Cell-TIMP: Cellular Trajectory Inference based on Morphological Parameter.

Cellular morphology, shaped by various genetic and environmental influences, is pivotal to studying experimental cell biology, necessitating precise measurement and analysis techniques. Traditional approaches, which rely on geometric metrics derived from stained images, encounter obstacles stemming from both the imaging and analytical domains. Staining processes can disrupt the cell's natural state and diminish accuracy due to photobleaching, while conventional analysis techniques, which categorize cells based on shape to discern pathophysiological conditions, often fail to capture the continuous and asynchronous nature of biological processes such as cell differentiation, immune responses, and cancer progression. In this work, we propose the use of quantitative phase imaging for morphological assessment due to its label-free nature. For analysis, we repurposed the genomic analysis toolbox to perform trajectory inference analysis purely based on morphology information. We applied the developed framework to study the progression of leukemia and breast cancer metastasis. Our approach revealed a clear pattern of morphological evolution tied to the diseases' advancement, highlighting the efficacy of our method in identifying functionally significant shape changes where conventional techniques falter. This advancement offers a fresh perspective on analyzing cellular morphology and holds significant potential for the broader research community, enabling a deeper understanding of complex biological dynamics.

Coronary bypass surgery guided by computed tomography in a low-risk population.

BACKGROUND AND AIMS: In patients with three-vessel disease and/or left main disease, selecting revascularization strategy based on coronary computed tomography angiography (CCTA) has a high level of virtual agreement with treatment decisions based on invasive coronary angiography (ICA). METHODS: In this study, coronary artery bypass grafting (CABG) procedures were planned based on CCTA without knowledge of ICA. The CABG strategy was recommended by a central core laboratory assessing the anatomy and functionality of the coronary circulation. The primary feasibility endpoint was the percentage of operations performed without access to the ICA. The primary safety endpoint was graft patency on 30-day follow-up CCTA. Secondary endpoints included topographical adequacy of grafting, major adverse cardiac and cerebrovascular (MACCE), and major bleeding events at 30 days. The study was considered positive if the lower boundary of confidence intervals (CI) for feasibility was ≥75% (NCT04142021). RESULTS: The study enrolled 114 patients with a mean (standard deviation) anatomical SYNTAX score and Society of Thoracic Surgery score of 43.6 (15.3) and 0.81 (0.63), respectively. Unblinding ICA was required in one case yielding a feasibility of 99.1% (95% CI 95.2%-100%). The concordance and agreement in revascularization planning between the ICA- and CCTA-Heart Teams was 82.9% with a moderate kappa of 0.58 (95% CI 0.50-0.66) and between the CCTA-Heart Team and actual treatment was 83.7% with a substantial kappa of 0.61 (95% CI 0.53-0.68). The 30-day follow-up CCTA in 102 patients (91.9%) showed an anastomosis patency rate of 92.6%, whilst MACCE was 7.2% and major bleeding 2.7%. CONCLUSIONS: CABG guided by CCTA is feasible and has an acceptable safety profile in a selected population of complex coronary artery disease.

Heteroatom Doping in Pollutant Diesel Soot-Derived Nanocarbon for Enhanced Zn-Ion Storage Performance.

Herein, we have isolated onion-like nanocarbon (ONC) from the exhaust soot of diesel engines and further doped it with nitrogen (N) and sulfur (S) to fabricate N,S-co-doped ONC (N-S-ONC). To explore its application feasibility, we have assembled an aqueous Zn-ion hybrid supercapacitor (ZIHSC) with a N-S-ONC cathode, which attains high specific capacitance with good rate capability. In-depth analyses suggest that the mechanism of charge storage in the ONC is governed by both capacitive-controlled and diffusion-controlled processes, with the capacitive processes leading at all sweep rates. The ZIHSC demonstrated a good energy density of 50 Wh/kg, a maximum power density of 3.6 kW/kg, and an impressive cycle life with 73% capacitance retention after 50,000 charge-discharge cycles. The study suggests the potential possibly for the long-term application of BC derived nanocarbon in electrochemical energy storage systems (EESSs).

A narrative review of pulsed radiofrequency for the treatment of carpal tunnel syndrome.

OBJECTIVE: Carpal tunnel syndrome (CTS), which is the most common peripheral nerve entrapment syndrome, can commonly persist despite conservative treatment modalities such as wrist splinting or medications. Pulsed radiofrequency represents a minimally invasive pain intervention technique to alleviate pain. The literature was reviewed to establish the effectiveness of PRF therapy for CTS. STUDY DESIGN: This is a narrative review of relevant articles on the effectiveness of PRF for CTS. METHOD: Four databases, MEDLINE, Cochrane Central Register of Controlled Trials, Embase, OVID Emcare, and Web of Science, were systematically searched. 804 records were screened, and the reference lists of eligible articles were examined. For this review, eight extracted studies were narratively explored. RESULTS: One case report, three retrospective cohorts, one observational prospective study, and three randomized-controlled trials were included. PRF likely provides both an analgesic and functional benefit in patients with mild to severe CTS, and it also shows benefit as an adjunct to carpal tunnel release surgery. Long-term data is limited. It also appears likely that steroid injection may represent a comparable treatment modality to PRF, and there have been positive results when these modalities are used together. Notably, all studies differed in their methodology, making direct comparisons between studies challenging. CONCLUSIONS: The evidence for PRF in the treatment of CTS, across the range of spectrum of severity or peri-operative to CTS surgery, appears favorable and avoids known side effects of steroid injections. Potential mechanisms for PRF and future directions for research are explored.

Coronary computed tomography angiography-based SYNTAX score for comprehensive assessment of advanced coronary artery disease.

BACKGROUND: Since the initial attempt to adapt the anatomical SYNTAX score (aSS) to coronary computed tomography angiography (CCTA), CCTA imaging technology has evolved, and is currently used as a "decision-maker" for revascularization strategy in complex coronary artery disease (CAD) and has rendered necessary some updating of the aSS to the CCTA modality. OBJECTIVES: The aim is to provide updated definitions of the aSS derived from CCTA in patients with complex CAD undergoing CABG. METHODS: The modifications of CCTA-aSS are the following; (i) updated definition and detection criteria of total occlusion (TO) in CCTA based on length assessment, (ii) inclusion of scoring points for serial bifurcations located in one single coronary segment. (iii) inclusion of weighing score points for lesions located distal to a TO, not visualized on conventional coronary angiography, but visible in CCTA, (iv) removal of thrombus and bridging collateral items from the weighing score, considering the limited diagnostic capability of CCTA in detecting these specific lesion characteristics. RESULTS: the updated CCTA-aSS was tested in a first-in-man study using the sole guidance of CCTA for the planning and performance of bypass surgery in complex CAD (n â€‹= â€‹114). An interobserver analysis showed excellent reproducibility (ICC â€‹= â€‹0.96, 95 â€‹% confidence interval 0.94-0.97). CONCLUSION: The updated CCTA-aSS was implemented in a cohort of patients with complex CAD undergoing CABG with the sole guidance of CCTA and FFRCT and the Inter-reproducibility of the analysis of the updated score was found excellent. The prognostic value of the modified CCTA-aSS will be examined in future studies.

miRNA Expression Patterns in Early- and Late-Stage Prostate Cancer Patients: High-Throughput Analysis.

Prostate cancer (PCa) is one of the most common types of cancer among men. To date, there have been no specific markers identified for the diagnosis and prognosis or response to treatment of this disease. Thus, there is an urgent need for promising markers, which may be fulfilled by small non-coding RNAs known as microRNAs (miRNAs). Therefore, the present study aimed to investigate the miRNA profile in tissue samples obtained from patients with PCa using microarrays, followed by reverse transcriptase quantitative PCRs (RT-qPCRs). In the discovery phase, 754 miRNAs were screened in tissues obtained from patients (n = 46) with PCa in early and late stages. Expression levels of miRNA-324-3p, miRNA-429, miRNA-570, and miRNA-616 were found to be downregulated, and miRNA-423-5p expression was upregulated in patients with early-stage cancer compared to the late-stage ones. These five miRNAs were further validated in an independent cohort of samples (n = 39) collected from patients with PCa using RT-qPCR-based assays. MiRNA-324-3p, miRNA-429, miRNA-570, and miRNA-616 expression levels remained significantly downregulated in early-stage cancer tissues compared to late-stage tissues. Remarkably, for a combination of three miRNAs, PSA levels and Gleason scores were able to discriminate between patients with early-stage PCa and late-stage PCa, with an AUC of 95%, a sensitivity of 86%, and a specificity close to 94%. Thus, the data obtained in this study suggest a possible involvement of the identified miRNAs in the pathogenesis of PCa, and they may also have the potential to be developed into diagnostic and prognostic tools for PCa. However, further studies with a larger cohort are needed.

CCTA-based CABG SYNTAX Score: a tool to evaluate completeness of coronary segment revascularization after bypass surgery.

To describe the updated coronary computed tomographic angiography (CCTA)-based coronary artery bypass graft (CABG) anatomic SYNTAX Score (aSS) and assess its utility and reproducibility for assessing the completeness of revascularization after CABG. The CCTA-CABG aSS is a visual assessment using CCTA post-CABG which quantifies the failure in effectively grafting stenotic coronary segments, and therefore assesses the completeness of surgical revascularization. It is calculated by subtracting the aSS of successfully anastomosed coronary segments from the aSS of the native coronary tree. The inter-observer reproducibility of the CCTA-CABG aSS was evaluated in 45 consecutive patients with three-vessel disease with or without left main disease who underwent a CCTA 30 days (± 7 days) after CABG. The CCTA-CABG aSS was evaluated in 45 consecutive patients with 117 bypass grafts and 152 anastomoses. The median native coronary aSS was 35.0 [interquartile range (IQR) 27.0-41.0], whilst the median CCTA-CABG aSS was 13.0 (IQR 9.0-20.5). The inter-observer level of agreement for the native coronary aSS and the CCTA-CABG aSS were both substantial with respective Kappas of 0.67 and 0.61. The CCTA-CABG aSS was feasible in all patients who underwent CABG for complex coronary artery disease with substantial inter-observer reproducibility, and therefore can be used to quantify the completeness of revascularization after CABG.

Scale-up of the Australian Fans in Training (Aussie-FIT) men's health behaviour change program: a protocol for a randomised controlled hybrid effectiveness-implementation trial.

INTRODUCTION: Improving physical activity (PA) and healthy eating is critical for primary and secondary prevention of cardiovascular disease (CVD). Behaviour change programmes delivered in sporting clubs can engage men in health behaviour change, but are rarely sustained or scaled-up post trial. Following the success of pilot studies of the Australian Fans in Training (Aussie-FIT) programme, a hybrid effectiveness-implementation trial protocol was developed. This protocol outlines methods to: (1) establish if Aussie-FIT is effective at supporting men with or at risk of CVD to sustain improvements in moderate-to-vigorous PA (primary outcome), diet and physical and psychological health and (2) examine the feasibility and utility of implementation strategies to support programme adoption, implementation and sustainment. METHODS AND ANALYSIS: A pragmatic multistate/territory hybrid type 2 effectiveness-implementation parallel group randomised controlled trial with a 6-month wait list control arm in Australia. 320 men aged 35-75 years with or at risk of CVD will be recruited. Aussie-FIT involves 12 weekly face-to-face sessions including coach-led interactive education workshops and PA delivered in Australian Football League (Western Australia, Northern Territory) and rugby (Queensland) sports club settings. Follow-up measures will be at 3 and 6 months (both groups) and at 12 months to assess maintenance (intervention group only). Implementation outcomes will be reported using the Reach, Effectiveness, Adoption, Implementation, Maintenance framework. ETHICS AND DISSEMINATION: This multisite study has been approved by the lead ethics committees in the lead site's jurisdiction, the South Metropolitan Health Service Human Research Ethics Committee (Reference RGS4254) and the West Australian Aboriginal Health Ethics Committee (HREC1221). Findings will be disseminated at academic conferences, peer-reviewed journals and via presentations and reports to stakeholders, including consumers. Findings will inform a blueprint to support the sustainment and scale-up of Aussie-FIT across diverse Australian settings and populations to benefit men's health. TRIAL REGISTRATION NUMBER: This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12623000437662).

MiRNA-146a-A Key Player in Immunity and Diseases.

miRNA-146a, a single-stranded, non-coding RNA molecule, has emerged as a valuable diagnostic and prognostic biomarker for numerous pathological conditions. Its primary function lies in regulating inflammatory processes, haemopoiesis, allergic responses, and other key aspects of the innate immune system. Several studies have indicated that polymorphisms in miRNA-146a can influence the pathogenesis of various human diseases, including autoimmune disorders and cancer. One of the key mechanisms by which miRNA-146a exerts its effects is by controlling the expression of certain proteins involved in critical pathways. It can modulate the activity of interleukin-1 receptor-associated kinase, IRAK1, IRAK2 adaptor proteins, and tumour necrosis factor (TNF) targeting protein receptor 6, which is a regulator of the TNF signalling pathway. In addition, miRNA-146a affects gene expression through multiple signalling pathways, such as TNF, NF-κB and MEK-1/2, and JNK-1/2. Studies have been carried out to determine the effect of miRNA-146a on cancer pathogenesis, revealing its involvement in the synthesis of stem cells, which contributes to tumourigenesis. In this review, we focus on recent discoveries that highlight the significant role played by miRNA-146a in regulating various defence mechanisms and oncogenesis. The aim of this review article is to systematically examine miRNA-146a's impact on the control of signalling pathways involved in oncopathology, immune system development, and the corresponding response to therapy.

Rapidly expanding chondromyxoid fibroma of the mandible: A case report of rare entity.

Chondromyxoid fibroma is an unusual, benign bone tumour that is usually sited in the metaphyseal region of the long bones. It accounts for less than 1% of all bone tumours. It manifests predominantly in males in their second and third decades of life. Rarely, it occurs in the bones of the craniofacial skeleton. For small, lesions enucleation and curettage and for larger lesions, resection followed by are the treatment modalities available. Here, we present a case of chondromyxoid fibroma with respect to the right side of the mandible which was managed by surgical resection followed by reconstruction under general anaesthesia. Resection followed by reconstruction provides satisfactory outcomes, especially in cases with large lesions. Chondromyxoid fibroma is an asymptomatic, benign, slow-growing lesion but can rapidly expand and involve the greater area of bone. Thus, its detection at an early stage and treatment at the proper time can lead to less morbidity associated with the lesion and improved quality of life of the patient.

Vaccine hesitancy in the post-vaccination COVID-19 era: a machine learning and statistical analysis driven study.

Background The COVID-19 pandemic has badly affected people of all ages globally. Therefore, its vaccine has been developed and made available for public use in unprecedented times. However, because of various levels of hesitancy, it did not have general acceptance. The main objective of this work is to identify the risk associated with the COVID-19 vaccines by developing a prognosis tool that will help in enhancing its acceptability and therefore, reducing the lethality of SARS-CoV-2. Methods: The obtained raw VAERS dataset has three files indicating medical history, vaccination status, and post vaccination symptoms respectively with more than 354 thousand samples. After pre-processing, this raw dataset has been merged into one with 85 different attributes however, the whole analysis has been subdivided into three scenarios ((i) medical history (ii) reaction of vaccination (iii) combination of both). Further, Machine Learning (ML) models which includes Linear Regression (LR), Random Forest (RF), Naive Bayes (NB), Light Gradient Boosting Algorithm (LGBM), and Multilayer feed-forward perceptron (MLP) have been employed to predict the most probable outcome and their performance has been evaluated based on various performance parameters. Also, the chi-square (statistical), LR, RF, and LGBM have been utilized to estimate the most probable attribute in the dataset that resulted in death, hospitalization, and COVID-19. Results: For the above mentioned scenarios, all the models estimates different attributes (such as cardiac arrest, Cancer, Hyperlipidemia, Kidney Disease, Diabetes, Atrial Fibrillation, Dementia, Thyroid, etc.) for death, hospitalization, and COVID-19 even after vaccination. Further, for prediction, LGBM outperforms all the other developed models in most of the scenarios whereas, LR, RF, NB, and MLP perform satisfactorily in patches. Conclusion: The male population in the age group of 50-70 has been found most susceptible to this virus. Also, people with existing serious illnesses have been found most vulnerable. Therefore, they must be vaccinated in close observations. Generally, no serious adverse effect of the vaccine has been observed therefore, people must vaccinate themselves without any hesitation at the earliest. Also, the model developed using LGBM establishes its supremacy over all the other prediction models. Therefore, it can be very helpful for the policymakers in administrating and prioritizing the population for the different vaccination programs.

Quality of life and its sociodemographic determinants in breast cancer patients.

Background: Breast cancer is the most common cancer in women worldwide. As the outcome of any cancer treatment is not only dependent on disease-free interval but also on the quality of life (QOL) of the survivor. Hence, this study was conducted to evaluate QOL of breast cancer patients and sociodemographic factors affecting QOL of patients. Subjects and Methods: A cross-sectional study was conducted among 50 breast cancer patients and 50 controls, which fulfilled the selection criteria. The sociodemographic profile and QOL using the World Health Organization QOL-BREF were analyzed using the descriptive statistical methods. Results: All the QOL indicators were statistically significantly (P = 0.0001) lower among breast cancer patients. QOL indicators were statistically significantly (P < 0.01) lower in young age. Not much difference was observed according to religion and these were significantly (P < 0.05) higher among the homemakers. There was no significant difference in all the QOL indicators according to the marital status of the cases. However, these were significantly (P < 0.05) higher among rural cases compared with urban one. The QOL indicators were statistically significantly (P < 0.05) higher among the cases living in joint families than nuclear. No difference was observed among different socioeconomic status. Conclusion: QOL was significantly lower among the breast cancer patients. Age, occupational status, type of family, and locality were the significant factors that affect the QOL of breast cancer patients. Hence, psychological and social support can play an important role in improving QOL of cancer patient.

Utilizing the Retrograde Flow of Internal Mammary Vessels as a Donor Pedicle.

Introduction The aim of this study is to assess the results of retrograde flow of internal mammary artery and vein (IMA/V) as a donor vessel for free flap microvascular anastomosis (MVA). This need arises with bipedicle deep inferior epigastric perforator (DIEP) flaps, when all four zones with extra fat need to be harvested for unilateral breast reconstruction coupled with poor midline crossover of circulation naturally or because of midline scar. Large anterolateral thigh flaps for chest wall cover, with multiple perforators from separate pedicles, also need supercharging. This needs an additional source of donor vessels, antegrade IMA/V being the first one. Materials and Methods Retrospective study of microvascular breast reconstruction using retrograde internal mammary donor vessels. Results Out of 35 cases, 20 cases had distal IMA/V, with retrograde flow, as donor vessel for second set of arterial and venous anastomosis. In two cases, retrograde IMA/V was used for the solitary set of MVA. In remaining 13 cases, either retrograde IMA or V was utilized either as a principal or accessory donor. No flap was lost. Venous and arterial insufficiency happened in one case each, both were salvaged. Two cases developed partial necrosis, needing debridement and suturing. One case developed marginal necrosis. Only one case developed fat necrosis with superadded infection on follow-up. Conclusion Distal end of IMA and IMV on retrograde flow is safe for MVA as an additional or sole pedicle. It is convenient to use being in the same field. It enables preservation of other including thoracodorsal pedicle and latissimus dorsi flap for use in case of a complication or recurrence.

Actinide-Oxygen Multiple Bonds from Air: Synthesis and Characterization of a Thorium Oxo Supported by Redox-Active Ligands.

The first non-uranyl, f-element oxo complex synthesized from dioxygen in dry air is presented in this work. The synthesis was accomplished by treating the redox-active thorium amidophenolate complex, [Th(dippap)3][K(15-c-5)2]2 (1-ap crown), with dioxygen in dry air, forming a rare terminal thorium oxo, [O═Th(dippisq)2(dippap)][K(15-c-5)2]2 (2-oxo). Compound 1-ap crown was regenerated by treating 2-oxo with potassium graphite. X-ray crystallography of 2-oxo revealed a comparatively longer bond length for the thorium-oxygen double bond when compared to other thorium oxos. As such, several thorium-oxygen single bonds were synthesized for comparison, including Th(dippisq)2(OSiMe3)2(THF) (4-OSiMe3), Th(OSiMe3)4(bipy)2 (5-OSiMe3), and [Th(OH)2 (dippHap)4][K(15-c-5)2]2 (6-OH). Full spectroscopic and structural characterization of the complexes was performed via 1H NMR spectroscopy, X-ray crystallography, EPR spectroscopy, and electronic absorption spectroscopy as well as SQUID magnetometry, which all confirmed the electronic structure of these complexes.

Prevalence of tobacco consumption and smoking and its effect on outcome among microbiologically confirmed new pulmonary tuberculosis patients on daily regimen of DOTS in Amritsar city.

Background: Tobacco consumption and smoking are causative factors that can create a favorable environment for tuberculosis and increase the morbidity and mortality attributed to it. Tobacco use is the leading global cause of preventable death (6 million deaths per year). This study compares the treatment outcome in pulmonary tuberculosis patients on DOTS daily regimen with respect to consumption of tobacco and smoking. Aims: 1. To study the prevalence of tobacco consumption and smoking among microbiologically confirmed new pulmonary tuberculosis patients. 2. To study the effect of tobacco consumption and smoking on the outcome of microbiologically confirmed new pulmonary tuberculosis patients. Material and Method: The prospective observational study was conducted on microbiologically confirmed new pulmonary tuberculosis patients enrolled during the first quarter of the year 2019 (i.e., from 01/01/2019 to 03/31/2019) at the four selected DMCs of Amritsar City. In total, 197 patients were included in the study depending on the inclusion and exclusion criteria. The prevalence of tobacco consumption and smoking at the start of treatment was noted and the effect on outcome was observed. Results: Prevalence of tobacco consumption and smoking was found to be 24.37% and 21.83%, respectively. In addition, 93.96% of non-tobacco consumers and 94.15% of non-smokers had favorable outcomes as compared to 83.34% of tobacco consumers and 81.4% of smokers, which is statistically significant. Conclusion: Tobacco consumption and smoking have significantly higher chances of unfavorable outcomes (loss to follow up, change in treatment regimen, and death) as compared to non-consumption and non-smoking.

Changing spectrum of infective endocarditis in India: An 11-year experience from an academic hospital in North India.

OBJECTIVE: Several studies have demonstrated a shift in the spectrum of infective endocarditis (IE) in the developed world. We aimed to investigate whether demographic and microbiologic characteristics of IE have changed in India. DESIGN: A retrospective analysis of patients with in north India between 2010 and 2020. METHODS: The clinical and laboratory profiles of 199 IE admitted to an academic hospital patients who met the modified Duke criteria for definite IE were analysed. RESULTS: The mean age was 34 years, and 84% were males. The main predisposing conditions were injection drug use (IDU) (n = 71, 35.7%), congenital heart disease (n = 46, 21.6%), rheumatic heart disease (n = 25, 12.5%), and prosthetic device (n = 19, 9.5%). 17.1% of patients developed IE without identified predispositions. Among 64.3% culture-positive cases, the most prevalent causative pathogens were Staphylococcus aureus (46.1%), viridans streptococci (7.0%), enterococci (6.0%), coagulase-negative staphylococci (5.5%), gram negative bacilli (5.5%), polymicrobial (5.5%), and Candida (1.0%). The tricuspid (30.3%), mitral (25.6%), and aortic (21.6%) valves were the most common sites of infection, and 60.3% had large vegetations (>10 mm). Systemic embolization occurred in 55.3% of patients at presentation. Cardiac surgery was required for 13.1%. In-hospital mortality was 17.1% and was associated with prosthetic devices (p-value, 0.001), baseline leucocytosis (p-value, 0.036) or acute kidney injury (p-value, 0.001), and a microbial etiology of gram negative bacilli or enterococci (p-value, 0.005). CONCLUSION: IDU is now the most important predisposition for IE in India, and S. aureus has become the leading cause of native valve endocarditis with or without IDU.

Elucidation of Thorium Redox-Active Ligand Complexes: Evidence for a Thorium-Tri(radical) Species.

A series of thorium(IV) complexes featuring the redox-active 4,6-di-tert-butyl-N-(2,6-di-isopropylphenyl)-o-iminobenzoquinone (dippiq) ligand family have been synthesized and characterized. The neutral iminoquinone ligand was used to generate Th(dippiq)Cl4(dme)2 (1-iq) and Th(dippiq)2Cl4 (2-iq), both of which show dative bonds between the thorium(IV) ion and the ligands. One electron reduction of the ligand forms the unique tris(iminosemiquinone) complex, Th(dippisq)3Cl (3-isq), which features a radical in each ligand. Further reduction furnishes the amidophenolate species, Th(dippap)3]K2(THF)2 (4-ap), which has the ligands in their dianionic form. Attempts to sequester the potassium ions with cryptand resulted in the [Th(dippap)3K][K(crypt)] (4-ap mono crypt) and [Th(dippap)3][K(crypt)]2 (4-ap crypt) species. A bis(amidophenolate) complex was accessed by incorporating bulky triphenylphosphine oxide (OPPh3) ligands to generate Th(dippap)2(OPPh)3 (5-ap). Spectroscopic and structural characterization of each derivative established the +4 oxidation state for thorium with redox chemistry occurring at the ligands rather than the thorium ion. The reported 3-isq complex is unprecedented as it is the first tri(radical) thorium complex with the highest reported magnetic moment for a thorium species as characterized by SQUID magnetometry.

Brain Magnetic Resonance Imaging Reveals Different Courses of Disease in Pediatric and Adult Cerebral Malaria.

BACKGROUND: Cerebral malaria is a common presentation of severe Plasmodium falciparum infection and remains an important cause of death in the tropics. Key aspects of its pathogenesis are still incompletely understood, but severe brain swelling identified by magnetic resonance imaging (MRI) was associated with a fatal outcome in African children. In contrast, neuroimaging investigations failed to identify cerebral features associated with fatality in Asian adults. METHODS: Quantitative MRI with brain volume assessment and apparent diffusion coefficient (ADC) histogram analyses were performed for the first time in 65 patients with cerebral malaria to compare disease signatures between children and adults from the same cohort, as well as between fatal and nonfatal cases. RESULTS: We found an age-dependent decrease in brain swelling during acute cerebral malaria, and brain volumes did not differ between fatal and nonfatal cases across both age groups. In nonfatal disease, reversible, hypoxia-induced cytotoxic edema occurred predominantly in the white matter in children, and in the basal ganglia in adults. In fatal cases, quantitative ADC histogram analyses also demonstrated different end-stage patterns between adults and children: Severe hypoxia, evidenced by global ADC decrease and elevated plasma levels of lipocalin-2 and microRNA-150, was associated with a fatal outcome in adults. In fatal pediatric disease, our results corroborate an increase in brain volume, leading to augmented cerebral pressure, brainstem herniation, and death. CONCLUSIONS: Our findings suggest distinct pathogenic patterns in pediatric and adult cerebral malaria with a stronger cytotoxic component in adults, supporting the development of age-specific adjunct therapies.

Estrogen deficiency induces memory loss via altered hippocampal HB-EGF and autophagy.

Estrogen deficiency reduces estrogen receptor-alpha (ERα) and promotes apoptosis in the hippocampus, inducing learning-memory deficits; however, underlying mechanisms remain less understood. Here, we explored the molecular mechanism in an ovariectomized (OVX) rat model, hypothesizing participation of autophagy and growth factor signaling that relate with apoptosis. We observed enhanced hippocampal autophagy in OVX rats, characterized by increased levels of autophagy proteins, presence of autophagosomes and inhibition of AKT-mTOR signaling. Investigating upstream effectors of reduced AKT-mTOR signaling revealed a decrease in hippocampal heparin-binding epidermal growth factor (HB-EGF) and p-EGFR. Moreover, 17ß-estradiol and HB-EGF treatments restored hippocampal EGFR activation and alleviated downstream autophagy process and neuronal loss in OVX rats. In vitro studies using estrogen receptor (ERα)-silenced primary hippocampal neurons further corroborated the in vivo observations. Additionally, in vivo and in vitro studies suggested the participation of an attenuated hippocampal neuronal HB-EGF and enhanced autophagy in apoptosis of hippocampal neurons in estrogen- and ERα-deficient conditions. Subsequently, we found evidence of mitochondrial loss and mitophagy in hippocampal neurons of OVX rats and ERα-silenced cells. The ERα-silenced cells also showed a reduction in ATP production and an HB-EGF-mediated restoration. Finally in concordance with molecular studies, inhibition of autophagy and treatment with HB-EGF in OVX rats restored cognitive performances, assessed through Y-Maze and passive avoidance tasks. Overall, our study, for the first time, links neuronal HB-EGF/EGFR signaling and autophagy with ERα and memory performance, disrupted in estrogen-deficient condition.

Popliteal neurovascular bundle is safe during inside-out repair of medial meniscus without a safety incision.

PURPOSE: There is a theoretical risk of injury to neurovascular structures during inside-out meniscal repair without a safety incision, although there are limited studies assessing this risk. This simulation study on archival MRI films was performed to assess the risk for the popliteal neurovascular bundle and the peroneal nerve during passage of needles for inside-out meniscus repair without a "safety incision", thereby defining a "safe zone" of the menisci that can be safely repaired using this technique. METHODS: Archival MRI scans (n = 50) were retrieved and axial sections through the menisci were used for simulation. The needle passage was simulated for different points on the posterior horn and body of lateral and medial menisci at "half-hour" intervals using clock method (15° intervals) with three different portals and two different needle cannulas, resulting in six different scenarios of needle passage for each point on the meniscus. The distance of the needle in each scenario was measured from popliteal vessels (n = 50) and peroneal nerve (n = 10). The value "mean-3SD" was calculated for positive means and "Mean + 3SD" was calculated if the mean was negative. An additional 2 mm was defined as "safe distance". Thus, simulation models in which the mean - 3SD was less than 2 mm (or mean + 3SD was greater than - 2 mm for negative means) were labelled as "unsafe". RESULTS: Needle passage through medial meniscus at and medial to 1 o'clock position for a right knee (or 11 o'clock position for a left knee) was safe, irrespective of the portal and needle type. For the lateral meniscus, only the equatorial region was found to be safe with this method. CONCLUSIONS: The popliteal neurovascular bundle is safe during the inside-out medial meniscal repair without a safety incision. For the terminal-most part of the posterior horn, the AM portal and the straight cannula should be avoided. However, this method without safety incision cannot be recommended for lateral meniscus because of the risk to the popliteal vessels and the peroneal nerve. Instead, the inside-out method with a safety incision, or an all-inside method should be used for lateral meniscus. LEVEL OF EVIDENCE: III.