Vestibular Perception following Acute Unilateral Vestibular Lesions.

Little is known about the vestibulo-perceptual (VP) system, particularly after a unilateral vestibular lesion. We investigated vestibulo-ocular (VO) and VP function in 25 patients with vestibular neuritis (VN) acutely (2 days after onset) and after compensation (recovery phase, 10 weeks). Since the effect of VN on reflex and perceptual function may differ at threshold and supra-threshold acceleration levels, we used two stimulus intensities, acceleration steps of 0.5°/s(2) and velocity steps of 90°/s (acceleration 180°/s(2)). We hypothesised that the vestibular lesion or the compensatory processes could dissociate VO and VP function, particularly if the acute vertiginous sensation interferes with the perceptual tasks. Both in acute and recovery phases, VO and VP thresholds increased, particularly during ipsilesional rotations. In signal detection theory this indicates that signals from the healthy and affected side are still fused, but result in asymmetric thresholds due to a lesion-induced bias. The normal pattern whereby VP thresholds are higher than VO thresholds was preserved, indicating that any 'perceptual noise' added by the vertigo does not disrupt the cognitive decision-making processes inherent to the perceptual task. Overall, the parallel findings in VO and VP thresholds imply little or no additional cortical processing and suggest that vestibular thresholds essentially reflect the sensitivity of the fused peripheral receptors. In contrast, a significant VO-VP dissociation for supra-threshold stimuli was found. Acutely, time constants and duration of the VO and VP responses were reduced - asymmetrically for VO, as expected, but surprisingly symmetrical for perception. At recovery, VP responses normalised but VO responses remained shortened and asymmetric. Thus, unlike threshold data, supra-threshold responses show considerable VO-VP dissociation indicative of additional, higher-order processing of vestibular signals. We provide evidence of perceptual processes (ultimately cortical) participating in vestibular compensation, suppressing asymmetry acutely in unilateral vestibular lesions

Recommendations for surveillance of pulmonary dysfunction among childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group

\ua9 2024. Childhood, adolescent, and young adult (CAYA) cancer survivors are at risk of pulmonary dysfunction. Current follow-up care guidelines are discordant. Therefore, the International Late Effects of Childhood Cancer Guideline Harmonization Group established and convened a panel of 33 experts to develop evidence-based surveillance guidelines. We critically reviewed available evidence regarding risk factors for pulmonary dysfunction, types of pulmonary function testing, and timings of surveillance, then we formulated our recommendations. We recommend that CAYA cancer survivors and healthcare providers are aware of reduced pulmonary function risks and pay vigilant attention to potential symptoms of pulmonary dysfunction, especially among survivors treated with allogeneic haematopoietic stem cell transplantation, thoracic radiotherapy, and thoracic surgery. Based on existing limited evidence and current lack of interventions, our panel recommends pulmonary function testing only for symptomatic survivors. Since scarce existing evidence informs our recommendation, we highlight the need for prospective collaborative studies to address pulmonary function knowledge gaps among CAYA cancer survivors

GSTM1 and GSTT1 double null genotypes determining cell fate and proliferation as potential risk factors of relapse in children with hematological malignancies after hematopoietic stem cell transplantation

Purpose This study aimed to retrospectively evaluate the genetic association of null variants of glutathione S-transferases GSTM1 and GSTT1 with relapse incidence in children with hematological malignancies (HMs) undergoing busulfan (BU)- containing allogeneic hematopoietic stem cell transplantation (HSCT) and to assess the impact of these variants on BU-induced cytotoxicity on the immortalized lymphoblastoid cell lines (LCLs) and tumor THP1 GST gene-edited cell models. Methods GSTM1- and GSTT1-null alleles were genotyped using germline DNA from whole blood prior to a conditioning BU-based regimen. Association of GSTM1- and GSTT1-null variants with relapse incidence was analyzed using multivariable competing risk analysis. BU-induced cell death studies were conducted in GSTs- null and non-null LCLs and CRISPR-Cas9 gene-edited THP1 leukemia cell lines. Results Carrying GSTM1/GSTT1 double null genotype was found to be an independent risk factor for post-HSCT relapse in 86 children (adjusted HR: 6.52 [95% Cl, 2.76-15.42; p = 1.9 x 10(-5)]). BU-induced cell death preferentially in THP1(GSTM1(non-null)) and LCLs(GSTM1(non-null)) as shown by decreased viability, increased necrosis and levels of the oxidized form of glutathione compared to null cells, while GSTT1 non-null cells showed increased baseline proliferation. Conclusion The clinical association suggests that GSTM1/GSTT1 double null genotype could serve as genetic stratification biomarker for the high risk of post-HSCT relapse. Functional studies have indicated that GSTM1 status modulates BU-induced cell death. On the other hand, GSTT1 is proposed to be involved in baseline cell proliferation.Transplantation and immunomodulatio

Correction to: GSTM1 and GSTT1 double null genotypes determining cell fate and proliferation as potential risk factors of relapse in children with hematological malignancies after hematopoietic stem cell transplantation

Transplantation and immunomodulatio

Association study of candidate DNA-repair gene variants and acute graft versus host disease in pediatric patients receiving allogeneic hematopoietic stem-cell transplantation

Acute Graft versus Host Disease (aGvHD) grades 2-4 occurs in 15-60% of pediatric patients undergoing allogeneic haematopoietic stem-cell transplantation (allo-HSCT). The collateral damage to normal tissue by conditioning regimens administered prior to allo-HSCT serve as an initial trigger for aGvHD. DNA-repair mechanisms may play an important role in mitigating this initial damage, and so the variants in corresponding DNA-repair protein-coding genes via affecting their quantity and/or function. We explored 51 variants within 17 DNA-repair genes for their association with aGvHD grades 2-4 in 60 pediatric patients. The cumulative incidence of aGvHD 2-4 was 12% (n = 7) in the exploratory cohort. MGMT rs10764881 (G>A) and EXO rs9350 (c.2270C>T) variants were associated with aGvHD 2-4 [Odds ratios = 14.8 (0 events out of 40 in rs10764881 GG group) and 11.5 (95% CI: 2.3-191.8), respectively, multiple testing corrected p A) remained significant (adjusted HR = 2.05 [95% CI: 1.06-3.94]; p = 0.03) in the presence of other clinical risk factors. Higher MGMT expression was seen in GG carriers for rs10764881 and was associated with higher IC50 of Busulfan in lymphoblastoid cells. MGMT rs10764881 carrier status could predict aGvHD occurrence in pediatric patients undergoing allo-HSCT.Transplantation and immunomodulatio

Somatosensory modulation of perceptual vestibular detection

Vestibular-multisensory interactions are essential for self-motion, navigation and postural stability. Despite evidence suggesting shared brain areas between vestibular and somatosensory inputs, no study has yet investigated whether somatosensory information influences vestibular perception. Here, we used signal detection methods to identify whether somatosensory stimulation might interact with vestibular events in a vestibular detection task. Participants were instructed to detect near-threshold vestibular roll-rotation sensations delivered by galvanic vestibular stimulation in one-half of experimental trials. A vibrotactile signal occurred to the index fingers of both hands in half of the trials, independent of vestibular signals. We found that vibrotactile somatosensory stimulation decreased perceptual vestibular sensitivity. The results are compatible with a gain regulation mechanism between vestibular and somatosensory modalities

Bilayers of phosphatidylglycerol : a deuterium and phosphorus nuclear magnetic resonance study of the head-group region

The structural properties of the phosphoglycerol polar head group in bilayers of 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol have been studied with deuterium and phosphorus-31 nuclear magnetic resonance. For this purpose, 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol was deuterated chemically or biosynthetically at all three segments of the glycerol head group. Both the D and the L configurations of the glycerol head group have been synthesized, and the correct stereochemical configuration of the polar group was verified by an enzymtic assay, as direct measurement of the optical rotation was insufficiently sensitive to distinguish between these diastereomers. The phosphatidylglycerol sodium salts were dispersed in excess buffer (0.1 M NaCl, pH 7.0), and the bilayer properties were characterized by small-angle X-ray diffraction and differential scanning calorimetry. The deuterium quadrupole splittings, delta vQ, and the phosphorus-31 chemical shielding anisotropy, delta sigma, were measured as a function of temperature in the range 20-60 degrees C, yielding the following results. (1) Well-resolved deuterium signals were obtained for all head-group segments and could be assigned unambiguously. (2) Almost identical spectra were obtained for 1,2-dipalmitoyl-sn-glycero-3-phospho-1'-glycerol (natural L,D configuration) and 1,2-dipalmitoyl-sn-glycero-3-phospho-3'-glycerol (L,L configuration), suggesting very similar head-group motions and orientations for both diastereomers. (3) The spatial anisotropy of motion and the segmental fluctuations of the negatively charged phosphoglycerol are similar to those of the zwitterionic phosphocholine and phosphoethanolamine head groups but differ distinctly from those of phosphoserine which also carries a net negative charge. (4) The motional inequivalence of geminal deuterons in 1,2-dipalmitoyl-sn-glycero-3-phospho-3'-glycerol was demonstrated by synthesis of a stereospecifically monolabeled analogue