Landscape of team-based care to manage hypertension: results from two surveys in low/middle-income countries.

OBJECTIVES: Team-based care is essential for improving hypertension outcomes in low-resource settings. We assessed perceptions of country representatives and healthcare workers (HCWs) on team-based hypertension care in low/middle-income countries. DESIGN: Two cross-sectional surveys. SETTING: The first survey (Country Profile Survey) was conducted in 17 countries and eight in-country regions: Algeria, Bangladesh, Burundi, Chile, China (Beijing, Henan, Shandong), Cuba, Ethiopia, India (Kerala, Madhya Pradesh, Maharashtra, Punjab, Telangana), Nepal, Nigeria, Philippines, Saint Lucia, Sri Lanka, Thailand, Turkey, Uganda and Vietnam. The second survey (HCW Survey) was conducted in four countries: Bangladesh, China, Ethiopia and Nigeria. PARTICIPANTS: Using convenience sampling, participants for the Country Profile Survey were representatives from 17 countries and eight in-country regions, and the HCW Survey was administered to HCWs in Bangladesh, China, Ethiopia and Nigeria. OUTCOME MEASURES: Country-level use of team-based hypertension care framework, comprising administrative, basic and advanced clinical tasks. Current practices of different HCW cadres, perspectives on team-based management of hypertension, barriers and facilitators. RESULTS: In the Country Profile Survey, all (23/23, 100%) countries/regions surveyed integrated team-based care for basic clinical hypertension management tasks, less for advanced tasks (7/23, 30%). In the HCW Survey, 854 HCWs participated, 47% of whom worked in rural settings. Most HCWs in the sample acknowledged the value of team-based hypertension care. Although there were slight variations by country in the study sample, overall, barriers to team-based hypertension care were identified as inadequate training (83%); regulatory issues (76%); resistance by patients (56%), physicians (42%) and nurses (40%). Facilitators identified were use of treatment algorithms (94%), telehealth/m-health technology (92%) and adequate compensation for HCWs (80%). CONCLUSIONS: Our findings revealed key lessons for health systems and governments regarding team-based care implementation. Specifically, policies to facilitate additional training, optimise HCWs' roles within care teams, use of hypertension treatment protocols and telehealth/m-health technology will be essential to promote team-based care.

Mitigating Cd and bacterial wilt stress in tomato plants through trico-synthesized silicon nanoparticles and Trichoderma metabolites.

There has been a growing apprehension in recent years about the harmful effects of environmental pollutants on agricultural output, encompassing both living organisms and non-living factors that cause stress. In this study, the soil application of bulk silicon (Si), silicon nanoparticles (SiNPs) and Trichoderma metabolites (TM) were investigated alone or in combination for the management of an important abiotic stress i.e. Cd toxicity and biotic stress i.e. bacterial wilt (BW) in tomato plants. SiNPs were synthesized by Trichoderma and confirmed through XRD, FTIR, and Ranman spectrum analysis. Results showed that Si, SiNPs and TM were all effective treatments. The combine treatment of SiNPs and TM followed by SiNPs alone were superior over other treatments in mitigating Cd toxicity and reducing BW disease on tomato plants. The soil application of these treatments reduced the Cd toxicity by enhancing Cd-tolerance index, decreasing bioavailability of soil Cd, reducing Cd contents and translocation in plants, improving gaseous exchange, photosynthesis, and increasing the antioxidant enzyme activities and their transcriptions. These treatments significantly suppressed BW pathogen leading to the significant decrease in disease index and severity on plants. In vitro evaluation and scanning electron microscopic (SEM) analysis revealed that SiNPs and TM significantly disrupted the cellular morphology of BW pathogen Ralstonia solanacearum. Findings of this study proposes the possible use of SiNPs and TM in mitigating the Cd and BW stress in tomato plants and possibly in other crops.

Paper-based colorimetric glucose sensor using Prussian blue nanoparticles as mimic peroxidase.

A novel paper-based colorimetric glucose sensor was proposed employing Prussian blue nanoparticles (PB NPs) as mimic peroxidase. The sensor was manufactured by spraying solution containing PB NPs, glucose oxidase and chromogenic agents into a paper, then coating the filter layer and spreading layer on the top. The layer-by-layer structure enabled the sensor detect glucose in whole blood, as well as elimination of the coffee-ring effect which ensure the performance. As a powerful alternative to natural peroxidase, PB NPs showed the mimic enzymatic activity well preserved in dry environment. The manufacture process of the sensor is easy to be industrialized. Under optimal conditions, the sensor exhibited a linear range from 2.5 mM to 25 mM for glucose in blood with satisfactory reproducibility (the coefficient of variant <4%), great storage stability (1 month at 45 °C) and excellent linearity compared with those commercial kits (R > 0.99). Coupled with a handhold device, the PB NPs-based test strip realized the goal of personal operation, user-friendly control, automatic readouts, and data storage, and able to link the Cloud, showing unique potential in clinical application, especially in community-level medical scenarios.

Ventromedial Thalamus-Projecting DCN Neurons Modulate Associative Sensorimotor Responses in Mice.

The deep cerebellar nuclei (DCN) integrate various inputs to the cerebellum and form the final cerebellar outputs critical for associative sensorimotor learning. However, the functional relevance of distinct neuronal subpopulations within the DCN remains poorly understood. Here, we examined a subpopulation of mouse DCN neurons whose axons specifically project to the ventromedial (Vm) thalamus (DCNVm neurons), and found that these neurons represent a specific subset of DCN units whose activity varies with trace eyeblink conditioning (tEBC), a classical associative sensorimotor learning task. Upon conditioning, the activity of DCNVm neurons signaled the performance of conditioned eyeblink responses (CRs). Optogenetic activation and inhibition of the DCNVm neurons in well-trained mice amplified and diminished the CRs, respectively. Chemogenetic manipulation of the DCNVm neurons had no effects on non-associative motor coordination. Furthermore, optogenetic activation of the DCNVm neurons caused rapid elevated firing activity in the cingulate cortex, a brain area critical for bridging the time gap between sensory stimuli and motor execution during tEBC. Together, our data highlights DCNVm neurons' function and delineates their kinematic parameters that modulate the strength of associative sensorimotor responses.

Renoprotective effect of isoliquiritigenin on cisplatin-induced acute kidney injury through inhibition of FPR2 in macrophage.

Acute kidney injury (AKI) is a serious complication in critically ill patients. Accumulating evidences indicated that macrophages play an important pro-inflammatory role in AKI and isoliquiritigenin (ISL) can inhibit macrophagic inflammation, but its role in AKI and the underlying mechanism are unknown. The present study aims to investigate the renoprotective effect of ISL on AKI and the role of Formyl peptide receptors 2 (FPR2) in this process. In this study, cisplatin-induced AKI model and lipopolysaccharide-induced macrophage inflammatory model were employed to perform the in vivo and in vitro experiments. The results showed that ISL strongly relieved kidney injury and inhibited renal inflammation in vivo and suppress macrophagic inflammatory response in vitro. Importantly, it was found that FPR2 was significantly upregulated compared to the control group in AKI and LPS-induced macrophage, whereas it was strongly suppressed by ISL. Interestingly, overexpression of FPR2 with transfection of pcDNA3.1-FPR2 effectively reversed the anti-inflammatory effect of ISL in macrophage, suggesting that FPR2 may be the potential target for ISL to prevent inflammation and improve kidney injury of AKI. Take together, these findings indicated that ISL improved cisplantin-induced kidney injury by inhibiting FPR2 involved macrophagic inflammation, which may provide a potential therapeutic option for AKI.

An immune risk score with potential implications in prognosis and immunotherapy of metastatic melanoma.

Melanoma is a highly aggressive cancer with a poor prognosis. We found that immune response played important roles in melanoma metastasis by GSEA analysis. Therefore, we constructed the immune risk score (IRS) by the LASSO-COX analysis in the sequencing metastatic samples from the TCGA database. Then, initial diagnosis patients with metastasis were selected as the test cohort. Importantly, we adopted overall survival (OS) as the survival outcome for initial diagnosis patients, while adopting the observed survival interval (OBS) as the survival outcome for sequencing samples which could avoid biologically meaningless associations. We found that the IRS had high power for predicting 2, 3 and 5-year survival in training (AUC = 0.70, 0.69 and 0.68) and test cohorts (AUC = 0.72, 0.70 and 0.65). The IRS was significantly associated with prognosis both in the metastatic samples (HR = 1.60, 95% CI = 1.16-2.19) and patients with metastasis (HR = 2.89, 95% CI = 1.69-4.53). we further used other independent melanoma cohorts from the GEO databases to confirm the reliability and validity of the IRS (P < 0.01 in all cohorts). The practical nomogram was also built using the IRS and clinical information with high c-index both in training (0.76, 95%CI = 0.72-0.80) and test cohorts (0.72, 95%CI = 0.65-0.79). Finally, IRS showed the predictive value of survival outcome and response of immunotherapy patients, and increased the predictive ability of current immune checkpoint gene markers. In conclusion, the IRS can serve as a potential biomarker for prognosis and responsiveness to immune checkpoint blockade immunotherapy in metastatic melanoma patients.

Predicting the Risk of Melanoma Metastasis Using an Immune Risk Score in the Melanoma Cohort.

Melanoma is a highly aggressive cancer, attracting increasing attention worldwide. The 5-year survival rate of patients with metastatic melanoma is low. Therefore, it is critical to identify potential effective biomarkers for diagnosis of melanoma metastasis. In the present study, the melanoma cohort and immune genes were obtained from the Cancer Genome Atlas (TCGA) database and the ImmPort database, respectively. Then, we constructed the immune risk score (IRS) using univariate and multivariate logistic analysis. The area under the curve (AUC) of IRS in sequencing samples and the initial diagnosis patients was 0.90 and 0.80, respectively. Besides, IRS could add benefits for metastasis diagnosis. For sequencing samples, IRS (OR = 16.35, 95% CI = 8.74-30.59) increased the odds for melanoma metastasis. Similar results were obtained in the initial diagnosis patients (OR = 8.93, 95% CI = 3.53-22.61). A composite nomogram was built based on IRS and clinical information with well-fitted calibration curves. We further used other independent melanoma cohorts from Gene Expression Omnibus (GEO) databases to confirm the reliability and validity of the IRS (AUC > 0.75, OR > 1.04, and P value < 0.01 in all cohorts). In conclusion, IRS is significantly associated with melanoma metastasis and can be a novel effective signature for predicting the metastasis risk.

X-ray induces mechanical and heat allodynia in mouse via TRPA1 and TRPV1 activation.

Radiotherapy-related pain is a common adverse reaction with a high incidence among cancer patients undergoing radiotherapy and remarkably reduces the quality of life. However, the mechanisms of ionizing radiation-induced pain are largely unknown. In this study, mice were treated with 20 Gy X-ray to establish ionizing radiation-induced pain model. X-ray evoked a prolonged mechanical, heat, and cold allodynia in mice. Transient receptor potential vanilloid 1 and transient receptor potential ankyrin 1 were significantly upregulated in lumbar dorsal root ganglion. The mechanical and heat allodynia could be transiently reverted by intrathecal injection of transient receptor potential vanilloid 1 antagonist capsazepine and transient receptor potential ankyrin 1 antagonist HC-030031. Additionally, the phosphorylated extracellular regulated protein kinases (ERK) and Jun NH2-terminal Kinase (JNK) in pain neural pathway were induced by X-ray treatment. Our findings indicated that activation of transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 is essential for the development of X-ray-induced allodynia. Furthermore, our findings suggest that targeting on transient receptor potential vanilloid 1 and transient receptor potential ankyrin 1 may be promising prevention strategies for X-ray-induced allodynia in clinical practice.

Fangchinoline supplementation attenuates inflammatory markers in experimental rheumatoid arthritis-induced rats.

The present study evaluated the anti-inflammatory activity of fangchinoline in rheumatoid arthritis-induced rats. Rats were grouped into sham (group I), rheumatoid arthritis (group II, control), fangchinoline (2 µM, group III), and fangchinoline (4 µM, group IV) groups. The serum levels of lipid peroxidation, superoxide dismutase (SOD), glutathione peroxidase (Gpx), catalase, reduced glutathione (GSH), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), matrix metalloproteinases (MMPs), prostaglandin-E2 (PGE2), nitric oxide (NO), zinc, ceruloplasmin, uric acid, and copper were determined. Chondrocyte cell proliferation, reactive oxygen species (ROS), and cellular levels of TNF-α and IL-6 were assessed. Lipid peroxidation, GSH, SOD, catalase, and Gpx levels recovered to near normal levels by fangchinoline treatment. Fangchinoline treatment significantly reduced the TNF-α level by 17.8% and 40.8% in groups III and IV respectively, whereas IL-6 was significantly decreased by 23.2% and 45%, respectively. Fangchinoline treatment significantly decreased the MMP-3 level by 23.1% and 65.1% in groups III and IV respectively, whereas PGE2 was significantly decreased by 31.8% and 63.8%, respectively. Fangchinoline treatment decreased NO, uric acid, ceruloplasmin, and copper levels, whereas the zinc content was increased. Chondrocyte proliferation was significantly reduced to 73.3%, 51.3%, and 42.4% at 2 µM, 4 µM, and 6 µM fangchinoline treatment respectively. Intracellular ROS, TNF-α, and IL-6 levels were significantly reduced in the chondrocytes. Protein expression of TNF-α was significantly decreased by 0.27-, 0.53-, and 0.67-fold at 2 µM, 4 µM, and 6 µM fangchinoline treatment respectively. In conclusion, fangchinoline is effective as an anti-inflammatory agent in rheumatoid arthritis-induced rats.

Aesthetic and Functional Evaluation of Large Full-Thickness Vermilion and Lower Lip Defects Reconstruction.

BACKGROUND: It is hardly to reconstruct a huge defect of lower lip by using of partial flap which brings no mouth closing functional problem. In this study, we would like to introduce our experience in large full-thickness vermilion and lower lip/chin defects reconstruction, and also focus on the evaluation of the surgery effects. METHODS: The large lower lip and chin (include vermilion) reconstruction were performed in Sichuan Provincial People's Hospital (2012-2015). The surgery experience was introduced in this study first. In the following section, after a statement of these basic problems, various situations involving are investigated, such as the surgical effects of aesthetic and function that were evaluated through a visual analogue scale (VAS) by doctors and patients separately. The VAS score assessments of 2 kinds of surgery were collected and compared. RESULTS: A total of 7 patients use the tongue flap alone. Four patients use the combination of the free forearm flap and the anterior ventral tongue flap (COMBO flap). The VAS score of doctors group was significantly lower than the patients group (P < 0.05), and the aesthetic appearance was excellent (>90 points). Language features were not affected (>90 points). Slight mouth opening problems exist on these patients who were used COMBO flaps (>80 points; <90 points). The drooling and drumming gas problems were not observed. These 11 patients had no recurrence within 12 months after the operation. CONCLUSION: The 1:1 ratio between upper and lower lip is crucial to the design of anterior ventral tongue flap which brings with an excellent 3-dimensional morphologic and anatomic structure outcome. The bite block might become an essential operation step for vermilion reconstruction by using of tongue flap. And the COMBO flap may enhance the facial aesthetics and oral function for the reconstruction.

Food Exclusion Based on IgG Antibodies Alleviates Symptoms in Ulcerative Colitis: A Prospective Study.

BACKGROUND: Most patients with ulcerative colitis (UC) rely predominantly on medication for disease control. Diet interventions can reduce pharmaceutical expenditures and prolong remission. We designed a prospective study to evaluate whether an immunoglobulin G (IgG)-guided exclusion diet would improve symptoms and quality of life (QoL) in patients with UC. METHODS: The 6-month diet intervention included 97 patients with UC, who were randomly divided into an intervention group (n = 49) and a control (n = 48) group. Individual diet plans were created for the intervention group according to IgG titers; the control group ate a healthy diet as normal. Observational indices included disease activity, extraintestinal manifestations, nutritional status, and QoL. Relationships between food-specific IgG antibodies and these indices were also analyzed. RESULTS: At baseline, there were no significant differences between the groups. Food-specific IgG antibodies were detected in 70.10% of participants. After intervention, the Mayo score was significantly lower in the intervention group than in the control group (2.41 ± 0.89 vs 3.52 ± 1.15, P < 0.05). The number of patients with extraintestinal manifestations decreased from 7 to 2 in the intervention group and from 6 to 5 in the control group. As for nutritive indices, the intervention group had higher mean body mass index and albumin than the control group (23.88 ± 3.31 vs 21.50 ± 6.24 kg/m2, respectively, P < 0.05; 48.05 ± 6.39 vs 45.72 ± 5.48 g/L, respectively, P < 0.05), whereas prealbumin and transferrin were not significantly different between the groups. QoL improved after food exclusion (P < 0.05). CONCLUSIONS: An IgG-guided exclusion diet ameliorated UC symptoms and improved QoL. Interactions between IgG-based food intolerance and UC warrant further study.

Preliminary Analysis of Parkinson-like Motor Coordination Abnormityin Brain-specific hS100B Transgenic Mice.

Objective To investigate the role of S100B in the development of Parkinson's disease (PD) and explore the possibility of brain-specific S100B transgenic mice as PD animal model. Methods The hS100B transgenic mice were established. The mice were divided into S100B transgenic group (TG),S100B knockout group (KG),and the non-transgenic control group (CG). Motor coordination ability of mice was measured by the rota-rod and pole-climbing test. The expressions of S100B,dopamine D1 receptor,dopamine D2 receptor,G protein-coupled receptor kinase (GRK)2,GRK5,and tyrosine hydroxylase in brain tissue were detected by reverse transcription-polymerase chain reaction and Western blot. The levels of tyrosine,levodopa,dopamine,and homovanillic acid in brain tissue were measured by high-performance liquid chromatography coupled with fluorescence detection. Results Compared with CG,the S100B protein expression in brain tissue significantly increased in TG (P<0.05);the motor coordination ability of mice showed progressive decline (P<0.05);the mRNA and protein expressions of dopamine D2 receptor and GRK2 significantly decreased (P<0.05);the levels of levodopa,dopamine,and homovanillic acid were significantly elevated (P<0.05);the expression of tyrosine hydroxylase was also down-regulated,although there was no significant difference (P>0.05). Compared with CG,there was no obvious change of the above indicators in KG (all P>0.05). Conclusion S100B plays an important role in the motor coordination abnormity of PD. The brain-specific S100B transgenic mice can be used in research on the role of S100B gene in the development of PD.

Pediatric rehabilitation with the reachMAN's modular handle.

This paper presents the results of a preliminary study with one cerebral palsy child using the ReHaptic Handle, a novel robotic device for the pediatric rehabilitation of upper limb function. The device has two degrees-of-freedom to train pinching, forearm supination/pronation and wrist flexion/extension movements. Interactive computer games have been implemented to increase subjects' participation and engagement, thus promoting motor recovery. Pinching, with the index finger and thumb, forearm supination/pronation as well as wrist flexion/extension were trained two or three times a week for 15 minutes each. An increase in forearm supination/pronation movement precision and smoothness was observed with the subject, as well as a reduction in the movement duration.

[Discrete potentials guided ablation for idiopathic outflow tract ventricular arrhythmias].

OBJECTIVE: Discrete potentials (DPs) have been recorded and targeted as the site of ablation of the outflow tract arrhythmias. The aim of the present study was to investigate the significance of DPs with respect to mapping and ablation for idiopathic outflow tract premature ventricular contractions (PVCs) or ventricular tachycardias (VTs). METHODS: Seventeen out of 24 consecutive patients with idiopathic right or left ventricular outflow tract PVCs/VTs who underwent radiofrequency catheter ablation between September 2012 and December 2013 in our department were included. Intracardiac electrograms during the mapping and ablation were analyzed. RESULTS: During sinus rhythm, sharp high-frequency DPs that displayed double or multiple components were recorded following or buried in the local ventricular electrograms in all of the 17 patients, peak amplitude was (0.51 ± 0.21) mV. The same potential was recorded prior to the local ventricular potential of the PVCs/VTs. Spontaneous reversal of the relationship of the DPs to the local ventricular electrogram was noted during the arrhythmias. The DPs were related to a region of low voltage showed by intracardiac high-density contact mapping. At the sites with DPs, unipolar and bipolar ventricular voltage of sinus beats were lower compared with the adjacent regions without DPs (unipolar: (6.1 ± 1.8) mV vs. (8.3 ± 2.3) mV, P < 0.05; bipolar: (0.62 ± 0.45) mV vs. (1.03 ± 0.60) mV, P < 0.05). The targeted DPs were still present in 12 patients after successful elimination of the ectopies. Discrete potentials were not present in seven controls. CONCLUSIONS: Discrete potentials and related low-voltage regions were common in idiopathic outflow tract ventricular arrhythmias. Discrete potential- and substrate-guided ablation strategy could help to reduce the recurrence of idiopathic outflow tract arrhythmias.

Hybridization chain reaction engineered DNA nanopolylinker for amplified electrochemical sensing of biomarkers.

A DNA nanopolylinker was designed as a three dimensional nanoprobe with high loading of signal molecules for amplifying the biosensing signal. The nanoprobe was prepared by hybridization chain reaction engineering dsDNA polymerization on initiator DNA modified Au nanoparticle with two kinds of small molecule, for example, FITC-labeled DNA hairpins. The core-shell conjugate that was formed contained approximately 320 FITC molecules for further binding of signal molecules. With a sandwich-type immunoreaction and a biotin-streptavidin affinity reaction, the biotinylated core-shell nanoprobe was immobilized on the immunosensor surface, and the FITC molecules then bound enzyme labeled anti-FITC antibody to catalyze a silver deposition process, leading to a novel cascade signal amplification strategy. By combining the proposed strategy with stripping analysis of the deposited silver, an ultrasensitive immunoassay method for biomarker detection was developed. Under optimal conditions, this method showed a linear detection range over 5 orders of magnitude for carcinoembryonic antigen with a detection limit of 1.2 fg mL(-1) (about 18 molecules in 5.0 µL sample). The preparation of DNA nanopolylinker was simple and economic, and it could be used as a universal and multifarious probe for different bioanalytical techniques and showed the promising potential of the signal amplification strategy in the future design of biosensing methodology.

A novel histidine-rich CPx-ATPase from the filamentous cyanobacterium Oscillatoria brevis related to multiple-heavy-metal cotolerance.

A novel gene related to heavy-metal transport was cloned and identified from the filamentous cyanobacterium Oscillatoria brevis. Sequence analysis of the gene (the Bxa1 gene) showed that its product possessed high homology with heavy-metal transport CPx-ATPases. The CPC motif, which is proposed to form putative cation transduction channel, was found in the sixth transmembrane helix. However, instead of the CXXC motif that is present in the N termini of most metal transport CPx-ATPases, Bxa1 contains a unique Cys-Cys (CC) sequence element and histidine-rich motifs as a putative metal binding site. Northern blotting and real-time quantitative reverse transcription-PCR showed that expression of Bxa1 mRNA was induced in vivo by both monovalent (Cu(+) and Ag(+)) and divalent (Zn(2+) and Cd(2+)) heavy-metal ions at similar levels. Experiments on heavy-metal tolerance in Escherichia coli with recombinant Bxa1 demonstrated that Bxa1 conferred resistance to both monovalent and divalent heavy metals. This is the first report of a CPx-ATPase responsive to both monovalent and divalent heavy metals.