An Integrated Analysis of miRNA and Gene Expression Changes in Response to an Obesogenic Diet to Explore the Impact of Transgenerational Supplementation with Omega 3 Fatty Acids

Insulin resistance decreases the ability of insulin to inhibit hepatic gluconeogenesis, a key step in the development of metabolic syndrome. Metabolic alterations, fat accumulation, and fibrosis in the liver are closely related and contribute to the progression of comorbidities, such as hypertension, type 2 diabetes, or cancer. Omega 3 (n-3) polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA), were identified as potent positive regulators of insulin sensitivity in vitro and in animal models. In the current study, we explored the effects of a transgenerational supplementation with EPA in mice exposed to an obesogenic diet on the regulation of microRNAs (miRNAs) and gene expression in the liver using high-throughput techniques. We implemented a comprehensive molecular systems biology approach, combining statistical tools, such as MicroRNA Master Regulator Analysis pipeline and Boolean modeling to integrate these biochemical processes. We demonstrated that EPA mediated molecular adaptations, leading to the inhibition of miR-34a-5p, a negative regulator of Irs2 as a master regulatory event leading to the inhibition of gluconeogenesis by insulin during the fasting–feeding transition. Omics data integration provided greater biological insight and a better understanding of the relationships between biological variables. Such an approach may be useful for deriving innovative data-driven hypotheses and for the discovery of molecular–biochemical mechanistic links.     

The olfactory fascia: an evo–devo concept of the fibrocartilaginous nose

Purpose

Evo–devo is the science that studies the link between evolution of species and embryological development. This concept helps to understand the complex anatomy of the human nose. The evo–devo theory suggests the persistence in the adult of an anatomical entity, the olfactory fascia, that unites the cartilages of the nose to the olfactory mucosa.

Methods

We dissected two fresh specimens. After resecting the superficial tissues of the nose, dissection was focused on the disarticulation of the fibrocartilaginous noses from the facial and skull base skeleton.

Results

Dissection shows two fibrocartilaginous sacs that were invaginated side-by-side in the midface and attached to the anterior skull base. These membranous sacs were separated in the midline by the perpendicular plate of the ethmoid. Their walls contained the alar cartilages and the lateral expansions of the septolateral cartilage, which we had to separate from the septal cartilage. The olfactory mucosa was located inside their cranial ends.

Conclusion

The olfactory fascia is a continuous membrane uniting the nasal cartilages to the olfactory mucosa. Its origin can be found in the invagination and differentiation processes of the olfactory placodes. The fibrous portions of the olfactory fascia may be described as ligaments that unit the different components of the olfactory fascia one to the other and the fibrocartilaginous nose to the facial and skull base skeleton. The basicranial ligaments, fixing the fibrocartilaginous nose to the skull base, represent key elements in the concept of septorhinoplasty by disarticulation.

     

The use of meta-analysis in cost-effectiveness analysis. Issues and recommendations.

Meta-analysis is used to statistically pool the results from individual studies, usually randomised trials, to obtain an estimate of the summary effect size across studies. The summary measure from a meta-analysis is often used to derive the probability of treatment success in a cost-effectiveness analysis. Recently, LeLorier and colleagues questioned the ability of meta-analysis to accurately predict the results of a subsequent large-scale trial, implying that the use of a summary measure from a meta-analysis may be inappropriate in an economic evaluation. We comment on this potential shortcoming by first providing an outline of the use of meta-analysis results in a cost-effectiveness analysis. Then, using examples of discrepancies between meta-analyses and subsequent large trials noted by LeLorier and colleagues, we examine the potential impact of using the results from a small trial versus a meta-analysis. We found that the meta-analyses were comparable to or better than small trials at predicting the results of subsequent large trials. We, therefore, argue that a meta-analysis of homogeneous studies can provide a reasonable estimate of the treatment effect for use in a cost-effectiveness analysis when no large, definitive clinical trial has been performed. However, care must be taken not to over-interpret the precision of the estimate, since both the homogeneity and quality of the primary studies need to be considered. We conclude by providing guidance on the appropriate use of summary measures derived from meta-analyses for cost-effectiveness studies.     

Creation of oral care flavours to deliver breath-freshening benefits

Objective:  Oral care products deliver breath freshening primarily via mechano-chemical cleaning or by antimicrobial active systems. Dental flavours provide taste benefits, and freshen breath mainly by sensorial masking. We aimed to determine whether flavours could deliver breath freshening in products by inhibiting bacterial volatile sulphide compound (VSC) production.
Subjects and methods:  Flavour materials were screened for inhibition of hydrogen sulphide formation by Klebsiella pneumoniae in vitro , grouped by efficacy, and data provided to flavourists. Flavours were formulated to maximize the content of VSC-effective ingredients and re-screened to confirm performance. Extensive, iterative testing of flavours identified reliable creative rules to deliver efficient inhibition of H₂S generation. Breath-freshening flavours in whole products were then tested in-house in a 'breath freshness panel'.
Main outcome measures:  Malodour of panellists (not preselected for malodour score) was scored before and after product use, on the 'Rosenberg' 0–5 scale, together with residual flavour score, by extensively trained judges. Products were tested in double-blind, crossover studies, and results analysed using ANOVA.
Results and conclusions:  Products flavoured using these rules delivered significantly greater breath freshening at 2 h than control products, and equivalent benefits to products containing 0.1% (w/w) triclosan or 0.2% (w/w) zinc sulphate.     

Oral manifestations of allograft recipients immediately before and after kidney transplantation

Abstract

Objective: To identify the oral lesions of individuals with kidney disease immediately before and shortly after kidney transplantation, taking into account the immunosuppressive regimen, antiviral prophylaxis and type of transplantation.

Methods: A prospective observational cohort study was carried from January 2017 to January 2018. Eighty individuals aged 18?years or older who were admitted for kidney transplantation were eligible to participate. Clinical data regarding medical history, immunosuppressive therapy, antiviral prophylaxis, laboratorial data and oral examination were performed by the same trained researcher, in three different moments: 24?hours before transplantation (1st time point), 15–20?days (2nd time point) and 45–60?days (3rd time point) after transplantation.

Results: In the first, second and third time points, it was found that 3.7% (3/80), 23.7% (18/76) and 25.7% (19/74) of the participants showed oral soft tissue lesions. Ulcers and candidiasis were the most frequent oral lesions, and they were associated with the use of everolimus (p?=?.005) and azathioprine (p?=?.034), respectively. Less patients reported xerostomia after transplantation than before (p?<?.001).

Conclusions: Oral lesions are common in the short term after renal transplantation and are particularly related to both toxicities of immunosuppressive drugs and immunosuppression.     

Two cousins with partial trisomy 12q and monosomy 12p recombinants of a familial pericentric inversion of the chromosome 12

Partial trisomy 12q and monosomy 12p lead to multiple malformation syndromes. Instead of trisomy 12q that has been reported as a clinically identifiable syndrome, monosomy 12p is characterized by a wide phenotypic spectrum. We report two cousins suffering from severe mental retardation, seizures, and dysmorphic features related to a trisomy 12q24.3-->qter and a monosomy 12p13-->pter resulting from a familial pericentric inversion of chromosome 12. In an attempt to improve the clinical delineation of these two syndromes, we compared our two patients with previous reports of these aneusomies. This review emphasizes the high frequency of familial translocations, including a breakpoint at 12q24 involved in trisomy 12q whereas monosomy 12p occurs most frequently de novo. Despite the poor specificity of the signs, this comparison allowed us to determine the clinical features present in more than 20% of patients with trisomy 12q or monosomy 12p. We particularly emphasize some consistent leading features of monosomy 12p, including microcephaly, dental, cardio-vascular, extremity, and sensorial abnormalities, initially not reported as recurrent in this syndrome.     

Congenital X-linked ataxia, progressive myoclonic encephalopathy, macular degeneration and recurrent infections.

We report on 2 boys (maternal cousins), with severe congenital ataxia with generalized hypotonia, psychomotor retardation and recurrent bronchopulmonary infections. Later, they developed myoclonic encephalopathy and macular degeneration. Serial brain imaging investigations showed a cyst of the septum pellucidum, persistence of the cavum vergae, corpus callosum and cerebellar vermis hypoplasia without cortical atrophy. In the maternal pedigree, 5 males had recurrent bronchopneumonia associated with severe congenital hypotonia and died during the first years of life. Neurophysiological studies, including nerve conduction velocities, brainstem auditory evoked responses, somatosensory evoked potentials were normal. Electroretinogram showed normal wave morphology. Visual evoked potentials were mildly impaired. Extensive screening for metabolic disease gave normal results. Immunologic investigations showed normal T and B cell number, T cell function and immunoglobulin levels in both patients with a reduced level of IgG2 subclass in one.     

The Society for Craniofacial Genetics and Developmental Biology 42nd Annual Meeting

The Society for Craniofacial Genetics and Developmental Biology (SCGDB) 42nd Annual Meeting was held at the MD Anderson Cancer Center in Houston, Texas from October 14–15, 2019. The SCGDB meeting included scientific sessions on the molecular regulation of craniofacial development, cell biology of craniofacial development, signaling during craniofacial development, translational craniofacial biology, and for the first time, a career development workshop. Over a one hundred attendees from 21 states, and representing over 50 different scientific institutions, participated. The diverse group of scientists included cell and developmental biologists and clinical geneticists, promoting excellent discussions about molecular pathways guiding abnormal cell behaviors and the resultant morphological changes to craniofacial development. The results were high‐quality science and a welcoming environment for trainees interested in craniofacial biology.