In vivo microstructural heterogeneity of white matter and cognitive correlates in aging using tissue compositional analysis of diffusion magnetic resonance imaging.

BACKGROUND: Age-related cognitive decline is linked to changes in the brain, particularly the deterioration of white matter (WM) microstructure that accelerates after the age of 60. WM deterioration is associated with mild cognitive impairment and dementia, but the origin and role of white matter signal abnormalities (WMSA) seen in standard MRI remain debated due to their heterogeneity. This study explores the potential of single-shell 3-tissue constrained spherical deconvolution (SS3T-CSD), a novel technique that models diffusion data in terms of gray matter (TG ), white matter (Tw ), and cerebrospinal fluid (TC ), to differentiate WMSA from normal-appearing white matter and better understand the interplay between changes in WM microstructure and decline in cognition. METHODS: A total of 189 individuals from the GENIC cohort were included. MRI data, including T1-weighted and diffusion images, were obtained. Preprocessing steps were performed on the diffusion MRI data, followed by the SS3T-CSD. WMSA were segmented using FreeSurfer. Statistical analyses were conducted to assess the association between age, WMSA volume, 3-tissue signal fractions (Tw , TG , and TC ), and neuropsychological variables. RESULTS: Participants above 60 years old showed worse cognitive performance and processing speed compared to those below 60 (p < .001). Age was negatively associated with Tw in normal-appearing white matter (p < .001) and positively associated with TG in both WMSA (p < .01) and normal-appearing white matter (p < .001). Age was also significantly associated with WMSA volume (p < .001). Higher processing speed was associated with lower Tw and higher TG , in normal-appearing white matter (p < .01 and p < .001, respectively), as well as increased WMSA volume (p < .001). Similarly, lower MMSE scores correlated with lower Tw and higher TG in normal-appearing white matter (p < .05). High cholesterol and hypertension were associated with higher WMSA volume (p < .05). CONCLUSION: The microstructural heterogeneity within normal-appearing white matter and WMSA is associated with increasing age and cognitive variation, in cognitively unimpaired individuals. Furthermore, the 3-tissue signal fractions are more specific to potential white matter alterations than conventional MRI measures such as WMSA volume. These findings also support the view that the WMSA volumes may be more influenced by vascular risk factors than the 3-tissue metrics. Finally, the 3-tissue metrics were able to capture associations with cognitive tests and therefore capable of capturing subtle pathological changes in the brain in individuals who are still within the normal range of cognitive performance.

Improving the ferroelectric properties of Lu doped Hf0.5Zr0.5O2thin films by capping a CeOxlayer.

Lu doped Hf0.5Zr0.5O2(HZO) ferroelectric films were prepared on Pt/TiN/SiO2/Si substrate by chemical solution deposition method, and an interfacial engineering strategy for improving the ferroelectric property was explored by capping the Lu doped HZO films with a cerium oxide layer. Compared with the Lu doped HZO film without the CeOxcoating layer, the Lu doped HZO film with the CeOxcoating layer has a larger remanent polarization (2Pr= 34.72µC cm-2) and presents weaker wake-up behavior, which result from the higher orthogonal phase ratio and the lower oxygen vacancy of the CeOxcoated Lu doped HZO film. In addition, the CeOxcoating can remarkably improve the fatigue resistance and retention performance of the Lu doped HZO films. It is hoped that the results can provide an effective approach for the realization of high-performance and highly reliable hafnium oxide based ferroelectric thin films.

Post-COVID reactivation of latent Bartonella henselae infection: a case report and literature review.

Cat scratch disease (CSD) is caused by Bartonella henselae (B. henselae) and presents as lymphadenopathy following close contact with cats. However, in context of the global COVID-19 pandemic, clinical manifestations of CSD may vary, posing new challenges for healthcare professionals. Here we describe a case of a 54-year-old male with painful left upper arm mass, which gradually resolved until he was infected with COVID-19. The mass then rapidly progressed before admission. Meanwhile, pulmonary symptoms including pleural effusion emerged simultaneously. The cause was undetermined with routine blood culture and pathological test until the next generation sequencing (NGS) confirmed the presence of B. henselae. We believe this case is the first to report localized aggravation of CSD after COVID-19 infection and hopefully, offers treatment experience for clinicians worldwide.

Cortical origin of theta error signals.

A multi-scale approach elucidated the origin of the error-related-negativity (ERN), with its associated theta-rhythm, and the post-error-positivity (Pe) in macaque supplementary eye field (SEF). Using biophysical modeling, synaptic inputs to a subpopulation of layer-3 (L3) and layer-5 (L5) pyramidal cells (PCs) were optimized to reproduce error-related spiking modulation and inter-spike intervals. The intrinsic dynamics of dendrites in L5 but not L3 error PCs generate theta rhythmicity with random phases. Saccades synchronized the phases of the theta-rhythm, which was magnified on errors. Contributions from error PCs to the laminar current source density (CSD) observed in SEF were negligible and could not explain the observed association between error-related spiking modulation in L3 PCs and scalp-EEG. CSD from recorded laminar field potentials in SEF was comprised of multipolar components, with monopoles indicating strong electro-diffusion, dendritic/axonal electrotonic current leakage outside SEF, or violations of the model assumptions. Our results also demonstrate the involvement of secondary cortical regions, in addition to SEF, particularly for the later Pe component. The dipolar component from the observed CSD paralleled the ERN dynamics, while the quadrupolar component paralleled the Pe. These results provide the most advanced explanation to date of the cellular mechanisms generating the ERN.

Are anti-calcitonin gene-related peptide monoclonal antibodies effective in treating migraine aura? A pilot prospective observational cohort study.

BACKGROUND: About 15% to one third of migraineurs experience aura symptoms. Aura is a reversible focal neurological phenomenon involving visual, sensory, speech, and motor symptoms that usually precede migraine pain. Monoclonal antibodies against calcitonin-related peptide (anti- CGRP mAbs) are effective in preventing chronic and episodic migraine, but little is known about their effectiveness on specifically preventing migraine with aura. METHODS: This is a pilot prospective observational cohort study, aiming at evaluating the effectiveness and safety of Erenumab, Fremanezumab or Galcanezumab for the treatment of migraine aura. We enrolled 14 patients at the Headache Centre of University Federico II of Naples. Duration of follow-up was 12 months. We assessed mean monthly days with aura symptoms, with or without subsequent headache, as well as mean monthly days with headache and mean monthly MIDAS score, by reviewing standardized paper patient headache diaries every three months. RESULTS: A significant decrease in mean monthly aura days was observed throughout the observation period (median baseline: 13, interquartile range: 4-16; after 12 months: 1, interquartile range: 0-3, p < 0.001). We observed a statistically significant decrease in mean monthly headache days as well (median baseline 21, interquartile range: 16-30; after 12 months: 5, interquartile range: 4-7, p < 0.001). During the 12-month treatment period, none of the 14 patients reported mild or serious adverse events. CONCLUSION: Our findings suggest that anti-CGRP mAbs are highly effective in migraine with aura, both in reducing mean monthly aura days and mean monthly days with headache.

Hypersensitivity of Intrinsically Photosensitive Retinal Ganglion Cells in Migraine Induces Cortical Spreading Depression.

Migraine is a complex disorder characterized by episodes of moderate-to-severe, often unilateral headaches and generally accompanied by nausea, vomiting, and increased sensitivity to light (photophobia), sound (phonophobia), and smell (hyperosmia). Photophobia is considered the most bothersome symptom of migraine attacks. Although the underlying mechanism remains unclear, the intrinsically photosensitive retinal ganglion cells (ipRGCs) are considered to be involved in photophobia associated with migraine. In this study, we investigated the association between the sensitivity of ipRGCs and migraines and cortical spreading depression (CSD), which may trigger migraine attacks. The pupillary responses closely associated with the function of ipRGCs in patients with migraine who were irradiated with lights were evaluated. Blue (486 nm) light irradiation elicited a response from ipRGCs; however, red light (560 nm) had no such effect. Melanopsin, a photosensitive protein, phototransduces in ipRGCs following blue light stimulation. Hypersensitivity of ipRGCs was observed in patients with migraine. CSD was more easily induced with blue light than with incandescent light using a mouse CSD model. Moreover, CSD was suppressed, even in the presence of blue light, after injecting opsinamide, a melanopsin inhibitor. The hypersensitivity of ipRGCs in patients with migraine may induce CSD, resulting in migraine attacks.

The effect of P2X7 antagonism on subcortical spread of optogenetically-triggered cortical spreading depression and neuroinflammation.

Migraine is a neurological disorder characterized by episodes of severe headache. Cortical spreading depression (CSD), the electrophysiological equivalent of migraine aura, results in opening of pannexin 1 megachannels that release ATP and triggers parenchymal neuroinflammatory signaling cascade in the cortex. Migraine symptoms suggesting subcortical dysfunction bring subcortical spread of CSD under the light. Here, we investigated the role of purinergic P2X7 receptors on the subcortical spread of CSD and its consequent neuroinflammation using a potent and selective P2X7R antagonist, JNJ-47965567. P2X7R antagonism had no effect on the CSD threshold and characteristics but increased the latency to hypothalamic voltage deflection following CSD suggesting that ATP acts as a mediator in the subcortical spread. P2X7R antagonism also prevented cortical and subcortical neuronal activation following CSD, revealed by bilateral decrease in c-fos positive neuron count, and halted CSD-induced neuroinflammation revealed by decreased neuronal HMGB1 release and decreased nuclear translocation of NF-kappa B-p65 in astrocytes. In conclusion, our data suggest that P2X7R plays a role in CSD-induced neuroinflammation, subcortical spread of CSD and CSD-induced neuronal activation hence can be a potential target.

A physical neural mass model framework for the analysis of oscillatory generators from laminar electrophysiological recordings.

Cortical function emerges from the interactions of multi-scale networks that may be studied at a high level using neural mass models (NMM) that represent the mean activity of large numbers of neurons. Here, we provide first a new framework called laminar NMM, or LaNMM for short, where we combine conduction physics with NMMs to simulate electrophysiological measurements. Then, we employ this framework to infer the location of oscillatory generators from laminar-resolved data collected from the prefrontal cortex in the macaque monkey. We define a minimal model capable of generating coupled slow and fast oscillations, and we optimize LaNMM-specific parameters to fit multi-contact recordings. We rank the candidate models using an optimization function that evaluates the match between the functional connectivity (FC) of the model and data, where FC is defined by the covariance between bipolar voltage measurements at different cortical depths. The family of best solutions reproduces the FC of the observed electrophysiology by selecting locations of pyramidal cells and their synapses that result in the generation of fast activity at superficial layers and slow activity across most depths, in line with recent literature proposals. In closing, we discuss how this hybrid modeling framework can be more generally used to infer cortical circuitry.

Targeting CGRP pathways and aura: A peripheral site with a central effect.

Targeting CGRP-pathways has substantially expanded our options for treating individuals with migraine. Although the efficacy of these drugs on migraine aura is yet to be fully revealed, it seems from existing studies that CGRP antagonism reduces the number of migraine auras. The present perspective summarizes the evidence linking CGRP to the migraine aura and proposes a model by which targeting the CGRP-pathways and, thus, inhibition the interaction between C- and Aδ-trigeminal fibers might reverse a possible high cortical glutamate level leading to a reduced number of migraine auras.

Genome-wide DNA methylation analysis in an antimigraine-treated preclinical model of cortical spreading depolarization.

BACKGROUND: Cortical spreading depolarization, the cause of migraine aura, is a short-lasting depolarization wave that moves across the brain cortex, transiently suppressing neuronal activity. Prophylactic treatments for migraine, such as topiramate or valproate, reduce the number of cortical spreading depression events in rodents. OBJECTIVE: To investigate whether cortical spreading depolarization with and without chronic treatment with topiramate or valproate affect the DNA methylation of the cortex. METHODS: Sprague-Dawley rats were intraperitoneally injected with saline, topiramate or valproate for four weeks when cortical spreading depolarization were induced and genome-wide DNA methylation was performed in the cortex of six rats per group. RESULTS: The DNA methylation profile of the cortex was significantly modified after cortical spreading depolarization, with and without topiramate or valproate. Interestingly, topiramate reduced by almost 50% the number of differentially methylated regions, whereas valproate increased them by 17%, when comparing to the non-treated group after cortical spreading depolarization induction. The majority of the differentially methylated regions lay within intragenic regions, and the analyses of functional group over-representation retrieved several enriched functions, including functions related to protein processing in the cortical spreading depolarization without treatment group; functions related to metabolic processes in the cortical spreading depolarization with topiramate group; and functions related to synapse and ErbB, MAPK or retrograde endocannabinoid signaling in the cortical spreading depolarization with valproate group. CONCLUSIONS: Our results may provide insights into the underlying physiological mechanisms of migraine with aura and emphasize the role of epigenetics in migraine susceptibility.

Validity and reliability of the Dutch translation of the OPUS' client satisfaction with device module in chronic users of hand orthoses.

BACKGROUND: Orthosis satisfaction is an important outcome in assessing quality of care. However, no measurement specifically assessing orthosis satisfaction is available in the Dutch language. Therefore, the aim of this study was to translate the Client Satisfaction with Device (CSD) module of the Orthotics and Prosthetics Users' Survey (OPUS) into Dutch, and to assess its content validity, structural validity and reliability in persons with chronic hand conditions. METHODS: The CSD was translated and cross-cultural adapted according to respective guidelines. To determine content validity, 10 chronic hand orthotic users and two professionals judged the relevance, comprehensibility, and comprehensiveness of the Dutch CSD (D-CSD). Thereafter, in a cross-sectional study, 76 persons were asked to complete the D-CSD twice, with a 2-week interval. Dimensionality of the D-CSD was examined by principal component analysis (PCA), and factor model fit was assessed by confirmatory factor analysis (CFA). Reliability was assessed as internal consistency and test-retest reliability, including the 95% limits of agreement (LoA), the standard error of measurement (SEM) and smallest detectable change (SDC). RESULTS: The D-CSD items and response options were deemed relevant and comprehensible. After adding an item on cleaning the orthosis, content validity was judged sufficient. PCA indicated a one-factor model, which was confirmed by CFA. We found good internal consistency (Cronbach's alpha = 0.82; 95%CI 0.75-0.87), and moderate to good test-retest reliability (ICC = 0.81; 95%CI 0.71-0.87). There was no difference between the mean D-CSD score at test (26.8 points) and retest (25.9 points) (mean (SD) difference: 0.86 points (4.00); 95%CI -0.06-1.79; p = 0.07). The 95% LoA were -6.99 to 8.71, and the SEM and SDC were 2.88 and 7.98 points, respectively. CONCLUSIONS: Based on sufficient content and structural validity, and good reliability, we consider the D-CSD a useful tool to evaluate orthosis satisfaction in persons with chronic hand conditions on group level. Because of a relatively high SDC, sensitivity to detect changes over time on individual level is limited. STUDY REGISTRATION NUMBER: NCT05320211.

Clinicopathologic and genetic characterization of invasive melanoma with BRAF V600K mutation: A study of 16 cases.

BACKGROUND: The clinicopathologic and genetic features of cutaneous melanoma with a BRAF V600K mutation are not well-known. We aimed to evaluate these characteristics in comparison with those associated with BRAF V600E. METHODS: Real-time polymerase chain reaction (PCR) and/or the MassARRAY® system were used to detect BRAF V600K in 16 invasive melanomas and confirm BRAF V600E in another 60 cases. Immunohistochemistry and panel next-generation sequencing were used to evaluate protein expression and tumor mutation burden, respectively. RESULTS: The median age of melanoma patients harboring the BRAF V600K mutation (72.5 years) was higher than those with the BRAF V600E (58.5 years). The two groups also differed in sex (13/16 [81.3%] male in the V600K group vs. 23/60 [38.3%] in V600E) and in the frequency of scalp involvement (8/16 [50.0%] in V600K vs. 1/60 [1.6%] in V600E). The clinical appearance was similar to a superficial spreading melanoma. Histopathologically, non-nested lentiginous intraepidermal spread and subtle solar elastosis were observed. One patient (1/13, 7.7%) had a pre-existing intradermal nevus. Diffuse PRAME immunoexpression was seen in only one (14.3%) of seven tested cases. Loss of p16 expression was observed in all 12 cases (100%) analyzed. The tumor mutation burden was 8 and 6 mutations/Mb in the two tested cases. CONCLUSIONS: Melanoma carrying the BRAF V600K mutation showed the predominance on the scalp of elderly men, lentiginous intraepidermal growth, subtle solar elastosis, possible existence of intradermal nevus component, frequent loss of p16 immunoexpression, limited immunoreactivity for PRAME, and intermediate tumor mutation burden.

Cortical Spreading Depolarization and Delayed Cerebral Ischemia; Rethinking Secondary Neurological Injury in Subarachnoid Hemorrhage.

Poor outcomes in Subarachnoid Hemorrhage (SAH) are in part due to a unique form of secondary neurological injury known as Delayed Cerebral Ischemia (DCI). DCI is characterized by new neurological insults that continue to occur beyond 72 h after the onset of the hemorrhage. Historically, it was thought to be a consequence of hypoperfusion in the setting of vasospasm. However, DCI was found to occur even in the absence of radiographic evidence of vasospasm. More recent evidence indicates that catastrophic ionic disruptions known as Cortical Spreading Depolarizations (CSD) may be the culprits of DCI. CSDs occur in otherwise healthy brain tissue even without demonstrable vasospasm. Furthermore, CSDs often trigger a complex interplay of neuroinflammation, microthrombi formation, and vasoconstriction. CSDs may therefore represent measurable and modifiable prognostic factors in the prevention and treatment of DCI. Although Ketamine and Nimodipine have shown promise in the treatment and prevention of CSDs in SAH, further research is needed to determine the therapeutic potential of these as well as other agents.

Calcitonin Gene-Related Peptide mRNA Synthesis in Trigeminal Ganglion Neurons after Cortical Spreading Depolarization.

Migraine is a debilitating neurovascular disorder characterized by recurrent headache attacks of moderate to severe intensity. Calcitonin gene-related peptide (GGRP), which is abundantly expressed in trigeminal ganglion (TG) neurons, plays a crucial role in migraine pathogenesis. Cortical spreading depolarization (CSD), the biological correlate of migraine aura, activates the trigeminovascular system. In the present study, we investigated CGRP mRNA expression in TG neurons in a CSD-based mouse migraine model. Our in situ hybridization analysis showed that CGRP mRNA expression was observed in smaller-sized neuronal populations. CSD did not significantly change the density of CGRP mRNA-synthesizing neurons in the ipsilateral TG. However, the cell sizes of CGRP mRNA-synthesizing TG neurons were significantly larger in the 48 h and 72 h post-CSD groups than in the control group. The proportions of CGRP mRNA-synthesizing TG neurons bearing cell diameters less than 14 µm became significantly less at several time points after CSD. In contrast, we found significantly greater proportions of CGRP mRNA-synthesizing TG neurons bearing cell diameters of 14-18 µm at 24 h, 48, and 72 h post-CSD. We deduce that the CSD-induced upward cell size shift in CGRP mRNA-synthesizing TG neurons might be causative of greater disease activity and/or less responsiveness to CGRP-based therapy.

An atlas of white matter anatomy, its variability, and reproducibility based on constrained spherical deconvolution of diffusion MRI.

Virtual dissection of white matter (WM) using diffusion MRI tractography is confounded by its poor reproducibility. Despite the increased adoption of advanced reconstruction models, early region-of-interest driven protocols based on diffusion tensor imaging (DTI) remain the dominant reference for virtual dissection protocols. Here we bridge this gap by providing a comprehensive description of typical WM anatomy reconstructed using a reproducible automated subject-specific parcellation-based approach based on probabilistic constrained-spherical deconvolution (CSD) tractography. We complement this with a WM template in MNI space comprising 68 bundles, including all associated anatomical tract selection labels and associated automated workflows. Additionally, we demonstrate bundle inter- and intra-subject variability using 40 (20 test-retest) datasets from the human connectome project (HCP) and 5 sessions with varying b-values and number of b-shells from the single-subject Multiple Acquisitions for Standardization of Structural Imaging Validation and Evaluation (MASSIVE) dataset. The most reliably reconstructed bundles were the whole pyramidal tracts, primary corticospinal tracts, whole superior longitudinal fasciculi, frontal, parietal and occipital segments of the corpus callosum and middle cerebellar peduncles. More variability was found in less dense bundles, e.g., the fornix, dentato-rubro-thalamic tract (DRTT), and premotor pyramidal tract. Using the DRTT as an example, we show that this variability can be reduced by using a higher number of seeding attempts. Overall inter-session similarity was high for HCP test-retest data (median weighted-dice = 0.963, stdev = 0.201 and IQR = 0.099). Compared to the HCP-template bundles there was a high level of agreement for the HCP test-retest data (median weighted-dice = 0.747, stdev = 0.220 and IQR = 0.277) and for the MASSIVE data (median weighted-dice = 0.767, stdev = 0.255 and IQR = 0.338). In summary, this WM atlas provides an overview of the capabilities and limitations of automated subject-specific probabilistic CSD tractography for mapping white matter fasciculi in healthy adults. It will be most useful in applications requiring a reproducible parcellation-based dissection protocol, and as an educational resource for applied neuroimaging and clinical professionals.

Genome-wide identification of 14-3-3 gene family and characterization of their expression in developmental stages of Solanum tuberosum under multiple biotic and abiotic stress conditions.

GF14 proteins are a family of conserved proteins involved in many cellular processes including transport, growth, metabolism, and stress response. However, only few reports are available regarding the 14-3-3 genes in potato. In this study, twelve 14-3-3 genes were detected in the potato genome. Based on their phylogenetic relationships, the StGF14 family members were categorized into two classes. Gene expression analysis demonstrated that StGF14h, StGF14a, and StGF14k had the highest gene expression, induced by abiotic and biotic stresses in all three tissues. The number of exons in 14-3-3 genes ranged from four to seven and most of these genes in the same subfamily had similar exon-intron patterns. The results of our study showed that the conserved motifs are similar in most of the proteins in each group. The intron-exon patterns and the composition of conserved motifs validated the 14-3-3 gene phylogenetic classification. According to the genome distribution results, 14-3-3 genes were located unevenly on the 12 Solanum tuberosum chromosomes. We find out 97 orthologous gene pairs between potato and Arabidopsis as well as 15 paralogous genes among potato genomes. Our results showed that GF-14 genes have an effective role in functional and molecular mechanisms in response to environmental stresses.

Se⋠⋠⋠O/S and S⋠⋠⋠O Chalcogen Bonds in Small Molecules and Proteins: A Combined CSD and PDB Study.

The importance of selenium-centered noncovalent chalcogen bonds represented as Se⋅⋅⋅A (A=O/S) has been explored for short directional contacts in small molecules and proteins. In addition, S⋅⋅⋅O centered contacts have been analyzed. Computational analyses involving the quantitative assessment of the associated energetics, the molecular electrostatic potentials (MEP), and electron density derived topological parameters, namely, quantum theory of atom in molecules (QTAIM) analyses, and NBO (natural bond orbital) based calculations, have been performed to unequivocally establish the strength, stability, and attractive role of chalcogen bonds in the solid-state. This investigation has been performed in molecules from both the Cambridge Structural Database (CSD) and Protein Data Bank (PDB). Thus futuristic materials may be designed keeping in mind the significance of these interactions, including their relevance in biology.

Merging Arcs to Produce Acyclic Phylogenetic Networks and Normal Networks.

As phylogenetic networks grow increasingly complicated, systematic methods for simplifying them to reveal properties will become more useful. This paper considers how to modify acyclic phylogenetic networks into other acyclic networks by contracting specific arcs that include a set D. The networks need not be binary, so vertices in the networks may have more than two parents and/or more than two children. In general, in order to make the resulting network acyclic, additional arcs not in D must also be contracted. This paper shows how to choose D so that the resulting acyclic network is "pre-normal". As a result, removal of all redundant arcs yields a normal network. The set D can be selected based only on the geometry of the network, giving a well-defined normal phylogenetic network depending only on the given network. There are CSD maps relating most of the networks. The resulting network can be visualized as a "wired lift" in the original network, which appears as the original network with each arc drawn in one of three ways.

Distinct-Cluster Tree-Child Phylogenetic Networks and Possible Uses to Study Polyploidy.

As phylogenetic networks become more widely studied and the networks grow larger, it may be useful to "simplify" such networks into especially tractable networks. Recent results have found methods to simplify networks into normal networks. By definition, normal networks contain no redundant arcs. Nevertheless, there may be redundant arcs in networks where speciation events involving allopolyploidy occur. It is therefore desirable to find a different tractable class of networks that may contain redundant arcs. This paper proposes distinct-cluster tree-child networks as such a class, here abbreviated as DCTC networks. They are shown to have a number of useful properties, such as quadratic growth of the number of vertices with the number of leaves. A DCTC network is shown to be essentially a normal network to which some redundant arcs may have been added without losing the tree-child property. Every phylogenetic network can be simplified into a DCTC network depending only on the structure of the original network. There is always a CSD map from the original network to the resulting DCTC network. As a result, the simplified network can readily be interpreted via a "wired lift" in which the original network is redrawn with each arc represented in one of two ways.

Bacterial colonization at caesarean section defects in women of secondary infertility: an observational study.

BACKGROUND: Delayed childbearing has been noted in a high percentage of women with a previous Caesarean section (CS). Many women with CS scar defects (CSDs) present with clinical symptoms of irregular vaginal bleeding. The present study aimed to investigate bacterial colonies at CSDs in women suffering from secondary infertility. METHODS: This observational study included 363 women with secondary infertility who visited the Assisted Reproduction Unit between 2008 and 2013. Among them, 172 women with a previous CS and 191 women with no previous CS were approached. The women with a previous CS had their CS operations in the past 1 to 14 years, with a mean of 3.5 years. The presence of CSDs was detected by vaginal ultrasonography. Bacteriology cultures of specimens taken from the uterine niches in those with CSDs were collected during Day 7 to Day 10 of the follicular phase. Specimens were obtained from the endocervical canal for bacterial culture in those without CSDs. The main outcome measure was the detection of the growth of bacterial colonies. RESULTS: CSDs were found in 60.4% (96 of 159) of women with a previous CS. In women with a previous CS, bacterial colonies were identified in 89.6% (86 of 96) and 69.8% (44 of 63) of women with and without CSDs, respectively. In women with no previous CS, 49.7% (88 out of 177) of bacterial cultures of endocervical samples showed bacterial colony growth. Gram-positive cocci (P = 0.0017, odds ratio (OR) = 1.576, 95% confidence intervals (CI) -22.5 to - 5.4) and Gram-negative rods (P = 0.0016, OR = 1.74, CI - 20.8 to - 5.0) were the most commonly isolated bacteria and contributed to approximately 90% of all microorganisms found in those with a previous CS. In women with a previous CS, more Gram-negative rods were isolated (P = 0.01, OR = 1.765, CI - 27.2 to - 3.8), especially Pseudomonas species (P = 0.02, OR = 1.97, CI - 16.7 to - 1.0), in those with visible CSDs than in those without CSDs. CONCLUSIONS: Bacterial colonization at CSDs was found in a high percentage of women with secondary infertility.