Search

Introduction: Approximately 4% of the UK population experiences PTSD. Individuals must exhibit symptoms across four clusters to receive a diagnosis: intrusion, avoidance, altered reactivity, and altered mood. Evidence suggests that cannabinoid agonists such as nabilone and tetrahydrocannabinol (THC) may alleviate PTSD symptoms. We investigated the safety and effectiveness of THC-predominant cannabis flowers for inhalation to manage PTSD symptoms in a real-world setting. Methods: We analysed data from the UK patient registry, T21. Validated questionnaires were used to collect PROMs for health-related quality of life (HRQoL), mood/anxiety, sleep, and PTSD-specific symptoms. Inclusion criteria were (i) a confirmed diagnosis of PTSD, (ii) completed PROMs questionnaires at baseline and at the 3-month follow-up, and (iii) received a prescription for a chemotype 1 (THC-predominant) cannabis flower. Results: Fifty-eight patients were included, 34 of which also had PROMs recorded at 6 months. Most were males (65.5%) with an average age of 39.2 years who had previously used cannabis illicitly (95.6%). At 3 months, participants reported significant improvements in overall health, mood, and sleep quality (p < 0.001) but not in the proxy for HRQoL (p = 0.052). Similarly, participants reported substantial benefits in managing intrusion symptoms (p < 0.001), mood alterations (p < 0.001), and reactivity alterations (p = 0.002), which were sustained or further improved at 6 months. Participants did not report any side effects associated with CBMPs. Conclusions: Inhalation of THC is well tolerated and useful for managing symptoms of PTSD in cannabis-experienced individuals. However, further research is needed to evaluate the long-term safety and outcomes of controlled inhalation of CBMP in patients naïve to cannabis.

Abstract The resident microbiome in food industries may impact on food quality and safety. In particular, microbes residing on surfaces in dairy industries may actively participate in cheese fermentation and ripening and contribute to the typical flavor and texture. In this work, we carried out an extensive microbiome mapping in 73 cheese-making industries producing different types of cheeses (fresh, medium and long ripened) and located in 4 European countries. We sequenced and analyzed metagenomes from cheese samples, raw materials and environmental swabs collected from both food contact and non-food contact surfaces, as well as operators’ hands and aprons. Dairy plants were shown to harbor a very complex microbiome, characterized by high prevalence of genes potentially involved in flavor development, probiotic activities, and resistance to gastro-intestinal transit, suggesting that these microbes may potentially be transferred to the human gut microbiome. More than 6100 high-quality Metagenome Assembled Genomes (MAGs) were reconstructed, including MAGs from several Lactic Acid Bacteria species and putative new species. Although microbial pathogens were not prevalent, we found several MAGs harboring genes related to antibiotic resistance, highlighting that dairy industry surfaces represent a potential hotspot for antimicrobial resistance (AR) spreading along the food chain. Finally, we identified facility-specific strains that can represent clear microbial signatures of different cheesemaking facilities, suggesting an interesting potential of microbiome tracking for the traceability of cheese origin.

The gut microbiome is indispensable for the host physiological functioning. Yet, the impact of non-nutritious dietary compounds on the human gut microbiota and the role of the gut microbes in their metabolism and potential adverse biological effects have been overlooked. Identifying potential hazards and benefits would contribute to protecting and harnessing the gut microbiome’s role in supporting human health. We discuss the evidence on the potential detrimental impact of certain food additives and microplastics on the gut microbiome and human health, with a focus on underlying mechanisms and causality. We provide recommendations for the incorporation of gut microbiome science in food risk assessment and identify the knowledge and tools needed to fill these gaps. The incorporation of gut microbiome endpoints to safety assessments, together with well-established toxicity and mutagenicity studies, might better inform the risk assessment of certain contaminants in food, and/or food additives.

Fundamento: La integración básico clínica en la enseñanza-aprendizaje de las Ciencias Básicas Biomédicas en la carrera de Medicina ha dirigido los procesos de formación basado en paradigmas pedagógicos que tienen como eje central el aprendizaje significativo y social constructivista. Objetivo: Proponer un modelo de integración básico clínica que tenga en consideración la interdisciplinariedad como alternativa didáctica y motivacional en las Ciencias Básicas Biomédicas. Metodología: Se realizó un estudio cualitativo en la educación médica. Se aplicaron métodos empíricos y teóricos que permitieron la elaboración de la propuesta. Se desarrolló un grupo focal con profesores del departamento de Ciencias Básicas Biomédicas. Resultados: Se diseñó un modelo para la integración básico clínica basado en la aplicación de situaciones didácticas, que permite la vinculación de contenidos teóricos con la futura actividad práctica del médico general. El modelo se muestra como una opción factible para la vinculación básico clínica, el desarrollo de habilidades lógico-intelectuales y profesionales mediante la interdisciplinariedad. Incluye la recursividad como vía para reintegrar los conocimientos clínicos a los básicos. Conclusiones: La utilización de procesos didácticos a través de la interdisciplinariedad según propone el modelo, es una alternativa para favorecer la vinculación básico clínica. Permite a los estudiantes desde el inicio, el desarrollo de habilidades intelectuales y una mayor motivación por la medicina, al acercarlo desde los primeros años de estudio a situaciones de salud que deberá enfrentar en su vida profesional.

Paciente masculino de 45 años que acude por cuadro clínico de 12 horas de evolución caracterizado por dolor abdominal, en flanco y fosa ilíaca derecha, asociado a vómitos de aspecto bilioso.

ABSTRACT Emerging evidence suggests that gut microbes can significantly contribute to central nervous system (CNS) well functioning through several gut microbiome-brain signaling mechanisms, among which the production of neurotransmitters by commensal microbes is very relevant. Hence, there is increasing interest in developing probiotics with capacity to deliver, locally within the gut ecosystem, neurotransmitters. The gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the CNS, and its disbalance has been associated with numerous disorders, including depression or anxiety. Furthermore, some commensal gut microorganisms are capable to produce GABA from its precursor, glutamate, whose concentration is generally higher in patients from disorders such as fibromyalgia, chronic fatigue, and pain. Therefore, we postulate that the administration of GABA-producing probiotic microorganisms may contribute to ameliorate conditions related to high glutamate/low GABA concentrations. In a prior work, we demonstrated a significant reduction of serum glutamate concentration in mice following 2-week administration of a GABA-producing Bifidobacterium adolescentis strain, IPLA60004. Herein, we further investigate the impact that the probiotic administration may have on the gut microbiome composition and metabolism. Remarkably, the gut microbiota modulation observed was different in animals receiving the GABA-producing strain, IPLA60004, as compared to animals receiving a closely related strain without GABA-producing ability. Genera of commensal and beneficial microorganisms, including Lactobacillus, Roseburia, and novel Lachnospiraceae genera, reached significantly higher representation at late intervention points in the fecal microbiota of animals receiving the GABA-producing strain, suggesting that some of the physiological effects of the probiotic administration may be linked to specific gut modulation effects. IMPORTANCE The gut microbiome-brain communication signaling has emerged in recent years as a novel target for intervention with the potential to ameliorate some conditions associated with the central nervous system. Hence, probiotics with capacity to produce neurotransmitters, for instance, have come up as appealing alternatives to treat disorders associated with disbalanced neurotransmitters. Herein, we further deep into the effects of administering a gamma-aminobutyric acid (GABA)-producing Bifidobacterium strain, previously demonstrated to contribute to reduce serum glutamate levels, in the gut microbiome composition and metabolic activity in a mouse model. Our results demonstrate that the GABA-producing strain administration results in a specific pattern of gut microbiota modulation, different from the one observed in animals receiving non-GABA-producing strains. This opens new avenues to delineate the specific mechanisms by which IPLA60004 administration contributes to reducing serum glutamate levels and to ascertain whether this effect could exert health benefits in patients of diseases associated with high-glutamate serum concentrations.

ABSTRACT Therapeutic options to treat bacterial infections caused by Gram-negative pathogens are limited due to the spread of multidrug resistance. Protein engineering of phage-derived lysins can play a key role in the search for new antimicrobial compounds targeting Gram-negative pathogens. A previous high-throughput screen of a combinatorial lysin library identified lysin 1D10 active against Acinetobacter baumannii under elevated human serum concentrations. The engineered lysin consists of four modules: cecropin A, a linker, cell wall-binding domain, and an enzymatic active domain. Using time-lapse microscopy, we show that 1D10 has a distinct antibacterial mode of action resulting in local cell wall bulging at the septum instead of cell-wide lysis, as observed for previously reported engineered lysins that target Gram-negative bacteria. Our results indicate that the activity of 1D10 relies on the antibacterial activity of both cecropin A (CecA) and the enzymatically active domain. Based on a truncation analysis, the role of each of the four modules of 1D10 was dissected. We further compared the antibacterial spectrum, thermostability, and cytotoxicity of cecropin A alone and lysin 1D10. Both lysin 1D10 and CecA are most active against A. baumannii and are not cytotoxic toward human keratinocytes. Lysin 1D10 unfolds at 57°C and has a remarkable refolding capacity, as it regains its activity even after exposure to 90°C and sterilization conditions, whereas CecA is inactivated at 70°C. Overall, the present study shows that an improved understanding of the killing mechanism and the protein properties will further support lysin engineering designs in the future. IMPORTANCE Engineered lysins are considered as highly promising alternatives for antibiotics. Our previous screening study using VersaTile technology identified 1D10 as a possible lead compound with activity against Acinetobacter baumannii strains under elevated human serum concentrations. In this manuscript, we reveal an unexpected mode of action and exceptional thermoresistance for lysin 1D10. Our findings shed new light on the development of engineered lysins, providing valuable insights for future research in this field.

ABSTRACT Several studies have described the contribution of glutamate-transforming microbiota to the development of chronic ailments. For instance, the blood concentration of glutamate is higher in some patients with fibromyalgia, chronic fatigue, and pain. Taking advantage of a naturally occurring strain of Bifidobacterium that is able to transform glutamate in γ-aminobutyric caid (GABA), B. adolescentis IPLA60004, we designed a placebo-controlled intervention to test if the presence of this GABA-producing bifidobacteria in mice was able to impact the concentration of glutamate in the blood in comparison with the administration of other strain of the same species lacking the genes of the glutamate decarboxylase (gad) cluster. Animals were fed every day with 8 log CFU of bacteria in a sterilized milk vehicle for 14 days. Samples from feces and blood were collected during this period, and afterwards animals were sacrificed, tissues were taken from different organs, and the levels of different metabolites were analyzed by ultrahigh-performance liquid chromatography coupled to mass spectrometry. The results showed that both bacterial strains orally administered survived in the fecal content, and animals fed B. adolescentis IPLA60004 showed a significant reduction of their glutamate serum concentration, while a nonsignificant decrease was observed for animals fed a reference strain, B. adolescentis LGM10502. The variations observed in GABA were influenced by the gender of the animals, and no significant changes were observed in different tissues of the brain. These results suggest that orally administered GABA-producing probiotics could reduce the glutamate concentration in blood, opening a case for a clinical trial study in chronic disease patients. IMPORTANCE This work presents the results of a trial using mice as a model that were fed with a bacterial strain of the species B. adolescentis, which possesses different active genes capable of degrading glutamate and converting it into GABA. Indeed, the bacterium is able to survive the passage through the gastric tract and, more importantly, the animals reduce over time the concentration of glutamate in their blood. The importance of this result lies in the fact that several chronic ailments, such as fibromyalgia, are characterized by an increase in glutamate. Our results indicate that an oral diet with this probiotic-type bacteria could reduce the concentration of glutamate and, therefore, reduce the symptoms associated with the excess of this neurotransmitter.

Introduction: educational systems recognize the importance of raising the quality of the teaching-learning process, because a quality education favors the growth of each nation. Objective: to describe the theoretical references of professional improvement and dimensions of the doctoral training process in medical sciences universities. Method: 28 documents available on the Internet were reviewed. Methods of analysis-synthesis, induction-deduction, empirical level and transit from the abstract to the concrete were used. Results: the proposals for improvement should inform the process of reflection on the relationships and specificities that correspond, according to the university training profile in which they are performed, so that it can articulate with the expectations and intentions of the training process of the teacher and the university student; the theoretical references also recognize that this should be conceived as "a process aimed at reviewing and updating the knowledge, attitudes and skills of this professional, which is given by the need to renew the knowledge in order to adapt them to changes and advances in society". Conclusions: higher education policies should ensure that the system of professional improvement is favorable to the elevation of the scientific category of university graduates and guarantee the conditions for achieving better results in doctoral training. The training of doctors of science in medical universities requires the approach from three dimensions given by the direction, the scientific-methodological dimension and the institutional strategic dimension of the doctoral training process.

Here, Lopaticki et al. show that Plasmodium falciparum expresses a Dpy19 C-mannosyltransferase in the endoplasmic reticulum that glycosylates TSR domains. Functional characterization shows that PfDpy19 plays a critical role in transmission through mosquitoes as PfDpy19-deficiency abolishes C-glycosylation and destabilizes proteins relevant for gametogenesis and oocyst formation.

Fermented foods are often erroneously equated with probiotics. Although they might act as delivery vehicles for probiotics, or other ‘biotic’ substances, including prebiotics, synbiotics, and postbiotics, stringent criteria must be met for a fermented food to be considered a ‘biotic’. Those criteria include documented health benefit, sufficient product characterization (for probiotics to the strain level) and testing. Similar to other functional ingredients, the health benefits must go beyond that of the product’s nutritional components and food matrix. Therefore, the ‘fermented food’ and ‘probiotic’ terms may not be used interchangeably. This concept would apply to the other biotics as well. In this context, the capacity of fermented foods to deliver one, several, or all biotics defined so far will depend on the microbiological and chemical level of characterization, the reproducibility of the technological process used to produce the fermented foods, the evidence for health benefits conferred by the biotics, as well as the type and amount of testing carried out to show the probiotic, prebiotic, synbiotic, and postbiotic capacity of that fermented food.