Gene-environment interplay between parent-child relationship problems and externalizing disorders in adolescence and young adulthood.

BACKGROUND: Previous studies have shown that genetic risk for externalizing (EXT) disorders is greater in the context of adverse family environments during adolescence, but it is unclear whether these effects are long lasting. The current study evaluated developmental changes in gene-environment interplay in the concurrent and prospective associations between parent-child relationship problems and EXT at ages 18 and 25 years. METHOD: The sample included 1382 twin pairs (48% male) from the Minnesota Twin Family Study, participating in assessments at ages 18 years (mean = 17.8, s.d. = 0.69 years) and 25 years (mean = 25.0, s.d. = 0.90 years). Perceptions of parent-child relationship problems were assessed using questionnaires. Structured interviews were used to assess symptoms of adult antisocial behavior and nicotine, alcohol and illicit drug dependence. RESULTS: We detected a gene-environment interaction at age 18 years, such that the genetic influence on EXT was greater in the context of more parent-child relationship problems. This moderation effect was not present at age 25 years, nor did parent-relationship problems at age 18 years moderate genetic influence on EXT at age 25 years. Rather, common genetic influences accounted for this longitudinal association. CONCLUSIONS: Gene-environment interaction evident in the relationship between adolescent parent-child relationship problems and EXT is both proximal and developmentally limited. Common genetic influence, rather than a gene-environment interaction, accounts for the long-term association between parent-child relationship problems at age 18 years and EXT at age 25 years. These results are consistent with a relatively pervasive importance of gene-environmental correlation in the transition from late adolescence to young adulthood.

Medication adherence in a comparative effectiveness trial for bipolar disorder.

OBJECTIVE: Psychopharmacology remains the foundation of treatment for bipolar disorder, but medication adherence in this population is low (range 20-64%). We examined medication adherence in a multisite, comparative effectiveness study of lithium. METHOD: The Lithium Moderate Dose Use Study (LiTMUS) was a 6-month, six-site, randomized effectiveness trial of adjunctive moderate dose lithium therapy compared with optimized treatment in adult out-patients with bipolar I or II disorder (N=283). Medication adherence was measured at each study visit with the Tablet Routine Questionnaire. RESULTS: We found that 4.50% of participants reported missing at least 30% of their medications in the past week at baseline and non-adherence remained low throughout the trial (<7%). Poor medication adherence was associated with more manic symptoms and side-effects as well as lower lithium serum levels at mid- and post-treatment, but not with poor quality of life, overall severity of illness, or depressive symptoms. CONCLUSION: Participants in LiTMUS were highly adherent with taking their medications. The lack of association with possible predictors of adherence, such as depression and quality of life, could be explained by the limited variance or other factors as well as by not using an objective measure of adherence.

A review of the evidence on the effectiveness of children's vision screening.

Screening programmes enable health conditions to be identified so that effective interventions can be offered. The aim of this review was to determine: (1) the effectiveness of children's vision screening programmes; (2) at what age children should attend vision screening; and (3) what form vision screening programmes should take to be most effective. A literature review on the effectiveness of vision screening programmes in children aged 0-16 years was undertaken. Eligible studies/reviews were identified through clinical databases, hand searches and consultation with expert reviewers. The methodological quality of papers was rated using National Health and Medical Research Council (NHMRC) guidelines. Screening of children 18 months to 5 years, and subsequent early treatment, led to improved visual outcomes. The benefit was primarily through treatment of amblyopia, with improved visual acuity of the amblyopic eye. However, the overall quality of the evidence was low. The implication of improved visual acuity (e.g. any potential impact on quality of life) was not considered. Without consideration of 'quality of life' values, such as loss of vision in one eye or possibility of future bilateral vision loss, the cost-effectiveness of screening is questionable. Screening and treating children with uncorrected refractive error can improve educational outcomes. Evidence suggested that screening occur in the preschool years. Orthoptists were favoured as screening personnel; however, nurses could achieve high sensitivity and specificity with appropriate training. Further research is required to assess the effectiveness of neonatal screening. Most studies suggested that children's vision screening was beneficial, although programme components varied widely (e.g. tests used, screening personnel and age at testing). Research is required to clearly define any improvements to quality of life and any related economic benefits resulting from childhood vision screening. The evidence could be used to guide optimization of existing programmes.

American Brachytherapy Society Task Group Report: Use of androgen deprivation therapy with prostate brachytherapy-A systematic literature review.

PURPOSE: Prostate brachytherapy (PB) has well-documented excellent long-term outcomes in all risk groups. There are significant uncertainties regarding the role of androgen deprivation therapy (ADT) with brachytherapy. The purpose of this report was to review systemically the published literature and summarize present knowledge regarding the impact of ADT on biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS). METHODS AND MATERIALS: A literature search was conducted in Medline and Embase covering the years 1996-2016. Selected were articles with >100 patients, minimum followup 3 years, defined risk stratification, and directly examining the role and impact of ADT on bPFS, CSS, and OS. The studies were grouped to reflect disease risk stratification. We also reviewed the impact of ADT on OS, cardiovascular morbidity, mortality, and on-going brachytherapy randomized controlled trials (RCTs). RESULTS: Fifty-two selected studies (43,303 patients) were included in this review; 7 high-dose rate and 45 low-dose rate; 25 studies were multi-institutional and 27 single institution (retrospective review or prospective data collection) and 2 were RCTs. The studies were heterogeneous in patient population, risk categories, risk factors, followup time, and treatment administered, including ADT administration and duration (median, 3-12 months);71% of the studies reported a lack of benefit, whereas 28% showed improvement in bPFS with addition of ADT to PB. The lack of benefit was seen in low-risk and favorable intermediate-risk (IR) disease and most high-dose rate studies. A bPFS benefit of up to 15% was seen with ADT use in patients with suboptimal dosimetry, those with multiple adverse risk factors (unfavorable IR [uIR]), and most high-risk (HR) studies. Four studies reported very small benefit to CSS (2%). None of the studies showed OS advantage; however, three studies reported an absolute 5-20% OS detriment with ADT. Literature suggests that OS detriment is more likely in older patients or those with pre-existing cardiovascular disease. Four RCTs with an adequate number of patients and well-defined risk stratification are in progress. One RCT will answer the question regarding the role of ADT with PB in favorable IR patients and the other three RCTs will focus on optimal duration of ADT in the uIR and favorable HR population. CONCLUSIONS: Patients treated with brachytherapy have excellent long-term disease outcomes. Existing evidence shows no benefit of adding ADT to PB in low-risk and favorable IR patients. UIR and HR patients and those with suboptimal dosimetry may have up to 15% improvement in bPFS with addition of 3-12 months of ADT, with uncertain impact on CSS and a potential detriment on OS. To minimize morbidity, one should exercise caution in prescribing ADT together with PB, in particular to older men and those with existing cardiovascular disease. Due to the retrospective nature of this evidence, significant selection, and treatment bias, no definitive conclusions are possible. RCT is urgently needed to define the potential role and optimal duration of ADT in uIR and favorable HR disease.

Use of amphipathic polymers to deliver a membrane protein to lipid bilayers.

Data are presented which suggest that a class of amphiphilic polymers known as 'amphipols' may serve as a vehicle for delivering complex integral membrane proteins into membranes. The integral membrane protein diacylglycerol kinase (DAGK) was maintained in soluble form by either of two different amphipols. Small aliquots of these solutions were added to pre-formed lipid vesicles and the appearance of DAGK catalytic activity was monitored as an indicator of the progress of productive protein insertion into the bilayers. For one of the two amphipols tested, DAGK was observed to productively transfer from its amphipol complex into vesicles with moderate efficiency. Results were not completely clear for the other amphipol.

A methodology for building an AIDS research file using Medicaid claims and administrative data bases.

There is a current and continuing need for health services research on the epidemiology of AIDS and its impact on health care systems. However, large data bases designed for other purposes, such as hospital discharge abstract systems and medical claims systems, are the primary source of data for AIDS research. Thus, methodologies must be developed that enable researchers to investigate AIDS using data bases designed for other purposes. In this report, we describe a methodology for utilizing Medicaid Management Information Systems (MMIS) data to conduct health services research on AIDS. We developed an ICD-9-CM diagnosis-based algorithm that accurately identified the majority of AIDS cases, both before and after AIDS-specific ICD-9-CM codes became available in October 1986. Using diagnostic categories that we had developed previously to identify AIDS cases among disabled young men in California on Medicaid, we expanded the methodology to include children, men, and women of all ages in California and New York. The algorithm worked best with young disabled males, older males, and females between 18 and 50 years of age. The algorithm worked least well with nondisabled males, females over age 50 years, and children. We also developed methodologies for defining Medicaid AIDS onset, risk group, and date of death. Our research resulted in the identification of a study population representing the majority of Medicaid AIDS cases between 1983 and 1986 in California and New York. The AIDS study population data base was used in further research on eligibility patterns, the epidemiology of the AIDS epidemic, lifetime Medicaid utilization and expenditures, and the development of a survival-based severity index for Medicaid recipients with AIDS.

Lifetime Medicaid service utilization and expenditures for AIDS in New York and California.

Several important gaps exists in information on the health care resources used by people with AIDS, including patterns of outpatient care, differences between populations at risk of the disease, and services paid for by Medicaid. To address the shortage of information in these areas, this study examined average Medicaid expenditures and service use for the time period a person has AIDS. The study population was Medicaid enrollees with AIDS in New York and California who died between October 1985 and September 1986. The study focused on the differences between the two states and between four groups that were proxies for at-risk populations: children, women, drug-using men, and non-drug-using men. Mean lifetime Medicaid expenditures were about $30,000 in New York and $20,000 in California. Inpatient use was higher and outpatient service use was lower in New York than in California after controlling for risk group, diagnosis, and Medicaid eligibility group (a proxy for income level). In California, women had higher expenditures and inpatient use than men. In New York, women and drug-using men had higher expenditures and use of inpatient and outpatient services (except home health care) than the non-drug-using men. Children in New York had higher expenditures and hospital use than adults but similar outpatient service use. Multivariate analyses suggest that differences between risk groups were largely attributable to differences in diagnosis and income level (as measured by Medicaid eligibility group).

Chronic cerebral hypoperfusion elicits neuronal apoptosis and behavioral impairment.

Chronic reductions in cerebral blood flow associated with aging and progressive neurodegenerative disorders can precipitate cognitive failure. To assess whether chronic cerebrovascular insufficiency elicits neuronal apoptosis, apoptotic cell death in the hippocampus was quantitated in a rat model of permanent carotid occlusion. Bilateral carotid artery occlusion (2VO) was shown to induce apoptotic morphology and DNA strand breaks in hippocampal neurons 2 and 27 weeks after ligation. The rate of pyramidal cell apoptosis was higher at chronic (27 weeks) compared to sub-chronic (2 weeks) time points. 2VO-induced apoptosis resulted in a decrease in total pyramidal cell number at 27 weeks but not at earlier time points, indicating progressive neuronal loss. Working and reference memory errors in the radial arm maze were strongly correlated with the number of apoptotic neurons in CA1 but not CA3 pyramidal cell fields. These data provide the first indication that apoptotic loss of pyramidal neurons may play a role in memory impairment associated with clinical conditions of chronic cerebrovascular insufficiency.

Chronic reduction of cerebral blood flow in the adult rat: late-emerging CA1 cell loss and memory dysfunction.

Ten-month-old rats were subjected to permanent bilateral occlusion of both common carotid arteries (2-VO) to chronically but moderately reduce brain blood flow. 2-VO impaired Morris water maze acquisition as soon as 7 days post-surgery. 2-VO also caused a later-appearing impairment on the radial arm maze which did not reach significance until 63 days post-surgery. At 14 dats post-surgery there were no effects of 2-VO on hippocampal CA1 pyramidal cell number or density of glial fibrillary acidic protein (GFAP). Hippocampal choline acetyltransferase activity at 70 days was also unaffected by 2-VO. At 190 days post-surgery, however, the 2-VO rats showed loss of cells and increased GFAP density in CA1. The increased density of hippocampal GFAP correlated with radial arm maze but not Morris water maze impairment. It is suggested that 2-VO causes neuronal dysfunction which can be exacerbated by stress and thereby manifested on aversively motivated tasks such as the water maze. As well, CA1 neurons begin to degenerate after several weeks of the reduced energy availability caused by 2-VO and this impairs memory. Since reduced neuronal energy metabolism is associated with the progressive neurodegeneration that underlies disorders such as Alzheimer's, research should further explore the possibility that the effects of 2-VO may model age-related dementia.

Longitudinal patterns of California Medicaid recipients with acquired immunodeficiency syndrome.

In this study, the authors examine the longitudinal experience, annual trends, and subpopulation differences in Medicaid use and expenditures for persons with acquired immunodeficiency syndrome (AIDS) in California from 1983 through 1986. About two-thirds of adult males were enrolled in Medicaid within 1 month of their AIDS diagnosis. These recipients averaged approximately 20-percent higher lifetime expenditures than those enrolled at a later time. Monthly expenditures were higher in the beginning of enrollment and prior to death than in the months in between. From 1983 through 1986, there was a shift of care from inpatient to outpatient settings. In 1986, children and adult females had higher median expenditures than did adult males.

Acquired immunodeficiency syndrome in California's Medicaid program, 1981-84.

In this article, Medicaid enrollment, use, and expenditures for persons with acquired immunodeficiency syndrome in California from 1981-84 are examined. The data are from Tape-to-Tape, a person-level Medicaid enrollment and claims data base. It was found that expenditures per month of enrollment decreased as length of enrollment during the year increased. Average annual expenditures increased from 1982 to 1983 and then decreased in 1984. This decrease was most pronounced in hospital services with no indication of a substitution of ambulatory services. This decline is primarily a result of a decrease in hospital reimbursement per day as opposed to changes in use, because discharge rates decreased and length of stay increased.

Semisynthetic fluorohydrolases prepared by chemical modification of ribonuclease.

A process for conformational modification of protein, which we have previously reported, was investigated as a means of generating fluorohydrolase activity in bovine ribonuclease (RNase). The resulting modified RNase had catalytic activity that depended upon the chosen modifier. Bovine pancreatic ribonuclease, modified by addition of hexamethylphosphoramide (HMPA) at pH 3, was derivatized with diimidates of chain lengths from C1 to C8. The derivative with the highest activity was obtained when RNase was crosslinked with dimethyl pimelimidate (C5). This derivative, which was active over a pH range of 6.5 to 8.0 with an optimum pH of 7.4, hydrolyzed phenylmethylsulfonylfluoride (PMSF) and the potent acetylcholinesterase inhibitor, diisopropyl phosphorofluoridate (DFP). The mean fluorohydrolase activity for four preparations using dimethyl pimelimidate was 0.8 +/- 0.2 U mg-1. Gel filtration on G-75 Sephadex and SDS-polyacrylamide gel electrophoresis showed components having a molecular weight of 13,000 and 27,000, with activity restricted to the 27,000 molecular weight fraction. After gel filtration, the specific activity was 9.1 +/- 2.4 U mg-1, resulting in a molecular activity of 125 min-1. The mechanism of this unique transformation of RNase into a fluorohydrolase is not known, nor has the location of the active site been determined.

Observations on the infectivity of parasitic third-stage larvae of Uncinaria lucasi Stiles 1901 (Nematoda: Ancylostomatidae) of Northern fur seals, Callorhinus ursinus Linn., on St. Paul Island, Alaska.

Twelve fur seal pups, which had not nursed their mothers, were used in an infectivity experiment. Pups were exposed to parasitic 3rd-stage larvae of Uncinaria lucasi from belly tissues of fur seal bulls, bachelors, and pregnant cows, to determine maturation capability of the larvae. Hookworms were not recovered from the intestines of 3 pups receiving larvae from belly blubber of bulls, 6 pups receiving larvae from belly blubber of bachelors, and 1 nonexposed pup. Maturation of hookworms did occur in 2 pups exposed to larvae from a mixture of belly blubber, mammary tissue, and milk of pregnant cows. Parasitic 3rd-stage hookworm larvae from belly tissues of pregnant and "non-pregnant" fur seal cows averaged 938.1 and 802.1 micron long, and 34.1 and 31.5 micron wide, respectively; however, larvae from belly tissues of a fur seal bull, bachelors, 2-year-old males, male and female yearlings and pups, and Steller Sea Lion subadults averaged 640.5-732.0 micron long and 20.9-24.9 micron wide.

Timing of postoperative adjustment in adjustable suture strabismus surgery.

PURPOSE: The use of adjustable sutures in strabismus surgery has increased the rate of surgical success. Little data are available on the optimum timing for postoperative adjustment after strabismus surgery. We wanted to compare 2 common practices of adjustable suture technique after strabismus surgery. METHODS: Two comparable groups of 40 patients each, who had strabismus surgery with adjustable suture technique, were prospectively studied. Group A had early adjustment the same day of the surgery about 6 hours after the operation, and group B had late adjustment the next day about 24 hours after the operation. Subjective scoring tables were used to evaluate the pain felt by the patient before, during, and after the adjustment and any difficulties of the adjustment process. Requirements of postoperative pain medications and final alignment 6 weeks after surgery were also compared. RESULTS: Despite adequate statistical power, no significant differences were found between the groups regarding pain before, during, and after adjustment, difficulties performing the adjustment, and final alignment after 6 weeks (P > .05). Both adjustment schedules were equally associated with mild to moderate pain before, during, and after the adjustment. In the first 24 hours after surgery, no overall difference in the use of pain medications was found. Nausea and vomiting in the first 24 postoperative hours were more common in the early adjustment group (P = .02). CONCLUSION: The surgeon can feel free to choose the timing for postoperative adjustment. However, when performing an early adjustment, the surgeon should be especially prepared to control nausea and vomiting.

Activities of dichlorvos or disophenol against the hookworm (Uncinaria lucasi) and sucking lice of northern fur seal pups (Callorhinus ursinus) on St. Paul Island, Alaska.

One controlled and six critical tests were conducted in July, 1977 with northern fur seal pups (Callorhinus ursinus) to determine the efficacies of a single dose of dichlorvos capsules at 29.3 to 32.8 mg/kg, tablets at 10.5 to 11.5 mg/kg, or disophenol at 9.9 mg/kg given subcutaneously against natural infections of adult Uncinaria lucasi. In the controlled test, 20 pups were treated and 10 pups were nontreated. Removal of hookworms in this test was 99% for five pups receiving dichlorvos capsules, 99% for five pups receiving dichlorvos tablets, and 77% for 10 pups receiving disophenol. Also, both formulations of dichlorvos and the formulation of disophenol were highly active against natural infestations of two species of sucking lice (Proechinophthirus fluctus and Antarctopthirus callorhini). In critical tests with four pups treated with dichlorvos capsules at 28.6 to 30.6 mg/kg, removal of hookworms was uniformly 100%. Disophenol at 9.9 mg/kg removed 100% and less than 1% of hookworms in two pups, respectively, in critical tests.

Lymphosarcoma in an infant northern fur seal (Callorhinus ursinus).

An infant northern fur seal (Callhorinus ursinus) died in a rookery on St. Paul Island, Pribilof Islands, Alaska. Grossly, slight enlargement of the mesenteric lymph nodes was seen. Microscopically, a lymphosarcoma composed of sheets of monomorphic lymphoid cells in sections of lymph node and tonsil was seen. Electron microscopy of formalin-fixed tissues revealed several structures that were possible of viral origin in the cytoplasm of the neoplastic cells.

Populations, microhabitat preference and effects of infestation of two species of Orthohalarachne (Halarachnidae: Acarina) in the northern fur seal.

All of 116 northern fur seals examined, except black pups (up to 3 monts old), had nasal mites, Orthohalarachne attenuata and O. diminuata, with the mean density of 1,808 mites per subadult male, 435 per adult female, 251 per silver pup, and 21.5 per black pup. Only 63% of black pups examined were infested with both mites. Larvae represented as much as 99% of the total mite population (total samples), and the females of both species of Orthohalarachne accounted for more than 90% of the total population of adult mites. The O. attenuata adults inhabited the nasopharynx and O. diminuata adults were found primarily in the lungs. Larvae of both species occupied the mucus-filled turbinates. The heavy infestation with these mites appeared to result in impairment of respiration in fur seals, and could also cause lesions in the lungs and secondary alveolar emphysems, predispose to more serious diseases, or even kill the host animal.

Variable activity of disophenol against hookworms and lice of northern fur seal pups on St. Paul Island, Alaska.

Six critical tests with disophenol were conducted in July, 1978, in fur seal pups (Callorhinus ursinus) naturally-infected with adult hookworms, Uncinaria lucasi, and infested with various stages of two species of sucking lice, Proechinopthirus fluctus (Ferris) and Antarctophthirus callorhini (Osborn). Disophenol at a dose rate of 12.5 mg/kg was administered subcutaneously to each of six pups. Each pup was contained in an individual cage for 60 h posttreatment at which time pups were exmained at necropsy. Efficacy against hookworms ranged from 2% to 88% and of both species of lice ranged from 26% to 90% for the six pups. Disophenol removed approximately 90% of all adult lice but only slightly more than 60% of all nymphs. The only sign of toxicosis was a probable drug related fluid-like feces for four pups from 12 to 60 h posttreatment.

Lesions associated with Orthohalarachne attenuata (Halarachnidae) in the northern fur seal (Callorhinus ursinus).

In northern fur seals (Callorhinus ursinus) up to at least 4 years of age there is virtually 100% prevalence of infestation with the nasal mite Orthohalarachne attenuata. Although clinical observations and gross examination indicate that the condition is not serious, some erosion and inflammation of the nasal turbinates and nasopharynx were seen associated with mites in histological sections.

Renal fibrosarcoma in the northern fur seal.

A 2-week-old northern fur seal female pup (Callorhinus ursinus) found dead in the Pribilof Islands had an irregular mass at the anterior pole of the right kidney. Histopathological examination revealed a fibrosarcoma.