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The plant hormone gibberellin (GA) regulates multiple developmental processes. It accumulates in the root elongating endodermis, but how it moves into this cell file and the significance of this accumulation are unclear. Here we identify three NITRATE TRANSPORTER1/PEPTIDE TRANSPORTER (NPF) transporters required for GA and abscisic acid (ABA) translocation. We demonstrate that NPF2.14 is a subcellular GA/ABA transporter, presumably the first to be identified in plants, facilitating GA and ABA accumulation in the root endodermis to regulate suberization. Further, NPF2.12 and NPF2.13, closely related proteins, are plasma membrane-localized GA and ABA importers that facilitate shoot-to-root GA12 translocation, regulating endodermal hormone accumulation. This work reveals that GA is required for root suberization and that GA and ABA can act non-antagonistically. We demonstrate how the clade of transporters mediates hormone flow with cell-file-specific vacuolar storage at the phloem unloading zone, and slow release of hormone to induce suberin formation in the maturation zone.

Abstract Growth at the shoot apical meristem (SAM) is essential for shoot architecture construction. The phytohormones gibberellins (GA) play a pivotal role in coordinating plant growth, but their role in the SAM remains mostly unknown. Here, we developed a ratiometric GA signaling biosensor by engineering one of the DELLA proteins, to suppress its master regulatory function in GA transcriptional responses while preserving its degradation upon GA sensing. We demonstrate that this degradation-based biosensor accurately reports on cellular changes in GA levels and perception during development. We used this biosensor to map GA signaling activity in the SAM. We show that high GA signaling is found primarily in cells located between organ primordia that are the precursors of internodes. By gain- and loss-of-function approaches, we further demonstrate that GAs regulate cell division plane orientation to establish the typical cellular organization of internodes, thus contributing to internode specification in the SAM.

Introduction Anhedonia (loss of ability of experience pleasure) is a transdiagnostic symptom which is presented as a prominent complain in several psychiatric disorders, such as depressive disorders, schizophrenia, bipolar disorder, addictive disorders, certain personality disorders etc. Specific instruments for assessment of anhedonia have been published in the international literature but their Hungarian versions are not available so far, however, the prevalence of affective disorders and suicide are also high in Hungary. The Snaith-Hamilton Pleasure Scale (SHAPS) is an instrument developed in 1995 (Snaith et al. Br J Psychiatry1995;167:99-103) which purposley has been constructed with items that can be easily translated into other languages. Objectives The aim of our study was to translate the 14 items into Hungarian and analyse its reability and sensitivity in a Hungarian sample consists of patinets and control persons. Further aim was to explore the differences of anhedonia profiles among diagnostic categories and subgroup of major disorders. Methods We recruited 170 subjects (101 controls and 59 patients; 78 men and 82 women; mean age=37,9±6,1y) into our study. Among the patients there were 27 subjects with major depressive disorer (MDD), 10 subjects with bipolar disorder (BD), 9 patients with schizophrenia (SCZ), 6 patients with addictive disorder (AD) and 7 patients with anxiety disorder (ANX)±. We created two major subgorups from the dfferent diagnostic categories: affective and psychotic subgroups to compare the anhedonic profiles. Differences of mean values between case and control, men and women and subgroups were analysed by t-tests and diganostic categories by ANOVA tests performing in SPSS 20.0 software. Results Among the MDD, the BD, the SCZ, the AD and the ANX groups, patients with MDD produced the highest score (6.9±3.5; 3.9±2.4; 5.9±3.9; 2.8±2.7;2.3±1.8, respectively), while controls prohibited 1.6±1.3. The case group scored significantly higher on the SHAPS than the control group (5.3± 3.6 vs. 1.6±1.3; p=0.0001). The means of SHAPS did not differ significantly between the affective subgroup and the psychotic subgroup (6.0±3.7 vs. 4.8±3.2; p=0.24). Among the subgroup of women, the age was significantly associated with the SHAPS score (p=0,04), however, this association has been not detected in men. Conclusions The Hungarian version of the SHAPS detected marked difference between cases and controls with good reliability and sensitivity. The instrument can be useful in daily clinical routin becuase subjects could fill it easily and quickly. In case of patients with pronounced anhedonia, treatments with spcifically targeting anhedonia can be preferred (e.g. rTMS as it was demonstrated in our earlier publications, see Lazary et al. Sci Rep 2021,11:8867; Elemery et al. Front Psychiatry 2022, 13:806731). This study was supported by the grant EFOP 5.6.2. Disclosure of Interest None Declared

Abstract Total en bloc spondylectomy (TES) effectively treats spinal tumors. The surgery requires a vertebral body replacement (VBR), for which several solutions were developed, whereas the biomechanical differences between these devices still need to be completely understood. This study aimed to compare a femur graft, a polyetheretherketone implant (PEEK-IMP-C), a titan mesh cage (MESH-C), and a polymethylmethacrylate replacement (PMMA-C) using a finite element model of the lumbar spine after a TES of L3. Several biomechanical parameters (rotational stiffness, segmental range of motion (ROM), and von Mises stress) were assessed to compare the VBRs. All models provided adequate initial stability by increasing the rotational stiffness and decreasing the ROM between L2 and L4. The PMMA-C had the highest stiffness for flexion–extension, lateral bending, and axial rotation (215%, 216%, and 170% of intact model), and it had the lowest segmental ROM in the instrumented segment (0.2°, 0.5°, and 0.7°, respectively). Maximum endplate stress was similar for PMMA-C and PEEK-IMP-C but lower for both compared to MESH-C across all loading directions. These results suggest that PMMA-C had similar or better primary spinal stability than other VBRs, which may be related to the larger contact surface and the potential to adapt to the patient’s anatomy.

Study Design Retrospective open cohort study. Purpose The current study aimed to explore the pattern of complications after primary sacral tumor resection, to investigate the possible effect of several perioperative parameters on the development of complications, and to identify which complications are associated with the length of hospital stay (LOS). Overview of Literature Primary sacral tumor (pST) resection is associated with a high complication rate. However, the number of studies on these complications and their effect on LOS is limited. Methods The clinical data of 140 patients with pST surgeries and 106 subsequent patients with local recurrence surgeries in four subgroups (index surgery, local recurrence surgery, malignant, and benign tumor) were prospectively collected and analyzed. The prognostic value of several perioperative factors on the development of surgical site infection (SSI), bowel and bladder dysfunction (BBD), and LOS was investigated using the logistic and linear regression models. Results The overall complication rates were 61.2% after index surgeries and 50.9% after local recurrence surgeries. The most frequent complications were SSI, vegetative dysfunction, urinary tract infections, and neurological deterioration. Age >55 years, malignant tumors, and red blood cell transfusion had a predictive effect on the development of SSI in the logistic model (p

Abstract Percutaneous Cement Discoplasty (PCD) is a minimally invasive surgical technique to treat degenerated intervertebral discs. When the disc is severely degenerated, the vacuum observed in place of the nucleus pulposus can be filled with bone cement to restore the disc height, open the foramen space, and relieve pain. This study aimed to evaluate the foramen geometry change due to PCD, in the loaded spine. Cadaveric spines (n = 25) were tested in flexion and extension while Digital Image Correlation (DIC) measured displacements and deformations. Tests were performed on simulated pre-operative condition (nucleotomy) and after PCD. Registering DIC images and the 3D specimen geometry from CT scans, a 3D model of the specimens aligned in the experimental pose was obtained for nucleotomy and PCD. Foramen space volume was geometrically measured for both conditions. The volume of cement injected was measured to explore correlation with the change of foramen space. PCD induced a significant overall foraminal decompression in both flexion (foramen space increased by 835 ± 1289 mm3, p = 0.001) and extension (1205 ± 1106 mm3, p

Abstract Background Spine disorders are becoming more prevalent in today’s ageing society. Motion abnormalities have been linked to the prevalence and recurrence of these disorders. Various protocols exist to measure thoracolumbar spine motion, but a standard multi-segmental approach is still missing. This study aims to systematically evaluate the literature on stereophotogrammetric motion analysis approaches to quantify thoracolumbar spine kinematics in terms of measurement reliability, suitability of protocols for clinical application and clinical significance of the resulting functional assessment. Methods Electronic databases (PubMed, Scopus and ScienceDirect) were searched until February 2022. Studies published in English, investigating the intersegmental kinematics of the thoracolumbar spine using stereophotogrammetric motion analysis were identified. All information relating to measurement reliability; measurement suitability and clinical significance was extracted from the studies identified. Results Seventy-four studies met the inclusion criteria. 33% of the studies reported on the repeatability of their measurement. In terms of suitability, only 35% of protocols were deemed suitable for clinical application. The spinous processes of C7, T3, T6, T12, L1, L3 and L5 were the most widely used landmarks. The spine segment definitions were, however, found to be inconsistent among studies. Activities of daily living were the main tasks performed. Comparable results between protocols are however still missing. Conclusion The literature to date offers various stereophotogrammetric protocols to quantify the multi-segmental motion of the thoracolumbar spine, without a standard guideline being followed. From a clinical point of view, the approaches are still limited. Further research is needed to define a precise motion analysis protocol in terms of segment definition and clinical relevance.

Abstract Standing radiographs play an important role in the characterization of spinal sagittal alignment, as they depict the spine under physiologic loading conditions. However, there is no commonly available method to apply the lumbar lordosis of standing radiographs to supine CT-based virtual 3D models of the lumbar spine. We aimed to develop a method for the sagittal rigid-body registration of vertebrae to standing radiographs, using the exact geometry reconstructed from CT-data. In a cohort of 50 patients with monosegmental spinal degeneration, segmentation and registration of the lumbar vertebrae and sacrum were performed by two independent investigators. Intersegmental angles and lumbar lordosis were measured both in CT scans and radiographs. Vertebrae were registered using the X-ray module of Materialise Mimics software. Postregistrational midsagittal sections were constructed of the sagittal midplane sections of the registered 3D lumbar spine geometries. Mean Hausdorff distance was measured between corresponding registered vertebral geometries. The registration process minimized the difference between the X-rays’ and postregistrational midsagittal sections’ lordoses. Intra- and inter-rater reliability was excellent based on angle and mean Hausdorff distance measurements. We propose an accessible, accurate, and reproducible method for creating patient-specific 3D geometries of the lumbar spine that accurately represent spinal sagittal alignment in the standing position.

Study Design: Literature review with clinical recommendation. Objective: A concise curation of the latest spine literature exploring the relationship between expectations and satisfaction for patients with metastatic spinal disease (MSD). Deliver recommendations to practicing clinicians regarding interpretation and utilisation of this evidence. Methods: The latest spine literature in the topic of factors affecting the expectations of patients with MSD was reviewed and clinical recommendations were formulated. Recommendations are graded as strong or Conditional. Results: 5 articles were selected. Article 1: risk factors for the development of dissatisfaction from a cohort of 362 MSD patients. Strong recommendation to incorporate risk factor assessment when considering treatment. Article 2: systematic review assessing the relationship between pre-operative patient expectations and subsequent satisfaction in allied disciplines. Conditional recommendation to optimize patient expectation to positively modify patient satisfaction. Article 3: qualitative study of how clinicians, from different specialties, counsel patients with MSD pre-treatment. Strong recommendation to use a multidisciplinary approach. Article 4 qualitative study of how MSD patients experience their pre-treatment counselling and how that affected their appreciation of treatment success. Conditional recommendation to furnish patients with tailored, expected outcomes in the context of systemic progression. Article 5 Design and validation of a pre-treatment questionnaire specific to MSD. A conditional recommendation to incorporate this questionnaire in clinical and research MSD practice. Conclusion: Patients with MSD are approaching end of life care and high levels of treatment satisfaction are crucial at this juncture. The role of expectation management and comprehensive counselling is critical. [ABSTRACT FROM AUTHOR]

With the ageing of the population, there is an increasing need for minimally invasive spine surgeries to relieve pain and improve quality of life. Percutaneous Cement Discoplasty is a minimally invasive technique to treat advanced disc degeneration, including vacuum phenomenon. The present study aimed to develop an in vitro model of percutaneous cement discoplasty to investigate its consequences on the spine biomechanics in comparison with the degenerated condition. Human spinal segments (n = 27) were tested at 50% body weight in flexion and extension. Posterior disc height, range of motion, segment stiffness, and strains were measured using Digital Image Correlation. The cement distribution was also studied on CT scans. As main result, percutaneous cement discoplasty restored the posterior disc height by 41% for flexion and 35% for extension. Range of motion was significantly reduced only in flexion by 27%, and stiffness increased accordingly. The injected cement volume was 4.56 ± 1.78 ml (mean ± SD). Some specimens (n = 7) exhibited cement perforation of one endplate. The thickness of the cement mass moderately correlated with the posterior disc height and range of motion with different trends for flexions vs. extension. Finally, extreme strains on the discs were reduced by percutaneous cement discoplasty, with modified patterns of the distribution. To conclude, this study supported clinical observations in term of recovered disc height close to the foramen, while percutaneous cement discoplasty helped stabilize the spine in flexion and did not increase the risk of tissue damage in the annulus.

Background: Chordoma, the most frequent malignant primary spinal neoplasm, characterized by a high rate of recurrence, is an orphan disease where the clarification of the molecular oncogenesis would be crucial to developing new, effective therapies. Dysregulated expression of non-coding RNAs, especially microRNAs (miRNA) has a significant role in cancer development. Methods: Next-generation RNA sequencing (NGS) was used for the combinatorial analysis of mRNA-miRNA gene expression profiles in sacral chordoma and nucleus pulposus samples. Advanced bioinformatics workflow was applied to the data to predict miRNA-mRNA regulatory networks with altered activity in chordoma. Results: A large set of significantly dysregulated miRNAs in chordoma and their differentially expressed target genes have been identified. Several molecular pathways related to tumorigenesis and the modulation of the immune system are predicted to be dysregulated due to aberrant miRNA expression in chordoma. We identified a gene set including key regulators of the Hippo pathway, which is targeted by differently expressed miRNAs, and validated their altered expression by RT-qPCR. These newly identified miRNA/RNA interactions are predicted to have a role in the self-renewal process of chordoma stem cells, which might sustain the high rate of recurrence for this tumor. Conclusions: Our results can significantly contribute to the designation of possible targets for the development of anti-chordoma therapies.

O texto dialoga com os artigos publicados no número 25 da revista cadernos pagu (Unicamp), cujo tema é o mercado do sexo. A discussão engendrada pelos trabalhos que compõem a obra possui relevância quando se pretende compreender o fenômeno do turismo sexual e suas plurais possibilidades de análise. Os autores diversificaram o debate sobre a prostituição, lançando novos olhares acerca da autonomia dos indivíduos que se inserem no mercado do sexo pago. A partir de interfaces com diferentes campos de estudos, as produções procuram desconstruir estereótipos, colaborando com uma abordagem complexa do assunto, como a imagem limitada que se tem do chamado “turista sexual típico”. A contribuição do dossiê é a capacidade de instigar os pesquisadores do turismo sexual a repensar os marcos teóricos tradicionalmente relacionados ao tema, ampliando a visão preconceituosa de parte da academia e do senso comum relacionada a ele.

Purpose: Percutaneous cement discoplasty (PCD) is a minimally invasive surgical option to treat patients who suffer from the consequences of advanced disc degeneration. As the current two-dimensional methods can inappropriately measure the difference in the complex 3D anatomy of the spinal segment, our aim was to develop and apply a volumetric method to measure the geometrical change in the surgically treated segments. Methods: Prospective clinical and radiological data of 10 patients who underwent single- or multilevel PCD was collected. Pre- and postoperative CT scan-based 3D reconstructions were performed. The injected PMMA (Polymethylmethacrylate) induced lifting of the cranial vertebra and the following volumetric change was measured by subtraction of the geometry of the spinal canal from a pre- and postoperatively predefined cylinder. The associations of the PMMA geometry and the volumetric change of the spinal canal with clinical outcome were determined. Results: Change in the spinal canal volume (ΔV) due to the surgery proved to be significant (mean ΔV = 2266.5 ± 1172.2 mm3, n = 16; p = 0.0004). A significant, positive correlation was found between ΔV, the volume and the surface of the injected PMMA. A strong, significant association between pain intensity (low back and leg pain) and the magnitude of the volumetric increase of the spinal canal was shown (ρ = 0.772, p = 0.009 for LBP and ρ = 0.693, p = 0.026 for LP). Conclusion: The developed method is accurate, reproducible and applicable for the analysis of any other spinal surgical method. The volume and surface area of the injected PMMA have a predictive power on the extent of the indirect spinal canal decompression. The larger the ΔV the higher clinical benefit was achieved with the PCD procedure. The translational potential of this article: The developed method has the potential to be integrated into clinical software’s to evaluate the efficacy of different surgical procedures based on indirect decompression effect such as PCD, anterior lumbar interbody fusion (ALIF), lateral lumbar interbody fusion (LLIF), oblique lumbar interbody fusion (OLIF), extreme lateral interbody fusion (XLIF). The intraoperative use of the method will allow the surgeon to respond if the decompression does not reach the desired level.

AimVascular endothelial growth factor (VEGF) has been implicated in mediating the effect of antidepressant therapies as it plays a significant role in the neurogenesis. Anhedonia, an endophenotype of major depressive disorder (MDD), is related to the dorsolateral prefrontal cortex, the major focus of brain stimulation in MDD. The aim of our study was to analyze the change of serum VEGF level after rTMS treatment in association with anhedonia.Materials and MethodsA dataset of 17 patients with TRD who were treated with antidepressants and bilateral rTMS for 2 × 5 days was analyzed. Depression was measured by the Montgomery–Asberg Depression Scale (MADRS) and anhedonia by the Snaith–Hamilton Pleasure Scale (SHAPS) for monitoring the symptom changes. The serum VEGF levels and symptoms were assessed on the first (V1), on the 14th (V2), and on the 28th day (V3). The level of VEGF was measured by ELISA assay.ResultsThere was no significant association between MADRS scores and serum VEGF levels at any timepoint. The decrease in the SHAPS score was significantly associated with the increase in VEGF level between V1 and V2 (p = 0.001). The VEGF levels were significantly higher in non-responders than in responders (p = 0.04). The baseline VEGF level has been proven as a significant predictor of treatment response (p = 0.045).ConclusionOur results suggest that serum VEGF can be sensitive to the changes of anhedonia during rTMS treatment. Considering that the most widely used depression scales are not applicable for the assessment of anhedonia, measurement of anhedonia in rTMS treatment studies of patients with TRD can be suggested as more appropriate data on distinct pathogenic pathways and specific biomarkers of the disorder.

Finite element (FE) analyses contribute to a better understanding of the human lumbar spine’s biomechanics and serve as an effective predictive tool. This study aims to present the development of two L1–L5 FE models using literature-based (LBM) and patient-specific (PSM) bone material assignment approaches. The geometry of the lumbar spine was developed based on quantitative computed tomography scans. The LBM and the PSM were compared under pure and combined loads. Various biomechanical parameters were investigated to validate the models. The total range of motion of the LBM in pure flexion-extension, lateral bending, and axial rotation were 30.9°, 29°, and 13.7°, respectively, while for the PSM, it was 31.6°, 28.6°, and 14.1°. The required computational time of the PSM to complete against pure and combined loads were 12.1 and 16.6 times higher on average compared to the LBM. This study demonstrated that both models agree with experimental and in silico results, although the cumulative distribution of the stress and characterization of strain values showed a noteworthy difference between the two models. Based on these findings, the clinically-focused biomechanical FE studies must perceive the differences in internal mechanical parameters and computational demand between the different bone modelling approaches.

Introduction: The number of patients with iatrogenic spinal deformities is increasing due to the increase in instrumented spinal surgeries globally. Correcting a deformity could be challenging due to the complex anatomical and geometrical irregularities caused by previous surgeries and spine degeneration. Virtual and 3D printed models have the potential to illuminate the unique and complex anatomical-geometrical problems found in these patients.Case Presentation: We present a case report with 6-months follow-up (FU) of a 71 year old female patient with severe sagittal and coronal malalignment due to repetitive discectomy, decompression, laminectomy, and stabilization surgeries over the last 39 years. The patient suffered from severe low back pain (VAS = 9, ODI = 80). Deformity correction by performing asymmetric 3-column pedicle subtraction osteotomy (PSO) and stabilization were decided as the required surgical treatment. To better understand the complex anatomical condition, a patient-specific virtual geometry was defined by segmentation based on the preoperative CT. The geometrical accuracy was tested using the Dice Similarity Index (DSI). A complex 3D virtual plan was created for the surgery from the segmented geometry in addition to a 3D printed model.Discussion: The segmentation process provided a highly accurate geometry (L1 to S2) with a DSI value of 0.92. The virtual model was shared in the internal clinical database in 3DPDF format. The printed physical model was used in the preoperative planning phase, patient education/communication and during the surgery. The surgery was performed successfully, and no complications were registered. The measured change in the sagittal vertical axis was 7 cm, in the coronal plane the distance between the C7 plumb line and the central sacral vertical line was reduced by 4 cm. A 30° correction was achieved for the lumbar lordosis due to the PSO at the L4 vertebra. The patient ODI was reduced to 20 points at the 6-months FU.Conclusions: The printed physical model was considered advantageous by the surgical team in the pre-surgical phase and during the surgery as well. The model was able to simplify the geometrical problems and potentially improve the outcome of the surgery by preventing complications and reducing surgical time.

Introduction The COVID-19 pandemic made neccessary the declaration of emergency state in Hungary from 11 March 2020 to 18 June 2020. During this period hospitals were reserved for emergency use, ambulatory care was limited and replaced by telemedicine. Objectives We assessed the opinions of patients of two ambulatory psychiatric care units in Budapest regarding the emergency state. Methods We enrolled 438 outpatients in the survey (305 women and 133 men, mean age:51.9±16.2 years).Our questionnaire comprised 10 items on emotions and mental state and a 12 item „Problem evaluation scale”(included ’Fear’, ’Isolation’ and ’Health status’ subscales).General linear model (GLM), pairwise comparison and Tukey’s post hoc test were performed. Results Up to 34% of patients considered that their condition worsened during this period, but 12% of them thought that this was not related to emergency state. Twice as many participants (12.8%) were concerned about their financial situation than about their health status (6.1%). Worsening health status, higher fear and more common adaptation difficulties were reported by patients < 50 years, than by subjects> 50 years (p=0.001; p=0.045; p=0.003). Isolation caused higher distress among women than in men (p=0.003). The abundance of information caused higher distress in patients with anxiety disorder than with psychotic disorders (p=0.024).Patients with affective disorders perceived higher vulnerability compared to subjects with psychotic disorders (p=0.004). Conclusions Adaptation difficulties were reported by the half of the sample.Depletion of psychological resources can be expected during the next stage of the pandemic.

Introduction Introduciton: Repetetive transcranial magnetic stimulation (rTMS) is an effective and safety noninvasive technique for treatment of major depression disorder (MDD). There is a body of increasing evidences on the potential molecular mechanisms underlying its effectivity even in case of treatment resistant depression (TRD), however, the exact mechanism is still not clarified. Among multiple biological systems, inflammation can be a target of rTMS in MDD (Tian et al. 2020; Tateishi et al. 2020). Objectives Here we analysed serum cytokine levels in TRD before and after rTMS interventions. Methods We used bilateral stimulation (15Hz for left DLPC and 1Hz on the right side) in 18 patients with TRD (5 men and 13 women; mean age=47.7±12.1 year) for 2x5 days. Blood samples were collected before the first (V1) and after the last inetrevntion (V2). Phenotypic changes were measured by Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Snaith–Hamilton Pleasure Scale (SHAPS), Insomnia Severity Index (ISI) and Stroop Color-Word Test (SCWT) modified by Golden. Inflammatory cytokines were assessed by ELISA assays. Results Change of BDI and BAI scores between V1 and V2 is associated with difference of TNFalpha levels (p=0.043; adj.R2=0.42 p=0.011; adj R2=0.43). Decrease on SHAPS score has been depended on IL-6 level (p=0.027) and the interaction of TNFalpha and IL-10 (p=0.005; adj R2=0.63). Sleep disturbance and neurocognitive function was not associated with cytokine levels. Conclusions Our results confirmed the association between depressive, anxious and anhedonia symptom improvement and inflammatory mechansims during rTMS treatment. The study was supported by the OTKA 151513 grant.