Ribonucleotide synthesis by NME6 fuels mitochondrial gene expression.

Replication of the mitochondrial genome and expression of the genes it encodes both depend on a sufficient supply of nucleotides to mitochondria. Accordingly, dysregulated nucleotide metabolism not only destabilises the mitochondrial genome, but also affects its transcription. Here, we report that a mitochondrial nucleoside diphosphate kinase, NME6, supplies mitochondria with pyrimidine ribonucleotides that are necessary for the transcription of mitochondrial genes. Loss of NME6 function leads to the depletion of mitochondrial transcripts, as well as destabilisation of the electron transport chain and impaired oxidative phosphorylation. These deficiencies are rescued by an exogenous supply of pyrimidine ribonucleosides. Moreover, NME6 is required for the maintenance of mitochondrial DNA when the access to cytosolic pyrimidine deoxyribonucleotides is limited. Our results therefore reveal an important role for ribonucleotide salvage in mitochondrial gene expression.

The Atomically Precise Gold/Captopril Nanocluster Au25(Capt)18 Gains Anticancer Activity by Inhibiting Mitochondrial Oxidative Phosphorylation.

Atomically precise gold nanoclusters (AuNCs) are an emerging class of quantum-sized nanomaterials with well-defined molecular structures and unique biophysical properties, rendering them highly attractive for biological applications. We set out to study the impact of different ligand shells of atomically similar nanoclusters on cellular recognition and response. To understand the effects of atomically precise nanoclusters with identical composition on cells, we selected two different water-soluble gold nanoclusters protected with captopril (Capt) and glutathione (GSH): Au25(Capt)18 (CNC) and Au25(GSH)18 (GNC), respectively. We demonstrated that a change of the ligand of the cluster completely changes its biological functions. Whereas both nanoclusters are capable of internalization, only CNC exhibits remarkable cytotoxicity, more specifically on cancer cells. CNC shows enhanced cytotoxicity by inhibiting the OXPHOS of mitochondria, possibly by inhibiting the ATP synthase complex of the electron transport chain (ETC), and by initiating the leakage of electrons into the mitochondrial lumen. The resulting increase in both mitochondrial and total cellular ROS triggers cell death indicated by the appearance of cellular markers of apoptosis. Remarkably, this effect of nanoclusters is independent of any external light source excitation. Our findings point to the prevailing importance of the ligand shell for applications of atomically precise nanoclusters in biology and medicine.

RNA Granules in the Mitochondria and Their Organization under Mitochondrial Stresses.

The human mitochondrial genome (mtDNA) regulates its transcription products in specialised and distinct ways as compared to nuclear transcription. Thanks to its mtDNA mitochondria possess their own set of tRNAs, rRNAs and mRNAs that encode a subset of the protein subunits of the electron transport chain complexes. The RNA regulation within mitochondria is organised within specialised, membraneless, compartments of RNA-protein complexes, called the Mitochondrial RNA Granules (MRGs). MRGs were first identified to contain nascent mRNA, complexed with many proteins involved in RNA processing and maturation and ribosome assembly. Most recently, double-stranded RNA (dsRNA) species, a hybrid of the two complementary mRNA strands, were found to form granules in the matrix of mitochondria. These RNA granules are therefore components of the mitochondrial post-transcriptional pathway and as such play an essential role in mitochondrial gene expression. Mitochondrial dysfunctions in the form of, for example, RNA processing or RNA quality control defects, or inhibition of mitochondrial fission, can cause the loss or the aberrant accumulation of these RNA granules. These findings underline the important link between mitochondrial maintenance and the efficient expression of its genome.

Visualization of Mitochondrial RNA Granules in Cultured Cells Using 5-Bromouridine Labeling.

The incorporation of nucleoside analogs is a useful tool to study the various functions of DNA and RNA. These analogs can be detected directly by fluorescence or by immunolabeling, allowing to visualize, track, or measure the nucleic acid molecules in which they have been incorporated. In this chapter, methodologies to measure human mitochondrial transcription are described. The nascent RNA that is transcribed from mitochondrial DNA (mtDNA) has been shown to assemble into large ribonucleoprotein complexes that form discrete foci. These structures were called mitochondrial RNA granules (MRGs) and can be observed in vitro by the incorporation of a 5-Bromouridine (BrU), which is subsequently visualized by fluorescent immunolabeling. Here, a combined protocol for the MRGs detection is detailed, consisting of BrU labeling and visualization of one of their bona fide protein components, Fas-activated serine-threonine kinase domain 2 (FASTKD2). Based on immunodetection, the half-life and kinetics of the MRGs under various experimental conditions can further be determined by chasing the BrU pulse with an excess of Uridine.

Contribution to the Journal Ciência & Saúde Coletiva on Food and Nutrition in Brazil. / Contribuição da Revista Ciência & Saúde Coletiva para a área de Alimentação e Nutrição no Brasil.

A systematic review conducted in January 2020 using SciELO database with the objective of analyzing the scientific production from 1996-2019, of the Journal Ciência & Saúde Coletiva in the area of food and nutrition. We selected 509 out of the 904 articles screened by titles and abstracts. We grouped the articles into ten themes and discussed the most frequent ones: Nutritional Status Assessment (n=142), Food Intake (n=111), Food and Nutrition Policies and Programmes (n=105) and Breastfeeding (n=35). The publications were mostly original articles (75.6%) employing quantitative method (81.6%) and, among these, 18.8% used a probabilistic sampling. We assembled a wide range of topics and subthemes, a relevant production and repository of data and knowledge for health professionals and managers. As gaps, there was a scarcity of publications focused on micronutrient deficiency; the promotion of the Food Guide for the Brazilian Population; supporting the rise of breastfeeding, the impact and analyses of the disruption of the National Food and Nutrition Security Policy and its multi sector interactions with social policies to fight hunger.

Revisão sistemática realizada em janeiro de 2020 na base de dados SciELO com o objetivo de analisar a produção científica da Revista Ciência & Saúde Coletiva na área de alimentação e nutrição no período 1996-2019. A busca resultou em 904 artigos e 509 foram selecionados após leitura dos títulos e resumos. Os artigos foram agrupados em dez temas, sendo discutidos os de maior frequência: Avaliação do Estado Nutricional (n=142), Consumo Alimentar (n=111), Políticas e Programas de Alimentação e Nutrição (n=105) e Aleitamento Materno (n=35). As publicações foram em sua maioria artigos originais (75,6%) com método quantitativo (81,6%) e, entre estes, 18,8% utilizaram amostra probabilística. Observou-se um amplo leque de temas e subtemas abordados, evidenciando uma produção relevante que constitui um repositório importante de dados e conhecimentos para profissionais e gestores da área da saúde. Como lacunas, observou-se a escassez de publicações voltadas para a deficiência de micronutrientes; a popularização do Guia Alimentar para População Brasileira; a promoção da ascensão do aleitamento materno; os diagnósticos da descontinuidade da Política Nacional de Segurança Alimentar e Nutricional e suas articulações intersetoriais com as políticas sociais de combate à fome.

Contribuição da Revista Ciência & Saúde Coletiva para a área de Alimentação e Nutrição no Brasil / Contribution to the Journal Ciência & Saúde Coletiva on Food and Nutrition in Brazil

Resumo Revisão sistemática realizada em janeiro de 2020 na base de dados SciELO com o objetivo de analisar a produção científica da Revista Ciência & Saúde Coletiva na área de alimentação e nutrição no período 1996-2019. A busca resultou em 904 artigos e 509 foram selecionados após leitura dos títulos e resumos. Os artigos foram agrupados em dez temas, sendo discutidos os de maior frequência: Avaliação do Estado Nutricional (n=142), Consumo Alimentar (n=111), Políticas e Programas de Alimentação e Nutrição (n=105) e Aleitamento Materno (n=35). As publicações foram em sua maioria artigos originais (75,6%) com método quantitativo (81,6%) e, entre estes, 18,8% utilizaram amostra probabilística. Observou-se um amplo leque de temas e subtemas abordados, evidenciando uma produção relevante que constitui um repositório importante de dados e conhecimentos para profissionais e gestores da área da saúde. Como lacunas, observou-se a escassez de publicações voltadas para a deficiência de micronutrientes; a popularização do Guia Alimentar para População Brasileira; a promoção da ascensão do aleitamento materno; os diagnósticos da descontinuidade da Política Nacional de Segurança Alimentar e Nutricional e suas articulações intersetoriais com as políticas sociais de combate à fome.

Abstract A systematic review conducted in January 2020 using SciELO database with the objective of analyzing the scientific production from 1996-2019, of the Journal Ciência & Saúde Coletiva in the area of food and nutrition. We selected 509 out of the 904 articles screened by titles and abstracts. We grouped the articles into ten themes and discussed the most frequent ones: Nutritional Status Assessment (n=142), Food Intake (n=111), Food and Nutrition Policies and Programmes (n=105) and Breastfeeding (n=35). The publications were mostly original articles (75.6%) employing quantitative method (81.6%) and, among these, 18.8% used a probabilistic sampling. We assembled a wide range of topics and subthemes, a relevant production and repository of data and knowledge for health professionals and managers. As gaps, there was a scarcity of publications focused on micronutrient deficiency; the promotion of the Food Guide for the Brazilian Population; supporting the rise of breastfeeding, the impact and analyses of the disruption of the National Food and Nutrition Security Policy and its multi sector interactions with social policies to fight hunger.

Cystic renal-epithelial derived induced pluripotent stem cells from polycystic kidney disease patients.

Autosomal-dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, leading to kidney failure in most patients. In approximately 85% of cases, the disease is caused by mutations in PKD1. How dysregulation of PKD1 leads to cyst formation on a molecular level is unknown. Induced pluripotent stem cells (iPSCs) are a powerful tool for in vitro modeling of genetic disorders. Here, we established ADPKD patient-specific iPSCs to study the function of PKD1 in kidney development and cyst formation in vitro. Somatic mutations are proposed to be the initiating event of cyst formation, and therefore, iPSCs were derived from cystic renal epithelial cells rather than fibroblasts. Mutation analysis of the ADPKD iPSCs revealed germline mutations in PKD1 but no additional somatic mutations in PKD1/PKD2. Although several somatic mutations in other genes implicated in ADPKD were identified in cystic renal epithelial cells, only few of these mutations were present in iPSCs, indicating a heterogeneous mutational landscape, and possibly in vitro cell selection before and during the reprogramming process. Whole-genome DNA methylation analysis indicated that iPSCs derived from renal epithelial cells maintain a kidney-specific DNA methylation memory. In addition, comparison of PKD1+/- and control iPSCs revealed differences in DNA methylation associated with the disease history. In conclusion, we generated and characterized iPSCs derived from cystic and healthy control renal epithelial cells, which can be used for in vitro modeling of kidney development in general and cystogenesis in particular.

Plant growth and resistance promoted by Streptomyces spp. in tomato.

Plant Growth Promoting Rhizobacteria (PGPR) represent an alternative to improve plant growth and yield as well as to act as agents of biocontrol. This study characterized isolates of Streptomyces spp. (Stm) as PGPR, determined the antagonism of these isolates against Pectobacterium carotovorum subsp. brasiliensis (Pcb), evaluated the ability of Stm on promoting growth and modulating the defense-related metabolism of tomato plants, and the potential of Stm isolates on reducing soft rot disease in this species. The VOC profile of Stm was also verified. Promotion of plant growth was assessed indirectly through VOC emission and by direct interaction with Stm isolates in the roots. Evaluation of soft rot disease was performed in vitro on plants treated with Stm and challenged with Pcb. Enzymes related to plant defense were then analyzed in plants treated with three selected isolates of Stm, and PM1 was chosen for further Pcb-challenging experiment. Streptomyces spp. isolates displayed characteristics of PGPR. PM3 was the isolate with efficient antagonism against Pcb by dual-culture. Most of the isolates promoted growth of root and shoot of tomato plants by VOC, and PM5 was the isolate that most promoted growth by direct interaction with Stm. Soft rot disease and mortality of plants were significantly reduced when plants were treated with StmPM1. Modulation of secondary metabolism was observed with Stm treatment, and fast response of polyphenoloxidases was detected in plants pretreated with StmPM1 and challenged with Pcb. Peroxidase was significantly activated three days after infection with Pcb in plants pretreated with StmPM1. Results suggest that Streptomyces sp. PM1 and PM5 have the potential to act as PGPR.

B-1 cells contribute to susceptibility in experimental infection with Leishmania (Leishmania) chagasi.

The immune response to leishmaniasis is complex, and the result of infection depends on both the genetic composition of the Leishmania species and the immunity of the host. Clinical and experimental evidence suggest that the activation of B cells leads to exacerbation of visceral leishmaniasis. However, the role of B-1 cells (a subtype of B lymphocytes) in the pathogenesis of experimental visceral leishmaniasis has not yet been elucidated. In this study, we investigated the importance of B-1 cells in experimental infection with Leishmania. (L.) chagasi. Our results showed that BALB/XID mice (X-linked immunodeficient mice which are genetically deficient in B-1 cells) infected with L. (L.) chagasi for 45 days had a significant reduction in parasite load in the spleen when compared with control mice. Cytokine analysis showed that the BALB/XID mice had lower amounts of IL-10 in their sera compared with control group. In addition, the transfer of B-1 cells from wild type mice into IL-10KO animals led to an increase in susceptibility to L. (L.) chagasi infection in the IL-10KO mice, suggesting that the IL-10 produced by these cells is important in experimental infection. Our results suggest that B-1 cells may play an important role in susceptibility to L. (L.) chagasi.

Recent findings in the chemistry of odorants from four Baccharis species and their impact as chemical markers.

Baccharis is a widespread genus belonging to the Asteraceae family that includes almost 400 species exclusively from the Americas. Even when studied in detail, the taxonomic classification among species from this genus is not yet fully defined. Within the framework of our study of the volatile composition of the Baccharis genus, four species (B. trimera, B. milleflora, B. tridentata, and B. uncinella) were collected from the 'Campos de Cima da Serra' highlands of the Brazilian state of Rio Grande do Sul. The aerial parts were dried and extracted by the simultaneous distillation extraction (SDE) procedure. This is the first time that SDE has been applied to obtain and compare the volatile-extract composition in the Baccharis genus. Characterization of the volatile extracts allowed the identification of 180 peaks with many coeluting components; these latter being detailed for the first time for this genus. The multivariate statistical analyses allowed separating the volatile extracts of the four populations of Baccharis into two separate groups. The first one included the B. milleflora, B. trimera, and B. uncinella volatile extracts. The three species showed a high degree of similarity in their volatile composition, which was characterized by the presence of high contents of sesquiterpene compounds, in particular of spathulenol. The second group comprised the extract of B. tridentata, which contained α-pinene, ß-pinene, limonene, and (E)-ß-ocimene in high amounts.

Impact of gas chromatography and mass spectrometry combined with gas chromatography and olfactometry for the sex differentiation of Baccharis articulata by the analysis of volatile compounds.

The Baccharis genus has more than 400 species of aromatic plants. However, only approximately 50 species have been studied in oil composition to date. From these studies, very few take into consideration differences between male and female plants, which is a significant and distinctive factor in Baccharis in the Asteraceae family. Baccharis articulata is a common shrub that grows wild in south Brazil, northern and central Argentina, Bolivia, Paraguay and Uruguay. It is considered to be a medicinal plant and is employed in traditional medicine. We report B. articulata male and female volatile composition obtained by simultaneous distillation-extraction technique and analyzed by gas chromatography with mass spectrometry. Also, an assessment of aromatic differences between volatile extracts was evaluated by gas chromatography with olfactometry. The results show a very similar chemical composition between male and female extracts, with a high proportion of terpene compounds of which ß-pinene, limonene and germacrene D are the main components. Despite the chemical similarity, great differences in aromatic profile were found: male plant samples exhibited the strongest odorants in number and intensity of aromatic attributes. These differences explain field observations which indicate differences between male and female flower aroma, and might be of ecological significance in the attraction of pollinating insects.

Histopathological changes in the kidneys of vertebrate hosts infected naturally and experimentally with Paratanaisia bragai (Trematoda, Digenea).

Paratanaisia bragai is a trematode parasite that reaches sexual maturity in the kidney collecting ducts of domesticated and wild fowl and whose intermediate hosts are the snails Subulina octona and Leptinaria unilamellata. There are some discrepancies in descriptions of the pathology of this parasite in bird kidneys. Therefore, the purpose of this study was to analyze the kidneys of rock pigeons (Columba livia) naturally infected and of chickens (Gallus gallus) experimentally infected with Paratanaisia bragai, by means of macroscopic observation and by light and scanning electron microscopy. Both bird species showed significantly dilated collecting ducts. In addition, lymphocyte infiltration was observed in the kidneys of C. livia and metaplasia in the epithelial lining of the kidney collecting ducts of G. gallus.

Histopathological changes in the kidneys of vertebrate hosts infected naturally and experimentally withParatanaisia bragai (Trematoda, Digenea)

Paratanaisia bragai is a trematode parasite that reaches sexual maturity in the kidney collecting ducts of domesticated and wild fowl and whose intermediate hosts are the snails Subulina octona and Leptinaria unilamellata. There are some discrepancies in descriptions of the pathology of this parasite in bird kidneys. Therefore, the purpose of this study was to analyze the kidneys of rock pigeons (Columba livia) naturally infected and of chickens (Gallus gallus) experimentally infected with Paratanaisia bragai, by means of macroscopic observation and by light and scanning electron microscopy. Both bird species showed significantly dilated collecting ducts. In addition, lymphocyte infiltration was observed in the kidneys of C. livia and metaplasia in the epithelial lining of the kidney collecting ducts of G. gallus.

Paratanaisia bragai é um trematódeo que atinge sua maturidade sexual nos ductos coletores de rins de aves domésticas e silvestres, tendo os moluscos Subulina octona e Leptinaria unilamellata como hospedeiros intermediários. A patologia descrita no rim das aves apresenta uma série de divergências. Dessa forma, o presente estudo teve como objetivo analisar rins de Columba livia, naturalmente infectada, e de Gallus gallus infectados experimentalmente por Paratanaisia bragai. Através das análises, verificaram-se alterações macroscópicas, por microscopia de luz e eletrônica de varredura, sendo caracterizada significativa dilatação dos túbulos coletores. Essas alterações foram observadas nas aves infectadas naturalmente e experimentalmente. Por outro lado, foi observada infiltração linfocitária nos rins de C. livia, naturalmente infectada, e ocorrência de metaplasia no revestimento epitelial dos túbulos coletores dos rins de G. gallus, experimentalmente infectados.

[Quality assessment of long-term prescription records: QMP study]. / Avaliação da Qualidade dos Registos de Medicação Prolongada: Estudo QMP.

INTRODUCTION: The growing concern surrounding health safety issues makes it essential that everyone, in particular the elderly due to their commonly prescribed multiple drugs, has a complete and up to date list of prescriptions. We planned to assess the quality of the electronic records of prolonged medication. MATERIAL AND METHODS: This is an observational, transversal and descriptive study, with an analytical component, in which we assessed the technical quality of prolonged medication records of elderly patients of four primary health care, before and after a guided intervention. The doctors received training in good practice recording methods and both professionals and patients were stimulated to use the prolonged medication guide. RESULTS: We evaluated 388 medical records of 33 physicians. The ideal category 'Appropriated medication with posology' improved from 23.5% to 48% (p < 0,001). The remaining categories 'Inappropriated Medication' and 'Appropriated medication but absent posology' decreased from 16.7% to 7% (p = 0,006) and from 59.8% to 46.0% (p = 0,02), respectively. The variables mentor's training skills, workplace, length of family practice and the percentage of elderly in the physician's list showed statistical significance differences at the beginning of the study which disappeared after the intervention, except for the latter. DISCUSSION: In this study, physicians accepted the proposed changes, regardless of age, gender, mentor's training skills, workplace or length of family practice. Longer duration appointments in the eldery group may be an obstacle in achieving the best results. CONCLUSION: This original study reveals the necessity to implement periodic postgraduate training to encourage physicians to keep medical records up to date.

Introdução: A preocupação com a segurança na saúde torna essencial que todos os utentes, em particular os idosos por serem maioritariamente polimedicados, possuam uma lista completa e atualizada da sua medicação. Assim, propusemo-nos avaliar a qualidade dos registos eletrónicos de medicação prolongada.Material e Métodos: Estudo observacional, transversal e descritivo, com componente analítico, no qual avaliámos a qualidade técnica dos registos de medicação prolongada nos idosos de quatro unidades de cuidados de saúde primários da região norte, antes e após uma intervenção. Nesta, efetuámos formação de boas práticas de registo aos médicos e promovemos a utilização do guia de Medicação Prolongada aos profissionais e utentes.Resultados: Avaliámos 388 registos de 33 médicos. A categoria ideal, ‘Medicação apropriada e posologia presente’, aumentou de 23,5% para 48% (p < 0,001). As restantes categorias ‘Medicação inapropriada’ e ‘Medicação apropriada e posologia ausente’ diminuíram de 16,7% para 7% (p = 0,006) e de 59,8% para 46,0% (p = 0,02), respetivamente. As variáveis condição de orientador de formação, local de trabalho, anos de Medicina Geral e Familiar e percentagem de idosos, apresentaram diferenças com significado estatístico no início do estudo, no entanto após a ‘intervenção’, apenas a percentagem de idosos continuou a apresentá-las.Discussão: Neste estudo, os médicos aderiram à proposta de mudança, independentemente da idade, género, condição de orientador de formação, local de trabalho e anos de Medicina Geral e Familiar. Consultas mais prolongadas na população idosa poderão ter impedido alcançar a melhor categoria de registo.Conclusão: Este trabalho original mostra que é necessário implementar medidas periódicas de formação pós-graduada para manutenção de registos médicos atualizados.

Stabilized Wittig olefination for bioconjugation.

Stabilized Wittig olefination holds great potential as a bioconjugation reaction. We demonstrate that the reaction of stabilized phosphorus ylides (or phosphonium salts) with aryl aldehydes is sufficiently robust to be used for live cell affinity isolation and fluorescence tagging of a protein, FKBP12.

Rational design of resorcylic acid lactone analogues as covalent MNK1/2 kinase inhibitors by tuning the reactivity of an enamide Michael acceptor.

Recent biological and computational advances in drug design have led to renewed interest in targeted covalent inhibition as an efficient and practical approach for the development of new drugs. As part of our continuing efforts in the exploration of the therapeutic potential of resorcylic acid lactones (RALs), we report herein the design, synthesis, and biological evaluation of conveniently accessible RAL enamide analogues as novel covalent inhibitors of MAP kinase interacting kinases (MNKs). In this study, we have successfully demonstrated that the covalent binding ability of RAL enamides can be tuned by attaching an electron-withdrawing motif, such as an acyl group, to enhance its reactivity toward the cysteine residues at the MNK1/2 binding sites. We have also shown that ¹H NMR spectroscopy is a convenient and effective tool for screening the covalent binding activities of enamides using cysteamine as a mimic of the key cysteine residue in the enzyme, whereas mass spectrometric analysis confirms covalent modification of the kinases. Preliminary optimization of the initial hit led to the discovery of enamides with low micromolar activity in MNK assays. Cancer cell line assays have identified RAL enamides that inhibit the growth of cancer cells with similar potency to the natural product L-783,277.

An indirect comparison of the efficacy and safety of desvenlafaxine and venlafaxine using placebo as the common comparator.

BACKGROUND: This meta-analysis compared the efficacy and safety of desvenlafaxine and venlafaxine at the Australian approved doses. METHODS: A systematic literature search was conducted to identify all placebo-controlled studies of desvenlafaxine and venlafaxine in the treatment of major depression. The pivotal outcome measure used to assess comparative efficacy was the mean change in Hamilton Rating Scale for Depression-17 score from baseline. Tolerability and safety were compared by an evaluation of reported adverse events. Standard and Bayesian methods were used to conduct the indirect comparisons. Findings Using a mixed model repeated measures analysis, the pooled weighted mean difference for the mean change in Hamilton Rating Scale for Depression-17 score from baseline was -2.81 (-3.72, -1.91; p < 0.001) for desvenlafaxine and -2.61 (-3.17, -2.05; p < 0.001) for venlafaxine. An indirect Bayesian analysis adjusted for baseline Hamilton Rating Scale for Depression-17 score showed no significant difference between the two treatments (weighted mean difference -0.27; -1.17, 0.65). A standard indirect comparison of any adverse events showed no significant difference between desvenlafaxine and venlafaxine (relative risk 1.01; 0.96, 1.06; p = 0.70 and risk difference -0.01; -0.05, 0.03; p = 0.59). Standard indirect comparisons of both nausea and drop-outs identified potential differences between treatments, with the risk difference analyses suggesting a trend in favor of desvenlafaxine (nausea: relative risk 0.97; 0.77, 1.22; p = 0.80/RD -0.07; -0.12, -0.01; p = 0.02; and drop-outs due to adverse events: RR 0.86; 0.58, 1.29; p = 0.48/RD -0.04; -0.08, 0.00; p = 0.06). CONCLUSIONS: Based on the results of this meta-analysis, desvenlafaxine was shown to be non-inferior to venlafaxine in terms of efficacy, and has an advantage in terms of less nausea.