The Association of Patent Ductus Arteriosus with Inflammation: A Narrative Review of the Role of Inflammatory Biomarkers and Treatment Strategy in Premature Infants.

Patent ductus arteriosus (PDA) is a common cardiovascular complication that complicates clinical care in the intensive care of premature infants. Prenatal and postnatal infections and the inflammation process can contribute to PDA, and intrauterine inflammation is a known risk factor of PDA. A variety of inflammatory biomarkers have been reported to be associated with PDA. Chorioamnionitis induces the fetal inflammatory process via several cytokines that have been reported to be associated with the presence of PDA and may have a role in the vascular remodeling process or vessel dilation of the ductus. On the other hand, anti-inflammatory agents, such as antenatal steroids, decrease PDA incidence and severity in patients born to those with chorioamnionitis. Proinflammatory cytokines, which are expressed more significantly in preterm neonates and chorioamnionitis, are associated with the presence of PDA. In this review, we focus on the pathogenesis of PDA in preterm infants and the role of biomarkers associated with the perinatal inflammatory process.

Ovarian Follicular Growth through Intermittent Vaginal Gonadotropin Administration in Diminished Ovarian Reserve Women.

It is a challenge to obtain enough oocytes during in vitro fertilization (IVF) in women who have a poor ovarian response (POR) in achieving conception. We have adopted the characteristics of the first uterine pass effect, which we pioneered in employing the vaginal administration of gonadotropins in women receiving IVF treatments. In our previous study employing vaginal administration, faster absorption and slower elimination of gonadotropins were demonstrated, and, female subjects presented proper ovarian follicle growth and pregnancy rates. In this study, during 2016-2020, 300 to 675 IU of gonadotropins were administered vaginally every three days in 266 POR women for their controlled ovarian hyperstimulation (COH). The injections were performed with needles angled at 15-30° towards the middle-upper portions of the bilateral vaginal wall, with an injection depth of 1-2 mm. For the COH results, these women, on average, received 3.0 ± 0.9 vaginal injections and a total dose of 1318.4 ± 634.4 IU gonadotropins, resulting in 2.2 ± 1.9 mature oocytes and 1.0 ± 1.2 good embryos. Among these embryos, 0.9 ± 1.0 were transferred to reach a clinical pregnancy rate of 18.1% and a live birth rate of 16.7%. In conclusion, the intermittent vaginal administration of gonadotropins proved to be effective in POR women for their IVF treatments.

Extended Injection Intervals of Gonadotropins by Intradermal Administration in IVF Treatment.

CONTEXT: Gonadotropins can be administered every 5 days under intradermal injection in in vitro fertilization (IVF) treatment. OBJECTIVE: To explore the effectiveness of intradermal injection of recombinant human FSH (rhFSH) for women undergoing IVF. METHODS: Women who received their first IVF treatment enrolled in this prospective intervention in 2018. All women received a bolus of 900 IU rhFSH intradermally at day 2 of the treatment cycle followed by additional dosage of rhFSH at day 7 and/or day 10. The main outcome measures included the total dose of rhFSH and number of injections required, sequential serum FSH level detected, and number of mature oocytes retrieved. RESULTS: Seventy women completed the study. On average, 2.31 ±â€…0.73 injections and 1662 ±â€…397 IU of rhFSH were administered. While the baseline FSH level was 5.6 ±â€…2.2 IU/L, the serum concentrations of FSH after rhFSH administration were 35.3 ±â€…7.0 on the first day (24 hours) and 10.7 ±â€…3.7 IU/L on the fifth day (120 hours). A total of 10.5 ±â€…6.6 mature oocytes were retrieved, resulting in 7.3 ±â€…5.1 pronuclear embryos; 1.8 ±â€…0.6 embryos were transferred to the uterus. Our findings resulted in 72% fertilization, 91% cleavage, 31% implantation, and 36% live birth rates. Although fewer larger follicles were found, noninferiority results were noted in the mature oocytes retrieved, good embryos available, and clinical pregnancy rate compared with those received conventional daily subcutaneous rhFSH administration. CONCLUSION: Intradermal administration of rhFSH, with a smaller dose of rhFSH and fewer injections, may achieve the goal of a cost-effective and more patient-friendly regimen.

Evolution of transcriptional control of antigenic variation and virulence in human and ape malaria parasites.

BACKGROUND: The most severe form of human malaria is caused by the protozoan parasite Plasmodium falciparum. This unicellular organism is a member of a subgenus of Plasmodium called the Laverania that infects apes, with P. falciparum being the only member that infects humans. The exceptional virulence of this species to humans can be largely attributed to a family of variant surface antigens placed by the parasites onto the surface of infected red blood cells that mediate adherence to the vascular endothelium. These proteins are encoded by a large, multicopy gene family called var, with each var gene encoding a different form of the protein. By changing which var gene is expressed, parasites avoid immune recognition, a process called antigenic variation that underlies the chronic nature of malaria infections. RESULTS: Here we show that the common ancestor of the branch of the Laverania lineage that includes the human parasite underwent a remarkable change in the organization and structure of elements linked to the complex transcriptional regulation displayed by the var gene family. Unlike the other members of the Laverania, the clade that gave rise to P. falciparum evolved distinct subsets of var genes distinguishable by different upstream transcriptional regulatory regions that have been associated with different expression profiles and virulence properties. In addition, two uniquely conserved var genes that have been proposed to play a role in coordinating transcriptional switching similarly arose uniquely within this clade. We hypothesize that these changes originated at a time of dramatic climatic change on the African continent that is predicted to have led to significant changes in transmission dynamics, thus selecting for patterns of antigenic variation that enabled lengthier, more chronic infections. CONCLUSIONS: These observations suggest that changes in transmission dynamics selected for significant alterations in the transcriptional regulatory mechanisms that mediate antigenic variation in the parasite lineage that includes P. falciparum. These changes likely underlie the chronic nature of these infections as well as their exceptional virulence.

Daylight Photodynamic Therapy: An Update.

Daylight photodynamic therapy (dPDT) uses sunlight as a light source to treat superficial skin cancer. Using sunlight as a therapeutic device has been present for centuries, forming the basis of photodynamic therapy in the 20th century. Compared to conventional PDT, dPDT can be a less painful, more convenient and an effective alternative. The first clinical uses of dPDT on skin cancers began in Copenhagen in 2008. Currently, aminolevulinic acid-mediated dPDT has been approved to treat actinic keratosis patients in Europe. In this review article, we introduce the history and mechanism of dPDT and focus on the pros and cons of dPDT in treating superficial skin cancers. The future applications of dPDT on other skin diseases are expected to expand as conventional PDT evolves.