What is known and unknown about the effects of plastic pollution: A meta-analysis and systematic review.

As a consequence of the global ubiquity of plastic pollution, scientists, decision-makers, and the public often ask whether macroplastics (>5 mm) and microplastics (<5 mm) have a realized ecological threat. In 2016, we conducted a systematic review of the literature and made a call for further research testing hypotheses about ecological effects. In the subsequent years, the amount of relevant research has risen tremendously. Here, we reassess the literature to determine the current weight of evidence about the effects of plastic pollution across all levels of biological organization. Our data spans marine, freshwater, and terrestrial environments. We extracted data from 139 lab and field studies testing 577 independent effects across a variety of taxa and with various types, sizes, and shapes of plastic. Overall, 59% of the tested effects were detected. Of these, 58% were due to microplastics and 42% were due to macroplastics. Of the effects that were not detected, 94% were from microplastics and 6% were from macroplastics. We found evidence that whether or not an effect is detected, as well as the severity and direction of the effect, is driven by dose, particle shape, polymer type, and particle size. Based on our analyses, there is no doubt that macroplastics are causing ecological effects, however, the effects of microplastics are much more complex. We also assessed the environmental relevancy of experimental studies by comparing the doses used in each exposure to the concentrations and sizes of microplastics found in the environment. We determined that only 17% of the concentrations used in experimental studies have been found in nature, and that 80% of particle sizes used in experiments fall below the size range of the majority of environmental sampling. Based on our systematic review and meta-analysis, we make a call for future work that recognizes the complexity of microplastics and designs tests to better understand how different types, sizes, shapes, doses, and exposure durations affect wildlife. We also call for more ecologically and environmentally relevant studies, particularly in freshwater and terrestrial environments.

Efficient discovery of immune response targets by cyclical refinement of QSAR models of peptide binding.

Peptides that induce and recall T-cell responses are called T-cell epitopes. T-cell epitopes may be useful in a subunit vaccine against malaria. Computer models that simulate peptide binding to MHC are useful for selecting candidate T-cell epitopes since they minimize the number of experiments required for their identification. We applied a combination of computational and immunological strategies to select candidate T-cell epitopes. A total of 86 experimental binding assays were performed in three rounds of identification of HLA-A11 binding peptides from the six preerythrocytic malaria antigens. Thirty-six peptides were experimentally confirmed as binders. We show that the cyclical refinement of the ANN models results in a significant improvement of the efficiency of identifying potential T-cell epitopes.

Influence of age and HLA type on interferon-gamma (IFN-gamma) responses to a naturally occurring polymorphic epitope of Plasmodium falciparum liver stage antigen-1 (LSA-1).

Antigenic polymorphism and HLA restriction may limit the immunogenicity of a subunit vaccine against liver-stage Plasmodium falciparum. We examined 59 clinical isolates and five laboratory clones of P. falciparum for polymorphism in the N- and C-terminal regions of LSA-1, evaluated binding of the corresponding peptides to selected HLA class I alleles, and measured IFN-gamma responses in residents of a malaria-endemic area of Papua New Guinea where HLA-A*1101, -24, -B13, and -B40 are the most common class I alleles. LSA-1 polymorphism was limited to a single non-synonymous mutation encoding serine (S), proline (P), or threonine (T) at amino acid 85. Nine-mer 84-92 peptides with S, T, or P at the primary anchor position bound differentially to HLA-A11, -A2, and -B7. IFN-gamma ELISPOT responses increased with age in malaria-exposed subjects: 14-16% and 30-36% of 2-5- and 6-54-year-olds, respectively, had > or =10 IFN-gamma-secreting cells/106 peripheral blood mononuclear cells when stimulated with at least one peptide variant (P<0.05). IFN-gamma responses to all three peptides were also greater for older than younger individuals. No children < 3 years old had lymphocytes that responded to all three 84-92 peptides, whereas 45% of adults (mean age 48 years) had aggregated IFN-gamma responses. These data support the notion that age-related cumulative exposure to P. falciparum increases the frequency of IFN-gamma responses to polymorphic epitopes of liver-stage antigens such as LSA-1.

The influence of surface condition on the localized corrosion of 316L stainless steel orthopaedic implants.

The localized corrosion of austenitic stainless steel 316L intended for use as orthopaedic implants is determined as a function of the surface condition and metallurgical state. From the examination of samples exposed to a ferric chloride solution, at both 22 and 37 degrees C, the independent contribution of crevice and pitting corrosion to localized corrosion is determined. Both forms of localized corrosion occur to a greater extent at the higher temperature. The results indicate that weight loss measurements may not be sufficient to determine the extent of crevice corrosion separately from the influence of pitting corrosion. More importantly, the surface conditions required for the best resistance to crevice or pitting corrosion differ. Electropolished surfaces provide the best resistance to crevice corrosion, while "bead blasted" surfaces provide the best resistance to pitting corrosion. The implication of this result in terms of the serviceability as orthopaedic implants is discussed. The current results indicate the cold-worked state exhibits improved resistance to pitting corrosion. However, the influence of the metallurgical state could not be separated from a possible compositional effect.

Infertility in women: an update.

OBJECTIVE: To review pharmacologic therapy of infertility disorders in women. DATA SOURCES: Current clinical literature. STUDY SELECTION: Not applicable. DATA EXTRACTION: Not applicable. DATA SYNTHESIS: The complex interplay of hormones and cells is the focus of most pharmacotherapeutic interventions in women with infertility problems. Treatment remains more of an art than a science at this time. Since the cause of infertility cannot be identified in many cases, practitioners use medications to overcome potential problems with anovulation, secondary ovarian failures, hypothalamic-pituitary dysfunction, and hyperprolactinemia. This article reviews the use of clomiphene, human chorionic gonadotropin, menotropins such as human menopausal gonadotropin and urofollitropin, gonadotropin-releasing hormone, and dopamine agonists. CONCLUSION: Although few pharmacists are closely involved in the treatment of women with infertility, they can be sources of information, monitor families for signs and symptoms of psychologic stress associated with treatments, and help patients with practical instructions.

Increased interleukin-4 and interleukin-5 production in response to Schistosoma haematobium adult worm antigens correlates with lack of reinfection after treatment.

Acquired immunity to human schistosomiasis correlates with increased serum levels of schistosome antigen-specific IgE. Since interleukin (IL)-4 stimulates IgE production, the hypothesis that Th2-associated cell-mediated immunity participates in protection to reinfection was studied in a cohort of adolescent boys 12-18 months after chemotherapeutic cure in Upper Egypt. Initial Schistosoma haematobium prevalence was 51% and posttreatment incidence was 44%. Water contact was similar between putatively resistant and susceptible patients. Resistant persons had a 3.5- to 14-fold greater frequency of schistosome adult worm antigen (SWAP)-specific lymphocytes secreting IL-5 or IL-4 (by ELISPOT) and IL-5 or IL-4 production in peripheral blood lymphocyte culture supernatants (P < .05 to < .001, n = 48) versus susceptible subjects (n = 38). In contrast, SWAP-induced interferon-gamma and IL-10 production and lymphocyte proliferation were similar between the 2 groups. Schistosome egg antigen and streptolysin O each stimulated similar cytokine production in susceptible and resistant persons. Thus, enhanced SWAP-driven IL-4 and IL-5 production correlates with immunity to reinfection in adolescents exposed to urinary schistosomiasis.

T-cell immunity to peptide epitopes of liver-stage antigen 1 in an area of Papua New Guinea in which malaria is holoendemic.

Liver-stage antigen 1 (LSA1) is one of several pre-erythrocytic antigens considered for inclusion in a multiantigen, multistage subunit vaccine against falciparum malaria. We examined T-cell proliferation and cytokine responses to peptides corresponding to amino acids 84 to 107, 1813 to 1835, and 1888 to 1909 of LSA1 in asymptomatic adults living in an area of Papua New Guinea where malaria is holoendemic. Whereas T cells from North Americans never exposed to malaria did not respond to any of the peptides, those from 52 of 55 adults from the area where malaria is endemic had vigorous proliferation responses to one or more of the LSA1 peptides (mean stimulation indices of 6.8 to 7.2). Gamma interferon (IFN-gamma) production driven by LSA1 peptides ranged from 34 to more than 3,500 pg/2 x 10(6) cells, was derived primarily from CD8+ cells, and was dissociated from T-cell proliferation. The frequencies of IFN-gamma response to the amino acid 1819 to 1835 and 1888 to 1909 peptides were significantly greater than that to the amino acid 84 to 107 peptide (87 and 88% versus 33% of subjects; P < 0.0001). In contrast to proliferation and IFN-gamma, interleukin 4 (IL-4) and/or IL-5 responses to LSA1 peptides were detected in only 18% of the subjects. These data show that T-cell immunity to epitopes in the N- and C-terminal regions of LSA1 are common in persons living in this area of Papua New Guinea where malaria is endemic. The dominance of type 1 CD8 cell IFN-gamma responses is consistent with a role for this T-cell population in immunity to liver-stage Plasmodium falciparum in humans.

Drug samples and family practice residents.

OBJECTIVE: To describe residents' knowledge, attitudes, and behaviors regarding sample medications and to determine the education provided in residency training regarding sample use. METHODS: A 6-item survey was sent to directors of US family practice residency programs. Residents of a sample of these programs were sent an anonymous, self-administered, 21-item questionnaire assessing knowledge, attitudes, and practices relating to sample use. Both surveys consisted of initial and follow-up mailings. RESULTS: The residency directors' survey was returned by 232 of the 436 residency directors (53%). Although 66% of the programs had a policy regarding samples, only 15% of the policies completely incorporated recommendations of the Society of Teachers of Family Medicine. After two mailings, 248 resident responses were received from 43 of 47 residencies (92%). Only 21% of respondents thought that they received adequate training about sample use in medical school; this number increased to 49% for residency training. Agreement with the adequate training statement was highest among respondents from residencies that had both a sample distribution policy and a pharmacist (p = 0.044). Fifty-five percent thought that samples influenced their prescribing and 70% thought that samples helped them to learn more about the sampled medication. CONCLUSIONS: Family practice residents value and use samples, although they are often unaware of the rules governing the labeling of samples. While reported distribution of samples by residents often is appropriate, education about effective sample use could be improved. Drug samples play a significant role in residency training.

Factors motivating pharmacy students to pursue residency and fellowship training.

Factors that influence pharmacy students to pursue residency and fellowship training were studied. Directors of 514 residency or fellowship programs were asked to distribute to their residents or fellows a survey concerning factors that influenced their decision to enter a residency or fellowship. Deans of the 75 U.S. pharmacy schools were sent a related survey and asked to forward it to the faculty or staff member who was most involved in promoting residencies and fellowships to students. This survey asked about methods for promoting the programs and the faculty member's opinion on why students chose to become residents and fellows. Residents and fellows cited "to gain knowledge and experience," "recognition of new and challenging roles," and "desire for specialized training" as their leading reasons for entering their programs. The pharmacy school representatives also cited "to gain knowledge and experience" and "desire for specialized training" as leading reasons. The residents and fellows thought instruction on residencies and fellowships should occur earlier in the pharmacy degree programs than it was being provided. The pharmacy school respondents considered the largest barriers to entering such programs "financial" and "a job was available upon graduation from pharmacy school." The pharmacy school survey results were broken into two groups: the 9 schools that produced the most students who went on to residencies and fellowships, and the rest of the schools. The former group was more likely to offer the Pharm.D. degree and to involve preceptors, residents, and fellows in didactic and clerkship teaching. Two factors--"to gain knowledge and experience" and "desire for specialized training"--were cited most frequently by survey respondents as important factors in students' decisions to pursue residencies and fellowships, and schools that produce more residents and fellows tended to involve preceptors, residents, and fellows in didactic and clerkship training.

Dystonic-like reaction following cisapride therapy.

A 43-year-old woman with gastroesophageal reflux disease developed a dystonic-like reaction approximately 3 days after starting oral cisapride therapy. Office evaluation revealed a patient who moved her head rhythmically from side to side as she stared into space, generally unresponsive to external stimuli. She had increased tone of the sternocleidomastoid muscles bilaterally, with occasional tongue protrusion, and a slow shuffling gait. Following discontinuation of cisapride, the patient recovered completely.

Immunization requirements for pharmacy students.

OBJECTIVE: To identify current immunization requirements for pharmacy students throughout the US. DESIGN: Self-administered questionnaire. SETTING: Seventy-five colleges and schools of pharmacy in the US. MAIN OUTCOME MEASURES: Immunization policies, immunologic requirements, timing of vaccination in relation to the beginning of clerkship experience, payment, mechanism to revise policies. DATA ANALYSIS: Descriptive statistics. RESULTS: Overall, 57 programs (81 percent) have an immunization program in place, but 13 programs (19 percent) have no immunization program. More than 50 percent of the colleges or schools reported requiring that pharmacy students have measles, mumps, rubella, tetanus, and purified protein derivative of tuberculin (PPD) vaccinations upon entry of clerkship. Only 25 college or schools of pharmacy (44 percent) required students to have the hepatitis B vaccine and 8 (14 percent) to have a PPD evaluation upon completion of clerkship experience. Responsibility for the immunization program was shared evenly between the clerkship coordinator and the student health clinic. Approximately 65 percent of programs maintain an immunization record on file for each student. Completion of immunizations was required in 36 schools (64 percent) before entering clerkship activities, 15 (26 percent) before entrance to the professional program, and 3 (5 percent) in the first year of the program. Six schools (11 percent) had a program in place for less than one year, 27 (47 percent) between one and five years, and 24 (42 percent) for more than five years. At the majority of schools, students are responsible for the cost of immunization. CONCLUSIONS: Most schools of pharmacy do not adhere to the specific immunization recommendations described by the Centers for Disease Control and Prevention for healthcare workers. Pharmacy schools need to reexamine their immunization policies and update them to reflect the most current standards. We suggest a policy for immunization of pharmacy students.

A description of a pharmacotherapy curriculum in a university-based family medicine program.

OBJECTIVE: To describe the methods by which a family medicine residency program implements a pharmacotherapy curriculum. The goal of the curriculum is to teach family medicine residents the principles of rational drug therapy. SETTING: A university-based family medicine residency program. TEACHING STRATEGIES: Specific learning objectives are discussed and the following teaching strategies are expanded upon: (1) monthly noon conferences; (2) a printed formulary and pharmacotherapy handbook; (3) a pharmacy and therapeutics committee; (4) policy statements for drug representatives and use of samples; (5) an on-site pharmacy; (6) quarterly newsletter; and (7) inpatient consultation coverage. PHARMACIST ROLE: The role and responsibilities of the pharmacy faculty and pharmacist(s) who implement this curriculum and the methods used to evaluate its effectiveness are also described. The availability and funding of the pharmacy faculty member can sometimes be arranged with local schools of pharmacy seeking clerkship sites. Interaction with pharmacy students also serves to enhance the educational experience of the family medicine residents. CONCLUSIONS: The family medicine program implements a comprehensive curriculum designed to teach family medicine residents the principles of rational drug therapy. The curriculum may be expanded upon as necessary, or, if the entire program is not feasible, certain elements may be extracted and applied in other institutions.

Involvement of pharmacy faculty in the development of policies for pharmaceutical sales representatives.

BACKGROUND: Few studies evaluating the impact of the pharmaceutical industry on postgraduate medical education have been done. Recently, position statements and professional guidelines have emerged to ensure the integrity of physician-industry relationships in the areas of clinical judgement, research, and medical education. METHODS: The present study surveyed directors of family practice residency programs in the United States to define the level of pharmacotherapy curriculum development and the existence of policies for pharmaceutical sales representatives. RESULTS: Of the 383 directors, 325 (85%) responded to a mailed survey. Nearly one third (32%) of the responding programs had pharmacist faculty, the majority of whom held a doctor of pharmacy degree. Approximately 30% of programs reported that they had printed guidelines for pharmaceutical sales representatives. CONCLUSIONS: Programs with pharmacist faculty are more likely to have a well-developed pharmacotherapy curriculum and printed guidelines for pharmaceutical sales representatives.