Implementation of a robotic surgical practice in inflammatory bowel disease.

Robotics adoption has increased in colorectal surgery. While there are well-established advantages and standardised techniques for cancer patients, the use of robotic surgery in inflammatory bowel disease (IBD) has not been studied yet. To evaluate the feasibility and safety of robotic surgery for IBD patients. Prospectively data in IBD patients having robotic resection at Guy's and St Thomas' hospital. All resections performed by a single colorectal surgeon specialised in IBD, utilising DaVinci platform. July 2021 to January 2023, 59 robotic IBD cases performed, 14 ulcerative colitis (UC) and 45 Crohn's disease (CD). Average age; CD patients 35, UC 33 years. Average Body mass index (BMI); 23 for CD and 26.9 for UC patients. In total, we performed 31 ileo-caecal resections (ICR) with primary anastomosis (18 Kono-S anastomosis, 6 mechanical anastomosis and 7 ileo-colostomy), of those 4 had multivisceral resections (large bowel, bladder, ovary). Furthermore, 14 subtotal colectomy (1 emergency), 8 proctectomy, 3 panproctocolectomy and 3 ileoanal J pouch. 18 of the 45 patients (45.0%) with Crohn's disease had ongoing fistulating disease to other parts of the GI tract (small or large bowel). ICR were performed using different three ports position, depending on the anatomy established prior to surgery with magnetic resonance images (MRI). One patient had conversion to open due to anaesthetic problems and one patient required re-operation to refashion stoma. 98.0% cases completed robotically. Median Length of hospital stay (LOS) was 7 days for CD and 7 for UC cases, including LOS in patients on pre-operative parenteral nutrition. Robotic colorectal techniques can be safely used for patients with IBD, even with fistulating disease. Future research and collaborations are necessary to standardize technique within institutions.

The Effect of Dietary Components of the Mediterranean Diet on Food Allergies: A Systematic Review.

Allergies are a common and increasing health problem affecting millions of people worldwide. This increase is attributed to genetic predisposition, air pollution, climate change, lack of physical activity, and alterations in eating habits. The Mediterranean diet (MD), which includes a lot of fruits and vegetables, whole grains, legumes, nuts, olive oil, and fish, has been linked to a variety of health benefits, including a lower risk of chronic and allergic disease. This paper explores the effects of the dietary components of the MD on food allergies. Electronic databases PubMed, Scopus, Science Direct, and EBSCO were used to conduct this systematic review. Out of 696 studies initially identified, five human and four animal studies were included. Risk of bias was determined using the Office of Health Assessment and Translation tool. In human studies, when the intervention was given during pregnancy and lactation, a beneficial effect was observed. When the intervention was given during pregnancy and until birth or to the infant for six months, no effect was observed. The animal studies indicated a beneficial effect between the food components of the MD and food allergies. Although the results are promising, the limited number of studies highlights the need for more research.

Pathogenic and Low-Frequency Variants in Children With Central Precocious Puberty.

Background: Central precocious puberty (CPP) due to premature activation of GnRH secretion results in early epiphyseal fusion and to a significant compromise in the achieved final adult height. Currently, few genetic determinants of children with CPP have been described. In this translational study, rare sequence variants in MKRN3, DLK1, KISS1, and KISS1R genes were investigated in patients with CPP. Methods: Fifty-four index girls and two index boys with CPP were first tested by Sanger sequencing for the MKRN3 gene. All children found negative (n = 44) for the MKRN3 gene were further investigated by whole exome sequencing (WES). In the latter analysis, the status of variants in genes known to be related with pubertal timing was compared with an in-house Cypriot control cohort (n = 43). The identified rare variants were initially examined by in silico computational algorithms and confirmed by Sanger sequencing. Additionally, a genetic network for the MKRN3 gene, mimicking a holistic regulatory depiction of the crosstalk between MKRN3 and other genes was designed. Results: Three previously described pathogenic MKRN3 variants located in the coding region of the gene were identified in 12 index girls with CPP. The most prevalent pathogenic MKRN3 variant p.Gly312Asp was exclusively found among the Cypriot CPP cohort, indicating a founder effect phenomenon. Seven other CPP girls harbored rare likely pathogenic upstream variants in the MKRN3. Among the 44 CPP patients submitted to WES, nine rare DLK1 variants were identified in 11 girls, two rare KISS1 variants in six girls, and two rare MAGEL2 variants in five girls. Interestingly, the frequent variant rs10407968 (p.Gly8Ter) of the KISS1R gene appeared to be less frequent in the cohort of patients with CPP. Conclusion: The results of the present study confirm the importance of the MKRN3-imprinted gene in genetics of CPP and its key role in pubertal timing. Overall, the results of the present study have emphasized the importance of an approach that aligns genetics and clinical aspects, which is necessary for the management and treatment of CPP.

In silico analysis of a novel MKRN3 missense mutation in familial central precocious puberty.

BACKGROUND: The onset of puberty is influenced by the interplay of stimulating and restraining factors, many of which have a genetic origin. Premature activation of the GnRH secretion in central precocious puberty (CPP) may arise either from gain-of-function mutations of the KISS1 and KISS1R genes or from loss-of-function manner mutations of the MKRN3 gene leading to MKRN3 deficiency. OBJECTIVE: To explore the genetic causes responsible for CPP and the potential role of the RING finger protein 3 (MKRN3) gene. DESIGN AND PATIENTS: We investigated potential sequence variations in the intronless MKRN3 gene by Sanger sequencing of the entire 507 amino acid coding region of exon 1 in a family with two affected girls presented with CPP at the age of 6 and 5·7 years, respectively. RESULTS: A novel heterozygous g.Gly312Asp missense mutation in the MKRN3 gene was identified in these siblings. The imprinted MKRN3 missense mutation was also identified as expected in the unaffected father and followed as expected an imprinted mode of inheritance. In silico analysis of the altered missense variant using the computational algorithms Polyphen2, SIFT and Mutation Taster predicted a damage and pathogenic alteration causing CPP. The pathogenicity of the alteration at the protein level via an in silico structural model is also explored. CONCLUSION: A novel mutation in the MKRN3 gene in two sisters with CPP was identified, supporting the fundamental role of this gene in the suppression of the hypothalamic GnRH neurons.

Engagement of the CD4 receptor affects the redistribution of Lck to the immunological synapse in primary T cells: implications for T-cell activation during human immunodeficiency virus type 1 infection.

Understanding the molecular mechanisms underlying dysregulated immune responses in human immunodeficiency virus type 1 (HIV-1) infection is crucial for the control of HIV/AIDS. Despite the postulate that HIV envelope glycoprotein gp120-CD4 interactions lead to impaired T-cell responses, the precise mechanisms underlying such association are not clear. To address this, we analyzed Lck and F-actin redistribution into the immunological synapse in stimulated human primary CD4(+) T cells from HIV-1-infected donors. Similar experiments were performed with CD4(+) T cells from HIV-uninfected donors, which were exposed to anti-CD4 domain 1 antibodies, as an in vitro model of gp120-CD4 interactions, or aldithriol-inactivated HIV-1 virions before stimulation. CD4(+) T cells from HIV-infected patients exhibited a two- to threefold inhibition of both Lck and F-actin recruitment into the synapse, compared to cells from uninfected donors. Interestingly, defective recruitment of Lck was ameliorated following suppressive highly active antiretroviral therapy. Engagement of the CD4 receptor on T cells from HIV-uninfected donors before anti-CD3/CD28 stimulation led to similar defects. Furthermore, the redistribution of Lck into lipid rafts was abrogated by CD4 preengagement. Our results suggest that the engagement of CD4 by HIV gp120 prior to T-cell receptor stimulation leads to dysregulation of early signaling events and could consequently play an important role in impaired CD4(+) T-cell function.