Identification and Characterization of VDAC Family in Maize.

The voltage-dependent anion channel (VDAC) is the most abundant protein in the outer mitochondrial membrane (OMM) of all eukaryotes, having an important role in the communication between mitochondria and cytosol. The plant VDAC family consists of a wide variety of members that may participate in cell responses to several environmental stresses. However, there is no experimental information about the members comprising the maize VDAC (ZmVDAC) family. In this study, the ZmVDAC family was identified, and described, and its gene transcription profile was explored during the first six days of germination and under different biotic stress stimuli. Nine members were proposed as bona fide VDAC genes with a high potential to code functional VDAC proteins. Each member of the ZmVDAC family was characterized in silico, and nomenclature was proposed according to phylogenetic relationships. Transcript levels in coleoptiles showed a different pattern of expression for each ZmVDAC gene, suggesting specific roles for each one during seedling development. This expression profile changed under Fusarium verticillioides infection and salicylic acid, methyl jasmonate, and gibberellic acid treatments, suggesting no redundancy for the nine ZmVDAC genes and, thus, probably specific and diverse functions according to plant needs and environmental conditions. Nevertheless, ZmVDAC4b was significantly upregulated upon biotic stress signals, suggesting this gene's potential role during the biotic stress response.

Real-world Evidence of COVID-19 Vaccines Effectiveness in Solid-organ Transplant Recipient Population in Colombia: A Study Nested in the Esperanza Cohort.

BACKGROUND: Solid-organ transplant recipients (SOTRs) have a higher risk of coronavirus disease 2019 (COVID-19) complications and death and a less powerful and lasting response to vaccines and to natural infection. In Colombia, this population was prioritized in the National Vaccination Plan against COVID-19 and received vaccines from different platforms. The aim of this study was to estimate the effectiveness of the complete vaccination schedule and of the vaccine booster for COVID-19 administered to SOTRs in Colombia. METHODS: A nested-cohort was assembled within the population-based ESPERANZA cohort and included the subset of 16 y and older SOTRs (n = 6963); the follow-up period spanned March 11, 2021, to May 11, 2022. The vaccine effectiveness was estimated with Cox proportional-hazards models so that the overall effectiveness of the complete vaccination schedule, the vaccine booster, each used vaccine, and the homologous and heterologous schedules were estimated, adjusting by the main confounders. RESULTS: The overall effectiveness of being fully vaccinated was 73.7% (95% confidence interval [CI], 68.9%-77.0%) to prevent COVID-19 infection, 83.7% (95% CI, 78.7%-87.5%) to prevent hospitalization, and 92.1% (95% CI, 88.8%-94.4%) to prevent death due to COVID-19. Similarly, the effectiveness of the vaccine booster was 76.7% (95% CI, 70.6%-81.5%), 86.9% (95% CI, 79.4%-91.6%), and 94.5% (95% CI, 89.8%-97.1%) to prevent confirmed COVID-19 infection, hospitalization, and death due to COVID-19, respectively. In both cases, there were no statistically significant differences across age groups. CONCLUSIONS: Findings from this work show a high protection of vaccination against infection, hospitalization, and death due to COVID-19 in SOTRs, which increases with the vaccine booster.

Moonlighting Proteins: The Case of the Hexokinases.

Moonlighting proteins are defined as proteins with two or more functions that are unrelated and independent to each other, so that inactivation of one of them should not affect the second one and vice versa. Intriguingly, all the glycolytic enzymes are described as moonlighting proteins in some organisms. Hexokinase (HXK) is a critical enzyme in the glycolytic pathway and displays a wide range of functions in different organisms such as fungi, parasites, mammals, and plants. This review discusses HXKs moonlighting functions in depth since they have a profound impact on the responses to nutritional, environmental, and disease challenges. HXKs' activities can be as diverse as performing metabolic activities, as a gene repressor complexing with other proteins, as protein kinase, as immune receptor and regulating processes like autophagy, programmed cell death or immune system responses. However, most of those functions are particular for some organisms while the most common moonlighting HXK function in several kingdoms is being a glucose sensor. In this review, we also analyze how different regulation mechanisms cause HXK to change its subcellular localization, oligomeric or conformational state, the response to substrate and product concentration, and its interactions with membrane, proteins, or RNA, all of which might impact the HXK moonlighting functions.

Diagnóstico de conducto radicular en C en segundos molares mandibulares mediante la evidencia del ángulo obtenido: estudio piloto de validación / Diagnosis of C-shaped root canals in mandibular second molars through the evidence of the obtained angle: a pilot validation study

Antecedentes: El estándar dorado para diagnosticar segundos molarescon conducto radicular en C antes del inicio de un tratamiento endodóntico restaurador es la tomografía cone beam. La difi cultad para accedera los servicios tomográfi cos y su baja distribución en los consultorios odontológicos nos han llevado a diseñar una técnica alternativa enradiografías panorámicas nombrada «evidencia del ángulo obtenido¼(EAO). Objetivo: El objetivo de este trabajo fue crear un punto de cortey estimar la precisión diagnóstica del mismo mediante un estudio pilotocuyo resultado será utilizado en una futura investigación de validación de pruebas diagnósticas...

Background: The gold standard to diagnose second molars withC-shaped root canals prior to beginning an endodontic and restorative treatment is cone-beam tomography. Tomographic services are hard to access and have a low distribution in dental clinics this has led usto design an alternative technique in panoramic radiographs named«evidence of the obtained angle¼ (EAO). Objective: The aim of thisstudy was to create a breakpoint and estimate its diagnostic accuracy through a pilot study; its results will be used in a future investigation of validation of diagnostic tests...

Risk, predictors, and clinical characteristics of lymphoma development in primary Sjögren's syndrome.

OBJECTIVE: To assess the risk and predictors of lymphoma development in a large cohort of patients with primary Sjögren's syndrome (pSS). METHODS: Cox-regression analyses were used to study the predictive value of clinical and laboratory findings at pSS diagnosis, and Kaplan-Meier survival curves to compare survival probability between patients who developed lymphoma and the total cohort. Expected risk for lymphoma was calculated by comparison with the background population. RESULTS: Eleven (4.5%) from 244 patients developed a non-Hodgkin lymphoma (NHL). Diffuse large B-cell and mucosa-associated lymphoid tissue lymphomas occurred at a similar frequency. Three (27.3%) patients died: 2 due to transformation from mucosa-associated lymphoid tissue to diffuse large B-cell. Purpura (HR 8.04, 95% confidence interval [CI] 2.33-27.67), parotidomegaly (HR 6.75, 95%CI 1.89-23.99), anemia (HR 3.43, 95%CI 1.04-11.35), leukopenia (HR 8.70, 95%CI 2.38-31.82), lymphocytopenia (HR 16.47, 95%CI 3.45-78.67), hypergammaglobulinemia (HR 4.06, 95%CI 1.06-15.58), low C3 (HR 36.65, 95%CI 10.65-126.18), and low C4 (HR 39.70, 95%CI 8.85-126.18) levels at pSS diagnosis were significant predictors of NHL development, but only hypocomplementemia and lymphocytopenia were independent risk factors. Hypocomplementemia was related to earlier development of NHL and higher mortality. The cumulative risk of developing lymphoma ranged from 3.4% in the first 5 years to 9.8% at 15 years. Standardized incidence ratio (95%CI) for NHL development was 15.6 (95%CI 8.7-28.2). CONCLUSIONS: Patients with pSS have a 16-fold increased risk of developing lymphoma. This risk increases with time. Hypocomplementemia and lymphocytopenia at pSS diagnosis are the strongest predictors. Survival is clearly reduced in patients with hypocomplementemia. Indolent lymphomas tend to evolve over time toward a more aggressive histologic type.

Successful use of entecavir for a severe case of reactivation of hepatitis B virus following polychemotherapy containing rituximab.

BACKGROUNDS/AIMS: Hepatitis B virus (HBV) reactivation following treatment with rituximab has been reported in patients with either HBsAg-positive, or HBsAg-negative and anti-HBc positive infection. Patients with severe reactivation often have a fatal outcome despite treatment with lamivudine. The use of entecavir has not been reported in patients with severe HBV reactivation. METHODS: We present a case of a HBsAg-negative patient diagnosed with chronic lymphocytic leukemia who received a chemotherapeutic regimen that included rituximab, who subsequently presented with severe HBV reactivation with ascites, jaundice and coagulopathy and was treated with entecavir. A review of the literature and underlying HBV associated mutations are discussed. RESULTS: Entecavir produced a rapid and sustained suppression of HBV that was associated with rapid clinical improvement without any side effects. CONCLUSION: Entecavir is an efficacious and safe treatment for severe HBV reactivation.

GEMOX-R regimen is a highly effective salvage regimen in patients with refractory/relapsing diffuse large-cell lymphoma: a phase II study.

OBJECTIVES: The prognosis of old or immunocompromised patients with refractory or relapsing diffuse large-cell lymphoma (DLCL) is very poor as the current standard of salvage therapy with autologous stem cell transplantation (ASCT) is not feasible for most of them. New active regimens with an acceptable toxicity profile are needed. We aim to report the results of a phase II trial of the GEMOX-R regimen in DLCL. METHODS: A total of 32 patients received GEMOX-R regimen in 2-wk intervals if feasible or every 3 wk for a planned six to eight courses. RESULTS: Median age of the population was 69 yr. Forty-one percent of the patients were primary refractory and 59% after relapsing. At GEMOX-R, 75% of patients had a stage III-IV and an adjusted International Prognostic Index > 1 was observed in 69%. The response rate was 43% with 34% complete response. Neutropenia and thrombopenia grade III-IV were observed in 43% of the patients and neurotoxicity grade III-IV in 7% of cases. Median follow-up for alive patients was 13 months and the median survival was 9.1 months. At 12 months, the overall survival and progression-free survival were 41% and 29%, respectively. CONCLUSIONS: GEMOX-R is a new salvage regimen for DLCL with high activity and relatively safe toxicity profile, which can be offered to elderly patients not candidates of ASCT consolidation. The high efficacy of the regimen in this unfavorable population and also in immunocompromised situations warrant further investigation of this regimen in all salvage situations of this type of lymphomas.

Rituximab, gemcitabine and oxaliplatin: an effective regimen in patients with refractory and relapsing mantle cell lymphoma.

Mantle cell lymphoma constitutes one of the lymphomas with poorest prognosis at relapse with limited effective salvage regimens due to advanced age. We present results of a new salvage regimen, rituximab, gemcitabine and oxaliplatin (GEMOX-R), in 14 patients with relapsing (n = 9) or refractory (n = 5) mantle cell lymphoma. The median number of cycles was 5.5 for a total of 72 cycles evaluated in the current study. The median age was 69.5 years with high-risk features. Patients received a mean number of prior treatment lines of 1.79. Sixty-four percent achieved CR (total response rate of 85%). With a median follow-up of 11 months, OS and PFS were 58% and 45% at 12 months. The major toxicity was thrombopenia grade III-IV (35%). Factors related with overall survival were ECOG performance status and a-IPI at GEMOX-R. We conclude that GEMOX-R displays an outstanding efficacy with an excellent toxicity profile in a pretreated elderly population.

Assessment of the markers of platelet and coagulation activation following transcatheter closure of atrial septal defects.

BACKGROUND: Aspirin has been routinely prescribed following transcatheter closure of secundum atrial septal defects (ASDs) but its rationale has not been clinically or biologically evaluated; and despite aspirin, thrombotic complications occur following transcatheter ASD closure. We therefore evaluated the presence, degree and timing of the activation of the coagulation and platelet systems following transcatheter closure of ASDs. METHODS AND RESULTS: Fourteen consecutive patients (9 females, mean age 41+/-22 years) who underwent successful transcatheter closure of an ASD defect with the Amplatzer septal occluder were prospectively studied. Measurements of the prothrombin fragment 1+2 (F1+2) levels and the percentage of activated platelets (determined by P-selectin expression detected by flow cytometry) were taken at baseline just before the procedure, and at 1, 7, 30 and 90 days following device implantation. F1+2 levels increased from 0.85+/-0.29 nmol/l at baseline to a maximal value of 1.20+/-0.52 nmol/l at 7 days, gradually returning to the baseline levels at 90 days (0.79+/-0.54 nmol/l) (p<0.001). F1+2 levels at 7 days were also significantly higher than those obtained in a control group of 20 healthy subjects (p=0.016). A greater increase in coagulation activation was observed in cases of residual shunt following ASD closure (r=0.53, p=0.050). No significant variations in the percentage of platelets expressing P-selectin were detected at any time. CONCLUSIONS: Transcatheter closure of ASDs with the Amplatzer septal occluder was associated with a significant increase in F1+2 levels during the first week after device implantation, but there was no detectable effect on platelet system activation. These findings raise the question whether the optimal prophylactic approach following transcatheter ASD closure should be anticoagulant instead of antiplatelet therapy.