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Glucocorticosteroids (GCS) have been frequently used for a number of dermatologic conditions since the early 1950s. These drugs continue to be very efficacious, yet there are serious side effects associated with their longterm use. Significant complications produced by GCS can be minimized by proper management and precautions. All health care professionals should be aware of these strategies and nursing personnel can play a vital role in helping patients adhere to the guidelines of preventing adverse events. [ABSTRACT FROM AUTHOR]

1 The efficacy of labetalol in the treatment of severe hypertension (diastolic greater than or equal to 115 mm Hg) was studied retrospectively. Ten patients were followed for more than 6 months. At 6 months, eight were well controlled and the mean dose in those was 975 mg daily. Four of these were receiving labetalol alone; two were on labetalol and diuretic only. 2 Three patients were resistant to doses of 1600, 1800 and 2400 mg daily respectively; two of these were controlled with increased doses of vasodilator drugs. In two cases labetalol had produced large falls in the standing BP while not influencing the supine BP. 3 Three other resistant patients were seen, of whom one merely required an increase in dose to 2200 mg daily and the addition of a diuretic. Both the others were elderly, had severe vascular disease, and suffered disabling postural hypotension on a dose of labetalol which did not influence the supine BP. 4 Labetalol can control severe hypertension. There remain patients whose supine BP is not influenced by a dose of labetalol which produces marked postural hypotension. [ABSTRACT FROM AUTHOR]

Objectives: To describe the incidence of head and neck trauma related to electric bicycles and to characterize head and neck injury patterns seen in electric bicycle (eBike) users versus pedal bicyclists in the United States., Methods: The National Electronic Injury Surveillance System (NEISS) was queried from 2009 to 2020 for patients with head and neck injuries related to electric and pedal bicycles. Extracted data included patient demographics, injury patterns, hospital admission, and helmet use. Univariate chi-squared analyses were performed to compare demographics and injury patterns between bicycle groups. Effect sizes were reported with Cramer V values (V)., Results: The incidence of eBike-related head and neck injuries increased from 2993 in 2009 to 9916 in 2020. Compared to pedal bicycle users, eBike users were more likely to have head injuries (60.4% vs. 52.0%) and fractures (10.9% vs. 6.0%), and were more likely to require hospitalization (20.6% vs. 10.4%). The effect size of helmet use was significantly greater in eBike users compared to pedal bicyclists when examining distributions of age group (V = 0.203 vs. V = 0.079), injury location (V = 0.220 vs. V = 0.082), and injury type (V = 0.162 vs. V = 0.059). Helmeted injuries in eBike users more commonly involved neck injuries and sprains, rather than head injuries and fractures., Conclusion: Head and neck trauma related to eBike use is increasing in the United States. Injury patterns and admission rates reflect greater injury severity in eBike users compared to pedal bicyclists. Helmet use may be particularly beneficial in mitigating head and neck injury in eBike users., Level of Evidence: 3 Laryngoscope, 134:2734-2740, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of infections to date and has led to a worldwide pandemic. Most patients had a complete recovery from the acute infection, however, a large number of the affected individuals experienced symptoms that persisted more than 3 months after diagnosis. These symptoms most commonly include fatigue, memory difficulties, brain fog, dyspnea, cough, and other less common ones such as headache, chest pain, paresthesias, mood changes, muscle pain, and weakness, skin rashes, and cardiac, endocrine, renal and hepatic manifestations. The treatment of this syndrome remains challenging. A multidisciplinary approach to address combinations of symptoms affecting multiple organ systems has been widely adopted. This narrative review aims to bridge the gap surrounding the broad treatment approaches by providing an overview of multidisciplinary management strategies for the most common long COVID conditions., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Prusinski et al.)

Objective: To evaluate the impact of age and frailty on 30-day outcomes following surgery for oral squamous cavity carcinoma (OSCC)., Study Design: Retrospective cross-sectional analysis., Setting: American College of Surgeons' National Quality Improvement Program (NSQIP) database., Methods: Patients who underwent OSCC resection were queried via NSQIP (2015-2020). Cases were stratified by age (18-65, 65-75, and older than 75) as well as by modified frailty index scores (mFI 0, mFI 1, and mFI 2+) for comparative analyses. Univariate and multivariable analyses were conducted to examine demographics, perioperative outcomes, and 30-day postoperative adverse events., Results: A total of 3238 patients who underwent OSCC surgery were identified and categorized as nongeriatric ("NGA," age 18-65), younger geriatric ("YGA," age 65-75), and older geriatric ("OGA," age >75) adults. Compared to NGA, geriatric patients had higher the American Society of Anesthesiologists classification, higher modified frailty index scores, and more comorbidities such as hypertension, congestive heart failure, chronic obstructive disease, and diabetes (p < .001). YGAs and OGAs were also less likely to undergo neck dissection (p < .001), composite resection (p = .006), and free flap reconstruction compared to NGAs (p < .001). When controlling for confounders, age was not independently associated with an increased risk of poor outcomes. On the other hand, frailty was found to be independently associated with a higher risk of adverse events (odds ratio: 1.40 [1.15-1.70], p < .001 for mFI 1, odds ratio: 1.45 [1.04-2.02], p = .027 for mFI 2+)., Conclusion: A higher mFI score, not older age, is associated with an increased risk of 30-day complications following OSCC surgery., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Antiestrogen medication is the only chemoprevention currently available for women at a high risk of developing breast cancer; however, antiestrogen therapy requires years to achieve efficacy and has adverse side effects. Therefore, it is important to develop an efficacious chemoprevention strategy that requires only a short course of treatment. PIK3CA is commonly activated in breast atypical hyperplasia, the known precancerous precursor of breast cancer. Targeting PI3K signaling in these precancerous lesions may offer a new strategy for chemoprevention. Here, we first established a mouse model that mimics the progression from precancerous lesions to breast cancer. Next, we demonstrated that a short-course prophylactic treatment with the clinically approved PI3K inhibitor alpelisib slowed early lesion expansion and prevented cancer formation in this model. Furthermore, we showed that alpelisib suppressed ex vivo expansion of patient-derived atypical hyperplasia. Together, these data indicate that the progression of precancerous breast lesions heavily depends on the PI3K signaling, and that prophylactic targeting of PI3K activity can prevent breast cancer., Prevention Relevance: PI3K protein is abnormally high in breast precancerous lesions. This preclinical study demonstrates that the FDA-approved anti-PI3K inhibitor alpelisib can prevent breast cancer and thus warrant future clinical trials in high-risk women., (©2022 American Association for Cancer Research.)

Purpose: Phonological representations are important for reading. In the current work, we examine the relationship between speech-perceptual memory encoding and consolidation to reading ability in skilled adult readers., Method: Seventy-three young adults (age 18-24) were first tested in their word and nonword reading ability, and then trained in the late evening to identify an unfamiliar speech sound contrast (Hindi retroflex-dental). Participants were assessed in their ability to perceive the target contrast immediately before training, after training, and 12 hours later., Results: While perceptual performance on the target at any time point was unassociated with reading ability, overnight changes to the post-training perceptual ability over the 12-hour delay was significantly associated with nonword reading (i.e. decoding) ability, but not real-word reading., Conclusion: These results provide preliminary support for the hypothesis that individual differences in memory processes that update phonological representations following acoustic-phonetic exposure relate to decoding performance, including in adulthood., Competing Interests: Conflict of interest statement The authors have no conflict of interest to report in relation to this work.

Competing Interests: The authors have no financial conflicts of interest to disclose.

Teaching the processes of transcription and translation is challenging due to the intangibility of these concepts and a lack of instructional, laboratory-based, active learning modules. Harnessing the genetic code in vitro with cell-free protein synthesis (CFPS) provides an open platform that allows for the direct manipulation of reaction conditions and biological machinery to enable inquiry-based learning. Here, we report our efforts to transform the research-based CFPS biotechnology into a hands-on module called the "Genetic Code Kit" for implementation into teaching laboratories. The Genetic Code Kit includes all reagents necessary for CFPS, as well as a laboratory manual, student worksheet, and augmented reality activity. This module allows students to actively explore transcription and translation while gaining exposure to an emerging research technology. In our testing of this module, undergraduate students who used the Genetic Code Kit in a teaching laboratory showed significant score increases on transcription and translation questions in a post-lab questionnaire compared with students who did not participate in the activity. Students also demonstrated an increase in self-reported confidence in laboratory methods and comfort with CFPS, indicating that this module helps prepare students for careers in laboratory research. Importantly, the Genetic Code Kit can accommodate a variety of learning objectives beyond transcription and translation and enables hypothesis-driven science. This opens the possibility of developing Course-Based Undergraduate Research Experiences (CUREs) based on the Genetic Code Kit, as well as supporting next-generation science standards in 8-12th grade science courses., (Copyright © 2020 Williams, Gregorio, So, Kao, Kiste, Patel, Watts and Oza.)

Background: Nonsurgical rhinoplasty using filler injections has become a common procedure in cosmetic practices. This is offered to patients that prefer a temporary outcome or would like to avoid general anesthesia. In addition, it can be used in postrhinoplasty patients to correct nasal deformities or irregularities. This systematic review highlights common filler types and injection techniques, and associated patient satisfaction and complications to further guide practitioners., Methods: A systematic review was performed using keywords and Medical Subject Headings search terms. PubMed, EmBase, the Cochrane Library, and Scopus were searched using the appropriate search terms. Data collected from each study included patient satisfaction and complications, in addition to injection material, location, and technique., Results: Four thousand six hundred thirty-two studies were found based on search criteria. After full-text screening for inclusion and exclusion criteria, 23 studies were included. A total of 1600 patients underwent nonsurgical rhinoplasty, most commonly with hyaluronic acid (73.38 percent), followed by calcium hydroxyapatite (12.44 percent). Nearly 95 percent of patients were satisfied with results, and there were only 26 relatively minor complications reported. There were no reports of vascular complications such as skin necrosis or visual compromise., Conclusions: Based on the authors' review of the literature, nonsurgical rhinoplasty is an effective temporary alternative to traditional augmentation rhinoplasty for corrections of nasal shape with a high degree of patient satisfaction. Complications may be underreported, and thus further investigation is needed to better understand the true incidence of major complications related to vascular compromise.

Cell-free protein synthesis (CFPS) is a platform biotechnology that enables a breadth of applications. However, field applications remain limited due to the poor shelf-stability of aqueous cell extracts required for CFPS. Lyophilization of E. coli extracts improves shelf life but remains insufficient for extended storage at room temperature. To address this limitation, we mapped the chemical space of ten low-cost additives with four distinct mechanisms of action in a combinatorial manner to identify formulations capable of stabilizing lyophilized cell extract. We report three key findings: (1) unique additive formulations that maintain full productivity of cell extracts stored at 4 °C and 23 °C; (2) additive formulations that enhance extract productivity by nearly 2-fold; (3) a machine learning algorithm that provides predictive capacity for the stabilizing effects of additive formulations that were not tested experimentally. These findings provide a simple and low-cost advance toward making CFPS field-ready and cost-competitive for biomanufacturing.

The metal-to-insulator transition (MIT) closest to room temperature of 68-70 °C as shown by vanadium oxide (VO 2 ), compared with other transition metal oxides, makes it a potential candidate for smart window coating. We have successfully fabricated a potential smart window device after the optimum design of a multilayered thin film structure made out of transparent conducting oxide (aluminum doped zinc oxide) and pure VO 2 using pulsed laser deposition technique. This comprehensive study is based on two different configurations for multi-layered structure approach, with the intention to reduce the transition temperature, as well as to maintain the MIT properties that would strengthen the potential of the structure to be used for a smart window device. By creating a multi-layered structure, we were able to create a low powered device that can operate less than 15 V that leads to significant decline in the infrared transmission by a magnitude of over 40% and provided sufficient heat to trigger the MIT at a temperature around 60 °C, which is almost 10 °C lower than its bulk counterpart. This finding would positively impact the research on VO 2 thin films, not only as smart windows but also for numerous other applications like bolometers, infrared detectors, Mott transistors and many more.

Purpose: To assess the clinical usefulness of genetic testing in a pediatric population with inherited retinal disease (IRD)., Design: Single-center retrospective case series., Participants: Eighty-five unrelated children with a diagnosis of isolated or syndromic IRD who were referred for clinical genetic testing between January 2014 and July 2016., Methods: Participants underwent a detailed ophthalmic examination, accompanied by electrodiagnostic testing (EDT) and dysmorphologic assessment where appropriate. Ocular and extraocular features were recorded using Human Phenotype Ontology terms. Subsequently, multigene panel testing (105 or 177 IRD-associated genes) was performed in an accredited diagnostic laboratory, followed by clinical variant interpretation., Main Outcome Measures: Diagnostic yield and clinical usefulness of genetic testing., Results: Overall, 78.8% of patients (n = 67) received a probable molecular diagnosis; 7.5% (n = 5) of these had autosomal dominant disease, 25.4% (n = 17) had X-linked disease, and 67.2% (n = 45) had autosomal recessive disease. In a further 5.9% of patients (n = 5), a single heterozygous ABCA4 variant was identified; all these participants had a spectrum of clinical features consistent with ABCA4 retinopathy. Most participants (84.7%; n = 72) had undergone EDT and 81.9% (n = 59) of these patients received a probable molecular diagnosis. The genes most frequently mutated in the present cohort were CACNA1F and ABCA4, accounting for 14.9% (n = 10) and 11.9% (n = 8) of diagnoses respectively. Notably, in many cases, genetic testing helped to distinguish stationary from progressive IRD subtypes and to establish a precise diagnosis in a timely fashion., Conclusions: Multigene panel testing pointed to a molecular diagnosis in 84.7% of children with IRD. The diagnostic yield in the study population was significantly higher compared with that in previously reported unselected IRD cohorts. Approaches similar to the one described herein are expected to become a standard component of care in pediatric ophthalmology. We propose the introduction of genetic testing early in the diagnostic pathway in children with clinical and/or electrophysiologic findings, suggestive of IRD., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

This study examined whether beliefs about face recognition ability differentially influence memory retrieval in older compared to young adults. Participants evaluated their ability to recognise faces and were also given information about their ability to perceive and recognise faces. The information was ostensibly based on an objective measure of their ability, but in actuality, participants had been randomly assigned the information they received (high ability, low ability or no information control). Following this information, face recognition accuracy for a set of previously studied faces was measured using a remember-know memory paradigm. Older adults rated their ability to recognise faces as poorer compared to young adults. Additionally, negative information about face recognition ability improved only older adults' ability to recognise a previously seen face. Older adults were also found to engage in more familiarity than item-specific processing than young adults, but information about their face recognition ability did not affect face processing style. The role that older adults' memory beliefs have in the meta-cognitive strategies they employ is discussed.

Aims: Due to the paucity of studies focusing on primary glomerulonephritis, the second commonest cause of end-stage-kidney-disease in most of the developed world, we sought to review outcomes of these renal pathologies., Methods: We reviewed renal outcomes and mortality for primary glomerulonephritis patients enrolled in the New Zealand Glomerulonephritis Study between 1972 and 1983., Results: There were 765 patients with median follow-up of 30 years (range 0.1-42 years). They were predominantly New Zealand European, male and hypertensive. Poor renal outcomes and increased mortality were associated with hypertension, heavy proteinuria, impaired renal function and older age at diagnosis. Ethnicity was not significantly associated with progression to end-stage-kidney-disease although NZ Maori patients were at significantly increased risk of death. Patients with rapidly progressive glomerulonephritis had the highest risk of reaching end-stage-kidney-disease while the cumulative incidence of end-stage-kidney-disease was 20% and 30% for those with immunoglobulin-A nephropathy and membranous nephropathy respectively. Mortality risk was high for patients with rapidly progressive glomerulonephritis and anti-glomerular basement membrane disease. The era of diagnosis did not have much effect on outcomes except for patients with focal segmental glomerulosclerosis or immunoglobulin A nephropathy but this could be type II error., Conclusion: We report one of the longest follow-up studies on biopsy-proven glomerulonephritides. Age, hypertension, and severity of chronic kidney disease at diagnosis were strong predictors of the development of end-stage-kidney-disease and death. The specific renal pathology had a profound impact upon prognosis and therefore should continue to drive efforts to find targeted therapeutic options for these glomerulonephritides., (© 2015 Asian Pacific Society of Nephrology.)

The transcription factor ThPOK promotes CD4(+) T cell differentiation in the thymus. Here, using a mouse strain that allows post-thymic gene deletion, we show that ThPOK maintains CD4(+) T lineage integrity and couples effector differentiation to environmental cues after antigenic stimulation. ThPOK preserved the integrity and amplitude of effector responses and was required for proper differentiation of types 1 and 2 helper T cells in vivo by restraining the expression and function of Runx3, a nuclear factor crucial for cytotoxic T cell differentiation. The transcription factor LRF acts redundantly with ThPOK to prevent the transdifferentiation of mature CD4(+) T cells into CD8(+) T cells. As such, the ThPOK-LRF transcriptional module was essential for CD4(+) T cell integrity and responses.

Background: Oxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity., Methodology: 165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100., Principal Findings: There was wide variation in SaO2 on air (78.5-99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up., Significance: Haemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses.

Caring for young infants can be stressful. Non-accidental brain or head injury (shaken baby syndrome) is a result of parental stress, and a lack of knowledge of how to respond to a crying infant and the dangers of shaking a child. This article demonstrates the value of international collaboration in projects to prevent child maltreatment. It includes reports of prevention of shaken baby syndrome programmes in Australia, Hungary, Greece, Brazil and Turkey.

Objective: To review the scientific literature on pediatric abusive head trauma as a form of physical abuse against infants and young children, highlighting the prevalence, signs and symptoms, consequences, risk factors for its occurrence, and prevention strategies., Data Source: The MEDLINE, SciELO, LILACS, and Web of Science databases from 2001 to 2012 were reviewed, using the terms "shaken baby syndrome" and "abusive head trauma" in English, Spanish, and Portuguese., Data Synthesis: Pediatric abusive head trauma is defined as injury to the skull or intracranial contents of a infant or child younger than 5 years due to intentional abrupt impact and/or violent shaking. It occurs mainly in infants and children under 1 year of age, and may result in severe consequences, from physical or mental disabilities to death. Although there are specific signs for this form of abuse, they can be mistaken for common illnesses in children or accidental head injury; thus, clinical training of professionals involved in the assessment of cases to attain the correct diagnosis is crucial. Prevention strategies should include early identification of cases, as well as parental education on child development, especially on the infant's crying pattern., Conclusions: Considering the severity of abusive head trauma in children, it is critical that prevention strategies be implemented and evaluated in the Brazilian context. It is suggested that its incidence indicators be assessed at the national level., (Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Purpose: Assess whether an insurer-provided Web-based wellness program results in cost and utilization improvements., Design: Quasi-experimental, pre-post, treatment-comparison design. Variables of interest were participation rates; medical, professional, and pharmacy expenditures; inpatient admissions; emergency room visits; and preventive service utilization., Setting: Six hundred forty-three employer-based wellness programs in Pennsylvania., Subjects: Forty-seven employers engaged in the Web-based wellness program and 596 employers who were not engaged. The engaged employer group included 10,463 wellness participants; an equal number of matched nonparticipant employees were identified from employers who were not engaged., Intervention: Web-based wellness program features were added to an on-site program in 2004. The program was followed through 2007., Measures: Outcomes were calculated using health insurance enrollment and claims history., Analysis: Participating employees were compared to nonparticipants using generalized linear mixed models to study changes in costs and utilization., Results: During the 2003 baseline year, engaged employers had greater costs, greater chronic disease prevalence, and greater hospitalization. Costs of program participants showed a lower rate of increase in 2004, and then dropped below those of the nonparticipants for the duration of the study. Between 2003 and 2007, the increase in medical expenditures of the participant group was significantly less than that of the nonparticipant group (31% vs. 46%, p < .01). In addition, the participant group showed a lower increase in professional service expenditures (p = .02) and greater utilization of preventive services (p < .01)., Conclusions: Web-based insurer-provided wellness programs may decrease health care costs and encourage preventive service utilization.

The analysis of the human genome has largely been undertaken in a research environment, but recent developments in technology and associated workflow have allowed diagnostic laboratories to interrogate DNA at significantly improved levels of resolution. Principally, whole genome-based analysis of copy number changes using microarrays has led to this method replacing conventional karyotyping as a routine diagnostic workhorse. The resolution offered by microarrays is an improvement of at least an order of magnitude compared to karyotyping, but it comes at a cost in terms of the time spent in data interpretation. Overall, however, the die has been cast and cytogeneticists need to become familiar with the tools use by molecular geneticists and bioinformaticists. The following review provides a brief background to array technology, but uses a series of case studies to illustrate the usefulness and challenges of interpreting array data.

Previous studies indicate that agonists of the group II metabotropic glutamate receptors (mGluRs), mGluR2 and mGluR3, may provide a novel approach for the treatment of anxiety disorders and schizophrenia. However, the relative contributions of the mGluR2 and mGluR3 subtypes to the effects of the group II mGluR agonists remain unclear. In the present study, we describe an alternate synthesis and further pharmacological characterization of a recently reported positive allosteric modulator of mGluR2 termed biphenyl-indanone A (BINA). In recombinant systems, BINA produced a robust and selective potentiation of the response of mGluR2 to glutamate with no effect on the glutamate response of other mGluR subtypes. In hippocampal brain slices, BINA (1 microM) significantly potentiated the mGluR2/3 agonist-induced inhibition of excitatory synaptic transmission at the medial perforant path-dentate gyrus synapse. BINA was also efficacious in several models predictive of antipsychotic- and anxiolytic-like activity in mice. The behavioral effects of BINA were blocked by the mGluR2/3 antagonist (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495), suggesting that the in vivo effects of BINA are mediated by increased activation of mGluR2. Collectively, these results indicate that BINA is a selective mGluR2 positive allosteric modulator and provide further support for the growing evidence that selective allosteric potentiators of mGluR2 mimic many of the in vivo actions of mGluR2/3 agonists that may predict therapeutic utility of these compounds.

The zebrafish (Danio rerio) provides an excellent model for studying vertebrate development and human disease because of its ex utero, optically transparent embryogenesis and amenability to in vivo manipulation. The rapid embryonic developmental cycle, large clutch sizes and ease of maintenance at large numbers also add to the appeal of this species. Considerable genomic data has recently become publicly available that is aiding the construction of zebrafish microarrays, thus permitting global gene expression analysis. The zebrafish is also suitable for chemical genomics, in part as a result of the permeability of its embryos to small molecules and consequent avoidance of external confounding maternal effects. Finally, there is increasing characterization and analysis of zebrafish models of human disease. Thus, the zebrafish offers a high-quality, high-throughput bioassay tool for determining the biological effect of small molecules as well as for dissecting biological pathways.

Although dermatology now has the most extensive group of systemic medications available for the treatment of skin diseases at any time, GCSs remain the most important agents for managing inflammatory disorders. It is important that the dermatologist have a broad knowledge of guidelines for clinical use, pharmacology, and adverse effects of these drugs. Acute and chronic side reactions should be well recognized. An understanding of the HPA axis and reasons for administering GCSs in different ways is of great value. A good medical history should be taken on any patient treated with GCSs, including knowledge of conditions that would make GCSs inadvisable and other concomitant systemic medications that might produce drug interactions. During the course of therapy, physical examination should include all systems pertinent to side effects caused by these agents, including frequent evaluations of weight and blood pressure. Blood chemistries should be performed on a regular basis, including glucose, electrolytes, and serum lipids. Osteoporosis is one of the most significant adverse affects to be evaluated, with bone mineral density studies recommended on an annual basis for persons continuing on GCS therapy. If hip or other joint pain develops, MR imaging is the most specific and sensitive radiologic examination for evaluating the possibility of osteonecrosis. An ophthalmology examination should be performed every 6 to 12 months to detect early cataract or glaucoma development. Any early signs of infection should be evaluated by appropriate smears, wet preparations, and cultures. Many other studies, including gastrointestinal and pulmonary examinations, may be dictated by specific acute situations. It is important to begin early prevention of the bone loss that occurs with GCS-induced osteoporosis. The 1996 guidelines of the American College of Rheumatology, including adequate calcium and vitamin D intake, should be followed. Hormonal replacement, a bisphosphonate, calcitonin, or a thiazide diuretic may be indicated. Restriction of sodium in the diet is important, as well as adequate potassium intake. The diet should be low in saturated fat and calories and should be high in vegetable protein. Because osteoporosis is so prevalent with GCSs, keeping the patient as active as possible with mild-to-moderate exercise is important. Whenever possible, exposure to persons with infectious processes should be avoided, and proper treatment should be instituted at the initial signs of systemic or cutaneous infection. Oral doses of GCSs are best taken with food to prevent gastrointestinal irritation, and agents for gastric acidity occasionally may be indicated. Significant trauma should be prevented, as should severe exposure to the sun. Many situations may call for consultation with other medical or surgical subspecialists. The patient must be aware of the importance of regular physician evaluations and reporting of any adverse effects while on long-term GCSs. A good relationship and understanding between the patient and physician are vital in minimizing potential problems from these agents. If the dermatologist maintains the proper guidelines of care, patients on GCSs have the highest benefits and lowest risks possible.

Specimens of macroscopically inflamed and normal intestine along with mesenteric lymph nodes were obtained at resection from patients with Crohn's disease. The samples were systematically examined by RT-PCR-nested PCR targeting N, M and H gene regions of the measles virus genome. None of the samples examined gave any evidence of the persistence of measles virus in the intestine of Crohn's disease patients. The study supports previous findings produced by this laboratory and others using highly sensitive measles virus specific PCR diagnostic technology.

The zebrafish has been the model of choice amongst developmental biologists for many years. This small freshwater species offers many advantages to the study of organ and tissue development that are not provided by other model systems. Against this background, modern molecular genetic approaches are being applied to expand the physical and genetic mapping of the zebrafish genome. These approaches complement the large-scale mutagenic screens that have led to the isolation of mutant phenotypes. Some of the phenotypes have been found to resemble human disease states, while mapping and sequencing data have revealed zebrafish genes with significant homology to human disease-causing genes. It is the realization that the zebrafish offers an amenable system for understanding disease, as opposed to development, that underpins this review. The adventitious identification of disease phenotypes amongst zebrafish mutants and the important area of deliberate disease modelling using transgenesis and gene targeting should lead to a better application of the zebrafish as a vertebrate model of human diseases.

PCR amplification of the CAG repeat in exon 1 of the IT15 gene is routinely undertaken to confirm a clinical diagnosis of Huntington disease (HD) and to provide predictive testing for at-risk relatives of affected individuals. Our studies have detected null alleles on the chromosome carrying the expanded repeat in three of 91 apparently unrelated HD families. Sequence analysis of these alleles has revealed the same mutation event, leading to the juxtaposition of uninterrupted CAG and CCG repeats. These data suggest that a mutation-prone region exists in the IT15 gene bounded by the CAG and CCG repeats and that caution should be exercised in designing primers that anneal to the region bounded by these repeats. Two of the HD families segregated null alleles with expanded uninterrupted CAG repeats at the lower end of the zone of reduced penetrance. The expanded repeats are meiotically unstable in these families, although this instability is within a small range of repeat lengths. The haplotypes of the disease-causing chromosomes in these two families differ, only one of which is similar to that reported previously as being specific for new HD mutations. Finally, no apparent mitotic instability of the uninterrupted CAG repeat was observed in the brain of one of the HD individuals.

The gene for a highly thermostable neutral proteinase (Npr) was isolated from Bacillus sp. strain EA1 by the polymerase chain reaction using consensus primers based on the sequences of npr genes from related species. The gene was sequenced and shown to be closely related to a neutral proteinase gene from Bacillus caldolyticus strain YP-T; the mature form of the enzyme differing by only a single amino acid. Enzyme samples were prepared from both the native organisms and also from recombinant Escherichia coli expressing the two npr genes. The proteinase from strain EA1 was shown to be significantly more thermostable than that from B. caldolyticus and that this difference is the result of a single amino acid substitution which is situated proximal to a region of the enzyme known to be crucial to conferring thermal stability. The phylogenetic relationship of EA1 to other Bacilli is also described.

A gene expressing xylanase activity was isolated from a genomic library of Thermotoga sp. strain FjSS3-B.1. The sequence of the gene shows that it encodes a single domain, family 10 xylanase. The recombinant enzyme has extremely high thermal stability, activity over a relatively broad pH range, and activity on Pinus radiata kraft pulp.

Serological typing of the streptococcal M protein has recently been challenged by a number of unique molecular methodologies based on oligonucleotide recognition of allelic variations within the M protein (emm) gene. In these methods, stringent hybridization of an oligonucleotide probe to a polymerase chain reaction amplified emm gene is used as confirmation of specific M type identity. A sample of 17 isolates from 7 previously defined distinct genotypes were tested using a single M1 oligonucleotide probe. Isolates from only three of the genotypes hybridized with the probe. The results demonstrate that a single emm-specific oligonucleotide probe can not identify all members of M type 1, as defined by conventional serotyping using polyclonal antisera.

The SSU rRNA gene of the extremely thermophilic bacterium strain AZ3 B.1, encodes an rRNA containing four large inserts. A secondary structure model has been constructed which predicts that the inserts form large stem loop structures with a common sequence motif at the base of the helices. To date, these structures have only been detected in related, thermophilic organisms.

1,490 nucleotides of the 16S rRNA gene of a Gram-negative, thermophilic and gliding bacterium, Thermonema lapsum, have been sequenced. Phylogenetic analysis indicates that T. lapsum is related to cytophaga-flavobacteria-bacteroides (CFB) and is confirmed by the identification signature nucleotides that define this group. Further phylogenetic analysis indicates that T. lapsum forms the deepest branch in the CFB group; this observation was confirmed by the identification of unique nucleotide and nucleotide pairs which separate T. lapsum from all other members of this group. The phospholipid fatty acid (PLFA) profile also confirmed that T. lapsum is related to the cytophaga-flavobacteria-bacteroides group and also to selected members of the genus Flexibacter; the PLFA profile is unique to T. lapsum.

Although the atrioventricular valve and its attachments can sometimes obscure the superior margin of a ventricular septal defect, concern for valvular competence has made surgeons hesitant to take down the atrioventricular valve. Over a 10-year period, the right atrioventricular valve was taken down to improve exposure for ventricular septal defect repair in 40 patients at our institution, and follow-up echocardiographic studies to determine the degree of valvular regurgitation were available in 32. On the basis of the area of the color flow jet, valvular regurgitation was graded as none in 22 and trivial in 10. Heart block did not develop in any patient, and there were no deaths. Takedown and resuspension of the atrioventricular valve is a safe and effective technique that improves exposure for ventricular septal defect repair and does not adversely affect valve competence.