Effects of changing environmental conditions on plastic ingestion and feeding ecology of a benthopelagic fish (Gadus morhua) in the Southwest Baltic Sea.

This study documents how the abundance of microplastics (<5 mm) in the Atlantic cod, Gadus morhua, relates to the changes of the fish diet during years with contrasting levels of anoxia for example following years of low or high major Baltic inflows (MBI). A MultiNet Maxi trawl and CTD were deployed annually to collect microplastic samples alongside oxygen, temperature, and salinity conditions. Microplastics were homogenously distributed both within the water column and across years. Gadus morhua diet shifted from dominantly benthic invertebrates (61 %) under oxygenated conditions to dominantly Sprattus sprattus (81 %) under anoxic conditions. The proportion of G. morhua with microplastics in their digestive tract increased when they fed on pelagic fish (38 %) versus on benthic invertebrates (15 %). The proportion of S. sprattus which ingested microplastics (~18 %) did not vary. As anoxia at depth is expected to increase due to climate change, microplastic ingestion by G. morhua will potentially increase.

Noninvasive genomic detection of melanoma.

BACKGROUND: Early detection and treatment of melanoma is important for optimal clinical outcome, leading to biopsy of pigmented lesions deemed suspicious for the disease. The vast majority of such lesions are benign. Thus, a more objective and accurate means for detection of melanoma is needed to identify lesions for excision. OBJECTIVES: To provide proof-of-principle that epidermal genetic information retrieval (EGIR™; DermTech International, La Jolla, CA, U.S.A.), a method that noninvasively samples cells from stratum corneum by means of adhesive tape stripping, can be used to discern melanomas from naevi. METHODS: Skin overlying pigmented lesions clinically suspicious for melanoma was harvested using EGIR. RNA isolated from the tapes was amplified and gene expression profiled. All lesions were removed for histopathological evaluation. RESULTS: Supervised analysis of the microarray data identified 312 genes differentially expressed between melanomas, naevi and normal skin specimens (P<0·001, false discovery rate q<0·05). Surprisingly, many of these genes are known to have a role in melanocyte development and physiology, melanoma, cancer, and cell growth control. Subsequent class prediction modelling of a training dataset, consisting of 37 melanomas and 37 naevi, discovered a 17-gene classifier that discriminates these skin lesions. Upon testing with an independent dataset, this classifier discerned in situ and invasive melanomas from naevi with 100% sensitivity and 88% specificity, with an area under the curve for the receiver operating characteristic of 0·955. CONCLUSIONS: These results demonstrate that EGIR-harvested specimens can be used to detect melanoma accurately by means of a 17-gene genomic biomarker.

Susceptibility to Coccidioides species in C57BL/6 mice is associated with expression of a truncated splice variant of Dectin-1 (Clec7a).

Coccidioides posadasii spherules stimulate macrophages to make cytokines via TLR-2 and Dectin-1. We used formalin-killed spherules and 1,3-beta-glucan purified from spherules to stimulate elicited peritoneal macrophages and myeloid dendritic cells (mDCs) from susceptible (C57BL/6) and resistant (DBA/2) mouse strains. DBA/2 macrophages produced more TNF-alpha and IL-6 than macrophages from C57BL/6 mice, and the amount of TNF-alpha made was dependent on both TLR2 and Dectin-1. DCs from C57BL/6 mice made more IL-10 and less IL-23p19 and IL-12p70 than did DBA/2 DC. These responses were inhibited by a monoclonal antibody to Dectin-1. DBA/2 mice expressed full-length Dectin-1, whereas C57BL/6 mice spliced out exon 3, which encodes most of the stalk. RAW cells transduced to express the full-length Dectin-1 responded better to FKS than cells expressing truncated Dectin-1. We compared the isoform of Dectin-1 expressed by 34 C57BL/6 X DBA/2 recombinant inbred (BXD RI) lines with their susceptibility to Coccidioides immitis. In 25 of 34 RI lines susceptibility or resistance corresponded to short or full-length isoforms, respectively. These results suggest that alternative splicing of the Dectin-1 gene contributes to susceptibility of C57BL/6 mice to coccidioidomycosis, and affects the cytokine responses of macrophages and mDCs to spherules.

Acetaminophen-induced hepatic failure with encephalopathy in a newborn.

We report a case of oral acetaminophen toxicity in a term newborn infant successfully treated with a 20 h intravenous N-acetylcysteine infusion protocol without any adverse effects. This case report supports the use of N-acetylcysteine to treat neonatal acetaminophen toxicity and highlights the need for better education of parents regarding the appropriate use and dosage of acetaminophen in newborns.

Board certification in optometry.

BACKGROUND: In keeping with current expectations in the health care community, the purpose of the American Board of Optometric Practice (ABOP) is to enhance the quality of optometric care available to the public by fostering continued competence for practitioners through administering education and examinations for certification and re-certification. The formation of ABOP makes possible for the first time a board certification process for optometrists. METHODS: The optometry model for board certification and recertification emphasizes the breadth of the profession. ABOP certification will be accomplished through a combination of examinations and high-quality, tested Board Certified Continuing Education (BCCE). Specific requirements for practitioners at various stages of their careers are presented. RESULTS: Board certification provides one important mechanism for an optometrist to demonstrate commitment to quality, professionalism, and ongoing clinical competence. The optometrist benefits from high-quality continuing education designed for timeliness, importance, and breadth. The public benefits by the enhancement of continued competence within the optometric profession. Health care agencies benefit by being able to recognize providers who have elected to demonstrate their qualifications through certification. CONCLUSIONS: Through board certification, optometrists will be able to demonstrate their commitment to maintaining clinical competence through a nationally uniform program, and they will be able to comply with standards that are generally recognized and required throughout the health care community.

Genetic evidence for the role of the Lv locus in early susceptibility but not IL-10 synthesis in experimental coccidioidomycosis in C57BL mice.

Loci on chromosome 4 near Lv and on chromosome 6 near Tnfr1 are associated with resistance to coccidioidomycosis in mice. To assess the importance of the Lv locus, we compared C57BL/6 (B6) with C57BL/10 (B10), strains that are nearly congenic for the Lv locus. Fourteen days after intraperitoneal infection, B6 mice had nearly 100-fold more Coccidioides immitis in their lungs than did B10 mice (log 6.2 vs. log 4.8). Furthermore, the time to 50% deaths was 15 days for B6 and 22 days for B10. Nevertheless, 90% of B10 mice had died by day 28. In other mouse strains, we found a direct correlation between lung colony-forming units and levels of interleukin (IL)-10 and IL-4 mRNA, but B10 mice had 100-fold higher lung levels of IL-10 and 10-fold higher levels of IL-4 mRNA than did B6 mice, despite having less C. immitis. In the absence of IL-10, B10 mice are resistant to lethal infection. These results suggest that a locus near Lv is responsible for early resistance to coccidioidomycosis but not for modulating the IL-10 and IL-4 responses. This locus is not sufficient to make C57BL mice resistant to coccidioidomycosis.

Genes influencing resistance to Coccidioides immitis and the interleukin-10 response map to chromosomes 4 and 6 in mice.

Coccidioidomycosis is a fungal infection that is endemic in the southwestern United States. Infection is more severe in blacks and Filipinos, which suggests that there is a genetic basis for susceptibility to this infection in humans. We found that there is also a difference in resistance to Coccidioides immitis infection among inbred mouse strains: B6 mice are susceptible, while DBA/2 mice are resistant (T. N. Kirkland and J. Fierer, Infect. Immun. 40:912-916, 1983). In this paper we report the results of our efforts to map the genes responsible for resistance to this infection in mice. Mice were infected by intraperitoneal inoculation, and 15 days later the numbers of viable fungi in their lungs and spleens were enumerated. We also determined the amounts of interleukin-10 mRNA made in the infected lungs. These three phenotypes were mapped as quantitative traits by using the 26 available lines of recombinant inbred mice derived from a cross between B6 and DBA/2 mice. The best associations were those between the regions near the Lv locus on chromosome 4 and the Tnfr1 locus on chromosome 6. We then infected backcross mice [(B6 x DBA/2) x B6] and confirmed these associations; 14 of 16 (87%) mice that were heterozygous at both Lv and Tnfr1 were resistant to infection, whereas only 4 of 16 (25%) mice that were homozygous B6 at both loci were resistant. These are the first genetic loci to be associated with susceptibility to C. immitis, but there may be additional genes involved in murine resistance to this infection.

Importance of interleukin-10 in genetic susceptibility of mice to Coccidioides immitis.

Inbred strains of mice vary in their susceptibility to Coccidioides immitis. We infected resistant DBA/2 (D2) mice and three susceptible strains of mice (C57BL/6 [B6], BALB/c, and CAST/Ei) by intraperitoneal injection of arthroconidia and determined the severity of infection based on colony counts of fungus in the spleens and lungs 14 days after infection. We used quantitative reverse transcription-PCR to measure the amounts of cytokines made in the spleens and lungs of infected mice. Susceptible mice made 1, 000-fold more interleukin-10 (IL-10) than resistant D2 mice and about 10-fold more IL-4. In contrast, D2 mice had more IL-12 p40 in their lungs than did B6 mice. Resistant and susceptible mice made equivalent amounts of gamma interferon, IL-6, and IL-2. In order to determine whether IL-10 adversely affected the response to C. immitis, we infected IL-10-deficient mice, and they were found to be as resistant as D2 mice. This result indicates that IL-10 plays a crucial role in determining susceptibility to C. immitis in inbred mice. Because IL-4 mRNA levels were higher in most strains of susceptible mice, we also infected IL-4-deficient B6 mice. They were more resistant than B6 controls but not as resistant as IL-10-deficient mice. Thus, both IL-10 and IL-4 adversely affect the ability of C57BL mice to resist infection with C. immitis, but IL-10 has a larger effect and is the cytokine that is consistently associated with susceptibility in all strains of inbred mice.

Issues for optometrists relating to interprofessional relations in a hospital and medical center.

Managed care and the changes in the health care system are golden opportunities for the optometric profession. There is a major role for optometry in the medical center and there is a major role for optometry in the various managed health care programs. Optometry is well positioned as a primary health care profession. The leaders of this noble profession must be on the alert and plan and work diligently to include optometry in all aspects of the ever-changing health care system.

Generation of Chinese hamster ovary cell glycosylation mutants by retroviral insertional mutagenesis. Integration into a discrete locus generates mutants expressing high levels of N-glycolylneuraminic acid.

Retroviral insertional mutagenesis can both generate somatic cell mutants and pinpoint the genomic locus associated with a mutant phenotype. In the present study, this approach was applied to Chinese hamster ovary cells (CHO) made susceptible to Moloney murine leukemia virus (MoMuLV) infection by stable expression of an ecotropic retrovirus receptor. These CHO cells were infected with a replication incompetent MoMuLV construct with a promoterless hygromycin phosphotransferase (hygro) gene inserted into the U3 region of the long terminal repeat and a second selectable marker, neomycin phosphotransferase (neo), expressed from an internal promoter. CHO clones containing integrated proviruses were selected with hygromycin or G418, and the subset of these with reduced cell surface Neu5Ac were then selected with wheat germ agglutinin (WGA). The majority of the resulting clones had a phenotype not previously described for WGA-resistant CHO mutants arising spontaneously or from chemical mutagenesis: Neu5Ac was almost completely replaced by Neu5Gc. We have provisionally termed these clones SAP mutants, for sialic acid phenotype. Southern analysis of HindIII digested DNA from four SAP mutants revealed that the MoMuLV provirus is present in a 10.4-kilobase (kb) fragment. Probing with a flanking CHO sequence resulted in equivalent hybridization to a 4.6-kb fragment and the 10.4-kb provirus-containing fragment in all four cases, while uninfected parental cells and non-SAP glycosylation mutants generated in the same retrovirus insertional mutagenesis experiments yielded only the 4.6-kb fragment. Sequencing of the 3'-flanking DNA revealed that each of the four SAP mutants had a unique provirus integration site falling within a 796 bp region of the CHO genome. The frequency with which SAP mutants arise suggests that this may be a preferred site for retrovirus integration.

A survey of eye and vision care in Oklahoma.

We examined the spectrum of vision care intensity, and the relationships of the three principal providers of vision care in Oklahoma. They were active family and general physicians (MD and DO), ophthalmologists (MD and DO), and optometrists. There were 1,356 surveys mailed to the three groups. We determined that vision care services in Oklahoma appear very accessible, are well distributed and generally affordable. The referral patterns appear to be less than optimal and optometrists are not fully utilized. This added cost and travel time for patients.

What are the pros and cons of requiring postgraduate residency training as an entry level practice requirement?

The technological and knowledge explosion that has occurred in this century has created a curriculum crunch within all health professional schools. The various optometric institutions are dealing with this crunch and important decisions need to be made in order to provide the best entry-level practitioners possible. This paper provides some of the pros and cons of requiring a year of postgraduate training as a requirement for entry level optometry practice.

AIDS-related behavioral research and nursing.

As efforts targeted at producing an effective vaccine or a definitive cure are still in early stages of development, health education and prevention continue to be this country's major line of defense against acquired immunodeficiency syndrome (AIDS). This defense is dependent on knowledge of behaviors that place individuals at risk of human immunodeficiency virus (HIV) exposure and disease progression. This article reviews the critical points in our state of knowledge and offers additional areas of need. Research is needed to determine a database of persons who use psychoactive substances and to understand the HIV-associated behaviors linked to drug use. Epidemiologic studies are necessary to appreciate the sexual, contraceptive, and childbearing practices of users of any psychoactive substance. Greater emphasis also is needed to investigate the inherent effects of various psychoactive substances on the immune, neurologic, and endocrine systems. While biomedical research continues, it is apparent that research from behavioral studies are crucial to education and prevention efforts. Nurse investigators are well-positioned to play an important role in accumulating this information. Given the critical role of drug abuse in the HIV epidemic, the public health significance cannot be overestimated.

Isolation of novel complementary DNA clones from T lymphoma cells: one encodes a putative multiple membrane-spanning protein.

Five novel complementary DNA (cDNA) clones which are differentially expressed between two closely related T lymphoma cell clones were isolated using subtraction-enriched differential screening. SL12.4 cells, from which the cDNAs were isolated, have characteristics of thymocytes at an intermediate stage in development and cause prominent extranodal ovarian tumors in syngeneic animals. A sister cell clone, SL12.3, derived from the same tumor, has a distinct phenotype and causes more aggressive, diffuse lymphomas. Four of the five novel genes are expressed in normal thymus, activated spleen cells, or gut-associated lymphoid tissue. The DNA sequence and predicted protein sequence are presented for one of the novel cDNA clones. This novel cDNA clone detects mRNA in normal thymus, gut-associated lymphoid tissue, and ovarian tissue. The predicted protein has four putative transmembrane-spanning regions. The expression of the transcript is repressed in somatic cell hybrids formed from SL12.4 cells fused with three different T lymphoma cell lines which lack detectable mRNA complementary to the novel cDNA clone. This trans-negative regulation suggests that the expression of the gene is regulated by repressional mechanisms.

Interaction of host cell proteins with the human T-cell leukemia virus type I transcriptional control region. II. A comprehensive map of protein-binding sites facilitates construction of a simple chimeric promoter responsive to the viral tax2 gene product.

We present a map describing the binding of cellular proteins to a 300-base pair (bp) region of the human T-cell leukemia virus type I (HTLV-I) long terminal repeat. The map accounts for nearly all of the DNase I protection reported in a previous study using crude nuclear extracts. Notable features include a complex arrangement of overlapping binding sites encompassing the 21-bp repeat elements (see accompanying paper) as well as binding sites for the transcription factors Sp1 and NF-I that significantly deviate from the previously defined consensus recognition sequences. Based on the binding results, we constructed simple chimeric promoters containing 21-bp repeat elements, Sp1-, and nuclear factor I-binding sites upstream of a TATA box. Transient transfection experiments show that these promoters are expressed in T-cells and are regulated by the viral tax2 gene product. Deletion of the Sp1 and nuclear factor I sites abolishes tax-induction, suggesting that one or both of these proteins play a role in mediating the tax-responsiveness conferred by the 21-bp repeat element.

Screening for rubella in schools of optometry.

Rubella can cause birth defects in fetuses of pregnant women who are susceptible to this disease. Because national immunization efforts have been relatively successful, most cases of rubella occur in young adults. The School of Optometry and Jefferson County Department of Health in Alabama, and the Division of Optometry in Northeastern Oklahoma, cooperated to provide a voluntary serologic rubella screening for their students. About 9% were seronegative and were immunized against rubella. To eliminate the risk of future optometrists transmitting rubella to susceptible patients, we recommend that optometry students be screened for rubella antibodies and be provided immunization if found to be seronegative.