Mecanismo y diseño de vacunas para el sars-cov-2, revisión narrativa / Mechanism and design of vaccines against sars-cov-2, narrative review / Mecanismo e desenho de vacinas para sars-cov-2, revisão narrativa

La infección por el virus SARS-CoV-2, conocida como COVID-19, ha causado alta morbilidad y mortalidad en el mundo. Después de haber descifrado el código genético del virus y haber desarrollado un gran trabajo investigativo en la creación de vacunas, con diversas estrategias de acción, se ha logrado disminuir la morbi mortalidad. Fue necesario acelerar el proceso de producción de vacunas, lo cual estuvo facilitado por el avanzado conocimiento científico en el campo de la genética y la virología, para brindar a la especie humana una protección eficaz y segura contra la agresiva y progresiva infección. Las vacunas se clasifican de acuerdo con su mecanismo de acción, existen vacunas basadas en vectores virales que no se replican, vacunas recombinantes, otras basadas en virus atenuados y virus inactivos, y (la gran novedad de la ciencia actual) las vacunas basadas en ARN mensajero y ADN. Estas últimas han demostrado una gran eficacia y seguridad en la prevención de la infección por el SARS-CoV-2, también han impactado de manera fuerte, por lo que han reducido la infección y la mortalidad en la población. En consecuencia, cada día que pasa desde que se inició el periodo de vacunación mundial, se evidencia una reducción en la curva de contagio y mortalidad por COVID-19.

The infection produced by the SARS-CoV-2 virus, known as COVID-19, has caused high morbidity and mortality across the world. After having deciphered the virus's genoma and carried out investigative endeavors that led to the creation of a variety of vaccines with different mechanisms of action, it has been possible to decrease the morbidity and mortality associated with the virus. It was necessary to accelerate the vaccine production process, which was facilitated by advanced scientific knowledge within the disciplines of genetics and virology, in order to provide the human species with a safe and effective form of protection against the aggressive and progressive infection. Vaccines are classified differently depending on their action mechanisms: there are some based on non-replicating viral vectors, recombinant vaccines, ones that are based on attenuated or inactivated viruses, and (the greatest novelty of current scientific developments) vaccines based on DNA and messenger RNA. The latter has demonstrated significant efficacy and safety in the prevention of the SARS-CoV-2 infection as observed in preliminary studies, and they have meaningfully impacted the population by reducing the rates of infection and mortality. As a result, decreased levels of spread of and mortality from COVID-19 have been evidenced across the globe following the beginning of the vaccine distribution period.

A infecção pelo vírus SARS-CoV-2, conhecido como COVID-19, tem causado elevada morbidade e mortalidade no mundo. Depois de ter decifrado o código genético do virus e de ter realizado um grande trabalho de investigação na criação de vacinas, com diversas estratégias de ação, a morbilidade e a mortalidade foram reduzidas. Foi necessário acelerar o processo de produção de vacinas, facilitado por conhecimentos científicos avançados no domínio da genética e da virologia, para proporcionar à espécie humana uma proteção eficaz e segura contra a infecção agressiva e progressiva. As vacinas são classificadas de acordo com seu mecanismo de ação, existem vacinas baseadas em vetores virais que não se replicam, vacinas recombinantes, outras baseadas em virus atenuados e vírus inativos, e (a grande novidade da ciência atual) vacinas baseadas em RNA mensageiro e ADN. Estas últimas demonstraram grande eficácia e segurança na prevenção da infecção por SARS-CoV-2, mas também tiveram um forte impacto, razão pela qual reduziram a infecção e a mortalidade na população. Consequentemente, a cada dia que passa desde o início do período global de vacinação, fica evidente uma redução na curva de contágio e mortalidade por COVID-19.

Bipolar radiofrequency ablation of genicular nerves in chronic knee pain: A novel technique for more complete sensory denervation.

BACKGROUND: Monopolar radiofrequency ablation (MRFA) of the genicular nerves has been considered the main interventional treatment for chronic knee pain. However, the variable locations of these nerves could suggest that traditional MRFA of genicular nerves may be insufficient to cover the area needed to provide complete sensory denervation. For these reasons, some alternatives have been proposed to achieve an increase in the lesion area that offers better outcomes such a bipolar radiofrequency ablation (BRFA). OBJECTIVE: To describe the efficacy and safety of the bipolar radiofrequency ablation (BRFA) of the genicular nerves in the patients with chronic knee pain. METHODS: A retrospective study was conducted in the Pain Medicine Department. Institutional review board approval from the Hospital Ethical Committee and informed consent were obtained. We reviewed our database for BRFA of genicular nerves from January 2018 to December 2021 for patients with chronic knee pain. The cannulas were placed using ultrasound guidance (10 cm, 22-gauge and 10 mm active curved tip), and each pair of cannulas were subjected to BRFA for 90 seconds at 80∘C. Data analysis was conducted using T-test for paired variables (Visual analogue scale and EuroQol, an instrument intended to complement other forms of quality-of-life measures). RESULTS: Twenty-five patients met inclusion criteria after excluding 7 based on the study design. The mean improvement of our patients according to the VAS was -3.98 (95%CI: -4.37 to -3.59) p< 0.0001 and EuroQol +0.416 (95%CI: 0.364 to 0.468) p< 0.0001. The mean duration of improvement was 8 (6-11) months after BRFA. There were no reported serious adverse events related to the procedure, only local pain for 24 to 48 hours in 3 patients. CONCLUSIONS: We can conclude that BRFA reduces procedural pain and increases the treatment area, providing more complete sensory denervation and improved clinical outcomes.

Intravitreal Anti-Vascular Endothelial Growth Factor Therapies for Retinal Disorders.

Vascular endothelial growth factors (VEGFs) are key mediator of retinal and choroidal neovascularization as well as retinal vascular leakage leading to macular edema. As such, VEGF plays an important role in mediating visually significant complications associated with common retinal disorders such as diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration. Various drugs that inhibit vascular endothelial growth factors (anti-VEGF therapies) have been developed to minimize vision loss associated with these disorders. These drugs are injected into the vitreous cavity in a clinic setting at regular intervals. This article provides an overview of the various anti-VEGF drugs used in ophthalmology and the common retinal conditions that benefit from this therapy.

The role of transcription factors in shaping regulatory T cell identity.

Forkhead box protein 3-expressing (FOXP3+) regulatory T cells (Treg cells) suppress conventional T cells and are essential for immunological tolerance. FOXP3, the master transcription factor of Treg cells, controls the expression of multiples genes to guide Treg cell differentiation and function. However, only a small fraction (<10%) of Treg cell-associated genes are directly bound by FOXP3, and FOXP3 alone is insufficient to fully specify the Treg cell programme, indicating a role for other accessory transcription factors operating upstream, downstream and/or concurrently with FOXP3 to direct Treg cell specification and specialized functions. Indeed, the heterogeneity of Treg cells can be at least partially attributed to differential expression of transcription factors that fine-tune their trafficking, survival and functional properties, some of which are niche-specific. In this Review, we discuss the emerging roles of accessory transcription factors in controlling Treg cell identity. We specifically focus on members of the basic helix-loop-helix family (AHR), basic leucine zipper family (BACH2, NFIL3 and BATF), CUT homeobox family (SATB1), zinc-finger domain family (BLIMP1, Ikaros and BCL-11B) and interferon regulatory factor family (IRF4), as well as lineage-defining transcription factors (T-bet, GATA3, RORγt and BCL-6). Understanding the imprinting of Treg cell identity and specialized function will be key to unravelling basic mechanisms of autoimmunity and identifying novel targets for drug development.

A comprehensive single cell data analysis of lymphoblastoid cells reveals the role of super-enhancers in maintaining EBV latency.

We probed the lifecycle of Epstein-Barr virus (EBV) on a cell-by-cell basis using single cell RNA sequencing (scRNA-seq) data from nine publicly available lymphoblastoid cell lines (LCLs). While the majority of LCLs comprised cells containing EBV in the latent phase, two other clusters of cells were clearly evident and were distinguished by distinct expression of host and viral genes. Notably, both were high expressors of EBV LMP1/BNLF2 and BZLF1 compared to another cluster that expressed neither gene. The two novel clusters differed from each other in their expression of EBV lytic genes, including glycoprotein gene GP350. The first cluster, comprising GP350- LMP1hi cells, expressed high levels of HIF1A and was transcriptionally regulated by HIF1-α. Treatment of LCLs with Pevonedistat, a drug that enhances HIF1-α signaling, markedly induced this cluster. The second cluster, containing GP350+ LMP1hi cells, expressed EBV lytic genes. Host genes that are controlled by super-enhancers (SEs), such as transcription factors MYC and IRF4, had the lowest expression in this cluster. Functionally, the expression of genes regulated by MYC and IRF4 in GP350+ LMP1hi cells were lower compared to other cells. Indeed, induction of EBV lytic reactivation in EBV+ AKATA reduced the expression of these SE-regulated genes. Furthermore, CRISPR-mediated perturbation of the MYC or IRF4 SEs in LCLs induced the lytic EBV gene expression, suggesting that host SEs and/or SE target genes are required for maintenance of EBV latency. Collectively, our study revealed EBV-associated heterogeneity among LCLs that may have functional consequence on host and viral biology.

Transvitreal and subretinal fibrinoid reaction following diabetic vitrectomy.

Purpose: To describe an unexpected and atypical transvitreal and subretinal fibrinoid reaction following vitrectomy for non-clearing vitreous hemorrhage due to proliferative diabetic retinopathy. Observations: A 58-year-old woman with bilateral proliferative diabetic retinopathy and non-clearing vitreous hemorrhage underwent combined phacoemulsification, intraocular lens implantation and vitrectomy in the right eye. Two months later she underwent staged phacoemulsification with intraocular lens implantation followed by vitrectomy in the left eye. The early postoperative course of each eye was complicated by choroidal effusion and submacular fibrinoid material on optical coherence tomography. The left eye also developed transvitreal fibrinoid bands. Conclusions and importance: Subretinal fibrin accumulation is a rare complication of diabetic vitrectomy. Optical coherence tomography (OCT) in the early post-operative period may assist in the recognition of this complication.

Celiac Artery Compression Syndrome: A Unique Presentation.

Celiac artery compression syndrome (CACS), also known as median arcuate ligament syndrome, celiac axis syndrome, and Dunbar Syndrome, is a rare disorder that results from compression of the celiac artery by the median arcuate ligament. The following is a case that depicts an interesting presentation of a patient diagnosed with this rare condition. A 44-year-old male with a history of mutism was brought in by his family for weight loss of 100 lbs with intermittent abdominal pain, weakness and lethargy over a period of five years. His family reported that he had poor nutritional intake, and could only eat a small amount before he seemed to be in pain, and eventually refused to eat. He had no other prior medical history except for mutism, no family history of malignancy, no history of trauma, surgeries, smoking or substance use, and did not take any medications. Physical exam was largely unremarkable. Mesenteric vascular duplex demonstrated severe grade stenosis of the celiac trunk with post-stenotic velocity of 520 cm/sec. Contrast enhanced computed tomography angiography revealed acute angle J-configuration of the takeoff of the celiac axis, with stenosis at its origin and focal post-stenotic dilatation, confirming the diagnosis of CACS. CACS is an elusive diagnosis that should be considered in patients where other causes of abdominal pain and weight loss have been ruled out. The disease can present with the classic triad of post-prandial abdominal pain, weight loss, and an abdominal bruit. Imaging modalities including mesenteric vascular duplex, computed tomography abdominal angiography, magnetic resonance angiography and celiac artery angiography can help make the diagnosis. Treatment involves surgical decompression via division of the median arcuate ligament, with most patients experiencing significant and long-lasting relief from their symptoms.

Spatial and Temporal Distribution of Hepatitis A Virus and Hepatitis E Virus Among Children with Acute Hepatitis in Mexico.

Hepatitis A virus (HAV) and hepatitis E virus (HEV) cause most of the global burden of viral hepatitis. Geographical and seasonal patterns contribute to the epidemiological status of infectious diseases. The extent of these features in the setting of HAV and HEV infections has not been analyzed in detail. This point is important in highly endemic countries of both viruses, where the pediatric population is at high risk of contracting these infections. A comparison between the frequency of antibodies to HAV and HEV and viral RNA detection in serum samples from pediatric patients with acute hepatitis from South and West Mexico was performed. All samples were positive for HAV mono-infection, which was most frequently detected in the metropolitan areas during the rainy season in the South (90%) and all year round in the West (42%). No HEV mono-infection was detected in the studied regions. A 58% frequency for HAV/HEV co-infection was found in the West, predominantly in the metropolitan areas during the rainy months. A 10% frequency for co-infection broadly distributed in the South throughout the year was also found. Our findings underscore that the distribution of HAV and HEV infections varies through the year and differs among Mexico's distinct geographical regions.

Host-Virus Chimeric Events in SARS-CoV-2-Infected Cells Are Infrequent and Artifactual.

The pathogenic mechanisms underlying severe SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection remain largely unelucidated. High-throughput sequencing technologies that capture genome and transcriptome information are key approaches to gain detailed mechanistic insights from infected cells. These techniques readily detect both pathogen- and host-derived sequences, providing a means of studying host-pathogen interactions. Recent studies have reported the presence of host-virus chimeric (HVC) RNA in transcriptome sequencing (RNA-seq) data from SARS-CoV-2-infected cells and interpreted these findings as evidence of viral integration in the human genome as a potential pathogenic mechanism. Since SARS-CoV-2 is a positive-sense RNA virus that replicates in the cytoplasm, it does not have a nuclear phase in its life cycle. Thus, it is biologically unlikely to be in a location where splicing events could result in genome integration. Therefore, we investigated the biological authenticity of HVC events. In contrast to true biological events like mRNA splicing and genome rearrangement events, which generate reproducible chimeric sequencing fragments across different biological isolates, we found that HVC events across >100 RNA-seq libraries from patients with coronavirus disease 2019 (COVID-19) and infected cell lines were highly irreproducible. RNA-seq library preparation is inherently error prone due to random template switching during reverse transcription of RNA to cDNA. By counting chimeric events observed when constructing an RNA-seq library from human RNA and spiked-in RNA from an unrelated species, such as the fruit fly, we estimated that ∼1% of RNA-seq reads are artifactually chimeric. In SARS-CoV-2 RNA-seq, we found that the frequency of HVC events was, in fact, not greater than this background "noise." Finally, we developed a novel experimental approach to enrich SARS-CoV-2 sequences from bulk RNA of infected cells. This method enriched viral sequences but did not enrich HVC events, suggesting that the majority of HVC events are, in all likelihood, artifacts of library construction. In conclusion, our findings indicate that HVC events observed in RNA-sequencing libraries from SARS-CoV-2-infected cells are extremely rare and are likely artifacts arising from random template switching of reverse transcriptase and/or sequence alignment errors. Therefore, the observed HVC events do not support SARS-CoV-2 fusion to cellular genes and/or integration into human genomes. IMPORTANCE The pathogenic mechanisms underlying SARS-CoV-2, the virus responsible for COVID-19, are not fully understood. In particular, relatively little is known about the reasons some individuals develop life-threatening or persistent COVID-19. Recent studies identified host-virus chimeric (HVC) reads in RNA-sequencing data from SARS-CoV-2-infected cells and suggested that HVC events support potential "human genome invasion" and "integration" by SARS-CoV-2. This suggestion has fueled concerns about the long-term effects of current mRNA vaccines that incorporate elements of the viral genome. SARS-CoV-2 is a positive-sense, single-stranded RNA virus that does not encode a reverse transcriptase and does not include a nuclear phase in its life cycle, so some doubts have rightfully been expressed regarding the authenticity of HVCs and the role played by endogenous retrotransposons in this phenomenon. Thus, it is important to independently authenticate these HVC events. Here, we provide several lines of evidence suggesting that the observed HVC events are likely artifactual.

Establishing the Biofidelity of a Multiphysics Finite Element Model of the Human Heart.

PURPOSE: Accelerating development of new therapeutic cardiac devices remains a clinical and technical priority. High-performance computing and the emergence of functional and complex in silico models of human anatomy can be an engine to accelerate the commercialization of innovative, safe, and effective devices. METHODS: An existing three-dimensional, nonlinear model of a human heart with flow boundary conditions was evaluated. Its muscular tissues were exercised using electrophysiological boundary conditions, creating a dynamic, electro-mechanical simulation of the kinetics of the human heart. Anatomic metrics were selected to characterize the functional biofidelity of the model based on their significance to the design of cardiac devices. The model output was queried through the cardiac cycle and compared to in vivo literature values. RESULTS: For the kinematics of mitral and aortic valves and curvature of coronary vessels, the model's performance was at or above the 95th percentile range of the in vivo data from large patient cohorts. One exception was the kinematics of the tricuspid valve. The model's mechanical use environment would subject devices to generally conservative use conditions. CONCLUSIONS: This conservative simulated use environment for heart-based medical devices, and its judicious application in the evaluation of medical devices is justified, but careful interpretation of the results is encouraged.

Host-virus chimeric events in SARS-CoV2 infected cells are infrequent and artifactual.

Pathogenic mechanisms underlying severe SARS-CoV2 infection remain largely unelucidated. High throughput sequencing technologies that capture genome and transcriptome information are key approaches to gain detailed mechanistic insights from infected cells. These techniques readily detect both pathogen and host-derived sequences, providing a means of studying host-pathogen interactions. Recent studies have reported the presence of host-virus chimeric (HVC) RNA in RNA-seq data from SARS-CoV2 infected cells and interpreted these findings as evidence of viral integration in the human genome as a potential pathogenic mechanism. Since SARS-CoV2 is a positive sense RNA virus that replicates in the cytoplasm it does not have a nuclear phase in its life cycle, it is biologically unlikely to be in a location where splicing events could result in genome integration. Here, we investigated the biological authenticity of HVC events. In contrast to true biological events such as mRNA splicing and genome rearrangement events, which generate reproducible chimeric sequencing fragments across different biological isolates, we found that HVC events across >100 RNA-seq libraries from patients with COVID-19 and infected cell lines, were highly irreproducible. RNA-seq library preparation is inherently error-prone due to random template switching during reverse transcription of RNA to cDNA. By counting chimeric events observed when constructing an RNA-seq library from human RNA and spike-in RNA from an unrelated species, such as fruit-fly, we estimated that ~1% of RNA-seq reads are artifactually chimeric. In SARS-CoV2 RNA-seq we found that the frequency of HVC events was, in fact, not greater than this background "noise". Finally, we developed a novel experimental approach to enrich SARS-CoV2 sequences from bulk RNA of infected cells. This method enriched viral sequences but did not enrich for HVC events, suggesting that the majority of HVC events are, in all likelihood, artifacts of library construction. In conclusion, our findings indicate that HVC events observed in RNA-sequencing libraries from SARS-CoV2 infected cells are extremely rare and are likely artifacts arising from either random template switching of reverse-transcriptase and/or sequence alignment errors. Therefore, the observed HVC events do not support SARS-CoV2 fusion to cellular genes and/or integration into human genomes.

Evidence for Increased Inflammatory Cytokine Profile in Hepatitis E Virus-Infected Obese Patients: Implications for Chronic Liver Disease.

We aimed to characterize the contribution of hepatitis E virus (HEV) in perpetuating the cytokine-mediated inflammatory setting related to liver damage in the context of obesity. Herein, serum samples from patients with liver disease were retrospectively analyzed and categorized as normal-weight patients (NW), overweight patients (OW), obese patients (ObP), and high alcohol consumer patients (HAC), and biochemical, anthropometrical, and transient elastography measurements were obtained. The positivity for immunoglobulin M (IgM) and immunoglobulin G (IgG) anti-HEV antibodies in samples was determined by enzyme-linked immunosorbent assay. Available samples from ObP were tested by reverse transcription-nested polymerase chain reaction for the presence of HEV-RNA. Cytokine profile in the serum of ObP was identified using a multiplexed immune assay. Globally, the highest frequency of IgG anti-HEV was found in ObP (57.5%), followed by HAC (20%), OW (15%), and NW (7.5%). A strong association between HEV serology and obesity was found (odds ratio = 4.21, confidence interval = 1.91.9.27) with a cutoff of 29.3 kg/m2 (area under curve [AUC] = 0-66; p = 0.003) and, a 23.7% of available samples of ObP provided amplification of HEV genome. Cytokine analysis revealed significantly higher levels of proinflammatory cytokines (interleukin [IL]-12, interferon [IFN]-γ, and IL-1ß) in IgG anti-HEV-positive ObP than in IgG anti-HEV-negative ObP. Moreover, a high proportion of patients with positive serology showed advanced liver damage. In conclusion, the high percentage of anti-HEV antibodies and viral RNA detection in the setting of an excess of fat, along with an associated proinflammatory cytokine profile found in IgG anti-HEV-positive ObP with more severe liver disease, support an interplay between HEV and obesity.

So much at stake: Ethical tradeoffs in accelerating SARSCoV-2 vaccine development.

BACKGROUND: A sense of urgency exists to develop vaccines against SARS CoV-2, responsible for numerous global cases and deaths, as well as widespread social and economic disruption. Multiple approaches have been proposed to speed up vaccine development, including accelerated randomized controlled trials (RCT), controlled human challenge trials (CHI), and wide distribution through an emergency use authorization after collecting initial data. There is a need to examine how best to accelerate vaccine development in the setting of a pandemic, without compromising ethical and scientific norms. METHODS: Trade-offs in scientific and social value between generating reliable evidence about safety and efficacy while promoting rapid vaccine availability are examined along five ethically relevant dimensions: (1) confidence in and generalizability of data, (2) feasibility, (3) speed and cost, (4) participant risks, and (5) social risks. RESULTS: Accelerated individually randomized RCTs permit expeditious evaluation of vaccine candidates using established methods, expertise, and infrastructure. RCTs are more likely than other approaches to be feasible, increase speed and reduce cost, and generate reliable data about safety and efficacy without significantly increasing risks to participants or undermining societal trust. CONCLUSION: Ethical analysis suggests that accelerated RCTs are the best approach to accelerating vaccine development in a pandemic, and more likely than other approaches to enhance social value without compromising ethics or science. RCTs can expeditiously collect rigorous data about vaccine safety and efficacy. Innovative and flexible designs and implementation strategies to respond to shifting incidence and test vaccine candidates in parallel or sequentially would add value, as will coordinated data sharing across vaccine trials. CHI studies may be an important complementary strategy when more is known. Widely disseminating a vaccine candidate without efficacy data will not serve the public health nor achieve the goal of identifying safe and effective SARS Co-V-2 vaccines.

El papel de la sintomatología depresiva, catastrofismo y expectativa en la eficacia de las técnicas intervencionistas para el tratamiento del dolor lumbar crónico / Role of depressive symptomatology, catastrophism and expectation in the efficacy of interventional treatment in chronic low back pain

Objetivo: Determinar el valor predictivo de las variables sintomatología depresiva, nivel de catastrofismo y expectativa en el éxito de la infiltración terapéutica de la articulación sacroilíaca para el tratamiento del dolor lumbar crónico. Material y métodos: Estudio piloto observacional, descriptivo de tipo transversal (mayo-junio de 2017) en pacientes nuevos con dolor lumbar crónico de origen sacroilíaco sin trastorno psicológico/psiquiátrico previo y a los que nunca se les había realizado ningún tipo de infiltración. Se hizo una valoración clínica inicial y se aplicó un cuestionario estructurado para determinar la presencia de las variables expectativa, catastrofismo y sintomatología depresiva. Se programó para la realización de una infiltración sacroilíaca ecoguiada y posteriormente se realizó una nueva valoración clínica comparativa a las 4 semanas. Resultados: Participaron 28 pacientes (75 % mujeres), con una media de edad de 60 +/- 11,8 años. La puntuación basal en la escala visual analógica (EVA) fue de 7,64 +/- 1,42 y la puntuación basal en el EuroQol fue de 0,451 +/- 0,202. A las 4 semanas del procedimiento la EVA fue de 6,32 +/- 1,66 y el EuroQol de 0,594 +/- 0,242. Si bien todas las variables estudiadas mostraron un papel relevante en la respuesta clínica, la variable catastrofismo fue la que presentó mayor asociación con una escasa mejoría clínica (p = 0,001). Conclusiones: La detección y tratamiento precoces de variables de vulnerabilidad como la sintomatología depresiva, el grado de catastrofismo y el nivel de expectativa son determinantes para la obtención de mejores resultados terapéuticos en los pacientes con dolor crónico

Objective: To determine the predictive value of psychological variables (depressive symptomatology, catastrophism and expectation) in the success of the therapeutic sacroiliac joint injection for the treatment of chronic low back pain. Methodology: An observational, descriptive crosssectional pilot study (May-June 2017) in new patients with chronic lumbar pain of sacroiliac origin without psychological/psychiatric previous disorder who had never undergone any type of infi ltration. An initial clinical assessment was made, a structured questionnaire was applied to determine the presence of the variables expectation, catastrophism and depressive symptomatology. An ultrasound-guided sacroiliac infiltration was scheduled and a new clinical comparative assessment was performed after 4 weeks. Results: 28 patients were obtained (75% women) with an average age of 60+/-11.8 years. A baseline VAS was 7.64+/-1.42 and basaline EuroQol of 0.451+/- 0.202. After 4 weeks of the procedure, the VAS was 6.32+/-1.66 and the EuroQol was 0.594+/-0.242. Although all the variables showed a relevant role in the clinical response, the catastrophism was the greatest associated with poor clinical improvement (p=0.001). Conclusions: The detection and early treatment of vulnerability variables such as depressive symptomatology, catastrophism and the level of expectation are determining factor to obtaining better therapeutic outcomes in patients with chronic pain

Challenges in Management of Hepatitis A Virus Epidemiological Transition in Mexico.

Hepatitis A virus (HAV) is the most common cause of acute viral hepatitis worldwide. The virus is mainly transmitted via the fecaloral route and, the incidence of infection is closely related to low socioeconomic conditions and poor sanitation. Mexico, previously categorized an area of high endemicity for HAV infection, is undergoing epidemiological transition. However, a limited number of HAV-related scientific reports regarding to virus burden is available. According to the local government health agency (Secretarla de Salud, SSA in Spanish), from 1994 to 2017 a reduction in the incidence of hepatitis related to HAV has been reported. However, HAV is still the most common cause of viral hepatitis in the country, and the pediatric population is the most prone to be infected with this virus. The analysis of the SSA data reveals that most of the reported cases from 1994 to 2017 were found in highly industrialized states. This information contradicts the documented relationship between the highest prevalence of infection and the lowest socio-economic status, and supports the necessity of viral detection and notification of HAV cases. Moreover, in spite that four HAV vaccines are available in Mexico and universal vaccination has been shown to be beneficial in developing countries in terms of declining endemicity, HAV vaccination is not mandatory in Mexico. In this review, preventive strategies including appropriate diagnosis, vaccination and public health policies on the basis of the epidemiologic status of HAV in Mexico are discussed.