Presence of focal usual interstitial pneumonia is a key prognostic factor in progressive pulmonary fibrosis.

AIMS: Progressive pulmonary fibrosis (PPF) is a newly recognised clinical phenotype of interstitial lung diseases in the 2022 interstitial pulmonary fibrosis (IPF) guidelines. This category is based entirely on clinical and radiological factors, and the background histopathology is unknown. Our objective was to investigate the histopathological characteristics of PPF and to examine the correlation between usual interstitial pneumonia (UIP) and prognosis in this new disease type. We hypothesised that the presence of UIP-like fibrosis predicts patients' survival in PPF cases. METHODS AND RESULTS: We selected 201 cases fulfilling the clinical criteria of PPF from case archives. Cases diagnosed as IPF by a multidisciplinary team were excluded. Whole slide images were evaluated by three pathologists who were blinded to clinical and radiological data. We measured areas of UIP-like fibrosis and calculated what percentage of the total lesion area they occupied. The presence of focal UIP-like fibrosis amounting to 10% or more of the lesion area was seen in 148 (73.6%), 168 (83.6%) and 165 (82.1%) cases for each pathologist, respectively. Agreement of the recognition of UIP-like fibrosis in PPF cases was above κ = 0.6 between all pairs. Survival analysis showed that the presence of focal UIP-like fibrosis correlated with worsened survival under all parameters tested (P < 0.001). CONCLUSIONS: The presence of UIP-like fibrosis is a core pathological feature of clinical PPF, and its presence within diseased areas is associated with poorer prognosis. This study highlights the importance of considering the presence of focal UIP-like fibrosis in the evaluation and management of PPF.

Pursuing Clinical Predictors and Biomarkers for Progression in ILD: Analysis of the Pulmonary Fibrosis Foundation (PFF) Registry.

INTRODUCTION: Pulmonary fibrosis is a characteristic of various interstitial lung diseases (ILDs) with differing etiologies. Clinical trials in progressive pulmonary fibrosis (PPF) enroll patients based on previously described clinical criteria for past progression, which include a clinical practice guideline for PPF classification and inclusion criteria from the INBUILD trial. In this study, we compared the ability of past FVC (forced vital capacity) progression and baseline biomarker levels to predict future progression in a cohort of patients from the PFF Patient Registry. METHODS: Biomarkers previously associated with pathobiology and/or progression in pulmonary fibrosis were selected to reflect cellular senescence (telomere length), pulmonary epithelium (SP-D, RAGE), myeloid activation (CXCL13, YKL40, CCL18, OPN) and fibroblast activation (POSTN, COMP, PROC3). RESULTS: PFF or INBUILD-like clinical criteria was used to separate patients into past progressor and non-past progressor groups, and neither clinical criterion appeared to enrich for patients with greater future lung function decline. All baseline biomarkers measured were differentially expressed in patient groups compared to healthy controls. Baseline levels of SP-D and POSTN showed the highest correlations with FVC slope over one year, though correlations were low. CONCLUSIONS: Our findings provide further evidence that prior decline in lung function may not predict future disease progression for ILD patients, and elevate the need for molecular definitions of a progressive phenotype. Across ILD subtypes, certain shared pathobiologies may be present based on the molecular profile of certain biomarker groups observed. In particular, SP-D may be a common marker of pulmonary injury and future lung function decline across ILDs.

Anti-fibrotic effects of nintedanib on lung fibroblasts derived from patients with Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs).

The tyrosine kinase inhibitor nintedanib has been recently approved for the treatment of Interstitial Lung Diseases (ILDs) that manifest a progressive fibrosis phenotype other than Idiopathic pulmonary Fibrosis (IPF). Nintedanib reduces the development of lung fibrosis in various animal models resembling features of PF-ILD and in vitro, it inhibits the fibrosing phenotype of human lung fibroblasts (HLFs) isolated from patients with IPF. To get insight on the cellular and molecular mechanisms that drive the clinical efficiency of nintedanib in patients with non-IPF PF-ILD, we investigated its effects on the fibrosing functions of HLFs derived from patients with PF-hypersensitivity pneumonitis (PF-HP, n = 7), PF-sarcoidosis (n = 5) and pleuroparenchymal fibroelastosis (PPFE, n = 4). HLFs were treated with nintedanib (10 nM-1 µM) and then stimulated with PDGF-BB (25-50 ng/ml) or TGF-ß1 (1 ng/ml) for 24-72 h to assess proliferation and migration or differentiation. At nanomolar concentrations, nintedanib reduced the levels of PDGF receptor and ERK1/2 phosphorylation, the proliferation and the migration of PF-HP, PF-sarcoidosis and PPFE HLFs stimulated with PDGF-BB. Moreover, nintedanib also attenuates the myofibroblastic differentiation driven by TGF-ß1 but only when it is used at 1 µM. The drug reduced the phosphorylation of SMAD2/3 and decreased the induction of collagen, fibronectin and α-smooth muscle actin expression induced by TGF-ß1. In conclusion, our results demonstrate that nintedanib counteracts fundamental fibrosing functions of lung fibroblasts derived from patients with PF-HP, PF-sarcoidosis and PPFE, at concentrations previously reported to inhibit control and IPF HLFs. Such effects may contribute to its clinical benefit in patients suffering from these irreversible ILDs.

An observational cohort study of interstitial lung abnormalities (ILAs) in a large Japanese health screening population (Kumamoto ILA study in Japan: KILA-J).

BACKGROUND: Interstitial lung abnormalities (ILAs) are subtle or mild parenchymal abnormalities observed in more than 5% of the lungs on computed tomography (CT) scans in patients in whom interstitial lung disease was not previously clinically suspected and is considered. ILA is considered to be partly undeveloped stages of idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF). This study aims to clarify the frequency of subsequent IPF or PPF diagnosis, the natural course from the preclinical status of the diseases, and the course after commencing treatment. METHODS: This is an ongoing, prospective, multicentre observational cohort study of patients with ILA referred from general health screening facilities with more than 70,000 annual attendances. Up to 500 participants will be enrolled annually over 3 years, with 5-year assessments every six months. Treatment intervention including anti-fibrotic agents will be introduced in disease progression cases. The primary outcome is the frequency of subsequent IPF or PPF diagnoses. Additionally, secondary and further endpoints are associated with the efficacy of early therapeutic interventions in cases involving disease progression, including quantitative assessment by artificial intelligence. DISCUSSION: This is the first prospective, multicentre, observational study to clarify (i) the aetiological data of patients with ILA from the largest general health check-up population, (ii) the natural course of IPF or PPF from the asymptomatic stage, and (iii) the effects and outcomes of early therapeutic intervention including anti-fibrotic agents for progressive cases of ILA. The results of this study could significantly impact the clinical practice and treatment strategy for progressive fibrosing interstitial lung diseases. TRIAL REGISTRATION NUMBER: UMIN000045149.

Effects of different soil moisture on the growth, quality, and root rot disease of organic Panax notoginseng cultivated under pine forests.

The under-forest economy in the agroforestry system can improve land use efficiency, protect ecological environment, and promote arable land sustainable development. However, the effects of soil moisture in the forest and irrigation strategies on the healthy growth of intercropping crops are still incomplete. Here, considering the organic Panax notoginseng cultivated under pine forests (PPF) as the research object, we explored the effects of different soil moisture on the physiological state, yield, quality and disease occurrence of PPF. Our results suggested that 80-85% and 95-100% field capacity (FC) treatments were more conducive to increased photosynthetic rate and biomass accumulation of PPF, but 50-55% and 65-70% FC treatments were more conducive to the accumulation of saponins in PPF leaves. Notably, the root rot index of PPF was highest under 95-100% FC (19.51) treatment, significantly higher than that under 65-70% FC (8.44) and 80-85% FC (10.21) treatments. Further, the rhizosphere microorganisms of PPF under different soil moisture treatments were sequenced, and the sequencing data analysis revealed that high soil moisture (95-100% FC) could destroy the microbial diversity balance and cause the accumulation of pathogens (Fusarium oxysporum and Ilyonectria radicicola), leading to a high incidence of root rot. The incidence of PPF root rot was negatively correlated with rhizosphere microbial diversity. Overall, our results highlight that the quantitative irrigation (80-85% FC) is conducive to maintaining the balance between yield, saponin content and disease occurrence of PPF, providing a practical basis for PPF irrigation strategy and promoting the sustainable development of PPF agroforestry system.

Decreased Survival and Lung Function in Progressive Pulmonary Fibrosis.

Background and Objectives: Progressive pulmonary fibrosis (PPF) is a recently described term reserved for patients with fibrotic ILD other than idiopathic pulmonary fibrosis (IPF) with fast clinical deterioration. Here, survival and prognostic biomarkers at the time of diagnosis for PPF are investigated in a fibrotic ILD other than IPF cohort (non-IPF). Materials and Methods: Patients diagnosed during the period of 2012-2018 at the ILD Center of Excellence (St. Antonius Hospital, Nieuwegein, The Netherlands) with a fibrotic ILD were included in this study. The presence of PPF was investigated using the criteria from the updated IPF/PPF guideline during the first year after diagnosis. Logistic regression analysis was used to determine risk factors for PPF. A Kaplan-Meier survival analysis with log-rank test was conducted to analyze survival in patients with and without PPF. Results: This study included 304 non-IPF patients and, for comparison, 379 IPF patients. In non-IPF patients, 146 (46%) fulfilled ≥2 criteria for PPF. These patients had a median transplant-free survival rate of 2.9 ± 0.4 years, which was worse than non-IPF patients without PPF (10.1 ± 1.8 years, p < 0.001). The risk for PPF was increased in patients with FVC < 50% (odds ratio (OR) of 2.50, 95% CI = 1.01-6.17, p = 0.047) or DLCOc ≤ 35% (OR = 2.57, 95% CI = 1.24-5.35, p = 0.011). In the first 3 years after diagnosis, survival in PPF and IPF is the same, while in the following years IPF has a significantly worse survival. Conclusions: The non-IPF cohort with PPF had a significantly worse transplant-free survival compared with the non-IPF cohort without PPF. Independent risk factors for PPF in non-IPF were FVC < 50% and DLCOc ≤ 35%.

Pyriproxyfen-treated bed nets reduce reproductive fitness and longevity of pyrethroid-resistant Anopheles gambiae under laboratory and field conditions.

BACKGROUND: The efficacy of insecticide-treated nets (ITNs) containing the insect growth regulator pyriproxyfen (PPF) and pyrethroid insecticides (PPF-ITNs) is being assessed in clinical trials to determine whether they provide greater protection from malaria than standard pyrethroid-treated ITNs in areas where mosquitoes are resistant to pyrethroids. Understanding the entomological mode of action of this new ITN class will aide interpretation of the results from these trials. METHODS: Anopheles gambiae sensu lato (s.l.) mosquitoes from a susceptible laboratory strain were exposed to PPF-treated netting 24 h, 6 h, and immediately prior to, or 24 h post blood feeding, and the impact on fecundity, fertility and longevity recorded. Pyrethroid-resistant populations were exposed to nets containing permethrin and PPF (PPF-ITNs) in cone bioassays and daily mortality recorded. Mosquitoes were also collected from inside houses pre- and post-distribution of PPF-ITNs in a clinical trial conduced in Burkina Faso; female An. gambiae s.l. were then assessed for fecundity and fertility. RESULTS: PPF exposure reduced the median adult lifespan of insecticide-susceptible mosquitoes by 4 to 5 days in all exposure times (p < 0.05) other than 6 h pre-blood meal and resulted in almost complete lifelong sterilization. The longevity of pyrethroid-resistant mosquitoes was also reduced by at least 5 days after exposure to PPF-ITNs compared to untreated nets, but was unaffected by exposure to standard pyrethroid only ITNs. A total of 386 blood-fed or gravid An. gambiae s.l. females were collected from five villages between 1 and 12 months before distribution of PPF-ITNs. Of these mosquitoes, 75% laid eggs and the remaining 25% appeared to have normal ovaries upon dissection. In contrast, only 8.6% of the 631 blood-fed or gravid An. gambiae s.l. collected post PPF-ITN distribution successfully oviposited; 276 (43.7%) did not oviposit but had apparently normal ovaries upon dissection, and 301 (47.7%) did not oviposit and had abnormal eggs upon dissection. Egg numbers were also significantly lower (average of 138/female prior distribution vs 85 post distribution, p < 0.05). CONCLUSION: Exposure to a mixture of PPF and pyrethroids on netting shortens the lifespan of mosquitoes and reduces reproductive output. Sterilization of vectors lasted at least one year under operational conditions. These findings suggest a longer effective lifespan of PPF-pyrethroid nets than reported previously.

Schistosoma mansoni-related periportal fibrosis; can we use APRI and PSDR levels in the real-time selection of patients for targeted endoscopy in a resource-limited setting? A case-control study.

BACKGROUND: Schistosoma mansoni related hepatic fibrosis is usually associated with hemodynamic alteration with increased mortality due to bleeding varices. The diagnosis of varices before bleeding imposes a big challenge in resource-limited countries using endoscopy. Published evidence on the utility of non-invasive clinical tools in predicting the presence of varices among patients with S. mansoni related periportal fibrosis is still inadequate including Aspartate to platelet ratio index (APRI) and Platelet to splenic diameter ratio (PSDR) levels. This study describes the determinants of portal varices and assesses the potential utility of the APRI and PSDR level in the discrimination of portal varices among patients with S. mansoni related periportal fibrosis (PPF). METHODS: A case-control study using cross-sectional data was done among patients with Schistosoma mansoni related periportal fibrosis at Bugando Medical Centre, in Mwanza Tanzania. The derivation cohort included patients enrolled between 2015 and 2019 and the validation cohort included patients enrolled from 2019 till March 2021. Socio-demographic, laboratory, ultrasound, and upper digestive endoscopic information were analyzed using STATA 13. The prevalence and determinants of varices were determined by logistic regression. The sensitivity and specificity of independent factors were determined to assess their utility in discriminating the presence of portal varices in patients with PPF. RESULTS: In total, 250 patients were included in the derivation cohort, 109 (43.6%; 95% CI 37.3-49.9) of them had varices. The odds of having varices were independently increased among patients with higher APRI levels than 1.51, (AOR: 5.8; 95% CI 3.1-11.1; p < 0.001) and PSDR levels that were lower than 5700 (AOR: 5.9; 95% CI 3.2-11.2; p < 0.001). Both APRI and PSDR levels had significantly high sensitivity and specificity in predicting the presence of esophageal varices. However, the combined values of APRI and PSDR had higher specificity than any of the two markers. Of the 200 patients in the validation cohort 94 (47.0%; 95% CI 40.0-54.2) had varices, the discriminative power of the final model and the predictive ability of both APRI, PSDR, and APRI-PSDR combined levels were highly maintained. CONCLUSIONS: This study indicates that varices are a common encounter among patients with S. mansoni related periportal fibrosis and it is independently associated with higher APRI and lower PSDR levels suggesting that these tools are potential discriminators of varices in this subgroup of patients. The reproducibility of these results should further be assessed longitudinally as potential non-invasive tools in selecting patients at high risk of having esophageal varices who could benefit from the targeted endoscopic intervention in a resource-limited setting like ours.

Propofol protects cardiomyocytes from hypoxia/reoxygenation injury via regulating MALAT1/miR-206/ATG3 axis.

Previous studies have shown that propofol (PPF) plays a protective role in ischemia-reperfusion (I/R) in multiple organs and tissues. This study was aimed to explore the mechanism of PPF in ameliorating myocardial ischemia-reperfusion injury (MIRI). MIRI model was established with Sprague-Dawley rats, and PPF pretreatment was performed before reperfusion. Creatine kinase isoform (CK-MB), lactate dehydrogenase (LDH), and hematoxylin and eosin stain were used to evaluate the severity of MIRI. H9c2 cells were treated with hypoxia/reoxygenation (H/R) to simulate I/R injury in vitro. Real-time quantitative polymerase chain reaction (qPCR) was employed to assess MALAT1 and microRNA (miR)-206 expressions. Autophagy-related 3 (ATG3), LC3BⅡ/LC3BⅠ, and Beclin-1 expression were examined by western blot. Apoptosis was monitored using flow cytometry. Interaction between MALAT1 and miR-206 was determined by bioinformatics analysis, dual-luciferase reporter gene assay, RIP assay, and RNA pull-down assay. PPF pretreatment remarkably reduced CK-MB level, LDH level, myocardial infarct size, and LC3BⅡ/LC3BⅠ ratio and Beclin-1 expression in the rats with MIRI, and repressed the apoptosis of H9c2 cells exposed to H/R. PPF pretreatment markedly suppressed MALAT1 expression and enhanced miR-206 expression in both in vivo and in vitro models. MiR-206 was identified as a target of MALAT1 in cardiomyocytes, and MALAT1 could increase the expression of ATG3. Additionally, the upregulation of MALAT1 partially reversed the protective effect of PPF on cardiomyocytes in vitro. PPF modulated MALAT1/miR-206/ATG3 axis to protect cardiomyocytes against I/R injury.

Porphyrin Based 2D-MOF Structures as Dual-Kinetic Sorafenib Nanocarriers for Hepatoma Treatment.

The existing clinical protocols of hepatoma treatment require improvement of drug efficacy that can be achieved by harnessing nanomedicine. Porphyrin-based, paddle-wheel framework (PPF) structures were obtained and tested as dual-kinetic Sorafenib (SOR) nanocarriers against hepatoma. We experimentally proved that sloughing of PPF structures combined with gradual dissolving are effective mechanisms for releasing the drug from the nanocarrier. By controlling the PPF degradation and size of adsorbed SOR deposits, we were able to augment SOR anticancer effects, both in vitro and in vivo, due to the dual kinetic behavior of SOR@PPF. Obtained drug delivery systems with slow and fast release of SOR influenced effectively, although in a different way, the cancer cells proliferation (reflected with EC50 and ERK 1/2 phosphorylation level). The in vivo studies proved that fast-released SOR@PPF reduces the tumor size considerably, while the slow-released SOR@PPF much better prevents from lymph nodes involvement and distant metastases.

Adaptive Synaptic Memory via Lithium Ion Modulation in RRAM Devices.

Biologically plausible computing systems require fine-grain tuning of analog synaptic characteristics. In this study, lithium-doped silicate resistive random access memory with a titanium nitride (TiN) electrode mimicking biological synapses is demonstrated. Biological plausibility of this RRAM device is thought to occur due to the low ionization energy of lithium ions, which enables controllable forming and filamentary retraction spontaneously or under an applied voltage. The TiN electrode can effectively store lithium ions, a principle widely adopted from battery construction, and allows state-dependent decay to be reliably achieved. As a result, this device offers multi-bit functionality and synaptic plasticity for simulating various strengths in neuronal connections. Both short-term memory and long-term memory are emulated across dynamical timescales. Spike-timing-dependent plasticity and paired-pulse facilitation are also demonstrated. These mechanisms are capable of self-pruning to generate efficient neural networks. Time-dependent resistance decay is observed for different conductance values, which mimics both biological and artificial memory pruning and conforms to the trend of the biological brain that prunes weak synaptic connections. By faithfully emulating learning rules that exist in human's higher cortical areas from STDP to synaptic pruning, the device has the capacity to drive forward the development of highly efficient neuromorphic computing systems.

Extended trochanteric osteotomy (ETO) fixation for femoral stem revision in periprosthetic fractures: Dall-Miles plate versus cables.

BACKGROUND: Extended trochanteric osteotomy (ETO) is a well-established surgical technique used for femoral stem retrieval in revision hip arthroplasty procedures. Fixation of ETO is commonly achieved through wire, cable or cable-plate fixation. No evidence exists to date to suggest which method is superior when used in an acute traumatic setting. METHODS: Thirty cases of acute periprosthetic fracture requiring femoral stem revision with an ETO were identified over a 10-year period. Each case had a loose femoral prosthesis which was revised using an ETO approach. Nineteen of these were fixed using cables only, and 11 were fixed using a cable-plate construct. Radiographic outcomes measured included greater trochanter migration, osteolysis, union, time to union and overall success using the Beals and Tower classification. Clinical outcomes were assessed using the modified Harris Hip Score. RESULTS: Twenty-three Vancouver B/C-type fractures were identified. The remaining seven consisted of other fracture types with a loose femoral stem requiring revision through ETO. Mean follow-up was 32 months in the cable group and 12 months in the cable-plate group. The cable-plate construct performed better than cables alone. Mean migration rates were 1.7 mm lower in the cable-plate group (p < 0.05). Beals and Tower classification of radiographic outcomes was significantly better in the cable-plate group (p < 0.01). Modified Harris Hip Scores were better in this group also (p < 0.05). CONCLUSION: When utilising an ETO approach for femoral stem revision in acute periprosthetic fractures, superior clinical and radiographic outcomes can be achieved if fixation involves a cable-plate system instead of cables only.

Flexible Ionic-Electronic Hybrid Oxide Synaptic TFTs with Programmable Dynamic Plasticity for Brain-Inspired Neuromorphic Computing.

Emulation of biological synapses is necessary for future brain-inspired neuromorphic computational systems that could look beyond the standard von Neuman architecture. Here, artificial synapses based on ionic-electronic hybrid oxide-based transistors on rigid and flexible substrates are demonstrated. The flexible transistors reported here depict a high field-effect mobility of ≈9 cm2 V-1 s-1 with good mechanical performance. Comprehensive learning abilities/synaptic rules like paired-pulse facilitation, excitatory and inhibitory postsynaptic currents, spike-time-dependent plasticity, consolidation, superlinear amplification, and dynamic logic are successfully established depicting concurrent processing and memory functionalities with spatiotemporal correlation. The results present a fully solution processable approach to fabricate artificial synapses for next-generation transparent neural circuits.

Selective expression of a constitutively active erythropoietin receptor in GABAergic neurons alters hippocampal network properties without affecting cognition.

We have previously shown that treatment with erythropoietin (EPO) improves cognition in patients with neuropsychiatric disorders as well as in healthy mice, and that transgenic expression of a constitutively active form of the EPO receptor (cEPOR) in glutamatergic neurons boosts higher cognitive functions in mice. In the present work, we examined whether selective activation of EPOR signaling in GABAergic neurons would also modulate cognitive performance. We generated transgenic mice that express cEPOR under the control of the vesicular inhibitory amino acid transporter (Viaat) promoter and subjected them to comprehensive behavioral, cognitive, and electrophysiological analyses. We demonstrate that transgenic expression of cEPOR in GABAergic neurons alters hippocampal gamma-oscillations and enhances long-term potentiation but neither impairs nor improves cognition. To conclude, constitutively active EPOR in GABAergic neurons changes hippocampal network properties without affecting cognition, which suggests that the effect of EPO on cognition is dominated by its effect on the glutamatergic system. Treatment with EPO improves cognitive performance. We previously demonstrated that this effect is replicated by constitutive autoactivation of cEPOR in glutamatergic neurons. By contrast, cEPOR in GABAergic neurons changes hippocampal network properties but neither impairs nor enhances cognition. Thus, EPO modulates neuronal plasticity, and the cognitive benefits may be mainly attributable to its effect on the glutamatergic system.

Perioperative Complications in Posterior Pharyngeal Flap Surgery: Review of the National Surgical Quality Improvement Program Pediatric (NSQIP-PEDS) Database.

BACKGROUND: Posterior pharyngeal flap (PPF) surgery is effective for treating velopharyngeal insufficiency but has historically been associated with risk of airway compromise. This study aims to identify risk factors for complications from and readmission after PPF using a national database. METHODS: Patients who underwent PPF surgery were selected from the 2012 American College of Surgeons National Surgical Quality Improvement Program Pediatric (NSQIP-PEDS) database. Patient characteristics, comorbidities, and complication/readmission data were analyzed. RESULTS: Among 225 study patients, 12 (5.3%) suffered perioperative complications. The most common complications were pulmonary in nature (5 patients, 2.2%), including prolonged postoperative mechanical ventilation (3 patients, 1.3%). Underlying asthma (P = .024) or any cardiac risk factor (P = .047) conveyed significant complication risk. Further, severe cardiac risk factors were associated with postoperative bleeding (P = .024). Readmission (4 patients, 1.7%) and reoperation (3 patients, 1.3%) occurred at mean intervals of 9 and 10 days after the original procedure. Seventy-nine patients (35%) were discharged postoperatively on an outpatient basis, and this subgroup included only one patient (1.2%) with a complication (P = .038). CONCLUSIONS: The overall perioperative complication rate for PPF surgery is low at 5.3%. Patients with underlying cardiac risk factors, severe American Society of Anesthesiologists Physical Status class, and asthma should prompt greater attention given their heightened risk profiles.

Surgical management of trigeminal schwannomas: defining the role for endoscopic endonasal approaches.

OBJECT: Because multiple anatomical compartments are involved, the surgical management of trigeminal schwannomas requires a spectrum of cranial base approaches. The endoscopic endonasal approach to Meckel's cave provides a minimal access corridor for surgery, but few reports have assessed outcomes of the procedure or provided guidelines for case selection. METHODS: A prospectively acquired database of 680 endoscopic endonasal cases was queried for trigeminal schwannoma cases. Clinical charts, radiographic images, and long-term outcomes were reviewed to determine outcome and success in removing tumor from each compartment traversed by the trigeminal nerve. RESULTS: Four patients had undergone endoscopic resection of trigeminal schwannomas via the transpterygoid approach (mean follow-up 37 months). All patients had disease within Meckel's cave, and 1 patient had extension into the posterior fossa. Gross-total resection was achieved in 3 patients whose tumors were purely extracranial. One patient with combined Meckel's cave and posterior fossa tumor had complete resection of the extracranial disease and 52% resection of the posterior fossa disease. One patient with posterior fossa disease experienced a sixth cranial nerve palsy in addition to a corneal keratopathy from worsened trigeminal neuropathy. There were no CSF leaks. Over the course of the study, 1 patient with subtotal resection required subsequent stereotactic radiosurgery for disease progression within the posterior fossa. CONCLUSIONS: Endoscopic endonasal approaches appear to be well suited for trigeminal schwannomas restricted to Meckel's cave and/or extracranial segments of the nerve. Lateral transcranial skull base approaches should be considered for patients with posterior fossa disease. Further multiinstitutional studies will be necessary for adequate power to help determine relative indications between endoscopic and transcranial skull base approaches.

Association between maternal mental health-related hospitalisation in the 5 years prior to or during pregnancy and adverse birth outcomes: a population-based retrospective cohort data linkage study in the Northern Territory of Australia.

Background: Mental health conditions prior to or during pregnancy that are not addressed can have adverse consequences for pregnancy and birth outcomes. This study aimed to determine the extent to which women's mental health-related hospitalisation (MHrH) prior to or during pregnancy was associated with a risk of adverse birth outcomes. Methods: We linked the perinatal data register for all births in the Northern Territory, Australia, from the year 1999 to 2017, to hospital admissions records to create a cohort of births to women aged 15-44 years with and without MHrH prior to or during pregnancy. We used Modified Poisson Regression and Latent Class Analysis to assess the association between maternal MHrH and adverse birth outcomes (i.e., stillbirth, preterm birth, low birth weight, and short birth length). We explored a mediation effect of covariates on theoretical causal paths. We calculated the adjusted Population Attributable Fraction (PAF) and Preventive Fractions for the Population (PFP) for valid associations. Findings: From 72,518 births, 70,425 births (36.4% for Aboriginal women) were included in the analysis. The Latent Class Analys identified two classes: high (membership probability of 10.5%) and low adverse birth outcomes. Births to Aboriginal women with MHrH were around two times more likely to be in the class of high adverse birth outcomes. MHrH prior to or during pregnancy increased the risk of all adverse birth outcomes in both populations with risk ranging from 1.19 (95% CI: 1.05, 1.35) to 7.89 (1.17, 53.37). Eight or more antenatal care visits and intrauterine growth restriction mostly played a significant mediation role between maternal MHrH and adverse birth outcomes with mediation effects ranging from 1.04 (1.01, 1.08) to 1.39 (1.14, 1.69). MHrH had a low to high population impact with a PAF ranging from 16.1% (5.1%, 25.7%) to 87.3% (14.3%, 98.1%). Eight or above antenatal care visits avert extra adverse birth outcomes that range from 723 (332-765) stillbirths to 3003 (1972-4434) preterm births. Interpretation: Maternal MHrH is a modifiable risk factor that explained a low to moderate risk of adverse birth outcomes in the Northern Territory. The knowledge highlights the need for the development and implementation of preconception mental health care into routine health services. Funding: The Child and Youth Development Research Partnership (CYDRP) data repository is supported by a grant from the Northern Territory Government.

Compare three diagnostic criteria of progressive pulmonary fibrosis.

Background: In patients with fibrotic interstitial lung disease (ILD), a progressive pulmonary fibrosis (PPF) typically demonstrates worsening respiratory symptoms, lung function decline and continuing fibrosis. The goal of this study was to compare the three different diagnostic criteria of PPF. Methods: Except for idiopathic pulmonary fibrosis (IPF), all consecutive adult patients with fibrotic ILD were retrospectively examined for the three predefined diagnostic criteria of PPF. The three criteria assessed the disease progression in preceding 6 (0.5-year), 12 (1-year) and 24 (2-year) months respectively. The clinical characteristics, decline in predicted percent of forced vital capacity (FVC%) and survival of three groups were compared, followed by determination of risk factors for mortality. Results: We identified 246 patients by 0.5-year standard, 154 patients by 1-year standard and 281 patients by 2-year standard. Among them, 95% of patients in 1-year group were also included in 2-year group. The average 1-year decline in FVC% was -1.0%, -2.7%, and -4.1% for 0.5-, 1-, and 2-year group respectively. The 4-year survival rate was 74% in 0.5-year group, 66% in 1-year group, and 62% in 2-year group. In multivariate Cox model, only baseline predicted percent diffusing capacity of the lungs for carbon monoxide (DLCO%) <50% was correlated with mortality, with a hazard ratio of 3.4 (95% CI: 1.1-10.6, P=0.03). Conclusions: In the current situations, both the 1- and 2-year criterion are the reasonable choice to define PPF both in researches and clinical practice, and DLCO% is an independent predictor for mortality of PPF.

Prevalence of Progressive Fibrosing Interstitial Lung Disease in Patients with Primary Sjogren Syndrome.

BACKGROUND: Interstitial lung disease (ILD) represents a frequent cause of morbidity and mortality in primary Sjogren syndrome (pSS). However, the prevalence and behavior of pSS-ILD remains incomplete, largely based on retrospective heterogeneous studies. AIM OF THE STUDY: To investigate the prevalence of progressive pulmonary fibrosis (PPF) in a multicentric cohort of patients with pSS-ILD. Additionally, this study explored possible correlations between PPF and clinical, demographic, and serological features of pSS. METHODS: All consecutive patients with pSS-ILD were enrolled in a 6-month period. Clinical, demographic, and serological features of pSS, other than functional and radiological lung features, were collected. Clinical behaviors of ILD other than PPF were also investigated. RESULTS: Seventy-two patients were enrolled. A fibrosing ILD pattern was observed in 65.3% of patients with pSS-ILD; among them, 55.3% showed a PPF. The radiologic pattern (NSIP, UIP, or others) was not associated with PPF; in particular, patients with PFF had UIP in 42.3% of cases and NSIP in 57.7%, without a significant difference with respect to the non-PPF group (p = 0.29). Shorter pSS disease duration, higher age at pSS diagnosis, and lower frequency of antinuclear antibodies were correlated with the PPF subgroup. However, multivariate analysis did not confirm these associations. DISCUSSION: This study provides valuable insights into the prevalence and characteristics of PPF in pSS-ILD. In particular, UIP and NSIP showed a similar evolution towards PPF in patients with pSS; for NSIP, this behavior was more frequent than for other rheumatic diseases. Our results emphasize the importance of early recognition of PPF for timely intervention and careful follow-up. CONCLUSIONS: This study provides valuable insights into the prevalence and characteristics of PPF in pSS-ILD. In particular, UIP and NSIP showed a similar evolution towards PPF in patients with pSS; for NSIP, this behavior was more frequent than for other rheumatic diseases. Our results emphasize the importance of early recognition of PPF for timely intervention and careful follow-up.

Dynamics of Open States and Promoter Functioning in the appY_red and appY_green Genetic Constructions Based on the pPF1 Plasmid.

BACKGROUND: Although the role of dynamic factors in DNA function still remains unclear, research in this direction is a rapidly developing area of molecular biology. In this work, the genetic constructions appY_red and appY_green, based on the plasmid pPF1 and containing a fragment of Escherichia coli (E. coli) DNA with predicted promoter-like regions, are considered complex dynamic systems in which local sites of double helix unwinding, called open states, can arise and propagate. The purpose of the article is to show the existence of a connection between the dynamics of open states and the functioning of predicted promoters. METHODS: We experimentally verified the functionality of the predicted promoters using a reporter vector. Using a reverse transcription reaction, transcription start sites were identified indicating the presence of two divergent promoters, one on each strand. In mathematical studies, a dynamic model was used that described open states as one-soliton solutions (kinks) of a system of nonlinear partial differential equations, and the influence of the torque Mτ on the dynamics of kinks was taken into account. RESULTS: Fluorescence analysis of colonies of E. coli cells transformed with plasmid constructions showed that one of the two promoters is stronger than the other and that the strength of the promoters depends on the orientation of the fragment under study in the plasmid. On the other hand, using mathematical modeling, the energy profiles of genetic constructions were calculated and the kink trajectories were constructed. In addition, by studying the effect of torsion moment in model studies, we found threshold torque values at which the behavior of kinks changes dramatically: from oscillatory to translational motion. The minimum values of torsion moment required to initiate the transcription process were also assessed. CONCLUSIONS: A comparative analysis of the results of experimental data and model calculations showed a good correlation between the preferred starting points and the direction of transcription, which in turn confirmed the existence of a relationship between the dynamics of open states and the functioning of promoters.