Needle aspiration versus tube thoracostomy in patients with symptomatic primary spontaneous pneumothorax: an updated meta-analysis of randomized controlled trials.

Primary spontaneous pneumothorax (PSP) is an important disease commonly seen in young males. While incidentally diagnosed cases can be managed conservatively, symptomatic patients often necessitate intervention. Chest tube placement (tube thoracostomy) is commonly used, at least in the USA as a primary treatment modality, which requires hospitalization. On the other hand, needle aspiration (NA) has been widely adopted due to simplicity and reported efficacy and safety. No consensus is reached regarding superiority and/or preferred modality, with a lack of guidelines agreement. Therefore, we conducted an updated meta-analysis of randomized controlled trials comparing NA to tube thoracostomy in patients with symptomatic PSP. Prespecified outcomes were immediate success rate, 12-month recurrence rate, post intervention complications rate, and hospital length of stay. We identified and pooled data from six randomized trials, with a total of 759 patients and a median follow up of 12 months. Our analysis showed that NA and tube thoracostomy have similar immediate success rate and 12-month recurrence rate. We also found that NA has less complication rate, need for surgical intervention, and less hospital stays. In conclusion, our review showed that in symptomatic patients with PSP, NA is as effective as tube thoracostomy regarding immediate success rate and 12-month recurrence rate, with the added benefit of less complications rate and need for surgical intervention.

Progressive Supranuclear Palsy: Subcortical Tau Depositions Are Associated with Cortical Perfusion in Frontal and Limbic Regions.

 In progressive supranuclear palsy (PSP), subcortical tau and cortical perfusion can be assessed using the tracer [18F]PI-2620. We investigated if subcortical tau (globus pallidus internus, dentate nucleus) and frontal/limbic perfusion correlate in a cohort of 32 PSP patients. Tau in subcortical regions showed significant negative correlation with perfusion in limbic cortex. Perfusion in frontal regions was negatively associated with tau in both subcortical regions, but the significance threshold was only passed for the dentate nucleus. A reason could be a diaschisis-like phenomenon; that is, subcortical tau could lead to reduced connectivity to frontal regions and, thereby, to decreased perfusion.

In a study of 32 patients with progressive supranuclear palsy (PSP), we used a molecular imaging tracer called [18F]PI-2620 to measure two things: the presence of a protein called tau in deep brain areas (specifically, the globus pallidus internus and dentate nucleus) and the function of the brain's cortex by assessing blood flow (perfusion). We found that higher amounts of tau in these deep brain areas were associated with reduced blood flow in the limbic cortex, which is involved in emotion regulation. Also, the frontal areas of the brain showed reduced blood flow related to tau in these deep brain regions. However, this connection was statistically significant only for the dentate nucleus. This study suggests that the buildup of tau protein in deeper brain areas can disrupt function in parts of the brain's cortex, highlighting the damaging role of tau in PSP.

The potential significance of hepcidin evaluation in progressive supranuclear palsy.

INTRODUCTION: Hepcidin is a peptide associated with controlling the distribution of iron in tissues. Growing interest is linked with its impact on neurodegenerative diseases, as disruption of the iron regulation may be considered an initiatory element of pathological protein accumulation. The possible impact of hepcidin was not previously sufficiently explored in progressive supranuclear palsy (PSP). METHODS: Twelve patients with PSP-Richardson's syndrome (PSP-RS), 12 with PSP-Parkinsonism Predominant (PSP-P), and 12 controls were examined using Unified Parkinson's Disease Rating Scale-III part (UPDRS-III) in OFF stage and analyzed in the context of hepcidin levels in the serum. RESULTS: The work revealed increased levels of hepcidin in PSP-RS when compared to PSP-P and controls. Moreover, hepcidin was found to be negatively correlated with UPDRS-III results in PSP-RS, whereas positively in PSP-P. CONCLUSION: The work may suggest a possible impact of hepcidin in PSP, possibly differing depending on its subtype.

Incidence and risk factors for recurrent primary spontaneous pneumothorax after video-assisted thoracoscopic surgery: a systematic review and meta-analysis.

Background: The incidence and risk factors for recurrent primary spontaneous pneumothorax (PSP) after video-assisted thoracoscopic surgery (VATS) remain controversial. A systematic review and meta-analysis were conducted to determine the incidence and risk factors for recurrence of PSP after VATS. Methods: A systematic search of PubMed, Web of Science, Embase, and Cochrane Library databases was conducted to identify studies that reported the rate and risk factors for recurrence of PSP after VATS published up to December 2023. The pooled recurrence rate and odds ratio (OR) with 95% confidence interval (CI) were calculated using a random-effects model. In addition, risk factors were similarly included in the meta-analysis, and sources of heterogeneity were explored using meta-regression analysis. Results: A total of 72 studies involving 23,531 patients were included in the meta-analysis of recurrence. The pooled recurrence rate of PSP after VATS was 10% (95% CI: 8-12%). Male sex (OR: 0.61; 95% CI: 0.41-0.92; P=0.02), younger age [mean difference (MD): -2.01; 95% CI: -2.57 to -1.45; P<0.001), lower weight (MD: -1.57; 95% CI: -3.03 to -0.11; P=0.04), lower body mass index (BMI) (MD: -0.73; 95% CI: -1.08 to 0.37; P<0.001), and history of contralateral pneumothorax (OR: 2.46; 95% CI: 1.56-3.87; P<0.001) were associated with recurrent PSP, whereas height, smoking history, affected side, stapling line reinforcement, and pleurodesis were not associated with recurrent PSP after VATS. Conclusions: The recurrence rate of PSP after VATS remains high. Healthcare professionals should focus on factors, including sex, age, weight, BMI, and history of contralateral pneumothorax, that may influence recurrence.

Subcortical tau is linked to hypoperfusion in connected cortical regions in 4-repeat tauopathies.

Four-repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent 4R tauopathies are progressive supranuclear palsy (PSP) and corticobasal degeneration characterized by subcortical tau accumulation and cortical neuronal dysfunction, as shown by PET-assessed hypoperfusion and glucose hypometabolism. Yet, there is a spatial mismatch between subcortical tau deposition patterns and cortical neuronal dysfunction, and it is unclear how these two pathological brain changes are interrelated. Here, we hypothesized that subcortical tau pathology induces remote neuronal dysfunction in functionally connected cortical regions to test a pathophysiological model that mechanistically links subcortical tau accumulation to cortical neuronal dysfunction in 4R tauopathies. We included 51 Aß-negative patients with clinically diagnosed PSP variants (n = 26) or corticobasal syndrome (n = 25) who underwent structural MRI and 18F-PI-2620 tau-PET. 18F-PI-2620 tau-PET was recorded using a dynamic one-stop-shop acquisition protocol to determine an early 0.5-2.5 min post tracer-injection perfusion window for assessing cortical neuronal dysfunction, as well as a 20-40 min post tracer-injection window to determine 4R-tau load. Perfusion-PET (i.e. early window) was assessed in 200 cortical regions, and tau-PET was assessed in 32 subcortical regions of established functional brain atlases. We determined tau epicentres as subcortical regions with the highest 18F-PI-2620 tau-PET signal and assessed the connectivity of tau epicentres to cortical regions of interest using a resting-state functional MRI-based functional connectivity template derived from 69 healthy elderly controls from the ADNI cohort. Using linear regression, we assessed whether: (i) higher subcortical tau-PET was associated with reduced cortical perfusion; and (ii) cortical perfusion reductions were observed preferentially in regions closely connected to subcortical tau epicentres. As hypothesized, higher subcortical tau-PET was associated with overall lower cortical perfusion, which remained consistent when controlling for cortical tau-PET. Using group-average and subject-level PET data, we found that the seed-based connectivity pattern of subcortical tau epicentres aligned with cortical perfusion patterns, where cortical regions that were more closely connected to the tau epicentre showed lower perfusion. Together, subcortical tau-accumulation is associated with remote perfusion reductions indicative of neuronal dysfunction in functionally connected cortical regions in 4R-tauopathies. This suggests that subcortical tau pathology may induce cortical dysfunction, which may contribute to clinical disease manifestation and clinical heterogeneity.

Deciphering the TCF19/miR-199a-5p/SP1/LOXL2 pathway: Implications for breast cancer metastasis and epithelial-mesenchymal transition.

Globally, breast cancer (BC) is the predominant malignancy with a significant death rate due to metastasis. The epithelial-mesenchymal transition (EMT) is a fundamental initiator for metastatic progression. Through advanced computational strategies, TCF19 was identified as a critical EMT-associated gene with diagnostic and prognostic significance in BC, based on a novel EMT score. Molecular details and the pro-EMT impact of the TCF19/miR-199a-5p/SP1/LOXL2 axis were explored in BC cell lines through in vitro validations, and the oncogenic and metastatic potential of TCF19 and LOXL2 were investigated using subcutaneous and tail-vein models. Additionally, BC-specific enrichment of TCF19 and LOXL2 was measured using a distribution landscape driven by diverse genomic analysis techniques. Molecular pathways revealed that TCF19-induced LOXL2 amplification facilitated migratory, invasive, and EMT activities of BC cells in vitro, and promoted the growth and metastatic establishment of xenografts in vivo. TCF19 decreases the expression of miR-199a-5p and alters the nuclear dynamics of SP1, modulating SP1's affinity for the LOXL2 promoter, leading to increased LOXL2 expression and more malignant characteristics in BC cells. These findings unveil a novel EMT-inducing pathway, the TCF19/miR-199a-5P/SP1/LOXL2 axis, highlighting the pivotal role of TCF19 and suggesting potential for novel therapeutic approaches for more focused BC interventions.

Late-life mood disorder as the initial presentation of progressive supranuclear palsy: A case series.

Aim: Progressive supranuclear palsy (PSP) is a rapidly progressive neurodegenerative disorder characterized by Parkinsonism, supranuclear ophthalmoplegia, postural instability, and cognitive impairment. Patients: This case series describes three patients initially diagnosed with late-life mood disorders (depression and bipolar disorder) who were later diagnosed with PSP because of the development of typical neurological symptoms. Result: The diagnostic challenge of PSP is highlighted in this case report, particularly in the early stages, when characteristic symptoms may not be present. The importance of considering PSP in the differential diagnosis of late-life mood disorders, especially in the absence of response to standard antidepressant therapy, is also emphasized. The heterogeneity of PSP is described, with various subtypes and atypical variants presenting with different clinical features. The psychiatric symptoms of PSP include apathy, disinhibition, depression, and anxiety, whereas hallucinations and delusions are less frequent. Tau positron emission tomography imaging is discussed as a potential biomarker for atypical PSP. Conclusion: Early diagnosis and intervention are crucial for improved outcomes in PSP, necessitating further research to enhance the diagnostic and treatment strategies for PSP and other neurodegenerative diseases.

Constrains in the articulation between profession, family, and personal life: a case study of the Portuguese police (PSP).

The dangers and stresses of a police officer's career cause physical and psychological distress which in turn cause considerable challenges for the integration of professional, family, and personal life. This study focuses on the conditions that influence this articulation between the personal, family, and professional lives of Portuguese Police (PSP) officers. A questionnaire survey was applied to 414 police officers from 11 divisions of COMETLIS. At the empirical level, several models were tested to assess the articulation between the professional, family, and personal lives of police officers. The results highlight the influence of having young children, elderly people or other dependents living in the family home, as well as the employee's age, on the job's interaction with professional life. At a professional level, the variables shift work, professional category, years of service and working away from home were identified by the officers as conditioning factors in the work-family-personal life balance. Sex differences in the articulation of professional, family, and personal life were also observed.

The phage shock protein (PSP) envelope stress response: discovery of novel partners and evolutionary history.

Bacterial phage shock protein (PSP) systems stabilize the bacterial cell membrane and protect against envelope stress. These systems have been associated with virulence, but despite their critical roles, PSP components are not well characterized outside proteobacteria. Using comparative genomics and protein sequence-structure-function analyses, we systematically identified and analyzed PSP homologs, phyletic patterns, domain architectures, and gene neighborhoods. This approach underscored the evolutionary significance of the system, revealing that its core protein PspA (Snf7 in ESCRT outside bacteria) was present in the last universal common ancestor and that this ancestral functionality has since diversified into multiple novel, distinct PSP systems across life. Several novel partners of the PSP system were identified: (i) the Toastrack domain, likely facilitating assembly of sub-membrane stress-sensing and signaling complexes, (ii) the newly defined HTH-associated α-helical signaling domain-PadR-like transcriptional regulator pair system, and (iii) multiple independent associations with ATPase, CesT/Tir-like chaperone, and Band-7 domains in proteins thought to mediate sub-membrane dynamics. Our work also uncovered links between the PSP components and other domains, such as novel variants of SHOCT-like domains, suggesting roles in assembling membrane-associated complexes of proteins with disparate biochemical functions. Results are available at our interactive web app, https://jravilab.org/psp.IMPORTANCEPhage shock proteins (PSP) are virulence-associated, cell membrane stress-protective systems. They have mostly been characterized in Proteobacteria and Firmicutes. We now show that a minimal PSP system was present in the last universal common ancestor that evolved and diversified into newly identified functional contexts. Recognizing the conservation and evolution of PSP systems across bacterial phyla contributes to our understanding of stress response mechanisms in prokaryotes. Moreover, the newly discovered PSP modularity will likely prompt new studies of lineage-specific cell envelope structures, lifestyles, and adaptation mechanisms. Finally, our results validate the use of domain architecture and genetic context for discovery in comparative genomics.

Progressive Supranuclear palsy (PSP) disease progression, management, and healthcare resource utilization: a retrospective observational study in the US and Canada.

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare neurodegenerative brain disease with rapid progression and currently limited treatment options. A comprehensive understanding of disease progression, management, and healthcare resource utilization is limited, and further research is challenging due to the small population of patients. To address these challenges in conducting PSP research, individuals with PSP were recruited using a multichannel approach tailored specifically to the PSP community. We performed a retrospective observational study using data abstracted from participant medical records collected from multiple patient care centers. RESULTS: Seventy-two individuals with PSP were eligible for inclusion. On average, 144 medical documents per participant were collected from an average of 2.9 healthcare centers per participant, with a mean study period of 7.9 years. Among participants with a date of symptom onset documented in the medical records, the median time for the onset of the first fall was 2.0 years (IQR 3.2) before diagnosis, the median onset of unsteady gait or gait impairment was 1.2 years (IQR 1.8) before diagnosis, and the median onset of mobility problems was 0.8 years (IQR 1.8) before diagnosis. The most widely utilized healthcare resources, with at least 85% of participants using each of these resources at some point during the disease course, were medications (100%), imaging (99%), assistive devices (90%), supportive care (86%), and surgeries and procedures (85%). CONCLUSIONS: This retrospective study adds to the current understanding of PSP symptoms, comorbidities, and healthcare resource utilization (HRU) across the disease journey. By involving individuals with PSP and their caregivers or legally authorized representatives in the research process, this study was unique in its approach to participant recruitment and enabled individuals to participate in research without the need for travel. We collected medical documents from multiple healthcare centers, allowing for broad data collection covering the entire disease journey. This approach to the collection of real-world data may be used to generate valuable insights into many aspects of disease progression and management in PSP and many other rare diseases.

Effects of temperature and nutrients on growth and toxicity of Alexandrium affine from southeastern Gulf of California.

An Alexandrium affine strain (AAJQ-1) from San José Island, Gulf of California was characterized for growth and toxicology. Fivefold of f/2 + Se cultures were incubated for 34 days in a temperature gradient (21-29 °C). Aliquots were collected every third day for cell counting, toxin determination, and nutrient analyses. In this study ELISA method was used to evaluate the PSP toxin production due to the lower detection limit than the HPLC method. The highest cell density (6724 cells mL-1) and growth rate (0.22 day-1) were obtained at 27 °C and they were related to temperature in all treatments. Cell density showed negative correlation with nitrate at temperatures ≥23 °C, and with orthophosphate 27 °C, furthermore, these correlations promote the toxin production (0.05-0.45 fmol STX cell-1); beyond that nitrite at high temperature seems to promote toxin production, which has not been sufficiently documented.

Examining pancreatic stone protein response in ICU-acquired bloodstream infections: a matched event analysis.

BACKGROUND: Pancreatic stone protein (PSP) exhibits potential as a plasma biomarker for infection diagnosis and risk stratification in critically ill patients, but its significance in nosocomial infection and intensive care unit (ICU)-acquired bloodstream infection (BSI) remains unclear. This study explores the temporal responses of PSP in ICU-acquired BSI caused by different pathogens. METHODS: From a large cohort of ICU patients, we selected episodes of ICU-acquired BSI caused by Gram-negative rods (GNRs), enterococci, or Candida species. Events were matched on length of ICU stay at infection onset, Severe Organ Failure Assessment (SOFA) score, presence of immune deficiency, and use of renal replacement therapy. PSP concentrations were measured at infection onset (T0) and at 24, 48 and 72 h prior to infection onset as defined by the first occurrence of a positive blood culture. Absolute and trend differences in PSP levels between pathogen groups were analysed using one-way analysis of variance. Sensitivity analyses were performed in events with a new or worsening systematic inflammatory response based on C-reactive protein, white cell count and fever. RESULTS: We analysed 30 BSI cases per pathogen group. Median (IQR) BSI onset was on day 9 (6-12). Overall, PSP levels were high (381 (237-539) ng/ml), with 18% of values exceeding the assay's measurement range. Across all 90 BSI cases, there was no clear trend over time (median change 34 (- 75-189) ng/ml from T-72 to T0). PSP concentrations at infection onset were 406 (229-497), 350 (223-608), and 480 (327-965) ng/ml, for GNR, enterococci, and Candida species, respectively (p = 0.32). At every time point, absolute PSP levels and trends did not differ significantly between pathogens. PSP values at T0 correlated with SOFA scores. Eighteen (20%) of 90 BSI events did not exhibit a systemic inflammatory response, primarily in Candida species. No clear change in PSP concentration before BSI onset or between-group differences were found in sensitivity analyses of 72 cases. CONCLUSIONS: Against a background of overall (very) high plasma PSP levels in critically ill patients, we did not find clear temporal patterns or any pathogen-specific differences in PSP response in the days preceding onset of ICU-acquired BSI.

Frontal hypometabolism in the diagnosis of progressive supranuclear palsy clinical variants.

OBJECTIVE: Frontal hypometabolism on FDG-PET is observed in progressive supranuclear palsy (PSP), although it is unclear whether it is a feature of all PSP clinical variants and hence whether it is a useful diagnostic feature. We aimed to compare the frequency, severity, and pattern of frontal hypometabolism across PSP variants and determine whether frontal hypometabolism is related to clinical dysfunction. METHODS: Frontal hypometabolism in prefrontal, premotor, and sensorimotor cortices was visually graded on a 0-3 scale using CortexID Z-score images in 137 PSP patients. Frontal asymmetry was recorded. Severity scores were used to categorize patients as premotor-predominant, prefrontal-predominant, sensorimotor-predominant, mixed-predominance, or no regional predominance. Frontal ratings were compared across PSP clinical variants, and Spearman correlations were used to assess relationships with the Frontal Assessment Battery (FAB). RESULTS: 97% showed evidence of frontal hypometabolism which was most common (100%) in the speech-language (PSP-SL), corticobasal (PSP-CBS), and frontal (PSP-F) variants and least common in the progressive gait freezing (PSP-PGF) variant (73%). PSP-SL and PSP-CBS showed more severe hypometabolism than Richardson's syndrome (PSP-RS), Parkinsonism (PSP-P), and PSP-PGF. A premotor-predominant pattern was most common in PSP-SL and PSP-CBS, with more mixed patterns in the other variants. Hypometabolism was most commonly asymmetric in PSP-SL, PSP-P, PSP-F and PSP-CBS. Worse hypometabolism in nearly all frontal regions correlated with worse scores on the FAB. CONCLUSIONS: Frontal hypometabolism is a common finding in PSP, although it varies in severity and pattern across PSP variants and will likely be the most diagnostically useful in PSP-SL and PSP-CBS.

Structural characterization of methylation-independent PP2A assembly guides alphafold2Multimer prediction of family-wide PP2A complexes.

Dysregulation of phosphorylation-dependent signaling is a hallmark of tumorigenesis. Protein phosphatase 2 (PP2A) is an essential regulator of cell growth. One scaffold subunit (A) binds to a catalytic subunit (C) to form a core AC heterodimer, which together with one of many regulatory (B) subunits forms the active trimeric enzyme. The combinatorial number of distinct PP2A complexes is large, which results in diverse substrate specificity and subcellular localization. The detailed mechanism of PP2A assembly and regulation remains elusive and reports about an important role of methylation of the carboxy terminus of PP2A C are conflicting. A better understanding of the molecular underpinnings of PP2A assembly and regulation is critical to dissecting PP2A function in physiology and disease. Here, we combined biochemical reconstitution, mass spectrometry, X-ray crystallography, and functional assays to characterize the assembly of trimeric PP2A. In vitro studies demonstrated that methylation of the carboxy-terminus of PP2A C was dispensable for PP2A assembly in vitro. To corroborate these findings, we determined the X-ray crystal structure of the unmethylated PP2A Aα-B56ε-Cα trimer complex to 3.1 Å resolution. The experimental structure superimposed well with an Alphafold2Multimer prediction of the PP2A trimer. We then predicted models of all canonical PP2A complexes providing a framework for structural analysis of PP2A. In conclusion, methylation was dispensable for trimeric PP2A assembly and integrative structural biology studies of PP2A offered predictive models for all canonical PP2A complexes.

Differential Synaptic Loss in ß-Amyloid Positive Versus ß-Amyloid Negative Corticobasal Syndrome.

BACKGROUND/OBJECTIVE: The corticobasal syndrome (CBS) is a complex asymmetric movement disorder, with cognitive impairment. Although commonly associated with the primary 4-repeat-tauopathy of corticobasal degeneration, clinicopathological correlation is poor, and a significant proportion is due to Alzheimer's disease (AD). Synaptic loss is a pathological feature of many clinical and preclinical tauopathies. We therefore measured the degree of synaptic loss in patients with CBS and tested whether synaptic loss differed according to ß-amyloid status. METHODS: Twenty-five people with CBS, and 32 age-/sex-/education-matched healthy controls participated. Regional synaptic density was estimated by [11C]UCB-J non-displaceable binding potential (BPND), AD-tau pathology by [18F]AV-1451 BPND, and gray matter volume by T1-weighted magnetic resonance imaging. Participants with CBS had ß-amyloid imaging with 11C-labeled Pittsburgh Compound-B ([11C]PiB) positron emission tomography. Symptom severity was assessed with the progressive supranuclear palsy-rating-scale, the cortical basal ganglia functional scale, and the revised Addenbrooke's Cognitive Examination. Regional differences in BPND and gray matter volume between groups were assessed by ANOVA. RESULTS: Compared to controls, patients with CBS had higher [18F]AV-1451 uptake, gray matter volume loss, and reduced synaptic density. Synaptic loss was more severe and widespread in the ß-amyloid negative group. Asymmetry of synaptic loss was in line with the clinically most affected side. DISCUSSION: Distinct patterns of [11C]UCB-J and [18F]AV-1451 binding and gray matter volume loss, indicate differences in the pathogenic mechanisms of CBS according to whether it is associated with the presence of Alzheimer's disease or not. This highlights the potential for different therapeutic strategies in CBSs. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Histologic tau lesions and magnetic resonance imaging biomarkers differ across two progressive supranuclear palsy variants.

Progressive supranuclear palsy is a neurodegenerative disease characterized by the deposition of four-repeat tau in neuronal and glial lesions in the brainstem, cerebellar, subcortical and cortical brain regions. There are varying clinical presentations of progressive supranuclear palsy with different neuroimaging signatures, presumed to be due to different topographical distributions and burden of tau. The classic Richardson syndrome presentation is considered a subcortical variant, whilst progressive supranuclear palsy with predominant speech and language impairment is considered a cortical variant, although the pathological underpinnings of these variants are unclear. In this case-control study, we aimed to determine whether patterns of regional tau pathology differed between these variants and whether tau burden correlated with neuroimaging. Thirty-three neuropathologically confirmed progressive supranuclear palsy patients with either the Richardson syndrome (n = 17) or speech/language (n = 16) variant and ante-mortem magnetic resonance imaging were included. Tau lesion burden was semi-quantitatively graded in cerebellar, brainstem, subcortical and cortical regions and combined to form neuronal and glial tau scores. Regional magnetic resonance imaging volumes were converted to Z-scores using 33 age- and sex-matched controls. Diffusion tensor imaging metrics, including fractional anisotropy and mean diffusivity, were calculated. Tau burden and neuroimaging metrics were compared between groups and correlated using linear regression models. Neuronal and glial tau burden were higher in motor and superior frontal cortices in the speech/language variant. In the subcortical and brainstem regions, only the glial tau burden differed, with a higher burden in globus pallidus, subthalamic nucleus, substantia nigra and red nucleus in Richardson's syndrome. No differences were observed in the cerebellar dentate and striatum. Greater volume loss was observed in the motor cortex in the speech/language variant and in the subthalamic nucleus, red nucleus and midbrain in Richardson's syndrome. Fractional anisotropy was lower in the midbrain and superior cerebellar peduncle in Richardson's syndrome. Mean diffusivity was greater in the superior frontal cortex in the speech/language variant and midbrain in Richardson's syndrome. Neuronal tau burden showed associations with volume loss, lower fractional anisotropy and higher mean diffusivity in the superior frontal cortex, although these findings did not survive correction for multiple comparisons. Results suggest that a shift in the distribution of tau, particularly neuronal tau, within the progressive supranuclear palsy network of regions is driving different clinical presentations in progressive supranuclear palsy. The possibility of different disease epicentres in these clinical variants has potential implications for the use of imaging biomarkers in progressive supranuclear palsy.

Evaluation of PSP1 biostimulant on Fusarium graminearum-wheat pathosystem: impact on disease parameters, grain yield, and grain quality.

BACKGROUND: Plant defense elicitors are valuable tools in sustainable agriculture, providing an environmentally friendly and effective means of enhancing plant defense and promoting plant health. Fusarium head blight (FHB) is one of the most important fungal diseases of cereal crops worldwide. The PSP1 is a novel biopesticide formulated based on an elicitor, the extracellular protein AsES, from the fungus Sarocladium strictum. The present work aimed to evaluate the effectiveness of PSP1 in controlling FHB under field conditions. Experiments were conducted during three consecutive growing seasons (2019, 2020, and 2021). Three biostimulant treatments were tested in different physiological stages (from late tillering to heading stage), and FHB inoculations were performed at anthesis. Disease parameters, seed parameters, grain yield, and grain quality parameters were evaluated. RESULTS: Depending on the year and the genotype, reductions in disease incidence (up to 11%) and disease severity (up to 5%) were reported, although these differences could not be attributed to the use of the PSP1 biostimulant. Occasional improvements in seed parameters and grain quality were observed, suggesting that early treatments could work better than late treatments, probably due to early activation/priming of defense response mechanisms. However, more studies are deemed necessary. CONCLUSION: The use of PSP1 biostimulant in commercial wheat crops could be a biological alternative or complement to traditional chemical fungicides to manage FHB. The reduced environmental impact and the potential benefits in grain yield and quality are other reasons that can generate new adherents of this technology in worldwide agriculture systems in the coming years. © 2024 Society of Chemical Industry.

Evaluating postoperative recovery in uniportal versus needlescopic video-assisted thoracoscopic surgery for primary spontaneous pneumothorax: a comparable study.

Objectives: Primary spontaneous pneumothorax (PSP) is a common disease in young and thin male. Operation has been regarded as definitive treatment for it. However, the operative methods for those patients are under dispute. This study aims to directly compare the outcomes of uniportal VATS vs. needlescopic VATS in the treatment of PSP, focusing on postoperative pain and safety outcomes. Methods: From July 2013 to December 2017, the patients who underwent video-assisted thoracic surgery for pneumothorax in National Taiwan University Hospital were retrospectively collected. The preoperative condition, surgical results, and postoperative outcomes was analyzed. Results: There were 60 patients undergoing needlescopic VATS and 91 undergoing uniportal VATS during the study period. There was no significant difference between the patients who underwent needlescopic VATS and those who underwent uniportal VATS in their demographic and clinical characteristics. The post-operative pain score was significantly lower in the uniportal VATS group compared to the needlescopic VATS group at day 1 (2.65 ± 1.59 vs. 1.74 ± 1.35, p = 0.001). Conclusion: Uniportal VATS offers an effective, safe alternative for PSP treatment, with benefits including reduced post-operative pain. Our findings support the use of uniportal VATS, supplemented by a wound protector, as a viable option for PSP patients.

BacA: a possible regulator that contributes to the biofilm formation of Pseudomonas aeruginosa.

Previously, we pointed out in P. aeruginosa PAO1 biofilm cells the accumulation of a hypothetical protein named PA3731 and showed that the deletion of the corresponding gene impacted its biofilm formation capacity. PA3731 belongs to a cluster of 4 genes (pa3732 to pa3729) that we named bac for "Biofilm Associated Cluster." The present study focuses on the PA14_16140 protein, i.e., the PA3732 (BacA) homolog in the PA14 strain. The role of BacA in rhamnolipid secretion, biofilm formation and virulence, was confirmed by phenotypic experiments with a bacA mutant. Additional investigations allow to advance that the bac system involves in fact 6 genes organized in operon, i.e., bacA to bacF. At a molecular level, quantitative proteomic studies revealed an accumulation of the BAC cognate partners by the bacA sessile mutant, suggesting a negative control of BacA toward the bac operon. Finally, a first crystallographic structure of BacA was obtained revealing a structure homologous to chaperones or/and regulatory proteins.

Association of Structural Forms of 17q21.31 with the Risk of Progressive Supranuclear Palsy and MAPT Sub-haplotypes.

Importance: The chromosome 17q21.31 region, containing a 900 Kb inversion that defines H1 and H2 haplotypes, represents the strongest genetic risk locus in progressive supranuclear palsy (PSP). In addition to H1 and H2, various structural forms of 17q21.31, characterized by the copy number of α, ß, and γ duplications, have been identified. However, the specific effect of each structural form on the risk of PSP has never been evaluated in a large cohort study. Objective: To assess the association of different structural forms of 17q.21.31, defined by the copy numbers of α, ß, and γ duplications, with the risk of PSP and MAPT sub-haplotypes. Design setting and participants: Utilizing whole genome sequencing data of 1,684 (1,386 autopsy confirmed) individuals with PSP and 2,392 control subjects, a case-control study was conducted to investigate the association of copy numbers of α, ß, and γ duplications and structural forms of 17q21.31 with the risk of PSP. All study subjects were selected from the Alzheimer's Disease Sequencing Project (ADSP) Umbrella NG00067.v7. Data were analyzed between March 2022 and November 2023. Main outcomes and measures: The main outcomes were the risk (odds ratios [ORs]) for PSP with 95% CIs. Risks for PSP were evaluated by logistic regression models. Results: The copy numbers of α and ß were associated with the risk of PSP only due to their correlation with H1 and H2, while the copy number of γ was independently associated with the increased risk of PSP. Each additional duplication of γ was associated with 1.10 (95% CI, 1.04-1.17; P = 0.0018) fold of increased risk of PSP when conditioning H1 and H2. For the H1 haplotype, addition γ duplications displayed a higher odds ratio for PSP: the odds ratio increases from 1.21 (95%CI 1.10-1.33, P = 5.47 × 10-5) for H1ß1γ1 to 1.29 (95%CI 1.16-1.43, P = 1.35 × 10-6) for H1ß1γ2, 1.45 (95%CI 1.27-1.65, P = 3.94 × 10-8) for H1ß1γ3, and 1.57 (95%CI 1.10-2.26, P = 1.35 × 10-2) for H1ß1γ4. Moreover, H1ß1γ3 is in linkage disequilibrium with H1c (R2 = 0.31), a widely recognized MAPT sub-haplotype associated with increased risk of PSP. The proportion of MAPT sub-haplotypes associated with increased risk of PSP (i.e., H1c, H1d, H1g, H1o, and H1h) increased from 34% in H1ß1γ1 to 77% in H1ß1γ4. Conclusions and relevance: This study revealed that the copy number of γ was associated with the risk of PSP independently from H1 and H2. The H1 haplotype with more γ duplications showed a higher odds ratio for PSP and were associated with MAPT sub-haplotypes with increased risk of PSP. These findings expand our understanding of how the complex structure at 17q21.31 affect the risk of PSP.