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ABSTRACT Treatment outcomes for Mycobacteroides abscessus (Mab, also known as Mycobacterium abscessus) disease are still unsatisfactory, mainly due to issues with drug toxicity, tolerability, and efficacy. Treating Mab disease is challenging due to its high baseline antibiotic resistance, initial requirement for intravenous therapy, and poor medication tolerance. Omadacycline, a new tetracycline, is active against Mab. Since any new antibiotic effective against Mab is expected to be used in combination with other antibiotics, we evaluated the efficacy of two triple-drug combinations comprising omadacycline, omadacycline + amikacin + imipenem, and omadacycline + clofazimine + linezolid against two contemporary Mab clinical isolates in a mouse model of Mab lung disease. Antibiotic administration was initiated 1-week post-infection and was given daily, with Mab burden in the lungs at treatment completion serving as the endpoint. Omadacycline alone moderately reduced Mab levels and maintained better health in mice compared to untreated ones, which typically suffered from the infection. The omadacycline + clofazimine + linezolid combination showed immediate bactericidal activity and enhanced efficacy over 6 weeks, particularly against the more resistant strain (M9507). However, the clofazimine + linezolid combination lacked early bactericidal activity. When combined with amikacin and imipenem, omadacycline did not improve the regimen’s effectiveness over 4 weeks of treatment. Our study showed that omadacycline + clofazimine + linezolid exhibited significant bactericidal activity over an extended treatment duration. However, adding omadacycline to amikacin and imipenem did not improve regimen effectiveness against the evaluated clinical isolates within 4 weeks. Further research in Mab disease patients is needed to determine the most effective omadacycline-containing regimen.IMPORTANCEMycobacteroides abscessus is a common environmental bacterium that causes infections in people with compromised lung function, including those with bronchiectasis, cystic fibrosis, chronic obstructive pulmonary disease, and weakened immune systems, especially among older individuals. Treating M. abscessus disease is challenging due to the limited effectiveness and toxicity of current antibiotics, which often require prolonged use. Omadacycline, a new antibiotic, shows promise against M. abscessus. Using a mouse model that mimics M. abscessus disease in humans, we studied the effectiveness of including omadacycline with recommended antibiotics. Adding omadacycline to clofazimine and linezolid significantly improved treatment outcomes, rapidly clearing the bacteria from the lungs and maintaining effectiveness throughout. This oral combination is convenient for patients. However, adding omadacycline to amikacin and imipenem did not improve treatment effectiveness within 4 weeks. Further study with M. abscessus patients is necessary to optimize omadacycline-based treatment strategies for this disease.

With the 2019 coronavirus disease (COVID-19) pandemic, there is an increasing demand for remote monitoring technologies to reduce patient and provider exposure. One field that has an increasing potential is teleguided ultrasound, where telemedicine and point-of-care ultrasound (POCUS) merge to create this new scope. Teleguided POCUS can minimize staff exposure while preserving patient safety and oversight during bedside procedures. In this paper, we propose the use of teleguided POCUS supported by AI technologies for the remote monitoring of COVID-19 patients by non-experienced personnel including self-monitoring by the patients themselves. Our hypothesis is that AI technologies can facilitate the remote monitoring of COVID-19 patients through the utilization of POCUS devices, even when operated by individuals without formal medical training. In pursuit of this goal, we performed a pilot analysis to evaluate the performance of users with different clinical backgrounds using a computer-based system for COVID-19 detection using lung ultrasound. The purpose of the analysis was to emphasize the potential of the proposed AI technology for improving diagnostic performance, especially for users with less experience.

Liver fibrosis, a major global health issue, is marked by excessive collagen deposition that impairs liver function. Noninvasive methods for the direct visualization of collagen content are crucial for the early detection and monitoring of fibrosis progression. This study investigates the potential of spectral photoacoustic imaging (sPAI) to monitor collagen development in liver fibrosis. Utilizing a novel data-driven superpixel photoacoustic unmixing (SPAX) framework, we aimed to distinguish collagen presence and evaluate its correlation with fibrosis progression. We employed an established diethylnitrosamine (DEN) model in rats to study liver fibrosis over various time points. Our results revealed a significant correlation between increased collagen photoacoustic signal intensity and advanced fibrosis stages. Collagen abundance maps displayed dynamic changes throughout fibrosis progression. These findings underscore the potential of sPAI for the noninvasive monitoring of collagen dynamics and fibrosis severity assessment. This research advances the development of noninvasive diagnostic tools and personalized management strategies for liver fibrosis.

Tendon injury and healing involve significant changes to tissue biology and composition. Current techniques often require animal sacrifice or tissue destruction, limiting assessment of dynamic changes in tendons, including treatment response, disease development, rupture risk, and healing progression. Changes in tendon composition, such as altered collagen content, can significantly impact tendon mechanics and function. Analyses of compositional changes typically require ex vivo techniques with animal sacrifice or destruction of the tissue. In vivo evaluation of tendons is critical for longitudinal assessment. We hypothesize that photoacoustic ultrasound detects differences in collagen concentration throughout healing. We utilized photoacoustic ultrasound, a hybrid imaging modality that combines ultrasound and laser-induced photoacoustic signals to create detailed and high-resolution images of tendons, to identify its endogenous collagen composition. We correlated the photoacoustic signal to picrosirius red staining. The results show that the photoacoustic ultrasound-estimated collagen content in tendons correlates well with picrosirius red staining. This study demonstrates that photoacoustic ultrasound can assess injury-induced compositional changes within tendons and is the first study to image these targets in rat Achilles tendon in vivo.

Guillain-Barre syndrome (GBS) is one of the common causes for acute flaccid paralysis in adults and mostly preceded by infection. Miller Fisher syndrome (MFS) is a rare variant of GBS with incidence of 1 to 2 in 1,000,000. This syndrome has a triad of ataxia, areflexia, and ophthalmoplegia and diagnosed when two out above three features are present. It usually preceded by viral infection, most commonly Campylobacter jejuni, cytomegalovirus, and Epstein–Barr virus. However, it is very rarely reported in pulmonary tuberculosis. The pathogenesis involves an aberrant immune response due to molecular mimicry against myelin gangliosides. Hereby we are presenting an unusual case of MFS variant of GBS associated with pulmonary tuberculosis.

Abstract Background Glottic insufficiency, or glottic gap as it is commonly called, is a common cause of dysphonia, producing symptoms of soft voice, decreased projection, and vocal fatigue. The etiology of glottic gap can occur from issues related to muscle atrophy, neurologic impairment, structural abnormalities, and trauma related causes. Treatment of glottic gap can include surgical and behavioral therapies or a combination of the two. When surgery is chosen, closure of the glottic gap is the primary goal. Options for surgical management include injection medialization, thyroplasty, and other methods of medializing the vocal folds. Methods This manuscript reviews the current literature regarding the options for treatment of glottic gap. Discussion This manuscript discusses options for treatment of glottic gap, including the indications for temporary and permanent treatment modalities; the differences between the available materials for injection medialization laryngoplasty and how they affect the vibratory function of the vocal folds and vocal outcome; and the evidence that supports an algorithm for treatment of glottic gap. Level of Evidence 3a—Systematic review of case–control studies.

Machine learning for medical imaging not only requires sufficient amounts of data for training and testing but also that the data be independent. It is common to see highly interdependent data whenever there are inherent correlations between observations. This is especially to be expected for sequential imaging data taken from time series. In this study, we evaluate the use of statistical measures to test the independence of sequential ultrasound image data taken from the same case. A total of 1180 B-mode liver ultrasound images with 5903 regions of interests were analyzed. The ultrasound images were taken from two liver disease groups, fibrosis and steatosis, as well as normal cases. Computer-extracted texture features were then used to train a machine learning (ML) model for computer-aided diagnosis. The experiment resulted in high two-category diagnosis using logistic regression, with AUC of 0.928 and high performance of multicategory classification, using random forest ML, with AUC of 0.917. To evaluate the image region independence for machine learning, Jenson–Shannon (JS) divergence was used. JS distributions showed that images of normal liver were independent from each other, while the images from the two disease pathologies were not independent. To guarantee the generalizability of machine learning models, and to prevent data leakage, multiple frames of image data acquired of the same object should be tested for independence before machine learning. Such tests can be applied to real-world medical image problems to determine if images from the same subject can be used for training.

A machine learning approach based on nutrient loading observations and physical large scale climate indices improves early seasonal prediction of harmful algal bloom activity between July and October in Lake Erie, which can help local fisheries management.

ABSTRACT Mycobacteroides abscessus is an opportunistic pathogen in people with structural lung conditions such as bronchiectasis, chronic obstructive pulmonary disease, and cystic fibrosis. Pulmonary M. abscessus infection causes progressive symptomatic and functional decline as well as diminished lung function and is often incurable with existing antibiotics. We investigated the efficacy of a new tetracycline, omadacycline, in combination with existing antibiotics recommended to treat this indication, in a mouse model of M. abscessus lung disease. Amikacin, azithromycin, bedaquiline, biapenem, cefoxitin, clofazimine, imipenem, linezolid, and rifabutin were selected as companions to omadacycline. M. abscessus burden in the lungs of mice over a 4-week treatment duration was considered the endpoint. Omadacycline in combination with linezolid, imipenem, cefoxitin, biapenem, or rifabutin exhibited early bactericidal activity compared to any single drug. Using three M. abscessus isolates, we also determined the in vitro frequency of spontaneous resistance against omadacycline to be between 1.9 × 10−10 and 6.2 × 10−10 and the frequency of persistence against omadacycline to be between 5.3 × 10−6 and 1.3 × 10−5. Based on these findings, the combination of omadacycline and select drugs that are included in the recent treatment guidelines may exhibit improved potency to treat M. abscessus lung disease. IMPORTANCE M. abscessus disease incidence is increasing in the United States. This disease is difficult to cure with existing antibiotics. In this study, we describe the efficacy of a new tetracycline antibiotic, omadacycline, in combination with an existing antibiotic to treat this disease. A mouse model of M. abscessus lung disease was used to assess the efficacies of these experimental treatment regimens. Omadacycline in combination with select existing antibiotics exhibited bactericidal activity during the early phase of treatment.

In recent years, advances in ultrasound therapeutics have been implemented into treatment algorithms for the adult population; however, the use of therapeutic ultrasound in the pediatric population still needs to be further elucidated. In order to better characterize the utilization and practicality of sonothrombolysis in the juvenile population, the authors conducted a literature review of current pediatric research in therapeutic ultrasound. The PubMed database was used to search for all clinical and preclinical studies detailing the use and applications of sonothrombolysis, with a focus on the pediatric population. As illustrated by various review articles, case studies, and original research, sonothrombolysis demonstrates efficacy and safety in clot dissolution in vitro and in animal studies, particularly when combined with microbubbles, with potential applications in conditions such as deep venous thrombosis, peripheral vascular disease, ischemic stroke, myocardial infarction, and pulmonary embolism. Although there is limited literature on the use of therapeutic ultrasound in children, mainly due to the lower prevalence of thrombotic events, sonothrombolysis shows potential as a noninvasive thrombolytic treatment. However, more pediatric sonothrombolysis research needs to be conducted to quantify the safety and ethical considerations specific to this vulnerable population.

Recently, the Government of Uttar Pradesh (UP) unveiled a draft bill of the UP Population Policy (2021–2030) on World Population Day to bring down the gross fertility rate and stabilization of the population. The history of the two-child norm in India has shown that different state governments had tried to implement it at different timelines during the past 20 years. Global evidence suggests that Vietnam and Bangladesh have stabilized their population and control birth rate despite not having two-child policies. Moreover, sex-selective abortion, preference for male children, denying the paternity of female children, pre-natal sex determination, and violence against women for giving birth to girl children will be on rise. Female literacy, empowerment, and addressing unmet needs of contraceptives are the time-tested solutions for population control rather than raising a new social problem with a “two-child policy” bill/act.

Abstract Inhibitors of the lipogenic enzyme fatty acid synthase (FASN) have attracted much attention in the last decade as potential targeted cancer therapies. However, little is known about the molecular determinants of cancer cell sensitivity to FASN inhibitors (FASNis), which is a major roadblock to their therapeutic application. Here, we find that pharmacological starvation of endogenously produced FAs is a previously unrecognized metabolic stress that heightens mitochondrial apoptotic priming and favors cell death induction by BH3 mimetic inhibitors. Evaluation of the death decision circuits controlled by the BCL-2 family of proteins revealed that FASN inhibition is accompanied by the upregulation of the pro-death BH3-only proteins BIM, PUMA, and NOXA. Cell death triggered by FASN inhibition, which causally involves a palmitate/NADPH-related redox imbalance, is markedly diminished by concurrent loss of BIM or PUMA, suggesting that FASN activity controls cancer cell survival by fine-tuning the BH3 only proteins-dependent mitochondrial threshold for apoptosis. FASN inhibition results in a heightened mitochondrial apoptosis priming, shifting cells toward a primed-for-death state “addicted” to the anti-apoptotic protein BCL-2. Accordingly, co-administration of a FASNi synergistically augments the apoptosis-inducing activity of the dual BCL-XL/BCL-2 inhibitor ABT-263 (navitoclax) and the BCL-2 specific BH3-mimetic ABT-199 (venetoclax). FASN inhibition, however, fails to sensitize breast cancer cells to MCL-1- and BCL-XL-selective inhibitors such as S63845 and A1331852. A human breast cancer xenograft model evidenced that oral administration of the only clinically available FASNi drastically sensitizes FASN-addicted breast tumors to ineffective single-agents navitoclax and venetoclax in vivo. In summary, a novel FASN-driven facet of the mitochondrial priming mechanistically links the redox-buffering mechanism of FASN activity to the intrinsic apoptotic threshold in breast cancer cells. Combining next-generation FASNis with BCL-2-specific BH3 mimetics that directly activate the apoptotic machinery might generate more potent and longer-lasting antitumor responses in a clinical setting.

Abstract This study investigates the use of hydralazine to enhance ultrasound hyperthermia for the treatment of hepatocellular carcinoma (HCC) by minimizing flow-mediated heat loss from the tumor. Murine HCC tumors were treated with a continuous mode ultrasound with or without an intravenous administration of hydralazine (5 mg/kg). Tumor blood flow and blood vessels were evaluated by contrast-enhanced ultrasound (CEUS) imaging and histology, respectively. Hydralazine markedly enhanced ultrasound hyperthermia through the disruption of tumor blood flow in HCC. Ultrasound treatment with hydralazine significantly reduced peak enhancement (PE), perfusion index (PI), and area under the curve (AUC) of the CEUS time-intensity curves by 91.9 ± 0.9%, 95.7 ± 0.7%, and 96.6 ± 0.5%, compared to 71.4 ± 1.9%, 84.7 ± 1.1%, and 85.6 ± 0.7% respectively without hydralazine. Tumor temperature measurements showed that the cumulative thermal dose delivered by ultrasound treatment with hydralazine (170.8 ± 11.8 min) was significantly higher than that without hydralazine (137.7 ± 10.7 min). Histological assessment of the ultrasound-treated tumors showed that hydralazine injection formed larger hemorrhagic pools and increased tumor vessel dilation consistent with CEUS observations illustrating the augmentation of hyperthermic effects by hydralazine. In conclusion, we demonstrated that ultrasound hyperthermia can be enhanced significantly by hydralazine in murine HCC tumors by modulating tumor blood flow. Future studies demonstrating the safety of the combined use of ultrasound and hydralazine would enable the clinical translation of the proposed technique.

We present a theoretical study on the energy dispersion of an ultrathin film of periodically-aligned single-walled carbon nanotubes (SWCNTs) with the help of the Bogoliubov–Valatin transformation. The Hamiltonian of the film was derived using the many-particle green function technique in the Matsubara frequency formalism. The periodic array of SWCNTs was embedded in a dielectric with comparatively higher permittivity than the substrate and the superstrate such that the SWCNT film became independent with the axis of quantization but keeps the thickness as the variable parameter, making the film neither two-dimensional nor three-dimensional, but transdimensional. It was revealed that the energy dispersion of the SWCNT film is thickness dependent.

A metal- and additive-free, highly efficient, step-economical deoxygenative C2-heteroarylation of quinolines and isoquinolines was achieved from readily available N-oxides and N-sulfonyl-1,2,3-triazoles. A variety of α-triazolylquinoline derivatives were synthesized with good regioselectivity and in excellent yields under mild reaction conditions. Further, a gram-scale and one-pot synthesis illustrated the efficacy and simplicity of the developed protocol. The current transformation was also found to be compatible for the late-stage modification of natural products.

Abstract Hepatocellular carcinoma (HCC) is a highly vascular solid tumor. We have previously shown that ultrasound (US) therapy significantly reduces tumor vascularity. This study monitors US-induced changes in tumor oxygenation on murine HCC by photoacoustic imaging (PAI). Oxygen saturation and total hemoglobin were assessed by PAI before and after US treatments performed at different intensities of continuous wave (CW) bursts and pulsed wave (PW) bursts US. PAI revealed significant reduction both in HCC oxygen saturation and in total hemoglobin, proportional to the US intensity. Both CW bursts US (1.6 W/cm2) and the PW bursts US (0.8 W/cm2) significantly reduced HCC oxygen saturation and total hemoglobin which continued to diminish with time following the US treatment. The effects of US therapy were confirmed by power Doppler and histological examination of the hemorrhage in tumors. By each measure, the changes observed in US-treated HCC were more prevalent than those in sham-treated tumors and were statistically significant. In conclusion, the results show that US is an effective vascular-targeting therapy for HCC. The changes in oxygenation induced by the US treatment can be noninvasively monitored longitudinally by PAI without the use of exogenous image-enhancing agents. The combined use of PAI and the therapeutic US has potential for image-guided vascular therapy for HCC.

We calculate the fully retarded one-photon exchange interaction potential between electrically neutral, identical atoms, one of which is assumed to be in an excited state, by matching the scattering matrix (S matrix) element with the effective Hamiltonian. Based on the Feynman prescription, we obtain the imaginary part of the interaction energy. Our results lead to precise formulas for the distance-dependent enhancement and suppression of the decay rates of entangled superradiant and subradiant Dicke states (Bell states), as a function of the interatomic distance. The formulas include a long-range tail due to entanglement. We apply the result to an example calculation involving two hydrogen atoms, one of which is in an excited P state.

Objective: The study evaluates quantitative ultrasound (QUS) texture features with machine learning (ML) to enhance the sensitivity of B-mode ultrasound (US) for the detection of fibrosis at an early stage and distinguish it from advanced fibrosis. Different ML methods were evaluated to determine the best diagnostic model. Methods: 233 B-mode images of liver lobes with early and advanced-stage fibrosis induced in a rat model were analyzed. Sixteen features describing liver texture were measured from regions of interest (ROIs) drawn on B-mode images. The texture features included a first-order statistics run length (RL) and gray-level co-occurrence matrix (GLCM). The features discriminating between early and advanced fibrosis were used to build diagnostic models with logistic regression (LR), naïve Bayes (nB), and multi-class perceptron (MLP). The diagnostic performances of the models were compared by ROC analysis using different train-test sampling approaches, including leave-one-out, 10-fold cross-validation, and varying percentage splits. METAVIR scoring was used for histological fibrosis staging of the liver. Results: 15 features showed a significant difference between the advanced and early liver fibrosis groups, p < 0.05. Among the individual features, first-order statics features led to the best classification with a sensitivity of 82.1–90.5% and a specificity of 87.1–89.8%. For the features combined, the diagnostic performances of nB and MLP were high, with the area under the ROC curve (AUC) approaching 0.95–0.96. LR also yielded high diagnostic performance (AUC = 0.91–0.92) but was lower than nB and MLP. The diagnostic variability between test-train trials, measured by the coefficient-of-variation (CV), was higher for LR (3–5%) than nB and MLP (1–2%). Conclusion: Quantitative ultrasound with machine learning differentiated early and advanced fibrosis. Ultrasound B-mode images contain a high level of information to enable accurate diagnosis with relatively straightforward machine learning methods like naïve Bayes and logistic regression. Implementing simple ML approaches with QUS features in clinical settings could reduce the user-dependent limitation of ultrasound in detecting early-stage liver fibrosis.

Descriptive statistics are an important part of biomedical research which is used to describe the basic features of the data in the study. They provide simple summaries about the sample and the measures. Measures of the central tendency and dispersion are used to describe the quantitative data. For the continuous data, test of the normality is an important step for deciding the measures of central tendency and statistical methods for data analysis. When our data follow normal distribution, parametric tests otherwise nonparametric methods are used to compare the groups. There are different methods used to test the normality of data, including numerical and visual methods, and each method has its own advantages and disadvantages. In the present study, we have discussed the summary measures and methods used to test the normality of the data.

Background and Aims: Not all patients with dementia are the same, and Global Deterioration Scale (GDS) helps in staging dementia. Ophthalmologists usually prefer general anesthesia (GA) for cataract surgery in patients with dementia. We evaluated the impact of “Choosing Wisely” initiative on anesthesia options for cataract surgery in patients with dementia undergoing cataract surgery. Material and Methods: A retrospective review of electronic perioperative database was performed over a 4-year period of patients with a specific diagnosis of dementia undergoing cataract surgery, after the introduction of the “Choosing Wisely” based on preoperative GDS assessment. Preferred method by the listing ophthalmologist, changes in anesthesia modality based on GDS, and the occurrence of intraoperative events were analyzed. Results: One hundred and thirty-six patients with dementia underwent cataract surgery over a 4-year period. The mean patient age was 78 years, 73.5% female, and 55% ASA physical status III. GA was administered for GDS stage 6–7, and regional anesthesia (RA) for GDS stages 1–5. Surgery was uneventful under RA in 64% of the patients (87 out of 136), and 2% (3 patients) originally deemed suitable for RA were converted to GA. Conclusions: The authors found a reduced requirement for GA when “Choosing Wisely' initiative was used based on the GDS stage.

Student's t test (t test), analysis of variance (ANOVA), and analysis of covariance (ANCOVA) are statistical methods used in the testing of hypothesis for comparison of means between the groups. The Student's t test is used to compare the means between two groups, whereas ANOVA is used to compare the means among three or more groups. In ANOVA, first gets a common P value. A significant P value of the ANOVA test indicates for at least one pair, between which the mean difference was statistically significant. To identify that significant pair(s), we use multiple comparisons. In ANOVA, when using one categorical independent variable, it is called one-way ANOVA, whereas for two categorical independent variables, it is called two-way ANOVA. When using at least one covariate to adjust with dependent variable, ANOVA becomes ANCOVA. When the size of the sample is small, mean is very much affected by the outliers, so it is necessary to keep sufficient sample size while using these methods.

Abstract Background and objective Lung ultrasound is an inherently user‐dependent modality that could benefit from quantitative image analysis. In this pilot study we evaluate the use of computer‐based pleural line (p‐line) ultrasound features in comparison to traditional lung texture (TLT) features to test the hypothesis that p‐line thickening and irregularity are highly suggestive of coronavirus disease 2019 (COVID‐19) and can be used to improve the disease diagnosis on lung ultrasound. Methods Twenty lung ultrasound images, including normal and COVID‐19 cases, were used for quantitative analysis. P‐lines were detected by a semiautomated segmentation method. Seven quantitative features describing thickness, margin morphology, and echo intensity were extracted. TLT lines were outlined, and texture features based on run‐length and gray‐level co‐occurrence matrix were extracted. The diagnostic performance of the 2 feature sets was measured and compared using receiver operating characteristics curve analysis. Observer agreements were evaluated by measuring interclass correlation coefficients (ICC) for each feature. Results Six of 7 p‐line features showed a significant difference between normal and COVID‐19 cases. Thickness of p‐lines was larger in COVID‐19 cases (6.27 ± 1.45 mm) compared to normal (1.00 ± 0.19 mm), P

Pressure shifts inside an atomic beam are among the more theoretically challenging effects in high-precision measurements of atomic transitions. A crucial element in their theoretical analysis is the understanding of long-range interatomic interactions inside the beam. For excited reference states, the presence of quasi-degenerate states leads to additional challenges, due to the necessity to diagonalize large matrices in the quasi-degenerate hyperfine manifolds. Here, we focus on the interactions of hydrogen atoms in reference states composed of an excited nD state (atom A), and in the metastable 2S state (atom B). We devote special attention to the cases n=3 and n=8. For n=3, the main effect is generated by quasi-degenerate virtual P states from both atoms A and B and leads to experimentally relevant second-order long-range (van-der-Waals) interactions proportional to the sixth inverse power of the interatomic distance. For n=8, in addition to virtual states with two states of P symmetry, one needs to take into account combined virtual P and F states from atoms A and B. The numerical value of the so-called C6 coefficients multiplying the interaction energy was found to grow with the principal quantum number of the reference D state; it was found to be of the order of 1011 in atomic units. The result allows for the calculation of the pressure shift inside atomic beams while driving transitions to nD states.

We study the magic wavelength for two-photon 1S–nS transitions in a hydrogen and deuterium atom, as well as 2S–nS transitions, where the lower level is the metastable 2S state. At the magic wavelength, the dynamic Stark shifts of the ground and the excited state of the transition coincide, so that the transition frequency is independent of the intensity of the trapping laser field. Experimentally feasible magic wavelengths of transitions with small slopes in the atomic polarizabilities are determined; these are the most stable magic wavelengths against variations of the laser frequency. We provide data for the magic wavelengths for the 1S–nS and 2S–nS transitions in hydrogen and deuterium, with n=2,⋯,8. We also analyze the stability of the elimination of the ac Stark shift at the magic wavelength against tiny variations of the trapping laser frequency from the magic value.

Abstract Background Herpes simplex virus 1 (HSV-1) infection can result in a life-threatening condition known as herpes simplex encephalitis (HSE). Trafficking patterns by which the virus reaches the central nervous system (CNS) following ocular infection are unresolved. We evaluated early viral dissemination pathways following ocular infection that involve trafficking to the olfactory bulb (OB). Additionally, we have characterized the capacity of HSV-1 to establish latency within OB tissue and profiled the local T lymphocyte response over the course of the acute infection into latency. Methods Scarified corneas of C57BL/6 or reporter-inducible Rosa mice (RosaTd/Tm) were inoculated with HSV-1 and assessed for viral dissemination into the peripheral nervous system (PNS) and CNS by RT-PCR and confocal microscopy. T cells and the resident microglia activation signatures were analyzed by flow cytometry. T cell effector function in the form of IFN-γ secretion was measured by T cells isolated from OB in comparison to T cells from other nervous system sites known to harbor HSV-1-specific memory T cells. Results Following ocular infection, HSV-1 viral titers from nasal secretions were detected as early as 48 h through 8 days post infection (8 DPI). HSV-1 gene expression was expressed as early as 2 days following ocular infection in the OB and was consistent with an enhanced expression in the ophthalmic, maxillary, and mandibular branch of the trigeminal nerve ganglia (TG). Rosa fluorescence protein expression (RFP+) representing HSV-1-infected cells from RosaTd/Tm mice was detected in the OB before other areas of the CNS (2 DPI). Additionally, during acute infection, most infected cells appeared to be anatomically distributed within the OB rather than other regions of the CNS. During latency (i.e., 30 DPI and beyond) despite no detectable infectious virus or lytic gene expression and low levels of latency associated transcripts, total effector (CD44+ CD62−) CD4+ T, CD8+ T, HSV-1-specific CD8+ T cells, and MHC class II positive resident microglia numbers continued to increase. CD4+ and CD8+ T cell populations isolated from the OB during latency were capable of responding to PMA/ionomycin in the production of IFN-γ similar to T cells from other tissue that possess latent virus including the TG and brain stem. Conclusions It is currently understood that HSV-1 traffics to the TG following ocular infection. We have identified a second conduit by which HSV-1 can directly access the CNS bypassing the brain stem. We have also recognized that the OB is unique in that during HSV-1 latency, latency-associated transcripts levels were marginally above uninfected controls. Despite these findings, the local immune response mimicked the phenotype of an active infection during latency.

Malignant pleural mesothelioma (MPM) is an aggressive inflammatory cancer with a poor survival rate. Treatment options are limited at best and drug resistance is common. Thus, there is an urgent need to identify novel therapeutic targets in this disease in order to improve patient outcomes and survival times. MST1R (RON) is a trans-membrane receptor tyrosine kinase (RTK), which is part of the c-MET proto-oncogene family. The only ligand recognized to bind MST1R (RON) is Macrophage Stimulating 1 (MST1), also known as Macrophage Stimulating Protein (MSP) or Hepatocyte Growth Factor-Like Protein (HGFL). In this study, we demonstrate that the MST1-MST1R (RON) signaling axis is active in MPM. Targeting this pathway with a small molecule inhibitor, LCRF-0004, resulted in decreased proliferation with a concomitant increase in apoptosis. Cell cycle progression was also affected. Recombinant MST1 treatment was unable to overcome the effect of LCRF-0004 in terms of either proliferation or apoptosis. Subsequently, the effect of an additional small molecular inhibitor, BMS-777607 (which targets MST1R (RON), MET, Tyro3, and Axl) also resulted in a decreased proliferative capacity of MPM cells. In a cohort of MPM patient samples, high positivity for total MST1R by IHC was an independent predictor of favorable prognosis. Additionally, elevated expression levels of MST1 also correlated with better survival. This study also determined the efficacy of LCRF-0004 and BMS-777607 in xenograft MPM models. Both LCRF-0004 and BMS-777607 demonstrated significant anti-tumor efficacy in vitro, however BMS-777607 was far superior to LCRF-0004. The in vivo and in vitro data generated by this study indicates that a multi-TKI, targeting the MST1R/MET/TAM signaling pathways, may provide a more effective therapeutic strategy for the treatment of MPM as opposed to targeting MST1R alone.

Background: Pediatric mycotic infections in the eye are uncommon. However, ophthalmic infections by several fungal species have been described in immunocompetent subjects. Mycotic keratitis with or without conjunctivitis (MK) may account for more than 50% of all cases, particularly in tropical and sub-tropical areas. The leading mechanism is trauma. Treatment of MK is managed by medical (antifungal agents) and/or surgical means. This is the first case report of a patient with MK by Fusarium spp. successfully treated with keratoplasty and intravenous voriconazole, along with topical natamycin. Methods: Keratoplasty was performed and cultures obtained. Both Blood and Sabouraud Agars were used for cultures, and Lactophenol Cotton Blue Staining for microscopic observation. Results: A healthy, 10 year-old female, from the sub-tropical area of Sinaloa, Mexico, was admitted at both the CODET Vision Institute and the General Hospital of Tijuana, Mexico. Seven days after a direct trauma of the right cornea, the patient complained of progressive blurred vision, burning sensation, and itchiness. Clinical examination showed severe keratoconjunctivitis, and a necrotic slough on the cornea. Fungal colonies grew, and microscopic visualization showed typical ovoid, sickle-cell shaped macroconidia characteristics of Fusarium spp. The patient received intravenous voriconazole (200 mg every 12 h) and topical natamycin for 7 days prior and 6 days after keratoplasty. Topical natamycin was continued for 3 weeks. At 1-month follow-up, the patient’s outcome was significantly improved, with 90% vision recovery. Conclusion: This is the first pediatric case report of severe MK by Fusarium spp. successfully treated with combined intravenous voriconazole, keratoplasty and topical natamycin.

The response of hepatocellular carcinoma (HCC) to anti-vascular ultrasound therapy (AVUS) can be affected by the inherent differences in tumor vascular structure, and the functionality of tumor vessels at the time of treatment. In this study, we evaluate the hypothesis that repeated subsequent AVUS therapies are a possible approach to overcome these factors and improve the therapeutic efficacy of AVUS. HCC was induced in 30 Wistar rats by oral ingestion of diethylnitrosamine (DEN) for 12 weeks. A total of 24 rats received treatment with low intensity, 2.8 MHz ultrasound with an intravenous injection of microbubbles. Treated rats were divided into three groups: single therapy group (ST), 2-days subsequent therapy group (2DST), and 7-days subsequent therapy group (7DST). A sham control group did not receive ultrasound therapy. Tumor perfusion was measured by quantitative contrast-enhanced ultrasound (CEUS) nonlinear and power-Doppler imaging. Tumors were harvested for histologic evaluation of ultrasound-induced vascular changes. ANOVA was used to compare the percent change of perfusion parameters between the four treatment arms. HCC tumors treated with 2DST showed the largest reduction in tumor perfusion, with 75.3% reduction on average for all perfusion parameters. The ST group showed an average decrease in perfusion of 54.3%. The difference between the two groups was significant p < 0.001. The 7DST group showed a reduction in tumor perfusion of 45.3%, which was significant compared to the 2DST group (p < 0.001) but not different from the ST group (p = 0.2). The use of subsequent targeted AVUS therapies applied shortly (two days) after the first treatment enhanced the anti-vascular effect of ultrasound. This gain, however, was lost for a longer interval (1 week) between the therapies, possibly due to tumor necrosis and loss of tumor viability. These findings suggest that complex interplay between neovascularization and tumor viability plays a critical role in treatment and, therefore, must be actively monitored following treatment by CEUS for optimizing sequential treatment.

Background: The eating behavior of children is important to maintain a healthy weight. This current study explored the differences in children’s eating behaviors and their relation to weight status and maternal education level, using the child eating behavior questionnaire (CEBQ). Methods: The study recruited 169 participants aged between six and ten years. Multinomial logistic regression was conducted to examine the association between the CEBQ factors and children’s body weight status. The association between the CEBQ scores and maternal educational levels was examined using a one-way analysis of variance (ANOVA). Results: The multinomial logistic regression findings indicate that children in the obese group exhibited a significant increase in food responsiveness, enjoyment of food, emotional overeating, and a decrease in satiety responsiveness compared to normal weight children. The one-way ANOVA showed a significant difference in subscales under the food approach (food responsiveness, desire to drink, emotional overeating) and food avoidance (satiety responsiveness) based upon the child’s weight status. The three subscales under the food approach category were significantly dependent upon the maternal education but did not have a significant association with food avoidance. Conclusions: The results suggest that the increase in food responsiveness and emotional overeating in obese children is influenced by maternal education.

Himalayan forests are dominated by different species of oaks (Quercus spp.) at different altitudes. These oaks are intimately linked with hill agriculture as they protect soil fertility, watershed, and local biodiversity. They also play an important role in maintaining ecosystem stability. This work was carried out to study the diversity and regeneration status of some oak forests in Garhwal Himalaya, India. A total of 18 tree species belonging to 16 genera and 12 families were reported from the study area. Species richness varied for trees (4–7), saplings (3–10), and seedlings (2–6). Seedling and sapling densities (Ind/ha) varied between 1,376 Ind/ha and 9,600 Ind/ha and 167 Ind/ha and 1,296 Ind/ha, respectively. Species diversity varied from 1.27 to 1.86 (trees), from 0.93 to 3.18 (saplings), and from 0.68 to 2.26 (seedlings). Total basal area (m2/ha) of trees and saplings was 2.2–87.07 m2/ha and 0.20–2.24 m2/ha, respectively, whereas that of seedlings varied from 299 cm2/ha to 8,177 cm2/ha. Maximum tree species (20–80%) had “good” regeneration. Quercus floribunda, the dominant tree species in the study area, showed “poor” regeneration, which is a matter of concern, and therefore, proper management and conservation strategies need to be developed for maintenance and sustainability of this oak species along with other tree species that show poor or no regeneration.

Chronic liver inflammation progressively evokes fibrosis and cirrhosis resulting in compromised liver function, and often leading to cancer. Early diagnosis and staging of fibrosis is crucial because the five-year survival rate of early-stage liver cancer is high. This study investigates the progression of hepatic fibrosis induced in rats following ingestion of diethylnitrosamine (DEN). Changes in oxygen saturation and hemoglobin concentration resulting from chronic inflammation were assayed longitudinally during DEN ingestion by photoacoustic imaging (PAI). Accompanying liver tissue changes were monitored simultaneously by B-mode sonographic imaging. Oxygen saturation and hemoglobin levels in the liver increased over 5 weeks and peaked at 10 weeks before decreasing at 13 weeks of DEN ingestion. The oxygenation changes were accompanied by an increase in hepatic echogenicity and coarseness in the ultrasound image. Histology at 13 weeks confirmed the development of severe fibrosis and cirrhosis. The observed increase in PA signal representing enhanced blood oxygenation is likely an inflammatory physiological response to the dietary DEN insult that increases blood flow by the development of neovasculature to supply oxygen to a fibrotic liver during the progression of hepatic fibrosis. Assessment of oxygenation by PAI may play an important role in the future assessment of hepatic fibrosis.

Color Doppler is used in the clinic for visually assessing the vascularity of breast masses on ultrasound, to aid in determining the likelihood of malignancy. In this study, quantitative color Doppler radiomics features were algorithmically extracted from breast sonograms for machine learning, producing a diagnostic model for breast cancer with higher performance than models based on grayscale and clinical category from the Breast Imaging Reporting and Data System for ultrasound (BI-RADSUS). Ultrasound images of 159 solid masses were analyzed. Algorithms extracted nine grayscale features and two color Doppler features. These features, along with patient age and BI-RADSUS category, were used to train an AdaBoost ensemble classifier. Though training on computer-extracted grayscale features and color Doppler features each significantly increased performance over that of models trained on clinical features, as measured by the area under the receiver operating characteristic (ROC) curve, training on both color Doppler and grayscale further increased the ROC area, from 0.925 ± 0.022 to 0.958 ± 0.013. Pruning low-confidence cases at 20% improved this to 0.986 ± 0.007 with 100% sensitivity, whereas 64% of the cases had to be pruned to reach this performance without color Doppler. Fewer borderline diagnoses and higher ROC performance were both achieved for diagnostic models of breast cancer on ultrasound by machine learning on color Doppler features.

CLC secondary active transporters exchange Cl- for H+. Crystal structures have suggested that the conformational change from occluded to outward-facing states is unusually simple, involving only the rotation of a conserved glutamate (Gluex) upon its protonation. Using 19F NMR, we show that as [H+] is increased to protonate Gluex and enrich the outward-facing state, a residue ~20 Å away from Gluex, near the subunit interface, moves from buried to solvent-exposed. Consistent with functional relevance of this motion, constriction via inter-subunit cross-linking reduces transport. Molecular dynamics simulations indicate that the cross-link dampens extracellular gate-opening motions. In support of this model, mutations that decrease steric contact between Helix N (part of the extracellular gate) and Helix P (at the subunit interface) remove the inhibitory effect of the cross-link. Together, these results demonstrate the formation of a previously uncharacterized 'outward-facing open' state, and highlight the relevance of global structural changes in CLC function.