Essential anatomy for core clerkships: A clinical perspective.

Clerkships are defining experiences for medical students in which students integrate basic science knowledge with clinical information as they gain experience in diagnosing and treating patients in a variety of clinical settings. Among the basic sciences, there is broad agreement that anatomy is foundational for medical practice. Unfortunately, there are longstanding concerns that student knowledge of anatomy is below the expectations of clerkship directors and clinical faculty. Most allopathic medical schools require eight "core" clerkships: internal medicine (IM), pediatrics (PD), general surgery (GS), obstetrics and gynecology (OB), psychiatry (PS), family medicine (FM), neurology (NU), and emergency medicine (EM). A targeted needs assessment was conducted to determine the anatomy considered important for each core clerkship based on the perspective of clinicians teaching in those clerkships. A total of 525 clinical faculty were surveyed at 24 United States allopathic medical schools. Participants rated 97 anatomical structure groups across all body regions on a 1-4 Likert-type scale (1 = not important, 4 = essential). Non-parametric ANOVAs determined if differences existed between clerkships. Combining all responses, 91% of anatomical structure groups were classified as essential or more important. Clinicians in FM, EM, and GS rated anatomical structures in most body regions significantly higher than at least one other clerkship (p = 0.006). This study provides an evidence-base of anatomy content that should be considered important for each core clerkship and may assist in the development and/or revision of preclinical curricula to support the clinical training of medical students.

A unique and effective method of anatomy education: Small-group learning with prosected plastinated specimens.

OBJECTIVE: At the New York University College of Dentistry, we are faced with the challenge of teaching Head and Neck Anatomy to a class of approximately 380 first-year students. We have developed an innovative anatomy curriculum that has proven effective in facilitating students' learning and long-term retention of the material. It has the added benefit of being time- and cost-efficient. Here, we share the structure of our curriculum and examine the student outcomes and student feedback. MATERIALS AND METHODS: In this paper, we describe the evidence-based methods used in our course and present measures of student success. We also surveyed students about aspects of the anatomy curriculum. RESULTS: Our curriculum efficiently manages cost, instructional time, and classroom space, while promoting student success. Over the last 9 years, NYU Dentistry students have achieved a mean first-time pass rate of 98.6% and an average anatomy score of 1.74 standard deviations above the national mean on the National Board Dental Examination Part I. Students agree with instructor assessments of which features of the curriculum are valuable and state that the course helps them prepare for clinical courses. CONCLUSION: We believe that the main factors in the success of our course are the small group setting, the benefits of spaced repetition and frequent quizzes, and the use of plastinated specimens in place of wet cadavers.

Deletion Mutants of the Attenuated Recombinant ASF Virus, BA71ΔCD2, Show Decreased Vaccine Efficacy.

African swine fever (ASF) has become the major threat to the global swine industry. Lack of available commercial vaccines complicates the implementation of global control strategies. So far, only live attenuated ASF viruses (ASFV) have demonstrated solid protection efficacy at the experimental level. The implementation of molecular techniques has allowed the generation of a collection of deletion mutants lacking ASFV-specific virulence factors, some of them with promising potential as vaccine candidates against the pandemic genotype II ASFV strain currently circulating in Africa, Europe, Asia and Oceania. Despite promising results, there is room for improvement, mainly from the biosafety point of view. Aiming to improve the safety of BA71∆CD2, a cross-protective recombinant live attenuated virus (LAV) lacking the ASFV CD2v gene (encoding ß-glucuronidase as a reporter gene) available in our laboratory, three new recombinants were generated using BA71∆CD2 as a template: the single mutant BA71∆CD2f, this time containing the fluorescent mCherry reporter gene instead of CD2v, and two double recombinants lacking CD2v and either the lectin gene (EP153R) or the uridine kinase (UK) gene (DP96R). Comparative in vivo experiments using BA71∆CD2f, BA71∆CD2DP96R and BA71∆CD2EP153R recombinant viruses as immunogens, demonstrated that deletion of either DP96R or EP153R from BA71∆CD2f decreases vaccine efficacy and does not improve safety. Our results additionally confirm ASFV challenge as the only available method today to evaluate the protective efficacy of any experimental vaccine. We believe that understanding the fine equilibrium between attenuation and inducing protection in vivo deserves further study and might contribute to more rational vaccine designs in the future.

Live Attenuated African Swine Fever Viruses as Ideal Tools to Dissect the Mechanisms Involved in Cross-Protection.

African swine fever (ASF) has become the major threat for the global swine industry. Furthermore, the epidemiological situation of African swine fever virus (ASFV) in some endemic regions of Sub-Saharan Africa is worse than ever, with multiple virus strains and genotypes currently circulating in a given area. Despite the recent advances on ASF vaccine development, there are no commercial vaccines yet, and most of the promising vaccine prototypes available today have been specifically designed to fight the genotype II strains currently circulating in Europe, Asia, and Oceania. Previous results from our laboratory have demonstrated the ability of BA71∆CD2, a recombinant LAV lacking CD2v, to confer protection against homologous (BA71) and heterologous genotype I (E75) and genotype II (Georgia2007/01) ASFV strains, both belonging to same clade (clade C). Here, we extend these results using BA71∆CD2 as a tool trying to understand ASFV cross-protection, using phylogenetically distant ASFV strains. We first observed that five out of six (83.3%) of the pigs immunized once with 106 PFU of BA71∆CD2 survived the tick-bite challenge using Ornithodoros sp. soft ticks naturally infected with RSA/11/2017 strain (genotype XIX, clade D). Second, only two out of six (33.3%) survived the challenge with Ken06.Bus (genotype IX, clade A), which is phylogenetically more distant to BA71∆CD2 than the RSA/11/2017 strain. On the other hand, homologous prime-boosting with BA71∆CD2 only improved the survival rate to 50% after Ken06.Bus challenge, all suffering mild ASF-compatible clinical signs, while 100% of the pigs immunized with BA71∆CD2 and boosted with the parental BA71 virulent strain survived the lethal challenge with Ken06.Bus, without almost no clinical signs of the disease. Our results confirm that cross-protection is a multifactorial phenomenon that not only depends on sequence similarity. We believe that understanding this complex phenomenon will be useful for designing future vaccines for ASF-endemic areas.

Fecal microbiota transplantation from warthog to pig confirms the influence of the gut microbiota on African swine fever susceptibility.

African swine fever virus (ASFV) is the causative agent of a devastating hemorrhagic disease (ASF) that affects both domestic pigs and wild boars. Conversely, ASFV circulates in a subclinical manner in African wild pigs, including warthogs, the natural reservoir for ASFV. Together with genetic differences, other factors might be involved in the differential susceptibility to ASF observed among Eurasian suids (Sus scrofa) and African warthogs (Phacochoerus africanus). Preliminary evidence obtained in our laboratory and others, seems to confirm the effect that environmental factors might have on ASF infection. Thus, domestic pigs raised in specific pathogen-free (SPF) facilities were extremely susceptible to highly attenuated ASFV strains that were innocuous to genetically identical domestic pigs grown on conventional farms. Since gut microbiota plays important roles in maintaining intestinal homeostasis, regulating immune system maturation and the functionality of the innate/adaptive immune responses, we decided to examine whether warthog fecal microbiota transplantation (FMT) to domestic pigs affects host susceptibility to ASFV. The present work demonstrates that warthog FMT is not harmful for domestic weaned piglets, while it modifies their gut microbiota; and that FMT from warthogs to pigs confers partial protection against attenuated ASFV strains. Future work is needed to elucidate the protective mechanisms exerted by warthog FMT.

African swine fever vaccines: a promising work still in progress.

ABSTRACT: African swine fever (ASF), a disease of obligatory declaration to the World Organization for Animal Health (OIE), has contributed to poverty and underdevelopment of affected areas. The presence of ASF has been historically neglected in Africa, contributing to its uncontrolled expansion and favouring its spread to continental Europe on at least three occasions, the last one in 2007 through the Republic of Georgia. Since then, African swine fever virus (ASFV) has spread to neighbouring countries, reaching the European Union in 2014, China in the summer of 2018 and spreading through Southeast Asia becoming a global problem. Lack of available vaccines against ASF makes its control even more difficult, representing today the number one threat for the swine industry worldwide and negatively affecting the global commerce equilibrium. MAIN BODY: In this review, we intend to put in perspective the reality of ASF vaccination today, taking into account that investment into ASF vaccine development has been traditionally unattractive, overall since ASF-free areas with large swine industries applied a non-vaccination policy for diseases listed by the OIE. The dramatic situation suffered in Asia and the increasing threat that ASF represents for wealthy countries with large swine industries, has dramatically changed the perspective that both private and public bodies have about ASF vaccinology, although this is controversial. The feasibility of modifying the ASFV genome has led to safe and efficacious experimental recombinant live attenuated viruses (LAVs). The main challenge today will be confirming the safety and efficacy of these technologies in the field, accelerating transfer to the industry for official registration and commercialization. The complexity of ASFV, together with the lack of knowledge about the mechanisms involved in protection and the specific antigens involved in it, requires further investment in research and development. Although far from the efficacy achieved by LAVs, subunit vaccines are the optimal choice for the future. If the world can wait for them or not is a contentious issue. CONCLUSION: Despite their inherent disadvantages, LAVs will be the first technology to reach the market, while subunit vaccines will need much further research to become a successful commercial reality.

Deletion of the Gene for the Type I Interferon Inhibitor I329L from the Attenuated African Swine Fever Virus OURT88/3 Strain Reduces Protection Induced in Pigs.

Live attenuated vaccines are considered to be the fastest route to the development of a safe and efficacious African swine fever (ASF) vaccine. Infection with the naturally attenuated OURT88/3 strain induces protection against challenge with virulent isolates from the same or closely related genotypes. However, adverse clinical signs following immunisation have been observed. Here, we attempted to increase the OURT88/3 safety profile by deleting I329L, a gene previously shown to inhibit the host innate immune response. The resulting virus, OURT88/3ΔI329L, was tested in vitro to evaluate the replication and expression of type I interferon (IFN) and in vivo by immunisation and lethal challenge experiments in pigs. No differences were observed regarding replication; however, increased amounts of both IFN-ß and IFN-α were observed in macrophages infected with the deletion mutant virus. Unexpectedly, the deletion of I329L markedly reduced protection against challenge with the virulent OURT88/1 isolate. This was associated with a decrease in both antibody levels against VP72 and the number of IFN-γ-producing cells in the blood of non-protected animals. Furthermore, a significant increase in IL-10 levels in serum was observed in pigs immunised with OURT88/3ΔI329L following challenge. Interestingly, the deletion of the I329L gene failed to attenuate the virulent Georgia/2007 isolate.

BA71ΔCD2: a New Recombinant Live Attenuated African Swine Fever Virus with Cross-Protective Capabilities.

African swine fever is a highly contagious viral disease of mandatory declaration to the World Organization for Animal Health (OIE). The lack of available vaccines makes its control difficult; thus, African swine fever virus (ASFV) represents a major threat to the swine industry. Inactivated vaccines do not confer solid protection against ASFV. Conversely, live attenuated viruses (LAV), either naturally isolated or obtained by genetic manipulation, have demonstrated reliable protection against homologous ASFV strains, although little or no protection has been demonstrated against heterologous viruses. Safety concerns are a major issue for the use of ASFV attenuated vaccine candidates and have hampered their implementation in the field so far. While trying to develop safer and efficient ASFV vaccines, we found that the deletion of the viral CD2v (EP402R) gene highly attenuated the virulent BA71 strain in vivo Inoculation of pigs with the deletion mutant virus BA71ΔCD2 conferred protection not only against lethal challenge with the parental BA71 but also against the heterologous E75 (both genotype I strains). The protection induced was dose dependent, and the cross-protection observed in vivo correlated with the ability of BA71ΔCD2 to induce specific CD8+ T cells capable of recognizing both BA71 and E75 viruses in vitro Interestingly, 100% of the pigs immunized with BA71ΔCD2 also survived lethal challenge with Georgia 2007/1, the genotype II strain of ASFV currently circulating in continental Europe. These results open new avenues to design ASFV cross-protective vaccines, essential to fight ASFV in areas where the virus is endemic and where multiple viruses are circulating.IMPORTANCE African swine fever virus (ASFV) remains enzootic in most countries of Sub-Saharan Africa, today representing a major threat for the development of their swine industry. The uncontrolled presence of ASFV has favored its periodic exportation to other countries, the last event being in Georgia in 2007. Since then, ASFV has spread toward neighboring countries, reaching the European Union's east border in 2014. The lack of available vaccines against ASFV makes its control difficult; so far, only live attenuated viruses have demonstrated solid protection against homologous experimental challenges, but they have failed at inducing solid cross-protective immunity against heterologous viruses. Here we describe a new LAV candidate with unique cross-protective abilities: BA71ΔCD2. Inoculation of BA71ΔCD2 protected pigs not only against experimental challenge with BA71, the virulent parental strain, but also against heterologous viruses, including Georgia 2007/1, the genotype II strain of ASFV currently circulating in Eastern Europe.

Genetic polymorphisms located in genes related to immune and inflammatory processes are associated with end-stage renal disease: a preliminary study.

BACKGROUND: Chronic kidney disease progression has been linked to pro-inflammatory cytokines and markers of inflammation. These markers are also elevated in end-stage renal disease (ESRD), which constitutes a serious public health problem. OBJECTIVE: To investigate whether single nucleotide polymorphisms (SNPs) located in genes related to immune and inflammatory processes, could be associated with ESRD development. DESIGN AND METHODS: A retrospective case-control study was carried out on 276 patients with ESRD and 288 control subjects. Forty-eight SNPs were genotyped via SNPlex platform. Logistic regression was used to assess the relationship between each sigle polymorphism and the development of ESRD. RESULTS: Four polymorphisms showed association with ESRD: rs1801275 in the interleukin 4 receptor (IL4R) gene (OR: 0.66 (95%CI = 0.46-0.95); p = 0.025; overdominant model), rs4586 in chemokine (C-C motif) ligand 2 (CCL2) gene (OR: 0.70 (95%CI = 0.54-0.90); p = 0.005; additive model), rs301640 located in an intergenic binding site for signal transducer and activator of transcription 4 (STAT4) (OR: 1.82 (95%CI = 1.17-2.83); p = 0.006; additive model) and rs7830 in the nitric oxide synthase 3 (NOS3) gene (OR: 1.31 (95%CI = 1.01-1.71); p = 0.043; additive model). After adjusting for multiple testing, results lost significance. CONCLUSION: Our preliminary data suggest that four genetic polymorphisms located in genes related to inflammation and immune processes could help to predict the risk of developing ESRD.

Genetic polymorphisms located in TGFB1, AGTR1, and VEGFA genes are associated to chronic renal allograft dysfunction.

BACKGROUND: Persistent inflammation and fibrosis have been related to active progression of renal deterioration and reduced survival of kidney transplant. The aim of this study was to determine the impact of single-nucleotide polymorphisms (SNPs) located in regions related to inflammatory and immune processes on the development of chronic renal allograft dysfunction (CRAD). METHODS: A retrospective study was carried out on 276 patients who received kidney transplant (KT). SNPs were genotyped via the SNPlex platform. Statistical analysis was performed with SNPstat and regression logistic analyses were adjusted by age and gender of recipients and donors, cold ischemia time and the number of human leukocyte antigen (HLA) mismatches. RESULTS: From 276 patients with KT, 118 were non-CRAD and 158 were CRAD. Three SNPs showed significant associations with CRAD development: rs1800471 in transforming growth factor beta 1 (TGFB1), rs5186 in angiotensin II receptor type 1 (AGTR1), and rs699947 in vascular endothelial growth factor A (VEGFA). GC genotype of rs1800471 was associated with increased odds of CRAD compared to GG genotype (OR=2.65 (95% confidence interval (CI)=1.09; 6.47), p=0.025), as well as AC and AA genotype of rs699947 assuming a dominant model (OR=1.80 (95% CI=1.02; 3.20), p=0.044). Besides, AC and CC genotypes of rs5186 were associated with reduced odds of CRAD assuming a dominant model (OR=0.56 (95% CI=0.33; 0.96), p=0.033). CONCLUSION: Our findings suggest that three genes related to immunity and inflammation (rs1800471, rs5186 and rs699947) are associated to susceptibility or protection to CRAD, and might have diagnostic utility in predicting the likelihood of developing CRAD.

Estudio cualitativo sobre la autopercepción del estigma social en personas con esquizofrenia / Qualitative study about the self perception of social stigma in people with schizophrenia

Introducción y objetivos: Pocos son los estudios que evaluan la autopercepción del estigma social en las personas que padecen esquizofrenia. El objetivo del presente estudio consiste en analizar la percepción sobre la esquizofrenia que tienen las personas que la padecen. Material y métodos: Se realizaron dos sesiones en cuatro grupos focales de personas con esquizofrenia que estaban siendo atendidas en servicios de rehabilitación psicosocial del Parc Sanitari de Sant Joan de Déu. A partir de un guión establecido se valoraron un total de 11 áreas abordadas en los grupos. Resultados: Las áreas de peligrosidad, culpa, pérdida de roles sociales y miedo al rechazo fueron aquellas que más mencionaron y más preocupaban a las personas que participaron en los grupos focales. Conclusión: Intervenciones para reducir el estigma social en la comunidad y en los propios usuarios/as deberían ser tenidas en cuenta, especialmente en estas área (AU)

Introduction and Objetives: Few studies evaluated the perception of social stigma in people with schizophrenia. The aim of this study was to analyze the perception of people who suffers schizophrenia. Material and methods: Two sessions in four focus groups of people with schizophrenia who were being treated in psychosocial rehabilitation services Sanitari Parc de Sant Joan de Déu were done. A total of 11 areas (guided by a screenplay) were assessed in the groups. Results: The areas of danger, guilt, lost of social roles and fear of rejection were those most concerned and most mencioned by the people who took part in focus groups. Conclusion: Interventions to reduce social stigma in the community and in the self- users should be taken into account, especially in these areas (AU)

Using "Mighty Mouse" to understand masticatory plasticity: myostatin-deficient mice and musculoskeletal function.

Knockout mice lacking myostatin (Mstn), a negative regulator of the growth of skeletal muscle, develop significant increases in the relative mass of masticatory muscles as well as the ability to generate higher maximal muscle forces. Wild-type and Mstn-deficient mice were compared to investigate the postnatal influence of elevated masticatory loads due to increased jaw-adductor and bite forces on the biomineralization of mandibular articular and cortical bone, the internal structure of the jaw joints, and the composition of temporomandibular joint (TMJ) articular cartilage. To provide an interspecific perspective on the long-term responses of mammalian jaw joints to altered loading conditions, the findings on mice were compared to similar data for growing rabbits subjected to long-term dietary manipulation. Statistically significant differences in joint proportions and bone mineral density between normal and Mstn-deficient mice, which are similar to those observed between rabbit loading cohorts, underscore the need for a comprehensive analysis of masticatory tissue plasticity vis-à-vis altered mechanical loads, one in which variation in external and internal structure are considered. Differences in the expression of proteoglycans and type-II collagen in TMJ articular cartilage between the mouse and rabbit comparisons suggest that the duration and magnitude of the loading stimulus will significantly affect patterns of adaptive and degradative responses. These data on mammals subjected to long-term loading conditions offer novel insights regarding variation in ontogeny, life history, and the ecomorphology of the feeding apparatus.

A novel transgenic mouse model of fetal encephalization and craniofacial development.

There are surprisingly few experimental models of neural growth and cranial integration. This, and the dearth of information regarding fetal brain development, detracts from a mechanistic understanding of cranial integration and its relevance to the ontogenetic and interspecific patterning of the form of the skull. To address this shortcoming, our research uses transgenic mice expressing a stabilized form of ß-catenin to isolate the effects of encephalization on the development of the basi- and neuro-cranium. These mice develop highly enlarged brains due to an increase in neural precursor cells, and differences between transgenic and wild-type mice are predicted to result solely from variation in relative brain size. By focusing on prenatal growth, this project adds to our understanding of a critically important period when major structural and functional interrelationships are established in the skull. Comparisons of wild-type and transgenic mice were performed using microcomputed tomography (microCT) and magnetic resonance imaging (MRI). These analyses show that the larger brains of the transgenic mice are associated with a larger neurocranium and an altered basicranial morphology. However, body size and postcranial ossification do not seem to be affected by the transgene. Comparisons of the rate of postcranial and cranial ossification also point to an unexpected effect of neural growth on skull development: increased fetal encephalization may result in a compensatory decrease in the level of cranial ossification. Therefore, if other life-history factors are held constant, the ontogeny of a metabolically costly structure, such as a brain, may occur at the expense of other cranial structures. These analyses indicate the benefits of a multifactorial approach to cranial integration using a mouse model.