Science in the Service of Patients: Lessons from the Past in the Moral Battle for the Future of Medical Education

Medical schools instill a classic moral standoff in which the responsibility for the betterment of the patient stands at odds with the responsibility for the betterment of society. In critical ways, the latter, in the form of a robust research and technology-driven enterprise, has taken precedence over the former, resulting in harm to patients and individual dignity. This tradeoff can be traced to Abraham Flexner, the father of American medical education. In the wake of the Flexner report, American medicine set out on a course of exponential scientific advancement, but the mistreatment of research subjects and the erosion of the doctor-patient relationship in a health care system that is increasingly unaffordable, complex, and impersonal suggest that such progress has come at a price. Recent efforts by medical schools to emphasize humanism in their curricula and admissions processes have shown promise in orienting the values of academic medicine toward the individual patient’s well-being.     

The Case for Intervention Bias in the Practice of Medicine

Bias is an inclination to present or hold a partial perspective at the expense ofpossibly equal or more valid alternatives. In this paper, we present a series ofconditional arguments to prove that intervention bias exists in the practice ofmedicine. We then explore its potential causes, consequences, and criticisms. Weuse the term to describe the bias on the part of physicians and the medicalcommunity to intervene, whether it is with drugs, diagnostic tests, non-invasiveprocedures, or surgeries, when not intervening would be a reasonablealternative. The recognition of intervention bias in medicine is criticallyimportant given today’s emphasis on providing high-value care and reducingunnecessary and potentially harmful interventions.     

Focus: Sex and Gender Health: Patient Preference for Physician Gender in the Emergency Department

Despite historical gender bias against female physicians, few studies have investigated patients’ physician gender preference in the emergency department (ED) setting. We sought to determine if there is an association between ED patient demographics and physician gender preference. We surveyed patients presenting to an ED to determine association between patient demographics and patient physician gender preference for five ED situations: 1) ‘routine’ visit, 2) emergency visit, 3) ‘sensitive’ medical visit, 4) minor surgical/‘procedural’ visit, and 5) ‘bad news’ delivery. A total of 200 ED patients were surveyed. The majority of ED patients reported no physician gender preference for ‘routine’ visits (89.5 percent), ‘emergent’ visits (89 percent), ‘sensitive’ medical visits (59 percent), ‘procedural’ visits (89 percent) or when receiving ‘bad news’ (82 percent). In the setting of ‘routine’ visits and ‘sensitive’ medical visits, there was a propensity for same-sex physician preference.     

Interaction between Paracoccidioides brasiliensis conidia and the coagulation system: involvement of fibrinogen

The infectious process starts with an initial contact between pathogenand host. We have previously demonstrated that Paracoccidioidesbrasiliensis conidia interact with plasma proteins includingfibrinogen, which is considered the major component of the coagulation system.In this study, we evaluated the in vitro capacity of P.brasiliensis conidia to aggregate with plasma proteins andcompounds involved in the coagulation system. We assessed the aggregation ofP. brasiliensis conidia after incubation with human serumor plasma in the presence or absence of anticoagulants, extracellular matrix(ECM) proteins, metabolic and protein inhibitors, monosaccharides and othercompounds. Additionally, prothrombin and partial thromboplastin times weredetermined after the interaction of P. brasiliensis conidiawith human plasma. ECM proteins, monosaccharides and human plasma significantlyinduced P. brasiliensis conidial aggregation; however,anticoagulants and metabolic and protein inhibitors diminished the aggregationprocess. The extrinsic coagulation pathway was not affected by the interactionbetween P. brasiliensis conidia and plasma proteins, while theintrinsic pathway was markedly altered. These results indicate that P.brasiliensis conidia interact with proteins involved in thecoagulation system. This interaction may play an important role in the initialinflammatory response, as well as fungal disease progression caused byP. brasiliensis dissemination.     

Nematicides and Nonconventional Soil Amendments in the Management of Root-Knot Nematode on Cotton

Granular and liquid commercial humates, with micronutrients, and a microbial fermentation product were compared in several combinations with nematicides for their effects on cotton lint yield and root-knot nematode suppression. Fumigant nematicides effectively reduced cotton root galling caused by root-knot nematodes, and cotton lint yields increased. Organophosphates and carbamates were not effective. Occasionally, cotton lint yields were increased or maintained with combination treatments o f humates, micronutrients, and a microbial fermentation product, but galling o f cotton roots by root-knot nematodes was usually not reduced by these treatments.     

Phytoalexins and their Role in the Resistance of Plants to Nematodes

Phytoalexins are antibiotic compounds synthesized in an infected plant in response to infection. Nematodes are capable of eliciting phytoalexins in resistant plants. Resistant lima bean (Phaseolus lunatus) infected by Pratylenchus penetrans produces the phytoalexin coumestrol; soybean (Glycine max) infected by Meloidogyne incognita produces glyceollin; cotton (Gossypium hirsuturn) infected by M. incognita produces terpenoid aldehydes.     

Domestic,peridomestic and wild hosts in the transmission of Trypanosoma cruzi in the Caatinga area colonised by Triatoma brasiliensis

The role played by different mammal species in the maintenance of Trypanosoma cruzi is not constant and varies in time and place. This study aimed to characterise the importance of domestic, wild and peridomestic hosts in the transmission of T. cruzi in Tauá, state of Ceará, Caatinga area, Brazil, with an emphasis on those environments colonised by Triatoma brasiliensis. Direct parasitological examinations were performed on insects and mammals, serologic tests were performed on household and outdoor mammals and multiplex polymerase chain reaction was used on wild mammals. Cytochrome b was used as a food source for wild insects. The serum prevalence in dogs was 38% (20/53), while in pigs it was 6% (2/34). The percentages of the most abundantly infected wild animals were as follows: Thrichomys laurentius 74% (83/112) and Kerodon rupestris 10% (11/112). Of the 749 triatomines collected in the household research, 49.3% (369/749) were positive for T. brasiliensis, while 6.8% were infected with T. cruzi (25/369). In captured animals, T. brasiliensis shares a natural environment with T. laurentius, K. rupestris, Didelphis albiventris, Monodelphis domestica, Galea spixii, Wiedomys pyrrhorhinos, Conepatus semistriatus and Mus musculus. In animals identified via their food source, T. brasiliensis shares a natural environment with G. spixii, K. rupestris, Capra hircus, Gallus gallus, Tropidurus oreadicus and Tupinambis merianae. The high prevalence of T. cruzi in household and peridomiciliar animals reinforces the narrow relationship between the enzootic cycle and humans in environments with T. brasiliensis and characterises it as ubiquitous.     

Gametogenesis and the Chromosomes of Meloidogyne nataliei: Not Typical of Other Root-knot Nematodes

Studies of oogenesis and spermatogenesis revealed that Meloidogyne nataliei is a diploid, amphimictic species with four (n), relatively large chromosomes, and possibly with an XX ♀-XY ♂ mechanism of sex determination. It differs considerably from all other amphimictic, or meiotically parthenogenetic, species of Meloidogyne which have 13-18 smaller chromosomes and from Meloidogyne (Hypsoperine) spartinae which has seven. Consequently, the taxonomic position of M. nataliei needs to be re-evaluated. The chromosomes of M. nataliei and their behavior during gametogenesis resemble more closely chromosomes of the genus Heterodera than those of the genus Meloidogyne. This resemblance, however, may not imply a closer phyletic relationship of M. nataliei to heteroderid nematodes.     

Biomarkers of therapeutic responses in chronic Chagas disease: state of the art and future perspectives

The definition of a biomarker provided by the World Health Organization is any substance, structure, or process that can be measured in the body, or its products and influence, or predict the incidence or outcome of disease. Currently, the lack of prognosis and progression markers for chronic Chagas disease has posed limitations for testing new drugs to treat this neglected disease. Several molecules and techniques to detect biomarkers in Trypanosoma cruzi-infected patients have been proposed to assess whether specific treatment with benznidazole or nifurtimox is effective. Isolated proteins or protein groups from different T. cruzi stages and parasite-derived glycoproteins and synthetic neoglycoconjugates have been demonstrated to be useful for this purpose, as have nucleic acid amplification techniques. The amplification of T. cruzi DNA using the real-time polymerase chain reaction method is the leading test for assessing responses to treatment in a short period of time. Biochemical biomarkers have been tested early after specific treatment. Cytokines and surface markers represent promising molecules for the characterisation of host cellular responses, but need to be further assessed.     

Ionic imbalance and lack of effect of adjuvant treatment with methylene blue in the hamster model of leptospirosis

Leptospirosis in humans usually involves hypokalaemia andhypomagnesaemia and the putative mechanism underlying such ionic imbalances maybe related to nitric oxide (NO) production. We previously demonstrated thecorrelation between serum levels of NO and the severity of renal disease inpatients with severe leptospirosis. Methylene blue inhibits soluble guanylylcyclase (downstream of the action of any NO synthase isoforms) and was recentlyreported to have beneficial effects on clinical and experimental sepsis. Weinvestigated the occurrence of serum ionic changes in experimental leptospirosisat various time points (4, 8, 16 and 28 days) in a hamster model. We alsodetermined the effect of methylene blue treatment when administered as anadjuvant therapy, combined with late initiation of standard antibiotic(ampicillin) treatment. Hypokalaemia was not reproduced in this model: all ofthe groups developed increased levels of serum potassium (K). Furthermore,hypermagnesaemia, rather than magnesium (Mg) depletion, was observed in thishamster model of acute infection. These findings may be associated with anaccelerated progression to acute renal failure. Adjuvant treatment withmethylene blue had no effect on survival or serum Mg and K levels duringacute-phase leptospirosis in hamsters.     

Blending Genetics and Sociocultural Historical Inquiry: Ethics, Culture,and Human Subjects Protection in International Cross Cultural Research

In this paper, we examine the implementation and difficulties when conductinggenetics research in a rural, traditional West African culture within the frameof the United States’ grounded research ethics. Research challenges arehighlighted by Western researchers following U.S. Institutional Review Board(IRB) guidelines and practices in a non-Western country. IRB concepts areculture bound in Western ideals that may not have synchronicity andcompatibility with non-Western cultures. Differences in sociocultural norms,traditions, language, and geography were influencing factors that can affectapplication of IRB principles. Suggestions for change are offered, which willpotentially aid researchers considering application of IRB requirements whenconducting research in non-Westernized, non-industrialized countries.     

Seasonal variation and natural infection of Lutzomyia antunesi (Diptera: Psychodidae: Phlebotominae), an endemic species in the Orinoquia region of Colombia

Lutzomyia antunesi has been commonly reported in outbreaks of cutaneous leishmaniasis (CL) in the Orinoquia region of Colombia. The bionomics of this species were studied in the municipality of Villavicencio (Meta, Colombia). Sandflies were captured over the course of one week per month for one year in intradomiciliary, peridomiciliary and extradomiciliary housing areas. The captures were performed from 06:00 pm-06:00 am using CDC light traps and the females were processed for polymerase chain reaction (PCR) to detect Leishmania spp. A total of 22,097 specimens and 19 species were captured of which Lu. antunesi (89%) and Lutzomyia walkeri (5%) were the most abundant. Other species recognised as anthropophilic (Lutzomyia panamensis, Lutzomyia gomezi, Lutzomyia flaviscutellata and Lutzomyia fairtigi) were present in very low abundance (< 2%). Natural infection with Leishmania spp was detected using PCR in Lu. antunesi, Lu. panamensis and Lu. flavicutellata, showing infection rates of 1%, 4.8% and 7.5%, respectively. The present paper provides information on various ecological aspects of Lu. antunesi. An analysis of seasonality shows that this species increases in abundance in the hottest months (December, January and February), directly correlating with the maximum temperature and inversely correlating with precipitation. The natural infection rate is associated with the peaks of highest abundance.     

Frequency and molecular characterisation of Entamoeba histolytica,Entamoeba dispar,Entamoeba moshkovskii,and Entamoeba hartmanni in the context of water scarcity in northeastern Brazil

This study aimed to estimate the frequency, associated factors, and molecularcharacterisation of Entamoeba histolytica, Entamoebadispar, Entamoeba moshkovskii, andEntamoebahartmanni infections. We performed a survey (n = 213 subjects) to obtainparasitological, sanitation, and sociodemographic data. Faecal samples were processedthrough flotation and centrifugation methods.E. histolytica,E. dispar, E. moshkovskii, and E.hartmanni were identified by nested-polymerase chain reaction (PCR). Theoverall prevalence of infection was 22/213 (10.3%). The infection rate among subjectswho drink rainwater collected from roofs in tanks was higher than the rate insubjects who drink desalinated water pumped from wells; similarly, the infection rateamong subjects who practice open defecation was significantly higher than that ofsubjects with latrines. Out of the 22 samples positive for morphologicallyindistinguishableEntamoeba species, the differentiation by PCRwas successful for 21. The species distribution was as follows: 57.1% to E.dispar, 23.8% to E. histolytica, 14.3% toE.histolytica and E. dispar, and 4.8% E.dispar and E. hartmanni. These data suggest a highprevalence of asymptomatic infection by the group of morphologicallyindistinguishable Entamoebahistolytica/dispar/moshkovskiicomplexand E. hartmanni species. In this context of water scarcity, thesanitary and socioenvironmental characteristics of the region appear to favourtransmission.     

The role of chromosomal rearrangements and geographical barriers in the divergence of lineages in a South American subterranean rodent (Rodentia: Ctenomyidae: Ctenomys minutus)

Identifying factors and the extent of their roles in the differentiation of populations is of great importance for understanding the evolutionary process in which a species is involved. Ctenomys minutus is a highly karyotype–polymorphic subterranean rodent, with diploid numbers ranging from 42 to 50 and autosomal arm numbers (ANs) ranging from 68 to 80, comprising a total of 45 karyotypes described so far. This species inhabits the southern Brazilian coastal plain, which has a complex geological history, with several potential geographical barriers acting on different time scales. We assessed the geographical genetic structure of C. minutus, examining 340 individuals over the entire distributional range and using information from chromosomal rearrangements, mitochondrial DNA (mtDNA) sequences and 14 microsatellite loci. The mtDNA results revealed seven main haplogroups, with the most recent common ancestors dating from the Pleistocene, whereas clustering methods defined 12 populations. Some boundaries of mtDNA haplogroups and population clusters can be associated with potential geographical barriers to gene flow. The isolation-by-distance pattern also has an important role in fine-scale genetic differentiation, which is strengthened by the narrowness of the coastal plain and by common features of subterranean rodents (that is, small fragmented populations and low dispersal rates), which limit gene flow among populations. A step-by-step mechanism of chromosomal evolution can be suggested for this species, mainly associated with the metapopulation structure, genetic drift and the geographical features of the southern Brazilian coastal plain. However, chromosomal variations have no or very little role in the diversification of C. minutus populations.     

Delay and failure in treatment seeking after first onset of mental disorders in the World Health Organization's World Mental Health Survey Initiative

Data are presented on patterns of failure and delay in making initial treatmentcontact after first onset of a mental disorder in 15 countries in the WorldHealth Organization (WHO)''s World Mental Health (WMH) Surveys. Representativeface-to-face household surveys were conducted among 76,012 respondents aged18 and older in Belgium, Colombia, France, Germany, Israel, Italy, Japan,Lebanon, Mexico, the Netherlands, New Zealand, Nigeria, People''s Republicof China (Beijing and Shanghai), Spain, and the United States. The WHO CompositeInternational Diagnostic Interview (CIDI) was used to assess lifetime DSM-IVanxiety, mood, and substance use disorders. Ages of onset for individual disordersand ages of first treatment contact for each disorder were used to calculatethe extent of failure and delay in initial help seeking. The proportion oflifetime cases making treatment contact in the year of disorder onset rangedfrom 0.8 to 36.4% for anxiety disorders, from 6.0 to 52.1% for mood disorders,and from 0.9 to 18.6% for substance use disorders. By 50 years, the proportionof lifetime cases making treatment contact ranged from 15.2 to 95.0% for anxietydisorders, from 7.9 to 98.6% for mood disorders, and from 19.8 to 86.1% forsubstance use disorders. Median delays among cases eventually making contactranged from 3.0 to 30.0 years for anxiety disorders, from 1.0 to 14.0 yearsfor mood disorders, and from 6.0 to 18.0 years for substance use disorders.Failure and delays in treatment seeking were generally greater in developingcountries, older cohorts, men, and cases with earlier ages of onset. Theseresults show that failure and delays in initial help seeking are pervasiveproblems worldwide. Interventions to ensure prompt initial treatment contactsare needed to reduce the global burdens and hazards of untreated mental disorders.     

Morphology of the larvae,male genitalia and DNA sequences of Anopheles (Kerteszia) pholidotus (Diptera: Culicidae) from Colombia

Since 1984, Anopheles (Kerteszia) lepidotus has been considered amosquito species that is involved in the transmission of malaria in Colombia, afterhaving been incriminated as such with epidemiological evidence from a malariaoutbreak in Cunday-Villarrica, Tolima. Subsequent morphological analyses of femalescaptured in the same place and at the time of the outbreak showed that the speciesresponsible for the transmission was not An. lepidotus, but ratherAnopheles pholidotus. However, the associated morphologicalstages and DNA sequences of An. pholidotus from the foci ofCunday-Villarrica had not been analysed. Using samples that were caught recently fromthe outbreak region, the purpose of this study was to provide updated and additionalinformation by analysing the morphology of female mosquitoes, the genitalia of malemosquitoes and fourth instar larvae of An. pholidotus, which wasconfirmed with DNA sequences of cytochrome oxidase I and rDNA internal transcribedspacer. A total of 1,596 adult females were collected in addition to 37 larvalcollections in bromeliads. Furthermore, 141 adult females, which were captured fromthe same area in the years 1981-1982, were analysed morphologically. Ninety-five DNAsequences were analysed for this study. Morphological and molecular analyses showedthat the species present in this region corresponds to An.pholidotus. Given the absence of An. lepidotus, even inrecent years, we consider that the species of mosquitoes that was previouslyincriminated as the malaria vector during the outbreak was indeed An.pholidotus, thus ending the controversy.     

Bacterial diversity in relation to secondary production and succession on surfaces of the kelp Laminaria hyperborea

Kelp forests worldwide are known as hotspots for macroscopic biodiversity and primary production, yet very little is known about the biodiversity and roles of microorganisms in these ecosystems. Secondary production by heterotrophic bacteria associated to kelp is important in the food web as a link between kelp primary production and kelp forest consumers. The aim of this study was to investigate the relationship between bacterial diversity and two important processes in this ecosystem; bacterial secondary production and primary succession on kelp surfaces. To address this, kelp, Laminaria hyperborea, from southwestern Norway was sampled at different geographical locations and during an annual cycle. Pyrosequencing (454-sequencing) of amplicons of the 16S rRNA gene of bacteria was used to study bacterial diversity. Incorporation of tritiated thymidine was used as a measure of bacterial production. Our data show that bacterial diversity (richness and evenness) increases with the age of the kelp surface, which corresponds to the primary succession of its bacterial communities. Higher evenness of bacterial operational taxonomical units (OTUs) is linked to higher bacterial production. Owing to the dominance of a few abundant OTUs, kelp surface biofilm communities may be characterized as low-diversity habitats. This is the first detailed study of kelp-associated bacterial communities using high-throughput sequencing and it extends current knowledge on microbial community assembly and dynamics on living surfaces.     

Focus: Preventive Medicine: Before the Bullets Fly: The Physician’s Role in Preventing Firearm Injury

Firearm injury is a disease that is disproportionately prevalent in the United States. When a bullet hits a human being, it brings together multiple structural determinants of health into one acute, life-changing event. Firearm injury can lead to long-term mental and physical challenges for individuals, families, and communities. Despite the impact of this disease, physicians often underestimate their role in not only treating but also preventing firearm injury. Physicians can intervene through screening, counseling, community engagement, and advocacy, and can mobilize the health care systems they serve to engage with injury prevention. Physicians also play a key role in expanding the knowledge base on firearm injury through much-needed research on the epidemiology, context, and outcomes of firearm injury. When we treat firearm injury as a disease, we can develop and implement interventions from the clinic to the statehouse that can curb profound harms. This work and these opportunities belong not only to emergency physicians and trauma surgeons, but to all fields that evaluate and assess patients over the life course.     

Effects of Cholesterol-Loaded Cyclodextrins on the Rate and the Quality of Motility in Frozen and Thawed Rabbit Sperm

The motility of sperm after freezing and thawing is critical for effective cryopreservation. It is known that supplementation with cholesterol-loaded cyclodextrin (CLC) improves cryosurvival of sperm in various animals. To clarify the effects of supplementation with CLC on rabbit sperm motility after freezing and thawing, rabbit sperm motility was analyzed using a computer-assisted sperm analysis system. Sperm motility with CLC supplementation was 29.4 ± 9.6% (mean ± SD), which was significantly higher than that of controls (20.8 ± 7.1%, P<0.05). The curvilinear velocity of sperm with CLC exceeded that of controls, whereas the values for linearity and wobble were significantly lower in sperm with CLC compared with controls. After artificial insemination, 44.3% of recovered ova were fertilized in the CLC-supplemented group, which was higher than the percentage in the control group (36.4%). The results indicate that supplementation with CLC improves the rate and quality of motility in rabbit sperm after freezing and thawing, and would be advantageous for successful cryopreservation.