocabulary of wellness. It involved creating a mechanism to train staff to recognize how cognitive health could be prioritized in treatment planning as well as implementing CR in state-operated adult outpatient psychiatry clinics.ResultsBy 2017, CR was available at clinics serving people with serious mental illness in 13 of 16 adult Psychiatric Centers, located in rural and urban settings throughout New York state. The embedded quality assurance program evaluation tools indicated that CR was acceptable, sustainable, and effective.ConclusionsCognitive remediation can be feasibly implemented in large systems of care that provide a multilevel system of supports, a training program that educates broadly about cognitive health and specifically about the delivery of CR, and embedded, ongoing program evaluation that is linked to staff supervision.

International audience

The authors discusses the reasons why they believe that cognitive health is necessary to ensure quality of life and independence across an individual's life span, and it mentions the U.S. Centers for Disease Control and Prevention's views about intuition, judgment, and brain health. America's National Institute on Aging is addressed, along with cognition in children and young adults. Cognitive deficits and U.S. public health are assessed, along with mentally ill individuals in the country.

The incidence of suicide is rising, with devastating consequences. Suicide prevention is one of the greatest challenges facing our health care systemand society.Many efforts around the world—randomized controlled trials (RCTs), public information campaigns, primary care initiatives, and restriction of access to lethal means—aim to reduce suicide rates. A 2005 comprehensive analysis of 93 suicide prevention studies concluded that improving education and restricting access to lethal means were the most efficacious preventive efforts. Subsequent studies have had similar findings. For example, a 2008 five-country RCT of brief intervention and contact— assessing low-cost suicide screening and prevention efforts in acute care settings—found that professional encounters for at-risk clients enhanced protective factors and reduced suicide risk. Governmental programs have also had success. For example, Denmark’s 1989 program for adolescents curbed access to over-the-counter drugs commonly used in suicide attempts, and Danish rates of suicide, which were once equivalent toU.S. rates in the early 1990s,were halvedby 2012. In the United States, several large-scale and important prevention programs have been initiated, with titles such as Zero Suicide or Vision Zero. The Vision Zero program ofMichigan’s Henry Ford Health System has succeeded in holding the mean annual suicide rate for its members to 5.77 per 100,000, whereas rates of suicide in the state of Michigan, which follows the current suicide prevention standard of care, have increased significantly to 10.82 per 100,000. “Zero Suicide” has been the call to action for programs from the Suicide Prevention Resource Center and the National Action Alliance for Suicide Prevention (the Action Alliance). The National Institute of Mental Health and the Action Alliance are now rigorously studying Vision Zero and other suicide prevention efforts. These efforts are the vanguard of innovation desperately needed to prevent suicide. But more remains to be understood to develop successful approaches. Current best practices involve minimizing nonstatic risk factors, improving structured followup services, and maintaining contact with the at-risk individual. Programs such as Vision Zero enhance current prevention resources. However, we strongly recommend that Vision Zero and Zero Suicide be expanded to themore aspirational “Envision Zero.”Wehave concerns about the unintended consequences of rallying around absolute zero. Given the present state of our science and community practice, most would agree that zero is not yet obtainable. So why worry about the word “zero”? Our fear is that given the devastation of suicide to caregivers, families, friends, and health care practitioners, the promise of zero may enhance the already problematic guilt and sense of failure among survivors, caregivers, and clinicians alike. Feelings of shame, accordingly, may erode the focus on “postvention” efforts, which are critical for survivors. Therefore, a balanced approach must also bolster resources for managing survivor guilt and providing postvention resources, which should also become a standard of care. With envisioning zero, we acknowledge that prevention efforts must continue as the primary goal of reducing suicide while we also recognize that prevention needs to be balanced with postvention efforts. Suicide postvention, a crisis intervention strategy, aims to provide support to survivors attempting to cope with a suicide death, reduce the possibility of suicide contagion, and tackle the social stigma associated with suicide. Postvention is a critical proactive prevention effort when suicide occurs. Postvention efforts help diminish shame surrounding a suicide event and promote recovery for survivors (physicians, clinicians, peers, family members, and friends). Postvention is most effective when providers or peers reach out to bereaved survivors. For example, the peer-led Local Outreach to Suicide Survivors offers immediate support to a loved one, from counseling to helping clean up a victim’s home, with a team that includes a caregiver-survivor. Postvention efforts are heterogeneous and imperfect; moreover, there are considerably fewer postvention best practices to guide survivors. Trauma-informed therapies, psychological first aid, and bereavement counseling are effective, but they lack an operationalized approach. Most postvention resources exist to manage school-age and adolescent suicide in order to facilitate appropriate mourning and grief, teach individuals potential warning signs of their own distress, and assist with reestablishing successful coping strategies. Evidence for the success of these efforts for adolescents and their caregivers varies. Two aspects are clear: postvention efforts need to be enhanced for all age groups, andmore resources need to be invested in postvention. Suicide prevention is a primary public health goal, andwe seek the day when postvention efforts are unnecessary. Until then, postvention efforts and best practices need to be strengthened. Our language is important. “Envisioning zero” acknowledges the need to vigorously intervene after a suicide until postvention is no longer relevant.

Objective:Using data from a multi-site study of parent–child symptom reporting concordance, this secondary analysis explored the role of parent self-efficacy related to pain management for seriously ill school-age children and adolescents.Method:In the initial study, 50 children and adolescents who were expected to survive 3 years or less were recruited along with their parent/primary caregiver. Parent self-report data were used in this secondary analysis to describe parent self-efficacy for managing their child's pain, caregiver strain, mood states, and perception of the child's pain; to explore relationships among these variables; and to determine predictors of greater self-efficacy.Results:Parents expressed a wide range of self-efficacy levels (Chronic Pain Self-Efficacy Scale; possible range 10–100, mean 76.2, SD 14.7) and higher levels on average than reported previously by family caregivers of adult patients. Caregiver Strain Index scores were markedly high (possible range 0–13, mean 8.1, SD 3.8) and inversely correlated with self-efficacy (r = −0.44, p = 0.001). On the Profile of Mood States parents reported more negative moods (t = 4.0, p t = −5.0, p R2 = 0.51).Significance of results:Findings advance knowledge of parent self-efficacy in managing the pain of a child with life-threatening illness. Results can be used to design supportive interventions enhancing parents’ caregiving roles during their child's last stages of life.

Autosomal dominant hypercholesterolemia (ADH) is characterized by isolated increase in plasmatic low-density lipoprotein (LDL) cholesterol levels associated with high risk of premature cardiovascular disease. Mutations in LDLR, APOB, and PCSK9 genes have been shown to cause ADH. We now report further genetic heterogeneity of ADH through the study of a large French family in which the involvement of these three genes was excluded. A genome-wide scan mapped the disease-causing gene, named HCHOLA4, at 16q22.1 in a 7.89-Mb interval containing 154 genes with a maximum LOD score of 3.9. To reduce the linked region, we genotyped 18 smaller non-LDLR/non-APOB/non-PCSK9-ADH families at the HCHOLA4 locus. Six families did not exclude linkage to the locus, but none allowed reduction of the disease interval. The 154 regional genes were sorted according to the function of the encoded protein and tissue expression profiles, and 57 genes were analyzed through sequencing of their coding region and close flanking intronic parts. No disease-causing mutation was identified in these families, particularly in the LCAT gene. Finally, our results also show the existence of other ADH genes as nine families were neither linked to LDLR, APOB, and PCSK9 genes nor to the new HCHOLA4 locus.

Plasma lipid parameters (triglycerides, total cholesterol and high density lipoprotein cholesterol) were measured in 7 children with juvenile chronic granulocytic leukaemia, of whom 3 were with and 4 without xanthomas. In all cases, whatever the stage of the disease, these parameters were extremely altered. Plasma triglycerides were generally increased, total and HDL cholesterols were very low. No relationship seems to exist between these values and the occurrence of xanthomas.

Aunque el enfoque pragmadialéctico al estudio de la argumentación permite conocer la dinámica de un debate, puede complementarse con otros aportes teóricos que enriquecen en análisis. En este artículo se describe desde varias perspectivas el papel que desempeña el moderador con el fin de explorar aspectos de su comportamiento discursivo en el desarrollo y resolución de la discusión. Se aplican criterios relativos a la pragmadialéctica, la articulación del debate, la interlocución y la progresión temática. Paralelamente, se observa en el plano interpersonal de la comunicación, con apoyo en criterios propios de la teoría de la cortesía verbal, de qué manera el moderador favorece o se opone a las posturas sostenidas por los participantes en el debate. Los resultados del análisis arrojan luces acerca de la producción discursiva del moderador en el contexto particular de un debate producido en la televisión venezolana

Patients with schizophrenia experience three categories of symptoms: positive (delusions and hallucinations); negative (blunting of affective expression, loss of volition, and apathy); and disorganized (as reflected by a formal thought disorder). A diagnosis of schizophrenia requires that continuous signs of illness, which may include prodromal and residual symptoms, be present for at least 6 months. Research indicates that schizophrenia is likely a neurodevelopmental illness with clear heritable risk factors. Patients with schizophrenia tend to have an illness onset by young adulthood and a generally debilitating and long-term course, but the degree of disability and functional impairment is widely variable. Other illnesses characterized by prominent psychotic symptoms include schizoaffective disorder and delusional disorder. Treatment for psychotic illnesses includes antipsychotic medication and recovery-oriented psychosocial interventions aimed at “psychiatric rehabilitation” wherein patients can learn or relearn skills necessary to live independently and work competitively.

R'esume En 1999, le suivi biologique de la fonction renale est effectue par la creatinine plasmatique. Si les avantages du dosage de la creatinine sont indeniables (faible cout, automatisation aisee), ses concentrations plasmatiques ne sont qu'un reflet imprecis du debit de filtration glomerulaire (production non constante, metabolisme tubulaire imprevisible, nombreuses interferences analytiques). Des les annees 1985, la cystatine C a ete proposee comme etant un meilleur marqueur du debit de filtration glomerulaire que la creatinine. Son dosage par immunonephelemetrie ou immunoturbidimetrie est aujourd'hui disponible sur le marche. La plupart des etudes suggerent que la cystatine C est un marqueur plus precis du debit de filtration glomerulaire que la creatinine, en particulier chez l'insuffisant renal et chez l'enfant. Chez le transplante renal, la cystatine C permettrait plus facilement de diagnostiquer la defaillance du greffon, le rejet aigu et la nephrotoxicite des traitements medicamenteux. Son comportement biologique sous hemodialyse semble tres different de celui de la creatinine et etroitement dependant du type de membrane utilise.

We evaluated a new sodium dodecyl sulfate-agarose gel electrophoresis (SDS-AGE) for urinary protein analysis in patients with multiple myeloma (MM; n = 47; ages, 62 ± 2 years, mean ± SE). Abnormal proteinuria (mean = 1872 ± 360 mg/24 h) was present in 95% of the samples; 75% of the patients had some sign of renal dysfunction (glomerular and/or tubular) according to their SDS-AGE pattern. A band suggesting Bence Jones proteinuria (BJP) was detected in 40 vs 33 specimens by routine AGE. Immunofixation identified BJP in 38 patients; the calculated sensitivity of SDS-AGE for BJP was 97%. Excellent correlation (P

Familial ligand-defective apolipoprotein B-100 (FDB) is an autosomal dominant disorder leading to plasma LDL cholesterol elevation and coronary artery disease (CAD). Two specific mutations in the APOB gene—R3500Q and R3531C—induce FDB. We report an original method to detect both mutations simultaneously, based upon PCR-mediated, site-directed mutagenesis and double restriction of a unique PCR product. With this method we have investigated the prevalence of these mutations in 1,040 French patients. The R3500Q mutation was found in five probands. Genotypes were determined for 10 APOB polymorphic markers and were consistent with the common European ancestral haplotype previously reported. The only exception was one FDB proband who did not harbor the 48 repeat allele of the 3′HVR. Additionally, the first two R3531C mutations were identified in French probands. Genotypes were consistent with a previously reported haplotype, suggesting that this is another mutation of European ancestry. Hum Mutat 10:160–163, 1997. © 1997 Wiley-Liss, Inc.

This column describes recent policy and program initiatives implemented by the New York State Office of Mental Health to enhance integration of general medical and behavioral health services throughout the state public mental health system. Recent initiatives were implemented to improve access to health and wellness-oriented services, redesign managed care programs to improve engagement and retention of high-need individuals, and raise the bar on quality while lowering costs. Taken as a whole, these initiatives represent a 21st-century transformation of a state mental health authority into an accountable and more fully integrated public health delivery system.

Autosomal dominant hypercholesterolemia (ADH; OMIM144400), a risk factor for coronary heart disease, is characterized by an increase in low-density lipoprotein cholesterol levels that is associated with mutations in the genes LDLR (encoding low-density lipoprotein receptor) or APOB (encoding apolipoprotein B). We mapped a third locus associated with ADH, HCHOLA3 at 1p32, and now report two mutations in the gene PCSK9 (encoding proprotein convertase subtilisin/kexin type 9) that cause ADH. PCSK9 encodes NARC-1 (neural apoptosis regulated convertase), a newly identified human subtilase that is highly expressed in the liver and contributes to cholesterol homeostasis.

Apolipoprotein (apo) E mutants are associated with type III hyperlipoproteinemia characterized by high cholesterol and triglycerides levels. Autosomal dominant hypercholesterolemia (ADH), due to the mutations in the LDLR, APOB, or PCSK9 genes, is characterized by an isolated elevation of cholesterol due to the high levels of low-density lipoproteins (LDLs). We now report an exceptionally large family including 14 members with ADH. Through genome-wide mapping, analysis of regional/functional candidate genes, and whole exome sequencing, we identified a mutation in the APOE gene, c.500_502delTCC/p.Leu167del, previously reported associated with sea-blue histiocytosis and familial combined hyperlipidemia. We confirmed the involvement of the APOE p.Leu167del in ADH, with (1) a predicted destabilization of an alpha-helix in the binding domain, (2) a decreased apo E level in LDLs, and (3) a decreased catabolism of LDLs. Our results show that mutations in the APOE gene can be associated with bona fide ADH.

Evaluate the Freelite free light chain immunoassay for urine analysis in myeloma. Urine specimens from 20 patients were analyzed by Freelite (The Binding Site) and SDS-agarose gel electrophoresis (Hydragel protéinurie, Sebia). Using the kappa/lambda ratio, Freelite was more sensitive than electrophoresis to detect free light chains, but concentration was overestimated in 75% of cases. Despite high sensitivity and full automation, Freelite inaccurately measures monoclonal free light chains in urine.

Autosomal Dominant Hypercholesterolemia (ADH), characterized by isolated elevation of plasmatic LDL cholesterol and premature cardiovascular complications, is associated with mutations in 3 major genes: LDLR (LDL receptor), APOB (apolipoprotein B) and PCSK9 (proprotein convertase subtilisin-kexin type 9). Through the French ADH Research Network, we collected molecular data from 1358 French probands from eleven different regions in France. Mutations in the LDLR gene were identified in 1003 subjects representing 391 unique events with 46.0% missense, 14.6% frameshift, 13.6% splice, and 11.3% nonsense mutations, 9.7% major rearrangements, 3.8% small in frame deletions/insertions, and 1.0% UTR mutations. Interestingly, 175 are novel mutational events and represent 45% of the unique events we identified, highlighting a specificity of the LDLR mutation spectrum in France. Furthermore, mutations in the APOB gene were identified in 89 probands and in the PCSK9 gene in 10 probands. Comparison of available clinical and biochemical data showed a gradient of severity for ADH-causing mutations: FH=PCSK9>FDB>‘Others’ genes. The respective contribution of each known gene to ADH in this French cohort is: LDLR 73.9%, APOB 6.6%, PCSK9 0.7%. Finally, in 19.0% of the probands, no mutation was found, thus underscoring the existence of ADH mutations located in still unknown genes. © 2010 Wiley-Liss, Inc.