Pharmacosmos (Denmark)

Background/Objectives: Iron (Fe) is a co-factor for enzymes of the developing brain necessitating sufficient supply. We investigated the effects of administering ferric derisomaltose/Fe isomaltoside (FDI) subcutaneously to Fe-deficient (ID) pregnant rats on cerebral and hepatic concentrations of essential metals and the expression of iron-relevant genes. Methods: Pregnant rats subjected to ID were injected with FDI on the day of mating (E0), 14 days into pregnancy (E14), or the day of birth (postnatal (P0)). The efficacy was evaluated by determination of cerebral and hepatic Fe, copper (Cu), and zinc (Zn) and gene expression of ferroportin, hepcidin, and ferritin H + L in pups on P0 and as adults on P70. Results: Females fed an ID diet (5.2 mg/kg Fe) had offspring with significantly lower cerebral and hepatic Fe compared to female controls fed a standard diet (158 mg/kg Fe). Cerebral Cu increased irrespective of supplying a standard diet or administering FDI combined with the standard diet. Hepatic hepcidin mRNA was significantly lower following ID. Cerebral hepcidin mRNA was hardly detectable irrespective of iron status. Conclusions: In conclusion, administering FDI subcutaneously to ID pregnant rats on E0 normalizes fetal cerebral and hepatic Fe. When applied at later gestational ages, supplementation with additional Fe to the offspring is needed to normalize cerebral and hepatic Fe.

Caracterizada por ser um processo introspectivo e retrospectivo no qual o tradutor tece comentários que justificam suas escolhas de forma autocrítica, consciente e reflexiva, a Tradução Comentada vem crescendo exponencialmente no campo dos Estudos da Tradução. Propomo-nos apresentar uma tradução comentada do gênero literário poesia da obra Poesia Surda para Sempre, de autoria de Rodrigo Custódio da Silva. Optamos por seguir uma perspectiva bakhtiniana do enunciado. Centramos nossos comentários em aspectos sócio históricos relativos ao sujeito surdo e a sua afirmação identitária manifestada por meio da resistência e uso da língua de sinais.

This Python script generates a confusion matrix heatmap from an array of classification data using the <code>numpy</code>, <code>pandas</code>, <code>seaborn</code>, and <code>matplotlib</code> libraries. The script defines the confusion matrix data and class labels, creates a pandas dataframe, and generates a heatmap with annotations and rotated axis labels. This script may be useful for researchers and practitioners working in the field of classification analysis and data visualization

Recent studies suggested induction of 40 Hz neural activity as a potential treatment for Alzheimer's disease (AD). However, prolonged exposure to flickering light raises adherence and safety concerns, encouraging investigation of tolerable light stimulation protocols. To investigate the safety, feasibility, and exploratory measures of efficacy. This two-stage randomized placebo-controlled double-blinded clinical trial, recruited first cognitive healthy participants (n = 3/2 active/placebo), and subsequently patients with mild-to-moderate AD (n = 5/6, active/placebo). Participants were randomized 1:1 to receive either active intervention with 40 Hz Invisible Spectral Flicker (ISF) or placebo intervention with color and intensity matched non-flickering white light. Few and mild adverse events were observed. Adherence was above 86.1% of intended treatment days, with participants remaining in front of the device for >51.3 min (60 max) and directed gaze >34.9 min. Secondary outcomes of cognition indicate a tendency towards improvement in the active group compared to placebo (mean: -2.6/1.5, SD: 6.58/6.53, active/placebo) at week 6. Changes in hippocampal and ventricular volume also showed no tendency of improvement in the active group at week 6 compared to placebo. At week 12, a potential delayed effect of the intervention was seen on the volume of the hippocampus in the active group compared to placebo (mean: 0.34/-2.03, SD: 3.26/1.18, active/placebo), and the ventricular volume active group (mean: -0.36/2.50, SD: 1.89/2.05, active/placebo), compared to placebo. Treatment with 40 Hz ISF offers no significant safety or adherence concerns. Potential impact on secondary outcomes must be tested in larger scale clinical trials.

Acute upper respiratory tract infections (URTIs) are caused by numerous viruses and bacteria. URTIs can be a cause of morbidity and are among the most common reasons for visiting healthcare practitioners and prescribing antibiotics to children in addition to causing absenteeism from school and work. Oral intake of Lacticaseibacillus rhamnosus GG DSM 33156 has shown beneficial health effects in several clinical trials, primarily relating to immune function and gastrointestinal health in children and adults. It has also been suggested that oral intake of L. rhamnosus GG DSM 33156 can reduce the incidence rate and alleviate symptoms of URTIs in children. We here report the results of a randomised, double-blind, placebo-controlled trial of 619 children aged 2-6 years conducted at a single centre in Scotland. The children, who were in day care or primary school, were followed over a 16-week intervention period with 309 randomised in the active group and 310 in the placebo group. The parents or guardians reported a daily healthcare status and any presumed episodes of URTI, which were subsequently confirmed by a general practitioner. The investigational product was well tolerated in the trial. Although a general trend towards a beneficial effect was observed, this trial did not demonstrate that L. rhamnosus GG DSM 33156 significantly reduced the incidence of URTIs, diagnosed by a general practitioner according to prespecified criteria (primary endpoint). Moreover, none of the secondary efficacy endpoints were met. Applying a Ward's hierarchical clustering, two separate clusters, focussing on four quality of life-related endpoints, were identified. Cluster 1 was associated with more severe URTI characteristics than cluster 2. Cluster 2 was significantly enriched with children who consumed the product, indicating that the symptoms children experience during an URTI are alleviated by the intake of L. rhamnosus GG DSM 33156. The study is registered at ClinicalTrials.gov ID: NCT03636191.

Relevance: According to the International Agency for Research on Cancer (IARС), lung cancer (LC) today ranks first in cancer&#x0D; incidence worldwide [1]. In the Republic of Kazakhstan, about 3800 new cases of LC and more than 2000 deaths from LC are&#x0D; registered each year (one-year mortality exceeds 49.4%) [2]. This supports the relevance of early LC diagnostics. The study of&#x0D; DNA methylation in human peripheral blood mononuclear cells (PBMC) suggests its use as an early diagnostic and prognostic&#x0D; marker for LC before detecting a malignant neoplasm by visual diagnostic methods.&#x0D; The purpose of the study was to find specific diagnostic and prognostic markers by DNA methylation profiling of PBMC&#x0D; in patients with LC.&#x0D; Results: Methylation markers of blood mononuclear fraction were detected in CG islets associated with genes ICAM5,&#x0D; mir138, SYNE1, and KLK4 in 97% of plasma samples from patients with LC and were absent in healthy people. The usability of&#x0D; these markers to differentiate LC from 16 other cancers using NCBI GEO and TCGA methylation data was demonstrated with a&#x0D; specificity level of 0.96 and a sensitivity of 0.84.&#x0D; Conclusion: The specificity and sensitivity of the method of LC early diagnostics and prognosis based on the methylation of&#x0D; blood mononuclear cells (detection of methylation of CG islets associated with the ICAM5, mir138, SYNE1, and KLK4 genes in&#x0D; PBMC) are enough to use it in screening for LC.

Alzheimer’s disease (AD) not only takes an emotional toll on the individual with the disease, their families, relatives, and caretakers, it also has immense socioeconomic consequences on the health care system and society. Moreover, the socioeconomic consequences are expected to increase significantly, thus reducing the social and economic cost of AD is of high importance. Recently, exposure to 40 Hz stroboscopic light therapy, for one hour a day, resulted in slowing the progression of AD in mice and has a considerable potential for treatment in humans. However, exposure to such stroboscopic light carries its own consequences being that it is difficult to implement in a patient’s daily routine, irksome to use, and can cause visual discomfort which may result in a lack of patient adherence. Here, we demonstrate a novel technology based on controlling multiple single-color LEDs to produce white light where its spectral composition alternates at a given modulation frequency without visible flicker. We coin this technique as Invisible Spectral Flicker (ISF). We present 40 Hz invisible spectral flicker light as a potential alternative in reducing discomfort compared to 40 Hz stroboscopic light, whilst still entraining oscillations in various areas of the brain. Furthermore, we demonstrate a distinct way to generate a 40 Hz metameric light source with the presented color mixing scheme, and validate that the CIE 1931 (x, y) coordinates match for two different spectral power distributions. Finally, we illustrate the light characteristics of seven 40 Hz color fusion light sources and two 40 Hz stroboscopic light sources. The technology presented here will lead to new, and hopefully improved, designs of light therapy systems for the treatment of Alzheimer’s and dementia.