Early Pulmonary Interstitial Emphysema in Preterm Neonates-Respiratory Management and Case Report in Nonventilated Very Low Birth Weight Twins

Early pulmonary interstitial emphysema in extreme preterm neonates is closely linked with respiratory distress syndrome and exposure to mechanical ventilation. In severe cases, maintaining adequate gas exchange aiming to avoid further lung damage and other neonatal morbidities associated with systemic/pulmonary hypoperfusion, prolonged hypoxia, and respiratory acidosis can be challenging and requires in-depth knowledge into the pathophysiology of the disease. Herein, we report on very low birth weight twins who developed early pulmonary interstitial emphysema during noninvasive respiratory support. We further review the current evidence from the literature, specifically addressing on possible preventive measures and the respiratory management options of this acute pulmonary disease in high-risk neonates

Efficient RNA interference in patients' acute lymphoblastic leukemia cells amplified as xenografts in mice

<p>Abstract</p> <p>Background</p> <p>Signaling studies in cell lines are hampered by non-physiological alterations obtained in vitro. Physiologic primary tumor cells from patients with leukemia require passaging through immune-compromised mice for amplification. The aim was to enable molecular work in patients' ALL cells by establishing siRNA transfection into cells amplified in mice.</p> <p>Results</p> <p>We established delivering siRNA into these cells without affecting cell viability. Knockdown of single or multiple genes reduced constitutive or induced protein expression accompanied by marked signaling alterations.</p> <p>Conclusion</p> <p>Our novel technique allows using patient-derived tumor cells instead of cell lines for signaling studies in leukemia.</p

Oral supplementation of specific collagen peptides has beneficial effects on human skin physiology: a double-blind, placebo-controlled study

Various dietary supplements are claimed to have cutaneous anti-aging properties; however, there are a limited number of research studies supporting these claims. The objective of this research was to study the effectiveness of collagen hydrolysate (CH) composed of specific collagen peptides on skin biophysical parameters related to cutaneous aging. In this double-blind, placebo-controlled trial, 69 women aged 35-55 years were randomized to receive 2.5 g or 5.0 g of CH or placebo once daily for 8 weeks, with 23 subjects being allocated to each treatment group. Skin elasticity, skin moisture, transepidermal water loss and skin roughness were objectively measured before the first oral product application (t0) and after 4 (t1) and 8 weeks (t2) of regular intake. Skin elasticity (primary interest) was also assessed at follow-up 4 weeks after the last intake of CH (t3, 4-week regression phase). At the end of the study, skin elasticity in both CH dosage groups showed a statistically significant improvement in comparison to placebo. After 4 weeks of follow-up treatment, a statistically significantly higher skin elasticity level was determined in elderly women. With regard to skin moisture and skin evaporation, a positive influence of CH treatment could be observed in a subgroup analysis, but data failed to reach a level of statistical significance. No side effects were noted throughout the study

Oral intake of specific bioactive collagen peptides reduces skin wrinkles and increases dermal matrix synthesis

Dietary consumption of food supplements has been found to modulate skin functions and can therefore be useful in the treatment of skin aging. However, there is only a limited number of clinical studies supporting these claims. In this double-blind, placebo-controlled study, the effectiveness of the specific bioactive collagen peptide (BCP) VERISOL® on eye wrinkle formation and stimulation of procollagen I, elastin and fibrillin biosynthesis in the skin was assessed. A hundred and fourteen women aged 45-65 years were randomized to receive 2.5 g of BCP or placebo, once daily for 8 weeks, with 57 subjects being allocated to each treatment group. Skin wrinkles were objectively measured in all subjects, before starting the treatment, after 4 and 8 weeks as well as 4 weeks after the last intake (4-week regression phase). A subgroup was established for suction blister biopsies analyzing procollagen I, elastin and fibrillin at the beginning of the treatment and after 8 weeks of intake. The ingestion of the specific BCP used in this study promoted a statistically significant reduction of eye wrinkle volume (p < 0.05) in comparison to the placebo group after 4 and 8 weeks (20%) of intake. Moreover a positive long-lasting effect was observed 4 weeks after the last BCP administration (p < 0.05). Additionally, after 8 weeks of intake a statistically significantly higher content of procollagen type I (65%) and elastin (18%) in the BCP-treated volunteers compared to the placebo-treated patients was detected. For fibrillin, a 6% increase could be determined after BCP treatment compared to the placebo, but this effect failed to reach the level of statistical significance. In conclusion, our findings demonstrate that the oral intake of specific bioactive collagen peptides (Verisol®) reduced skin wrinkles and had positive effects on dermal matrix synthesis

In vivo imaging enables high resolution preclinical trials on patients' leukemia cells growing in mice.

Xenograft mouse models represent helpful tools for preclinical studies on human tumors. For modeling the complexity of the human disease, primary tumor cells are by far superior to established cell lines. As qualified exemplary model, patients' acute lymphoblastic leukemia cells reliably engraft in mice inducing orthotopic disseminated leukemia closely resembling the disease in men. Unfortunately, disease monitoring of acute lymphoblastic leukemia in mice is hampered by lack of a suitable readout parameter

The Potentials and Caveats of Mesenchymal Stromal Cell-Based Therapies in the Preterm Infant

Preponderance of proinflammatory signals is a characteristic feature of all acute and resulting long-term morbidities of the preterm infant. The proinflammatory actions are best characterized for bronchopulmonary dysplasia (BPD) which is the chronic lung disease of the preterm infant with lifelong restrictions of pulmonary function and severe consequences for psychomotor development and quality of life. Besides BPD, the immature brain, eye, and gut are also exposed to inflammatory injuries provoked by infection, mechanical ventilation, and oxygen toxicity. Despite the tremendous progress in the understanding of disease pathologies, therapeutic interventions with proven efficiency remain restricted to a few drug therapies with restricted therapeutic benefit, partially considerable side effects, and missing option of applicability to the inflamed brain. The therapeutic potential of mesenchymal stromal cells (MSCs)-also known as mesenchymal stem cells-has attracted much attention during the recent years due to their anti-inflammatory activities and their secretion of growth and development-promoting factors. Based on a molecular understanding, this review summarizes the positive actions of exogenous umbilical cord-derived MSCs on the immature lung and brain and the therapeutic potential of reprogramming resident MSCs. The pathomechanistic understanding of MSC actions from the animal model is complemented by the promising results from the first phase I clinical trials testing allogenic MSC transplantation from umbilical cord blood. Despite all the enthusiasm towards this new therapeutic option, the caveats and outstanding issues have to be critically evaluated before a broad introduction of MSC-based therapies

Multidimensional assessment of infant, parent and staff outcomes during a family centered care enhancement project in a tertiary neonatal intensive care unit:study protocol of a longitudinal cohort study

Background: The therapeutic advances and progress in the care for preterm infants have enabled the regular survival of very immature infants. However, the high burden of lifelong sequelae following premature delivery constitutes an ongoing challenge. Regardless of premature delivery, parental mental health and a healthy parent–child relationship were identified as essential prerogatives for normal infant development. Family centered care (FCC) supports preterm infants and their families by respecting the particular developmental, social and emotional needs in the Neonatal Intensive Care Unit. Due to the large variations in concepts and goals of different FCC initiatives, scientific data on the benefits of FCC for the infant and family outcome are sparse and its effects on the clinical team need to be elaborated. Methods: This prospective single centre longitudinal cohort study enrols preterm infants ≤ 32 + 0 weeks of gestation and/or birthweight ≤ 1500 g and their parents at the neonatal department of the Giessen University Hospital, Giessen, Germany. Following a baseline period, the rollout of additional FCC elements is executed following a stepwise 6-months approach that covers the NICU environment, staff training, parental education and psychosocial support for parents. Recruitment is scheduled over a 5.5. year period from October 2020 to March 2026. The primary outcome is corrected gestational age at discharge. Secondary infant outcomes include neonatal morbidities, growth, and psychomotor development up to 24 months. Parental outcome measures are directed towards parental skills and satisfaction, parent-infant-interaction and mental health. Staff issues are elaborated with particular focus on the item workplace satisfaction. Quality improvement steps are monitored using the Plan- Do- Study- Act cycle method and outcome measures cover the infant, the parents and the medical team. The parallel data collection enables to study the interrelation between these three important areas of research. Sample size calculation was based on the primary outcome. Discussion: It is scientifically impossible to allocate improvements in outcome measures to individual enhancement steps of FCC that constitutes a continuous change in NICU culture and attitudes covering diverse areas of change. Therefore, our trial is designed to allocate childhood, parental and staff outcome measures during the stepwise changes introduced by a FCC intervention program. Trial registration: Clinicaltrials.gov, trial registration number NCT05286983, date of registration 03/18/2022, retrospectively registered, http://clinicaltrials.gov .</p

Attenuated PDGF signaling drives alveolar and microvascular defects in neonatal chronic lung disease

Neonatal chronic lung disease (nCLD) affects a significant number of neonates receiving mechanical ventilation with oxygen-rich gas (MV-O2). Regardless, the primary molecular driver of the disease remains elusive. We discover significant enrichment for SNPs in the PDGF-Rα gene in preterms with nCLD and directly test the effect of PDGF-Rα haploinsufficiency on the development of nCLD using a preclinical mouse model of MV-O2. In the context of MV-O2, attenuated PDGF signal