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Pregnancy is often thought of as a time of happiness and anticipation, however, for some women, it can bring about significant emotional distress and feelings of vulnerability. The physiological changes that occur during pregnancy, including hormonal fluctuations and alterations to the immune and physical systems, can affect various parts of the body, including the central nervous system (CNS). As a result, existing conditions may be intensified or new ones, such as neurologic or psychiatric disorders, may arise, exposing women to increased risk of life-threatening conditions or suicide, in the worst-case scenarios. Given the impact of pregnancy on CNS diseases, it is crucial for healthcare providers and patients alike to be aware of these potential effects. By understanding how pregnancy may affect the CNS, clinicians can take appropriate steps to ensure that women receive the care and support they need to minimize any negative outcomes for both the mother and the baby. This paper aims to review the available evidence on the impact of pregnancy on CNS diseases, including mental health conditions, from both the clinical and biomolecular perspectives. By illuminating this crucial subject, this study fosters a delicate understanding within both patients and healthcare providers, thereby paving the way for enhanced outcomes for women throughout their pregnancy journey and beyond.

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OBJECTIVES: Define the cutoff thresholds of the Kappa (K) and Lambda (L) free light chains (FLC) indices for the detection of intrathecal immunoglobulin synthesis (IIS) using the new K and L FLC ELISA from SEBIA. The reference technique, which is not readily standardized between laboratories, is based on the demonstration of oligoclonal banding (OCB) in cerebrospinal fluid (CSF) which is absent in serum. For the past 6 years, we have also routinely calculated the K FLC index using The Binding Site (TBS) reagents on an Optilite instrument, an approach increasingly used as an alternative and/or a complement to electrophoretic analysis. METHODS: We analyzed 391 serum/CSF pairs divided into three groups. The first group were cases without OCB and with normal albumin CSF/serum ratio (n=174). The second group were cases with specific OCB (n=73). The last group included patients with increased albumin CSF/sera ratio without OCB (n=142). RESULTS: Analysis of the first group determined that the cutoffs for detection of IIS are respectively 2.55 and 1.02 for the K FLC and L FLC indices. Of the 73 cases with IIS, only 2 had a K FLC index below this threshold (sensitivity of 97.26%), while 16 out of 73 cases (78.08%) and 13 out of 72 cases (81.94%) had an IgG and L FLC index below the cutoffs, respectively. Additionally, we illustrate equivalent performances for prediction of the presence of OCB between SEBIA and TBS methods. CONCLUSIONS: Sebia K FLC and L FLC assays are adequate alternative methods for the diagnosis of IIS.

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Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)-induced disease (COVID-19) and Gaucher disease (GD) exhibit upregulation of complement 5a (C5a) and its C5aR1 receptor, and excess synthesis of glycosphingolipids that lead to increased infiltration and activation of innate and adaptive immune cells, resulting in massive generation of pro-inflammatory cytokines, chemokines and growth factors. This C5a-C5aR1-glycosphingolipid pathway- induced pro-inflammatory environment causes the tissue damage in COVID-19 and GD. Strikingly, pharmaceutically targeting the C5a-C5aR1 axis or the glycosphingolipid synthesis pathway led to a reduction in glycosphingolipid synthesis and innate and adaptive immune inflammation, and protection from the tissue destruction in both COVID-19 and GD. These results reveal a common involvement of the complement and glycosphingolipid systems driving immune inflammation and tissue damage in COVID-19 and GD, respectively. It is therefore expected that combined targeting of the complement and sphingolipid pathways could ameliorate the tissue destruction, organ failure, and death in patients at high-risk of developing severe cases of COVID-19.

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Life Position, one of the central concepts in Transactional Analysis, is a person's convictions about the worth of the self and others-a basic psychological stand, which is deeply ingrained. There are four Life Positions: "I'm OK-You're OK", "I'm OK-You're not OK", "I'm not OK-You're OK", and "I'm not OK-You're not OK". Contradicting Berne's theory of only one depressive position ("I'm not OK-You're OK"), past findings showed that both "I'm not OK-You're OK" and "I'm not OK-You're not OK" positions relate to depression, with the "I'm not OK-You're not OK" position relating to depression more strongly than the "I'm not OK-You're OK" position. The disparity between Berne's original theorizing of depression and the empirical findings may support an alternative conceptualization of the depressive's Life Position, which was the theoretical gap of this research. This research aimed to investigate the differences in how each Life Position relates to depression, and how the underlying convictions of Life Position predict depression. The Life Position Scale and Center for Epidemiologic Studies Depression Scale were filled in by individuals of the general population. Post hoc analysis revealed that the "I'm not OK-You're not OK" position related most to depression, followed by the "I'm not OK-You're OK" position, the "I'm OK-You're not OK" position, and finally the "I'm OK-You're OK" position. The results also showed that both negative convictions of the self and others contributed significantly to depression, but the former predicted depression more than the latter. Applications of these findings into theoretical and therapy settings were explored.

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Cultural life scripts are shared knowledge about personal events expected to be experienced by individuals within a society and used as a framework for life story narration. Differences in cultural life scripts for individuals with depression and trauma, and their relations to anxiety, stress, and well-being, have not been investigated. Malaysian participants (N = 120) described and rated seven significant events most likely to be experienced by a prototypical infant from their culture, and seven significant events they had experienced or expected to experience in their own life. Participants then answered questionnaires about depression and trauma symptoms and about anxiety, stress, and well-being. The subclinical depression group listed less typical cultural life scripts events, whereas the subclinical post-traumatic stress disorder group listed less positive individual life story events. The findings indicate that, although individuals with depression and trauma possess knowledge of the cultural life scripts, there may be small differences in the cognitive processing of cultural life scripts and individual life story events.

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OBJECTIVE: To identify factors associated with efficacy of rituximab (RTX) infusions in patients with anti-myelin associated glycoprotein (MAG) neuropathy. METHODS: 33 patients with anti-MAG neuropathy treated with RTX were retrospectively evaluated. All patients underwent neurological, biological, and electrophysiological examinations. Good response was defined as an improvement of at least one point of the Overall Neuropathy Limitation Scale (ONLS) at 6months or at the last follow-up. Disease evolution was defined as sub-acute if the ONLS increased by at least 2 points the year before therapy. RESULTS: Ten patients (30%) were improved 6months after RTX and 6/20 (30%) at the last follow-up (mean 42months). Response to RTX was significantly associated with subacute evolution and proximal weakness of the lower limbs at the onset of disease. Improvement was not correlated with electrophysiological data and anti-MAG antibodies titers. DISCUSSION: This study suggests that RTX may be efficacious in a sub-population of patients with anti-MAG neuropathy, particularly in those with proximal weakness of the lower limbs or sub-acute evolution.

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A new multicopper oxidase gene AaMco1 was identified in Acidomyces acidophilus, a pigmented extremophile ascomycete originally isolated from acidic water. Sequence analysis revealed that it encodes a 682 amino acid protein with an apparent molecular mass of 85 kDa as determined by denaturing SDS-PAGE. Interestingly, AaMco1 has a predicted N-terminal transmembrane helix and no signal peptide. To obtain an active and soluble protein, AaMco1 was truncated at its N-terminal to remove the transmembrane helix, but even in this form the protein was found in the insoluble fraction. AaMco1 and its truncated form were then denatured, purified and renatured before characterization. Structural analysis and protein characterization by enzymatic assays indicate that AaMco1 has ferroxidase activity. AaMco1 is also able to oxidize the DMPPDA compound and could be part of a new phylogenetic cluster, the ascomycete MCOs family, described for the first time here.

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Endo-inulinase INU2 from Aspergillus ficuum belongs to glycosidase hydrolase family 32 (GH32) that degrades inulin into fructo oligosaccharides consisting mainly of inulotriose and inulotetraose. The 3D structure of INU2 was recently obtained (Pouyez et al., 2012, Biochimie, 94, 2423-2430). An enlarged cavity compared to exo-inulinase formed by the conserved motif W-M(I)-N-D(E)-P-N-G, the so-called loop 1 and the loop 4, was identified. In the present study we have characterized the importance of 12 residues situated around the enlarged cavity. These residues were mutated by site-directed mutagenesis. Comparative activity analysis was done by plate, spectrophotometric and thin-layer chromatography assay. Most of the mutants were less active than the wild-type enzyme. Most interestingly, mutant N42G differed in the size distribution of the FOS synthesized.

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Endo-inulinase is a member of glycosidase hydrolase family 32 (GH32) degrading fructans of the inulin type with an endo-cleavage mode and is an important class of industrial enzyme. In the present study, we report the first crystal structure of an endo-inulinase, INU2, from Aspergillus ficuum at 1.5 Å. It was solved by molecular replacement with the structure of exo-inulinase as search model. The 3D structure presents a bimodular arrangement common to other GH32 enzymes: a N-terminal 5-fold ß-propeller catalytic domain with four ß-sheets and a C-terminal ß-sandwich domain organized in two ß-sheets with five ß-strands. The structural analysis and comparison with other GH32 enzymes reveal the presence of an extra pocket in the INU2 catalytic site, formed by two loops and the conserved motif W-M(I)-N-D(E)-P-N-G. This cavity would explain the endo-activity of the enzyme, the critical role of Trp40 and particularly the cleavage at the third unit of the inulin(-like) substrates. Crystal structure at 2.1 Å of INU2 complexed with fructosyl molecules, experimental digestion data and molecular modelling studies support these hypotheses.

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In common forms of Alzheimer disease (AD), anterograde memory impairment is the first deficit to occur. However, the disease, especially in its presenile forms, may also manifest itself through initial deficits that are predominantly of a nonmemory type. These distinct clinical profiles, which reflect the distinct topography of the underlying pathologic processes, may also differ in terms of their cerebrospinal fluid (CSF) markers. The aim of this study was to assess the levels of total tau, phosphorylated tau, and amyloid-beta 42 peptide in the CSF of "atypical" (nonmemory) early-onset AD patients. CSF biomarkers were evaluated in 22 atypical patients, and compared with those from a group of 13 "typical" patients, with a memory onset form of the disease. Our results show that independently of age, disease duration, education level, and clinical severity indices, patients with an atypical onset have significantly higher levels of total tau in the CSF (P=0.023). These findings indicate that an assessment of CSF biomarkers may be of particular use in the clinical diagnosis of "atypical-onset" forms of early-onset AD in which the initial symptoms involve language and visuospatial abilities rather than memory. In addition, they highlight the heterogeneity of pathologic processes in AD, suggesting more intense degeneration in the forms of the disease that primarily involve neocortical structures.

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Oxalis tuberosa is an important crop cultivated in the highest Andean zones. A germplasm collection is maintained ex situ by CIP, which has developed a morphological markers system to classify the accessions into morphotypes, i.e. groups of morphologically identical accessions. However, their genetic uniformity is currently unknown. The ISSR technique was used in two experiments to determine the relationships between both morphological and molecular markers systems. The intra-morphotype genetic diversity, the spatial structures of the diversity and the congruence between both markers systems were determined. In the first experience, 44 accessions representing five morphotypes, clearly distinct from each other, were analyzed. At the molecular level, the accessions exactly clustered according to their morphotypes. However, a genetic variability was observed inside each morphotype. In the second experiment, 34 accessions gradually differing from each other on morphological base were analyzed. The morphological clustering showed no geographical structure. On the opposite, the molecular analysis showed that the genetic structure was slightly related to the collection site. The correlation between both markers systems was weak but significant. The lack of perfect congruence between morphological and molecular data suggests that the morphological system may be useful for the morphotypes management but is not appropriate to study the genetic structure of the oca. The spatial structure of the genetic diversity can be related to the evolution of the species and the discordance between the morphological and molecular structures may result from similar selection pressures at different places leading to similar forms with a different genetic background.

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This report describes congenital radial and thumb aplasia in a neonatal owl monkey. Congenital limb deformities in human neonates and Old World primate species have been well characterized. The many probable causes of these congenital defects in skeletal structure include fetal exposure to environmental toxins and genetic influences. In nonhuman primates, the cause frequently remains undetermined. In the case we present, the neonate presented for examination because of inability to cling to the dam. The forelimbs were contracted distally, and thumbs were absent. Radiographs indicated complete radial aplasia and other skeletal abnormalities. This description is the fi rst case study of congenital radial and thumb aplasia in a New World primate species.

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We report a case of BCR-ABL-negative atypical chronic myeloid leukemia (CML) with translocation t(4;22) (q12;q11.2) juxtaposing the breakpoint cluster region (BCR) and platelet-derived growth factor receptor-alpha (PDGFRA) genes. The patient was a 57-year-old man with a history of stage IV diffuse large B-cell lymphoma, status post-6 cycles of combination chemotherapy in 1999, who presented in August 2002 with enlarged lymph nodes, anemia, and marked leukocytosis (50 x 10(9) g/dL) consistent with a myeloproliferative disorder (MPD). A bone marrow biopsy showed granulocytic hyperplasia, neutrophilia, and mild eosinophilia. Initial cytogenetic evaluation by interphase FISH for BCR-ABL, to rule out a translocation 9;22, showed a variant signal pattern consistent with rearrangement of BCR at 22q11.2, but not ABL at 9q34. Analysis of the patient's cDNA by polymerase chain reaction (PCR) for BCR-ABL was negative. Cytogenetic analysis showed an abnormal karyotype with rearrangement of chromosomes 4 and 22. PCR amplification and subsequent sequence analysis demonstrated an in-frame 5'-BCR/3'-PDGFRA fusion in the patient's cDNA. PDGFRA encodes a receptor tyrosine kinase and shares structural and organizational homology with the KIT and CSf1R receptor genes. However, although the incidence of MPD involving translocations of PDGFRB has been well established, to our knowledge there are only two previous reports describing a BCR-PDGFRA fusion gene, in 3 patients diagnosed with atypical CML. Here, we report the molecular and cytogenetic characterization of a patient with BCR-PDGFRA-positive MPD who had a complete hematologic response after treatment with imatinib mesylate.

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