Intersubject representational similarity analysis uncovers the impact of state anxiety on brain activation patterns in the human extrastriate cortex.

The current study used functional magnetic resonance imaging (fMRI) and showed that state anxiety modulated extrastriate cortex activity in response to emotionally-charged visual images. State anxiety and neuroimaging data from 53 individuals were subjected to an intersubject representational similarity analysis (ISRSA), wherein the geometries between neural and behavioral data were compared. This analysis identified the extrastriate cortex (fusiform gyrus and area MT) to be the sole regions whose activity patterns covaried with state anxiety. Importantly, we show that this brain-behavior association is revealed when treating state anxiety data as a multidimensional response pattern, rather than a single composite score. This suggests that ISRSA using multivariate distances may be more sensitive in identifying the shared geometries between self-report questionnaires and brain imaging data. Overall, our findings demonstrate that a transient state of anxiety may influence how visual information - especially those relevant to the valence dimension - is processed in the extrastriate cortex.

The JNK signaling pathway against titanium-particle-induced osteoclastogenesis and bone resorption in vivo.

OBJECTIVE: The c-Jun N-terminal kinases (JNK) signaling pathway may be involved in the regulation of osteoclast development. The purpose of this investigation was to investigate whether SB600125, a JNK inhibitor, could attenuate titanium-particle-induced inflammatory osteolysis in vivo. MATERIALS AND METHODS: A total of 45 mice were randomly divided into a Sham group, a Titanium group, and a Titanium + JNK inhibitor group, 15 mice per group. After establishing an air pouch bone graft model, we injected phosphate-buffered saline (PBS), titanium particles, or titanium particles + JNK inhibitor into the air pouch of the three groups. The pouch membranes containing bone implants were taken for morphological and molecular analysis 14 days after the mice were sacrificed. RESULTS: General morphological structure observation results, Hematoxylin and Eosin (H&E)-Stained Sections, anti-tartaric acid phosphatase (TRAP) staining, and the transmission electron microscope showed that SB600125, by inhibiting the expression of JNK, attenuated titanium particle-induced inflammatory osteolysis (p<0.05). Immunohistochemical appearance results and reverse transcription-polymerase chain reaction (RT-PCR) results showed SB600125 reduced expression of IL-6, and TNF-α in osteolytic sites stimulated with wear debris (p<0.05). The Western blot results showed the expression of the p-JNK protein in the titanium particle + SB600125 group was significantly reduced compared to the titanium particle stimulation group (p<0.05). CONCLUSIONS: Interfering with the JNK signaling pathway may be beneficial in reducing osteolysis, providing a therapeutic target for preventing and treating aseptic loosening caused by debris-induced inflammatory osteolysis.

A low-cost edge AI-chip-based system for real-time algae species classification and HAB prediction.

Harmful Algal Blooms (HAB) are damaging to ecosystem functions and pose challenges to environmental and fisheries management. The key to HAB management and understanding the complex algal growth dynamics is the development of robust systems for real-time monitoring of algae populations and species. Previous algae classification studies mainly rely on the combination of an in-situ imaging flow cytometer and an off-site lab-based algae classification model such as Random Forest (RF) for the analysis of high-throughput images. An on-site AI algae monitoring system on top of an edge AI chip embedded with the proposed Algal Morphology Deep Neural Network (AMDNN) model is developed to achieve real-time algae species classification and HAB prediction. Based on a detailed examination of real-world algae images, dataset augmentation is first performed: consisting of orientation, flipping, blurring, and Resizing with Aspect ratio Preserved (RAP). The dataset augmentation is shown to significantly improve classification performance which is superior to that of the competitive RF model. And the attention heatmaps show that for relatively regular-shaped algal species (e.g., Vicicitus), the model weights the color and texture information heavily; while the shape-related features are more important for complex-shaped algae (e.g., Chaetoceros). The AMDNN is tested on a dataset of 11,250 algae images containing the 25 most common HAB classes in Hong Kong subtropical waters with 99.87% test accuracy. Based on the fast and accurate algae classification, the AI-chip-based on-site system is applied to a one-month dataset in February 2020; the predicted trends of total cell counts and targeted HAB species counts are in good agreement with observations. The proposed edge AI algae monitoring system provides a platform for the development of practical HAB early warning systems that can effectively support environmental risk and fisheries management.

Characteristics of US military personnel with atrial fibrillation and associated deployment and retention rates.

INTRODUCTION: Atrial fibrillation (AF) is an arrhythmia impacting military occupational performances. Despite being a recognised disqualifying condition, there is no literature describing US military service members with AF. This study aims to describe members with AF diagnoses, the distribution of treatment strategies and associated deployment and retention rates. METHODS: Active duty service members identified with AF from 2004 to 2019 were investigated. Cardiovascular profiles, AF management strategies and military dispositions were assessed by electronic medical record review. RESULTS: 386 service members (mean age 35.0±9.4 years; 94% paroxysmal AF) with AF diagnoses were identified. 91 (24%) had hypertension followed by 75 (19%) with sleep apnoea. Mean CHA2DS2-VASc scores were low (0.39±0.65). Rhythm treatments were used in 173 (45%) followed by rate control strategies in 155 (40%). 161 (42%) underwent pulmonary vein isolation (PVI). In subgroup analysis of 365 personnel, 147 (40%) deployed and 248 (68%) remained active duty after AF diagnosis. Deployment and retention rates did not differ between those who received no medical therapy, rate control or rhythm strategies (p=0.9039 and p=0.6192, respectively). PVI did not significantly impact deployment or retention rates (p=0.3903 and p=0.0929, respectively). CONCLUSION: Service members with AF are young with few AF risk factors. Rate and rhythm medical therapies were used evenly. Over two-thirds met retention standards and 40% deployed after diagnosis. There were no differences in deployment or retention between groups who receive rate therapy, rhythm medical therapy or PVI. Prospective evaluation of the efficacy of specific AF therapies on AF burden and symptomatology in service members is needed.

Trabecular microstructure is influenced by race and sex in Black and White young adults.

Lower fracture rates in Black men and women compared to their White counterparts are incompletely understood. High-resolution imaging specific to trabecular bone may provide insight. Black participants have enhanced trabecular morphology. These differences may contribute to the lower fracture risk in Black versus White individuals. INTRODUCTION: Lower fracture rates in Black men and women compared to their White counterparts may be explained by favorable bone microstructure in Black individuals. Individual trabecular segmentation (ITS) analysis, which characterizes the alignment and plate- and rod-like nature of trabecular bone using high-resolution peripheral quantitative computed tomography (HR-pQCT), may provide insight into trabecular differences by race/ethnic origin. PURPOSE: We determined differences in trabecular bone microarchitecture, connectivity, and alignment according to race/ethnic origin and sex in young adults. METHODS: We analyzed HR-pQCT scans of 184 adult (24.2 ± 3.4 years) women (n = 51 Black, n = 50 White) and men (n = 34 Black, n = 49 White). We used ANCOVA to compare bone outcomes, and adjusted for age, height, and weight. RESULTS: Overall, the effect of race on bone outcomes did not differ by sex, and the effect of sex on bone outcomes did not differ by race. After adjusting for covariates, Black participants and men of both races had greater trabecular plate volume fraction, plate thickness, plate number density, plate surface area, and greater axial alignment of trabeculae, leading to higher trabecular bone stiffness compared to White participants and women, respectively (p < 0.05 for all). CONCLUSION: These findings demonstrate that more favorable bone microarchitecture in Black individuals compared to White individuals and in men compared to women is not unique to the cortical bone compartment. Enhanced plate-like morphology and greater trabecular axial alignment, established in young adulthood, may contribute to the improved bone strength and lower fracture risk in Black versus White individuals and in men compared to women.

Germocyte lesions caused by porcine circovirus type 2b in Kunming mice.

Porcine circovirus type 2 (PCV2) has been known as a causative agent of reproductive failure in the sow. In the present study mouse model was used to investigate PCV2 infection. In order to investigate whether PCV2 can induce lesions of spermatocytes and oocytes, 6 male and 6 female mice were each inoculated intraperitoneally with PCV2b, and 3 male and 3 female mice mock-infected with cell culture supernatant served as controls. Samples of testes and ovaries from PCV2b-inoculated and mock-infected mice were investigated using PCR, histopathological, ultrastructural and immunofluorescent histochemical methods at 14 and 21 day post infection (dpi). The study revealed that in the virus-inoculated mice leydig cells in testes and granulosa cells in ovaries were degenerated, and a small number of spermatocytes and oocytes showed apoptosis. Positive PCV2b antigen signals were also observed in these apoptotic cells. It can be suggested that PCV2 can cause lesions of spermatocyte and oocyte prior to zygotes formation in its host.

Tai Chi Exercise for Cancer-Related Fatigue in Patients With Lung Cancer Undergoing Chemotherapy: A Randomized Controlled Trial.

CONTEXT: Tai Chi is a traditional Chinese health-promoting exercise. It has been shown to enhance mental health and improve psychological condition. OBJECTIVES: We aimed to assess the effectiveness of Tai Chi exercise for cancer-related fatigue in patients with lung cancer undergoing chemotherapy. METHODS: We conducted a randomized trial of Tai Chi exercise as compared with low-impact exercise as a control intervention. Exercises were practiced every other day, a one-hour session for 12 weeks for each of the study groups. The primary end point was a change in total score of the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF). Secondary end points were changes in five subscale scores of the MFSI-SF. All assessments were repeated at three time points, T0: before first course of chemotherapy; T1: before third course of chemotherapy; and T2: at the end of the fourth course of chemotherapy. RESULTS: Between January 2012 and December 2014, 96 patients were enrolled in this trial. At six and 12 weeks, the Tai Chi group had a lower MFSI-SF total score compared with the control group (59.5 ± 11.3 vs. 66.8 ± 11.9, P < 0.05; 53.3 ± 11.8 vs. 59.3 ± 12.2, P < 0.05). At six weeks, the Tai Chi group had lower MFSI-SF general subscale scores (18.1 ± 4.6 vs. 20.4 ± 4.5, P < 0.05) and physical subscale scores (17.5 ± 4.4 vs. 19.1 ± 4.5, P < 0.05), and higher MFSI-SF vigor subscale scores (14.5 ± 3.3 vs. 11.6 ± 3.4, P < 0.05), compared with the control group. But no significant differences were found in emotional subscale (20.2 ± 3.6 vs. 20.0 ± 3.5, P > 0.05) and mental subscale (18.2 ± 4.0 vs. 18.9 ± 3.9, P > 0.05) scores between the Tai Chi group and the control group. At 12 weeks, the MFSI-SF subscale scores showed the same trends as at six weeks. CONCLUSION: Tai Chi is an effective intervention for managing cancer-related fatigue in patients with lung cancer undergoing chemotherapy, especially for decreasing general fatigue and physical fatigue, and increasing vigor.

[A novel open chest method of right ventricular hemodynamics measurement in pulmonary hypertensive mice].

Objective: Right heart catheterization is the gold-standard for measurement of right ventricular hemodynamics. However, it is difficult to perform in mice. We thus aimed to establish a new open chest method to record and analyze the right ventricular hemodynamic parameters in intubated mice connected to a respirator under anesthesia. Methods: Eight-week old male C57BL/6 mice were divided into the control group, and the hypoxia group using completely random method. Mice in the hypoxia group were exposed in low pressure oxygen chamber, which simulated the environment of plateau (5 500 m altitude, 10% oxygen) for 3 weeks. Mice in the control group were exposed in normal pressure and oxygen environment. The mice were intratracheally intubated and connected to a respirator, chest was opened, right ventricular hemodynamics were measured with a needle (0.7 mm×19 mm) punctured into right ventricle (5 mm in death), which was connected to the measuring equipment. Results: The open chest procedure could be finished within 5-10 minutes. The successful rate was 100%. There was no significant difference in heart rate between control group and hypoxia group under anesthetia ((306.4±11.5) bpm vs.(320.4±16.0) bpm, P>0.05). Compared with the control group, both the right ventricular systolic pressure (RVSP) and the mean right ventricular pressure(mRVP)were increased in hypoxia group ((17.1±1.0)mmHg(1 mmHg=0.133 kPa) vs. (22.6±1.0) mmHg, P<0.01; (9.6±0.8) mmHg vs.(12.4±0.3) mmHg, P<0.01). Moreover, the absolute value of the maximal rate of increase in right ventricular pressure (dp/dtmax) and the maximal rate of decrease in right ventricular pressure (dp/dtmin) were higher in the hypoxia group ((421.3±30.6)mmHg/s vs.(639.7±47.7)mmHg/s, P<0.01; (-324.3±24.0)mmHg/s vs. (-496.5±40.6) mmHg/s, P<0.01), indicating the pathological status after hypoxia treatment. Conclusions: Right ventricular hemodynamics measurement with this open chest technique is easy to handle and can accurately reflect the right ventricular pressure in mice under physiological and pathological conditions.

Oral chronic GVHD outcomes and resource utilization: a subanalysis from the chronic GVHD consortium.

OBJECTIVES: This study evaluated the extent to which oral chronic graft-versus-host disease (cGVHD) consensus assessments are predictive of management across institutions with and without oral medicine (OM) centers, and whether ancillary care guidelines are followed within clinical practice. METHODS: Longitudinal oral cGVHD data were abstracted from the cGVHD Consortium, and additional mouth-specific management data were analyzed across five transplant centers. RESULTS: Seventy-nine patients with 656 visits were observed for a median of 7.1 months with one visit per follow-up month. Ancillary therapies for oral cGVHD were prescribed for 67% of patients for a median of 0.46 months (per follow-up month) at OM centers and 0.78 months at non-OM centers. Patients treated with ancillary therapy were more likely to have an National Institutes of Health (NIH) mouth score of ≥1 (P < 0.001, odds ratio: 5.1) and mouth pain (P = 0.01, odds ratio: 2.6). The odds ratios of receiving ancillary therapy from OM experts were higher than transplant physicians (53%; P = 0.03). CONCLUSIONS: Oral cGVHD consensus assessments corresponding with ancillary therapy use were mouth pain and NIH mouth score, with higher odds ratios of receiving therapy from OM experts. Ancillary care guidelines for oral cGVHD are reflected in academic clinical practice with respect to utilization of recommended prescriptions.

Neurofilament subunits are integral components of synapses and modulate neurotransmission and behavior in vivo.

Synaptic roles for neurofilament (NF) proteins have rarely been considered. Here, we establish all four NF subunits as integral resident proteins of synapses. Compared with the population in axons, NF subunits isolated from synapses have distinctive stoichiometry and phosphorylation state, and respond differently to perturbations in vivo. Completely eliminating NF proteins from brain by genetically deleting three subunits (α-internexin, NFH and NFL) markedly depresses hippocampal long-term potentiation induction without detectably altering synapse morphology. Deletion of NFM in mice, but not the deletion of any other NF subunit, amplifies dopamine D1-receptor-mediated motor responses to cocaine while redistributing postsynaptic D1-receptors from endosomes to plasma membrane, consistent with a specific modulatory role of NFM in D1-receptor recycling. These results identify a distinct pool of synaptic NF subunits and establish their key role in neurotransmission in vivo, suggesting potential novel influences of NF proteins in psychiatric as well as neurological states.

Vaginal deployment and tenofovir delivery by microbicide gels.

Gels are one of the soft material platforms being evaluated to deliver topically acting anti-HIV drugs (microbicides) to the vaginal environment. For each drug, its loaded concentration, gel properties and applied volume, and frequency of dosing can be designed to optimize PK and, thence, PD. These factors also impact user sensory perceptions and acceptability. Deterministic compartmental modeling of vaginal deployment and drug delivery achieved by test gels can help delineate how multiple parameters characterizing drug, vehicle, vaginal environment, and dosing govern details of PK and PD and also gel leakage from the canal. Such microbicide delivery is a transport process combining convection, e.g., from gel spreading along the vaginal canal, with drug diffusion in multiple compartments, including gel, mucosal epithelium, and stroma. The present work builds upon prior models of gel coating flows and drug diffusion (without convection) in the vaginal environment. It combines and extends these initial approaches in several key ways, including: (1) linking convective drug transport due to gel spreading with drug diffusion and (2) accounting for natural variations in dimensions of the canal and the site of gel placement therein. Results are obtained for a leading microbicide drug, tenofovir, delivered by three prototype microbicide gels, with a range of rheological properties. The model includes phosphorylation of tenofovir to tenofovir diphosphate (which manifests reverse transcriptase activity in host cells), the stromal concentration distributions of which are related to reference prophylactic values against HIV. This yields a computed summary measure related to gel protection ("percent protected"). Analyses illustrate tradeoffs amongst gel properties, drug loading, volume and site of placement, and vaginal dimensions, in the time and space history of gel distribution and tenofovir transport to sites of its anti-HIV action and concentrations and potential prophylactic actions of tenofovir diphosphate therein.

High-throughput screening identifies small molecules that enhance the pharmacological effects of oligonucleotides.

The therapeutic use of antisense and siRNA oligonucleotides has been constrained by the limited ability of these membrane-impermeable molecules to reach their intracellular sites of action. We sought to address this problem using small organic molecules to enhance the effects of oligonucleotides by modulating their intracellular trafficking and release from endosomes. A high-throughput screen of multiple small molecule libraries yielded several hits that markedly potentiated the actions of splice switching oligonucleotides in cell culture. These compounds also enhanced the effects of antisense and siRNA oligonucleotides. The hit compounds preferentially caused release of fluorescent oligonucleotides from late endosomes rather than other intracellular compartments. Studies in a transgenic mouse model indicated that these compounds could enhance the in vivo effects of a splice-switching oligonucleotide without causing significant toxicity. These observations suggest that selected small molecule enhancers may eventually be of value in oligonucleotide-based therapeutics.

Langkocyclines: novel angucycline antibiotics from Streptomyces sp. Acta 3034(*).

Langkocyclines A1-A3 and B1 and B2, five new angucycline antibiotics produced by Streptomyces sp. Acta 3034, were detected in the course of our HPLC-diode array screening. The producing strain was isolated from the rhizospheric soil of a Clitorea sp. collected from Burau Bay, Langkawi, Malaysia, and was characterized by morphological, physiological and chemotaxonomic features in addition to 16S ribosomal RNA gene sequence information. Strain Acta 3034 is closely related to Streptomyces psammoticus NBRC 13971(T) and Streptomyces lanatus NBRC 12787(T). Langkocyclines consist of an angular tetracyclic benz[a]anthracene skeleton and hydrolyzable O-glycosidic sugar moieties. The yellow-colored A-type langkocyclines differ in their aglycon from the blue-lilac-colored B-type langkocyclines. The A-type langkocycline aglycon is identical to that of aquayamycin and urdamycin A. The chemical structures of the langkocyclines were elucidated by HR-MS, 1D and 2D NMR experiments. They are biologically active against Gram-positive bacteria and exhibit a moderate antiproliferative activity against various human tumor cell lines.

NanoFerrite particle based radioimmunonanoparticles: binding affinity and in vivo pharmacokinetics.

Dextran and PEG-coated iron oxide nanoparticles (NP), when suitably modified to enable conjugation with molecular targeting agents, provide opportunities to target cancer cells. Monoclonal antibodies, scFv, and peptides conjugated to 20 nm NP have been reported to target cancer for imaging and alternating magnetic field (AMF) therapy. The physical characteristics of NPs can affect their in vivo performance. Surface morphology, surface charge density, and particle size are considered important factors that determine pharmacokinetics, toxicity, and biodistribution. New NanoFerrite (NF) particles having improved specific AMF absorption rates and diameters of 30 and 100 nm were studied to evaluate the variation in their in vitro and in vivo characteristics in comparison to the previously studied 20 nm superparamagnetic iron oxide (SPIO) NP. SPIO NP 20 nm and NF NP 30 and 100 nm were conjugated to (111)In-DOTA-ChL6, a radioimmunoconjugate. Radioimmunoconjugates were conjugated to NPs using 25 microg of RIC/mg of NP by carbodiimide chemistry. The radioimmunonanoparticles (RINP) were purified and characterized by PAGE, cellulose acetate electrophoresis (CAE), live cell binding assays, and pharmacokinetics in athymic mice bearing human breast cancer (HBT 3477) xenografts. RINP (2.2 mg) were injected iv and whole body; blood and tissue data were collected at 4, 24, and 48 h. The preparations used for animal study were >90% monomeric by PAGE and CAE. The immunoreactivity of the RINP was 40-60% compared to (111)In-ChL6. Specific activities of the doses were 20-25 microCi/2.2 mg and 6-11 microg of mAb/2.2 mg of NP. Mean tumor uptakes (% ID/g +/- SD) of each SPIO 20 nm, NF 30 nm, and 100 nm RINP at 48 h were 9.00 +/- 0.8 (20 nm), 3.0 +/- 0.3 (30 nm), and 4.5 +/- 0.8 (100 nm), respectively; the ranges of tissue uptakes were liver (16-32 +/- 1-8), kidney (7.0-15 +/- 1), spleen (8-17 +/- 3-8), lymph nodes 5-6 +/- 1-2), and lung (2.0-4 +/- 0.1-2). In conclusion, this study demonstrated that 100 nm NF NP could be conjugated to (111)In-mAb so that the resulting RINP had characteristics suitable for AMF therapy. Although 100 nm RINP targeted tumor less than 20 nm SPIO RINP, their heating capacity is typically 6 times greater, suggesting the 100 nm NF RINP could still deliver better therapy with AMF.

Preventable deaths in patients admitted from emergency department.

BACKGROUND: There is limited data about how appropriate medical care is in the emergency department (ED). OBJECTIVES: To investigate the rate and types of preventable deaths among patients with early mortality after emergency admission from the ED. METHODS: We retrospectively reviewed charts of early mortality (defined as mortality which occurred within 24 hours after admission from the ED) over a 3 year period. Those patients with terminal cancer or out of hospital cardiac arrest (OHCA) at presentation were excluded. Two independent assessors reviewed each eligible chart and determined whether early mortality was preventable. Any disagreements were resolved through discussion between the investigators. A mortality event was considered preventable if actions or missed actions were identified that would have prevented the death. The types of preventability were categorised as misdiagnosis, delayed diagnosis, and inappropriate medical management. Interrater reliability in the initial determination was assessed using Cohen kappa statistic. RESULTS: Over a 3 year period, 210 early mortality cases were identified. Excluding patients with terminal cancer or OHCA, the rate of preventable deaths was 25.8% (32/124). The types of preventability were inappropriate medical management (17 patients), delayed diagnosis (eight), and misdiagnosis (seven). There was good agreement between assessors with a Cohen kappa statistic of 0.81. CONCLUSIONS: Preventable deaths in emergency admitted patients with early mortality are not uncommon. Analysis and identification of preventability early mortality by using a chart based method may be used as a quality assurance index in emergency medical care.