Unlocking the potential of microbiome editing: A review of conjugation-based delivery.

In recent decades, there has been a rapid increase in the prevalence of multidrug-resistant pathogens, posing a challenge to modern antibiotic-based medicine. This has highlighted the need for novel treatments that can specifically affect the target microorganism without disturbing other co-inhabiting species, thus preventing the development of dysbiosis in treated patients. Moreover, there is a pressing demand for tools to effectively manipulate complex microbial populations. One of the approaches suggested to address both issues was to use conjugation as a tool to modify the microbiome by either editing the genome of specific bacterial species and/or the removal of certain taxonomic groups. Conjugation involves the transfer of DNA from one bacterium to another, which opens up the possibility of introducing, modifying or deleting specific genes in the recipient. In response to this proposal, there has been a significant increase in the number of studies using this method for gene delivery in bacterial populations. This MicroReview aims to provide a detailed overview on the use of conjugation for microbiome engineering, and at the same time, to initiate a discussion on the potential, limitations and possible future directions of this approach.

La irrigación transanal como opción terapéutica para los pacientes con incontinencia y estreñimiento crónico severo refractarios a primera línea / Transanal irrigation as a therapeutic option for patients with incontinence and severe chronic constipation refractory to first line treatment

Introducción: El objetivo es evaluar la utilidad de la irrigación transanal como tratamiento de la incontinencia y estreñimiento crónico severo refractario a primera línea terapéutica, y valorar su impacto en la sintomatología y calidad de vida. Métodos: Estudio retrospectivo descriptivo de pacientes con incontinencia y estreñimiento crónico que han iniciado irrigación transanal en dos hospitales de la región. Se recogen variables sociodemográficas, comorbilidades, tratamientos previos, pruebas realizadas, parámetros e incidencias durante la irrigación, puntuación en las escalas de gravedad de incontinencia y estreñimiento de la Cleveland Clinic y calidad de vida EuroQol-5D antes y después del tratamiento. Resultados: Un total de 40 pacientes, 20 con incontinencia y 20 con estreñimiento crónico. Tras una media de 9 meses de tratamiento, en 14 pacientes con incontinencia hemos objetivado una media de mejoría de 7,45 puntos pre-post tratamiento en la escala de gravedad de incontinencia de la Cleveland Clinic, y una media de mejoría en la calidad de vida de 23 puntos pre-post tratamiento en la escala EQ5D (p<0,001); y en 16 pacientes con estreñimiento una media de mejoría de 7,6 puntos pre-post tratamiento en la escala de gravedad de estreñimiento de la Cleveland Clinic, y una media de mejoría en la calidad de vida de 31,5 puntos pre-post tratamiento en la escala EQ5D (p<0,001). Conclusiones: La irrigación transanal es una terapia efectiva para pacientes con incontinencia y estreñimiento crónico no respondedores a primera línea terapéutica. Es sencilla, autoadministrable y segura. Cuando el paciente aprende a emplearla, mejora su sintomatología y calidad de vida. (AU)

Introduction: The aim is to evaluate the utility of transanal irrigation such as treatment of incontinence and severe chronic constipation which is refractory to first-line therapy, and to assess its impact into the symptomatology and quality of life. Methods: Observational retrospective study of patients with incontinence and chronic constipation that had initiated transanal irrigation in two hospitals of the region. We collect sociodemographic variables, comorbidity, previous treatments, tests, parameters and incidences during the irrigation, and punctuation in the Cleveland Clinic Incontinence and Constipation Scores and EuroQol-5D Quality Of Life Scale before and after the treatment. Results: 40 patients, 20 with incontinence and 20 with chronic constipation. After an average period of 9 months of treatment, in 14 patients with incontinence we have observed a mean clinical improvement of 7,45 points before-after treatment measured with Cleveland Clinic Incontinence Score, and a mean improvement of 23 points in their quality of life before-after treatment measured with EQ5D Scale (p<0.001); and in 16 patients with constipation a mean clinical improvement of 7,6 points before-after treatment measured with Cleveland Clinic Constipation Score, and a mean improvement of 31,5 points in their quality of life before-after treatment measured with EQ5D Scale (p<0.001). Conclusions: Transanal irrigation is an effective therapy for patients with incontinence and chronic constipation that are refractory to first-line therapies. It's an easy, self-administered and safe procedure. When the patient learns how to use it, the symptomatology and quality of life are improved. (AU)

Isoliquiritigenin pretreatment regulates ER stress and attenuates cisplatin-induced nephrotoxicity in male Wistar rats.

Cisplatin (CP) is a chemotherapeutic drug used to treat solid tumors. However, studies have revealed its nephrotoxic effect. Oxidative stress, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction are involved in CP-induced renal damage. Thus, preconditioning (hormetic effect) of ER stress is a strategy to prevent CP-induced renal damage. On the other hand, isoliquiritigenin (IsoLQ) is recognized as a flavonoid with antioxidant properties and an inducer of ER stress. Therefore, we evaluated the ER stress-inducing capacity of IsoLQ and its possible protective effect against CP-induced nephrotoxicity in adult male Wistar rats. The findings reflected that IsoLQ pretreatment might decrease renal damage by reducing plasma creatinine and blood urea nitrogen levels in animals with CP-induced nephrotoxicity. These may be associated with IsoLQ activating ER stress and unfolded protein response (UPR). We found increased messenger RNA levels of the ER stress marker glucose-related protein 78 kDa (GRP78). In addition, we also found that pretreatment with IsoLQ reduced the levels of CCAAT/enhancer-binding protein-homologous protein (CHOP) and X-box-binding protein 1 (XBP1) in the renal cortex, reflecting that IsoLQ can regulate the UPR and activation of the apoptotic pathway. Moreover, this preconditioning with IsoLQ of ER stress had oxidative stress-regulatory effects, as it restored the activity of glutathione peroxidase and glutathione reductase enzymes. Finally, IsoLQ modifies the protein expression of mitofusin 2 (Mfn-2) and voltage-dependent anion channel (VDAC). In conclusion, these data suggest that IsoLQ pretreatment has a nephroprotective effect; it could functionally regulate the ER and mitochondria and reduce CP-induced renal damage by attenuating hormesis-mediated ER stress.

Perforación traqueal diferida tras cirugía tiroidea en un paciente con radioterapia cervical.

Tracheal perforation is a rare complication of thyroid surgery. A 36-year-old man with previous neck radiotherapy due to a nasopharyngeal cancer. After right hemithyoidectomy and isthmusectomy, the patient presented a tracheal perforation. The diagnosis was confirmed with computed tomography and bronchoscopy. A conservative management was performed with drainage and antibiotic therapy, and the evolution was satisfactory. If recognized at the time of the surgery, perforations should be closed primarily. Delayed perforations will be treated with an emergency surgery or conservatively depending on the clinical situation of the patient.

La perforación traqueal es una rara complicación de la cirugía tiroidea. Varón de 36 años con antecedente de radioterapia cervical por una neoplasia de cavum sometido a hemitiroidectomía derecha e istmectomía que durante el posoperatorio presentó una perforación traqueal confirmada por tomografía computarizada y broncoscopia. Se realizó manejo conservador con drenaje y antibioticoterapia, evolucionando de forma favorable. Las perforaciones identificadas durante la cirugía deben ser reparadas intraoperatoriamente, mientras que las diferidas se tratarán de forma quirúrgica urgente o de manera conservadora en función de la situación clínica del paciente.

Intramuscular Gluteoplasty: A Comparative Study between Different Incisional Access Routes.

BACKGROUND: Silicone implants have been used to improve volume and body contour in buttocks for almost 45 years. Although the intramuscular plane continues to be the standard, surgeons still diverge on the best incision technique: using a vertical incision, and thus without the preservation of the intergluteal groove, or preserving this area through a triangular dissection. The goal of this research study was to evaluate and compare these techniques of intramuscular augmentation gluteoplasty. METHODS: Two randomized groups were formed with 53 patients in each group. One of the groups underwent intramuscular gluteoplasty with a vertical incision in the intergluteal groove, and therefore without the preservation of said intergluteal groove (group A). In the other group, intramuscular gluteoplasty was performed using a triangular dissection, thus preserving the intergluteal groove (group B). The groups were compared in relation to the incidence of complications (ie, dehiscence, hematoma, seroma, and infection). RESULTS: A total of 7.5% of patients in group A presented dehiscence and 1.9% presented seroma. In group B, however, 28.3% of patients presented dehiscence and 7.5% presented seroma and dehiscence during the first 21 days after surgery. No patient had hematoma or infection in either group. CONCLUSION: In the comparison between the groups of patients, the technique with a vertical incision in the intergluteal groove showed a lower number of surgical wounds, dehiscences, and seromas when compared with the technique that preserves the intergluteal groove. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Increasing the Scalability of Toxin-Intein Orthogonal Combinations.

Inteins are proteins embedded into host proteins from which they are excised in an autocatalytic reaction. Specifically, split inteins are separated into two independent fragments that reconstitute the host protein during the catalytic process. We recently developed a novel strategy for the specific killing of pathogenic and antibiotic resistant bacteria based on toxin-intein combinations. Bacterial type II toxin-antitoxin systems are protein modules in which the toxin can provoke cell death whereas the antitoxin inhibits toxin activity. Although our previous system was based on a split intein (iDnaE) and the CcdB toxin, we demonstrated that iDnaE is able to reconstitute four different toxins. To expand the applicability of our system by widening the repertoire of toxin-intein combinations for complex set-ups, we introduced a second intein, iDnaX, which was artificially split. We demonstrate that iDnaX is able to reconstitute the four toxins, and we manage to reduce its scar size to facilitate their use. In addition, we prove the orthogonality of both inteins (iDnaE and iDnaX) through a toxin reconstitution assay, thus opening the possibility for complex set-ups based on these toxin-intein modules. This could be used to develop specific antimicrobial and other biotechnological applications.

GIST is not all that it seems.

We present a 41-year-old female who was admitted to our hospital with a history of 2-month epigastric pain and vomiting. Physical examination was normal. Upper gastrointestinal endoscopy showed a sessile submucosal tumor with central ulceration in the gastric body-antrum. Biopsies revealed a gastric mucosa without changes. Nevertheless, endoscopic ultrasound-guided biopsies showed interlacing bundles of spindle cells. The immunohistochemical study was negative for CD117 and smooth muscle actin and positive for S100 protein. A CT scan identified a heterogeneous mass in the stomach wall.

Transanal irrigation as a therapeutic option for patients with incontinence and severe chronic constipation refractory to first-line treatment.

INTRODUCTION: The aim is to evaluate the utility of transanal irrigation such as treatment of incontinence and severe chronic constipation which is refractory to first-line therapy, and to assess its impact into the symptomatology and quality of life. METHODS: Observational retrospective study of patients with incontinence and chronic constipation that had initiated transanal irrigation in two hospitals of the region. We collect sociodemographic variables, comorbidity, previous treatments, tests, parameters and incidences during the irrigation, and punctuation in the Cleveland Clinic Incontinence and Constipation Scores and EuroQol-5D Quality Of Life Scale before and after the treatment. RESULTS: 40 patients, 20 with incontinence and 20 with chronic constipation. After an average period of 9 months of treatment, in 14 patients with incontinence we have observed a mean clinical improvement of 7,45 points before-after treatment measured with Cleveland Clinic Incontinence Score, and a mean improvement of 23 points in their quality of life before-after treatment measured with EQ5D Scale (P < .001); and in 16 patients with constipation a mean clinical improvement of 7,6 points before-after treatment measured with Cleveland Clinic Constipation Score, and a mean improvement of 31,5 points in their quality of life before-after treatment measured with EQ5D Scale (P < .001). CONCLUSIONS: Transanal irrigation is an effective therapy for patients with incontinence and chronic constipation that are refractory to first-line therapies. It's an easy, self-administered and safe procedure. When the patient learns how to use it, the symptomatology and quality of life are improved.

No es GIST todo lo que parece / GIST is not all that it seems

We present a 41-year-old female who was admitted to our hospital with a history of 2-month epigastric pain and vomiting. Physical examination was normal. Upper gastrointestinal endoscopy showed a sessile submucosal tumor with central ulceration in the gastric body-antrum. Biopsies revealed a gastric mucosa without changes. Nevertheless, endoscopic ultrasound-guided biopsies showed interlacing bundles of spindle cells. The immunohistochemical study was negative for CD117 and smooth muscle actin and positive for S100 protein. A CT scan identified a heterogeneous mass in the stomach wall (AU)

Therapeutic Effect of Curcumin on 5/6Nx Hypertriglyceridemia: Association with the Improvement of Renal Mitochondrial ß-Oxidation and Lipid Metabolism in Kidney and Liver.

Chronic kidney disease (CKD) prevalence is constantly increasing, and dyslipidemia in this disease is characteristic, favoring cardiovascular events. However, the mechanisms of CKD dyslipidemia are not fully understood. The use of curcumin (CUR) in CKD models such as 5/6 nephrectomy (5/6Nx) has shown multiple beneficial effects, so it has been proposed to correct dyslipidemia without side effects. This work aimed to characterize CUR's potential therapeutic effect on dyslipidemia and alterations in lipid metabolism and mitochondrial ß-oxidation in the liver and kidney in 5/6Nx. Male Wistar rats were subjected to 5/6Nx and progressed by 4 weeks; meanwhile, CUR (120 mg/kg) was administered for weeks 5 to 8. Our results showed that CUR reversed the increase in liver and kidney damage and hypertriglyceridemia induced by 5/6Nx. CUR also reversed mitochondrial membrane depolarization and ß-oxidation disorders in the kidney and the increased lipid uptake and the high levels of proteins involved in fatty acid synthesis in the liver and kidney. CUR also decreased lipogenesis and increased mitochondrial biogenesis markers in the liver. Therefore, we concluded that the therapeutic effect of curcumin on 5/6Nx hypertriglyceridemia is associated with the restoration of renal mitochondrial ß-oxidation and the reduction in lipid synthesis and uptake in the kidneys and liver.

DNA barcoding reveals global and local influences on patterns of mislabeling and substitution in the trade of fish in Mexico.

Mislabeling of seafood is a global phenomenon that can misrepresent the status and level of consumption of wild fish stocks while concealing the use of many other wild species or those originating from aquaculture and sold as substitutes. We conducted a DNA barcoding study in three cities within Mexico (Mazatlan, Mexico City and Cancun) and sequenced the COI gene in 376 fish samples sold as 48 distinct commercial names at fish markets, grocery stores, and restaurants. Our goal was to identify the main species sold, their mislabeling rates and the species most used as substitutes. Overall, the study-wide mislabeling rate was 30.8% (95% CI 26.4-35.6). Half of the samples collected belonged to five species traded globally (yellowfin tuna, Atlantic salmon, mahi, swai, and tilapia), most of them with important aquaculture or ranching production levels. These species were commonly used as substitutes for other species and showed low mislabeling rates themselves (≤ 11%, except mahi mahi with 39% mislabeling). The other half of the samples revealed nearly 100 species targeted by small-scale fishers in Mexico and sold under 42 distinct commercial names. Popular local commercial names (dorado, marlin, mero, robalo, mojarra, huachinango, pargo, sierra) showed the highest mislabeling rates (36.3% to 94.4%) and served to sell many of the 53 species identified as substitutes in our study. We discuss the observed patterns in relation to landing and import data showing differences in availability of commercial species and the links to explain observed mislabeling rates and the use of a species as a substitute for other species. We also outline some of the implications of establishing a labeling and traceability standard as an alternative to improve transparency in the trade of seafood products in Mexico.

Idiopathic myointimal hyperplasia of the mesenteric veins, an uncommon cause of intestinal ischemia.

Idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) is an uncommon cause of intestinal ischemia. It was firstly described by Genta and Haggit in 1991. Only a few cases have been reported and it is difficult to know the true incidence.