Int22h1/Int22h2‐mediated Xq28 duplication syndrome: de novo duplications,prenatal diagnoses,and additional phenotypic features

Int22h1/Int22h2‐mediated Xq28 duplication syndrome is a relatively new X‐linked intellectual disability syndrome, arising from duplications of the subregion flanked by intron 22 homologous regions 1 and 2 on the q arm of chromosome X. Its primary manifestations include variable cognitive deficits, distinct facial dysmorphia, and neurobehavioral abnormalities that mainly include hyperactivity, irritability, and autistic behavior. Affected males are hemizygous for the duplication, which explains their often more severe manifestations compared with heterozygous females. In this report, we describe the cases of nine individuals recently identified having the syndrome, highlighting unique and previously unreported findings of this syndrome. Specifically, we report for the first time in this syndrome, two cases with de novo duplications, three receiving prenatal diagnosis with the syndrome, and three others having atypical versions of the duplication. Among the latter, one proband has a shortened version spanning only the centromeric half of the typical duplication, while the other two cases have a nearly identical length duplication as the classical duplication, with the exception that their duplication's breakpoints are telomerically shifted by about 0.2 Mb. Finally, we shed light on two new manifestations in this syndrome, vertebral anomalies and multiple malignancies, which possibly expand the phenotypic spectrum of the syndrome.     

Changes in whole-brain functional networks and memory performance in aging

We used resting-functional magnetic resonance imaging data from 98 healthy older adults to analyze how local and global measures of functional brain connectivity are affected by age, and whether they are related to differences in memory performance. Whole-brain networks were created individually by parcellating the brain into 90 cerebral regions and obtaining pairwise connectivity. First, we studied age-associations in interregional connectivity and their relationship with the length of the connections. Aging was associated with less connectivity in the long-range connections of fronto-parietal and fronto-occipital systems and with higher connectivity of the short-range connections within frontal, parietal, and occipital lobes. We also used the graph theory to measure functional integration and segregation. The pattern of the overall age-related correlations presented positive correlations of average minimum path length (r = 0.380, p = 0.008) and of global clustering coefficients (r = 0.454, p < 0.001), leading to less integrated and more segregated global networks. Main correlations in clustering coefficients were located in the frontal and parietal lobes. Higher clustering coefficients of some areas were related to lower performance in verbal and visual memory functions. In conclusion, we found that older participants showed lower connectivity of long-range connections together with higher functional segregation of these same connections, which appeared to indicate a more local clustering of information processing. Higher local clustering in older participants was negatively related to memory performance.     

Alendronate prevents loss of bone density associated with discontinuation of hormone replacement therapy: a randomized controlled trial

BACKGROUND: Many women using hormone replacement therapy (HRT) will discontinue HRT and lose its bone-protective effect. Methods to preserve bone density in these women need to be explored. This multicenter, international, randomized, blinded, 12-month study was conducted to assess the effect of alendronate sodium on bone density in women who had recently discontinued HRT. METHODS: The 144 postmenopausal women included in the study were diagnosed as having low bone mineral density (BMD) and had recently discontinued HRT. They were randomized to receive either a daily dose of 10 mg of alendronate sodium or matching placebo. The main outcome measures were spine, hip, and total body BMD; biochemical markers of bone turnover; and tolerability. RESULTS: Alendronate treatment was associated with a 2.3% mean increase (95% confidence interval [CI], 1.7%-3.0%) in spine BMD compared with a mean loss of 3.2% (95% CI, - 4.6% to - 1.7%) in patients receiving placebo, for a difference of 5.5% (95% CI, 4.2%-6.8%) between alendronate and placebo. Greater hip and total body BMD preservation was also observed with alendronate use. Bone turnover decreased significantly with alendronate (bone-specific alkaline phosphatase levels decreased by 20% and urinary N-telopeptide/creatinine ratio by 47%), but increased in the placebo group (by 18% and 36%, respectively). Alendronate was well tolerated, with no increase in adverse events compared with placebo. CONCLUSIONS: A high rate of bone loss was observed in the first 12 to 15 months after discontinuation of HRT in postmenopausal women with low BMD. Treatment with alendronate increased or maintained both spine and hip BMD and prevented the increase in bone resorption seen with withdrawal of HRT in this population.     

Vitamin D Deficiency and Gestational Diabetes Mellitus in Relation to Body Mass Index

A relationship between vitamin D deficiency (VDD) and gestational diabetes mellitus (GDM) has been described. Considering that GDM prevalence depends on body mass index (BMI), our main objective was to determine if VDD is associated with GDM, independent of BMI. A cross-sectional study with 886 pregnant women was conducted in Elda (Spain) from September 2019 to June 2020. To assess the association, Poisson regression models with robust variance were used to estimate the prevalence ratio (PR). The observed GDM prevalence was 10.5%, while the VDD prevalence was 55.5%. In the crude model, both VDD and obesity were associated with GDM, but in the adjusted model, only VDD was statistically significant (PR = 1.635, p = 0.038). A secondary event analysis did not detect differences in VDD, but BMI yielded a higher frequency of births by cesarean section and newborns with a >90 percentile weight in the obesity group. In conclusion, VDD is associated with GDM, independent of BMI. Future longitudinal studies could provide information on causality.     

Anxiolytic Effect and Improved Sleep Quality in Individuals Taking Lippia citriodora Extract

The current fast-moving, hectic lifestyle has increased the number of individuals worldwide with difficulties in managing stress, which in turn is also affecting their sleep quality. Therefore, the objective of the current study was to assess a natural plant-based dietary supplement comprised of lemon verbena (Lippia citriodora) extract, purified in phenylpropanoids, in alleviating stress and improving quality of sleep. A double-blind, placebo-controlled study was conducted for 8 weeks, followed by a 4-week washout period. Both validated questionnaires and functional tests were performed during the study, whereas questionnaires were used after the washout. As a result, the group taking the lemon verbena extract significantly reduced their perception of stress after 8 weeks, which was corroborated by a significant decrease in cortisol levels. After the washout period, the subjects reported to present even lower stress levels, due to the lasting effect of the ingredient. As for sleep quality, the subjects taking the supplement reported feeling better rested, with a stronger effect observed in women. Sleep tracking using a wearable device revealed that the supplement users improved their times in the deeper stages of sleep, specifically their percentage of time in deep sleep and REM. In conclusion, lemon verbena extract purified in phenylpropanoids is revealed as a natural solution to help individuals to improve their stress and sleep quality.     

Gene expression profiles of breast cancer metastasis according to organ site

In advanced breast cancer, biomarker identification and patient selection using a metastatic tumor biopsy is becoming more necessary. However, the biology of metastasis according to the organ site is largely unknown. Here, we evaluated the expression of 771 genes in 184 metastatic samples across 11 organs, including liver, lung, brain, and bone, and made the following observations. First, all PAM50 molecular intrinsic subtypes were represented across organs and within immunohistochemistry‐based groups. Second, HER2‐low disease was identified across all organ sites, including bone, and HER2 expression significantly correlated with ERBB2 expression. Third, the majority of expression variation was explained by intrinsic subtype and not organ of metastasis. Fourth, subtypes and individual subtype‐related genes/signatures were significantly associated with overall survival. Fifth, we identified 74 genes whose expression was organ‐specific and subtype‐independent. Finally, immune profiles were found more expressed in lung compared to brain or liver metastasis. Our results suggest that relevant tumor biology can be captured in metastatic tissues across a variety of organ sites; however, unique biological features according to organ site were also identified and future studies should explore their implications in diagnostic and therapeutic interventions.     

Ramadan Nutritional Strategy: Professional Soccer Player Case Study

The period of Ramadan induces changes in the usual eating patterns of individuals. During this period, Muslims must abstain from drinking and eating from dawn to dusk. Therefore, some research conducted on professional soccer players has observed that during and/or after Ramadan, performance, running speed, agility, dribbling speed, and endurance and/or skill performance in athletic events may be negatively affected by Ramadan intermittent fasting (RIF). The objective of this study was to analyze the influence of a dietary plan during RIF on performance and body composition in a professional soccer player. A 20-year-old elite player (86.0 kg, 188.5 cm) followed a dietary-nutritional plan with an isocaloric diet and was supplemented with glycerol. The athlete’s strength and power in the lower limbs was assessed by performing a countermovement jump (CMJ) and Abalakov vertical jump (ABK) before and after Ramadan. After nutritional planning, the patient’s body composition improved in terms of fat loss (6.61 to 5.70%) and muscle mass gain (50.26 to 51.50%). In addition, this translated into improvements in performance tests, both in the CMJ (36.72 to 40.00 cm) and ABK (39.16 to 49.34 cm). In conclusion, during a period of fasting, personalised nutritional planning and an appropriate supplementation and rest protocol can improve the body composition and performance of soccer players.     

Rethinking Human Embryo Research Policies

It now seems technically feasible to culture human embryos beyond the “fourteen‐day limit,” which has the potential to increase scientific understanding of human development and perhaps improve infertility treatments. The fourteen‐day limit was adopted as a compromise but subsequently has been considered an ethical line. Does it remain relevant in light of technological advances permitting embryo maturation beyond it? Should it be changed and, if so, how and why? What justifications would be necessary to expand the limit, particularly given that doing so would violate some people's moral commitments regarding human embryos? Robust stakeholder engagement preceded adoption of the fourteen‐day limit and should arguably be part of efforts to reassess it. Such engagement could also consider the need for enhanced oversight of human embryo research. In the meantime, developing and implementing reliable oversight systems should help foster high‐quality research and public confidence in it.     

Curcumin encapsulation in Pickering emulsions co-stabilized by starch nanoparticles and chitin nanofibers

This study examined the stability and release of curcumin encapsulated in Pickering emulsions stabilized by starch nanoparticles and chitin nanofibers under different conditions. Curcumin stability under UV exposure and the release of curcumin from Pickering emulsions in excess water were evaluated over 24 h; while the storage stability of curcumin was assessed over 16 d. The amount of curcumin remaining in the emulsions was quantified spectrophotometrically to characterize its stability and kinetics of release. The progress of lipid oxidation was also monitored by determining peroxide (PV) and p-anisidine (AV) values. The results of passive release measurements indicated over 60% of curcumin was retained after 24 h. SNP/ChF-stabilized Pickering emulsions showed approximately 50% and 45% of curcumin retention upon 16 d of storage and under UV exposure, respectively. Moreover, significant improvement in the curcumin retention was found when higher concentrations of both solid nanoparticles were used. The degradation kinetics of curcumin over storage time and under UV exposure were found to follow first order kinetics. When both emulsifiers were doubled (C4S2), shelf-life was extended to longer than 60 d (AV < 10). This study provides a promising approach to protect encapsulated curcumin, which could potentially be used in functional food products with extended shelf-life.

This study examined the stability and release of curcumin encapsulated in Pickering emulsions co-stabilized by starch nanoparticles and chitin nanofibers under different conditions.