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To date, little research has systematically investigated perceptions of mental health professionals regarding motivations for self-injury among prison inmates. To help fill this gap, the authors used descriptive techniques to examine self-injurious behavior among inmates from the perspective of correctional mental health professionals. A quantitative survey assessed perceptions of mental health staff regarding etiology, motivations, and manifestations of self-injury. A qualitative interview component was used to explicate responses from the survey. Inmate cutting, scratching, opening old wounds, and inserting objects were the most commonly witnessed behaviors. Findings suggest that self-injury occurred regularly and that a subset of inmates are responsible for recurrent events. Mental health professionals perceived the motivation for inmate self-injury to be both manipulative and a coping mechanism. They described current management strategies and corresponding needs for training and resources. [ABSTRACT FROM AUTHOR]

The pathways framework represents an emerging body of work that emphasizes gendered-based influences on crime and incarceration. To date, studies on female pathways often minimize or exclude the role of mental illness. The current study employs Life Course Theory and the use of Life History Calendar to examine the pathways of a sample of 15 female prison inmates diagnosed with serious and persistent mental health conditions. Findings indicate that mental illness carried criminogenic risk throughout the life course, with crucial transitions of risk leading these women toward long term incarceration. Self-reported pathways included repeated victimization, substance use, psychological trauma, delinquency, and/or crime. This study suggests that the pathway framework would benefit from the increased recognition of the role of mental illness on female criminality. Trauma-informed policy implications are provided and discussed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The normalization of deviance in the form of prison rape finds common themes in media, rape myths, and common discourse. However, these portrayals fail to include real world policies and the perspectives of incarcerated populations. As such, the normalization of deviance is assessed in the context of the implementation of the Prison Rape Elimination Act (PREA). A thematic analysis was conducted using qualitative survey responses from 407 males incarcerated in three medium-level security state prisons in the Southern United States. Surprisingly, respondents rejected stereotypical notions of sexuality (institutional deviancy) and snitching (cultural deviancy) surrounding prison rape. Rather, respondents favored standardized safety procedures and institutional responses designed to reduced risk, while also endorsing views that traditional snitching codes were not applicable to prison rape. This study provides implications for researchers and practitioners, particularly in the context of the implementation of PREA., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Many facets of military life are contributors to child health including frequent mobility, family separation, and increased risk to parental physical and mental health, as well as strong social networks and military support systems; yet, there has not been an examination of adverse childhood experiences (ACEs) and positive childhood experiences (PCEs) among military children., Materials and Methods: This study used the 2020-2021 National Survey of Children's Health, limited to children aged 6 to 17 years of age, to examine the association between a child who has ever had a caregiver on active duty and their exposure to ACEs and PCEs (n = 54,256 children). Bivariate analyses used Pearson's chi-squared tests and were weighted to be nationally representative. Multivariable regression models were used to examine the association between military status and selected ACEs., Results: There were no statistically significant differences in PCEs between military and civilian children. Compared to children with a civilian caregiver, children who had a caregiver who had ever served on active duty had a higher odds of experiencing domestic violence (adjusted Odds Ratio (aOR), 1.61; 95% CI 1.23-2.11), mental health issues or depression in the household (aOR 1.28; 95% CI 1.07-1.52), and substance use (aOR 1.28; 95% CI 1.06-1.55)., Conclusions: This study complements and extends previous research that has taken a deficit approach and focused exclusively on the hardships faced by children in military families. The findings from this study may be instructive for child welfare advocates and policymakers as they intervene in communities with programming that promotes PCEs among children and adolescents., (© The Association of Military Surgeons of the United States 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Regulatory T cells (T regs ) are protective in atherosclerosis but reduced during disease progression due to cell death and loss of stability. However, the mechanisms of T reg dysfunction remain unknown. Oxidized phospholipids are abundant in atherosclerosis and can activate innate immune cells, but little is known regarding their impact on T cells. Given T reg loss during atherosclerosis progression and oxidized phospholipid levels in the plaque microenvironment, we investigated whether oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (oxPAPC), an oxidized phospholipid associated with atherosclerotic plaques, alters T reg differentiation and function., Methods: CD4 + T cells were polarized to T reg , T helper (Th) 1, and Th17 cells with or without oxPAPC and assessed by flow cytometry. Gene expression in oxPAPC-treated T regs was analyzed by bulk RNA sequencing. Functional studies of oxPAPC-induced T regs were performed by coculturing T regs with CellTrace Violet-labeled cells in vitro, and by adoptively transferring T regs to hyperlipidemic Ldlr -/- mice to measure atherosclerosis progression., Results: Compared with controls, oxPAPC-treated T regs were less viable, but surviving cells expressed higher levels of the Th1-associated markers T-bet, CXCR3, and IFN (interferon)-γ. Th1 and Th17 skewing cultures were unaltered by oxPAPC. IFN-γ is linked to T reg instability, thus T reg polarization experiments were repeated using Ifngr1 -/- CD4 + T cells. IFNγR1 (INF gamma receptor 1) deficiency did not improve cell viability in oxPAPC-treated T regs ; however, T-bet and IFN-γ expression was not increased in surviving cells suggesting a role for IFN-γsignaling. OxPAPC-treated T regs were less suppressive in vitro, and adoptive transfer studies in hyperlipidemic Ldlr -/- mice showed that oxPAPC-induced T regs possessed altered tissue homing and were insufficient to inhibit atherosclerosis progression., Conclusions: OxPAPC elicits T reg -specific changes altering T reg differentiation and inducing a Th1-like phenotype in surviving cells partially through IFN-γ signaling. This is biologically relevant as oxPAPC-treated T regs do not reduce atherosclerosis progression in Ldlr -/- mice. This study supports the role of oxidized phospholipids in negatively impacting T reg differentiation and atheroprotective function., Competing Interests: Disclosures None.

This research explores representations of non-suicidal self-injury (NSSI) on social media. The current study aims to examine the applicability of a functional model of NSSI to videos posted on YouTube by analyzing the 100 most viewed YouTube videos relating to NSSI at a point in time in 2018. Motivations for continued engagement in NSSI were examined for each content creator who posted one of the top 100 most viewed videos relating to NSSI. Categorizations of a content creator's motivation were based on Nock and Prinstein (2004) four-function model (FFM) of NSSI, in which the motivations, or functions, of NSSI are categorized by two dichotomous factors: (a) positive (i.e., involves the addition of a favorable stimulus) or negative (i.e., involves the removal of an aversive stimulus) and (b) automatic (i.e., intrapersonal) or social (i.e., interpersonal). Uploaders most endorsed automatic negative reinforcement (50%), followed by automatic positive (26%), social positive (3%), and social negative (3%). Considering the growing number of children and adolescents with near constant access to internet and social media, there may be implications for further development of safety measures for social media platforms. The results of this study may be valuable for parents, health care professionals, and educators, who should be aware of available social media content relating to NSSI and consider implementing additional media-literacy and media-safety education in school curriculums and programming for children and adolescents. Furthermore, health care professional should be aware that misconceptions of NSSI may have an impact on patients' willingness to seek treatment, or the attitude with which treatment is sought.

Sideroblastic anaemia is a rare condition. We report a unique case of concomitant sideroblastic anaemia in a patient with sickle cell disease with long-standing blood transfusion history. Due to a low prevalence of sideroblastic anaemia, the diagnosis of sideroblastic anaemia is often difficult, especially when coexisting with common types of anaemia, including sickle cell disease. This case highlights the detrimental effects of anchoring bias. Rare causes of refractory anaemia should be considered in patients with haemoglobin disorders as the therapeutic approaches for these conditions are different. High suspicion on the part of the clinician and low threshold for workup of anaemia often aids in the diagnosis of coexisting conditions such as sideroblastic anaemia. Early diagnosis and treatment of sideroblastic anaemia improves patient outcomes and prevents long-term complications., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The involvement of the endocrine pancreas leading to bronze diabetes is well studied. However, little is known about the pathophysiology of iron dysregulation involving the exocrine pancreas. We present a unique association between the exocrine pancreas and iron dysregulation. A 45-year-old female presented with chronic diarrhea and low fecal elastase indicative of pancreatic exocrine dysfunction. MRI of the abdomen/pelvis showed iron deposition in the pancreas, suggesting an associated iron-storage disorder without features suggesting chronic pancreatitis. Association of an iron-storage disorder with pancreatic exocrine dysfunction has been reported only in one other case report. Pancreatic exocrine dysfunction can be directly associated with an iron-storage disorder that involves the pancreas. This should be included in the differential and diagnostic work-up of chronic diarrhea of unclear etiology. Based on the literature, we have highlighted the potential pathophysiology relevant to the case., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Vobugari et al.)

Considerable research has focused on factors that put individuals at risk for recidivism after their release from incarceration. While recent research has increased the focus on protective factors and resilience, the experiences of people with mental health issues who successfully reintegrate into the community are not well-understood. The present study was conducted to determine which positive factors are implicated in the successful reintegration of people with mental health issues. In-depth, semi-structured interviews were conducted with four male former federal inmates on supervised release in Canada. The interviewees were nominated by staff who knew them to have previously been diagnosed with a mental disorder and perceived them to be doing well in the community. Volunteering and social support were found to be of the greatest importance in their successful outcomes. Additionally, all interviewees had access to mental health services, which likely influenced their success.

The Prison Rape Elimination Act (PREA) was designed to address sexual violence in prison. While previous has focused on sexual violence occurring in correctional facilities, there has been a dearth of studies that document the expertise, experience, or reflections of program following the cimplementation of PREA- within a correctional system. The current study utilizes a "lessons learned" approach to discuss the impact of the PREA Demonstration Project on a state prison system that includes 19 correctional institutions. Results indicate the benefits of merging the philosophical orientation of key stakeholders, establishing benchmarks, and the need for partnerships with prosecutors. A comparison of the perceptions of correctional administrators, inmates, and front-line correctional officers regarding PREA is included. Also featured are the "lessons learned" from the implementation of PREA into four prison sites, along with the concept of building trust and the impact of lockdowns due to staff shortages., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A 57-year-old man with mild haemophilia B was admitted for coronary artery bypass graft surgery. His factor IX (FIX) activity was 15% on admission. Our goal was to maintain his FIX activity at 80%-100% for post-op days (PODs) 0-3, and at 60%-80% for PODs 4-14. Preoperatively, the patient was given recombinant FIX (rFIX) bolus using the formula:Dosage needed=%(desired FIX level-current level of FIX)×weight (kg)×1.3.This increased his activity to 100%. One IU of rFIX increased FIX activity by 0.8%; the half-life of rFIX is 18-24 hours. The rFIX infusion was started intraoperatively and continued after surgery to maintain target FIX activity. He was discharged on POD 9 on rFIX bolus dosing of 5000 IU every 12 hours for an additional 5 days. Using continuous factor infusion, we managed to decrease the amount rFIX used by >60% while maintaining steady state FIX activity level., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Sickle cell disease (SCD) is characterized by painful vaso-occlusive crises (VOCs). Self-reported pain intensity is often assessed with the Numeric Rating Scale (NRS), whereas newer patient-reported outcome measures (PROMs) assess multidimensional pain in SCD. We describe pain experiences among hospitalized adults with VOCs, using 2 PROMs: the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health and the Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me). Adults with SCD hospitalized with VOCs at 2 academic centers in Boston, Massachusetts, from April 2016 to October 2017 were eligible. Participants completed the NRS and PROMs at admission and 7 days postdischarge. PROM scores were described and compared with population norms. Length of stay (LOS) and 30-day readmission rates were assessed. Forty-two (96%) of 44 eligible patients consented and completed admission assessments. Mean age was 30.2 years (standard deviation, 9.1), 60% were women, 76% were non-Hispanic black, and 64% had hemoglobin SS. Twenty-seven participants (64%) completed postdischarge assessments. Sixty percent had ≥4 VOCs in the last year. Nearly all PROMIS Global Health and ASCQ-Me scores were worse than population norms. NRS and PROMIS Global Physical Health scores improved after discharge, the latter driven principally by improvements in pain. Overall median LOS was 7 days, and 30-day readmission rate was 40.5%. Administration of PROMs among adults with SCD hospitalized for VOCs is feasible and demonstrates participants experienced recurrent, prolonged, and severe VOCs. PROMIS Global and ASCQ-Me scores indicated substantial suffering, and the striking 30-day readmission rate highlights the vulnerability of these patients., (© 2019 by The American Society of Hematology.)

Objective: Dog programs occurring in prison tend to generate positive public opinion and media portrayals, yet they often lack empirical validation. This is the first study to examine the key themes that drive a dog program aimed at incarcerated youth serving time in an adult prison., Design and Sample: A sample of male youth (n = 31) were provided survey questions on a rescue dog program. A grounded qualitative approach was employed with open-ended responses., Results: The following themes emerged: the symbolism of the dog its role in therapy, perceptions of positive behaviors and rehabilitation, a sense of normality, and universal support by inmates., Conclusion: This study supports the potential for utilizing rescue dogs in therapeutic interventions in which the vulnerable inmate can discuss early trauma, interpersonal dysfunction and histories of deviance. The dog symbolized the potential for incarcerated youth to engage in discussion of sensitive topics in a safe manner. Policy implications also include the function of dogs in creating a normalizing effect on the prison unit itself, one that can promote rehabilitation. There was universal support for the program which is rare in the prison milieu. Theoretically, positive outcomes occurred in an indirect manner, though more research is needed., (© 2019 Wiley Periodicals, Inc.)

Background: Rates of self-harm are high among prisoners. Most research focuses on the vulnerable prisoner, and there is little on the impact of these behaviours on staff., Aims: To investigate staff perceptions of self-harming behaviours by prisoners, including their views on its causes, manifestation, prevention in institutions, and impact on them., Methods: Semistructured interviews were conducted with 20 administrative and 21 therapeutic prison staff who are responsible in various ways for prisoners who self-harm. Their narratives were explored using interpretative phenomenological analysis., Results: Despite prison staff being experienced with prisoners' self-harming behaviours, including severe acts of self-harm, they were apt to reject any negative impact on their own mental health or well-being. This denial of negative impact was accompanied by perceptions of the inmate's actions being manipulative and attention seeking. Prison staff also perceived institutional responses to self-harming behaviours by prisoners as being mixed, ambiguous, or showing preference for relying on existing suicide protocols rather than task-specific guidance., Conclusions: Although staff gave explanations of prisoner self-harm in terms of "manipulative behaviour," prisoners' self-harm is, in fact, complex, challenging, and often severe. This staff perception may reflect denial of impact of often distressing behaviours on them personally and their own coping mechanisms. This could be feeding in to a perceived lack of clear and effective institutional responses to the self-harm, so further research is needed to determine how staff could broaden their views, and respond more effectively to prisoners. Psychologically informed group work and/or reflective practice are among the candidates for such help for staff., (© 2019 John Wiley & Sons, Ltd.)

A vailable tyrosine kinase inhibitors for chronic myeloid leukemia bind in an adenosine 5'-triphosphate-binding pocket and are affected by evolving mutations that confer resistance. Rebastinib was identified as a switch control inhibitor of BCR-ABL1 and FLT3 and may be active against resistant mutations. A Phase 1, first-in-human, single-agent study investigated rebastinib in relapsed or refractory chronic or acute myeloid leukemia. The primary objectives were to investigate the safety of rebastinib and establish the maximum tolerated dose and recommended Phase 2 dose. Fifty-seven patients received treatment with rebastinib. Sixteen patients were treated using powder-in-capsule preparations at doses from 57 mg to 1200 mg daily, and 41 received tablet preparations at doses of 100 mg to 400 mg daily. Dose-limiting toxicities were dysarthria, muscle weakness, and peripheral neuropathy. The maximum tolerated dose was 150 mg tablets administered twice daily. Rebastinib was rapidly absorbed. Bioavailability was 3- to 4-fold greater with formulated tablets compared to unformulated capsules. Eight complete hematologic responses were achieved in 40 evaluable chronic myeloid leukemia patients, 4 of which had a T315I mutation. None of the 5 patients with acute myeloid leukemia responded. Pharmacodynamic analysis showed inhibition of phosphorylation of substrates of BCR-ABL1 or FLT3 by rebastinib. Although clinical activity was observed, clinical benefit was insufficient to justify continued development in chronic or acute myeloid leukemia. Pharmacodynamic analyses suggest that other kinases inhibited by rebastinib, such as TIE2, may be more relevant targets for the clinical development of rebastinib ( clinicaltrials.gov Identifier:00827138 )., (Copyright© Ferrata Storti Foundation.)

The relationship between types of childhood abuse, suicide attempts, and nonsuicidal self-injury (NSSI) was examined in a sample of 415 incarcerated adults (268 men, 147 women). Men and women were equally likely to experience childhood abuse, although women were more likely to report sexual abuse and men were more likely to report emotional neglect. Sexual abuse was the only type of abuse found to predict NSSI and suicide attempts in women. For men, physical abuse and physical neglect were significant predictors of NSSI and suicide attempts, respectively. Gender differences exist and should be examined in future research in this area., (© 2016 The American Association of Suicidology.)

Infectious laryngotracheitis (ILT) is a significant viral disease of chickens in many countries around the globe. In this report the status of ILT in Australia has been used as a model to evaluate the evolution of the ILT viruses (ILTVs). Due to its geographical isolation, Australia harbored a distinct lineage of ILT viruses (ILTV) up to 2007. However examination of the ILT viruses (ILTV) involved in outbreaks between 2007 and 2009 has revealed that many of the outbreaks were caused by two new viral genotypes, class 8 and class 9. These two recombinant viruses were found to emerge as a result of recombination between previously existing live vaccine strains (SA2 and A20), and another live vaccine strain (Serva) introduced into the country in 2007. The new recombinant ILTVs were also shown to possess significantly higher virulence and replication capacity compared with a previously predominant ILTV, class 2. In the current study, examination of a large number of ILTVs isolated from outbreaks between 2009 and 2015 revealed the emergence of yet another recombinant virus (class 10) that appears to have become a predominant genotype in New South Wales. In Victoria however, the recombinant class 9 gradually became the predominant virus, replacing class 2. Therefore, there was an unusual pattern in geographical spread of the newly emerged viruses in different states of the country. These results suggest that ILTV is fast evolving towards a greater transmissibility and therefore greater capacity to spread into ILTV-free areas., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Nonsuicidal self-injury (NSSI) is the deliberate bodily harm or disfigurement without suicidal intent and for purposes not socially sanctioned (e.g., cutting, burning, head banging). Nock and Prinstein (2004) proposed a 4-function model (FFM) of NSSI, in which the functions of NSSI are categorized by two dichotomous factors: (a) positive (i.e., involves the addition of a favorable stimulus) or negative (i.e., involves the removal of an aversive stimulus; and (b) automatic (i.e., intrapersonal) or social (i.e., interpersonal). This study examined the validity of this model with incarcerated populations. In-depth semistructured interviews with 201 incarcerated offenders were analyzed and categorized based on the FFM. Participants' descriptions of functions of NSSI were most commonly categorized as automatic negative reinforcement (25.0%; e.g., coping with negative emotions), followed by automatic positive reinforcement (31.3%; e.g., self-punishment), social positive reinforcement (31.3%; e.g., to communicate with others), and social negative reinforcement (12.5%; e.g., to avoid hurting someone else). While the uniqueness of the correctional environment affects some of the specific functions evident in offenders, FFM can be used to adequately organize the functions of NSSI in offenders, providing a useful tool for explaining this complex behavior. Clinically, NSSI in offenders can be viewed has having the same underlying motivations, although automatic positive reinforcement is more prevalent in offenders and social positive reinforcement is more prevalence in nonoffenders. Given that the motivations underlying nonsuicidal self-injury are similar for offender and nonoffender populations, similar treatment approaches may be effective with both populations. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

Comorbidity is more common in older patients and can increase the cost of care by increasing toxicity. Using the SEER-Medicare database from 2000 to 2007, we examined the costs and life-year benefit of Auto-HSCT for MM patients over the age of 65 by evaluating the difference over time relative to comorbidity burden. One hundred ten patients had an Auto-HSCT in the early time period (2000-2003) and 160 in the late time period (2004-2007). Patients were divided by a Charlson Comorbidity Index (CCI) of 0 or greater than 1 (CCI1+). Median overall survival was 53.5 months for the late time period patients compared to 40.3 months for the early time period patients ( p = 0.031). Median costs for CCI0 versus CCI1+ in the early period were, respectively, $70,900 versus $72,000 (100 d); $86,100 versus $98,300 (1 yr); and $139,200 versus $195,300 (3 yrs). Median costs for late period were, respectively, $58,400 versus $60,400 (100 d); $86,300 versus $77,700 (1 yr); and $124,400 versus $110,900 (3 yrs). Comorbidity had a significant impact on survival and cost among early time period patients but not among late time period patients. Therefore, older patients with some comorbidities can be considered for Auto-HSCT depending on clinical circumstances.

In the past decade, the number of autologous hematopoietic stem cell transplants (Auto HSCT) for older patients with multiple myeloma (MM) has increased dramatically, as has the cost of transplantation. The cost-effectiveness of this modality in patients over age 65 is unclear. Using the Surveillance, Epidemiology, and End Results-Medicare database to create a propensity-score matched sample of patients over age 65 between 2000 and 2007, we compared the survival and cost for those who received Auto HSCT to those who did not undergo transplantation but survived at least 6 months after diagnosis, and we calculated an incremental cost-effectiveness ratio (ICER). Two hundred seventy patients underwent transplantation. Median overall survival from diagnosis in those who underwent transplantation was significantly longer than in patients who did not (58 months versus 37 months, P < .001). For patients living longer than 2 years, the median monthly cost during the first year was significantly different, but the middle and last year of life costs were similar. The median cost of the first 100 days after transplantation was $60,000 (range, $37,000 to $85,000). The resultant ICER was $72,852 per life-year gained. Survival after transplantation was comparable to that in those who underwent transplantation patients under 65 years and significantly longer than older patients who did not undergo transplantation. With an ICER less than $100,000/life-year gained, Auto HSCT is cost-effective when compared with nontransplantation care in the era of novel agents and should be considered, where clinically indicated, for patients over the age of 65., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of study was to identify a list of performance measures for schizophrenia treatment services and to assemble a multistakeholder group to reach consensus on a core list., Methods: The study was conducted in two stages: first, a systematic review of the literature was conducted to identify a comprehensive list of measures; second, a consensus-building technique, the Delphi process, was used with participants from six groups of stakeholders: schizophrenia experts, mental health clinicians, mental health administrators, the payer (the Alberta Ministry of Health and Wellness), patients, and family members. Thirty stakeholders participated in three rounds of self-completed questionnaires. The degree of consensus achieved in the Delphi process was defined as the semi-interquartile range for each measure., Results: Ninety-seven measures were identified in the literature review. The Delphi method reduced the list to 36 measures rated as essential. The measures address eight domains of service-level evaluation: acceptability, accessibility, appropriateness, competence, continuity, effectiveness, efficiency, and safety. Despite the diversity in backgrounds of the stakeholder groups, the Delphi technique was effective in moving participants' ratings toward consensus through successive questionnaire rounds. The resulting measures reflected the interests of all stakeholders., Conclusions: Several further steps are required before these measures are implemented and include working toward reliability and validity of specific measures, assessing the feasibility and cost-effectiveness of collecting the data, and finally, undertaking risk adjustment for outcome measures.

The mammalian proprotein convertase subtilisin kexins (PCSKs) previously called proprotein or prohormone convertases (PCs) are a family of Ca(+2)-dependent endoproteases in the subtilisin family. These proteolytic enzymes exert their many crucial physiological and biological functions in vivo via their ability to cleave larger inactive precursor proteins into their biologically active mature forms. This event takes place in a highly efficient and selective manner. Such actions of PCSKs either alone or in combination to cleave specific protein bonds are the hallmark events that not only define the normal functions and metabolism of the body but also may lead to a variety of diseases or disorders with associated conditions. These include among others, diabetes, obesity, cancer, cardiovascular diseases, reproduction abnormalities as well as viral bacterial infections. These conditions were the direct consequences of an enhanced level of enzymatic activity of one or more PCSKs except only PCSK9, whose protease activity in relation to its physiological substrate has yet to be characterized. Owing to this finding, a large number of research studies have been exclusively devoted to develop rapid, efficient and reliable in vitro methods for examining the protease activity of these enzymes. Several assays have been developed to monitor PCSK activity and these are widely used in chemical, biochemical, cellular and animal studies. This review will cover various methodologies and protocols that are currently available in the literature for PCSK activity assays. These include liquid phase methods using fluorogenic, chromogenic and intramolecularly quenched fluorescent substrates as well as a newly developed novel solid phase fluorescence method. This review will also highlight the usefulness of these methodologies and finally a comparative analysis has been made to examine their merits and demerits with some key examples.

A young woman originally from Cape Verde islands presented with mild sickle cell disease. Her blood counts and hemoglobin analysis results initially suggested that she might be either homozygous for the sickle cell hemoglobin (Hb S) with concomitant alpha-thalassemia, or compound heterozygous for Hb S and beta0-thalassemia, deletional deltabeta-thalassemia or hereditary persistence of fetal hemoglobin (HPFH). We utilized a novel polymerase chain reaction (PCR)-based screening technique and found a hitherto unrecognized 7.7-kb deletion, starting from the HBB IVSII to 3' downstream of the beta-globin gene. This diagnostic approach can be applied to decipher other similar deletional mutations. This is the second known deletion that removes the 3'-end but preserves the integrity of the 5'-end of the beta-globin gene. Furthermore, the identification of the deletion allows proper genetic counseling for affected families.

Restorative justice offers several innovative methods designed to heal the injury that the offender may have caused to the victim. One of these innovative methods is victim compensation, a form of income redistribution designed to redistribute wealth from offenders to victims of crime. Restitution, particularly through the Victim of Crime Act (VOCA), is a needs-based form of justice designed to assist the most needy victims of violent crime. Recent studies suggest that while state-level compensation programs may target poor, young, African American men, compensation at the national level tends to be received more by older, White women who experienced domestic violence. The author suggests that this disparity between state and local resource distribution in the allocation of victim compensation is a reflection of the ideological differences between the established theoretical frameworks of liberalism and radical feminism.

The N-n-propyl analog of dihydrexidine ((+/-)-trans-10, 11-dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridine) is a dopamine receptor agonist with high affinity for dopamine D2 and D3 receptors (K0.5 = 26 and 5 nM, respectively). Members of the hexahydrobenzo[a]phenanthridine structural class are atypical because they display high intrinsic activity at post-synaptic dopamine D2 receptors, but low intrinsic activity at dopamine D2 autoreceptors. The present study examined the effects of (+/-)-N-n-propyl-dihydrexidine on unconditioned behaviors in rats. The most striking results observed were large, dose-dependent decreases in locomotor activity (e.g., locomotor inhibition), and increases in vacuous chewing; yawning was also increased at the highest dose of (+/-)-N-n-propyl-dihydrexidine. The locomotor inhibition and yawning induced by (+/-)-N-n-propyl-dihydrexidine were blocked by pre-treatment with (-)-remoxipride (S(-)-3-bromo-N-((1-ethyl-2-pyrrolidinyl)-methyl)-2, 6-dimethoxybenzamide), a dopamine D2 receptor antagonist, but not by the dopamine D1 receptor antagonist (+)-SCH23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine). Vacuous chewing was decreased by both (-)-remoxipride and (+)-SCH23390. These data support the hypothesis that a subpopulation of post-synaptic dopamine D2 receptors has a critical role in decreases in locomotor activity and induction of vacuous chewing and yawning.

Between June 1992 and June 1994, six children underwent laparoscopic or thoracoscopic assistance in the management of cerebrospinal fluid (CSF) shunts. Four children (3 to 12 years of age) required laparoscopic assistance. Two children (5 and 10 years of age) underwent thoracoscopy with insertion of syringopleural shunts for decompression of cervicothoracic hydromyelia. Most children who require CSF decompression do not need endoscopic assistance for placement of the terminal portion of the shunt. However, in selected patients who have undergone previous abdominal procedures, in patients with a persistent pseudocyst occupying an extensive portion of the abdominal cavity, and in patients requiring removal of a disconnected shunt, laparoscopy is the ideal approach. Thoracoscopy for a syringopleural shunt prevents the need for minithoracotomy.

Previous analyses of a TCR V beta 8.1 transgenic mouse revealed multiple mechanisms of tolerance to the retroviral superantigen, Mls-1. Whereas some T cells were clonally deleted in the thymus, others became anergic in the periphery, or remained unaffected by the expression of Mls-1. In addition, a strong correlation between TCR alpha-chain usage and Mls-1 reactivity of individual transgenic V beta 8.1+ T cell hybridomas was established. Based on these observations, we speculated that the different mechanisms of tolerance were a consequence of the alpha-chain-mediated differences in Mls-1 reactivity. In the current studies, we make use of a V alpha 2-specific mAb to directly examine the role of the alpha-chain on tolerance in this transgenic model. We show, first, that V alpha 2+ CD4+ T cells, as a group, are relatively less Mls-1-reactive, and are elevated twofold in the periphery of Mls-1+ compared with Mls-1-V beta 8.1 transgenic mice. This elevated expression is also seen in the V alpha 2+ CD4+ population of mature thymocytes, but not in immature thymocytes. Second, Mls-1-induced neonatal tolerance in Mls-1-negative mice caused an increase of V alpha 2+ CD4+ T cells, comparable with the frequency of expression in transgenic mice that endogenously expressed Mls-1. Third, we have demonstrated a general correlation between the age-dependent increase in Mls-1-expression and the levels of V alpha 2+ CD4+ T cells during the first 4 wk of life. Taken together, these data suggest that the over-expression of V alpha 2+ CD4+ T cells in Mls-1+ mice is a consequence of mechanisms of tolerance, predominantly mediated by preferential lack of clonal deletion in the thymus. These data support the idea that clonal deletion is a competitive process and the influence of the TCR alpha-chain on the strength of Mls-1 reactivity of individual V beta 8.1+ transgenic T cells controls their susceptibility to clonal deletion.

We have recently shown that recognition of the mouse mammary tumor virus 9-associated superantigen (vSAG-9) by murine V beta 17+ T cells is strongly influenced by the major histocompatibility complex (MHC) class II haplotype of the presenting cells, resulting in a form of MHC-restricted recognition. This finding was unexpected, because T cell recognition of another well-characterized retroviral superantigen, minor lymphocyte-stimulating antigen 1 (Mls-1), had been shown to be independent of the MHC haplotype of the presenting cell. To determine whether recognition of vSAG-9 and Mls-1 is fundamentally different, we undertook an extensive analysis of MHC haplotype influences on vSAG-9 and Mls-1 recognition by panels of T cell hybridomas. Our results show that, although most hybridomas recognized Mls-1 regardless of the MHC haplotype of the presenting cells, as previously described by others, some hybridomas exhibited unique patterns of MHC fine specificity. Thus, T cell recognition of vSAG-9 and Mls-1 is not fundamentally different, but the apparent differences can be explained in terms of frequency. The MHC fine specificity of individual Mls-1-reactive hybridomas was influenced by both V beta and non-V beta T cell receptor (TCR) elements. First, the influence of the V beta element was apparent from the observation that V beta 8.2+ hybridomas were significantly more MHC specific in their recognition of Mls-1 than V beta 8.1 hybridomas. Second, a role for the TCR alpha chain was implicated from the distinct patterns of fine specificity of Mls-1 reactivity among a panel of transgenic hybridomas that expressed an identical beta chain (V beta 8.1D beta 2J beta 2.3C beta 2). Sequence analysis revealed that junctional residues of the TCR alpha chain and/or V alpha/J alpha combinations influenced the MHC haplotype fine specificity for Mls-1. Third, D beta J beta influences were implicated, in that the transgenic hybridomas expressed distinctive patterns of Mls-1 fine specificity not represented among V beta 8.1+ nontransgenic hybridomas. The findings that T cell recognition of endogenous superantigen is MHC specific, and that this specificity correlates with non-V beta elements of the TCR, support the hypothesis that there is a direct interaction between the TCR and either polymorphic residues of the MHC class II molecule or haplotype-specific dominant peptides presented by class II.

Most, but not all, V beta 8.1+ T cells respond to M1s-1 and are clonally deleted in the thymus of M1s-1-expressing animals. To formally examine the role of the TCR alpha-chain in reactivity and tolerance to M1s-1, we have analyzed M1s-1 reactivity in a large panel of CD4+ hybridomas generated from TCR V beta 8.1 transgenic mice, that express an identical, potentially M1s-1-reactive beta-chain. The data show that the alpha-chain strongly influences the M1s-1 reactivity of the hybridomas and that the differences in reactivity had relevance for tolerance. Thus, V alpha 11+ hybridiomas were biased toward M1s-1 reactivity and V alpha 11+ T cells were correspondingly absent from the peripheral repertoire of M1s-1-expressing transgenic mice. V alpha 2+ hybridomas, on the other hand, were biased against M1s-1 reactivity, and V alpha 2+ T cells were correspondingly amplified in the M1s-1-expressing transgenic mice. Structural analysis of the alpha-chains revealed that the M1s-1 reactivity of the V alpha 11+ hybridomas segregated precisely with family member, such that V alpha 11.1+ hybridomas were M1s-1-reactive and V alpha 11.3+ hybridomas were not M1s-1-reactive. On the other hand, there was not a clear correlation between family member and M1s-1 reactivity in the V alpha 2+ hybridomas. The hybridomas also showed striking variation in their reactivity to staphylococcal enterotoxin B (SEB), and the SEB reactivity of the V alpha 11+ hybridomas correlated precisely with family member and with M1s-1 reactivity. In contrast, there was not a clear correlation with V alpha 2+ alpha-chain structure and SEB reactivity. Also, there was no correlation between M1s-1 reactivity and SEB reactivity in individual V alpha 2+ hybridomas, suggesting that the recognition of the two superantigens by the same TCR is not equivalent. Taken together, these data define a role for the TCR alpha-chain in superantigen reactivity and T cell tolerance, and provide a structural explanation for the different fates of M1s-1-reactive T cells in normal and transgenic mice.

Orbital-cranial injuries have the greatest potential for death and disability of any condition treated by the ophthalmologist. An object that penetrates through the orbit into the brain may leave only a small entrance wound. Patients can have normal vision, neurologic exam, and plain x-rays despite trauma that may lead to meningitis, brain abscess, or pneumocephalus. The CT scan greatly aids in both the early and late management of blunt and penetrating orbital-cranial trauma. The detection of pneumocephalus may be the only clue that intracranial penetration has occurred. Blunt trauma can cause vision loss, ophthalmoplegia, ptosis, and intracranial injury. Management of orbital-cranial trauma frequently requires a team approach by the ophthalmologist and neurosurgeon due to the complexity of these injuries.

Although meningiomas are known to cause varying degrees of cerebral edema, the relative importance of their location, size, histological subtype, and other histological features in the production of cerebral edema has not been studied adequately. Therefore, we undertook a retrospective analysis of 43 meningiomas excised between 1975 and 1980. The results indicate that histological subtype has no relationship to the production of cerebral edema, with one exception. Meningiomas containing partly or completely a hemangiopericytic component were the only histological subtype associated consistently with cerebral edema. The location of a meningioma per se may not determine the production of cerebral edema. A relationship between size, aggressive histological features, vascular proliferative changes, and the production of cerebral edema was seen. The need for and the nature of further studies required to explain the cerebral edema that may be associated with small meningiomas are discussed.

Eighty patients sustaining head injuries and presenting with Glasgow Coma Scale scores of 8 or less were entered into a prospective randomized study to assess the benefit of intracranial pressure (ICP) monitoring with two regimens of mannitol administration. Group I was treated with mannitol for ICP elevations greater than 25 mm Hg, while Group II received empirical mannitol therapy irrespective of ICP readings. No statistically significant differences in mortality rate or neurological outcome were demonstrated between the two groups. These results are comparable to those of several published series of head-injured patients receiving similar treatment from 1977 to 1982. However, those series must be reassessed in light of recently published studies with treatment initiated at lower levels of ICP.

Among 481 children with myelomeningocele seen at the North Carolina Baptist Hospital since 1949, 46 have undergone a urinary diversion procedure, as follows: ileal loop in 43; sigmoid loop in two; and transverse colon conduit in one. The indications for diversion were incontinence in 28, urinary infection or pyelonephritis in 27, and hydronephrosis, pyelocaliectasis, and reflux in 12 patients. No deaths resulted from the diversionary procedures. One patient required early surgical revision and seven patients required late surgical revision. Two patients have since died, 44 have been followed for an average of 7.9 years, 15 for more than 10 years. Overall, of 26 patients with normal prediversionary intravenous pyelograms (IVP's), 88% now have normal or nearly normal IVP's; of 14 patients with abnormal prediversionary IVP's, 79% now have normal, improved, or unaltered IVP's. Renal function has remained normal in all 44 patients, and renal calculi have developed in 10 patients. Ileal loop diversion appears to convert a high-pressure system into a low-pressure system, thereby helping to prevent further renal damage. This procedure tends to stabilize, rather than improve, urinary-tract function. For these children already so incapacitated by their basic disease, this goal is acceptable, particularly since it also provides continence and independence from parental nursing.

A patient with oculomotor palsy with pupillary sparing was shown angiographically to have an aneurysm of the internal carotid artery, which proved at operation to arise distal to the origin of the ophthalmic artery. It did not impinge on the oculomotor nerve at any point. The oculomotor palsy persisted postoperatively, and complete intrinsic and extrinsic ophthalmoplegia developed. Cytological studies of cerebrospinal fluid were then made and were positive for malignant lymphocytic leukemic cells. Despite the fact that an aneurysm causing oculomotor palsy with pupillary sparing has been reported, we recommend that nonaneurysmal causes be considered first in patients presenting with that neurological sign.

Cervical spine involvement by rheumatoid arthritis is common; brain-stem compression secondary to vertical subluxation of the odontoid in patients with rheumatoid arthritis is rare. Vertical subluxation results from 1) destruction of the transverse atlantal, apical, and alar ligaments of the atlas and odontoid, and 2) bone resorption in the occipital condyles, lateral masses of the atlas, and basilar processes of the skull. Neurological symptoms result from direct compression of the brain stem or from ischemia secondary to compression of vertebral arteries, anterior spinal arteries, or small perforating arteries of the brain stem and spinal cord. A case is reported in which a slowly progressive neurological deficit developed in a woman with rheumatoid arthritis following a fall from a stretcher. Neruological symptoms represented direct compression of the medulla by the dens, a mechanism confirmed at operation and autopsy. Recognition of progressive neurological deficit is often difficult in patients with rheumatoid arthritis because of their inactivity and their atrophic and immobile joints, but is essential if appropriate decompressive or stabilizing procedures are to be done. In patients with vertical subluxation of the dens, the transoral approach with removal of the odontoid is recommended. Decompression should be extensive, including the fibrous capsule around the odontoid and overlying synovial tissue as well as the odontoid itself.

A 1-year-old boy was treated for histiocytosis X involving the cervical dura which caused spinal cord compression.

Lipomas of the intracranial vault are uncommon lesions. Rarely, lipomas of the cerebellopontine angle have been identified. The two cases of cerebellopontine angle lipomas reported herein brings the number of recorded cases to 13.

Virtually all patients with anterior sacral meningocele have a pelvic mass with symptoms and signs relating to pressure of the mass on adjacent structures. Constipation is a universal complaint; urinary incontinence is common. A headache often develoips when the patient stands, due to lowered spinal fluid pressure as the meningocele sac fills. A scimitar-shaped sacrum on anterioposterior plain roentgenograms of the spine is pathognomonic. The coccyx may be absent, and the lower sacral laminate may be absent or incomplete. Myelography confirms the diagnosis and should be done with large volumes of iophendylate in order to fill the sac. Only approximately 130 anterior sacral meningoceles have been reported in the literature. This article presents 2 more cases, both seen at the North Carolina Baptist Hospital. The surgical approach to both was through a sacral laminectomy; the communicating stalk was ligated and the meningocele was removed. One patient was 11 years old and had a large suprapubic pelvic mass found on routine examination. She is neurologically normal postoperatively. The other was 7 years old and had had fecal incontinence since birth. That incontinence is less severe postoperatively and the patient is neurologaically normal.

Exposure of a very rostral carotid bifurcation for endarterectomy may occasionally be difficult. We are reporting a simple yet effective way to gain several centimetres of exposure of the distal cervical portion of the internal carotid artery in this circumstance.