An in-depth multiphasic analysis of the chocolate production chain, from bean to bar, demonstrates the superiority of Saccharomyces cerevisiae over Hanseniaspora opuntiae as functional starter culture during cocoa fermentation.

Hanseniaspora opuntiae is a commonly found yeast species in naturally fermenting cocoa pulp-bean mass, which needed in-depth investigation. The present study aimed at examining effects of the cocoa isolate H. opuntiae IMDO 040108 as part of three different starter culture mixtures compared with spontaneous fermentation, regarding microbial community, substrate consumption, and metabolite production dynamics, including volatile organic compound (VOC) and phytochemical compositions, as well as compositions of the cocoa beans after fermentation, cocoa liquors, and chocolates. The inoculated H. opuntiae strain was unable to prevail over background yeasts present in the fermenting cocoa pulp-bean mass. It led to under-fermented cocoa beans after four days of fermentation, which was however reflected in higher levels of polyphenols. Cocoa fermentation processes inoculated with a Saccharomyces cerevisiae strain enhanced flavour production during the fermentation and drying steps, which was reflected in richer and more reproducible aroma profiles of the cocoa liquors and chocolates. Sensory analysis of the cocoa liquors and chocolates further demonstrated that S. cerevisiae led to more acidic notes compared to spontaneous fermentation, as a result of an advanced fermentation degree. Finally, different VOC profiles were found in the cocoa beans throughout the whole chocolate production chain, depending on the fermentation process.

Quality differentiation of cocoa beans: implications for geographical indications.

Geographical indications may stimulate collective actions of governance for quality control, trade and marketing as well as innovation based on the use of local resources and regional biodiversity. Cocoa production, however, dominated by small family agriculture in tropical regions, has rarely made use of such strategies. This review is aimed at understanding major research interests and emerging technologies helpful for the origin differentiation of cocoa quality. Results from literature search and cited references of publications on cocoa research were imported into VOSviewer for data analysis, which aided in visualizing major research hotpots. Co-occurrence analysis yielded major research clusters which guided the discussion of this review. Observed was a consensus recognizing cocoa quality resulting from the interaction of genotype, fermentation variables and geographical origin. A classic view of cocoa genetics based on the dichotomy of 'fine versus bulk' has been reexamined by a broader perspective of human selection and cocoa genotype evolution. This new approach to cocoa genetic diversity, together with the understanding of complex microbiome interactions through fermentation, as well as quality reproducibility challenged by geographical conditions, have demonstrated the importance of terroir in the production of special attributes. Cocoa growing communities around the tropics have been clearly enabled by new omics and chemometrics to systematize producing conditions and practices in the designation of specifications for the differentiation of origin quality. © 2021 Society of Chemical Industry.

Isolated central nervous system (CNS) relapse of multiple myeloma 11 years after autologous stem cell transplantation: a case report.

Background: Multiple myeloma (MM) relapse in the central nervous system (CNS) confers an adverse prognosis, usually occurring in a short period after stem cell transplant and with a short overall survival. Isolated CNS relapse is so rare that there is no current standard treatment. Case Description: We present a 59-year-old male with an isolated CNS MM relapse, who had received autologous stem-cell transplant (ASCT) and thalidomide maintenance 11 years prior. He returned to our clinic with cauda equina syndrome and a nuclear magnetic resonance (NMR) identified a spinal lesion, a lumbar puncture was performed and plasma cells were identified in his cerebrospinal fluid (CSF). He was initially treated with intrathecal (IT) chemotherapy with methotrexate and steroid + radiotherapy and plasma cells disappeared after a few bi-weekly doses. Later on, treatment with pomalidomide/dexamethasone was given for 12 cycles with good clinical response with 80% recovery of his motor function. Conclusions: In this rare case of a very late CNS MM relapse, we demonstrate that IT chemotherapy complemented with a systemic pomalidomide-based treatment is safe and effective. This is particularly important in contexts where newer therapies such as bispecifics, chimeric antigen receptor-T (CAR-T) cells or even daratumumab or selinexor are not widely available. Further clinical experience in this particular scenario will be required to confirm this observation and define overall the best strategy for this rare group of patients.

Synthesis and toxicity of monothiooxalamides against human red blood cells, brine shrimp (Artemia salina), and fruit fly (Drosophila melanogaster).

A new family of monothiooxalamides derived from 2-aminobenzimidazole was synthesized, and their structures were confirmed by 1H and 13C one-dimensional and 2D NMR experiments (COSY, HSQC, and HMBC). The antioxidant capacity was evaluated by free radical scavenging assays: 1,1-diphenyl-2-picrylhydrazyl (DPPH•), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS•+), ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), and the Fe(II) chelating ability. Our work group has previously reported the synthesis and antioxidant activity of monothiooxalamides derived from 2-aminopyridine (I). In this study, the in vitro hemolytic activity of compounds from the 2-aminopyridine (I) and 2-aminobenzimidazole (II) families was evaluated against human red blood cells (RBCs). The concentration at which monothiooxalamides showed no hemolytic activity was chosen to assess their ability to inhibit free radical-induced membrane damage in human RBCs, acute toxicity in brine shrimp, and in vivo toxicity against Drosophila melanogaster. Compounds with morpholine fragments (1g, 1h, 2g, and 2h) showed time- and concentration-dependent protective effects against radical-induced oxidative hemolysis. Moreover, they had the lowest acute toxicity in the brine shrimp lethality assay and a significant increase in chelating activity compared with the other molecules. In particular, monothiooxalamide 2g showed lower toxicity and can be considered for further biological screening and application trials.

Yeast strains do have an impact on the production of cured cocoa beans, as assessed with Costa Rican Trinitario cocoa fermentation processes and chocolates thereof.

The microbiological and metabolic outcomes of good cocoa fermentation practices can be standardized and influenced through the addition of starter culture mixtures composed of yeast and bacterial strains. The present study performed two spontaneous and 10 starter culture-initiated (SCI) cocoa fermentation processes (CFPs) in Costa Rica with local Trinitario cocoa. The yeast strains Saccharomyces cerevisiae IMDO 050523, Hanseniaspora opuntiae IMDO 020003, and Pichia kudriavzevii IMDO 060005 were used to compose starter culture mixtures in combination with the lactic acid bacterium strain Limosilactobacillus fermentum IMDO 0611222 and the acetic acid bacterium strain Acetobacter pasteurianus IMDO 0506386. The microbial community and metabolite dynamics of the cocoa pulp-bean mass fermentation, the metabolite dynamics of the drying cocoa beans, and the volatile organic compound (VOC) profiles of the chocolate production were assessed. An amplicon sequence variant approach based on full-length 16S rRNA gene sequencing instead of targeting the V4 region led to a highly accurate monitoring of the starter culture strains added, in particular the Liml. fermentum IMDO 0611222 strain. The latter strain always prevailed over the background lactic acid bacteria. A similar approach, based on the internal transcribed spacer (ITS1) region of the fungal rRNA transcribed unit, was used for yeast strain monitoring. The SCI CFPs evolved faster when compared to the spontaneous ones. Moreover, the yeast strains applied did have an impact. The presence of S. cerevisiae IMDO 050523 was necessary for successful fermentation of the cocoa pulp-bean mass, which was characterized by the production of higher alcohols and esters. In contrast, the inoculation of H. opuntiae IMDO 020003 as the sole yeast strain led to underfermentation and a poor VOC profile, mainly due to its low competitiveness. The P. kudriavzevii IMDO 060005 strain tested in the present study did not contribute to a richer VOC profile. Although differences in VOCs could be revealed in the cocoa liquors, no significant effect on the final chocolates could be obtained, mainly due to a great impact of cocoa liquor processing during chocolate-making. Hence, optimization of the starter culture mixture and cocoa liquor processing seem to be of pivotal importance.

Triterpenoids from Angiopteris palmiformis.

Two new fernane triterpenoids, 7alpha-hydroxyfern-8-en-11-one (1) and 11beta-hydroxyfern-8-en-7-one (2), and two new filicane triterpenoids, 3beta-hydroxyfilic-4(23)-ene (3) and filicenol (5), together with one known filicane-type triterpenoid, 3alpha-hydroxyfilic-4(23)-ene (4), were isolated from the methyl alcohol extract of the leaves of Angiopteris palmiformis. Their structures were elucidated on the basis of extensive analyses of their spectroscopic data (NMR, MS, IR) and comparison with spectroscopic data in the literature.

Curing of Cocoa Beans: Fine-Scale Monitoring of the Starter Cultures Applied and Metabolomics of the Fermentation and Drying Steps.

Starter culture-initiated cocoa fermentation processes can be applied to improve the quality of cured cocoa beans. However, an accurate monitoring of the microbial strains inoculated in fresh cocoa pulp-bean mass to assess their contribution to the cocoa bean curing process is still lacking. In the present study, eight different cocoa fermentation processes were carried out with Trinitario cocoa in vessels in Costa Rica to assess the contribution of two candidate yeast starter culture strains, namely Saccharomyces cerevisiae IMDO 050523 and Pichia kudriavzevii IMDO 020508, inoculated in combination with Limosilactobacillus fermentum IMDO 0611222 and Acetobacter pasteurianus IMDO 0506386. A multiphasic approach, consisting of culture-dependent selective plating and incubation, rRNA-PCR-DGGE community profiling of agar plate washes, and culture-independent high-throughput amplicon sequencing, combined with a metabolite target analysis of non-volatile and volatile organic compounds (VOCs), was performed on samples from the fermentation and/or drying steps. The different starter culture mixtures applied effectively steered the cocoa fermentation processes performed. Moreover, the use of an amplicon sequence variant (ASV) approach, aligning these ASVs to the whole-genome sequences of the inoculated strains, allowed the monitoring of these inoculated strains and their differentiation from very closely related variants naturally present in the background or spontaneous fermentation processes. Further, traits such as malolactic fermentation during the fermentation step and acetoin and tetramethylpyrazine formation during the drying step could be unraveled. Finally, the yeast strains inoculated influenced the substrate consumption and metabolite production during all starter culture-initiated fermentation processes. This had an impact on the VOC profiles of the cured cocoa beans. Whereas the P. kudriavzevii strain produced a wide range of VOCs in the cocoa pulp, the S. cerevisiae strain mostly influenced the VOC composition of the cured cocoa beans.

Adenoma adrenocortical ectópico parahiliar renal, en paciente con síndrome de Cushing independiente de ACTH. Abordaje laparoscópico. Reporte de caso y revisión de la literatura / Adrenocortical ectopic adenoma in a patient with ACTH independent Cushing's syndrome. Laparoscopic approach. Case report and review of literature

El síndrome de Cushing (SC) endógeno se caracteriza por la sobreproducción crónica de cortisol y está asociado con aumento en la morbimortalidad. Presenta un conjunto de manifestaciones clínicas que pueden variar dependiendo del nivel de cortisol de cada paciente, siendo los signos más característicos de esta enfermedad la obesidad central con debilidad muscular proximal, hematomas, estrías violáceas mayores de 1 cm e hipertensión arterial.1,2 En niños la presentación clínica es diferente, siendo el aumento de peso y el retardo del crecimiento lo más frecuente.1 Se ha visto involucrado en el 2 al 3% los casos de pacientes con síndrome metabólico, principalmente diabetes mellitus e hipertensión arterial, que presentan pobre respuesta al tratamiento farmacológico

Endogenous Cushing syndrome (CS) is characterized by chronic overproduction of cortisol and is associated with increased morbidity and mortality. It presents a set of clinical manifestations that may vary depending on the level of cortisol in each patient, the most characteristic signs of this disease being central obesity with proximal muscle weakness, hematomas, purplish striae greater than 1 cm and arterial hypertension.1,2 In children the clinical presentation is different, with weight gain and growth retardation being the most frequent.1 Cases of patients with cortisol have been involved in 2 to 3%. metabolic syndrome, mainly diabetes mellitus and hypertension, which have a poor response to diabetes. pharmacological treatment