Maternal age, morphology, development and chromosome abnormalities in over 6000 cleavage-stage embryos

Previous studies assessing the relationship between embryo development, maternal age and chromosome abnormalities were either small or analysed mostly embryos not suitable for replacement. The present study includes >6000 embryos, including many suitable for replacement. Embryos with the best morphology and development were 44% euploid in patients younger than 35, decreasing to 21% in patients 41 and older. The worst morphology group had only 30% normal embryos from patients younger than 35, and 12% in embryos from patients 41 and older. Thus morphological analysis was able to improve the population of normal embryos only from 30 to 44% in the best of cases. Regarding specific abnormalities, 20% of embryos were aneuploid, 32% aneuploid plus other abnormalities, and the rest had post-meiotic abnormalities. Of those, only aneuploidy increased with maternal age. There were no big differences in the frequency of chromosome abnormalities depending on patient indication, within a similar age group. In summary, previous trends detected in suboptimal embryos were also confirmed in the best embryos for replacement. Although dysmorphism and advanced maternal age are both related to chromosome abnormalities, these parameters can yield at most <50% euploid embryos, and other techniques such as preimplantation diagnosis are required to ensure that only euploid embryos are replaced.     

Congenital fusion of jaw and ankyloblepharon filiforme adnatum: Malformation and multiple systems anomaly

Congenital fusion of jaw and its association with ankyloblepharon filiforme adnatum is reported but is a quite rare congenital benign anomaly. It may be unilateral or bilateral and can present with a single system or multiple systems involvement. This report concentrates on describing the clinical features of above disease, likely aetiological causes, and embryogenesis with classification, diagnostic, and, treatment modality, anesthesia problems and review of literature.     

Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase

A small population of plasmacytoid DCs (pDCs) in mouse tumor-draining LNs can express the immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO). We show that these IDO+ pDCs directly activate resting CD4+CD25+Foxp3+ Tregs for potent suppressor activity. In vivo, Tregs isolated from tumor-draining LNs were constitutively activated and suppressed antigen-specific T cells immediately ex vivo. In vitro, IDO+ pDCs from tumor-draining LNs rapidly activated resting Tregs from non-tumor-bearing hosts without the need for mitogen or exogenous anti-CD3 crosslinking. Treg activation by IDO+ pDCs was MHC restricted, required an intact amino acid-responsive GCN2 pathway in the Tregs, and was prevented by CTLA4 blockade. Tregs activated by IDO markedly upregulated programmed cell death 1 ligand 1 (PD-L1) and PD-L2 expression on target DCs, and the ability of Tregs to suppress target T cell proliferation was abrogated by antibodies against the programmed cell death 1/PD-L (PD-1/PD-L) pathway. In contrast, Tregs activated by anti-CD3 crosslinking did not cause upregulation of PD-Ls, and suppression by these cells was unaffected by blocking the PD-1/PD-L pathway. Tregs isolated from tumor-draining LNs in vivo showed potent PD-1/PD-L-mediated suppression, which was selectively lost when tumors were grown in IDO-deficient hosts. We hypothesize that IDO+ pDCs create a profoundly suppressive microenvironment within tumor-draining LNs via constitutive activation of Tregs.     

Rapid stimulation of presynaptic serotonin transport by A(3) adenosine receptors

The inactivation of synaptic serotonin (5-hydroxytryptamine, 5-HT) is largely established through the actions of the presynaptic, antidepressant-sensitive 5-HT transporter (SERT, SLC6A4). Recent studies have demonstrated post-translational regulation of SERT mediated by multiple Ser/Thr kinases, including protein kinases C and G (PKC and PKG) and p38 mitogen-activated protein kinase (MAPK), as well as the Ser/Thr phosphatase PP2A. Less well studied are specific surface receptors that target these signaling pathways to control SERT surface expression and/or catalytic rates. Using rat basophilic leukemia 2H3 cell line (RBL-2H3), we previously established that activation of A(3) adenosine receptors (A(3)AR) stimulates SERT activity via both PKG and p38 MAPK (Zhu et al., 2004a). Whether A(3)ARs regulate SERT in the central nervous system (CNS) is unknown. Here we report that the A(3)AR agonist N(6)-(3-iodobenzyl)-N-methyl-5'carbamoyladenosine (IB-MECA) rapidly (10 min) and selectively stimulates 5-HT transport in mouse midbrain, hippocampal, and cortical synaptosomes. IB-MECA-induced stimulation of 5-HT uptake is blocked by the selective A(3)AR antagonist 3-ethyl-5-benzyl-2-methyl-phenylethynyl-6-phenyl-1,4(+/-)dihydropyridine-3,5-dicarboxylate (MRS1191) and is absent from synaptosomes prepared from A(3)AR knockout mice. Kinetic analyses demonstrate that IB-MECA induces an increase of 5-HT transport V(max) with no significant change in K(m). As in RBL-2H3 cells, IB-MECA stimulation of synaptosomal 5-HT uptake can be blocked by preincubation with PKG antagonists N-[2-(methylamino)ethy]-5-isoquinoline-sulfonamide (H8) and DT-2 (YGRKKRRQRRRPPLRK(5)H), as well as by the p38 MAPK inhibitor SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole]. Chronoamperometry studies in the anesthetized rat hippocampus support a role for A(3)ARs in SERT regulation in vivo. Together, these results identify a novel, region-specific action of CNS A(3)ARs in the modulation of SERT-mediated 5-HT transport that may be relevant for the etiology and/or therapy of 5-HT-linked brain disorders.     

Effect of specialized bathing systems on resident cleanliness and water quality in nursing homes: a randomized controlled trial

A randomized controlled trial evaluated the impact of different methods of water agitation on clinical and microbiological outcomes in 31 nursing home residents. Four conditions were tested: a) whirlpool tub, jets on, using standard soap products; b) ultrasound tub, ultrasound on, using the standard soap products; c) ultrasound tub, ultrasound on, using specialized soap and skin conditioner; and d) either tub (randomized), water circulation off, using standard soap products (the control condition). Outcomes of interest included skin microbial flora, water microbial flora, skin condition, time spent bathing, and staff satisfaction. Resident skin condition and skin microbial flora did not differ between the four treatments. The tubs also did not differ in terms of bacterial colonization; however, there was a non-statistically significant trend for the highest counts to occur in whirlpool tubs after being idle overnight. The ultrasound and whirlpool tubs were preferred by staff over the control treatment (still water) in terms of sound and overall suitability. In addition, staff reported that the ultrasound tub using enhanced skin cleansers made bathing residents easier and faster than the same tub using standard cleansers.     

Survival and Prognosis of Chondrosarcoma Subtypes: SEER Database Analysis

Chondrosarcomas are rare tumors and, historically, investigation of these tumors has been limited to small series and single-institution studies. There have been no studies that evaluated the identification or comparison of differences in prognostic factors between the five known non-conventional chondrosarcoma subtypes (myxoid, juxtacortical, clear-cell, mesenchymal, and dedifferentiated). The purpose of this paper was to determine the demographic, clinical, incidence, and tumor characteristics of all five known non-conventional chondrosarcoma subtypes, determine the 1-, 5-year, and median survival differences between these subtypes, and to determine the demographic and clinical variables that are significant prognostic indicators for each chondrosarcoma subtypes. We retrospectively reviewed the SEER database for all patients with non-conventional chondrosarcoma. χ² testing was used for correlations between clinical variables. Kaplan–Meier and Cox proportional hazard analysis were used to compare survival of the subtypes, and to assess the prognostic value of age group, race, sex, grade, anatomic location, and metastatic involvement. Several demographic characteristics including gender, race, age, and grade varied between chondrosarcoma subtypes. The tumor characteristics showed marked differences in presence of metastasis on presentation between the subtypes with increasing order of rate of metastasis with juxtacortical (2.1%), clear cell (5.7%), myxoid (7.6%), mesenchymal (10.6%), and the highest in dedifferentiated (19.8%). One-, 5-year, and median survival differed significantly between chondrosarcomas subtypes. The highest median survival was found in the juxtacortical subtype (97 months), followed by clear cell (79 months), myxoid (60 months), mesenchymal (33.5 months), and lowest in dedifferentiated (11 months). The only prognostic variable that was shown to significantly impact the survival of each non-conventional chondrosarcoma subtype was a metastatic disease at diagnosis (p = 0.03 to p < 0.001). Subtyping classification of chondrosarcoma should be made whenever possible, given differences in survival and prognostic factors between chondrosarcoma subtypes. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:311-319, 2020     

Opposing biological functions of tryptophan catabolizing enzymes during intracellular infection

Recent studies have underscored physiological and pathophysiological roles for the tryptophan-degrading enzyme indolamine 2,3-dioxygenase (IDO) in immune counterregulation. However, IDO was first recognized as an antimicrobial effector, restricting tryptophan availability to Toxoplasma gondii and other pathogens in vitro. The biological relevance of these findings came under question when infectious phenotypes were not forthcoming in IDO-deficient mice. The recent discovery of an IDO homolog, IDO-2, suggested that the issue deserved reexamination. IDO inhibition during murine toxoplasmosis led to 100% mortality, with increased parasite burdens and no evident effects on the immune response. Similar studies revealed a counterregulatory role for IDO during leishmaniasis (restraining effector immune responses and parasite clearance), and no evident role for IDO in herpes simplex virus type 1 (HSV-1) infection. Thus, IDO plays biologically important roles in the host response to diverse intracellular infections, but the dominant nature of this role--antimicrobial or immunoregulatory--is pathogen-specific.