Genome-wide investigation of maize RAD51 binding affinity through phage display.

BACKGROUND: RAD51 proteins, which are conserved in all eukaryotes, repair DNA double-strand breaks. This is critical to homologous chromosome pairing and recombination enabling successful reproduction. Work in Arabidopsis suggests that RAD51 also plays a role in plant defense; the Arabidopsis rad51 mutant is more susceptible to Pseudomonas syringae. However, the defense functions of RAD51 and the proteins interacting with RAD51 have not been thoroughly investigated in maize. Uncovering ligands of RAD51 would help to understand meiotic recombination and possibly the role of RAD51 in defense. This study used phage display, a tool for discovery of protein-protein interactions, to search for proteins interacting with maize RAD51A1. RESULTS: Maize RAD51A1 was screened against a random phage library. Eleven short peptide sequences were recovered from 15 phages which bound ZmRAD51A1 in vitro; three sequences were found in multiple successfully binding phages. Nine of these phage interactions were verified in vitro through ELISA and/or dot blotting. BLAST searches did not reveal any maize proteins which contained the exact sequence of any of the selected phage peptides, although one of the selected phages had a strong alignment (E-value = 0.079) to a binding domain of maize BRCA2. Therefore, we designed 32 additional short peptides using amino acid sequences found in the predicted maize proteome. These peptides were not contained within phages. Of these synthesized peptides, 14 bound to ZmRAD51A1 in a dot blot experiment. These 14 sequences are found in known maize proteins including transcription factors putatively involved in defense. CONCLUSIONS: These results reveal several peptides which bind ZmRAD51A1 and support a potential role for ZmRAD51A1 in transcriptional regulation and plant defense. This study also demonstrates the applicability of phage display to basic science questions, such as the search for binding partners of a known protein, and raises the possibility of an iterated approach to test peptide sequences that closely but imperfectly align with the selected phages.

Comparison of meiotic transcriptomes of three maize inbreds with different origins reveals differences in cell cycle and recombination.

BACKGROUND: Cellular events during meiosis can differ between inbred lines in maize. Substantial differences in the average numbers of chiasmata and double-strand breaks (DSBs) per meiotic cell have been documented among diverse inbred lines of maize: CML228, a tropical maize inbred line, B73 and Mo17, temperate maize lines. To determine if gene expression might explain these observed differences, an RNA-Seq experiment was performed on CML228 male meiocytes which was compared to B73 and Mo17 male meiocytes, where plants were grown in the same controlled environment. RESULTS: We found that a few DSB-repair/meiotic genes which promote class I crossovers (COs) and the Zyp1 gene which limits newly formed class I COs were up-regulated, whereas Mus81 homolog 2 which promotes class II COs was down-regulated in CML228. Although we did not find enriched gene ontology (GO) categories directly related to meiosis, we found that GO categories in membrane, localization, proteolysis, energy processes were up-regulated in CML228, while chromatin remodeling, epigenetic regulation, and cell cycle related processes including meiosis related cell cycle processes were down-regulated in CML228. The degree of similarity in expression patterns between the three maize lines reflect their genetic relatedness: B73 and Mo17 had similar meiotic expressions and CML228 had a more distinct expression profile. CONCLUSIONS: We found that meiotic related genes were mostly conserved among the three maize inbreds except for a few DSB-repair/meiotic genes. The findings that the molecular players in limiting class I CO formation (once CO assurance is achieved) were up-regulated and those involved in promoting class II CO formation were down-regulated in CML228 agree with the lower chiasmata number observed in CML228 previously. In addition, epigenetics such as chromatin remodeling and histone modification might play a role. Transport and energy-related processes was up-regulated and Cyclin13 was down-regulated in CML228. The direction of gene expression of these processes agree with that previously found in meiotic tissues compared with vegetative tissues. In summary, we used different natural maize inbred lines from different climatic conditions and have shown their differences in expression landscape in male meiocytes.

End-stage renal disease patients undergoing angioplasty and bypass for critical limb ischemia have worse outcomes compared to non-ESRD patients: Systematic review and meta-analysis.

BACKGROUND: End-stage renal disease (ESRD) is associated with increased morbidity and mortality following lower extremity amputation for critical limb ischemia (CLI). Angioplasty and bypass are used in ESRD patients with CLI; however, the treatment of choice remains controversial. We compared the long-term outcomes in patients with CLI undergoing angioplasty or bypass to evaluate the differences between patients with ESRD and those without ESRD. METHODS: Established databases were searched for observational studies comparing outcomes following bypass or angioplasty for CLI in patients with ESRD to those in non-ESRD patients. End points included survival, limb salvage, amputation-free survival (AFS), and primary and secondary patency at 1-year post-procedure. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random effect model. RESULTS: We included 20 studies with a total of 24,851 patients. ESRD patients compared to non-ESRD patients with CLI had significantly lower survival post-angioplasty (OR 0.51, 95% CI 0.36-0.72, p < .001) and post-bypass (OR 0.26, 95% CI 0.15-0.45, p < .001). ESRD patients had lower rates of limb salvage post-bypass (OR 0.33, 95% CI 0.21-0.53, p < .001) and post-angioplasty (OR 0.54, 95% CI 0.41-0.70, p < .001). AFS was significantly lower in ESRD patients compared to non-ESRD patients following angioplasty (OR 0.48, 95% CI 0.32-0.71, p < .001) and bypass (OR 0.28, 95% CI 0.16-0.47, p < .001) despite no significant differences in primary patency. ESRD patients had overall worse secondary patency post-angioplasty and/or bypass (OR 0.54, 95% CI 0.32-0.94, p = .03) compared to non-ESRD patients. A meta-analysis of four studies directly comparing survival in ESRD patients with CLI based on whether they underwent angioplasty or bypass showed no difference (OR 0.93, 95% CI 0.64-1.35, p = .69). CONCLUSION: ESRD patients have worse survival, limb salvage, and AFS outcomes following angioplasty and bypass for CLI compared to non-ESRD patients. Large randomized controlled trials comparing these two modalities of treatment in this patient population are needed for further clarity.

Maize defective kernel mutant generated by insertion of a Ds element in a gene encoding a highly conserved TTI2 cochaperone.

We have used the newly engineered transposable element Dsg to tag a gene that gives rise to a defective kernel (dek) phenotype. Dsg requires the autonomous element Ac for transposition. Upon excision, it leaves a short DNA footprint that can create in-frame and frameshift insertions in coding sequences. Therefore, we could create alleles of the tagged gene that confirmed causation of the dek phenotype by the Dsg insertion. The mutation, designated dek38-Dsg, is embryonic lethal, has a defective basal endosperm transfer (BETL) layer, and results in a smaller seed with highly underdeveloped endosperm. The maize dek38 gene encodes a TTI2 (Tel2-interacting protein 2) molecular cochaperone. In yeast and mammals, TTI2 associates with two other cochaperones, TEL2 (Telomere maintenance 2) and TTI1 (Tel2-interacting protein 1), to form the triple T complex that regulates DNA damage response. Therefore, we cloned the maize Tel2 and Tti1 homologs and showed that TEL2 can interact with both TTI1 and TTI2 in yeast two-hybrid assays. The three proteins regulate the cellular levels of phosphatidylinositol 3-kinase-related kinases (PIKKs) and localize to the cytoplasm and the nucleus, consistent with known subcellular locations of PIKKs. dek38-Dsg displays reduced pollen transmission, indicating TTI2's importance in male reproductive cell development.

Correlation of Left Atrial Appendage Ejection Velocities with the CHADS2 and CHA2DS2-VASc Scores.

BACKGROUND: In patients with atrial fibrillation or flutter, a left atrial appendage ejection velocity measured via transesophageal echocardiography equal to or less than 40 cm/sec has been shown to correlate with an increased risk of developing left atrial appendage thrombus while velocities greater than 40 cm/sec are at lower risk. The CHADS2 and CHA2DS2-VASc scores calculated from clinical variables have been developed to risk stratify patients with atrial fibrillation/flutter in regard to the need for anticoagulation. This study was designed to assess whether a relationship exists between left atrial appendage ejection velocities and the respective CHADS2 and CHA2DS2-VASc scores, and whether this relationship is affected by the presence of atrial fibrillation or atrial flutter. METHODS: A retrospective chart review was performed on patients in the last 5 years who had undergone a transesophageal echocardiogram in which LAA velocity was measured. Once these patients were identified, relevant clinical information allowing for the calculation of the CHADS2 and CHA2DS2-VASc scores was also extracted from the medical record. RESULTS: Data from a total of 151 patients were included in the study. A statistically significant correlation between LAA velocity and CHADS2 score (P = 0.942) or between LAA velocity and CHA2DS2-VASc scores (P = 0.723) was not found. CONCLUSIONS: We could not identify a relationship between either the CHADS2 or CHA2DS2-VASc scores and LAA velocities. This was true regardless of whether patients were in sinus rhythm or AF at the time of the TEE. While reduced LAA velocities increase the risk of LAA thrombus, the development of stroke in patients with AF is secondary to a complex interplay of multiple clinical variables.

Genome-wide histone acetylation correlates with active transcription in maize.

Gene expression is regulated at many different levels during the life cycle of all plant species. Recent investigations have taken advantage of next-generation sequencing to study the relevance of DNA methylation and sRNAs in controlling tissue-specific gene expression in maize at the genome-wide level. Here, we profiled H3K27ac in maize, which has one of the largest sequenced plant genomes due to the amplification of retrotransposons. Because transcribed genes represent only a small proportion of its genome, gene-specific epigenetic modifications are concentrated in a relatively small percentage of the genome. Indeed, H3K27ac marks are mostly in gene-rich, in contrast to gene-poor regions. A large proportion of those marks are located in transcribed regions of genes, including 111 out of 458 known genetic loci. Moreover, increased transcription correlates with the presence of H3K27ac modification in gene bodies. Using maize as an example, we suggest that H3K27ac marks actively transcribed genes in plants.

Safety of Stromal Vascular Fraction Cell Therapy for Chronic Kidney Disease of Unknown Cause (Mesoamerican Nephropathy).

Chronic kidney disease of unknown cause (CKDu), also known as Mesoamerican nephropathy, typically presents as an ischemic nephropathy with chronic tubulointerstitial fibrosis in normotensive patients, rapidly progressing to kidney failure. In this first-in-human, open-label, safety study, we followed 18 patients with CKDu (stages 3-5) for 36 months after receiving a single infusion of angiogenic/anti-fibrotic autologous adipose-derived stromal vascular fraction (SVF) cells into their kidneys bilaterally via renal artery catheterization. SVF therapy was safe and well tolerated. There were no SVF-related serious adverse events and no procedural complications. Color Doppler evaluation at 2 months demonstrated increased perfusion to the interlobar and/or arcuate artery levels in each kidney evaluated (36/36) with a reduction in resistance index at the hilar artery (35/36) kidneys. Beyond 12 months, patients with initial eGFR <30 mL/minute/1.73 m2 deteriorated, whereas those ≥30 mL/minute/1.73 m2 further sustained their renal function, suggesting a possible renal protective effect in that group.

A tool for rapid, automated characterization of population epigenomics in plants.

Epigenetic variation in plant populations is an important factor in determining phenotype and adaptation to the environment. However, while advances have been made in the molecular and computational methods to analyze the methylation status of a given sample of DNA, tools to profile and compare the methylomes of multiple individual plants or groups of plants at high resolution and low cost are lacking. Here, we describe a computational approach and R package (sounDMR) that leverages the benefits of long read nanopore sequencing to enable robust identification of differential methylation from complex experimental designs, as well as assess the variability within treatment groups and identify individual plants of interest. We demonstrate the utility of this approach by profiling a population of Arabidopsis thaliana exposed to a demethylating agent and identify genomic regions of high epigenetic variability between individuals. Given the low cost of nanopore sequencing devices and the ease of sample preparation, these results show that high resolution epigenetic profiling of plant populations can be made more broadly accessible in plant breeding and biotechnology.

UV-B Irradiation Results in Inhibition of Hypocotyl Elongation, Cell Cycle Arrest, and Decreased Endoreduplication Mediated by miR5642.

UV-B as a component of natural solar radiation can induce damage and morphological development in plants. The UV-B response from germination and early development in seedlings is still largely unknown, with most studies focused on older, light-exposed seedlings. We used fluence response curves measuring hypocotyl length after UV-B exposure coupled with RNA-seq and sRNA-seq evaluation of the early seedling response in the model organism Arabidopsis thaliana. We identified miR5642 as a potential novel key regulator of UV-B responses. miR5642 is a noncanonical miRNA predicted to target previously known and unknown components involved in hypocotyl growth inhibition. These include (i) SMAX1, a signal transmitter for seedling germination and growth; (ii) ZAT1, an uncharacterized transcription factor; and (iii) membrane pores and transporters (VHA-E1, VHA-E3, EPSIN-LIKE and PIP1.4) implicated in cell elongation. In addition, HY5 and HYH, two homologous and redundant transcription factors involved in seedling photomorphogenesis, may interact with these newly identified components. Interestingly, UV-B-induced DNA photodimer formation seems to be the direct trigger leading to inhibition of hypocotyl growth through a combination of cellular decisions including cell cycle arrest, reduced endoreduplication and reduced cell elongation, and this inhibition appears to be modulated by miR5642 target genes.

Treatment of chronic diabetic foot ulcers with adipose-derived stromal vascular fraction cell injections: Safety and evidence of efficacy at 1 year.

Diabetes affects multiple systems in complex manners. Diabetic foot ulcers (DFUs) are a result of diabetes-induced microarterial vessel disease and peripheral neuropathy. The presence of arteriosclerosis-induced macroarterial disease can further complicate DFU pathophysiology. Recent studies suggest that mesenchymal stromal cell therapies can enhance tissue regeneration. This phase I study was designed to determine the safety and explore the efficacy of local injections of autologous adipose-derived stromal vascular fraction (SVF) cells to treat nonhealing DFUs greater than 3 cm in diameter. Sixty-three patients with type 2 diabetes with chronic DFU-all amputation candidates-were treated with 30 × 106 SVF cells injected in the ulcer bed and periphery and along the pedal arteries. Patients were seen at 6 and 12 months to evaluate ulcer closure. Doppler ultrasounds were performed in a subset of subjects to determine vascular structural parameters. No intervention-related serious adverse events were reported. At 6 months, 51 subjects had 100% DFU closure, and 8 subjects had ≥75% closure. Three subjects had early amputations, and one subject died. At 12 months, 50 subjects had 100% DFU healing and 4 subjects had ≥85% healing. Five subjects died between the 6- and 12-month follow-up visits. No deaths were intervention related. Doppler studies in 11 subjects revealed increases in peak systolic velocity and pulsatility index in 33 of 33 arteries, consistent with enhanced distal arterial runoff. These results indicate that SVF can be safely used to treat chronic DFU, with evidence of efficacy (wound healing) and mechanisms of action that include vascular repair and/or angiogenesis.

Guidelines for prophylaxis and anti-thrombotic treatment for patients with COVID-19. Consensus of the Latin American Cooperative Group on Hemostasis and Thrombosis (CLAHT) / Guía de profilaxia y tratamiento antitrombótico para pacientes con COVID-19. Consenso del Grupo Cooperativo Latinoamericano en Hemostasia y Trombosis (CLAHT)

Coagulopathy and thrombosis associated with coronavirus disease 2019 (COVID-19) represent a major issue in the management of this disease. In the past months, clinical studies have demonstrated that COVID-19 patients present with a particular hypercoagulable state, in which a markedly increased D-dimer concomitant with increased levels of fibrinogen are observed. This hypercoagulable state leads to an increased risk of thrombosis, which seems to be higher among those patients with critical symptoms of COVID-19. The best therapeutic approach to prevent thrombotic events in COVID-19 has not been determined yet and several questions regarding thromboprophylaxis therapy, such as the time to initiate anticoagulation, type of anticoagulant and dose regimen, have emerged among physicians. To address these concerns, several medical societies have published position papers to provide the opinion of thrombosis experts on the management of coagulopathy and thrombosis associated with COVID-19. In line with this, the Latin America Cooperative Group of Hemostasis and Thrombosis (Grupo CLAHT) has constituted a panel of experts in thrombosis and hemostasis to discuss the available data on this topic. The aim of this review is to summarize the current evidence regarding hemostatic impairment and thrombotic risk in COVID-19 and to provide a carefully revised opinion of Latin American experts on the thromboprophylaxis and management of thrombotic events and coagulopathy in patients with suspected COVID-19.

La coagulopatía y la trombosis asociadas a la enfermedad por coronavirus 2019 (COVID-19) representan un problema importante en el manejo de esta enfermedad. Los estudios clínicos de los últimos meses han demostrado que los pacientes con COVID-19 presentan un estado de hipercoagulabilidad particular, en el que se observa un aumento notable del dímero D concomitante con niveles elevados de fibrinógeno. El estado de hipercoagulabilidad conduce a un mayor riesgo de trombosis, que parece ser mayor entre aquellos pacientes con síntomas críticos de COVID-19. El mejor enfoque terapéutico para prevenir los eventos trombóticos en esta nueva enfermedad aún no se ha determinado y han surgido varias preguntas con respecto a la tromboprofilaxia, como el momento adecuado para iniciar la anticoagulación, el tipo de anticoagulante y el régimen de dosis. Para abordar estas preocupaciones, varias sociedades médicas han publicado artículos de posición para brindar la opinión de expertos en trombosis sobre el manejo de la coagulopatía y trombosis asociadas a COVID-19. Grupo Cooperativo Latinoamericano de Hemostasia y Trombosis (Grupo CLAHT) ha convocado a un panel de expertos en trombosis y hemostasia para discutir los datos disponibles sobre este tema. El objetivo de esta revisión es resumir la evidencia actual con respecto al deterioro hemostático y el riesgo trombótico en el COVID-19 y proporcionar una opinión cuidadosamente revisada de los expertos latinoamericanos sobre la tromboprofilaxis y el manejo de eventos trombóticos y coagulopatía en pacientes con sospecha de COVID-19.

Isolating Male Meiocytes from Maize and Wheat for "-Omics" Analyses.

Genome-wide gene expression studies have become a routine approach due to the advances in sequencing technologies, their ease of use, and increasing affordability. Simultaneous investigation of small RNA expression adds further valuable information but is not adopted as widely yet. Both RNA-seq and small RNA-seq benefit from the use of specific cell types. Here, we describe a protocol for the isolation of male meiotic cells from maize or wheat plants, along with the application of downstream RNA sequencing, extendable to other -omics approaches.

Suicide Attempt as the Presenting Symptom in a Patient with COVID-19: A Case Report from the United States.

Coronavirus disease 2019 (COVID-19) has attained a pandemic status and is associated with a high morbidity and mortality. Social isolation, fear of ostracization, and illness itself and limited access to care can lead to worsening of mental illnesses. We report a case from the United States describing a young male with a suicidal attempt who was subsequently found to have COVID-19 infection. Further research is needed to evaluate potential factors for this unique association.

Protective effects of D-005, a lipid extract from Acrocomia crispa fruits, against ischemia/reperfusion-induced acute kidney injury in rats.

BACKGROUND: Acute kidney injury (AKI) induced by renal ischemia/reperfusion (IR) is associated with enhanced production of reactive oxygen species in renal tissues. D-005, a lipid extract obtained from Acrocomia crispa fruit, has previously shown antioxidant effects. The aim of this work was to evaluate the effects of D-005 on renal IR-induced AKI in rats. METHODS: Rats were randomized into seven groups including a negative control group (vehicle) without AKI and six groups with renal IR-induced AKI as follows: a positive control (vehicle); D-005 treatment at 25, 100, 200, or 400 mg/kg; and dexamethasone at 3 mg/kg. All treatments were orally administered as single doses 1 hour before AKI induction. Biomarkers (serum creatinine, urea, and uric acid concentrations), oxidative variables, and histopathological AKI changes were evaluated in blood and kidney tissues. RESULTS: All D-005 doses protected against IR-induced AKI in rats by significantly decreasing biomarkers and histopathological AKI changes as assessed by reduced serum concentrations of creatinine, urea, and uric acid. In addition, all D-005 doses decreased tubular damage, as shown by fewer detached cells and casts in the tubular lumen. D-005 reversed oxidation disturbance markers by decreasing malondialdehyde and sulfhydryl group concentrations in plasma and in kidney homogenates and by increasing kidney catalase activity. Dexamethasone, the reference substance, protected against IR-induced AKI in rats by reducing biochemical and histological variables of renal damage in a similar manner. CONCLUSION: Administration of single oral doses of D-005 markedly and significantly protected against renal IR-induced AKI, possibly due to its known antioxidant effects.

JM-20 protects memory acquisition and consolidation on scopolamine model of cognitive impairment.

OBJECTIVE: JM-20, a novel hybrid synthetic molecule, has been reported to have antioxidant, mitoprotective, anti-excitotoxic, anti-apoptotic and anti-inflammatory properties. However, the neuroprotective effect of JM-20 against memory impairment in preclinical AD-like models has not been analyzed. The aim of this study was to evaluate the potential neuroprotection of JM-20 that preserves essential memory process from cholinergic dysfunction and other molecular damages. METHODS: The effects of JM-20 on scopolamine (1 mg/kg)-induced cognitive disorders were studied. Male Wistar rats (220-230 g) were treated with JM-20 and/or scopolamine, and behavioral tasks were performed. The AChE activity, superoxide dismutase activity, catalase activity, MDA and T-SH level on brain tissue were determined by spectrophotometric methods. Mitochondrial functionality parameters were measured after behavioral tests. Histological analyses on hippocampus and prefrontal cortex were processed with hematoxylin and eosin, and neuronal and axonal damage were determined. RESULTS: The behavioral, biochemical and histopathological studies revealed that oral pre-treatment with JM-20 (8 mg/kg) significantly attenuated the scopolamine-induced memory deficits, mitochondrial malfunction, oxidative stress, and prevented AChE hyperactivity probably due to specific inhibition of AChE enzyme. It was also observed marked histological protection on hippocampal and prefrontal-cortex regions. CONCLUSIONS: The multimodal action of this molecule could mediate the memory protection here observed and suggest that it may modulate different pathological aspects of memory deficits associated with AD in humans.

Non-vitamin K antagonists oral anticoagulants are as safe and effective as warfarin for cardioversion of atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: Current guidelines recommend anticoagulation using warfarin with bridging parenteral anticoagulation or one of the non-vitamin K antagonist oral anticoagulants (NOACs) to prevent thromboembolic events in patients undergoing cardioversion for atrial fibrillation (AF). We aimed to compare by meta-analytical techniques, the safety and efficacy of NOACs versus warfarin in patients undergoing cardioversion. METHODS: PUBMED, EMBASE, Cochrane CENTRAL and CINAHL were searched electronically in addition to manual search for randomized controlled trials (RCTs) comparing NOACs and warfarin in patients undergoing cardioversion for AF. Mortality, major bleeding and ischemic and hemorrhagic stroke were compared between the two agents. RESULTS: A total of 7 trials with 7588 total patients were included in the meta-analysis. NOACs, as compared to warfarin, resulted in similar risk of ischemic stroke [odds ratio (OR): 0.49 (95% confidence interval (CI): 0.20-1.19; P = 0.12], major bleeding [0.71 (0.37-1.38), P = 0.32], mortality [0.73 (0.32-1.67); P = 0.45], and hemorrhagic stroke [0.96 (0.11-8.70); P = 0.97]. The results were consistent across subgroup analyses. CONCLUSIONS: Based on the current meta-analysis, NOACs and warfarin have comparable efficacy and safety in patients with atrial fibrillation undergoing cardioversion.

TTT and PIKK Complex Genes Reverted to Single Copy Following Polyploidization and Retain Function Despite Massive Retrotransposition in Maize.

The TEL2, TTI1, and TTI2 proteins are co-chaperones for heat shock protein 90 (HSP90) to regulate the protein folding and maturation of phosphatidylinositol 3-kinase-related kinases (PIKKs). Referred to as the TTT complex, the genes that encode them are highly conserved from man to maize. TTT complex and PIKK genes exist mostly as single copy genes in organisms where they have been characterized. Members of this interacting protein network in maize were identified and synteny analyses were performed to study their evolution. Similar to other species, there is only one copy of each of these genes in maize which was due to a loss of the duplicated copy created by ancient allotetraploidy. Moreover, the retained copies of the TTT complex and the PIKK genes tolerated extensive retrotransposon insertion in their introns that resulted in increased gene lengths and gene body methylation, without apparent effect in normal gene expression and function. The results raise an interesting question on whether the reversion to single copy was due to selection against deleterious unbalanced gene duplications between members of the complex as predicted by the gene balance hypothesis, or due to neutral loss of extra copies. Uneven alteration of dosage either by adding extra copies or modulating gene expression of complex members is being proposed as a means to investigate whether the data supports the gene balance hypothesis or not.

Linfomas asociados a infección por el virus de inmunodeficiencia humana

Objetivos: describir el perfil clínico y resultados del tratamiento de casos de Linfoma asociado a infección por el Virus de Inmunodeficiencia Humana. Métodos: estudio retrospectivo de casos de linfoma asociado a infección por el Virus de Inmunodeficiencia Humana, atendidos en el servicio de Hematología del Hospital Materno Infantil, La Paz, Bolivia durante el periodo 2010-2021. Resultados: se estudiaron ocho casos, de los cuales 6 (75%) eran del sexo masculino. En relación a la edad, la media fue de 40,75 años. 7 (87,5%) eran Linfoma no Hodgkin y un caso a Linfoma de Hodgkin. En siete pacientes el diagnóstico de linfoma fué posterior a la detección de la infección por el Virus de Inmunodeficiencia Humana, con un tiempo medio de 4,6 años. El 75% de los casos se presentaron con un estadio avanzado. De los siete casos de Linfoma no Hodgkin, cinco correspondían al Linfoma Difuso de Células Grandes B. El tratamiento quimioterápico se inició en todos los casos pero solo tres completaron los ciclos programados, el restante dejaron el tratamiento principalmente debido a complicaciones infecciosas. Se registraron cuatro (50%) fallecimientos, de los cuales tres ocurrieron en los primeros cuatro meses desde el diagnóstico de linfoma. Conclusiones: en el presente estudio, el Linfoma no Hodgkin fue el más frecuente, representado principalmente por el Linfoma Difuso de Células Grandes B. Una característica común fue la presentación en estadios avanzados. La quimioterapia no se pudo completar en la mayoría de los casos debido a complicaciones relacionadas con la inmunodepresión, la mitad de los casos fallecieron durante el periodo de estudio.

Objectives: to describe the clinical profile and treatment outcomes of cases of lymphoma associated with Human Immunodeficiency Virus infection. Methods: retrospective study of cases of lymphoma associated with Human Immunodeficiency Virus infection treated at the Hematology Department of the Materno Infantil Hospital, La Paz, Bolivia during the period 2010-2021. Results: Eight cases were studied, of which 6 (75%) were male. The mean age was 40.75 years. 7 (87.5%) were Non-Hodgkin's Lymphoma and one case was Hodgkin's Lymphoma. In seven patients, the diagnosis of lymphoma was made after the detection of Human Immunodeficiency Virus infection, with a mean time of 4.6 years. 75% of the cases presented with advanced stage. Of the seven cases of Non-Hodgkin's Lymphoma, five corresponded to Large B-Cell Lymphoma. Chemotherapy was started in all cases but only three completed the scheduled cycles, the remainder stopped treatment mainly due to infectious complications. Four (50%) deaths were recorded, three of which occurred within the first four months after the diagnosis of lymphoma. Conclusions: In this study, Non-Hodgkin's Lymphoma was the most frequent, represented mainly by Large B-Cell Lymphoma. A common characteristic was the presentation at advanced stages. Chemotherapy could not be completed in the majority of cases due to complications related to immunodepression, and half of the cases died during the study period.

1H NMR, a rapid method to monitor organic acids during cupuassu (Theobroma grandiflorum Spreng) processing.

The development of an analytical method using 1H nuclear magnetic resonance (1H NMR) spectrometry to monitor cupuassu (Theobroma grandiflorum Spreng) bean fermentation, drying, and roasting processes is reported. The analysis of organic acids and alcohols of crude water extracts of cupuassu ground kernels were monitored by HPLC and 1H NMR spectroscopy. The residual protein signals caused deleterious effects on acid and alcohol quantifications. Therefore, the analytical procedures were optimized by sample cleanup and water suppression pulse sequences in order to obtain compatible data using HPLC and 1H NMR. The quantification of lactic acid, acetic acid, and 2,3-butanediol by NMR is 5- to 10-fold faster than by HPLC, with the advantage of providing the identification of several chemical species in a single experiment. Application of these analytical conditions to some cupuassu samples revealed that this methodology can be applied to the quality profiles of fermentation and roasting processes.