Mutations in DYNC2H1, the cytoplasmic dynein 2, heavy chain 1 motor protein gene, cause short-rib polydactyly type I, Saldino-Noonan type.

The short-rib polydactyly syndromes (SRPS) are autosomal recessively inherited, genetically heterogeneous skeletal ciliopathies. SRPS phenotypes were historically categorized as types I-IV, with type I first delineated by Saldino and Noonan in 1972. Characteristic findings among all forms of SRP include short horizontal ribs, short limbs and polydactyly. The SRP type I phenotype is characterized by a very small thorax, extreme micromelia, very short, poorly mineralized long bones, and multiple organ system anomalies. To date, the molecular basis of this most severe type of SRP, also known as Saldino-Noonan syndrome, has not been determined. We identified three SRP cases that fit the original phenotypic description of SRP type I. In all three cases, exome sequence analysis revealed compound heterozygosity for mutations in DYNC2H1, which encodes the main component of the retrograde IFT A motor, cytoplasmic dynein 2 heavy chain 1. Thus SRP type I, II, III and asphyxiating thoracic dystrophy (ATD), which also result from DYNC2H1 mutations. Herein we describe the phenotypic features, radiographic findings, and molecular basis of SRP type I.

Collagen duplicate genes of bone and cartilage participate during regeneration of zebrafish fin skeleton.

The zebrafish fin is widely used as a model for skeleton regeneration. For years, the nature of the fin skeleton has been controversial as its extracellular matrix shows hybrid characteristics of both bone and cartilage. The presence of co-orthologs genes also increases the complexity of these tissues. In this article, we have identified and described the expression of fibrillar collagens in zebrafish fin skeleton. We found that genes coding for types I, II, V, XI and XXVII collagens are duplicated, showing in several cases, different expression domains. We also identified specific genomic features, such as the presence of type XXIV collagen and the absence of type III collagen in the zebrafish genome. Our study showed that actinotrichia-forming cells and osteoblasts synthesize a wide variety of these fibrillar collagens during fin regeneration. An intertrichial domain expressing most of the collagens was located in the transition between the mesenchyme condensations of actinotrichia and lepidotrichia and may determine an important niche associated with fin skeleton morphogenesis. We also confirmed the hybrid nature of the fin exoskeleton and provided a complete description of those fibrillar collagens expressed during the formation of the fin skeleton.

Effect of Field Crops on Population Densities of Pratylenchus neglectus and P. thornei in Southeastern Australia; Part 1: P. neglectus.

Eighty-one cultivars from 12 field crop species were assessed for suitability as hosts to the root lesion nematode, Pratylenchus neglectus, in two field trials. Host status was assessed on the basis of either final P. neglectus densities in soil or multiplication rate under different crops. Both techniques gave consistent results for crop and cultivar ranking, and it was therefore concluded that, in these trials, final population density could be used for screening cultivars for resistance to P. neglectus. Differences were observed among crops and cultivars for host suitability to P. neglectus. Chickpea, wheat, and canola were good hosts, while barley, oat, durum wheat, medic, and vetch were moderate hosts. Field pea, faba bean, and triticale were poor hosts. A range in host suitability was observed for wheat, barley, and oat cultivars.

Effect of Field Crops on Density of Pratylenchus in SouthEastern Australia; Part 2: P. thornei.

The effect of 93 field crop and pasture cultivars on the end-of-season population densities of Pratylenchus thornei in soil was determined in the field in southeastern Australia. Wheat and barley cultivars had different effects on the population densities of P. thornei. Most commercial wheat cultivars that are grown in southeastern Australia were susceptible, while the barley cultivars were resistant or moderately resistant. Lentil, field pea, fenugreek, linseed, and medic were found to be resistant to P. thornei, while faba bean and canola were moderately resistant and narbon bean, subterranean clover, and vetch were susceptible. This study will enable growers to select rotational crops to reduce the population densities of these nematodes and therefore minimize the yield loss they cause.

Experimental inoculation of avian polyomavirus in chemically and virally immunosuppressed chickens.

The purpose of this series of experiments was to determine the effect of various types of immunosuppressive treatments (cyclophosphamide, infectious bursal disease virus [IBDV], chicken anemia virus [CAV], and combination infection with IBDV and CAV) on susceptibility of chickens to challenge with avian polyomavirus. In the first experiment, chickens were chemically bursectomized with intraperitoneal injections of cyclophosphamide; in the second study, chickens were orally inoculated with IBDV; in the third study, birds were intramuscularly inoculated with CAV; and in the final study, birds were inoculated with both IBDV and CAV. In all experiments, chickens were challenged with 10(4.7) tissue culture infective doses of polyomavirus intraperitoneally. Only chemically bursectomized chickens developed lesions similar to those found in the naturally occurring multisystemic fatal form of polyomavirus infection seen in psittacine nestlings, including hepatic necrosis and large pale intranuclear inclusions.

Effects of clorazepate, diazepam, and oxazepam on a laboratory measurement of aggression in men.

The effects of three benzodiazepines on human aggressive behavior were examined in 44 medically healthy men. Volunteers were administered either placebo, 10 mg diazepam, 15 mg chlorazepate, or 50 mg oxazepam orally using double-blind procedures. Approximately 90 min after drug ingestion, participants were given the opportunity to administer electric shocks to an increasingly provocative fictitious opponent during a competitive reaction-time task. Aggression was defined as the level of shock the participant was willing to administer to the opponent. Results support the notion that diazepam (but not all benzodiazepines) can elicit aggressive behavior under controlled, laboratory conditions. Implications regarding the clinical use of various benzodiazepines for the tranquilization of potentially assaultive patients are discussed.

Accuracy of recall of the legal number plate testing distance by U.K. drivers.

A consecutive sample of 100 drivers attending practice for a routine eye examination were asked to specify the legal vision test distance for compliance with U.K. driving requirements. Also recorded were age, gender, vision uncorrected and acuity. The aim of the study was to investigate the accuracy of estimation by drivers and to determine whether there were any age or gender differences. The results show that 97% of the sample were unable to specify the distance printed in the Highway Code and that 41% underestimated the distance as below 60 feet. This figure is discussed in the context of better education of drivers and the potential role this could have in improving road safety.

The role of transrectal ultrasound-guided biopsy-based staging, preoperative serum prostate-specific antigen, and biopsy Gleason score in prediction of final pathologic diagnosis in prostate cancer.

OBJECTIVES: To evaluate the role of ultra sound-guided systematic and lesion-directed biopsies, biopsy gleason score, preoperative serum prostate-specific antigen (PSA) as three objective and reproducible variables to provide a reliable combination in preoperative identification of risk of extraprostatic extension in patients with clinically localized prostate cancer. METHODS: The case records of 813 patients who underwent radical prostatectomy for clinically localized prostate cancer were analyzed. All had multiple systematic biopsies, two to three from each lobe, in addition to lesion-directed biopsies. Additionally, biopsies were done on seminal vesicles (SVs), if abnormal. Based on biopsy results, patients were classified as having stage B1 (T2a-T2b) or B2 (T2c) disease, depending on whether biopsies from one or both lobes were positive and stage C (T3) if there was evidence of SV involvement by biopsy of biopsies from areas of extracapsular extension as seen on transrectal ultrasound (TRUS) were positive. Logistic regression analyses with log likelihood chi-square test was used to define the correlation between individual as well as combination of preoperative variables and pathologic stage. RESULTS: On final pathologic examination, 473 (58%) patients had organ-confined disease, 188 (23%) had extracapsular extension (ECE), with or without positive surgical margins, and 72 (9%) had SV involvement. Eighty (10%) patients had pelvic lymph node metastases. Biopsy-based staging was superior to clinical staging in predicting final pathologic diagnosis. Logistic regression analyses revealed that the combination of biopsy-based stage, preoperative serum PSA, and biopsy Gleason score provided the best prediction of final pathologic stage. Probability plots constructed with these data can provide significant information on risk of extraprostatic extension in individual patients. CONCLUSIONS: This study demonstrates that TRUS-guided systematic biopsy in combination with preoperative serum PSA and biopsy Gleason score may provide a cost-effective approach for management decisions and prognostication in patients with prostate cancer.

Alcohol and human physical aggression: pharmacological versus expectancy effects.

OBJECTIVE: Research has demonstrated that there is a relationship between alcohol consumption and aggressive behavior. Two basic theoretical positions have been proposed to account for this relationship: the pharmacological perspective and the expectancy perspective. This study examined these two competing explanations of the alcohol-aggression relationship. METHOD: Subjects were 40 males selected from a pool of 233 potential subjects who were interviewed by telephone regarding their alcohol expectancies. Subjects who believed that alcohol increases their aggression and subjects who believed that alcohol decreases their aggression were selected to participate. These subjects were randomly assigned to one of two dose conditions: active-placebo or high dose of alcohol. Subjects were given the opportunity to behave in an aggressive manner within the context of a competitive reaction time task. Aggression was operationalized as the intensity of electric shock subjects set for their opponent during the task. RESULTS: It was found that the high dose of alcohol resulted in significantly higher levels of aggression than the active-placebo dose regardless of subjects' alcohol-aggression expectancies. For the intoxicated subjects, the expectancy that alcohol increases aggressiveness tended to facilitate intense levels of aggression during conditions of high provocation. CONCLUSIONS: The results suggest that the pharmacological effects of alcohol play a primary role in the relationship between alcohol ingestion and aggression.

The Health and Safety (Display Screen Equipment) Regulations 1992.

A European Community directive issued in 1990 set down minimum requirements for health and safety of visual display equipment users. These requirements have now become a legal reality in the UK with the Parliamentary approval of the Health and Safety (Display Screen Equipment) Regulations 1992. While only a relatively small section of the legislation is directly relevant to optometric and dispensing practice it is important that the overall content of the legislation is known by members of these professions to assist them in their work with display screen equipment users. This brief review identifies the elements that make up the new legislation.

A reinvestigation of the D-homoannular rearrangement and subsequent degradation pathways of (11 beta,16 alpha)-9-fluoro-11,16,17,21- tetrahydroxypregna-1,4-diene-3,20-dione (triamcinolone).

The commercial anti-inflammatory drug triamcinolone has been shown to rearrange by similar, but distinct pathways when exposed to certain trace metal ions or to dilute aqueous base. In the presence of aqueous base, the 16-hydroxy-20-keto system undergoes reverse aldol cleavage of the 16,17-bond, followed by aldol cyclization linking C-16 to C-20. This base-catalyzed rearrangement gives a 16 beta,17 alpha-dihydroxy product and a corresponding 16 alpha,17 alpha-dihydroxy product in roughly 4 to 1 ratio. Metal-catalyzed rearrangement provides the 16 alpha,17 alpha-dihydroxy product with extremely high stereoselectivity. Mechanistic models are proposed that help explain the ratio of products isolated from each route. The studies presented suggest that similar forms of rearrangement could be of preparative value in syntheses requiring specific stereochemistry of appropriately substituted bicyclic alpha,beta-dihydroxyketones. Under more vigorous conditions of aqueous base treatment these rearrangement products undergo further decomposition with loss of formaldehyde from the hydroxymethyl group, followed by beta-elimination of water. Reaction of the beta-elimination product with formaldehyde results in the formation of a dimeric species linked by a methylene group.

Effect of alcohol and risk of physical harm on human physical aggression.

Forty male undergraduate students ingested either a high dose of alcohol or a placebo and were provided with feedback regarding their risk of receiving electric shock from an opponent in a competitive reaction-time situation. Intoxicated subjects (blood concentration of 96mg/dL) responded more aggressively than did the sober subjects on measures of physical aggression. Results indicated that the feedback manipulation had no effect on the aggressive responses of the intoxicated subjects. The findings are discussed in terms of current cognitive models of alcohol-related aggression.

Alcohol, drugs and human physical aggression.

Research on the relationship between alcohol, drugs and aggression is reviewed. The findings indicate that alcohol is a potent antecedent of aggressive behavior. Studies conducted in our laboratory demonstrate that aggressive behavior is related to the quantity of alcohol ingested, that the effect of social pressure to aggress and of intense provocation is enhanced by alcohol, that the instigating effect of alcohol depends upon the aggressive disposition of the alcohol consumer, that the aggressive behavior of the intoxicated person can be regulated by altering cues that affect cognitive processes and that other depressant increase aggressive responding. A hypothetical model is described that summarizes the experimental findings and provides a vehicle for discussing the major factors and psychological processes involved in alcohol-induced aggression.

The effect of acetone on the viability of chicken anemia agent.

To study the effect of acetone on the viability of CAA, a sample of CAA with a known titer was treated with 90% acetone for 24 hours at room temperature. The remaining viable CAA was quantitated by titrating the treated preparation in MDCC-MSB1 cell culture. Results indicated that CAA is very resistant to inactivation by acetone.

Effects of long-term visual display terminal usage on visual functions.

Since their rapid introduction into the workplace visual display terminals (VDT's) have been the source of a number of studies aimed at detecting effects on office workers. The published studies have been either short-term or cross-sectional, with one exception. The results have shown varying degrees of relation but by not having a comparable control group all have been limited in their value. We set out to monitor at regular intervals over a 2-year period specific visual functions that have been reported to be affected by VDT usage, and to compare VDT and non-VDT users in the same office environment. By assessing the VDT operators from the time the systems were introduced we have an accurate baseline to work from when assessing change due to the introduction of the VDT.

A methodology for resource allocation in health care for South Africa. Part IV. Application of South African Health Resource Allocation formula.

The primary concern of this concluding article in a series is the application of the South African Health Resource Allocation (SAHRA) formula proposed in the previous article (SAMJ 1990; 77: 456-459). Target allocations based on this formula are compared with current budgets to estimate the extent of geographical maldistribution of health care resources. Under the present health service structure, the direction of redistribution of these resources should be from the provinces to 'homelands'. A number of refinements to the crude formula, such as the introduction of a more rational regionalisation policy and accounting for the teaching commitments of academic hospitals, are considered and their effects illustrated. Despite data deficiencies and the wide range of possible technical modifications to SAHRA, the concept of basing resource allocation decisions on an internationally applied formula is worthy of public debate.

The Optical Services Audit Committee (OSAC) and UK optometry.

In 1989, following a series of legislative moves by the UK Government to remove the 'monopoly' within optical services, a proposal was made to introduce a two-tier system of eye care. Within the two tiers would be a cheap, rapid spectacle prescription assessment that took no account of binocularity or ocular health. The initial response to this within professional groups involved was split, dispensing opticians keen to see the arrival of the system, the optometric profession concerned over the possible health consequences. In order to provide an overview of the situation the General Optical Council proposed the establishment of the Optical Services Audit Committee to investigate the whole of UK eye care services and recommend direction for future developments. The main conclusions of the report produced by this committee are discussed here.

The Opticians Act 1989 and UK optometry.

The build-up to the original 1958 Opticians Act is used as an introduction to the more recent developments in UK optics that have culminated in the introduction of the Opticians Act 1989. The changes introduced as a result of the Health and Social Security Act 1984 and the Health and Medicines Act 1988 are briefly described before discussing the sectional arrangement of the new Act. This new legislation pulls together much of the law relating to optometry and dispensing optics in the UK and provides a single accessible source.

The effects of long-term VDT usage on the nature and incidence of asthenopic symptoms.

An opportunity arose in 1985 to become involved in a transition of working practice from hard copy to VDT. Over a two-year period, 161 VDT users and 65 control subjects in the same office environment were regularly and routinely examined for symptoms of asthenopia. The analysis of data shows that there are no significant differences in type, number and frequency of the work-related symptoms between VDT users and non-VDT users. It appears that reporting of symptoms within the group may be random, although certain symptoms do appear more frequently than others. Additionally, it appears that there is a significant difference between male and female users in the frequency of symptom reporting.