Immunohistochemical pattern of hMSH2/hMLH1 in familial and sporadic colorectal, gastric, endometrial and ovarian carcinomas with instability in microsatellite sequences

Alterations of DNA mismatch repair (MMR) genes are involved in carcinogenesis of sporadic and inherited human cancers characterised by instability of DNA microsatellite sequences (MSI). MSI tumours are usually identified using molecular analysis. In the present investigation, hMLH1 and hMSH2 immunohistochemistry was tested in order to evaluate the utility of this method in predicting MMR deficiency. Colorectal (72), gastric (68), endometrial (44) and ovarian (17) carcinomas were independently evaluated for familial history, histological type of tumour, MSI status and immunohistochemical results. Loss of expression of either hMLH1 or hMSH2 was observed in 51 of 55 (92.8%) MSI tumours, while 145 of 146 microsatellite stable (MSS) tumours expressed both the hMLH1 and hMSH2 gene products. Independently of tumour site, an overall agreement between immunohistochemical and molecular results was observed in 15 hereditary non-polyposis colorectal cancer-related tumours. Among sporadic tumours, only 2 of 60 colorectal and 2 of 66 gastric carcinomas, displaying MSI, expressed both hMLH1 and hMSH2 gene products. All 39 endometrial and 16 ovarian tumours presented a concordant molecular and immunohistochemical profile. These data show that immunohistochemistry is an accurate and rapid method to predict the presence of defective DNA MMR genes and to identify both sporadic and familial MSI tumours.     

A microcirculatory technique for evaluating intravascular and topical administration of vasoactive agents: Response to AVP in the SHR

A "closed bath" cremaster muscle preparation is described which permits the administration of vasoactive materials to the microvasculature via intraarterial injection and topical suffusion. The technique is evaluated in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats by comparing arteriolar responses to intraarterial and topically suffused arginine vasopressin. The preparation utilizes a thermostatically heated brass suffusion chamber overlying the cremaster. The chamber is closed with a glass coverslip. Experimental materials are presented to the microvessels via intraarterial injection or suffusion through the chamber. The coverglass permits high optical resolution with both routes of administration. Following vasopressin administration, changes in arteriolar diameter were continuously monitored by image-shearing techniques or variable-resistance calipers. The responses were analyzed by comparing both the peak 5-sec vasoconstriction and a 60-sec integrated response. Intraarterial and topical suffusion of vasopressin (1.25 X 10(-10)-3.75 X 10(-7) M) caused dose-dependent vasoconstriction among 23-microns arterioles. Compared to the WKY, vasoconstriction was greater in the SHR when vasopressin was administered intraarterially. A similar strain difference was not observed with topical suffusion. The dose-response curves with intraarterial vasopressin were shifted approximately 100-fold in concentration to the right relative to those with topically suffused vasopressin. The "closed bath" cremaster muscle preparation described has several distinct advantages: (1) it permits introduction of different vasoactive materials in the most physiological manner in the same animal, and (2) it maintains high optical resolution and clarity for critical observation of the smallest vessels, even with suffusion.     

The Excess Preterm Birth Rate Among US-Born (Compared to Foreign-Born) Black Women: The Role of Father’s Education

Maternal and Child Health Journal - To ascertain the component of the excess preterm birth (<?37 weeks, PTB) rate among US-born (compared to foreign-born) Black women...     

Component-Resolved Diagnosis of Hazelnut Allergy in Children

Hazelnuts commonly elicit allergic reactions starting from childhood and adolescence, with a rare resolution over time. The definite diagnosis of a hazelnut allergy relies on an oral food challenge. The role of component resolved diagnostics in reducing the need for oral food challenges in the diagnosis of hazelnut allergies is still debated. Therefore, three electronic databases were systematically searched for studies on the diagnostic accuracy of specific-IgE (sIgE) on hazelnut proteins for identifying children with a hazelnut allergy. Studies regarding IgE testing on at least one hazelnut allergen component in children whose final diagnosis was determined by oral food challenges or a suggestive history of serious symptoms due to a hazelnut allergy were included. Study quality was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Eight studies enrolling 757 children, were identified. Overall, sensitivity, specificity, area under the curve and diagnostic odd ratio of Cor a 1 sIgE were lower than those of Cor a 9 and Cor a 14 sIge. When the test results were positive, the post-test probability of a hazelnut allergy was 34% for Cor a 1 sIgE, 60% for Cor a9 sIgE and 73% for Cor a 14 sIgE. When the test results were negative, the post-test probability of a hazelnut allergy was 55% for Cor a 1 sIgE, 16% for Cor a9 sIgE and 14% for Cor a 14 sIgE. Measurement of IgE levels to Cor a 9 and Cor a 14 might have the potential to improve specificity in detecting clinically tolerant children among hazelnut-sensitized ones, reducing the need to perform oral food challenges.     

Implementing a Transition Program from Paediatric to Adult Services in Phenylketonuria: Results after Two Years of Follow-Up with an Adult Team

We aimed to report the implementation of a phenylketonuria (PKU) transition program and study the effects of follow-up with an adult team on metabolic control, adherence, and loss of follow-up. Fifty-five PKU patients were analysed in the study periods (SP): 2 years before (SP1) and after the beginning of adult care (SP2). Retrospective data on metabolic control and number of clinic appointments were collected for each SP, and protein intakes were analysed. In SP2, three patients (6%) were lost to follow-up. There was a small but statistically significant increase in median number of annual blood spots from SP1 to SP2: 11 (7–15) vs. 14 (7–20); p = 0.002. Mean ± SD of median blood Phe remained stable (525 ± 248 µmol/L vs. 552 ± 225 µmol/L; p = 0.100); median % of blood Phe < 480 µmol/L decreased (51 (4–96)% vs. 37 (5–85)%; p = 0.041) and median number of clinic appointments increased from SP1 to SP2: (5 (4–6) vs. 11 (8–13); p < 0.001). No significant differences were found regarding any parameter of protein intake. Our results suggest that the implementation of an adult service was successful as impact on metabolic control was limited and attendance remained high. Continuous dietetic care likely contributed to these results by keeping patients in follow-up and committed to treatment.     

Ketogenic Diet as a Preventive and Supportive Care for COVID-19 Patients

Severe obesity is associated with an increased risk of admission to intensive care units and need for invasive mechanical ventilation in patients with COVID-19. The association of obesity and COVID-19 prognosis may be related to many different factors, such as chronic systemic inflammation, the predisposition to severe respiratory conditions and viral infections. The ketogenic diet is an approach that can be extremely effective in reducing body weight and visceral fat in the short term, preserving the lean mass and reducing systemic inflammation. Therefore, it is a precious preventive measure for severely obese people and may be considered as an adjuvant therapy for patients with respiratory compromise.     

Caregivers’ Perceived Emotional and Feeding Responsiveness toward Preschool Children: Associations and Paths of Influence

Although there is a large body of research connecting emotion to eating behaviors, little is known about the role of caregivers’ responses to children’s emotions in the context of child feeding. The purpose of this study was to analyze the relation between caregivers’ emotional responsiveness and feeding responsiveness. The mothers of 137 children between 2 and 6 years of age reported on their responses to children’s negative emotions using the Coping with Children’s Negative Emotions Scale and on their feeding practices using the Comprehensive Feeding Practices Questionnaire. The results showed that mothers’ supportive emotion responses (e.g., problem-focused, emotion-focused, and expressive encouragement reactions) tend to be positively associated with responsive feeding practices (e.g., encouraging, modelling, and teaching healthy food-related behaviors). Instead, mothers’ unsupportive responses (e.g., distress, punitive and minimization reactions) tend to be positively associated with nonresponsive feeding practices (e.g., food as reward or to regulate emotions, and pressure to eat) and negatively associated with responsive feeding practices. Our results suggest that emotional and feeding responsiveness may be intertwined and that differences in parent’s emotional responsiveness may translate into differences in their feeding styles, setting the stage for parents’ use of positive vs. negative feeding practices.     

Characterization of an Agarophyton chilense Oleoresin Containing PPARγ Natural Ligands with Insulin-Sensitizing Effects in a C57Bl/6J Mouse Model of Diet-Induced Obesity and Antioxidant Activity in Caenorhabditis elegans

The biomedical potential of the edible red seaweed Agarophyton chilense (formerly Gracilaria chilensis) has not been explored. Red seaweeds are enriched in polyunsaturated fatty acids and eicosanoids, which are known natural ligands of the PPARγ nuclear receptor. PPARγ is the molecular target of thiazolidinediones (TZDs), drugs used as insulin sensitizers to treat type 2 diabetes mellitus. Medical use of TZDs is limited due to undesired side effects, a problem that has triggered the search for selective PPARγ modulators (SPPARMs) without the TZD side effects. We produced Agarophyton chilense oleoresin (Gracilex^®), which induces PPARγ activation without inducing adipocyte differentiation, similar to SPPARMs. In a diet-induced obesity model of male mice, we showed that treatment with Gracilex^® improves insulin sensitivity by normalizing altered glucose and insulin parameters. Gracilex^® is enriched in palmitic acid, arachidonic acid, oleic acid, and lipophilic antioxidants such as tocopherols and β-carotene. Accordingly, Gracilex^® possesses antioxidant activity in vitro and increased antioxidant capacity in vivo in Caenorhabditis elegans. These findings support the idea that Gracilex^® represents a good source of natural PPARγ ligands and antioxidants with the potential to mitigate metabolic disorders. Thus, its nutraceutical value in humans warrants further investigation.     

Lycium barbarum polysaccharide fraction associated with photobiomodulation protects from epithelium thickness and collagen fragmentation in a model of cutaneous photodamage

Lasers in Medical Science - Ultraviolet radiation (UVR) is the major etiologic agent of cutaneous photoaging, and different strategies are used to prevent and treat this condition. The...