The maintenance of classism in medical education: "time" as a form of social capital in first-generation and low-income medical students.

As first generation (FG)/low income (LI) students enter the elite profession of medicine, schools make presumptions about how FGLI students allocate their time. However, their lives are markedly different compared to their peers. This study argues that while all forms of capital are necessary for success, time as a specific form keeps classism in place. Using constructivist grounded theory techniques, we interviewed 48 FGLI students to understand where, why and how they allocated their time, and the perceived impact it had on them. Using open coding and constant comparison, we developed an understanding of FGLI students' relationship to time and then contextualized it within larger conversations on how time is conceptualized in a capitalist system that demands time efficiency, and the activities where time is needed in medical school. When students discussed time, they invoked the concept of 'time famine;' having too much to do and not enough time. In attempting to meet medicine's expectations, they conceptualized time as something that was 'spent' or 'given/taken' as they traversed different marketplaces, using their time as a form of currency to make up for the social capital expected of them. This study shows that because medical education was designed around the social elite, a strata of individuals who have generational resources, time is a critical aspect separating FGLI students from their peers. This study undergirds the idea that time is a hidden organizational framework that helps to maintain classism, thus positioning FGLI students at a disadvantage.

Who wears the face mask? Preventive measures against COVID-19 in Latin America before vaccination.

OBJECTIVES: We analyze the profile of adults who used a mask in the context of the COVID-19 pandemic in Latin America, between October and November 2020, right before the mass vaccination campaigns. STUDY DESIGN: Based on the Latinobarometer 2020 data, we assess the individual, regional, cultural and political factors of people who used a mask in the context of the COVID-19 pandemic in 18 countries of Latin America. METHODS: We applied a logistic regression to model the probability of using the mask regularly to avoid being infected with the COVID-19 virus. RESULTS: Women, older people, those with higher education, those being employed and not working in temporarily jobs, retirees, students, people with a centrist political ideology, and Catholics had a higher chance of using a face mask on a regular basis. People living in Venezuela, Chile, Costa Rica and Brazil were the most likely to use face masks. CONCLUSION: These results highlight the need to understand the social forces behind the willingness to adopt non-pharmacological preventive measures to make them more effective in health crisis emergencies.

P1 of Sweet Potato Feathery Mottle Virus Shows Strong Adaptation Capacity, Replacing P1-HCPro in a Chimeric Plum Pox Virus.

Potyviridae is the largest family of plant RNA viruses. Their genomes are expressed through long polyproteins that are usually headed by the leader endopeptidase P1. This protein can be classified as type A or type B based on host proteolytic requirements and RNA silencing suppression (RSS) capacity. The main Potyviridae genus is Potyvirus, and a group of potyviruses infecting sweet potato presents an enlarged P1 protein with a polymerase slippage motif that produces an extra product termed P1N-PISPO. These two proteins display some RSS activity and are expressed followed by HCPro, which appears to be the main RNA silencing suppressor in these viruses. Here, we studied the behavior of the P1 protein of Sweet potato feathery mottle virus (SPFMV) using a viral system based on a canonical potyvirus, Plum pox virus (PPV), and discovered that this protein is able to replace both PPV P1 and HCPro. We also found that P1N-PISPO, produced after polymerase slippage, provides extra RNA silencing suppression capacity to SPFMV P1 in this viral context. In addition, the results showed that presence of two type A P1 proteins was detrimental for viral viability. The ample recombination spectrum that we found in the recovered viruses supports the strong adaptation capacity of P1 proteins and signals the N-terminal part of SPFMV P1 as essential for RSS activity. Further analyses provided data to add extra layers to the evolutionary history of sweet potato-infecting potyvirids. IMPORTANCE Plant viruses represent a major challenge for agriculture worldwide and Potyviridae, being the largest family of plant RNA viruses, is one of the primary players. P1, the leader endopeptidase, is a multifunctional protein that contributes to the successful spread of these viruses over a wide host range. Understanding how P1 proteins work, their dynamic interplay during viral infection, and their evolutionary path is critical for the development of strategic tools to fight the multiple diseases these viruses cause. We focused our efforts on the P1 protein of Sweet potato feathery mottle virus, which is coresponsible for the most devastating disease in sweet potato. The significance of our research is in understanding the capacity of this protein to perform several independent functions, using this knowledge to learn more about P1 proteins in general and the potyvirids infecting this host.

Unraveling the modulatory actions of serotonin on male rat sexual responses.

Animal studies and clinical investigations reveal that serotonin plays a central role in the control of the ejaculatory threshold. The chronic use of selective serotonin reuptake inhibitors (SSRIs) frequently results in sexual dysfunction, inviting to analyze the modulatory actions of serotonin on male sexual function in depth. Even though the main effect of serotonin on male sexual responses is inhibitory, this neuromodulator also mediates brief important stimulatory actions. Serotonin (5-HT) can activate two intracellular signaling pathways: a lower-threshold facilitatory pathway, and a higher-threshold inhibitory pathway, leading to biphasic effects. We propose that these divergent actions are related to the stimulation or inhibition of glutamatergic and GABAergic interneurons. Experimental evidence suggests that low 5-HT concentrations produce stimulatory actions on male ejaculatory aspects that might be mediated by the blockade of the GABAergic neurotransmission in the MPOA and spinal cord, which in turn releases a tonic inhibition that allows other neurotransmitters such as glutamate, noradrenaline, oxytocin and dopamine to initiate a sequence of molecular events resulting in the expression of ejaculation. Similar serotonin actions, mediated via interneurons, have been proposed for the regulation of other processes and occur in many central nervous system areas, indicating that it is not an isolated phenomenon.

Novel computer-based assessment of asthma strategies in inner-city children.

BACKGROUND: Childhood asthma continues to be a growing medical concern in the United States, affecting > 17 million children in 1998. The mortality rate from asthma in children aged 5 to 14 years has nearly doubled, from 1.7 deaths per million to 3.2 deaths per million between 1980 and 1993. OBJECTIVE: To evaluate the use of artificial neural networks (ANNs) to rate problem-based strategies for asthma management in a defined population of children. METHODS: The participants in our study were recruited from a local inner-city medical facility in Los Angeles. The majority of participants had received the diagnosis of mild-to-moderate-persistent asthma. Each participant was given 10 asthma-based problems and asked to manage them. Each management decision and its order were entered into a database. This database was used to train an artificial neural network (ANN). The trained ANN was then used to cluster the various performances, and outputs were evaluated graphically. RESULTS: Three hundred five performances were analyzed through our trained neural network. Our ANN classified five major clusters representing different approaches to solving an acute asthma case. CONCLUSIONS: ANNs can build rich models of complex phenomena through a training and pattern-recognition process. Such networks can solve classification problems with ill-defined categories in which the patterns are deeply hidden within the data, and models of behavior are not well defined. In our pilot study, we have shown that ANNs can be useful in automating evaluation and improving our understanding of how children manage their asthma.

Problem-solving skills among precollege students in clinical immunology and microbiology: classifying strategies with a rubric and artificial neural network technology.

Educators emphasize the importance of problem solving that enables students to apply current knowledge and understanding in new ways to previously unencountered situations. Yet few methods are available to visualize and then assess such skills in a rapid and efficient way. Using a software system that can generate a picture (i.e., map) of students' strategies in solving problems, we investigated methods to classify problem-solving strategies of high school students who were studying infectious and noninfectious diseases. Using maps that indicated items students accessed to solve a software simulation as well as the sequence in which items were accessed, we developed a rubric to score the quality of the student performances and also applied artificial neural network technology to cluster student performances into groups of related strategies. Furthermore, we established that a relationship existed between the rubric and neural network results, suggesting that the quality of a problem-solving strategy could be predicted from the cluster of performances in which it was assigned by the network. Using artificial neural networks to assess students' problem-solving strategies has the potential to permit the investigation of the problem-solving performances of hundreds of students at a time and provide teachers with a valuable intervention tool capable of identifying content areas in which students have specific misunderstandings, gaps in learning, or misconceptions.

Enhancement of allergic inflammation by diesel exhaust particles: permissive role of reactive oxygen species.

BACKGROUND: Diesel emission particulates (DEP) exert effects on the immune system and act as an adjuvant which enhances allergic inflammation. Animal and human models have delineated the effects of DEP chemicals in enhancing IgE production and promoting T-helper cell-2 (Th2) differentiation. An important primary effect that can explain the DEP-associated humoral and cellular immune responses is the induction of macrophage responses by DEP chemicals. This includes effects on macrophage production of cytokines and chemokines, which may play a role in enhancing allergic inflammation. A potent mechanism in macrophages exposed to DEP chemicals involves the generation of reactive oxygen species (ROS), leading to cellular activation or apoptosis which can be abrogated by antioxidants. CONCLUSION: These findings may establish a role for antioxidant therapy in diminishing the effects of particulate pollutants in asthma.

Determination of diesel genotoxicity in firebreathers by micronuclei and nuclear abnormalities in buccal mucosa.

Diesel or its derivatives could have aneuploidogenic and/or clastogenic activity. Hence, the genotoxicity of diesel gases has been studied, considering exposure to them as potentially carcinogenic. The results obtained by different authors suggest the need to know the effects of direct and chronic exposure to diesel in humans, as in the case of the street workers called 'firebreathers' who fill their buccal cavity with diesel and then spread it to a burning torch many times during the day in order to give a 'dragon show' for 5 h a day and 6 days a week. The buccal samples of eight firebreathers were collected, processed and scored according to the criterion established by Tolbert et al., 1992 and then compared with positive and negative control groups. The results revealed that diesel was not micronucleogenic although it induces some nuclear abnormalities.

An update on the immunopathogenesis of asthma as an inflammatory disease enhanced by environmental pollutants.

The pathogenesis of asthma now centers on the role of bronchial mucosal inflammation of mixed cellularity in addition to the characteristic airways hyperresponsiveness and reversible obstruction. Mast cell mediators play an early role in the asthmatic airway response but through induced arachidonic acid metabolites and cytokine production may also participate in the late phase response. A unique feature of the late phase response is the abundant accumulation of eosinophils in the bronchial respiratory mucosa that is enabled by profound effects of the Th2 cytokine, IL-5. Additionally, the IL-4 gene cluster that is responsible for the levels of total serum IgE production has now been linked to asthma. With this new insight into the inflammatory mechanisms causing asthma, a mounting body of evidence exists to explain the recent increases in allergic disease prevalence resulting from environmental pollution. Air pollution, including the contribution by diesel exhaust particle emissions, has been shown to enhance both nasal IgE production and the gene expression of Th2 cytokines. It is believed that diesel particulates act as adjuvants in the immune system that promote the development of allergic inflammation.

Enhanced nasal cytokine production in human beings after in vivo challenge with diesel exhaust particles.

BACKGROUND: Diesel exhaust particles (DEPs) have been implicated in the worldwide increased incidence of allergic airway disorders over the past century. They can enhance in vivo IgE production in the human upper respiratory mucosa. OBJECTIVES: The study was carried out to determine whether DEPs can alter the production of cytokines by cells residing in the nasal mucosa. METHODS: Eighteen hours after intranasal challenge with saline solution or DEPs, we studied the levels of messenger RNA for cytokines in nasal lavage cells and the number of subjects in whom cytokine mRNA could be detected. RESULTS: Before challenge, most subjects' nasal lavage cells had detectable levels of only interferon-gamma, Il-2, and IL-13 mRNA. After challenge, the cells produced readily detectable mRNA for IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, and interferon-gamma. In addition, the levels of all cytokine mRNA increased. Enhanced IL-4 protein was also present in the postchallenge lavage fluid. Although the cells in nasal lavage before and after challenge do not necessarily represent the same cells either in number or type, the broad increase in cytokine production was not simply the result of an increase in T cells recovered in the lavage fluid. CONCLUSION: An increase in nasal cytokine expression after exposure to DEPs can be predicted to contribute to enhanced local IgE production and thus play a role in the increased incidence of respiratory allergic disease.

RAG-1 and RAG-2 gene expression and V(D)J recombinase activity are enhanced by protein phosphatase 1 and 2A inhibition in lymphocyte cell lines.

Expression of the recombination activating genes, RAG-1 and RAG-2, in lymphocytes, has been shown to depend on second messenger systems. An increase in intracellular cAMP upon stimulation with caffeine increases RAG expression while activation of protein kinase C (PKC) with phorbol myristate acetate (PMA) results in decreased RAG expression. The stringent regulation of recombination appears to be partially dependent on protein kinase activities which, alone, are not likely to be sufficient to regulate recombinase activity. We provide evidence implicating a role for serine/threonine phosphatases in the signal transduction pathway which regulates RAG gene expression and consequently the recombination process in lymphocytes. The cell permeable tumor promoter, calyculin-A (CLA), which is a potent inhibitor of the type 1 and 2A serine/threonine protein phosphatases (PP1 and PP2A, respectively), was shown to upregulate the expression of RAG-1 and RAG-2 in pre-B as well as mature B- and T-lymphocyte cell lines. Although agents such as caffeine known to increase intracellular cAMP levels induce RAG expression, synergy between CLA and caffeine was not detected in pre-B cells. An in vivo assessment of recombination activity after transfection of pre-B cells with an extrachromosomal recombination vector revealed a moderate increase in recombinase activity which paralleled RAG expression after CLA stimulation. Although increased cAMP levels in pre-B cells has been associated with upregulation of RAG expression we found no such upregulation in a surface immunoglobulin M positive (sIgM+) cell line, WEHI-231, and a T cell receptor positive (TCR+) murine cell line, EL-4. Moreover, in these mature lymphocyte cell lines there was no evidence of synergy in the regulation of RAG-1 and RAG-2 mRNA upon stimulation with CLA and caffeine. These results suggest novel intracellular mechanisms for the upregulation of RAG gene expression and confirm a role for type 1 and 2A phosphatases in the control of RAG gene expression and recombinase activity in lymphocyte cell lines.

Contrasting effects of two tumour promoters, phorbol myristate acetate and okadaic acid, on T-cell responses and activation of p42 MAP-kinase/ERK-2.

The induction of T-cell growth by the T-cell antigen receptor (TcR) is dependent on a co-ordinated process of phosphorylation and dephosphorylation of intracellular proteins. An intermediary in this signalling pathway is the serine kinase, p42 mitogen-activated protein kinase (p42MAPK), also known as microtubule-associated protein-2 kinase (MAP-2K). MAP-kinase is activated upon the acquisition of tyrosine as well as threonine phosphate groups and removal of either by specific tyrosine or serine/threonine phosphatases abrogates kinase activity. Okadaic acid (OA), a tumour promoter and potent inhibitor of type 1 and 2A serine/threonine protein phosphatases (PP1 and PP2A), induced MAP-kinase activity in Jurkat T cells in a dose-dependent fashion with optimal effect at 1 microM. Compared to rapid activation (peak < 10 min) of MAP-kinase by another tumour promoter, the phorbol ester, PMA, the effect of OA was delayed (> 30 min) and more sustained. In spite of activating a growth-promoting kinase, OA differed from PMA by its lack of mitogenic activity and failure to induce CD25 [interleukin-2R alpha (IL-2R alpha)] expression in normal human T cells. This implies that PP1 and PP2A also act downstream of MAP-kinase to facilitate later cell cycle events. PMA induced a 42,000 MW tyrosine phosphoprotein which co-electrophoresed and co-chromatographed with ERK-2, a p42 MAP-kinase. Although OA induced an identical Mono-Q peak, there was less avid tyrosine phosphorylation of p42. OA also differed from PMA to the extent by which it induced mobility shift of the tyrosine protein kinase, p56lck, which has been implicated in p42MAPK activation in T cells. Taken together, these results indicate that OA and PMA exert both overlapping as well as divergent effects on lymphocyte growth pathways.

[Endocarditis due to penicillin-sensitive and -resistant pneumococci: the current perspectives on the disease]. / Endocarditis por neumococos sensibles y resistentes a penicilina: perspectivas actuales de la enfermedad.

BACKGROUND: To evaluate the clinic characteristics and therapeutic aspects of endocarditis by Streptococcus pneumoniae sensitive and resistant to penicillin. METHODS: Twelve cases of pneumococcal endocarditis evaluated in 4 Spanish hospitals over the last 10 years were studied, analyzing their clinical characteristics and the existence of resistance to penicillin. The features were compared with a series of 98 cases found in a review of the literature. RESULTS: All the patients were males, most being alcoholics. The course of the disease was acute (2 weeks) in all the cases and evolved with great aggressivity: cardiac failure (9 patients), myocardial abscess (7 patients), multiple arterial embolisms (5 patients), septic arthritis (4 patients). Three patients had simultaneous pneumococcal meningitis but only one had pneumonia. The valve most affected was the aortic (9 cases). Three cases were due to strains of Streptococcus pneumoniae with moderate resistance to penicillin (CMI 0.5-1 micrograms/ml). Global mortality was 42%. All the patients receiving inadequate antibiotic treatment died. Vancomycin and cefotaxime appear to be effective in the treatment of cases produced by strains of pneumococcus with intermediate sensitivity to penicillin. There were no apparent differences in mortality between the cases of endocarditis by pneumococcus sensitive or moderately resistant to penicillin. CONCLUSIONS: Pneumococcal endocarditis continues to condition a high mortality similar to that produced in previously made series. The classic relation with meningitis and pneumonia is infrequent today. The appearance of strains resistant to penicillin may increase the incidence of this infection and further worsen prognosis.

Okadaic acid activates p42 mitogen-activated protein kinase (MAP kinase; ERK-2) in B-lymphocytes but inhibits rather than augments cellular proliferation: contrast with phorbol 12-myristate 13-acetate.

Ligation of the membrane immunoglobulin M receptor as well as stimulation with the protein kinase C agonist phorbol 12-myristate 13-acetate leads to a B-lymphocyte proliferation and differentiation. Both stimuli activate p42 mitogen-activated protein (MAP) kinase in human B-lymphocytes [Casillas, Hanekom, Williams, Katz and Nel (1991) J. Biol. Chem. 266, 19088-19094]. MAP kinase activation is dependent on tyrosine as well as threonine phosphorylation of the kinase and its activity is inhibited by tyrosine as well as threonine/serine phosphatases. Okadaic acid, a specific inhibitor of type 1 and 2A serine/threonine phosphatases, induced MAP kinase activity in a potent and dose-dependent fashion, but failed to induce [3H]thymidine incorporation into normal human tonsil B-cells. Moreover, in combination with membrane immunoglobulin M ligation, okadaic acid decreased rather than increased [3H]thymidine incorporation. The kinetics of MAP kinase activation by okadaic acid differed from phorbol 12-myristate 13-acetate and anti-membrane immunoglobulin M stimulation. Okadaic acid induced tyrosine phosphorylation of 42 kDa and 44 kDa proteins which co-electrophoresed and co-chromatographed with ERK-2 and ERK-1 respectively. Ramos cells also contained a constitutively active 46 kDa MAP kinase which appeared as a separate peak in chromatography and could be immunoprecipitated by an antiserum against a rat ERK-1 fusion protein.

Stimulation of B-cells via the membrane immunoglobulin receptor or with phorbol myristate 13-acetate induces tyrosine phosphorylation and activation of a 42-kDa microtubule-associated protein-2 kinase.

Engagement of membrane IgM on a number of human and murine B-cell lines induced activation of a Mn(2+)-preferring serine/threonine kinase that phosphorylated microtubule-associated protein-2 (MAP-2) in vitro. B-cell MAP-2 kinase (MAP-2K) activity could be fractionated into two peaks by sequential DEAE and hydrophobic chromatography. Although peak I included two tyrosine phosphoproteins of molecular mass 36 and 38 kDa, peak II showed a single 42-kDa tyrosine phosphoprotein (pp42). Since all kinase activity could be removed from peak II material over an antiphosphotyrosine immune affinity column, it suggests that pp42 is identical with lymphoid MAP-2K. Although peak I activity showed a similarity to peak II with regard to its preference for Mn2+, sensitivity to phosphatase exposure, and resistance to a range of common serine kinase inhibitors, it is not clear whether these activities are related. MAP-2 kinase activity could also be induced by treatment with the phorbol ester, phorbol myristate 13-acetate, suggesting that protein kinase C may also be involved with MAP-2K regulation. Although MAP-2K activity reached a peak response within minutes of receptor ligation, there were differences in the rates of dephosphorylation of pp42 and decline of MAP-2K activity in different B-cell lines. The tyrosine phosphatase inhibitor, vanadate, transformed a rapidly reversible MAP-2K response in BAL 17.2 cells into a sustained state of activation that resembled the kinetics of activation in WEHI-231 cells. The latter finding implies involvement of a tyrosine phosphatase, which opposes the effect of an inducing tyrosine kinase.

Acute familial myositis with a common autoimmune response.

In 1986, we diagnosed and treated 4 patients, all members of 1 rural family, who presented simultaneously with a polymyositis-like syndrome, anticytoplasmic antibodies (on HEp-2 cells), and precipitating antibodies of anti-Jo-1 and anti-PM-Scl specificities. Serum samples from these patients reacted by immunodiffusion against serum from a rodent that had been caught in the patients' house. The precipitin line showed complete immunologic identity with anti-Jo-1. To study the specificity of this serum-serum reaction, 2 mice (Mus musculus) and 1 rat (Rattus rattus) from the neighboring areas of the patients' house were caught and killed. Sections of the liver, kidney, spleen, and skeletal muscle were processed for histopathologic examination and for direct and indirect immunofluorescence studies of the patients' sera. The rodents' sera were tested by immunodiffusion against serum samples from 25 patients with systemic lupus erythematosus, 11 with rheumatoid arthritis, 6 with mixed connective tissue disease, and 11 with various other rheumatic diseases, as well as 16 healthy controls. A serum-serum precipitin reaction was noted between the rodents' sera and sera from 2 of the patients with polymyositis-like syndrome. A distinct, but weaker, reaction was found with 2 lupus patients' sera (8%), and with 1 healthy control serum (6%). The rodents' sera were antinuclear antibody positive by indirect immunofluorescence on HEp-2 cells. These results, suggest that some rodents could be carriers of an as-yet-unknown transmissible agent that, in susceptible individuals, induces clinical and serologic manifestations similar to those of polymyositis.