Intrapulmonary artery Doppler to predict mortality and morbidity in fetuses with mild or moderate left-sided congenital diaphragmatic hernia.

OBJECTIVES: In fetuses with isolated left-sided congenital diaphragmatic hernia (LCDH), prenatal detection of severe pulmonary hypoplasia is important, as fetal therapy can improve survival. Cases with mild or moderate lung hypoplasia still carry a considerable risk of mortality and morbidity, but there has been less interest in the accurate prediction of outcome in these cases. In this study of fetuses with mild or moderate isolated LCDH, we aimed to investigate: (1) the association between intrapulmonary artery (IPA) Doppler findings and mortality at discharge; (2) whether adding IPA Doppler findings improves the prediction of mortality based on lung size and liver herniation; and (3) the association between IPA Doppler findings and early neonatal morbidity. METHODS: This was a retrospective study of all consecutive fetuses assessed at the BCNatal and UZ Leuven hospitals between 2008 and 2020 with a prenatal diagnosis of isolated, non-severe LCDH, defined as observed-to-expected lung-to-head ratio (o/e-LHR) > 25%, that were managed expectantly during pregnancy followed by standardized neonatal management. An additional inclusion criterion was the availability of IPA Doppler measurements. The primary outcome was the association between IPA Doppler findings and mortality at discharge. Other predictors included o/e-LHR, liver herniation and gestational age at birth. Secondary outcomes were the association between IPA Doppler findings and the presence of pulmonary hypertension (PHT), need for supplemental oxygen at discharge and need for extracorporeal membrane oxygenation. IPA pulsatility index (PI) values were converted into Z-scores. Logistic regression analysis was performed to investigate the associations between predictor variables and outcome, and the best model was chosen based on the Nagelkerke R2 . RESULTS: Observations for 70 non-severe LCDH cases were available. Fifty-four (77%) fetuses survived until discharge. On logistic regression analysis, higher IPA-PI was associated with an increased risk of mortality (odds ratio (OR), 3.96 (95% CI, 1.62-9.70)), independently of o/e-LHR (OR, 0.87 (95% CI, 0.79-0.97)). An IPA-PI Z-score cut-off of 1.8 predicted mortality with a detection rate of 69% and specificity of 93%. Adding IPA-PI to o/e-LHR improved significantly the model's performance (Nagelkerke R2 , 46% for o/e-LHR + IPA-PI vs 28% for o/e-LHR (P < 0.002)), with a detection rate of 81% at a 10% false-positive rate. IPA-PI was associated with PHT (OR, 2.20 (95% CI, 1.01-4.59)) and need for oxygen supplementation at discharge (OR, 1.90 (95% CI, 1.10-3.40)), independently of lung size. CONCLUSIONS: In fetuses with mild or moderate LCDH, IPA-PI was associated with mortality and morbidity, independently of lung size. A model combining o/e-LHR with IPA-PI identified up to four in five cases that eventually died, despite being considered to have non-severe pulmonary hypoplasia. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Anatomical variations of the mandibular canal and their clinical implications in dental practice: a literature review.

INTRODUCTION: The anatomical variations of the mandibular canal have been described according to the number of additional branches it presents, bifid and trifid. Within the bifids we can also find subtypes of variations such as the retromolar mandibular canal. These anatomical variations can have important clinical implications for the work of dental professionals. METHODS: A systematic search of the literature was carried out in different databases that met the following criteria: articles published between 2000 and 2020, and articles that established a clinical correlation with variations in the mandibular canal. RESULTS: After applying inclusion and exclusion criteria, 32 articles were obtained, in which the variations of the mandibular canal were identified, their prevalence and incidence, which was very varied between the different articles, it was also found that the CBCT was the main technique to identify the anatomical variations of the mandibular canal. Lastly, the anatomical variations of the mandibular canal have a direct clinical correlation with pre-surgical, intra-surgical and postsurgical complications in pathologies that require surgical intervention. CONCLUSIONS: The anatomical variations of the mandibular canal have a high incidence, so knowing them is of vital importance both for clinicians and anatomy professors who provide morphological training. We believe that research should focus on describing and diagnosing the causes of these anatomical variations. That said, there is also a continuous challenge for all health professionals to learn about the different anatomical variations that the human body presents and how these can affect clinical practice.

Functional outcomes after physiotherapy program in patients with massive and irreparable rotator cuff tear.

OBJECTIVE: To evaluate the short term and 1-year follow-up functional effects of a physiotherapy programme in patients over 60 years of age with massive and irreparable Rotator Cuff (RC) tear. METHODS: A total of 96 patients with massive and irreparable RC tear were prospectively recruited. All patients were treated with a 12-week physiotherapy programme. Three evaluations were performed, at the beginning, at the end of the treatment and at one year of follow-up. The Constant-Murley questionnaire was used to assess shoulder function, the DASH questionnaire for upper limb function, and the Visual Analogue Scale (VAS) for pain intensity. RESULTS: At the end of the treatment, all the variables showed a clinically and statistically significant difference (p<.05). At one year of follow-up, the Constant-Murley showed an increase of 26.5 points (Cohen's d=1.7; 95% CI: 23.5-29.5; p<.001), DASH showed a decrease of 31.4 points (Cohen's d=2.2; 95% CI: 28.5-34.3; p<.001), and the VAS showed a decrease of 3.9cm (Cohen's d=3.6; 95% CI: 3.6-4.1; p<.001). CONCLUSION: In the short term and 1-year follow-up, a physiotherapy programme showed clinically and statistically significant results in all functional variables in patients older than 60 years with massive and irreparable RC tear.

Biophysical analysis of the molecular interactions between polysaccharides and mucin.

Mucoadhesive materials adhere persistently to mucosal surfaces. A mucoadhesive delivery system could therefore facilitate the controlled release of drugs and optimize their bioavailability in mucosal tissues. Polysaccharides are the most versatile class of natural polymers for transmucosal drug delivery. We used microviscosimetry to explore the mucoadhesion of a library of polysaccharide families with diverse structural characteristics as a first step toward the rational design of mucoadhesive polysaccharide-based nanoformulations. Here we show that the magnitude of deviation between the viscosity of mixed polysaccharide-mucin solutions and the corresponding individual stock solutions can indicate underlying molecular interactions. We found that nonlinear monotonic curves predicted a correlation between the magnitude of interaction and the ability of polysaccharide coils to contract in the presence of salt (i.e., chain flexibility). Charge-neutral polysaccharides such as dextran and Streptococcus thermophilus exopolysaccharide did not interact with mucin. Synchrotron small-angle X-ray scattering (SAXS) data supported the previously described structural features of mucin. Furthermore, high-q scattering data (i.e., sensitive to smaller scales) revealed that when mucin is in dilute solution (presumably in an extended conformation) in the presence of low-Mw alginate, its structure resembles that observed at higher concentrations in the absence of alginate. This effect was less pronounced in the case of high-Mw alginate, but the latter influenced the bulk properties of mucin-alginate mixtures (e.g., hydrodynamic radius and relative viscosity) more prominently than its low-Mw counterpart.

Structure of chitosan determines its interactions with mucin.

Synthetic and natural mucoadhesive biomaterials in optimized galenical formulations are potentially useful for the transmucosal delivery of active ingredients to improve their localized and prolonged effects. Chitosans (CS) have potent mucoadhesive characteristics, but the exact mechanisms underpinning such interactions at the molecular level and the role of the specific structural properties of CS remain elusive. In the present study we used a combination of microviscosimetry, zeta potential analysis, isothermal titration calorimetry (ITC) and fluorescence quenching to confirm that the soluble fraction of porcine stomach mucin interacts with CS in water or 0.1 M NaCl (at c < c*; relative viscosity, η(rel), ∼ 2.0 at pH 4.5 and 37 °C) via a heterotypic stoichiometric process significantly influenced by the degree of CS acetylation (DA). We propose that CS-mucin interactions are driven predominantly by electrostatic binding, supported by other forces (e.g., hydrogen bonds and hydrophobic association) and that the DA influences the overall conformation of CS and thus the nature of the resulting complexes. Although the conditions used in this model system are simpler than the typical in vivo environment, the resulting knowledge will enable the rational design of CS-based nanostructured materials for specific transmucosal drug delivery (e.g., for Helicobacter pylori stomach therapy).

Dopamine D1 and corticotrophin-releasing hormone type-2α receptors assemble into functionally interacting complexes in living cells.

BACKGROUND AND PURPOSE: Dopamine and corticotrophin-releasing hormone (CRH; also known as corticotrophin-releasing factor) are key neurotransmitters in the interaction between stress and addiction. Repeated treatment with cocaine potentiates glutamatergic transmission in the rat basolateral amygdala/cortex pathway through a synergistic action of D1 -like dopamine receptors and CRH type-2α receptors (CRF2 α receptors). We hypothesized that this observed synergism could be instrumented by heteromers containing the dopamine D1 receptor and CRF2 α receptor. EXPERIMENTAL APPROACH: D1 /CRF2 α receptor heteromerization was demonstrated in HEK293T cells using co-immunoprecipitation, BRET and FRET assays, and by using the heteromer mobilization strategy. The ability of D1 receptors to signal through calcium, when singly expressed or co-expressed with CRF2 α receptors, was evaluated by the calcium mobilization assay. KEY RESULTS: D1 /CRF2 α receptor heteromers were observed in HEK293T cells. When singly expressed, D1 receptors were mostly located at the cell surface whereas CRF2 α receptors accumulated intracellularly. Interestingly, co-expression of both receptors promoted D1 receptor intracellular and CRF2 α receptor cell surface targeting. The heteromerization of D1 /CRF2 α receptors maintained the signalling through cAMP of both receptors but switched D1 receptor signalling properties, as the heteromeric D1 receptor was able to mobilize intracellular calcium upon stimulation with a D1 receptor agonist. CONCLUSIONS AND IMPLICATIONS: D1 and CRF2 α receptors are capable of heterodimerization in living cells. D1 /CRF2 α receptor heteromerization might account, at least in part, for the complex physiological interactions established between dopamine and CRH in normal and pathological conditions such as addiction, representing a new potential pharmacological target.

Affinity protein-based FRET tools for cellular tracking of chitosan nanoparticles and determination of the polymer degree of acetylation.

Chitosan (CS) is a family of linear polysaccharides with diverse applications in medicine, agriculture, and industry. Its bioactive properties are determined by parameters such as the degree of acetylation (DA), but current techniques to measure the DA are laborious and require large amounts of substrate and sophisticated equipment. It is also challenging to monitor the fate of chitosan-based nanoparticles (CS-NPs) in vitro because current tools cannot measure their enzymatic or chemical degradation. We have developed a method based on the Förster resonance energy transfer (FRET) that occurs between two independent fluorescent proteins fused to a CS-binding domain, who interact with CS polymers or CS-NPs. We used this approach to calibrate a simple and rapid analytical method that can determine the DA of CS substrates. We showed unequivocally that FRET occurs on the surface of CS-NPs and that the FRET signal is quenched by enzymatic degradation of the CS substrate. Finally, we provide in vitro proof-of-concept that these approaches can be used to label CS-NPs and colocalize them following their interactions with mammalian cells.

[Myocardial infarction and pregnancy]. / Infarto del miocardio y embarazo.

We show a clinic case of a female patient 42 years old that suffered a myocardial infarction by coronary spasm, while she was in her 30th and a half weeks of gestation. We analyze the bases of the diagnostic its evolution and the neonatal complications.

[Spontaneous liver rupture in pregnancy-induced hypertension]. / Ruptura hepática espontanea en hipertensión inducida por el embarazo.

Spontaneous rupture of liver during pregnancy is associated with a very high maternal mortality. This lesion is an unusual complication of the preeclampsia-eclampsia syndrome. We report the case of a 34 years old woman who suffered this complication; responding satisfactorily after conservative surgical treatment.