Six induced pluripotent stem cell lines from fibroblasts of individuals with CLN3-related conditions.

Primary fibroblasts from six individuals with CLN3-related conditions were used to generate induced pluripotent stem cell (iPSC) lines CHDTRi001-B, CHDTRi002-B, CHDTRi003-A, CHDTRi004-B, CHDTRi005-A, and CHDTRi006-E through the expression of four reprogramming factors: human OCT3/4, KLF4, SOX2, and c-MYC. The iPSC lines were characterized to confirm their pluripotency via immunocytochemistry, flow cytometry, and teratoma formation. Genomic stability, cell line identity, and CLN3 genotype were confirmed. These iPSC lines may be used as participant-derived experimental models for further investigation of CLN3, a rare, fatal, pediatric, blindness and neurodegenerative lysosomal disorder with no cure.

Response styles to positive affect during a positive psychology intervention for veterans with PTSD and moral injury: Preliminary results from a moral elevation intervention pilot trial.

OBJECTIVE: Veterans with posttraumatic stress disorder (PTSD) or moral injury are at risk of maladaptive response styles to positive emotions, such as emotional numbing. A potential pathway to target problematic responses to positive affect is a positive psychology intervention that elicits moral elevation-feeling inspired after witnessing someone perform a virtuous act. This study aims to examine responses to positive affect in a pilot trial of a web-based moral elevation intervention titled, MOVED: Moral Elevation Online Intervention for Veterans Experiencing Distress Related to PTSD and Moral Injury. Method: Veterans who reported moral injury distress and probable PTSD were randomized into an intervention or control condition (n = 48). We examined repeated measures data during the trial and focused on three subscales of the Response to Positive Affect Questionnaire: rumination on positive mood and somatic experiences (emotion-focus), rumination on positive aspects of the self and pursuit of relevant goals (self-focus), and efforts to dampen positive moods (dampening). Three multilevel models were fitted with time and condition as predictors and subscale scores as outcomes. Qualitative data reported at intervention sessions was also reviewed and coded based on the three subscales. RESULTS: Veterans in the MOVED condition reported more positive rumination than the control condition for both emotion-focus (b = 2.70, p = .023) and self-focus styles (b = 2.90, p = .003). There was no group difference in the dampening style. Qualitative responses after elevation-eliciting exercises and session-based goals were most frequently coded as including emotion-focused positive rumination, followed by dampening, then self-focused rumination. CONCLUSION: These results provide preliminary evidence that a moral elevation intervention might contribute to positive responses to positive affect in a sample predisposed to emotional numbing. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

[Correlation analysis of polyclonal plasma cell proportion in the bone marrow with clinical characteristics of patients with newly diagnosed multiple myeloma].

Objective: To explore the correlation of bone marrow polychonal plasma cell proportion (pPC% ) and clinical features in newly diagnosed multiple myeloma (NDMM) patients. Methods: A retrospective analysis of 317 patients with NDMM admitted to Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2018 to January 2023 was performed. The results of the pPC% in all patients were clear. The relationship between the pPC% and clinical characteristics was analyzed. Results: A total of 317 patients were included, comprising 180 males and 137 females. The median age at diagnosis was 61 (26-91) years, and 55.8% were 60 years or older. The pPC% in the bone marrow of patients with NDMM was different in the DS, International Staging System (ISS), and revised ISS (R-ISS) stages (P=0.002, 0.010, and 0.049, respectively), whereas no statistical difference in pPC% was observed among patients with different FISH risk stratigrams (P=0.971). The correlation coefficient between pPC% and hemoglobin (HGB) at the first diagnosis in patients was 0.211 (P<0.01). The correlation coefficients with serum calcium, serum creatinine, M protein level, and ß(2)-microglobulin were -0.141, -0.120, -0.181, and -0.207, respectively, and the results of the significance test were P=0.012, 0.033, 0.004, and 0.002, respectively, indicating a negative correlation. Compared with the patients with a pPC% of ≥2.5%, the group of patients with a pPC% of <2.5% had significantly higher levels of light chain, serum calcium, serum creatinine, M protein, and ß(2)-microglobulin at the initial diagnosis (P<0.05) ; lower HGB level (P<0.001) ; and a higher proportion of patients in ISS stage Ⅲ (P=0.034) . Conclusion: In this study, the pPC% in patients with NDMM was associated with clinical features of good prognosis, including higher HGB, lower serum calcium, serum creatinine, M protein quantity, ß(2)-microglobulin, light chain involvement, lower proportion of advanced disease (DS stage and ISS stage Ⅲ), and clinical features showing lower tumor burden.

Pan-cancer analysis of heterogeneity of tumor mutational burden and genomic mutation under treatment pressure.

BACKGROUND: High tumor mutational burden (TMB) is one of the widely researched predictive biomarkers of immune checkpoint inhibitors and has been shown to be closely related with response to immunotherapy in multiple cancer types. However, for patients who have failed conventional therapy and are about to undergo immunotherapy, there is no consensus recommendation on the timing of tumor sampling for TMB analysis, and the effects of different therapies on TMB have not been clarified. This retrospective observational study aimed to investigate the heterogeneity of TMB and genomic mutation under the treatment pressure. PATIENTS AND METHODS: We retrospectively collected the available genomic and therapeutic information from 8051 samples across 15 tumor types (>50 samples/tumor) found in 30 published studies and investigated the distribution and heterogeneity of TMB under treatment across diverse cohorts. RESULTS: This integrated analysis has shown anticancer treatments increased TMB. Significant effects of treatment on TMB were more frequently observed in tumor types with lower treatment-naïve TMB, including breast, prostate, and pediatric cancers. For different cancer therapies, chemotherapy was prone to be correlated with an increased TMB in most cancer types. Meanwhile, the fraction of the TMB-high category of breast, prostate, and bladder cancers and glioma increased significantly after chemotherapy. Several actionable genes including ERS1 and NF1 in breast cancer, as well as some prognostic markers including TERT in bladder cancer and IDH1 in glioma, were significantly changed in post-chemotherapy tumors compared to treatment-naïve tumors. CONCLUSION: Our study reveals the heterogeneity of TMB under treatment across diverse cancer types and provides evidences that chemotherapy was associated with increases in TMB as well as the fraction of TMB-high category, suggesting that resampling tumor tissues for calculating post-chemotherapy TMB could be a better option for predicting the response to immunotherapy, especially for tumors with initially low TMB.

Uncovering strain- and age-dependent innate immune responses to SARS-CoV-2 infection in air-liquid-interface cultured nasal epithelia.

Continuous assessment of the impact of SARS-CoV-2 on the host at the cell-type level is crucial for understanding key mechanisms involved in host defense responses to viral infection. We investigated host response to ancestral-strain and Alpha-variant SARS-CoV-2 infections within air-liquid-interface human nasal epithelial cells from younger adults (26-32 Y) and older children (12-14 Y) using single-cell RNA-sequencing. Ciliated and secretory-ciliated cells formed the majority of highly infected cell-types, with the latter derived from ciliated lineages. Strong innate immune responses were observed across lowly infected and uninfected bystander cells and heightened in Alpha-infection. Alpha highly infected cells showed increased expression of protein-refolding genes compared with ancestral-strain-infected cells in children. Furthermore, oxidative phosphorylation-related genes were down-regulated in bystander cells versus infected and mock-control cells, underscoring the importance of these biological functions for viral replication. Overall, this study highlights the complexity of cell-type-, age- and viral strain-dependent host epithelial responses to SARS-CoV-2.

[Venous cerebral complications after microsurgery for complex aneurysms of the middle cerebral arteries]. / Venoznye tserebral'nye oslozhneniya mikrokhirurgicheskikh operatsii po povodu slozhnykh anevrizm srednikh mozgovykh arterii.

Microsurgeries are common for complex aneurysms of the middle cerebral artery (MCA). OBJECTIVE: To evaluate the incidence and types of venous cerebral disorders after microsurgeries for complex MCA aneurysms. MATERIAL AND METHODS: A retrospective study included 285 patients with complex MCA aneurysms between 2009 and 2020. Pterional craniotomy and transsylvian approach were used in all cases. Aneurysm clipping was performed in 230 cases, revascularization - 27, trapping without bypass - 17, reinforcement - in 11 cases. Computed tomography within 1-3 days after surgery recognized venous cerebral disorders as heterogeneous foci of abnormal brain density with unclear boundaries. These foci were crescent-shaped as a rule and located in deep and basal parts of the frontal lobes. RESULTS: Venous abnormalities occurred in 76 (26.7%) patients. Thirty-five (12.3%) patients had mild venous edema of the frontal lobe alone. In 35 (12.3%) patients, we found moderate disorders with focus in the frontal lobe and compression of anterior horn of the left lateral ventricle with or without hemorrhagic imbibition. Severe disorders occurred in 6 (2.1%) patients with lesion extending to the frontal, insular and temporal lobes. These lesions were accompanied by hemorrhagic imbibition, and lateral dislocation exceeded 5 mm. CONCLUSION: Careful dissection of veins in Sylvian fissure with preservation of bridging veins is likely to reduce the risk of this complication. Cauterization of a large vein in Sylvian fissure should be followed by careful hemostasis within frontal or temporal cortex. Bleeding and cortical tension can indicate intracerebral hematoma whose likelihood is higher in patients with venous cerebral disorders.

Evaluation of Hemodynamic Alterations after Flow Diverter Placement using the AneurysmFlowTM tool.

Background: AneurysmFlow (Phillips Healthcare) is the flow measurement tool, utilizing an optical flow-based algorithm from DSA, lacks sufficient published studies. This study aimed to assess the significance of flow velocity changes and the Mean Aneurysm Flow Amplitude (MAFA) ratio in evaluating outcomes following flow-diverting treatments. Methods: Between June 2021 and October 2022, 41 patients with 42 aneurysms underwent FDS treatment with AneurysmFlow measu-rement at the Bach Mai Radiology Center. Results: The tool achieved a 90.5% success rate in 38 out of 42 patients. Most aneurysms (89.5%) were small to medium-sized (<10 mm), and a decrease in flow velocity post-stent deployment was ob-served in 78.9% of cases. Conversely, 21.1% showed increased flow, mainly in aneurysms smaller than 5 mm. No significant association was found between flow changes or MAFA ratio and aneurysm size characteristics. Twenty-two patients (59.5%) underwent re-examination at 6 months, revealing no correlation in MAFA ratio between completely and incompletely occluded aneurysms. Conclusions: Our current investigation, primarily centered on small and medium-sized aneurysms, did not uncover any link between quantitative flow changes assessed using the AneurysmFlow software and the occlusion status of aneurysms at the 6-month follow-up post-flow diverter treatment. Larger case series with extended follow-up imaging are necessary to further explore these findings.

The Current State of Neonatal Neurodevelopmental Follow-up Programs in North America: A Children's Hospitals Neonatal Consortium Report.

OBJECTIVE: This study aimed to determine neonatal neurodevelopmental follow-up (NDFU) practices across academic centers. STUDY DESIGN: This study was a cross-sectional survey that addressed center-specific neonatal NDFU practices within the Children's Hospitals Neonatal Consortium (CHNC). RESULTS: Survey response rate was 76%, and 97% of respondents had a formal NDFU program. Programs were commonly staffed by neonatologists (80%), physical therapists (77%), and nurse practitioners (74%). Median gestational age at birth identified for follow-up was ≤32 weeks (range 26-36). Median duration was 3 years (range 2-18). Ninety-seven percent of sites used Bayley Scales of Infant and Toddler Development, but instruments used varied across ages. Scores were recorded in discrete electronic data fields at 43% of sites. Social determinants of health data were collected by 63%. Care coordination and telehealth services were not universally available. CONCLUSION: NDFU clinics are almost universal within CHNC centers. Commonalities and variances in practice highlight opportunities for data sharing and development of best practices. KEY POINTS: · Neonatal NDFU clinics help transition high-risk infants home.. · Interdisciplinary neonatal intensive care unit follow-up brings together previously separated outpatient service lines.. · This study reviews the current state of neonatal NDFU in North America..

[Comparison of polymethyl methacrylate skull implant fixation by three types of titanium fasteners]. / Sravnenie sposobov fiksatsii implantov cherepa iz polimetilmetakrilata tremya vidami titanovykh krepezhei.

OBJECTIVE: To evaluate mechanical strength of three methods of polymethyl methacrylate skull implant fixation in two experimental models. MATERIAL AND METHODS: The first experiment was performed on a plastic model that was as close as possible to bone in structural characteristics. The second experiment was performed on a biological specimen (a ram's head). We assessed the quality of implant fixation to bone window edges by craniofixes, ties and microscrews and lateral intercortical screws. RESULTS: Craniofixes are feasible for small flat flaps, but not advisable for wide highly curved implants. They are also the most expensive method of fixation. Implant fixation by ties and microscrews is a universal method comparable in price to craniofix. Lateral intercortical fixation is effective both for small flat implants and wide implants with large curvature. However, this method is not always applicable. CONCLUSION: Combined fixation by lateral intercortical screws and ties allows for the most effective fixation while reducing the overall price of consumables.

Unlocking the potentials of Ustilago trichophora for up-cycling polyurethane-derived monomer 1,4-butanediol.

Plastic usage by microbes as a carbon source is a promising strategy to increase the recycling quota. 1,4-butanediol (BDO) is a common monomer derived from polyesters and polyurethanes. In this study, Ustilago trichophora was found to be an efficient cell-factory to valorize BDO. To investigate product formation by U. trichophora, we refined the traditional ion exclusion liquid chromatography method by examining eluent, eluent concentrations, oven temperatures, and organic modifiers to make the chromatography compatible with mass spectrometry. An LC-UV/RI-MS2 method is presented here to identify and quantify extracellular metabolites in the cell cultures. With this method, we successfully identified that U. trichophora secreted malic acid, succinic acid, erythritol, and mannitol into the culture medium. Adaptive laboratory evolution followed by medium optimization significantly improved U. trichophora growth on BDO and especially malic acid production. Overall, the carbon yield on the BDO substrate was approximately 33% malic acid. This study marks the first report of a Ustilaginaceae fungus capable of converting BDO into versatile chemical building blocks. Since U. trichophora is not genetically engineered, it is a promising microbial host to produce malic acid from BDO, thereby contributing to the development of the envisaged sustainable bioeconomy.

Starting early: Case study of mentoring for undergraduate training through the Veterans Health Administration and implications for promoting equity.

Undergraduate mentoring and research internships promote entry into graduate training, academic success, research productivity, and greater career satisfaction. Most pathway programs to enhance representation within academia and health care intervene at the graduate level, leaving a critical gap in undergraduate training. The Veterans Health Administration's (VHA's) national network of clinicians and researchers is uniquely suited to provide equitable access to quality mentorship and education for undergraduates interested in health care careers. We present a program evaluation case study of a VHA undergraduate training program incorporating empirically supported components that promote success and transition to graduate school, including tiered mentorship, a didactic-preceptor model, hands-on experience, and interdisciplinary work. We describe participant characteristics and consider the program elements that may contribute to trainees' success, highlighting the importance of undergraduate training within a health care system like VHA. We found that all program completers attained their bachelor's degree and nearly 70% advanced to graduate studies. Despite some differences based on participant characteristics, all program components were deemed useful preparation for professional success, with hands-on research experience and mentoring cited as the most helpful. The promising results of our case study demonstrate the feasibility of successfully implementing an undergraduate training program to provide a pathway to advanced careers in health care within the VHA. We posit that programs like ours can serve as a framework for creating pathway training programs that target undergraduates traditionally underrepresented, subsequently empowering them to pursue health care careers, and ultimately increasing diversity by training professionals who are better prepared to assist with diverse patient needs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Horizontal gene transfer facilitates the molecular reverse-evolution of antibiotic sensitivity in experimental populations of H. pylori.

Reversing the evolution of traits harmful to humans, such as antimicrobial resistance, is a key ambition of applied evolutionary biology. A major impediment to reverse evolution is the relatively low spontaneous mutation rates that revert evolved genotypes back to their ancestral state. However, the repeated re-introduction of ancestral alleles by horizontal gene transfer (HGT) could make reverse evolution likely. Here we evolve populations of an antibiotic-resistant strain of Helicobacter pylori in growth conditions without antibiotics while introducing an ancestral antibiotic-sensitive allele by HGT. We evaluate reverse evolution using DNA sequencing and find that HGT facilitates the molecular reverse evolution of the antibiotic resistance allele, and that selection for high rates of HGT drives the evolution of increased HGT rates in low-HGT treatment populations. Finally, we use a theoretical model and carry out simulations to infer how the fitness costs of antibiotic resistance, rates of HGT and effects of genetic drift interact to determine the probability and predictability of reverse evolution.

Prediction of outcome of hypoxic-ischemic encephalopathy in newborns undergoing therapeutic hypothermia using heart rate variability.

OBJECTIVE: To assess the use of continuous heart rate variability (HRV) as a predictor of brain injury severity in newborns with moderate to severe HIE that undergo therapeutic hypothermia. STUDY DESIGN: Two cohorts of newborns (n1 = 55, n2 = 41) with moderate to severe hypoxic-ischemic encephalopathy previously treated with therapeutic hypothermia. HRV was characterized by root mean square in the short time scales (RMSS) during therapeutic hypothermia and through completion of rewarming. A logistic regression and Naïve Bayes models were developed to predict the MRI outcome of the infants using RMSS. The encephalopathy grade and gender were used as control variables. RESULTS: For both cohorts, the predicted outcomes were compared with the observed outcomes. Our algorithms were able to predict the outcomes with an area under the receiver operating characteristic curve of about 0.8. CONCLUSIONS: HRV assessed by RMSS can predict severity of brain injury in newborns with HIE.

Biopsychosocial Correlates and Individual Differences for Eliciting Moral Elevation in Veterans With PTSD: An Experimental Case Series.

ABSTRACT: A promising approach to enhancing trauma-focused treatment is moral elevation-feeling inspired by witnessing a virtuous act. This study explored potential links between eliciting elevation and relevant outcomes in a series of case examples. Veterans with probable posttraumatic stress disorder completed experimental tasks including a written trauma narrative exercise and watching elevation-eliciting videos. Participants also completed baseline assessments, repeated measures of trauma-related cognitions, emotions, elevation, and saliva sample collection. Four cases were identified and reviewed: two positive responders (high elevation after videos) and two nonresponders (restricted elevation response). Positive responder cases reported decreased cognitions, emotions, and moral injury distress from after the trauma narrative to after elevation exercises, whereas nonresponders reported minimal to no changes. Positive responders also demonstrated decreases in cortisol, whereas nonresponders demonstrated increases in cortisol. Future work should examine whether elevation contributes to changes in biopsychosocial outcomes and identify individual factors that indicate who might benefit from elevation-based interventions.

[Surgical treatment of intracranial aneurysms in acute period of hemorrhage in Hunt-Hess grade IV-V patients at Burdenko Neurosurgical Center between 2006 and 2020]. / Analiz rezul'tatov khirurgicheskogo lecheniya tserebral'nykh anevrizm v ostrom periode krovoizliyaniya u patsientov so stepen'yu tyazhesti Hunt­Hess IV­V v FGAU «Natsional'nyi meditsinskii issledovatel'skii tsentr neirokhirurgii im. akad. N.N. Burdenko¼ za 2006­2020 gg.

BACKGROUND: Management of patients in acute period of aneurysmal subarachnoid hemorrhage Hunt-Hess grade IV-V is still a complex and unsolved problem, especially regarding surgical treatment and various complications. OBJECTIVE: To analyze postoperative outcomes in patients undergoing surgery in acute period of aneurysmal subarachnoid hemorrhage Hunt-Hess grade IV-V between 2006 and 2020, as well as to assess various factors influencing treatment outcomes. MATERIAL AND METHODS: We analyzed 163 patients who underwent surgery within 21 days after aneurysmal subarachnoid hemorrhage Hunt-Hess grade IV-V. All patients were divided into 2 groups depending on the period: 2006-2011 (group 1) and 2012-2020 (group 2). RESULTS: Mortality reduced from 28.6% in group 1 to 8.3% in group 2. At the same time, incidence of vegetative state (GOS grade 2) increased from 4.8% to 17.4%. Incidence of outcomes GOS grade 3 - 5 was similar. CONCLUSION: Large or giant aneurysm, repeated preoperative subarachnoid hemorrhage, intraoperative aneurysm rupture and prolonged temporary clipping can impair postoperative outcomes in patients with hemorrhage Hunt-Hess grade IV-V. External ventricular drainage, intraarterial injection of verapamil, intracisternal administration of calcium channel blockers and active surgical tactics improve postoperative outcomes and reduce mortality.

High-quality physiology of Alcanivorax borkumensis SK2 producing glycolipids enables efficient stirred-tank bioreactor cultivation.

Glycine-glucolipid, a glycolipid, is natively synthesized by the marine bacterium Alcanivorax borkumensis SK2. A. borkumensis is a Gram-negative, non-motile, aerobic, halophilic, rod-shaped γ-proteobacterium, classified as an obligate hydrocarbonoclastic bacterium. Naturally, this bacterium exists in low cell numbers in unpolluted marine environments, but during oil spills, the cell number significantly increases and can account for up to 90% of the microbial community responsible for oil degradation. This growth surge is attributed to two remarkable abilities: hydrocarbon degradation and membrane-associated biosurfactant production. This study aimed to characterize and enhance the growth and biosurfactant production of A. borkumensis, which initially exhibited poor growth in the previously published ONR7a, a defined salt medium. Various online analytic tools for monitoring growth were employed to optimize the published medium, leading to improved growth rates and elongated growth on pyruvate as a carbon source. The modified medium was supplemented with different carbon sources to stimulate glycine-glucolipid production. Pyruvate, acetate, and various hydrophobic carbon sources were utilized for glycolipid production. Growth was monitored via online determined oxygen transfer rate in shake flasks, while a recently published hyphenated HPLC-MS method was used for glycine-glucolipid analytics. To transfer into 3 L stirred-tank bioreactor, aerated batch fermentations were conducted using n-tetradecane and acetate as carbon sources. The challenge of foam formation was overcome using bubble-free membrane aeration with acetate as the carbon source. In conclusion, the growth kinetics of A. borkumensis and glycine-glucolipid production were significantly improved, while reaching product titers relevant for applications remains a challenge.

[Complicated course of the postoperative period with the development of epidural hygroma and intracranial hypotension after removal of cranio-orbital meningioma. Clinical case and literature review]. / Oslozhnennoe techenie posleoperatsionnogo perioda s razvitiem epidural'noi gigromy i vnutricherepnoi gipotenzii posle udaleniya kranioorbital'noi meningiomy. Klinicheskii primer i obzor literatury.

Surgical removal of cranio-orbital meningiomas is an effective method of treating this pathology. Modern surgical techniques and technologies make it possible to perform operations with a low risk of complications. Lumbar drainage or repeated lumbar punctures are often used intraoperatively or in the early postoperative period to prevent nasal CSF leak; this rarely leads to the development of significant neurological symptoms. We present a case of the development of severe intracranial hypotension with the formation of a subdural hygroma in the early postoperative period after removal of a cranio-orbital meningioma in a 41-year-old patient. The operation was performed using an individual model and molds for simultaneous reconstruction of the bone defect with an implant made of polymethyl methacrylate. On the 1st and 2nd days after surgery, lumbar punctures were performed. From the 2nd day there was a progressive deterioration with the development of symptoms characteristic of intracranial hypotension. Computed tomography revealed an increasing displacement of the midline structures of the brain and an increasing volume of epidural fluid accumulation in the area of surgical intervention. Magnetic resonance imaging revealed characteristic signs of intracranial hypotension. Conservative treatment (bed rest, active hydration) had no effect. On the 6th day after surgery, an epidural blood patch procedure was performed and closed external drainage of the epidural hygroma was performed, and a rapid regression of neurological symptoms was noted. Our experience and literature data indicate that it is necessary to remember the possibility of developing clinically significant intracranial hypotension even after a single lumbar puncture. The formation of hygromas in the surgical area is characteristic of intracranial hypotension, but in most cases does not require additional surgical intervention and does not have a negative impact on the outcome of treatment. Conservative treatment of intracranial hypotension is the first choice and often sufficient. If there is no effect and the patient's condition worsens, it is necessary to perform an epidural blood patch procedure.