Risk Factors Associated with COVID-19 Mortality in the State of Durango, Mexico.

The coronavirus disease 2019 (COVID-19) has caused over six million deaths worldwide since its emergence in Wuhan China, factors associated with COVID-19 mortality, such as comorbidities, age, and observed symptomatology still remain a major subject of study. In the present work, a total of 16,345 SARS-CoV-2 positive cases from Durango Mexico diagnosed from May 2020 to December 2021 were analyzed to establish an association of COVID-19 mortality with clinical and demographic variables in a case-control study. Selected variables include patient age, smoking status, sex, presence of comorbidities such as hypertension, diabetes and obesity, as well as patient symptomatology such as fever, dyspnea, abdominal pain and diarrhea. Results indicate that among analyzed data, the median age was 43 years; 54% were female, with a mortality rate of 5.66%. Multivariate regression analysis indicated that the comorbidities associated with the highest risk factor were advanced age (>60) with an odds ratio of 4.127 (IC 95%, 3.37-5.05), hypertension with 1.961 (IC 95%, 1.57-2.45), diabetes with 1.753 (IC 95%, 1.39-2.20) and obesity with 1.413 (IC 95%, 1.11-1.78) respectively. On the other hand, the symptom associated with the highest risk factor was dyspnea with an odds ratio of 18.369 (IC 95%, 14.42-23.39). Our data suggests an association between hypertension and old age with COVID-19 mortality. Other findings include the prevalence of dyspnea, polypnea and cyanosis as a major predictor for COVID-19 mortality, as well as lower mortality risks among health workers.

HPV Meets APOBEC: New Players in Head and Neck Cancer.

Besides smoking and alcohol, human papillomavirus (HPV) is a factor promoting head and neck squamous cell carcinoma (HNSCC). In some human tumors, including HNSCC, a number of mutations are caused by aberrantly activated DNA-modifying enzymes, such as the apolipoprotein B mRNA editing enzyme catalytic polypeptide-like (APOBEC) family of cytidine deaminases. As the enzymatic activity of APOBEC proteins contributes to the innate immune response to viruses, including HPV, the role of APOBEC proteins in HPV-driven head and neck carcinogenesis has recently gained increasing attention. Ongoing research efforts take the cue from two key observations: (1) APOBEC expression depends on HPV infection status in HNSCC; and (2) APOBEC activity plays a major role in HPV-positive HNSCC mutagenesis. This review focuses on recent advances on the role of APOBEC proteins in HPV-positive vs. HPV-negative HNSCC.

Synthesis and Biological Evaluation of Amidinourea Derivatives against Herpes Simplex Viruses.

Current therapy against herpes simplex viruses (HSV) relies on the use of a few nucleoside antivirals such as acyclovir, famciclovir and valacyclovir. However, the current drugs are ineffective against latent and drug-resistant HSV infections. A series of amidinourea compounds, designed as analogues of the antiviral drug moroxydine, has been synthesized and evaluated as potential non-nucleoside anti-HSV agents. Three compounds showed micromolar activity against HSV-1 and low cytotoxicity, turning to be promising candidates for future optimization. Preliminary mode of action studies revealed that the new compounds act in an early stage of the HSV replication cycle, just after the viral attachment and the entry phase of the infection.

Molecular and genetic characterization of the pOV plasmid from Pasteurella multocida and construction of an integration vector for Gallibacterium anatis.

BACKGROUND: The pOV plasmid isolated from the Pasteurella multocida strain PMOV is a new plasmid, and its molecular characterization is important for determining its gene content and its replicative properties in Pasteurellaceae family bacteria. METHODS: Antimicrobial resistance mediated by the pOV plasmid was tested in bacteria. Purified pOV plasmid DNA was used to transform E. coli DH5α and Gallibacterium anatis 12656-12, including the pBluescript II KS(-) plasmid DNA as a control for genetic transformation. The pOV plasmid was digested with EcoRI for cloning fragments into the pBluescript II KS(-) vector to obtain constructs and to determine the full DNA sequence of pOV. RESULTS: The pOV plasmid is 13.5 kb in size; confers sulfonamide, streptomycin and ampicillin resistance to P. multocida PMOV; and can transform E. coli DH5α and G. anatis 12656-12. The pOV plasmid was digested for the preparation of chimeric constructs and used to transform E. coli DH5α, conferring resistance to streptomycin (plasmid pSEP3), ampicillin (pSEP4) and sulfonamide (pSEP5) on the bacteria; however, similar to pBluescript II KS(-), the chimeric plasmids did not transform G. anatis 12656-12. A 1.4 kb fragment of the streptomycin cassette from pSEP3 was amplified by PCR and used to construct pSEP7, which in turn was used to interrupt a chromosomal DNA locus of G. anatis by double homologous recombination, introducing strA-strB into the G. anatis chromosome. CONCLUSION: The pOV plasmid is a wide-range, low-copy-number plasmid that is able to replicate in some gamma-proteobacteria. Part of this plasmid was integrated into the G. anatis 12656-12 chromosome. This construct may prove to be a useful tool for genetic studies of G. anatis.

Accuracy of the BAR score in the prediction of survival after liver transplantation.

INTRODUCTION AND AIM: The Balance of Risk (BAR) Score, a simple scoring system that combines six independent donor and recipient variables to predict outcome after liver transplantation (LT), was validated in a large U.S./European cohort of patients. This study aims to assess the performance of the BAR score to predict survival after liver transplantation and determine the factors associated with short and long-term survival in Latin-American patients. MATERIAL AND METHODS: A retrospective cohort study was performed in 194 patients [112 (55.4%) males; mean age 52±14 years] who underwent 202 LT during the period 2003-2015. Demographic, clinical, pathological and surgical variables, as well as mortality and survival rates, were analyzed. The BAR score was investigated through a receiver operating characteristics (ROC) curve with the calculation of the area under the curve (AUC) to evaluate the predictive score power for 3-month, 1 and 5-year mortality in a matched donor-recipient cohort. Youden index was calculated to identify optimal cutoff points. RESULTS: The AUC of BAR score in predicting 3-month, 1-year and 5-year mortality were 0.755 (CI95% 0.689-0.812), 0.702 (CI95% 0.634-0.764) and 0.610 (CI95% 0.539-0.678) respectively. The best cut-off point was a BAR score ≥15 points. In the multivariate analysis BAR score <15 was associated with higher survival rates at 3 months and 1 and 5-years. CONCLUSIONS: BAR score <15 points is an independent predictor of better short and long-term survival in Latin-American patients undergoing LT. The BAR scoring system has an adequate diagnostic capacity allowing to predict 3 and 12-month mortality.

Prevalence of Disability in Patients With Musculoskeletal Pain and Rheumatic Diseases in a Population From Cuenca, Ecuador.

OBJECTIVE: The aim of this study was to determine the prevalence of disability in patients with musculoskeletal pain and rheumatic diseases in Cuenca, Ecuador. METHODS: We performed a cross-sectional analytical study with randomized sampling in 4877 subjects, from urban and rural areas. COPCORD (Community Oriented Program for Control of Rheumatic Diseases)-validated questionnaire was administered house-to-house to identify subjects with nontraumatic musculoskeletal pain and rheumatic diseases. The subjects were assessed by rheumatologists for diagnostic accuracy, and the Health Assessment Questionnaire Disability Index was administered to assess functional capacity. A logistic regression analysis was conducted to determine the association of rheumatic diseases with functional disability. RESULTS: Functional disability was found in 221 subjects (73.1% women), with mean age 62 (SD, 18.2) years, residing in rural areas (201 [66.5%]), with education of 6.9 (SD, 5.3) years, and of low income (77 [47.2%]). The value of HAQ-DI was a mean of 0.2 (0-2.9). The real prevalence of physical disability was 9.5%. Moderate and severe disability predominated in activities such as kneeling (4.9% and 3.3%), squatting (4.8% and 2.7%), and leaning to pick up objects (3.7% and 0.9%), respectively. Rheumatic diseases associated with physical disabilities were knee osteoarthritis (95 [31.4%]) and hand osteoarthritis (69 [22.8%]), mechanical low-back pain (43 [14.2%]), fibromyalgia (27 [9.5%]), and rheumatoid arthritis (11 [3.6%]; P < 0.001). CONCLUSIONS: Physical disability was associated with older age, female sex, rural residence, lower education, and lower income. Moderate and severe disability predominated in the dimensions of kneeling, squatting, and picking up objects. Rheumatic diseases associated with disability were hand and knee osteoarthritis, back pain, fibromyalgia, and rheumatoid arthritis.

Arsenic exposure and risk of preeclampsia in a Mexican mestizo population.

BACKGROUND: Exposure to arsenic in drinking water has been associated with various complications of pregnancy including fetal loss, low birth weight, anemia, gestational diabetes and spontaneous abortion. However, to date, there are no studies evaluating its possible association with preeclampsia. METHODS: This case-control study involved 104 preeclamptic and 202 healthy pregnant women. The concentrations of arsenic in drinking water and urine were measured using a Microwave Plasma-Atomic Emission Spectrometer. RESULTS: We found relatively low levels of arsenic in household tap water (range of 2.48-76.02 µg/L) and in the urine of the participants (7.1 µg/L vs 6.78 µg/L in cases and controls, respectively). CONCLUSIONS: The analysis between groups showed for the first time that at these lower levels of exposure there is no association with preeclampsia.

Prevalence of musculoskeletal disorders and rheumatic diseases in Cuenca, Ecuador: a WHO-ILAR COPCORD study.

The aim of this study was to determine the prevalence of musculoskeletal pain and rheumatic diseases in subjects over 18 years of age from the canton of Cuenca, Ecuador. Cross-sectional analytical community-based study was conducted in subjects over 18 years of age using the validated Community-Oriented Program for the Control of Rheumatic Diseases (COPCORD) questionnaire. Random sampling was used. The questionnaire was administered by standardized health workers. Subjects were visited house by house. Subjects positive for musculoskeletal (MSK) pain in the last 7 days and at some point in life were assessed by rheumatologists to confirm the diagnosis. A total of 4877 subjects participated, with an average age of 42.8 (SD 18.8) years of age; 59.7 % were women; 69.7 % lived in urban areas. 32.5 % reported MSK pain in the last 7 days and 45.7 % at some point in life. The prevalence of knee osteoarthritis was 7.4 %, hand osteoarthritis 5.3 %, low back pain 9.3 %, rheumatoid arthritis 0.8 %, fibromyalgia 2 %, gout 0.4 %, and lupus 0.06 %. Subjects from rural areas reported experiencing more MSK pain in the last 7 days and at some point in life, lower income, poorer health-care coverage, and increased physical activity involving repetitive tasks such as lifting weights or cooking with firewood. MSK pain prevalence was high. Osteoarthritis and low back pain were the most common diseases. Age, sex, physical activity, repetitive tasks, living in a rural area, and lack of health-care coverage were found to be associated with MSK pain.

Jejunal Perforation Due to Histoplasmosis Regarding a Case.

Histoplasmosis is an increasing infection that mainly affects immunocompromised individuals such as patients with HIV/AIDS, with the disseminated form, especially gastrointestinal, being common in this population. The clinical presentation ranges from asymptomatic to symptoms that mimic other abdominal diseases. Jejunal perforation due to histoplasmosis, although rare, has been reported in a few cases, typically in men living with HIV in their fourth decade of life. We present the case of a 34-year-old male, with a history of HIV and colonic histoplasmosis who presented with acute abdominal pain requiring exploratory laparotomy and intestinal resection due to jejunal perforation, with histological confirmation of histoplasmosis in the resected intestinal segment.

Combination of HDAC and FYN inhibitors in synovial sarcoma treatment.

The SS18-SSX fusion protein is an oncogenic driver in synovial sarcoma. At the molecular level, SS18-SSX functions as both an activator and a repressor to coordinate transcription of different genes responsible for tumorigenesis. Here, we identify the proto-oncogene FYN as a new SS18-SSX target gene and examine its relation to synovial sarcoma therapy. FYN is a tyrosine kinase that promotes cancer growth, metastasis and therapeutic resistance, but SS18-SSX appears to negatively regulate FYN expression in synovial sarcoma cells. Using both genetic and histone deacetylase inhibitor (HDACi)-based pharmacologic approaches, we show that suppression of SS18-SSX leads to FYN reactivation. In support of this notion, we find that blockade of FYN activity synergistically enhances HDACi action to reduce synovial sarcoma cell proliferation and migration. Our results support a role for FYN in attenuation of anti-cancer activity upon inhibition of SS18-SSX function and demonstrate the feasibility of targeting FYN to improve the effectiveness of HDACi treatment against synovial sarcoma.

Prevalence and Classification of C-Shaped Canal and Radix in Mandibular Molars Using Cone-Beam Computed Tomography on Mexican Population.

The diverse morphological configurations in teeth present clinical challenges in root canal treatment, complicating instrumentation and irrigation processes, which can lead to treatment failure. Understanding anatomical variations, such as C-shaped canals and radix entomolaris, enhances clinical skills and improves long-term endodontic treatment success rates. Cone-beam computed tomography (CBCT) offers superior diagnostic capabilities over conventional radiography, enabling the pre-operative detection of root configurations and canal numbers, facilitating personalized endodontic treatments. A total of 2173 teeth of a Mexican population, including 1057 first mandibular molars and 1116 s mandibular molars, were studied using only CBCT to identify C-shaped canals and radix configurations of patients who were treated from 2018 to 2023 at the Department of Radiology at the Faculty of Dentistry, Juarez University of the State of Durango, Mexico. C-shaped canals were identified in 160 teeth, with a prevalence of 0.2% in first mandibular molars and 14.1% in second mandibular molars. The highest frequency was in the left second mandibular molar (3.7) at 14.8%. Gender differences were significant, with higher prevalence in females (27.3%) compared to males (13.3%). The most common C-shaped canal configuration was type C2 (39.3%). Radix entomolaris was found in 52 teeth, with a prevalence of 3.4% in first mandibular molars and 1.4% in second mandibular molars. This research on a Mexican population using cone-beam computed tomography (CBCT) highlights significant findings in the prevalence and types of C-shaped canals and radix entomolaris in mandibular molars for this population. The left second mandibular molar (3.7) showed the highest prevalence at 14.8%, followed closely by the right second mandibular molar (4.7) at 13.5%, with a significant difference (p < 0.001). We found a significant difference in the prevalence of C-shaped canals between genders (p = 0.004, OR 1.78). Additionally, radix entomolaris (p < 0.001) was more frequently identified in first mandibular molars to a significant degree. These insights underscore the importance of CBCT in diagnosing complex root anatomies, which can greatly enhance the success rates of endodontic procedures by allowing for more tailored and precise treatments for this population.

Detection of tidal recruitment/overdistension in lung-healthy mechanically ventilated patients under general anesthesia.

BACKGROUND: The volume-dependent single compartment model (VDSCM) has been applied for identification of overdistension in mechanically ventilated patients with acute lung injury. In this observational study we evaluated the use of the VDSCM to identify tidal recruitment/overdistension induced by tidal volume (Vt) and positive end-expiratory pressure (PEEP) in lung-healthy anesthetized subjects. METHODS: Fifteen patients (ASA physical status I-II) undergoing general anesthesia for elective plastic breast reconstruction surgery were mechanically ventilated in volume-controlled ventilation (VCV), with Vt of 8 mL•kg(-1) and PEEP of 0 cm H(2)O. With these settings, ventilatory mode was randomly adjusted in VCV or pressure-controlled ventilation (PCV) and PEEP was sequentially increased from 0 to 5 and 10 cm H(2)O, 5 min per step. Thereafter, PEEP was decreased to 0 cm H(2)O, Vt increased to 10 mL•kg(-1) and, keeping minute ventilation constant, PEEP was similarly increased to 5 and 10 cm H(2)O. Airway pressure and flow were continuously recorded and fitted to the VDSCM with or without considering flow-dependencies. A "distension index" (%E(2)) derived from the VDSCM was used to assess Vt and PEEP-induced recruitment/overdistension. Positive and negative values of %E(2) suggest tidal overdistension or tidal recruitment, respectively. In addition, the linear respiratory system elastance was calculated. Comparisons among variables at each PEEP value, Vt setting, ventilatory mode, and regression model considering or not considering flow-dependencies were performed with the Wilcoxon-sign rank test for paired samples (P < 0.05). Multiple comparisons were corrected with the Bonferroni method. The relative change in the estimated noisy variance was used as an index of the goodness of fit of the models. RESULTS: VDSCM including the flow-dependent parameter significantly improved estimated noisy variance in almost all experimental conditions (11.2 to 71.4, smallest of the lower and highest of the upper 95% confidence intervals). No differences in %E(2) were observed between VCV and PCV, at comparable Vt and PEEP levels, when flow-dependencies were included in the regression model. The negligence of the flow-dependent parameter systematically led to an underestimation of %E(2) in PCV compared to VCV mode (all P < 0.02). At a given Vt, %E(2) was negative at a PEEP of 0 cm H(2)O and significantly increased with PEEP, being almost 0 at a PEEP of 5 cm H(2)O. At a given level of PEEP, %E(2) significantly increased with Vt. CONCLUSIONS: The distension index %E(2), derived from the VDSCM considering flow-dependencies, seems able to identify tidal recruitment/overdistension induced by Vt and PEEP independent of flow waveform in healthy lung-anesthetized patients.

Inequity and vulnerability in Latin American Indigenous and non-Indigenous populations with rheumatic diseases: a syndemic approach.

Syndemics are a framework that documents health inequities and vulnerabilities in populations with rheumatic diseases. Compared with other approaches, syndemics are able to conjunctly consider epidemiological, biological, sociodemographic and economic factors, and their interactions. OBJECTIVE: To estimate health inequity and vulnerability among Indigenous and non-Indigenous populations with rheumatic and musculoskeletal diseases (RMD) in Latin America using the syndemic approach. DESIGN: This is a secondary analysis of a previously published large-scale study on the prevalence of RMD. SETTING: Studies carried out in five Latin American countries (Argentina, Colombia, Ecuador, Mexico and Venezuela). Health inequity and vulnerability in RMD were identified through a syndemic approach using network and cluster analysis. PARTICIPANTS: A total of 44 560 individuals were studied: 29.78% self-identified as Indigenous, 60.92% were female, the mean age was 43.25 years. Twenty clusters were identified in the Indigenous population and 17 in the non-Indigenous population. RESULTS: The variables associated with RMD among Indigenous populations were rurality, public health system, high joint biomechanical stress, greater pain, disability and alcoholism; and among non-Indigenous people they were being a woman, urban origin, older age, private health system, joint biomechanical stress, greater pain and disability. We identified different health inequities among patients with RMD (ie, lower educational attainment, more comorbidities), associated with factors such as Indigenous self-identification and rural residence. CONCLUSIONS: A syndemic approach enables us to identify health inequities in RMD, as shown by higher prevalence of comorbidities, disability and socioeconomic factors like lower educational attainment. These inequities exist for the overall population of patients with RMD, although it is more evident in Indigenous groups with added layers of vulnerability.

Differential expression of PSMC4, SKP1, and HSPA8 in Parkinson's disease: insights from a Mexican mestizo population.

Parkinson's disease (PD) is a complex neurodegenerative condition characterized by alpha-synuclein aggregation and dysfunctional protein degradation pathways. This study investigates the differential gene expression of pivotal components (UBE2K, PSMC4, SKP1, and HSPA8) within these pathways in a Mexican-Mestizo PD population compared to healthy controls. We enrolled 87 PD patients and 87 controls, assessing their gene expression levels via RT-qPCR. Our results reveal a significant downregulation of PSMC4, SKP1, and HSPA8 in the PD group (p = 0.033, p = 0.003, and p = 0.002, respectively). Logistic regression analyses establish a strong association between PD and reduced expression of PSMC4, SKP1, and HSPA8 (OR = 0.640, 95% CI = 0.415-0.987; OR = 0.000, 95% CI = 0.000-0.075; OR = 0.550, 95% CI = 0.368-0.823, respectively). Conversely, UBE2K exhibited no significant association or expression difference between the groups. Furthermore, we develop a gene expression model based on HSPA8, PSMC4, and SKP1, demonstrating robust discrimination between healthy controls and PD patients. Notably, the model's diagnostic efficacy is particularly pronounced in early-stage PD. In conclusion, our study provides compelling evidence linking decreased gene expression of PSMC4, SKP1, and HSPA8 to PD in the Mexican-Mestizo population. Additionally, our gene expression model exhibits promise as a diagnostic tool, particularly for early-stage PD diagnosis.

Using evidence on violence and injury prevention for policy development and decision making in Ciudad Juarez, Mexico.

This report describes the implementation process and functional structure of the Observatory of Security and Citizen Conviviality of the Juarez Municipality (Observatorio de Seguridad y Convivencia Ciudadanas del Municipio de Juárez) in Chihuahua, Mexico, and discusses the most relevant lessons learned and main challenges in the near future. The Observatory, created in 2008, is a joint effort of the Juarez Municipal Government, Autonomous University of Ciudad Juarez (Universidad Autónoma de Ciudad Juárez), and the Pan American Health Organization. The Observatory's main objective is to propose strategies and public policy recommendations to prevent and control violence and injuries in the Juarez Municipality. Most key federal, state, and local agencies have joined this independent autonomous citizen-based initiative, feed the databases, and benefit from the information produced by a multisectoral, multidisciplinary approach. The Observatory contributes far more than the technical data provided and its facilitating functions. The clear results obtained in such a short time-as seen in the preliminary results of the case study on road injuries from January 2009 to July 2011-demonstrate the appropriateness of this course of action and should stimulate the creation of new observatories whenever and wherever needed. Lessons learned, as discussed here, can open the way to new endeavors, and current challenges show how much work remains to be done.

IFI16 Impacts Metabolic Reprogramming during Human Cytomegalovirus Infection.

Cellular lipid metabolism plays a pivotal role in human cytomegalovirus (HCMV) infection, as increased lipogenesis in HCMV-infected cells favors the envelopment of newly synthesized viral particles. As all cells are equipped with restriction factors (RFs) able to exert a protective effect against invading pathogens, we asked whether a similar defense mechanism would also be in place to preserve the metabolic compartment from HCMV infection. Here, we show that gamma interferon (IFN-γ)-inducible protein 16 (IFI16), an RF able to block HCMV DNA synthesis, can also counteract HCMV-mediated metabolic reprogramming in infected primary human foreskin fibroblasts (HFFs), thereby limiting virion infectivity. Specifically, we find that IFI16 downregulates the transcriptional activation of the glucose transporter 4 (GLUT4) through cooperation with the carbohydrate-response element-binding protein (ChREBP), thereby reducing HCMV-induced transcription of lipogenic enzymes. The resulting decrease in glucose uptake and consumption leads to diminished lipid synthesis, which ultimately curbs the de novo formation of enveloped viral particles in infected HFFs. Consistently, untargeted lipidomic analysis shows enhanced cholesteryl ester levels in IFI16 KO versus wild-type (WT) HFFs. Overall, our data unveil a new role of IFI16 in the regulation of glucose and lipid metabolism upon HCMV replication and uncover new potential targets for the development of novel antiviral therapies. IMPORTANCE Human cytomegalovirus (HCMV) gathers all the substrates and enzymes necessary for the assembly of new virions from its host cell. For instance, HCMV is known to induce cellular metabolism of infected cells to favor virion assembly. Cells are, however, equipped with a first-line defense represented by restriction factors (RFs), which after sensing viral DNA can trigger innate and adaptive responses, thereby blocking HCMV replication. One such RF is IFN-γ-inducible protein 16 (IFI16), which we have shown to downregulate viral replication in human fibroblasts. Thus, we asked whether IFI16 would also play a role in preserving cellular metabolism upon HCMV infection. Our findings highlight an unprecedented role of IFI16 in opposing the metabolic changes elicited by HCMV, thus revealing new promising targets for antiviral therapy.

Glycogen synthase kinase 3 activation is important for anthrax edema toxin-induced dendritic cell maturation and anthrax toxin receptor 2 expression in macrophages.

Anthrax edema toxin (ET) is one of two binary toxins produced by Bacillus anthracis that contributes to the virulence of this pathogen. ET is an adenylate cyclase that generates high levels of cyclic AMP (cAMP), causing alterations in multiple host cell signaling pathways. We previously demonstrated that ET increases cell surface expression of the anthrax toxin receptors (ANTXR) in monocyte-derived cells and promotes dendritic cell (DC) migration toward the lymph node-homing chemokine MIP-3ß. In this work, we sought to determine if glycogen synthase kinase 3 (GSK-3) is important for ET-induced modulation of macrophage and DC function. We demonstrate that inhibition of GSK-3 dampens ET-induced maturation and migration processes of monocyte-derived dendritic cells (MDDCs). Additional studies reveal that the ET-induced expression of ANTXR in macrophages was decreased when GSK-3 activity was disrupted with chemical inhibitors or with small interfering RNA (siRNA) targeting GSK-3. Further examination of the ET induction of ANTXR revealed that a dominant negative form of CREB could block the ET induction of ANTXR, suggesting that CREB or a related family member was involved in the upregulation of ANTXR. Because CREB and GSK-3 activity appeared to be important for ET-induced ANTXR expression, the impact of GSK-3 on ET-induced CREB activity was examined in RAW 264.7 cells possessing a CRE-luciferase reporter. As with ANTXR expression, the ET induction of the CRE reporter was decreased by reducing GSK-3 activity. These studies not only provide insight into host pathways targeted by ET but also shed light on interactions between GSK-3 and CREB pathways in host immune cells.

Pseudomonas aeruginosa endophthalmitis after penetrating keratoplasty transmitted from the same donor to two recipients confirmed by pulsed-field gel electrophoresis.

Two devastating cases of multidrug-resistant Pseudomonas aeruginosa endophthalmitis after keratoplasty as the result of transmission from the same donor were confirmed by pulsed-field gel electrophoresis. Strategies for preventing donor-to-host transmission, such as the use of antimicrobial agents of greater efficacy and better methods for detecting microorganisms in preservation medium, could minimize this type of transmission.

Human Cytomegalovirus and Autoimmune Diseases: Where Are We?

Human cytomegalovirus (HCMV) is a ubiquitous double-stranded DNA virus belonging to the ß-subgroup of the herpesvirus family. After the initial infection, the virus establishes latency in poorly differentiated myeloid precursors from where it can reactivate at later times to cause recurrences. In immunocompetent subjects, primary HCMV infection is usually asymptomatic, while in immunocompromised patients, HCMV infection can lead to severe, life-threatening diseases, whose clinical severity parallels the degree of immunosuppression. The existence of a strict interplay between HCMV and the immune system has led many to hypothesize that HCMV could also be involved in autoimmune diseases (ADs). Indeed, signs of active viral infection were later found in a variety of different ADs, such as rheumatological, neurological, enteric disorders, and metabolic diseases. In addition, HCMV infection has been frequently linked to increased production of autoantibodies, which play a driving role in AD progression, as observed in systemic lupus erythematosus (SLE) patients. Documented mechanisms of HCMV-associated autoimmunity include molecular mimicry, inflammation, and nonspecific B-cell activation. In this review, we summarize the available literature on the various ADs arising from or exacerbating upon HCMV infection, focusing on the potential role of HCMV-mediated immune activation at disease onset.