ABSTRACT
Age-related episodic memory deficits imply that older and younger adults differentially retrieve and monitor contextual features that indicate the source of studied information. Such differences have been shown in subjective reports during recognition and cued recall as well as process estimates derived from computational models of free recall organisation. The present study extends the subject report method to free recall to characterise age differences in context retrieval and monitoring, and to test assumptions from a context-based computational model. Older and younger adults studied two lists of semantically related words and then recalled from only the first or second list. After each recall, participants indicated their subjective context retrieval using remember/know judgments. Compared to younger adults, older adults showed lower recall accuracy and subjective reports of context retrieval (i.e., remember judgments) that were less specific to correct recalls. These differences appeared after first-recall attempts. Recall functions conditioned on serial positions were more continual across correct recalls from target lists and intrusions from non-target lists for older than younger adults. Together with other analyses of context retrieval and monitoring reported here, these findings suggest that older adults retrieved context less distinctively across the recall period, leading to greater perceived similarity for temporally contiguous lists.
Subject(s)
Aging , Memory, Episodic , Humans , Aged , Mental Recall , Recognition, Psychology , CuesABSTRACT
The current study leveraged experimental and individual differences methodology to examine whether false memories across different list-learning tasks arise from a common cause. Participants completed multiple false memory (associative and conjunction lure), working memory (operation and reading span), and source monitoring (verbal and picture) tasks. Memory discriminability in the associative and conjunction tasks loaded onto a single (general) factor and were unaffected by warnings provided at encoding. Consistent with previous research, source-monitoring ability fully mediated the relation between working memory and false memories. Moreover, individuals with higher source monitoring-ability were better able to recall contextual information from encoding to correctly reject lures. These results suggest that there are stable individual differences in false remembering across tasks. The commonality across tasks may be due, at least in part, to the ability to effectively use disqualifying monitoring processes.
Subject(s)
Individuality , Recognition, Psychology , Humans , Memory, Short-Term , Mental RecallABSTRACT
Individual differences in working memory capacity (WMC) have long been known to relate to performance in domains outside of WM, including attentional control, long-term memory, problem-solving, and fluid intelligence to name a few. Complex span WM tasks, composed of a processing component and a storage component, are often used to index WMC in these types of investigations. Capacity estimates are derived from performance on the storage component only, while processing performance is often largely ignored. Here, we explore the relationship between processing performance and WMC in a large dataset for each of three complex span tasks to better characterize how the components of these tasks might be related. We provide evidence that enforcing an 85% or better accuracy criterion for the processing portion of the task results in the removal of a disproportionate number of individuals exhibiting lower WMC estimates. We also find broad support for differences in processing task performance, characterized according to both accuracy and reaction time metrics, as a function of WMC. We suggest that researchers may want to include processing task performance measures, in addition to capacity estimates, in studies using complex span tasks to index WMC. This approach may better characterize the relationships between complex span task performance and performance in disparate domains of cognition.
Subject(s)
Intelligence , Memory, Short-Term , Attention , Humans , Problem Solving , Reaction TimeABSTRACT
BACKGROUND: Fungal infections impact over 25% of the global population. For the opportunistic fungal pathogen, Cryptococcus neoformans, infection leads to cryptococcosis. In the presence of the host, disease is enabled by elaboration of sophisticated virulence determinants, including polysaccharide capsule, melanin, thermotolerance, and extracellular enzymes. Conversely, the host protects itself from fungal invasion by regulating and sequestering transition metals (e.g., iron, zinc, copper) important for microbial growth and survival. RESULTS: Here, we explore the intricate relationship between zinc availability and fungal virulence via mass spectrometry-based quantitative proteomics. We observe a core proteome along with a distinct zinc-regulated protein-level signature demonstrating a shift away from transport and ion binding under zinc-replete conditions towards transcription and metal acquisition under zinc-limited conditions. In addition, we revealed a novel connection among zinc availability, thermotolerance, as well as capsule and melanin production through the detection of a Wos2 ortholog in the secretome under replete conditions. CONCLUSIONS: Overall, we provide new biological insight into cellular remodeling at the protein level of C. neoformans under regulated zinc conditions and uncover a novel connection between zinc homeostasis and fungal virulence determinants.
Subject(s)
Cryptococcus neoformans/pathogenicity , Molecular Chaperones/metabolism , Proteome/metabolism , Secretome/metabolism , Zinc/metabolism , Cryptococcus neoformans/metabolism , Fungal Capsules/metabolism , Fungal Proteins/genetics , Fungal Proteins/metabolism , Melanins/metabolism , Molecular Chaperones/genetics , Mutation , Proteomics , Thermotolerance , Virulence/geneticsABSTRACT
Although false memories have largely been examined with the Deese-Roediger-McDermott (DRM) paradigm, little research has focused on the semantic context in which associates are encoded. Across three experiments, we varied semantic context during a sentence-processing task with DRM associates embedded within sentences. More meaningful sentences resulted in greater memory errors (Experiment 1). Furthermore, providing contextual information to discriminate old from new items did not reduce false alarms relative to encoding words in isolation when sentences converged on the meaning of the critical lure (Experiment 2), and actually increased memory errors (Experiment 3). These results suggest that semantic context that allows for meaningful relational processing of items within-lists and that converge on the semantic meaning of the critical lure increases the likelihood that the list theme is identified, resulting in more errors at test.
Subject(s)
Mental Recall , Semantics , Humans , Memory , Probability , Repression, PsychologyABSTRACT
The key event in placentitis-induced preterm labor is myometrial activation with the subsequent initiation of labor. However, the molecular mechanisms underlying myometrial activation are not fully understood in the mares. Therefore, the equine myometrial transcriptome was characterized during placentitis (290.0 ± 1.52 days of GA, n = 5) and the prepartum period (330 days of GA, n = 3) in comparison to normal pregnant mares (289.8 ± 2.18 days of GA, n = 4). Transcriptome analysis identified 596 and 290 DEGs in the myometrium during placentitis and the prepartum period, respectively, with 138 DEGs in common. The placentitis DEGs included eight genes (MMP1, MMP8, S100A9, S100A8, PI3, APOBEC3Z1B, RETN, and CXCL2) that are exclusively expressed in the inflamed myometrium. Pathway analysis elucidated that inflammatory signaling, Toll-like receptor signaling, and apoptosis pathways dominate myometrial activation during placentitis. The prepartum myometrium was associated with overexpression of inflammatory signaling, oxidative stress, and 5-hydroxytryptamine degradation. Gene ontology enrichment analysis identified several chemoattractant factors in the myometrium during placentitis and prepartum period, including CCL2, CXCL1, CXCL3, and CXCL6 in common. Upstream regulator analysis revealed 19 potential upstream regulators in placentitis dataset including transcription regulators (E2F1, FOXM1, HIF1A, JUNB, NFKB1A, and STAT1), transmembrane receptors (FAS, ICAM1, SELP, TLR2, and TYROBP), growth factors (HGF and TGFB3), enzymes (PTGS2 and PRKCP), and others (S100A8, S100A9, CD44, and C5AR1). Additionally, three upstream regulators (STAT3, EGR1, and F2R) were identified in the prepartum dataset. These findings revealed the key regulators and pathways underlying myometrial activation during placentitis, which aid in understanding the disease and facilitate the development of efficacious therapies.
Subject(s)
Horse Diseases/metabolism , Myometrium/metabolism , Placenta Diseases/veterinary , Transcriptome , Animals , Female , Genomics , Horses , Immunoblotting , Immunohistochemistry , Placenta Diseases/metabolism , PregnancyABSTRACT
Steroid production varies widely among species, with these differences becoming more pronounced during pregnancy. As a result, each species has its own distinct pattern of steroids, steroidogenic enzymes, receptors, and transporters to support its individual physiological requirements. Although the circulating steroid profile is well characterized during equine pregnancy, there is much yet to be explored regarding the factors that support steroidogenesis and steroid signaling. To obtain a holistic view of steroid-related transcripts, we sequenced chorioallantois (45 days, 4 months, 6 months, 10 months, 11 months, and post-partum) and endometrium (4 months, 6 months, 10 months, 11 months, and diestrus) throughout gestation, then looked in-depth at transcripts related to steroid synthesis, conjugation, transportation, and signaling. Key findings include: 1) differential expression of HSD17B isoforms among tissues (HSD17B1 high in the chorioallantois, while HSD17B2 is the dominant form in the endometrium) 2) a novel isoform with homology to SULT1A1 is the predominant sulfotransferase transcript in the chorioallantois; and 3) nuclear estrogen (ESR1, ESR2) and progesterone (PGR) expression is minimal to nonexistant in the chorioallantois and pregnant endometrium. Additionally, several hypotheses have been formed, including the possibility that the 45-day chorioallantois is able to synthesize steroids de novo from acetate and that horses utilize glucuronidation to clear estrogens from the endometrium during estrous, but not during pregnancy. In summary, these findings represent an in-depth look at equine steroid-related transcripts through gestation, providing novel hypotheses and future directions for equine endocrine research.
Subject(s)
Chorion/metabolism , Endometrium/metabolism , Gene Expression Regulation, Developmental , Placenta/metabolism , Steroids/biosynthesis , Transcriptome , Animals , Chorion/cytology , Endometrium/cytology , Female , High-Throughput Nucleotide Sequencing , Horses , Oxidoreductases/genetics , Placenta/cytology , Pregnancy , Signal Transduction , Steroid Hydroxylases/geneticsABSTRACT
Equine placentitis is associated with alterations in maternal peripheral steroid concentrations, which could negatively affect pregnancy outcome. This study aimed to elucidate the molecular mechanisms related to steroidogenesis and steroid-receptor signaling in the equine placenta during acute placentitis. Chorioallantois (CA) and endometrial (EN) samples were collected from mares with experimentally induced placentitis (n = 4) and un-inoculated gestationally age-matched mares (control group; n = 4). The mRNA expression of genes coding for steroidogenic enzymes (3ßHSD, CYP11A1, CYP17A1, CYP19A1, SRD5A1, and AKR1C23) was evaluated using qRT-PCR. The concentration of these enzyme-dependent steroids (P5, P4, 5αDHP, 3αDHP, 20αDHP, 3ß-20αDHP, 17OH-P, DHEA, A4, and estrone) was assessed using liquid chromatography-tandem mass spectrometry in both maternal circulation and placental tissue. Both SRD5A1 and AKR1C23, which encode for the key progesterone metabolizing enzymes, were downregulated (P < 0.05) in CA from the placentitis group compared to controls, and this downregulation was associated with a decline in tissue concentrations of 5αDHP (P < 0.05), 3αDHP (P < 0.05), and 3ß-20αDHP (P = 0.052). In the EN, AKR1C23 was also downregulated in the placentitis group compared to controls, and this downregulation was associated with a decline in EN concentrations of 3αDHP (P < 0.01) and 20αDHP (P < 0.05). Moreover, CA expression of CYP19A1 tended to be lower in the placentitis group, and this reduction was associated with lower (P = 0.057) concentrations of estrone in CA. Moreover, ESR1 (steroid receptors) gene expression was downregulated (P = 0.057) in CA from placentitis mares. In conclusion, acute equine placentitis is associated with a local withdrawal of progestins in the placenta and tended to be accompanied with estrogen withdrawals in CA.
Subject(s)
Chorioamnionitis/veterinary , Estradiol Congeners/biosynthesis , Horses/metabolism , Placenta/enzymology , Progesterone/biosynthesis , Animals , Chorioamnionitis/enzymology , Chorioamnionitis/pathology , Female , Placenta/pathology , PregnancyABSTRACT
Monitoring the environment for the occurrence of prospective memory (PM) targets is a resource-demanding process that produces cost (e.g., slowing) to ongoing activities. Prior research has shown that older adults are able to monitor strategically, which involves the activation of monitoring when contextually appropriate and deactivation of monitoring when it is not thereby affording conservation of limited-capacity attentional resources. However, the time course and efficiency with which these processes operate with increased age are unknown. In the current study, participants performed an ongoing lexical decision task in which words/nonwords were blocked by font color in sets of ten trials (ten red trials followed by ten blue trials). Importantly, participants were informed that PM targets ("TOR" syllable) would only occur in red trials. Replicating previous work, both younger and older adults were successfully able to disengage monitoring upon encountering the unexpected (i.e., blue) context. However, while younger adults completely disengaged monitoring in the unexpected context, older adults continued to show monitoring across the majority of trials. Additionally, younger, but not older, adults showed a re-engagement of monitoring at the end of the unexpected context in preparation for the upcoming expected context. These findings suggest that while strategic monitoring generally remains intact with increased age, the disengagement and preparatory re-engagement of strategic monitoring may operate less optimally for older adults.
Subject(s)
Aging/physiology , Attention/physiology , Executive Function/physiology , Memory, Episodic , Psychomotor Performance/physiology , Adolescent , Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Young AdultABSTRACT
Output monitoring refers to memory for one's previously completed actions. In the context of prospective memory (PM) (e.g., remembering to take medication), failures of output monitoring can result in repetitions and omissions of planned actions (e.g., over- or under-medication). To be successful in output monitoring paradigms, participants must flexibly control attention to detect PM cues as well as engage controlled retrieval of previous actions whenever a particular cue is encountered. The current study examined individual differences in output monitoring abilities in a group of younger adults differing in attention control (AC) and episodic memory (EM) abilities. The results showed that AC ability uniquely predicted successful cue detection on the first presentation, whereas EM ability uniquely predicted successful output monitoring on the second presentation. The current study highlights the importance of examining external correlates of PM abilities and contributes to the growing body of research on individual differences in PM.
Subject(s)
Attention/physiology , Cues , Individuality , Memory, Episodic , Adolescent , Adult , Cognition/physiology , Female , Humans , Male , Mental Recall/physiology , Neuropsychological Tests , Recognition, Psychology/physiology , Repetition Priming/physiology , Young AdultABSTRACT
The cervical mucus plug (CMP) is believed to play an integral role in the maintenance of pregnancy in the mare, primarily by inhibiting microbial entry. Unfortunately, very little is known about its composition or origin. To determine the proteomic composition of the CMP, we collected CMPs from mares (n = 4) at 9 months of gestation, and proteins were subsequently analyzed by nano-LC-MS/MS. Results were searched against EquCab2.0, and proteomic pathways were predicted by Ingenuity Pathway Analysis. Histologic sections of the CMP were stained with H&E and PAS. To identify the origin of highly abundant proteins in the CMP, we performed qPCR on endometrial and cervical mucosal mRNA from mares in estrus, diestrus as well as mares at 4 and 10 m gestation on transcripts for lactotransferrin, uterine serpin 14, uteroglobin, uteroferrin, deleted in malignant brain tumors 1 and mucins 4, 5b and 6. Overall, we demonstrated that the CMP is composed of a complex milieu of proteins during late gestation, many of which play an important role in immune function. Proteins traditionally considered to be endometrial proteins were found to be produced by the cervical mucosa suggesting that the primary source of the CMP is the cervical mucosa itself. In summary, composition of the equine CMP is specifically regulated not only during pregnancy but also throughout the estrous cycle. The structural and compositional changes serve to provide both a structural barrier as well as a physiological barrier during pregnancy to prevent infection of the fetus and fetal membranes.
Subject(s)
Cervix Mucus/chemistry , Horses/physiology , Animals , Cervix Mucus/physiology , Coloring Agents , Estrous Cycle/metabolism , Female , Gestational Age , Lactoferrin/genetics , Mucins/genetics , Pregnancy , Proteins/analysis , Proteins/immunology , Proteomics , RNA, Messenger/analysis , Real-Time Polymerase Chain Reaction/veterinary , Serpins/genetics , Tartrate-Resistant Acid Phosphatase/genetics , Uteroglobin/genetics , Uterus/chemistryABSTRACT
OBJECTIVES: To evaluate the use of dual-energy CT imaging of the lung perfused blood volume (PBV) for the detection of pulmonary fat embolism (PFE). METHODS: Dual-energy CT was performed in 24 rabbits before and 1 hour, 1 day, 4 days and 7 days after artificial induction of PFE via the right ear vein. CT pulmonary angiography (CTPA) and lung PBV images were evaluated by two radiologists, who recorded the presence, number, and location of PFE on a per-lobe basis. Sensitivity, specificity, and accuracy of CTPA and lung PBV for detecting PFE were calculated using histopathological evaluation as the reference standard. RESULTS: A total of 144 lung lobes in 24 rabbits were evaluated and 70 fat emboli were detected on histopathological analysis. The overall sensitivity, specificity and accuracy were 25.4 %, 98.6 %, and 62.5 % for CTPA, and 82.6 %, 76.0 %, and 79.2 % for lung PBV. Higher sensitivity (p < 0.001) and accuracy (p < 0.01), but lower specificity (p < 0.001), were found for lung PBV compared with CTPA. Dual-energy CT can detect PFE earlier than CTPA (all p < 0.01). CONCLUSION: Dual-energy CT provided higher sensitivity and accuracy in the detection of PFE as well as earlier detection compared with conventional CTPA in this animal model study. KEY POINTS: ⢠Fat embolism occurs commonly in patients with traumatic bone injury. ⢠Dual-energy CT improves diagnostic performance for pulmonary fat embolism detection. ⢠Dual-energy CT can detect pulmonary fat embolism earlier than CTPA.
Subject(s)
Embolism, Fat/diagnostic imaging , Pulmonary Embolism/diagnostic imaging , Tomography, X-Ray Computed/methods , Angiography/methods , Animals , Disease Models, Animal , Humans , Pulmonary Artery/diagnostic imaging , Rabbits , Radiography, Dual-Energy Scanned Projection/methods , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
OBJECTIVES: The aim of this study was to investigate the minimum iodine delivery rate (IDR) and contrast media (CM) volume required for diagnostic contrast enhancement of 350 HU (Hounsfield units) in the ascending aorta at different kV settings. METHODS: Dynamic computed tomography acquisitions from 70 to 150 kV were performed in a circulation phantom. First, injections with IDR ranging from 0.1 to 2.0 g I/s were tested for each kV. In the second part, the IDR was held constant, whereas the CM volume was reduced from 50 to 10 mL. Diagnostic aortic peak enhancement for each kV was compared using the Kruskal-Wallis test. P < 0.05 was considered statistically significant. RESULTS: The mean aortic peak enhancement for all diagnostic IDRs was 368.7 ± 11.1 HU. Diagnostic IDRs returned similar aortic peak enhancement values for all protocols (all P ≥ 0.18). For the second part of the study, a diagnostic enhancement was yielded by using a minimum of 30 mL of CM for 110 kV, 25 mL for 100 and 90 kV, and 15 mL for 80 and 70 kV. CONCLUSION: Our study suggests that a differentiated approach reducing the CM volume for tube voltages of less than 120 kV and increasing the IDR for higher kV settings seems to be the most effective approach.
Subject(s)
Computed Tomography Angiography/methods , Contrast Media/administration & dosage , Iohexol/analogs & derivatives , Phantoms, Imaging , Radiographic Image Enhancement/methods , Iohexol/administration & dosageABSTRACT
Participants use simple contextual cues to reduce deployment of costly monitoring processes in contexts in which prospective memory (PM) targets are not expected. This study investigated whether this strategic monitoring pattern is observed in response to complex and probabilistic contextual cues. Participants performed a lexical decision task in which words or nonwords were presented in upper or lower locations on screen. The specific condition was informed that PM targets ("tor" syllable) would occur only in words in the upper location, whereas the nonspecific condition was informed that targets could occur in any location or word type. Context was blocked such that word type and location changed every 8 trials. In Experiment 1, the specific condition used the complex contextual cue to reduce monitoring in unexpected contexts relative to the nonspecific condition. This pattern largely was not evidenced when the complex contextual cue was probabilistic (Experiment 2). Experiment 3 confirmed that strategic monitoring is observed for a complex cue that is deterministic, but not one that is probabilistic. Additionally, Experiments 1 and 3 demonstrated a disadvantage associated with strategic monitoring-namely, that the specific condition was less likely to respond to a PM target in an unexpected context. Experiment 3 provided evidence that this disadvantage is attributable to impaired noticing of the target. The novel findings suggest use of a complex contextual cue per se is not a boundary condition for the strategic, context-specific allocation of monitoring processes to support prospective remembering; however, strategic monitoring is constrained by the predictive utility of the complex contextual cue.
Subject(s)
Attention/physiology , Cues , Executive Function/physiology , Memory, Episodic , Pattern Recognition, Visual/physiology , Space Perception/physiology , Adolescent , Adult , Female , Humans , Male , Young AdultABSTRACT
In the horse, breeding induces a transient endometrial inflammation. A subset of mares are unable to resolve this inflammation, and they are considered susceptible to persistent mating-induced endometritis PMIE Select seminal plasma proteins cysteine-rich secretory protein-3 (CRISP-3) and lactoferrin have been shown to affect the innate immune response to sperm in vitro. The objective of this study was to determine whether the addition of CRISP-3 and lactoferrin at the time of insemination had an effect on the mRNA expression of endometrial cytokines in susceptible mares after breeding. Six mares classified as susceptible to PMIE were inseminated during four consecutive oestrous cycles with treatments in randomized order of: 1 mg/ml CRISP-3, 150 µg/ml lactoferrin, seminal plasma (positive control) or lactated Ringer's solution (LRS; negative control) to a total volume of 10 ml combined with 1 × 109 spermatozoa pooled from two stallions. Six hours after treatment, an endometrial biopsy was obtained for qPCR analysis of selected genes associated with inflammation (pro-inflammatory cytokines interleukin (IL)-1ß, IL-8, tumour necrosis factor (TNF)-α, interferon (INF)-γ, anti-inflammatory cytokines IL-1RN and IL-10, and inflammatory-modulating cytokine IL-6). Seminal plasma treatment increased the mRNA expression of IL-1ß (p = .019) and IL-8 (p = .0068), while suppressing the mRNA expression of TNF (p = .0013). Lactoferrin also suppressed the mRNA expression of TNF (p = .0013). In conclusion, exogenous lactoferrin may be considered as one modulator of the complex series of events resulting in the poorly regulated pro-inflammatory response seen in susceptible mares.
Subject(s)
Cytokines/metabolism , Endometritis/veterinary , Horse Diseases/pathology , Horses/genetics , Lactoferrin/genetics , Seminal Plasma Proteins/genetics , Animals , Breeding , Cytokines/genetics , Endometritis/pathology , Endometrium/pathology , Estrous Cycle/immunology , Female , Insemination, Artificial/veterinary , Male , RNA, Messenger/genetics , Random Allocation , Semen/metabolismABSTRACT
OBJECTIVE: To evaluate the correlation between aortic root calcification (ARC) markers and coronary artery calcification (CAC) derived from coronary artery calcium scoring (CACS) and their ability to predict obstructive coronary artery disease (CAD). METHODS: We retrospectively analyzed 189 patients (47% male, age 60.3 ± 11.1 years) with an intermediate probability of CAD who underwent clinically indicated CACS and coronary CT angiography (CCTA). ARC markers [aortic root calcium score (ARCS) and volume (ARCV)] were calculated and compared to CAC markers: coronary artery calcium score (CACS), volume (CACV), and mass (CACM). CCTA datasets were visually evaluated for significant CAD (stenosis ≥ 50%) and the ability of ARC markers to predict obstructive CAD was assessed. RESULTS: ARCS (mean 67.7 ± 189.5) and ARCV (mean 67.3 ± 184.7) showed significant differences between patients with and without CAC (109.4 ± 238.6 vs 9.42 ± 31.4, p < 0.0001; 108.5 ± 232.4 vs 9.9 ± 30.5, p < 0.0001). A strong correlation was found for ARCS and ARCV with CACS, CACM, and CACV (all p < 0.0001). In a multivariate analysis, ARCS (OR 1.09, p = 0.033) and ARCV (OR 1.12, p = 0.046) were independent markers for CAC. Using a receiver-operating characteristics analysis, the AUC to detect severe CAC was 0.71 (p < 0.0001) and 0.71 (p < 0.0001) for ARCS and ARCV, respectively. ARCS (0.67, p < 0.0001) and ARCV (0.68, p < 0.0001) showed discriminatory power for predicting obstructive CAD, yielding sensitivities 61 and 78% and specificities of 62 and 80%, respectively. CONCLUSION: ARC markers are associated with and independently predict the presence of CAC and obstructive CAD. Further testing is required in patients with severe ARC and significant CAD in order to reliably obtain these markers from thoracic-CT or X-ray for proper risk classification.
Subject(s)
Aortic Valve Stenosis/diagnostic imaging , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Coronary Stenosis/diagnostic imaging , Tomography, X-Ray Computed , Vascular Calcification/diagnostic imaging , Aged , Aortic Valve Stenosis/complications , Body Mass Index , Coronary Angiography/methods , Coronary Artery Disease/complications , Coronary Stenosis/complications , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Sensitivity and Specificity , Severity of Illness Index , Tomography, X-Ray Computed/methods , Vascular Calcification/complicationsABSTRACT
Mammalian pregnancies need progestogenic support and birth requires progestin withdrawal. The absence of progesterone in pregnant mares, and the progestogenic bioactivity of 5α-dihydroprogesterone (DHP), led us to reexamine progestin withdrawal at foaling. Systemic pregnane concentrations (DHP, allopregnanolone, pregnenolone, 5α-pregnane-3ß, 20α-diol (3ß,20αDHP), 20α-hydroxy-5α-dihydroprogesterone (20αDHP)) and progesterone) were monitored in mares for 10days before foaling (n=7) by liquid chromatography-mass spectrometry. The biopotency of dominant metabolites was assessed using luciferase reporter assays. Stable transfected Chinese hamster ovarian cells expressing the equine progesterone receptor (ePGR) were transfected with an MMTV-luciferase expression plasmid responsive to steroid agonists. Cells were incubated with increasing concentrations (0-100nM) of progesterone, 20αDHP and 3α,20ßDHP. The concentrations of circulating pregnanes in periparturient mares were (highest to lowest) 3α,20ßDHP and 20αDHP (800-400ng/mL respectively), DHP and allopregnanolone (90 and 30ng/mL respectively), and pregnenolone and progesterone (4-2ng/mL). Concentrations of all measured pregnanes declined on average by 50% from prepartum peaks to the day before foaling. Maximum activation of the ePGR by progesterone occurred at 30nM; 20αDHP and 3α,20ßDHP were significantly less biopotent. At prepartum concentrations, both 20αDHP and 3α,20ßDHP exhibited significant ePGR activation. Progestogenic support of pregnancy declines from 3 to 5days before foaling. Prepartum peak concentrations indicate that DHP is the major progestin, but other pregnanes like 20αDHP are present in sufficient concentrations to play a physiological role in the absence of DHP. The authors conclude that progestin withdrawal associated with parturition in mares involves cessation of pregnane synthesis by the placenta.
Subject(s)
Parturition/physiology , Pregnenolone/metabolism , Progesterone/metabolism , Progestins/deficiency , Animals , Female , Horses , Humans , Pregnancy , Withholding TreatmentABSTRACT
The traditional assessment of stallion sperm comprises evaluation of sperm motility and membrane integrity and identification of abnormal morphology of the spermatozoa. More recently, the progressive introduction of flow cytometry is increasing the number of tests available. However, compared with other sperm structures and functions, the evaluation of mitochondria has received less attention in stallion andrology. Recent research indicates that sperm mitochondria are key structures in sperm function suffering major changes during biotechnological procedures such as cryopreservation. In this paper, mitochondrial structure and function will be reviewed in the stallion, when possible specific stallion studies will be discussed, and general findings on mammalian mitochondrial function will be argued when relevant. Especial emphasis will be put on their role as source of reactive oxygen species and in their role regulating sperm lifespan, a possible target to investigate with the aim to improve the quality of frozen-thawed stallion sperm. Later on, the impact of current sperm technologies, principally cryopreservation, on mitochondrial function will be discussed pointing out novel areas of research interest with high potential to improve current sperm technologies.
Subject(s)
Horses , Mitochondria/physiology , Reproductive Techniques/veterinary , Spermatozoa/ultrastructure , Animals , Apoptosis , Cell Separation , Cell Survival , Cryopreservation/veterinary , Fertilization , Male , Mitochondria/ultrastructure , Osmolar Concentration , Oxidative Stress , Reactive Oxygen Species , Semen Preservation/adverse effects , Semen Preservation/methods , Semen Preservation/veterinary , Sex Preselection/methods , Spermatozoa/physiologyABSTRACT
BACKGROUND: The science of dental materials and restorative care in children and adolescent is constantly evolving, and the ongoing search for ideal restorative materials has led to plethora of research. AIM: To provide an evidence base to assist dental practitioners choose appropriate restorative care for children and adolescents. STUDY DESIGN: This evidence-based review appraises this literature, primarily between the years 1995-2013, for efficacy of dental amalgam, composites, glass ionomer cements, compomers, preformed metal crowns and anterior esthetic restorations. The assessment of evidence for each dental material was based on a strong evidence, evidence in favor, expert opinion, and evidence against by consensus of the authors. RESULTS: There is varying level of evidence for the use of restorative materials like amalgam, composites, glass ionomers, resin-modified glass-ionomers, compomers, stainless steel crowns and anterior crowns for both primary and permanent teeth. CONCLUSIONS: A substantial amount data is available on restorative materials used in pediatric dentistry; however, there exists substantial evidence from systematic reviews and randomized clinical trials and clinicians need to examine and understand the available literature evidence carefully to aid them in clinical decision making.