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1.
Pediatr Clin North Am ; 71(2): 111-125, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38423712

ABSTRACT

Autism has been the subject of large-scale public health investment. These investments are increasingly shifting toward mitigating the lifelong disability and impairment associated with autism. Key efforts include bolstering screening schedules, accelerating the path to diagnosis and early entry into evidence-based therapies, and providing preventive management of common co-occurring conditions. Enhancing their implementation will necessitate addressing neurodiversity and health equity. Pediatric primary care teams continue to be important stewards in population-level initiatives to promote autistic health. To thrive in this role, these providers will benefit from specific educational and logistical supports from the health care system.


Subject(s)
Autistic Disorder , Humans , Child , Autistic Disorder/diagnosis , Autistic Disorder/therapy , Public Health , Delivery of Health Care
2.
Perm J ; 26(4): 62-68, 2022 12 19.
Article in English | MEDLINE | ID: mdl-36001391

ABSTRACT

Background The American Academy of Pediatrics recommends routine screening and resource provision for food insecurity (FI). The authors describe documentation of FI, as well as social, developmental, and health care utilization characteristics, among patients with and without FI in a pediatric clinic. Methods This data-only case-control study describes patients with and without FI seen by pediatricians who identified at least 10 patients with FI between January 2019 and January 2020. Controls were seen by the same pediatrician on the same day, matched 2:1 with cases. Chart review identified FI documentation. Bivariate analyses were used to describe demographic, clinical, and health care utilization characteristics. Results The authors identified 74 patients with FI (cases) and 144 controls. Pediatricians documented FI in the medical record for 76% of patients identified with FI, although only 43% had FI in the problem list. There were no differences between cases and controls in the distribution of age or sex. A larger proportion of cases used the emergency department (25.7% vs 9.6%; p < 0.05), were Black (36.5% vs 15.3%; p < 0.05) or Hispanic (44.6% vs 18.8%; p < 0.05), utilized Medi-Cal (41.9% vs 16.7%; p < 0.05), had developmental delay (13.5% vs 4.2%; p < 0.05), received speech therapy (20.3% vs 4.9%; p < 0.05), or were referred to a social worker (37.8% vs 3.5%; p < 0.05). Discussion Our findings show inconsistent documentation of FI in medical records and that FI is associated with increased social, developmental, and health care utilization needs. Conclusion Further research is needed to assess the impact of documenting FI in patient charts.


Subject(s)
Ambulatory Care Facilities , Patient Acceptance of Health Care , Child , Humans , Case-Control Studies , Food Insecurity , Documentation
3.
Disaster Med Public Health Prep ; 17: e231, 2022 07 04.
Article in English | MEDLINE | ID: mdl-35781121

ABSTRACT

OBJECTIVE: The transfer rate for patients from an Alternate Care Site (ACS) back to a hospital may serve as a metric of appropriate patient selection and the ability of an ACS to treat moderate to severely ill patients accepted from overwhelmed health-care systems. During the coronavirus infectious disease 2019 (COVID-19) pandemic, hospitals worldwide experienced acute surges of patients presenting with acute respiratory failure. METHODS: An ACS in Imperial County, California was re-established in November 2020 to help decompress 2 local hospitals experiencing surges of COVID-19 cases. The patients treated often had multiple comorbid illnesses and required a median supplemental oxygen of 3 L/min (LPM) on admission. Numerous interventions were initiated during a 2-wk period to improve clinical care delivery. RESULTS: The objectives of this retrospective observational study are to evaluate the impact of these clinical and staff interventions at an ACS on the transfer rate and to provide issues to consider for future ACS sites managing COVID-19 patients. CONCLUSIONS: The data suggest that continuous, real-time process-improvement interventions helped reduce the transfer rate back to hospitals from 36.7% to 14.5% and that an ACS is a viable option for managing symptomatic COVID-19 positive patients requiring hospital-level care when hospitals are overburdened.


Subject(s)
COVID-19 , Communicable Diseases , Humans , COVID-19/epidemiology , COVID-19/therapy , Surge Capacity , Critical Care , Hospitals
4.
Burns ; 43(7): 1441-1448, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28803724

ABSTRACT

INTRODUCTION: There is significant nationwide interest in transitioning new and new-to-specialty nurses into practice, especially in burn care. Lack of a structured transition program in our Burn Center was recognized as a contributing factor for nursing dissatisfaction and increased turnover compared to other hospital units. Employee evaluations exposed a need for more didactic instruction, hands-on learning, and preceptor support. The goal of this project was to implement an evidence-based transition to practice program specific to the burn specialty. MATERIAL AND METHODS: The Iowa Model of Evidence-based Practice served as the model for this project. A working group was formed consisting of nurse scientists, clinical nurse leaders, clinical nurse specialists, lead preceptors, staff nurse preceptors and wound care coordinators. A systematic review of the literature was conducted focusing on nurse transition; preceptor development and transitioning nurse training programs with competency assessment, ongoing multifaceted evaluation and retention strategies were created. The evidence-based Vermont Nurses in Partnership (VNIP) Clinical Transition Framework was selected and subsequent education was provided to all Burn Center leaders and staff. Benchmarks for basic knowledge assessment (BKAT) and burn wound care were established among current staff by work site and education level to help evaluate transitioning nurses. Policies were modified to count each preceptor/transitioning nurse dyad as half an employee on the schedule. Multiple high-fidelity simulation scenarios were created to expand hands-on opportunities. RESULTS: From September 2012-December 2013, 110 (57% acute care nursing) Burn Center staff attended the VNIP Clinical Coaching Course, to include 34 interdisciplinary staff (rehabilitation, education, respiratory therapy, and outpatient clinic staff) and 100% of identified preceptors (n=33). A total of 30 new nurses participated in the transition program: 26 (87%) completed, 3 (10%) did not complete, and 1 (3%) received exception (no patient care). Transitioning nurses achieved passing BKAT scores (n=22; 76%) and WC scores (n=24; 93%); individual remediation was provided for those failing to achieve unit benchmarks and transition training was modified to improve areas of weakness. Transitioning nurses' weekly competency progression average initial ratings on a 10 point scale (10 most competent) were 5±2; final ratings averaged 9±1 (n=25) (p<0.0001). CONCLUSIONS: An evidence-based team practice approach toward preceptorship created a standardized, comprehensive and flexible precepting program to assist and support transition to specialty burn practice for experienced nurses. Use of objective metrics enabled ongoing assessment and made training adaptable, individualized, and cost effective. Application of this standardized approach across our organization may improve consistency for all transitions in practice specialty.


Subject(s)
Burns/nursing , Clinical Competence , Education, Nursing/methods , Evidence-Based Practice , Preceptorship/methods , Burn Units , Humans , Job Satisfaction , Personnel Turnover
5.
ANZ J Surg ; 85(5): 334-8, 2015 May.
Article in English | MEDLINE | ID: mdl-24989960

ABSTRACT

BACKGROUND: Urgent assessment of haematuria is critical to exclude malignancy. The objective of this study is to report the outcomes of the first 3 years of a dedicated haematuria clinic at the Royal Melbourne Hospital, a Victorian tertiary hospital. METHODS: All patients assessed in the haematuria clinic from April 2010 to April 2013 were included in the analysis. Outcomes were recorded prospectively and analysed retrospectively. RESULTS: A total of 643 patients were seen in the haematuria clinic with non-visible (170, 26%) and visible haematuria (463, 72%) during this time period, all within 28 days of referral being triaged. Sixty-five (10%) patients were diagnosed with urothelial carcinoma, 63 with lower tract disease and two with upper tract urothelial carcinoma and another five (1%) patients with other tumours. Thirty out of 63 (48%) of the bladder urothelial carcinomas were invasive or high-grade. Two hundred and sixty-seven (42%) patients were discharged from the clinic after a single point of contact. One hundred and fifty-three (24%) patients were referred for further definitive management of suspected pathology. Two hundred and twenty-three (34%) patients were referred to outpatients clinic for further investigations. Urothelial carcinoma was diagnosed more often in males, older patients and patients with visible haematuria. CONCLUSION: The Royal Melbourne Hospital haematuria clinic has served as an effective tool for rapid, streamlined assessment of patients presenting with haematuria. Follow-up of investigations by nurses and moving towards a 'one-stop' approach are helping to further decrease the number of patients requiring a second clinic visit.


Subject(s)
Carcinoma, Transitional Cell/diagnosis , Hematuria/etiology , Outpatient Clinics, Hospital/organization & administration , Urinary Bladder Neoplasms/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Transitional Cell/complications , Female , Humans , Male , Middle Aged , Referral and Consultation , Retrospective Studies , Tertiary Care Centers/organization & administration , Urinary Bladder Neoplasms/complications , Victoria , Young Adult
6.
Burns ; 40(3): 374-87, 2014 May.
Article in English | MEDLINE | ID: mdl-24331408

ABSTRACT

AIM: To provide a systematic review of the literature regarding development of an evidence-based Precepting Program for nurses transitioning to burn specialty practice. BACKGROUND: Burned patients are admitted to specialty Burn Centers where highly complex nursing care is provided. Successful orientation and integration into such a specialized work environment is a fundamental component of a nurse's ability to provide safe and holistic patient care. DESIGN: A systematic review of the literature was performed for the period 1995-2011 using electronic databases within PUBMED and Ovid search engines. DATA SOURCES: Databases included Medline, CINHAL, ProQuest for Dissertations and Thesis, and Cochran Collaboration using key search terms: preceptor, preceptee, preceptorship, precept*, nurs*, critical care, personality types, competency-based education, and learning styles. REVIEW METHODS: Nurses graded the level and quality of evidence of the included articles using a modified 7-level rating system and the Johns Hopkins Nursing Quality of Evidence Appraisal during journal-club meetings. RESULTS: A total of 43 articles related to competency (n=8), knowledge acquisition and personality characteristics (n=8), learning style (n=5), preceptor development (n=7), and Precepting Programs (n=14). CONCLUSIONS: A significant clinical gap existed between the scientific evidence and actual precepting practice of experienced nurses at the Burn Center. Based on this extensive review of the literature, it was determined that a sufficient evidence base existed for development of an evidence-based Precepting Program.


Subject(s)
Burn Units , Burns/nursing , Clinical Competence , Education, Nursing, Continuing/methods , Evidence-Based Practice , Preceptorship/methods , Humans
7.
BJU Int ; 110 Suppl 4: 46-50, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23194125

ABSTRACT

OBJECTIVE: • To present our initial experience implementing a nurse-led flexible cystoscopy (NLFC) service in a Victorian tertiary hospital and our initial results from that service, as NLFC has developed over the past decade with reports suggesting that adequately trained nurses can undertake FC competently. PATIENTS AND METHODS: • We describe the implementation of a NLFC service including approval, funding, nurses' training, and protocols. • Outcomes of all patients having a NLFC or subsequent interventions were recorded prospectively and analysed retrospectively. • To gauge patients' response to NLFC, an anonymous feedback questionnaire was administered to 60 consecutive participating patients in the recovery unit. • The effect of NLFC on waiting times was determined from surgical scheduling records. RESULTS: • In all, 272 patients had 720 NLFC done over a 2-year period. In all, 150 (21%) FCs had a suspected bladder cancer recurrence and were referred for a rigid cystoscopy. Of those, 83 (58%) revealed a recurrence comprising of 14 (17%) high-grade lesions, 45 (54%) low-grade lesions and 24 (29%) were diathermied without a biopsy. In all, 41 (27%) had benign pathology on biopsy and 21 (14%) had normal rigid cystoscopy. • There were two significant adverse events. • There was a 65% reduction in the waiting list for surveillance FC after introduction of the service. • Of 60 patients who completed the feedback questionnaire, 95% reported that they were given enough information by the nurses, 92% had all their questions answered satisfactorily and 97% had enough confidence and trust in the nurse. In all, 90% had a positive perception of the service overall and 93% were happy to have a FC performed by a nurse rather than a doctor. CONCLUSIONS: • Results from our NLFC audit compare favourably with other published reports. NLFC is a safe and feasible option when established alongside strong departmental support, comprehensive nurses' training according to established guidelines, service supervision by a designated consultant and regular audits. • NLFC clinics can provide an efficient service and excellent continuity of care for patients with non-muscle-invasive bladder cancer.


Subject(s)
Cystoscopes , Cystoscopy/nursing , Early Detection of Cancer/methods , Practice Patterns, Nurses' , Urinary Bladder Neoplasms/diagnosis , Aged , Aged, 80 and over , Cystoscopy/methods , Equipment Design , Feasibility Studies , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Reproducibility of Results , Retrospective Studies , Surveys and Questionnaires , Urinary Bladder Neoplasms/nursing , Victoria
8.
Sex Abuse ; 21(1): 76-92, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19218479

ABSTRACT

A sample of 505 Internet sex offenders and 526 contact sex offenders were compared on a range of psychological measures relating to offense-supportive beliefs, empathic concern, interpersonal functioning, and emotional management. Internet offenders could be successfully discriminated from contact offenders on 7 out of 15 measures. Contact offenders were found to have significantly more victim empathy distortions and cognitive distortions than Internet offenders. Internet offenders were found to have significantly higher identification with fictional characters than contact offenders. Further analysis indicated that an increase in scores on scales of fantasy, underassertiveness, and motor impulsivity were predictive of an Internet offense type. An increase in scores of scales of locus of control, perspective taking, empathic concern, overassertiveness, victim empathy distortions, cognitive distortions, and cognitive impulsivity were found to be predictive of a contact offense type. These findings are discussed in the context of the etiology of sexual offending.


Subject(s)
Cognition Disorders/psychology , Internet , Interpersonal Relations , Self Concept , Sex Offenses/psychology , Adult , Cognition Disorders/epidemiology , Comorbidity , Criminal Psychology/methods , Fantasy , Humans , Impulsive Behavior/psychology , Internal-External Control , Male , Self-Assessment , Sex Offenses/statistics & numerical data , Surveys and Questionnaires , United Kingdom/epidemiology , Young Adult
9.
J Microbiol Biol Educ ; 10(1): 25-31, 2009.
Article in English | MEDLINE | ID: mdl-23653687

ABSTRACT

There has been a dramatic increase in the availability of case studies for use in the biology classroom, and perceptions of the effectiveness of case-study-based learning are overwhelmingly positive. Here we report the results of a study in which we evaluated the ability of interrupted case studies to improve critical thinking in the context of experimental design and the conventions of data interpretation. Students were assessed using further case studies designed to evaluate their ability to recognize and articulate problematic approaches to these elements of experimentation. Our work reveals that case studies have broad utility in the classroom. In addition to demonstrating a small but statistically significant increase in the number of students capable of critically evaluating selected aspects of experimental design, we also observed increased student engagement and documented widespread misconceptions regarding the conventions of data acquisition and analysis.

11.
Augment Altern Commun ; 23(2): 177-86, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17487630

ABSTRACT

The purpose of the current research was to investigate the intelligibility of synthesized speech in noise, when listeners are able to watch an individual using augmentative and alternative communication (AAC) formulate messages on-line and when they are listening to a speaker without any visual information. A total of 80 participants were randomly assigned to four groups, with 20 participants in each group. Each group listened to sentences delivered using a different message formulation strategy: prestored; audibly formulated (messages are formulated on-line and the listener is able to hear the formulation as the message is being encoded); audibly formulated with no repeat (the full sentence at the end is not repeated); and quietly formulated (the message is formulated on-line, but the listener is not able to hear the system feedback throughout the formulation). The speaker for this study was a 35-year-old woman with cerebral palsy who used a VOCA with DECTalk (Beautiful Betty, American English) to communicate. Half of the sentences were presented in an auditory-only condition and half were presented in an auditory-visual condition. The dependent variable was intelligibility, as measured by the percentage of words correctly transcribed by each listener. The overall intelligibility of the sentences in the Audibly Formulated with No Repeat group was statistically significantly lower than in each of the other message formulation type groups. Visual information did not have an effect on intelligibility for this speaker. Clinical implications, limitations, and directions for future research and development are discussed.


Subject(s)
Cerebral Palsy/rehabilitation , Communication Aids for Disabled , Noise , Speech Intelligibility , Speech Perception , Acoustic Stimulation , Adolescent , Adult , Communication , Female , Humans , Male , Photic Stimulation , United States
12.
Differentiation ; 73(5): 212-21, 2005 Jun.
Article in English | MEDLINE | ID: mdl-16026543

ABSTRACT

An exostosis or osteochondroma is an aberrant bony growth occurring next to the growth plate either as an isolated growth abnormality or as part of the Hereditary Multiple Exostosis (HME) syndrome. Mutations in either exostosin 1 (EXT1) or exostosin 2 (EXT2) gene cause the HME syndrome and also some isolated osteochondromas. The EXT1 and EXT2 genes are glycosyltransferases that function as hetero-oligomers in the Golgi to add repeating glycosaminoglycans (GAGs) to heparan sulfate (HS) chains. Previously, we demonstrated that HS is markedly diminished in the exostosis cartilage cap and that the HS proteoglycan, perlecan, has an abnormal distribution in these caps. The present studies were undertaken to evaluate which chondrocyte-specific functions are associated with diminished HS synthesis in human chondrocytes harboring either EXT1 or EXT2 mutations. Systematic evaluation of exostosis cartilage caps and chondrocytes, both in vitro and in vivo, suggests that chondrocyte-specific cell functions account for diminished HS levels. In addition, we provide evidence that perichondrial cells give rise to chondrocytes that clonally expand and develop into an exostosis. Undifferentiated EXT chondrocytes synthesized amounts of HS similar to control chondrocytes; however, EXT chondrocytes displayed very poor survival in vitro under conditions that promote normal chondrocyte differentiation with high efficiency. Collectively, these observations suggest that loss of one copy of either the EXT1 or EXT2 gene product compromises the perichondrial chondrocytes' ability to differentiate normally and to survive in a differentiated state in vitro. In vivo, these compromised responses may lead to abnormal chondrocyte growth, perhaps from a perichondrial stem cell reserve.


Subject(s)
Cell Differentiation/physiology , Chondrocytes/metabolism , Exostoses/metabolism , Heparitin Sulfate/metabolism , Cells, Cultured , Chondrocytes/cytology , Chondrocytes/pathology , Collagen Type II , Exostoses/pathology , Humans , Mutation , N-Acetylglucosaminyltransferases/biosynthesis , N-Acetylglucosaminyltransferases/genetics
13.
Matrix Biol ; 23(8): 525-33, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15694129

ABSTRACT

Cartilage oligomeric matrix protein (COMP) is a large extracellular pentameric glycoprotein found in the territorial matrix surrounding chondrocytes. More than 60 unique COMP mutations have been identified as causing two skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED/EDM1). Recent studies demonstrate that calcium-binding and calcium induced protein folding differ between wild type and mutant COMP proteins and abnormal processing of the mutant COMP protein causes the characteristic large lamellar appearing rough endoplasimic reticulum (rER) cisternae phenotype observed in PSACH and EDMI growth plate chondrocytes. To understand the cellular events leading to this intracellular phenotype, PSACH chondrocytes with a G427E, D469del and D511Y mutations were grown in 3-D culture to produce cartilage nodules. Each nodule was assessed for the appearance and accumulation of cartilage-specific proteins within the rER and for matrix protein synthesis. All three COMP mutations were associated with accumulation of COMP in the rER cisternae by 4 weeks in culture, and by 8 weeks the majority of chondrocytes had the characteristic cellular phenotype. Mutations in COMP also affect the secretion of type IX collagen and matrilin-3 (MATN3) but not the secretion of aggrecan and type II collagen. COMP, type IX collagen and MATN3 were dramatically reduced in the PSACH matrices, and the distribution of these proteins in the matrix was diffuse. Ultrastructural analysis shows that the type II collagen present in the PSACH matrix does not form organized fibril bundles and, overall, the matrix is disorganized. The combined absence of COMP, type IX collagen and MATN3 causes dramatic changes in the matrix and suggests that these proteins play important roles in matrix assembly.


Subject(s)
Cartilage/cytology , Cartilage/ultrastructure , Chondrocytes/metabolism , Collagen Type IX/physiology , Extracellular Matrix Proteins/genetics , Extracellular Matrix Proteins/physiology , Glycoproteins/genetics , Glycoproteins/physiology , Calcium/metabolism , Cartilage/metabolism , Cartilage/pathology , Cartilage Oligomeric Matrix Protein , Chondrocytes/cytology , Collagen Type II/chemistry , Collagen Type IX/chemistry , Dwarfism/genetics , Endoplasmic Reticulum/metabolism , Extracellular Matrix Proteins/chemistry , Humans , Matrilin Proteins , Microscopy, Fluorescence , Mutation , Phenotype , Protein Binding , Protein Folding , Time Factors
14.
J Orthop Res ; 22(4): 759-67, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15183431

ABSTRACT

Cartilage oligomeric matrix protein (COMP) is a large extracellular matrix protein expressed in cartilage, ligament and tendon. Mutations in the COMP gene cause two dominantly inherited skeletal dysplasias, pseudoachondroplasia (PSACH) and Multiple Epiphyseal Dysplasia (MED/EDM1). We report on a novel point mutation D511Y in the seventh calcium-binding repeat of the COMP gene and the resulting iliac crest growth plate pathology. The PSACH iliac crest growth plate is comprised of a large region of resting chondrocytes above a narrow region composed of clusters of disorganized proliferative and hypertrophic chondrocytes. Chondrocytes in all zones show massive intracellular retention of COMP and the surrounding extracellular matrix is deficient in COMP. Moreover, the 511Y COMP mutation selectively affects type IX collagen as little is found in the growth plate matrix whereas type II collagen and aggrecan are abundant in the matrix. Chondrocyte remnants are observed in the chondrocyte clusters and dead cells are found throughout the growth plate. Apoptosis studies demonstrate an unusual pattern of TUNEL staining in the PSACH chondrocytes compared to the control growth plate. These in vivo findings support our previous observation that retention of COMP leads to chondrocyte death. These results also add to the increasing evidence that PSACH and EDM1 are rER storage diseases and that impaired linear growth and joint erosion are caused by the disruptive effect of massive amounts of COMP within the chondrocytes.


Subject(s)
Achondroplasia/pathology , Apoptosis , Chondrocytes/pathology , Collagen Type X/metabolism , Extracellular Matrix Proteins/metabolism , Glycoproteins/metabolism , Growth Plate/metabolism , Achondroplasia/genetics , Achondroplasia/metabolism , Aggrecans , Cartilage Oligomeric Matrix Protein , Child , Chondrocytes/metabolism , Collagen Type II/metabolism , Collagen Type X/genetics , DNA Mutational Analysis , Extracellular Matrix/metabolism , Extracellular Matrix Proteins/genetics , Female , Glycoproteins/genetics , Growth Plate/pathology , Humans , Ilium , Immunoenzyme Techniques , In Situ Nick-End Labeling , Lectins, C-Type , Matrilin Proteins , Point Mutation , Proteoglycans/metabolism
15.
Int J Biochem Cell Biol ; 36(6): 1005-12, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15094116

ABSTRACT

Pseudoachondroplasia (PSACH) is a well-characterized dwarfing condition associated with disproportionate short stature, abnormal joints and osteoarthritis requiring joint replacement. PSACH is caused by mutations in cartilage oligomeric matrix protein (COMP). COMP, the fifth member of the thrombospondin (TSP) gene family, is a pentameric protein found primarily in the extracellular matrix of musculoskeletal tissues. Functional studies have shown that COMP binds types II and IX collagens but the role of COMP in the extracellular matrix remains to be defined. Mutations in COMP interfere with calcium-binding and protein conformation. PSACH growth plate and growth plate chondrocytes studies indicate that COMP mutations have a dominant negative effect with both COMP and type IX collagen being retained in large rER cisternae. This massive retention causes impaired chondrocyte function with little COMP secreted into the matrix and premature loss of chondrocytes. Deficiency of linear growth results from loss of chondrocytes from the growth plate. Secondarily, the matrix contains minimal COMP, which may be normal and/or mutant, and little type IX collagen. This deficiency results in abnormal joints that are easily eroded and cause painful osteoarthritis. Unlike other misfolded proteins that are targeted for degradation, much of the retained COMP escapes degradation, compromises cell function, and causes cell death. Gene therapy will need to target the reduction of COMP in order to restore normal chondrocyte function and longevity.


Subject(s)
Dwarfism/genetics , Extracellular Matrix Proteins/genetics , Extracellular Matrix Proteins/physiology , Glycoproteins/genetics , Glycoproteins/physiology , Osteochondrodysplasias/genetics , Achondroplasia/genetics , Achondroplasia/therapy , Cartilage Oligomeric Matrix Protein , Chondrocytes/pathology , Dwarfism/therapy , Extracellular Matrix Proteins/metabolism , Glycoproteins/metabolism , Humans , Matrilin Proteins , Mutation/genetics , Osteochondrodysplasias/therapy , Protein Structure, Tertiary/genetics , Thrombospondins/genetics
16.
Chem Commun (Camb) ; (19): 2408-9, 2003 Oct 07.
Article in English | MEDLINE | ID: mdl-14587705

ABSTRACT

A novel family of redox-active dinuclear transition metal based cryptands self-assembled from dithiocarbamate ligands has been synthesised; depending upon the nature of the spacer groups these new cryptand systems have been shown to electrochemically recognise the binding of cations or anions.

17.
Nat Med ; 9(7): 928-35, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12819779

ABSTRACT

The highly polymorphic human leukocyte antigen (HLA) class I molecules help to determine the specificity and repertoire of the immune response. The great diversity of these antigen-binding molecules confers differential advantages in responding to pathogens, but presents a major obstacle to distinguishing HLA allele-specific effects. HLA class I supertypes provide a functional classification for the many different HLA alleles that overlap in their peptide-binding specificities. We analyzed the association of these discrete HLA supertypes with HIV disease progression rates in a population of HIV-infected men. We found that HLA supertypes alone and in combination conferred a strong differential advantage in responding to HIV infection, independent of the contribution of single HLA alleles that associate with progression of the disease. The correlation of the frequency of the HLA supertypes with viral load suggests that HIV adapts to the most frequent alleles in the population, providing a selective advantage for those individuals who express rare alleles.


Subject(s)
HIV Infections/genetics , HIV Infections/immunology , HLA Antigens/genetics , Amino Acid Motifs , Blood/virology , Disease Progression , Genetic Predisposition to Disease , Genetic Variation , HLA Antigens/metabolism , Homozygote , Humans , Male , Predictive Value of Tests , RNA, Viral/metabolism , Viral Proteins/metabolism
18.
Inorg Chem ; 42(4): 1371-7, 2003 Feb 24.
Article in English | MEDLINE | ID: mdl-12588177

ABSTRACT

A novel series of triazine-appended macrocyclic complexes has been investigated as potential hydrogen bonding receptors for complementarily disposed heterocycles. Cocrystallization of a melamine-appended azacyclam complex of Cu(II) has been achieved with barbitone, the barbiturate anion and thymine. In each case, a complementary DAD/ADA hydrogen bonding motif between the melamine group and the heterocycle has been identified by X-ray crystallography. Electrochemical studies of the copper macrocycles in both nonaqueous and aqueous solution show anodic shifts of the Cu(II/)(I) redox couple of more than 60 mV upon addition of guest molecules with matching H-bonding motifs. The Zn(II) analogues have been synthesized via transmetalation of the Cu(II) complex, and their guest binding properties investigated by NMR spectroscopy. (1)H NMR shifts of up to 0.8 ppm were observed upon addition of guest, and stability constants are similar to those obtained electrochemically.

19.
Inorg Chem ; 41(11): 2892-902, 2002 Jun 03.
Article in English | MEDLINE | ID: mdl-12033897

ABSTRACT

A series of crown ether appended macrocyclic amines has been prepared comprising benzo-12-crown-4, benzo-15-crown-5, or benzo-18-crown-6 attached to a diamino-substituted cyclam. The Co(III) complexes of these three receptors have been prepared and characterized spectroscopically and structurally. Crystal structures of each receptor in complex with an alkali metal ion and structures of the benzo-12-crown-4 and benzo-15-crown-5-receptors without guest ions are reported. 2D NMR and molecular mechanics modeling have been used to examine conformational variations upon guest ion complexation. Addition of cations to these receptors results in an appreciable anodic shift in the Co(III/II) redox potential, even in aqueous solution, but little cation selectivity is observed. Evidence for complex formation has been corroborated by (23)Na and (7)Li NMR spectroscopy and electrospray mass spectrometry.

20.
Inorg Chem ; 37(17): 4214-4219, 1998 Aug 24.
Article in English | MEDLINE | ID: mdl-11670554

ABSTRACT

The macrocyclic compounds (6-(4',6'-diamino-1',3',5'-triazinyl)-1,4,6,8,11-pentaazacyclotetradecane)copper(II) triperchlorate dihydrate, [Cu(HL(2))](ClO(4))(3).2H(2)O, (6-(6'-amino-4'-oxo-1'H-1',3',5'-triazinyl)-1,4,6,8,11-pentaazacyclotetradecane)copper(II) diperchlorate hydrate, [CuL(3)](ClO(4))(2).H(2)O, and [(6-(4',6'-dioxo-1'H-1',3',5'-triazinyl)-1,4,6,8,11-pentaazacyclotetradecane)copper(II)] diperchlorate, [CuL(4)](ClO(4))(2), have been synthesized. The macrocycles synthesized contain respectively pendant melamine, ammeline, and ammelide rings. The X-ray cyrstallographic analyses of [Cu(HL(2))](ClO(4))(3).2H(2)O, triclinic, space group P&onemacr;, a = 9.489(10) Å, b = 12.340(2) Å, c = 24.496(4) Å, alpha = 87.74(10) degrees, beta = 85.51(10) degrees, gamma = 70.95(10) degrees, and Z = 4, and {[CuL(3)](ClO(4))(2).H(2)O}(2), monoclinic, space group C2/c, a = 18.624(8) Å, b = 17.160(2) Å, c = 15.998(6) Å, beta = 117.82(2) degrees, and Z = 4, are reported. The structure of [Cu(HL(2))](ClO(4))(3).2H(2)O shows the formation of linear tapes, formed by a combination of hydrogen bonds and pi-pi stacking interactions. The structure of [CuL(3)](ClO(4))(2).H(2)O displays formation of dimers, formed by a coordinate bond from the oxygen in one molecule to the copper atom of another. The tautomeric forms of the ammeline and ammelide moieties have been determined. The potential of these compounds as subunits for cocrystallization has been investigated.

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