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Abstract Purpose To evaluate the baseline characteristics of fundus autofluorescence (FAF) in patients with submacular hemorrhage (SMH). Methods This retrospective study included patients diagnosed with treatment-naive, foveal-involving subretinal hemorrhage (size > 2-disc diameters) of any etiology, presenting between June 2017 and June 2023. Only cases with good-quality color fundus photographs, optical coherence tomography (OCT) scans, and blue-light FAF images at baseline were included. SMH imaging characteristics were documented and correlated with treatment outcomes. A successful treatment outcome was defined as the reduction, displacement or clearance of the SMH from beneath the fovea. Results Nineteen cases of SMH (13 males, 6 females), ranging from 14 to 85 years, were analyzed. Neovascular age-related macular degeneration (nAMD) was the most common etiology (n = 11, 58%). Baseline visual acuity ranged from 6/9 to counting fingers at ½ meter, with a median presentation time of 7 days from symptom onset (range: 1–57 days). Treatment success was observed in 13 eyes (68%). Hypoautofluoroscence on FAF was significantly associated with SMH resolution (p = 0.021). However, no association was found between treatment success and clinical hemorrhage characteristics (p = 0.222), OCT findings (p = 0.222), or specific treatments (p > 0.05). Hypoautofluoroscence on FAF was the sole predictor of treatment success, as demonstrated by Spearman’s correlation (r = 0.637; p = 0.003) and linear regression analysis (p = 0.003). Conclusion FAF, in conjunction with color fundus photography and OCT, may provide valuable insights for clinicians in formulating treatment strategies for patients with SMH. Hypoautofluoroscence on FAF was a significant predictor of successful SMH resolution in this study.

Abstract This randomised, crossover, sham-controlled study explored the neural basis of source-monitoring, a crucial cognitive process implicated in schizophrenia. Left superior temporal gyrus (STG) and dorsolateral prefrontal cortex (DLPFC) were the key focus areas. Thirty participants without neurological or psychological disorders underwent offline sham and active tDCS sessions with specific electrode montage targeting the left STG and DLPFC. Source-monitoring tasks, reality monitoring (Hear-Imagine), internal source-monitoring (Say-Imagine), and external source monitoring (Virtual–Real) were administered. Paired t-test and estimation statistics was performed with Graphpad version 10.1.0. The Benjamini–Hochberg procedure was employed to control the false discovery rate in multiple hypothesis testing. A significant improvement in internal source monitoring tasks (p = 0.001, Cohen's d = 0.97) was observed, but reality monitoring tasks demonstrated moderate improvement (p = 0.02, Cohen's d = 0.44). The study provides insights into the neural mechanisms of source monitoring in healthy individuals and proposes tDCS as a therapeutic intervention, laying the foundation for future studies to refine tDCS protocols and develop individualized approaches to address source monitoring deficits in schizophrenia.

Abstract Rapid discovery and synthesis of future materials requires intelligent data acquisition strategies to navigate large design spaces. A popular strategy is Bayesian optimization, which aims to find candidates that maximize material properties; however, materials design often requires finding specific subsets of the design space which meet more complex or specialized goals. We present a framework that captures experimental goals through straightforward user-defined filtering algorithms. These algorithms are automatically translated into one of three intelligent, parameter-free, sequential data collection strategies (SwitchBAX, InfoBAX, and MeanBAX), bypassing the time-consuming and difficult process of task-specific acquisition function design. Our framework is tailored for typical discrete search spaces involving multiple measured physical properties and short time-horizon decision making. We demonstrate this approach on datasets for TiO2 nanoparticle synthesis and magnetic materials characterization, and show that our methods are significantly more efficient than state-of-the-art approaches. Overall, our framework provides a practical solution for navigating the complexities of materials design, and helps lay groundwork for the accelerated development of advanced materials.

Background: Second primary malignancy (SPM) is defined as a second de novo malignant neoplasm arising in a patient with known primary malignancy. SPM is common and can occur synchronously or metachronously. Methods: We retrospectively studied the epidemiological factors, patterns of occurrence and common associations of SPMs seen in our Department of Pathology during the period January 2016 and December 2020. The case details were retrieved from the medical records. SPM were diagnosed as per the International Association of Cancer Registries and International Agency for Research on Cancer criteria. Results: During the study period, 22 cases were seen. Their age ranged from 36 to 80 years; females had outnumbered males (female:male = 3.4:1). The most common site for metachronous primary was breast and the most common site for SPMs was head and neck. The median age for diagnosis of metachronous SPM was 59.2 years (range 41–80 years). The time interval for development of metachronous SPMs ranged from 6 months to 9 years. Conclusions: Our observations suggest that increased awareness regarding the entity and regular follow-up of patients can aid in early diagnosis of SPMs.

Purpose: To study the choroidal thickness (CT) and central macular thickness (CMT) in post-fever retinitis (PFR) and their correlation with visual acuity and treatment. Methods: A retrospective, observational study of patients presenting with PFR from 2013 to 2021 and with spectral domain optical coherence tomography (SD-OCT) (Heidelberg®, SpectralisTM, Heidelberg, Germany) images were included. The CT and CMT were measured at presentation and at the final visit. The CT was measured subfoveally and at points 2000 µm superior, inferior, medial, and lateral from the fovea using the caliper tool. Results: Seventy-nine eyes of 65 patients were included for this study. The mean age was 39.03 (±16.00) years with female preponderance of 53.84% (n = 35). Mean follow-up duration was 30 days. Mean CT at presentation and at follow-up was 254.12 µm and 241.51 µm, respectively. CT was decreased in majority of the eyes 67.1% (n = 53) from their baseline value. Mean CMTs at presentation and final visit were 454.8 µm and 223.7 µm, respectively. Best corrected visual acuity had a positive correlation with CMT (r = 0.340; P = 0.002) and negligible correlation with CT. A significant decrease in the mean CT was noted in patients who received doxycycline either alone or in combination with a steroid as compared to those who did not receive any treatment (P < 0.001). The significance of which is unknown presently. Conclusion: CMT has a greater role in determining the final visual outcome than CT. CT can be reduced post-treatment with no effect on vision.

Abstract Background Purtscher or Purtscher-like retinopathy is diagnosed by retinal hemorrhages and areas of retinal whitening on fundus examination, as well as a reduction in visual acuity due to microvascular occlusion of the precapillary retinal arterioles. We describe novel optical coherence tomography (OCT) findings of internal limiting membrane (ILM) separation and posterior hyperreflective dots in a case of Purtscher-like retinopathy in this report. Methods A 33-year-old man with acute pancreatitis and alcohol-induced liver disease presented to the retina department complaining of four days of painless vision loss in both eyes. Both eyes’ anterior segment examination and intraocular pressure were normal. Dilated fundus examination of both eyes revealed confluent areas of retinal whitening, hemorrhages, and cotton-wool spots over the posterior pole, indicating Purtscher-like retinopathy. OCT scans through the macula revealed dense inner retinal reflectivity, thickening, and loss of retinal layer stratification, as well as outer retinal layer shadowing and islands of ILM separation, posterior vitreous hyperreflective dots, and minimal subfoveal fluid, all of which corresponded to areas of retinal whitening on fundus photographs. The patient was given a brief course of systemic steroids. Results On the tenth day after the presentation, visual acuity in the right eye had improved to 6/18 and finger counting at 1 m in the left eye. The retinal findings had faded. The retina had reverted to its normal thickness on the OCT scans, with minimal hyperreflectivity remaining. The ILM separation and posterior vitreous hyperreflective dots were no longer present. Conclusion Following Purtscher or Purtscher-like retinopathy, we believe inflammation could play a major role in the development of these two novel OCT findings. This case offers an additional perspective on the underlying mechanisms responsible for the retinal manifestations observed in Purtscher or Purtscher-like retinopathy.

Water-stressed regions like Kenya rely on saline water sources, which can pose serious health hazards if not treated. While desalination is a burgeoning solution, safe disposal of desalination brine is often infeasible or too expensive. To circumvent this disposal challenge, we examine the maximum desalination recovery ratio (RRmax) for which desalination brine can safely be reused for many agricultural applications. Water samples from the Mara Triangle and data from past studies were collected and analyzed to measure contaminant concentrations against established safety limits of salinity and potentially hazardous elements for multiple agricultural use cases. The results suggest that high water recoveries were possible in the Mara Triangle, with the maximum recovery ratio reaching greater than 94% and 98% for crop irrigation and livestock watering, respectively. Brine reuse in this region was mostly limited by salinity, with Boron content ranking second. The most salt-tolerant crops (i.e., barley, sorghum, and wheat) were shown to be cultivable in all locations. According to calculations of the Heavy Metal Evaluation Index, groundwater in the Mara Triangle was generally safer for direct use by all users than the surface waters sampled in the past Lake Victoria and Nairobi studies.

Summary: Hippo was first identified in a genetic screen as a protein that suppressed proliferation and cell growth. Subsequently, it was shown that hippo acted in a so-called canonical cascade to suppress Yorkie, the Drosophila equivalent of Yes-activated protein (YAP), a mechanosensitive transcriptional cofactor that enhances the activity of the TEAD family of transcription factors. YAP promotes fibrosis, activation of cancer-associated fibroblasts, angiogenesis and cancer cell invasion. YAP activates the expression of the matricellular proteins CCN1 (cyr61) and CCN2 (ctgf), themselves mediators of fibrogenesis and oncogenesis, and coordination of matrix deposition and angiogenesis. This review discusses how therapeutically targeting YAP through YAP inhibitors verteporfin and celastrol and its downstream mediators CCN1 and CCN2 might be useful in treating melanoma.

Objective. Taybi syndrome is a rare genetical disorder with the symptoms of small stature, broad thumbs and first toes, a moderate to severe intellectual handicap, and unique facial traits. The present case study aimed with diagnose and therapeutic management of pediatric patients having Rubinstein-Taybi syndrome. Study area. The case study was carried out in Jawaharlal Nehru Medical College, Acharya Vinoba Bhave Rural Hospital, Sawangi Meghe, Wardha, Maharashtra, in department of Pediatrics. The present study follows case of male child, diagnosed with different degrees of compliance, in which the therapeutic approach was determined by the severity of the patient’s conditions. Outcomes. Case study on 3 years old male child was carried out and observed with some behavioral changes like unstable mood, distractibility and impulsivity along with attention problem, aggressive nature and self-injurious behavior etc. As the syndrome does not have a particular treatment but some therapies are applied to address issues that are frequently connected to the illness. The thumbs or toes surgically repaired might enhance grip or ease pain. The study was performed as per the scientific way, based on research literatures study.

Abstract Understanding the nature and origin of collective excitations in materials is of fundamental importance for unraveling the underlying physics of a many-body system. Excitation spectra are usually obtained by measuring the dynamical structure factor, S(Q, ω), using inelastic neutron or x-ray scattering techniques and are analyzed by comparing the experimental results against calculated predictions. We introduce a data-driven analysis tool which leverages ‘neural implicit representations’ that are specifically tailored for handling spectrographic measurements and are able to efficiently obtain unknown parameters from experimental data via automatic differentiation. In this work, we employ linear spin wave theory simulations to train a machine learning platform, enabling precise exchange parameter extraction from inelastic neutron scattering data on the square-lattice spin-1 antiferromagnet La2NiO4, showcasing a viable pathway towards automatic refinement of advanced models for ordered magnetic systems.

Abstract Purpose To report contributory factors and clinical outcomes of central posterior hyaloid fibrosis (CPHF) associated with neovascular age-related macular degeneration (nAMD). Methods In this retrospective, single-center study, patients with CPHF and nAMD were included. Demographic and imaging characteristics, as well as the anatomical and functional outcomes, of these patients were analysed. Results We identified 530 eyes in 273 patients with chronic predominantly scarred macular neovascularisation (MNV), and 32 eyes in 29 patients revealed CPHF, representing a prevalence of 6%. Patients had a mean age of 72.76 years. Before and during the development of CPHF, Type 2 MNV was observed in all eyes. At the time of MNV diagnosis, mean logMAR visual acuity was 1.308 ± 0.559 (20/407). The average time to develop CPHF was 27.3 months since the diagnosis of MNV. At the time of CPHF identification, the mean logMAR visual acuity was 1.498 ± 0.374 (20/630). RPE tear was observed in 6% (n = 2) of CPHF eyes. The average number of intravitreal anti-VEGF injections administered prior to the diagnosis of CPHF was 2.4 and after the onset of CPHF was 0.9. The final visual acuity was not significantly different at the final follow-up visit [1.304 ± 0.42 (20/402); p = 0.646]. Conclusion Rarely observed in eyes with predominantly scarred subfoveal type 2 MNVs and extensive subretinal fibrosis, CPHF is associated with poor visual outcomes. Its presence could possibly suggest a profibrotic effect of MNV on the posterior hyaloid. Trial Registration Number: Not applicable.

With applications in computer networks, robotics, genetics, data center network optimization, cryptocurrency exchange, transportation and logistics, cloud computing, and social network analysis, the problem of sorting permutations on transposition trees under various operations is highly relevant. The goal of the problem is to sort or rearrange the markers in a predetermined order by swapping them out at the vertices of a tree in the fewest possible swaps. Only certain classes of transposition trees, like path, star, and broom, have computationally efficient algorithms for sorting permutations. In this paper, we examine the so-called n−broom transposition trees. A single broom or simply a broom is a spanning tree formed by joining the center of the star graph with one end of the path graph. A generalized version of a broom known as an n−broom is created by joining the ends of n brooms to one vertex, known as the n−broom center. By using the idea of clear path markers, we present a novel algorithm for sorting permutations on an n−broom for n>2 that reduces to a novel 2−broom algorithm and that further reduces to two instances of a 1−broom algorithm. Our single-broom algorithm is similar to that of Kawahara et al.; however, our proof of optimality for the same is simpler.

Introduction: To study the clinical presentation, laboratory profile, echocardiographic details, management, and outcomes of children who were diagnosed to have multisystem inflammatory syndrome in children (MIS-C) in the immediate postoperative period after surgery for congenital heart defects (CHDs). Materials and Methods: This is a prospective case–control study that included children diagnosed to have MIS-C in the postoperative period based on clinical signs, rise in inflammatory markers, and echocardiographic features of ventricular dysfunction or coronary involvement. Management included intravenous immunoglobulin (IVIG), steroids, and antiplatelet medications in addition to routine postoperative care. Out of the 461 children who underwent surgery for CHD between April 1st, 2021, and November 30th, 2021, 18 children were diagnosed with MIS-C. After the initial routine postoperative course, all 18 children had sudden worsening in clinical and laboratory parameters. Other causes such as bacterial infection were ruled out. All of these children had features of MIS-C with ventricular dilatation and dysfunction, coronary artery involvement, and reactive COVID-19 immunoglobulin G antibody. There was a significant improvement in coronary artery dimensions after IVIG a ministration (P = 0.001). The involvement of the left main coronary artery was associated with significantly increased length of intensive care unit (ICU) and hospital stay (P = 0.019). Mean ICU and hospital stay was prolonged in the MIS-C group. There were two deaths in this group due to severe left ventricular dysfunction. Conclusions: During the pandemic, a proportion of patients undergoing elective cardiac surgery may develop unexpected worsening in clinical status due to MIS-C. A high index of suspicion and prompt treatment with IVIG and steroids may be helpful in improving outcomes.

Ru360, a mitochondrial Ca2+ uptake inhibitor, was tested in a unilateral fluid percussion TBI model in developing rats (P31). Vehicle and Ru360 treated TBI rats underwent sensorimotor behavioral monitoring between 24 and 72 h, thereafter which 185 brain metabolites were analyzed postmortem using LC/MS. Ru360 treatment after TBI improved sensorimotor behavioral recovery, upregulated glycolytic and pentose phosphate pathways, mitigated oxidative stress and prevented NAD+ depletion across both hemispheres. While neural viability improved ipsilaterally, it reduced contralaterally. Ru360 treatment, overall, had a global impact with most benefit near the strongest injury impact areas, while perturbing mitochondrial oxidative energetics in the milder TBI impact areas.

Abstract Purpose To compare real-life data on delayed intravitreal treatment of diabetic macular edema (DME) patients to early treatment. Methods In this single-centre, retrospective, interventional, comparative study, DME patients were divided into two groups based on when they received treatment: Group 1 - received treatment within 24 weeks and Group 2 - at or after 24 weeks from the time of treatment advice. Visual acuity and central subfield thickness (CSFT) changes were compared at various time points. Reasons for delaying treatment were noted. Results The study included 109 (Group 1–94; Group 2–15) eyes. When treatment was advised, demographic profile, diabetes duration, glucose control and VA between two groups were comparable. At this point, CSFT was higher in Group 1 than in Group 2 (p = 0.036). At injection time, Group 2 had better VA and lower CSFT than Group 1 (p

Targeting mitochondrial ion homeostasis using Kaempferol, a mitochondrial Ca2+ uniporter channel activator, improves energy metabolism and behavior soon after a traumatic brain injury (TBI) in developing rats. Because of broad TBI pathophysiology and brain mitochondrial heterogeneity, Kaempferol-mediated early-stage behavioral and brain metabolic benefits may accrue from diverse sources within the brain. We hypothesized that Kaempferol influences TBI outcome by differentially impacting the neural, vascular, and synaptic/axonal compartments. After TBI at early development (P31), functional magnetic resonance imaging and diffusion tensor imaging (DTI) were applied to determine imaging outcomes at adolescence (2 months post-injury). Vehicle and Kaempferol treatments were made at 1, 24, and 48 h post-TBI, and their effects were assessed at adolescence. A significant increase in neural connectivity was observed after Kaempferol treatment as assessed by the spatial extent and strength of the somatosensory cortical and hippocampal resting-state functional connectivity (RSFC) networks. However, no significant RSFC changes were observed in the thalamus. DTI measures of fractional anisotropy (FA) and apparent diffusion coefficient, representing synaptic/axonal and microstructural integrity, showed significant improvements after Kaempferol treatment, with highest changes in the frontal and parietal cortices and hippocampus. Kaempferol treatment also increased corpus callosal FA, indicating measurable improvement in the interhemispheric structural connectivity. TBI prognosis was significantly altered at adolescence by early Kaempferol treatment, with improved neural connectivity, neurovascular coupling, and parenchymal microstructure in select brain regions. However, Kaempferol failed to improve vasomotive function across the whole brain, as measured by cerebrovascular reactivity. The differential effects of Kaempferol treatment on various brain functional compartments support diverse cellular-level mitochondrial functional outcomes in vivo.

Background: COVID-19 pandemic posed a huge stress on health-care givers affecting their physical and mental health. Wellness strategies like yoga can improve flexibility, resilience, and outlook. Aim: The present study explored the effect of 8-week standard common yoga protocol (CYP) intervention on autonomic functions, emotional stress, oxidative stress, and inflammation markers in the nurse group of health-care givers. Materials and Methods: It is a randomized controlled trial where 50 nurses underwent CYP and 50 participated as controls. Anthropometric parameters, cardiovascular parameters, autonomic function including time and frequency domain parameters, biochemical parameters, and psychological stress using the questionnaire were assessed before and after 8-week CYP. Results: Total 88 nurses completed the study with 42 and 46 participants, respectively, in the CYP and control groups. CYP intervention resulted in a significant reduction in cardiovascular parameters systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse pressure, and rate pressure product (P < 0.001, P < 0.001, P < 0.001, P < 0.001, and P = 0.002, respectively), perceived stress score and Depression, Anxiety, and Stress Scale psychological variables of depression, anxiety, and stress, and serum lipid parameters compared to the control group. CYP significantly increased total power, low frequency, high frequency, root mean square of successive differences between adjacent NN intervals, change in successive normal sinus (NN) intervals exceeds 50 ms, and pNN50% (P < 0.001, P = 0.006, P = 0.006, P = 0.039, P < 0.001, and P = 0.013, respectively) suggesting improved resting autonomic modulation and parasympathodominance due to higher vagal efferent activity. There were significant reductions in serum cortisol, tumor necrosis factor-alpha, interleukin (IL)-1, and IL-6 in both the groups. Serum telomerase significantly reduced (P = 0.024) and total antioxidant capacity (P = 0.036) increased in the CYP group post intervention. Conclusion: CYP intervention was beneficial in improving psychophysiological, autonomic, and biochemical profile of the nurse group of health-care workers.

Dry eye disease (DED) can lead to ocular discomfort as well as visual disturbances. Older adults are more likely to develop DED. They are also more likely to develop retinal diseases such as diabetic retinopathy and age-related macular degeneration, which may require vitreoretinal surgeries, lasers, and intravitreal injections. Posterior segment surgery may cause or worsen existing dry eye symptoms, albeit temporarily. Despite good anatomic and functional outcomes, ocular surface dysfunction can have a significant impact on the quality of life, lowering a patient's satisfaction with the retinal treatment. Preexisting DED, intraoperative tissue handling, and postoperative treatment may all contribute to the severity of ocular surface dysfunction. In this article, we have reviewed all relevant studies on the development of ocular surface changes and DED, as well as the impact of vitreoretinal surgeries and procedures on the ocular surface.

Afferent nociceptive activity in the reorganizing spinal cord after SCI influences supraspinal regions to establish pain. Clinical evidence of poor motor functional recovery in SCI patients with pain, led us to hypothesize that sensory-motor integration transforms into sensory-motor interference to manifest pain. This was tested by investigating supraspinal changes in a rat model of hemicontusion cervical SCI. Animals displayed ipsilateral forelimb motor dysfunction and pain, which persisted at 6 weeks after SCI. Using resting state fMRI at 8 weeks after SCI, RSFC across 14 ROIs involved in nociception, indicated lateral differences with a relatively weaker right-right connectivity (deafferented-contralateral) compared to left-left (unaffected-ipsilateral). However, the sensory (S1) and motor (M1/M2) networks showed greater RSFC using right hemisphere ROI seeds when compared to left. Voxel seeds from the somatosensory forelimb (S1FL) and M1/M2 representations reproduced the SCI-induced sensory and motor RSFC enhancements observed using the ROI seeds. Larger local connectivity occurred in the right sensory and motor networks amidst a decreasing overall local connectivity. This maladaptive reorganization of the right (deafferented) hemisphere localized the sensory component of pain emerging from the ipsilateral forepaw. A significant expansion of the sensory and motor network s overlap occurred globally after SCI when compared to sham, supporting the hypothesis that sensory and motor interference manifests pain. Voxel-seed based analysis revealed greater sensory and motor network overlap in the left hemisphere when compared to the right. This left predominance of the overlap suggested relatively larger pain processing in the unaffected hemisphere, when compared to the deafferented side.

Abstract Background Idiopathic connective tissue disease juvenile dermatomyositis (JDM) is characterised by inflammatory myositis and distinctive skin abnormalities. Only a few cases of Dermatomyositis (DM) owing to chemotherapy used to treat cancer have been reported, despite the fact that the link between DM and cancer in adults is widely known. We describe the case of a female, age 14, who experienced DM as a side effect of chemotherapy following enucleation for retinoblastoma. We also discussed our patient's likely pathophysiology of JDM after treatment. Case presentation A 14-year-old female came to our facility complaining of trouble walking and bluish-black discoloration on her neck, elbows, forehead, and knees that had been present for eight months. The patient had undergone enucleation of the left eye due to retinoblastoma, followed by 40 cycles of radiation therapy and 13 cycles of chemotherapy with Cyclophosphamide, Etoposide, Carboplatin, Vincristine, and Dactinomycin. Her serum LDH and CPK levels were high, and she tested positive for ANA. The muscle biopsy was consistent with the changes of DM. When electromyography was performed, it revealed tiny, fibrillating, polyphasic motor unit potentials and sharp, positive waves that were suggestive with DM. A diagnosis of JDM was made after taking into account the symptoms, biochemical data, muscle biopsy, and electromyography results. The patient's symptoms started to get better once methotrexate and oral corticosteroids were started. Conclusion This case report emphasises the value of ongoing observation after cancer chemotherapy because specific cutaneous and muscle symptoms may lead paediatricians to consider the possibility of chemotherapy-induced JDM, which is uncommon in young patients.

Breast cancer (BC) continues to be one of the major causes of cancer deaths in women. Progress has been made in targeting hormone and growth factor receptor-positive BCs with clinical efficacy and success. However, little progress has been made to develop a clinically viable treatment for the triple-negative BC cases (TNBCs). The current study aims to identify potent agents that can target TNBCs. Extracts from microbial sources have been reported to contain pharmacological agents that can selectively inhibit cancer cell growth. We have screened and identified pigmented microbial extracts (PMBs) that can inhibit BC cell proliferation by targeting legumain (LGMN). LGMN is an oncogenic protein expressed not only in malignant cells but also in tumor microenvironment cells, including tumor-associated macrophages. An LGMN inhibition assay was performed, and microbial extracts were evaluated for in vitro anticancer activity in BC cell lines, angiogenesis assay with chick chorioallantoic membrane (CAM), and tumor xenograft models in Swiss albino mice. We have identified that PMB from the Exiguobacterium (PMB1), inhibits BC growth more potently than PMB2, from the Bacillus subtilis strain. The analysis of PMB1 by GC-MS showed the presence of a variety of fatty acids and fatty-acid derivatives, small molecule phenolics, and aldehydes. PMB1 inhibited the activity of oncogenic legumain in BC cells and induced cell cycle arrest and apoptosis. PMB1 reduced the angiogenesis and inhibited BC cell migration. In mice, intraperitoneal administration of PMB1 retarded the growth of xenografted Ehrlich ascites mammary tumors and mitigated the proliferation of tumor cells in the peritoneal cavity in vivo. In summary, our findings demonstrate the high antitumor potential of PMB1.

Oxidative energy metabolism is depressed after mild/moderate traumatic brain injury (TBI) during early development, accompanied by behavioral debilitation and secondary neuronal death. A TBI metabolome analysis revealed broad effects with a striking impact on energy metabolism. Our studies on mitochondrial modulators and their effects on brain function have shown that kaempferol, a stimulator of the mitochondrial Ca2+ uniporter channel (mCU), enhanced neural and neurovascular activity in the normal brain and improved stimulus-induced brain activation and behavior after TBI during early development. Because kaempferol enhances mitochondrial Ca2+ uptake and cycling, with protective effects after TBI, we tested the hypothesis that kaempferol treatment during the acute/subacute stage after TBI (0-72 h) acted on mitochondria in improving TBI outcome. Developmental age rats (P31) underwent TBI and were treated with vehicle or kaempferol (1 mg/kg intraperitoneally) in three doses at 1, 24, and 48 h after TBI. Brains were harvested at 72 h and subjected to liquid chromatography mass spectrometric measurements. Decrease in pyruvate and tricarboxylic acid (TCA) cycle flux were observed in the untreated and vehicle-treated group, consistent with previously established energy metabolic decline after TBI. Kaempferol improved TCA cycle flux, maintained mitochondrial functional integrity as observed by decreased acyl carnitines, improved neural viability as evidenced by higher N-acetyl aspartate levels. The positive outcomes of kaempferol on metabolic profile corresponded with improved sensorimotor behavior.

Traumatic brain injury (TBI) in general has varied neuropathological consequences depending upon the intensity and biomechanics of the injury. Furthermore, in pediatric TBI, intrinsic developmental changes add further complexity, necessitating a biochemical dimension for improved TBI characterization. In our earlier study investigating the subacute stage TBI metabolome (72 h post-injury) in a developmental rat model, significant ipsilateral brain biochemical changes occurred across 25 metabolite sets as determined by metabolite set enrichment analysis (MSEA). The broad metabolic perturbation was accompanied by behavioral deficits and neuronal loss across the ipsilateral hemisphere containing the injury epicenter. In order to obtain a consolidated biochemical profile of the TBI assessment, a subgrouping of the 190 identified brain metabolites was performed. Metabolites were divided into seven major subgroups: oxidative energy/mitochondrial, glycolysis/pentose phosphate pathway, fatty acid, amino acid, neurotransmitters/neuromodulators, one-carbon/folate and other metabolites. Subgroups were based on the chemical nature and association with critically altered biochemical pathways after TBI as obtained from our earlier untargeted analysis. Each metabolite subgroup extracted from the ipsilateral sham and TBI brains were modeled using multivariate partial least square discriminant analysis (PLS-DA) with the model accuracy used as a measurable index of TBI neurochemical impact. Volcano plots of each subgroup, corrected for multiple comparisons, determined the TBI neurochemical specificity. The results provide a ranked biochemical profile along with specificity of changes after developmental TBI, enabling a consolidated biochemical template for future classification of different TBI intensities and injury types in animal models.

The purposes of this paper are to better understand the design and impact of left turn lane offset and provide state transportation agencies recommendations on best practices and alternative design options to address left turn sight line obstruction issues. Research studies and existing guidelines on left turn lane offset were reviewed and summarized to offer insights in driver sight distance and behavior, intersection safety and operations, as well as design elements related to left turn lane offset. Studies showed that at both unsignalized intersections and signalized intersections with permitted left turns, obstructed sight line could cause higher possibilities of collisions between left turning vehicles and oncoming vehicles from the opposing direction. Existing evaluations of left turn lane offset, with data from multiple states in the United States, reported that positive left turn lane offsets were beneficial in terms of safety and operations. Most agency guidelines provided very limited discussions about left turn lane offset. This review demonstrated that positive left turn lane offsets are beneficial to intersection safety and operations. Based on the review of research and guidelines, recommendations were provided for transportation agencies for left turn lane offset implementation. A discussion on new left turn design concepts was also included to point out directions for future research and practice.