We demonstrate that forecASD has substantially better performance than previous predictors of autism association in three independent trio-based sequencing studies. Studying forecASD prioritized genes, we show that forecASD is a robust indicator of a gene's involvement in ASD etiology, with diverse applications to gene discovery, differential expression analysis, eQTL prioritization, and pathway enrichment analysis.Insulin resistance is associated with aging in mice and humans. We have previously shown that administration of recombinant GDF11 (rGDF11) to aged mice alters aging phenotypes in the brain, skeletal muscle, and heart. While the closely related protein GDF8 has a role in metabolism, limited data are available on the potential metabolic effects of GDF11 or GDF8 in aging. To determine the metabolic effects of these two ligands, we administered rGDF11 or rGDF8 protein to young or aged mice fed a standard chow diet, short-term high-fat diet (HFD), or long-term HFD. Under nearly all of these diet conditions, administration of exogenous rGDF11 reduced body weight by 3-17% and significantly improved glucose tolerance in aged mice fed a chow (~30% vs. saline) or HF (~50% vs. saline) diet and young mice fed a HFD (~30%). On the other hand, exogenous rGDF8 showed signifcantly lesser effect or no effect at all on glucose tolerance compared to rGDF11, consistent with data demonstrating that GFD11 is a more potent signaling ligand than GDF8. Collectively, our results show that administration of exogenous rGDF11, but not rGDF8, can reduce diet-induced weight gain and improve metabolic homeostasis.The presence of bronchial mucus plugs (BMP) in children with Mycoplasma pneumoniae pneumonia (MPP) results in delayed clinical and radiographic resolution and long-standing pulmonary sequelae. The predictive factors associated with BMP formation remains poorly defined. Nomograms to predict BMP presence in children with MPP were proposed using a cohort of patients who underwent bronchoscopy intervention at Children's Hospital in Eastern China. Patients with MPP in an earlier period formed the training cohort (n = 872) for nomogram development, and those thereafter formed the validation cohort (n = 399) to confirmed model's performance. BMP in children with MPP were found in 196 (22.5%) and 91(22.8%) patients in the training and validation cohorts, respectively. The independent risk factors associated with BMP were age >5years (OR 2.06; 95% CI 1.43 to 2.98), higher IL-10 level (>10 ng/L, 2.19; 95% CI 1.46 to 3.28), higher IFN-γ level (>30 ng/L, 1.69; 95% CI 1.13 to 2.54), and presence of complication (3.43; 95% CI 1.45 to 8.09). Incorporating these 4 factors, the nomogram achieved good concordance indexes of 0.771(95% CI, 0.734-0.808) and 0.796 (95% CI, 0.744-0.848) in predicting BMP in the training and validation cohorts, respectively. The nomogram achieved an optimal prediction of BMP in children with MPP. Using this model, the risk of BMP formation would be determined, contributing to a rational therapeutic choice.Breast cancer (BC) is a common cancer in women worldwide. Despite advances in treatment, up to 30% of women eventually relapse and die of metastatic breast cancer. Liquid biopsy analysis of circulating cell-free DNA fragments in the patients' blood can monitor clonality and evolving mutations as a surrogate for tumour biopsy. Next generation sequencing platforms and digital droplet PCR can be used to profile circulating tumour DNA from liquid biopsies; however, they are expensive and time consuming for clinical use. Here, we report a novel strategy with proof-of-concept data that supports the usage of loop-mediated isothermal amplification (LAMP) to detect PIK3CA c.3140 A > G (H1047R), a prevalent BC missense mutation that is attributed to BC tumour growth. Allele-specific primers were designed and optimized to detect the p.H1047R variant following the USS-sbLAMP method. The assay was developed with synthetic DNA templates and validated with DNA from two breast cancer cell-lines and two patient tumour tissue samples through a qPCR instrument and finally piloted on an ISFET enabled microchip. This work sets a foundation for BC mutational profiling on a Lab-on-Chip device, to help the early detection of patient relapse and to monitor efficacy of systemic therapies for personalised cancer patient management.The existence of methane in the Earth's mantle does not cause any doubt, however, its possible chemical transformation under the mantle thermobaric conditions is not enough known. Investigation of methane at the upper mantle thermobaric conditions, using diamond anvil cells, demonstrated the possible formation of ethane, propane and n-butane from methane, however, theoretical calculations of methane behaviour at extreme temperature and pressure predicted also heavier hydrocarbons. We experimentally investigated the chemical transformations of methane at the upper mantle thermobaric conditions, corresponding to the depth of 70-80 km (850-1000 K, 2.5 GPa), using "Toroid"-type Large reactive volume device and gas chromatography. The experimental results demonstrated the formation of the complex hydrocarbon mixture up to C7 with linear, branched and cycled structures and benzene. https://www.selleckchem.com/products/TSU-68(SU6668).html Unsaturated hydrocarbons were detected on the trace level in the products mixture. The increasing of exposure time leaded to growth of heavier components in the product systems. The data obtained suggest possible existence of complex hydrocarbon mixtures at the upper mantle thermobaric conditions and provide a new insight on the possible pathways of the hydrocarbons synthesis from methane in the upper mantle.Controlling the structural organization and crystallinity of functional oxides is key to enhancing their performance in technological applications. In this work, we report a strong enhancement of the structural organization and crystallinity of Bi2WO6 samples synthetized by a microwave-assisted hydrothermal method after exposing them to femtosecond laser irradiation. X-ray diffraction, UV-vis and Raman spectroscopies, photoluminescence emissions, energy dispersive spectroscopy, field emission scanning electron microscopy, and transmission electron microscopy were employed to characterize the as-synthetized samples. To complement and rationalize the experimental results, first-principles calculations were employed to study the effects of femtosecond laser irradiation. Structural and electronic effects induced by femtosecond laser irradiation enhance the long-range crystallinity while decreasing the free carrier density, as it takes place in the amorphous and liquid states. These effects can be considered a clear cut case of surface-enhanced Raman scattering.

57, 95% confidence interval (CI) 1.07-2.32, p = 0.022 and HR 2.01, 95% CI 1.10-3.69, p = 0.023 respectively]. CONCLUSIONS Patients with a low AGR level had an increased all-cause and cardiovascular mortality. AGR may be a useful index in identifying patients on PD at risk for CVD and all-cause of mortality.BACKGROUND Diabetes mellitus (DM) is thought to affect tuberculosis (TB) clinical presentation and treatment response. Whether DM impacts radiological manifestations of pulmonary TB is still not clear. This study investigated the impact of glycemic status on radiological manifestations of pulmonary TB cases and its relationship with concentration of biochemical parameters in peripheral blood. METHODS A retrospective cross-sectional study used data from 132 microbiologically confirmed pulmonary TB patients from Lima, Peru, evaluated in a previous investigation performed between February and December 2017. Chest radiographs were analyzed by a radiologist and a pulmonologist. Radiographic lesions were identified as cavities, alveolar infiltrates and fibrous tracts. Hyperglycemia in TB patients was identified by use of fasting plasma glucose, HbA1c and oral glucose tolerance test. Clinical, biochemical and hematological parameters were also analyzed. RESULTS TB patients with hyperglycemia presented more frequently with cavities, alveolar infiltrates and fibrous tracts than those with normoglycemia. https://www.selleckchem.com/products/agk2.html Hierarchical clustering analysis indicated that patients with more diverse and higher number of lung lesions exhibited a distinct laboratorial profile characterized by heightened white blood cell counts and circulating levels of total cholesterol, triglycerides and transaminases and simultaneously low levels of albumin and hemoglobin. Multivariable regression analyses adjusted for age, sex, prior TB, hemoglobin levels and acid-fast bacilli ≥2+ in sputum smears, demonstrated that presence of prediabetes or diabetes in TB patients was associated with increased odds of having 3 pulmonary lesion types (p = 0.003 and p  less then  0.01 respectively) or ≥ 4 lesions (p = 0.001 and p = 0.01 respectively). CONCLUSION Hyperglycemia (both DM and prediabetes) significantly affected the presentation of radiographic manifestations and the number of lesions in pulmonary TB patients as well as the biochemical profile in peripheral blood.BACKGROUND Chagas disease is caused by the haemoflagellate protozoan Trypanosoma cruzi. Currently, T. cruzi recognizes seven discrete typing units (DTUs) TcI to TcVI and Tcbat. The genetic diversity of T. cruzi is suspected to influence the clinical outcome. Acute clinical manifestations, which include myocarditis and meningoencephalitis, are sometimes fatal; occur most frequently in children and in immunocompromised individuals. Acute disease is often overlooked, leading to a poor prognosis. CASE PRESENTATION A 38-year-old man from a subtropical area of the Andes mountains of Ecuador was hospitalized after 3 weeks of evolution with high fever, chills, an enlarged liver, spleen, and lymph nodes, as well as facial edema. ECG changes were also observed. T. cruzi was identified in blood smears, culture and amplification of DNA by PCR. Tests for anti-T. cruzi IgG and IgM and HIV were negative. Molecular typing by restriction fragment length polymorphism (PCR-RFLP) determined the parasite to DTU TcI. In the absence of a timely anti-T. cruzi medication, the patient died. CONCLUSIONS This is a case of severe pathogenicity and the virulence of a DTU TcI strain in an adult patient. The severe acute Chagas disease was probably overlooked due to limited awareness and its low incidence. Our findings suggest that T. cruzi DTU TcI strains circulating in Ecuador are capable of causing fatal acute disease. Early diagnosis and prompt treatment is of paramount importance to avoid fatalities in acute infections.BACKGROUND Patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) have substantially better treatment response and overall survival (OS) than patients with HPV-negative disease. Treatment options for HPV+ OPC can involve either a primary radiotherapy (RT) approach (± concomitant chemotherapy) or a primary surgical approach (± adjuvant radiation) with transoral surgery (TOS). These two treatment paradigms have different spectrums of toxicity. The goals of this study are to assess the OS of two de-escalation approaches (primary radiotherapy and primary TOS) compared to historical control, and to compare survival, toxicity and quality of life (QOL) profiles between the two approaches. METHODS This is a multicenter phase II study randomizing one hundred and forty patients with T1-2 N0-2 HPV+ OPC in a 11 ratio between de-escalated primary radiotherapy (60 Gy) ± concomitant chemotherapy and TOS ± de-escalated adjuvant radiotherapy (50-60 Gy based on risk factors). Patients will be stratified based on smoking status ( less then  10 vs. ≥ 10 pack-years). The primary endpoint is OS of each arm compared to historical control; we hypothesize that a 2-year OS of 85% or greater will be achieved. Secondary endpoints include progression free survival, QOL and toxicity. DISCUSSION This study will provide an assessment of two de-escalation approaches to the treatment of HPV+ OPC on oncologic outcomes, QOL and toxicity. Results will inform the design of future definitive phase III trials. TRIAL REGISTRATION Clinicaltrials.gov identifier NCT03210103. Date of registration July 6, 2017, Current version 1.3 on March 15, 2019.BACKGROUND Currently, complete surgical resection represents the only potentially curative treatment option for Biliary Tract Cancer (BTC) including Gallbladder Cancer (GBC). Even after curative resection, 5-year OS is only 20-40%. Gallbladder carcinoma is relatively rare, but still the fifth most common neoplasm of the digestive tract and even the most frequent cancer of the biliary system. Gallbladder carcinoma is suspected preoperatively in only 30% of all pts., while the majority of cases are discovered incidentally by the pathologist after cholecystectomy for a benign indication. For improving curative rates in BTC and GBC, early systemic therapy combined with radical resection seems to be a promising approach. The earliest moment to apply chemotherapy would be in front of radical surgery. The encouraging results of neoadjuvant/perioperative concepts in other malignancies provide an additional rationale to use this treatment in the early phase of GBC management and even ICC/ECC. Especially because data regarding pure adjuvant chemotherapy in BTC's are conflicting.

Overall egg production and cumulative egg numbers were similar among treatments. Interestingly, a second increase in estradiol was observed at 52 woa under all treatments, suggesting an additional ovarian stimulation, possibly associated with an additional follicular recruitment at that age. Overall, changes in estradiol concentrations were more pronounced in hens maintained under LED-R light than in hens exposed to incandescent and CFL, especially for the second increase, suggesting that a higher amount of red light leads to stronger ovarian activity. Maintaining hens under LED-R bulbs also resulted in lower feed consumption, which combined with the lower energy consumption of LED-bulbs (LED-R 306 kW; incandescent 2,514 kW; CFL 422 kW) could reduce the production cost. 2019, Japan Poultry Science Association.This study aimed to evaluate the effect of dietary supplementation of a mixed yeast culture (MYC; Saccharomyces cerevisiae YJM1592 and Kluyveromyces maxianus TB7258 in a 11 ratio) on growth performance, nutrient digestibility, meat quality, blood parameters, and gut health of broiler chickens. In total, 576 one-day-old male broilers (Ross 308) with an average initial bodyweight (BW) of 37±0.51 g were used in a 35-day experiment with a completely randomized design. The broilers were randomly assigned to 3 dietary treatments CON, basal diet; TRT1, CON + 0.1% MYC; and TRT 2, CON + 0.2% MYC. From days 8 to 21, the feed conversion rate (FCR) was significantly decreased in broilers fed MYC-supplemented diets. From days 22 to 35, BW gain (BWG) significantly increased with increasing MYC concentration. Throughout the experiment, BWG increased (linear effect, P=0.002) and FCR decreased with increasing MYC in the diet. MYC supplementation increased the digestibility of dry matter (DM) in broilers in a dose-dependent manner. Relative organ weight of the bursa of Fabricius linearly increased in broilers fed MYC-supplemented diets. The white blood cell count showed linear and quadratic increases in broilers fed increasing concentrations of MYC. The population of Lactobacillus in the excreta linearly increased P=0.033, whereas that of Escherichia coli tended to linearly decrease (P=0.064) in the MYC groups. This study provides a basis for future research on MYC as a growth promoter in broilers. 2019, Japan Poultry Science Association.Cordyceps militaris is a well-known Chinese medicinal fungus that has been used as a nutraceutical food in several Asian countries. Cordycepin (3'-deoxyadenosine), a secondary metabolite produced from Cordyceps militaris, has been demonstrated to exert a wide spectrum of pharmacological activities, such as anti-microbial and antitumor activities. However, the effect of cordycepin on immunomodulation in broilers is poorly investigated. https://www.selleckchem.com/products/h3b-120.html In the current study, we investigated the effect of cordycepin (9.69, 19.38, and 38.76 mg) from Cordyceps militaris hot water extract (CMHW) on growth performance and immunocompetence in broilers. Results showed that CMHW significantly decreased inducible nitric oxide synthase (iNOS) mRNA levels in the bursa of Fabricius after 4 weeks of feeding (P less then 0.05). CMHW treatment reduced cyclooxygenase-2 (COX-2) mRNA levels in the spleen and bursa of Fabricius after 4 weeks of feeding (P less then 0.05). Supplementation of CMHW for 3 days after vaccination reduced iNOS mRNA level in the spleen of 14 and 28 day-old broilers (P less then 0.05). Prior to vaccination, CMHW pretreatment significantly down-regulated COX-2 mRNA levels in the spleen and bursa of Fabricius of 14-day-old broilers (P less then 0.05). Furthermore, CMHW significantly reduced lipopolysaccharide (LPS)-induced iNOS and COX-2 mRNA levels in the spleen and bursa of Fabricius (P less then 0.05). CMHW treatment attenuated LPS-induced IFN-γ expression in the spleen and bursa of Fabricius, whereas CMHW induced IL-4 expression in these organs in response to LPS challenge (P less then 0.05). Taken together, these observations demonstrate that CMHW exerts an immunomodulatory role in broilers. CMHW is a potential novel feed additive with applications in inflammation-related diseases and bacterial infection in broilers. 2019, Japan Poultry Science Association.This study was performed to investigate and compare the effects of using Artemisia annua leaves, probiotic, and organic acid on the performance, egg quality, blood biochemistry, and antioxidant status of laying hens. In total, 288 Hy-Line W-36 commercial layers (32 weeks old) were divided into six groups with six replicates per group (eight birds per replicate) and were fed one of six experimental diets. The hens were fed either a corn-soybean meal basal diet (control) or the basal diet supplemented with 2.5% A. annua leaves (AA1), 5% A. annua leaves (AA2), 7.5% A. annua leaves (AA3), 0.1% probiotic (Pro), and 0.005% organic acid (Org), respectively. The experiment lasted 10 weeks. Results showed that there were differences in the feed conversion ratio (FCR) among experimental groups (P less then 0.05). The highest yolk color index and shell thickness were observed in hens fed AA3 and AA2 diets (P less then 0.05). Egg yolk cholesterol was decreased (P less then 0.01) by the diet containing AA3 and Pro compared to the other groups. The atherogenic index was lower (P less then 0.01) in the plasma of hens fed AA3 than those in other groups. The glutathione peroxidase activity (GSH-Px) and malondialdehyde (MDA) contents in layers fed AA3 were lower and higher (P less then 0.05), respectively, than in layers fed the other diets. Moreover, the concentration of plasma cholesterol was decreased (P less then 0.05) in layers fed AA3 and Pro. In conclusion, feeding laying hens with A. annua leaves positively influenced the plasma antioxidant status, and the dietary inclusion of A. annua leaves plus a probiotic significantly decreased the egg yolk cholesterol, with no adverse effect on the egg productive traits. 2019, Japan Poultry Science Association.The growth performance, nutrient digestibility, hematology, serum chemistry, and lipoprotein concentrations of turkey (Meleagris gallopavo) poults fed diets supplemented with high or recommended concentrations of niacin were investigated in this study. A total of 120 four-week-old turkey poults were randomly divided into three treatment groups with five replicates of eight birds in each group. The poult diets were supplemented with 0.0, 60, and 180 mg/kg niacin in the three treatments, termed control, recommended niacin supplementation (RNS), and high niacin supplementation (HNS), respectively. The study lasted for four weeks. The results showed that the HNS treatment reduced the feed intake and increased the body weight gain of poults. The apparent, nitrogen-corrected, and true metabolizable energy contents were the highest in the HNS-group turkey poults (P less then 0.05). The red and white blood cell counts and hemoglobin concentration of the turkeys improved with increasing niacin supplementation (P less then 0.

BACKGROUND Adult T-cell leukemia-lymphoma (ATL) is an aggressive mature lymphoid proliferation associated with poor prognosis. Standard of care includes chemotherapy and/or the combination of zidovudine and interferon-alpha. However, most patients experience relapse less than 6 months after diagnosis. Allogeneic stem cell transplantation is the only curative treatment, but is only feasible in a minority of cases. We previously showed in a mouse model that Arsenic trioxide (As2O3) targets ATL leukemia initiating cells. RESULTS As2O3 consolidation was given in 9 patients with ATL (lymphoma n = 4; acute n = 2; and indolent n = 3), who were in complete (n = 4) and partial (n = 3) remission, in stable (n = 1) and in progressive (n = 1) disease. Patients received up to 8 weeks of As2O3 at the dose of 0.15 mg/kg/day intravenously in combination with zidovudine and interferon-alpha. One patient in progression died rapidly. Of the remaining eight patients, three with indolent ATL subtype showed overall survivals of 48, 53 and 97 months, and duration of response to As2O3 of 22, 25 and 73 months. The other 5 patients with aggressive ATL subtype had median OS of 36 months and a median duration of response of 10 months. Side effects were mostly hematological and cutaneous (one grade 3) and reversible with dose reduction of AZT/IFN and/or As2O3 discontinuation. The virus integration analysis revealed the regression of the predominant malignant clone in one patient with a chronic subtype. CONCLUSION These results suggest that consolidation with As2O3 could be an option for patients with ATL in response after induction therapy and who are not eligible for allogeneic stem cell transplantation.BACKGROUND Evoked potentials (EPs) are a measure of the conductivity of the central nervous system. They are used to monitor disease progression of multiple sclerosis patients. https://www.selleckchem.com/products/au-15330.html Previous studies only extracted a few variables from the EPs, which are often further condensed into a single variable the EP score. We perform a machine learning analysis of motor EP that uses the whole time series, instead of a few variables, to predict disability progression after two years. Obtaining realistic performance estimates of this task has been difficult because of small data set sizes. We recently extracted a dataset of EPs from the Rehabiliation & MS Center in Overpelt, Belgium. Our data set is large enough to obtain, for the first time, a performance estimate on an independent test set containing different patients. METHODS We extracted a large number of time series features from the motor EPs with the highly comparative time series analysis software package. Mutual information with the target and the Boruta method are preferably multi-center, are needed for further research. Given a large enough dataset, these models may be used to support clinicians in their decision making process regarding future treatment.BACKGROUND Wild boar-derived hepatitis E (HEV) genotype 3 virus has been successfully isolated in cell lines of human origin only. Considering the zoonotic potential and possible extrahepatic localisation of genotype 3 strain, it is important to investigate the viability of cell lines of different animal and tissue origins. Therefore, the objective of the present study was to determine the permissiveness of non-human primate (MARC-145 and Vero) and swine (PK-15) cell lines of kidney origin, and a mouse neuroblastoma (Neuro-2a) cell line for isolation of wild boar-derived HEV genotype 3. RESULTS This study showed that MARC-145, PK-15, Neuro-2a and Vero cell lines were permissive to wild boar-derived HEV genotype 3 subtype 3i harbouring viral genome equivalents of 1.12 × 107 copies/ml, 2.38 × 105 copies/ml, 2.97 × 107 copies/ml and 4.01 × 107 copies/ml after five serial passages respectively. In all permissive cell lines, HEV was continuously recovered from growth medium between five and at least 28 days post-ienerate more data on HEV transmission between wild animal populations and their role as sources of human infections.BACKGROUND The low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio constitutes a strong risk predictor of cardiovascular events. However, the association between this ratio and cardiovascular death in peritoneal dialysis (PD) patients is uncertain. The study aimed to investigate whether a high LDL-C/HDL-C ratio could predict both cardiovascular and all-cause mortalities in patients on PD. METHODS A total of 1616 incident patients on PD included from January 1, 2006 to December 31, 2013 were followed up with until 31 December 2018 in this single-center prospective cohort study. Participants were divided into three categories according to LDL-C/HDL-C ratio tertile. The primary endpoint was cardiovascular mortality; the secondary endpoint was all-cause mortality. RESULTS The mean age of the study cohort was 47.5 years and the mean body mass index (BMI) was 21.6 kg/m2. During a median follow-up period of 47.6 months, 492 patients died, including 246 (50.0%) due to cardiovascular disease (CVD). A multivariate analysis revealed that the highest LDL-C/HDL-C ratio tertile was significantly associated with increased CVD mortality [hazard ratio (HR) 1.69, 95% CI 1.24-2.29; P = 0.001] and all-cause mortality (HR 1.46, 95% CI 1.18-1.81; P = 0.001) relative to the lowest tertile. After adjusting for covariates, the HRs of cardiovascular and all-cause mortalities were 1.84 (95% CI 1.25-2.71; P = 0.002) and 1.35 (95% CI 1.03-1.77; P = 0.032). Subgroup analysis showed that the risk of CVD death rose with a higher LDL-C/HDL-C ratio among PD patients who were female, younger than 65 years old, without being malnourished (BMI ≥ 18.5 kg/m2 or albumin ≥35 g/L), and with a history of diabetes or CVD, respectively. CONCLUSIONS A high LDL-C/HDL-C ratio is an independent risk factor for both cardiovascular and all-cause mortalities among PD patients.BACKGROUND Attachment in the parent-infant dyads is fundamental for growth and development of children born prematurely. However, the natural process of attachment is interrupted just after preterm birth, and emotional and physical detachment, limited social interaction, and a traumatic, technologically heavy environment in a neonatal intensive care unit (NICU) may result in impaired attachment or bonding. To our knowledge, few studies have evaluated the effectiveness of interventions aimed at enhancing attachment, bonding, and relationships between parents and their preterm infants during the infant's hospitalization in the NICU. This study aims to perform a comprehensive systematic review and a meta-analysis survey of the effects of attachment- and relationship-based interventions in the NICU. METHOD A comprehensive literature review will be conducted in the following databases MEDLINE, CINAHL, PubMed, EMBASE (OVID), Scopus, PsycINFO (OVID), Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science.

BACKGROUND Mass-like lesions are an uncommon presentation of cytomegalovirus (CMV) disease. CASE We report on a case of disseminated CMV disease with bilateral adrenal pseudotumors in a patient with a history of acute leukemia in remission. CONCLUSION In the settings of advanced cancer therapy and organ transplantation, a high index of suspicion for CMV should be maintained for mass-like disease.OBJECTIVE This study aimed to determine the association between the severity of obstructive sleep apnea (OSA) and serum Clara cell protein (CC16) levels in non-smoking patients with OSA. METHODS This prospective study included non-smoking patients who presented with sleep-related disturbances and underwent polysomnography (PSG). The serum CC16 level was measured and its relationship to PSG parameters was investigated. RESULTS The study included 128 patients (83 men) with a mean age of 48.4 ± 11.9. OSA was detected in 66 men (70%) and 29 women (30%) (p = 0.051). https://www.selleckchem.com/products/mrt68921.html The severity of OSA was mild in 32 (25%), moderate in 28 (22%), and severe in 35 (27%) of the patients. There was no significant difference in CC16 levels between the OSA group (1746 ± 1006) and the OSA negative group (1721 ± 1201, p = 0.91) levels. There was no significant difference between the CC16 levels of the each four groups. Mean serum CC16 levels were significantly lower in OSA negative men than OSA positive men (777 vs 1462, p = 0.005). No significant difference was observed in CC16 values according to OSA severity in women. CONCLUSION The serum CC16 level does not differ between non-smoking OSA patients and OSA negative patients.We present the cases of a mother and daughter with osteogenesis imperfecta, also diagnosed later with rheumatoid arthritis. In our patients finding and treating the over-imposed arthritis improved the joint pain initially attributed to osteogenesis imperfecta. Exploring joint inflammation in this setting could help ease the disease burden. PURPOSE Osteogenesis imperfecta (OI) is a rare hereditary disease evolving with recurrent fractures upon minor trauma, blue sclerae, and hearing loss. Although inflammation was not generally considered a feature of the disease, systemic inflammation was recently reported in children with OI and in murine models of OI. METHOD We present the cases of a mother and a daughter with OI, without a personal or family history of autoimmune diseases, who were also diagnosed with rheumatoid arthritis seropositive for anti-cyclic citrullinated peptide autoantibodies and rheumatoid factor. RESULTS The genetic tests identified in both patients a deletion in COL1A1 gene (c.3399del, p.Ala1134Profs*105), not previously reported, not present in population databases, creating a premature translational stop signal in the COL1A1 gene in the collagen I major ligand binding region 3. In our patients finding and treating the over-imposed arthritis improved the joint pain initially attributed to OI. Possible pathogenic links between OI and RA are discussed. CONCLUSION The prevalence of joint inflammation in OI is unknown and may be underestimated. As musculoskeletal involvement affects the quality of life in most OI patients, exploring this relation may help ease the disease burden.The original version of this article inadvertently omitted the word "with" between "Polymorphisms" and "Antisocial" from the title. The title "The Association of Oxytocin Receptor Gene (OXTR) Polymorphisms Antisocial Behavior A Meta-Analysis" should be "The Association of Oxytocin Receptor Gene (OXTR) Polymorphisms with Antisocial Behavior A Meta-Analysis." as presented above.PURPOSE To determine factors associated with early (same-day) versus late (> 1 day) discharge of male patients following urethroplasty, and to compare short-term (30-day) postoperative morbidity and mortality across the two groups. METHODS Using the National Surgical Quality Improvement Program database (2005-2016), patients who underwent urethroplasty with same-day hospital discharge (early) and those who stayed > 1 day (late) were identified. Extracted data included patient characteristics, comorbidities, preoperative labs, and 30-day postoperative complications. Multivariable logistic regressions determined factors associated with early (vs. late) discharge and the likelihood of having a complication in those who were discharged early (vs. late). Adjusted odds ratios and 95% CIs were reported. RESULTS N = 1435 male urethroplasty patients were identified, of which 396 (27.6%) were discharged early and 1039 (72.4%) were discharged late. White race (OR [95% CI] 2.21 [1.44, 3.38]), urethroplasty performed in/after year 2011 (4.23 [2.51, 7.15]), and anterior (vs. posterior) urethroplasty without tissue transfer (1.65 [1.17, 2.34]) were significantly associated with increased likelihood of early discharge. However, every 10-min increase in operation time (0.88 [0.86, 0.90]) decreased the odds of early discharge. When short-term postoperative complications were compared between the two groups, patients discharged early had a lower likelihood of being readmitted (0.35 [0.14, 0.88]) compared to those discharged late. Rates of mortality, complications, or reoperation were similar between the groups. CONCLUSIONS Predictors of early discharge following urethroplasty include shorter operating time, white race, and having an anterior (vs. posterior) urethroplasty without tissue transfer. Patients discharged early had a lower likelihood of being readmitted.To investigate the effect of intracranial pressure (ICP) monitoring on the functional outcome of patients with hypertension-related spontaneous intracerebral hemorrhage (ICH). We included 196 patients with Glasgow Coma Scale (GCS) scores of 3-12 in this observational study, of which 103 underwent ICP monitors. Binary and ordinal regression analyses were used to estimate the effect of ICP monitoring on the functional outcome. The rate of adverse events, blood pressure control, and length of hospitalization were compared between the two groups. ICP monitoring had a significant impact on the clinical outcome of patients by shifting the Extended Glasgow Outcome Scale (GOS-E) scores in a favorable direction (p = 0.027) and reducing mortality at discharge (p = 0.004) and 6 months later (p = 0.02). The rate of favorable outcome at 6 months was higher in the ICP-monitored group (p = 0.03). However, subgroup analysis showed that no relationship between ICP monitoring and clinical outcome was found for patients with GCS scores of 3-8.

The intention of reoperation was recorded immediately after operation and 24 h after operation. The expectation and treatment credibility scale (ETCS) was used to evaluate the relationship between patients' expectation and efficacy 5 min before operation and immediately after operation. RESULTS At T2 and T3 during the operation, the MAP and HR in the obserrvation group were lower than those in the control group, while SpO2 was higher than that in the control group (P0.05). The scores of ETCS1, ETCS2 and ETCS3 immediately after operation in the observation group were higher than those in the control group (P less then 0.05). CONCLUSION The wrist-ankle acupuncture has positive auxiliary analgesic effect on lumbago during transforaminal endoscope surgery, and strengthens the patients' confidence on the operation effect.OBJECTIVE To observe the effect of electroacupuncture (EA) on the rehabilitation of knee joint function after anterior cruciate ligament (ACL) reconstruction. METHODS A total of 140 patients with ACL reconstruction were randomly divided into an observation group (58 cases recruited, 12 cases dropped out) and a control group (65 cases recruited, 5 cases dropped out). The patients in the control group were treated with routine rehabilitation treatment. The patients in the observation group, on the basis of the treatment in the control group, were treated with EA at Fengshi (GB 31), Futu (ST 32), Zusanli (ST 36), Shangjuxu (ST 37), Fenglong (ST 40), Xuanzhong (GB 39), Diji (SP 8) and Sanyinjiao (SP 6) on the affected side (2 Hz/100 Hz of dilatational wave, 2-5 mA). Each EA treatment lasted 20-30 min, twice a day for 7 days. The swelling degree (d), pain visual analogue scale (VAS), knee joint range of motion (ROM), scores of International Knee Documentation Committee (IKDC) subjective short form and scores of Lysholm were observed in the two groups 1 day, 1 month, 3 months, 6 months and 1 year after operation. RESULTS One month and 3 months after operation, the swelling degree (d) and VAS scores in the observation group were lower than those in the control group (P0.05). One month, 3 months, 6 months and 1 year after operation, the ROM of the knee joint in the observation group was higher than that in the control group (P less then 0.05), the IKDC score and Lysholm score were higher than those in the control group (P less then 0.05). Within one year, there were no relaxations, fractures and other related complications in the two groups. The pivot shift test, anterior drawer test and the Lachman test were all negative. CONCLUSION EA combined with routine rehabilitation training could obviously reduce the pain of knee joint, improve the swelling degree, increase the ROM of knee joint, promote the functional recovery in patients with ACL reconstruction, which are superior to rehabilitation training alone.OBJECTIVE To verify the clinical effect of laryngopharyngeal reflux (LPR) treated with acupuncture at the acupoints composed on the base of theory of the ascending and the descending of qi. METHODS A total of 84 patients of LPR were randomized into an observation group and a control group, 42 cases in each one. The conventional treatment was provided in the two groups. Additionally, in the control group, the medication was administered, i.e. esomeprazole tablets (20 mg, twice a day) and mosapride tablets (5 mg, three times a day), consecutively for 14 days. In the observation group, the oral medication was the same as the control group. Besides, acupuncture at the acupoints composed on the base of theory of the ascending and the descending of qi was supplemented. The acupoints were Tiantu (CV 22), Danzhong (CV 17), Zhongwan (CV 12), Zusanli (ST 36), Taichong (LR 3) and Neiguan (PC 6). The acupuncture treatment was given once a day, 5 times a week, consecutively for 10 times in 2 weeks (14 days in total). Befond physical signs. The therapeutic effect of this comprehensive therapy is better than the simple treatment with western medication.OBJECTIVE To observe the effect of electroacupuncture (EA) combined with lifestyle control on hepatic fat status, hepatic enzymology, glycolipid metabolism and anthropological parameters in patients with obese nonalcoholic fatty liver disease(NAFLD). METHODS A total of 90 patients with obese NAFLD were randomized into an observation group (45 cases, 4 cases dropped off) and a control group (45 cases, 1 case dropped off). Lifestyle control was implemented in the control group. On the basis of the treatment in the control group, acupuncture was applied at Zhongwan (CV 12), Quchi (LI 11), Shuifen (CV 9), Huaroumen (ST 24), Daheng (SP 15), Guanyuan (CV 4), Qihai (CV 6), etc. EA was provided at Huaroumen (ST 24) and Daheng (SP 15) with dilatational wave, 2 Hz/100 Hz in frequency, 30 min each time, once every other day, 3 times a week. The treatment for 12 weeks was required in both of the two groups. Hepatic fat status [controlled attenuation parameter (CAP) and liver stiffness measurement (LSM)], hepatic enzymolo the two groups (P less then 0.05, P less then 0.01),while the levels of HDL-C were increased (P less then 0.05). Compared before treatment, FPG after treatment in the observation group was reduced (P less then 0.05). https://www.selleckchem.com/products/AZD1480.html Compared with the control group, FINS, HOMA-IR, TC and TG in the observation group were lower than those in the control group after treatment (P less then 0.05). ③Compared before treatment, BW BMI, FP, WC, HC, WHR after treatment were obviously reduced in the two groups (P less then 0.01). After treatment, WC and WHR in the observation group were lower than the control group (P less then 0.05). CONCLUSION Electroacupuncture combined with lifestyle control can effectively treat obese nonalcoholic fatty liver disease, and present better therapeutic effect on hepatic fat status, glycolipid metabolism, insulin resistance, WC and WHR.OBJECTIVE To observe the efficacy of early treatment of suspension moxibustion for Bell's palsy and its influence on the prognosis, and to explore whether the early treatment of suspension moxibustion has non-inferiority effect to hormone treatment and whether suspension moxibustion combined with hormone treatment has the synergistic effect. METHODS A total of 132 patients with acute-stage Bell's palsy were divided into a hormone group (94 cases) and a moxibustion group (38 cases) by non-random method, and the hormone group was further randomly divided into a hormone with moxibustion group (48 cases) and a hormone without moxibustion group (46 cases). The acupuncture and oral administration of mecobalamin capsule were used as basic treatment. Acupuncture was applied at Yangbai (GB 14), Sibai (ST 2), Quanliao (SI 18), Dicang (ST 4), Jiache (ST 6), Yifeng (TE 17), etc., with the needles retained for 30 min, once a day, 5 consecutive days per week; there was an interval of 2 days between two weeks, and a total of 4-week treatment was given.

CONCLUSION Health organizations should be aware of the levels of customization available when selecting a de-identification deployment solution, in order to choose the one that best matches their resources and target performance level.BACKGROUND To detect annual alveolar bone loss in subjects with cardiovascular disease (CVD) adjusting for associated systemic diseases and risk factors. METHODS A total number of 132 subjects that reported having CVD from 2008 to 2015 (N = 132). https://www.selleckchem.com/products/brivudine.html For longitudinal data analysis, 58 subjects eligible for inclusion with at least two exposures of complete mouth set or repeated BW radiographs with at least one-year interval compared with a control group. Alveolar bone level on mesial and distal sites of posterior teeth was measured on bitewing (BW) radiographs available in the electronic health records of each subject. RESULTS Subjects who reported having cardiovascular diseases experienced higher annual mean alveolar bone loss (0.062 mm per year) compared to Subjects with no cardiovascular diseases (0.022 mm per year). CONCLUSION Subjects who have reported CVD had higher rate of annual bone loss compared to subjects who did not have any CVD. This observation indicates that targeting high-risk individuals for risk assessment is fundamental to provide the best healthcare possible to those who are the most in need. Periodic examination and assessment of periodontal health is an essential key factor for better oral health, however, it has to be more emphasized and prioritized for individuals that are more prone to the disease.BACKGROUND Following a neurological event, people's long-term health and well-being is hampered by a system that struggles to deliver person-centred communication and coordinated care and fails to harness individual and family capability to live well with the condition. We aimed to implement and evaluate a toolkit package to support these processes for people with long-term neurological conditions. METHODS This is a multi-phased study drawing on the principles of participatory research. In this pilot phase, the toolkit package was introduced to clinicians, who introduced it to clients in four neurorehabilitation settings (inpatient and community-based). Individual and focus group interviews were carried out with clients (n = 10) and clinicians (n = 9). Data were categorised by the four components of Normalisation Process Theory (NPT), and data within each component was then coded inductively. This analysis was used to inform revisions to the toolkit package and wider implementation processes. RESULTS There wa were intended to improve sense-making and minimise the cognitive barriers associated with implementation of a new intervention. CONCLUSION Understanding how supporting the client toolkit could add value to the therapeutic encounter was necessary for clinicians to invest time and perceive the worth of the toolkit package. TRIAL REGISTRATION ANZCTR ACTRN12614000537651. Registered 21 May, 2014.BACKGROUND To report a case of type III dens invaginatus associated with peri-invagination periodontitis in an immature permanent mandibular central incisor with open apex, in which only the invagination area was treated and vitality was preserved. CASE PRESENTATION A 9-year-old boy was referred complaining of pain in the mandibular left central incisor. After radiographic examination, an invagination into the pulp chamber of the tooth associated with periapical radiolucency was detected. Endodontic access was performed and the orifice was identified under a dental operating microscope. The invagination area was chemo-mechanically cleaned. After 1 week, the invagination was obturated with mineral trioxide aggregate. During the 2-year follow up period, the tooth was asymptomatic. Radiographic examination revealed significant progression of periapical healing and root development in the main root canal of the tooth. CONCLUSION Non-surgical root canal treatment of the invagination may preserve pulp vitality, and continuous root development of the tooth.BACKGROUND A persistent low inflammatory-oxidative status and the inadequacy of the antioxidant nuclear factor-E2-related factor 2 (Nrf2) have been implicated in chronic obstructive pulmonary disease (COPD) progression. Therefore this study was aimed to assess the association between lung function decline and oxidative-inflammatory markers and Nrf2 signaling pathway expression in peripheral blood mononuclear cells (PBMCs) over time. METHODS 33 mild-moderate COPD outpatients (mean age 66.9 ± 6.9 years) were age-sex matched with 37 no-COPD subjects. A clinical evaluation, blood sampling tests and a spirometry were performed at baseline and after a mean follow-up of 49.7 ± 6.9 months. RESULTS In COPD, compared to no-COPD, we found a faster lung function decline at follow-up. Although similar prevalence of smoking, hypertension, diabetes and dyslipidemia, systemic markers of inflammation (hs-CRP and white blood cells, WBCs) and oxidative stress (8-isoprostane) were significantly increased in COPD at follow-up, whaining 89.5% of its variance. CONCLUSIONS Although our results must be confirmed in larger trial they suggest that the down-regulation of Nrf2/ARE gene expression in PBMCs may be one of the determinants of FEV1 decline and of COPD progression. Therefore the future possibility to counteract Nrf2 decline in COPD patients may help in reducing the negative effects of the oxidative stress-induced progression of the disease.BACKGROUND Thyroid disorders are common in the adult German population. Little is known about guideline implementation in clinical practice and the prevalence of diagnostic procedures in ambulatory care. The study aims to investigate the use of thyroid hormone measurements, thyroid ultrasound, thyroid scintiscan and associated costs in ambulatory care at population level. METHODS Data were derived from two independent population-based cohorts of the Study of Health In Pomerania (SHIP). Ambulatory billing data from the Association of Statutory Health Insurance Physicians Mecklenburg-Vorpommern were individually linked for the period 2002-2016 with SHIP data. The main outcomes were the frequency of outpatient ultrasound, scintiscan, serum TSH level measurement, free triiodothyronine (fT3) and free thyroxine (fT4) measurement, TSH-receptor-antibodies and microsomal antibodies measurement within 1 year and 3 years prior to the study entrance of the participants. Multinomial logistic regression models were used to assess the association of age, sex, thyroid medication intake and Charlson-Comorbidity-Index with frequency of TSH measurements and ultrasound examinations.

an suggested in the literature. © The Author(s) 2020. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.BACKGROUND Models of care are needed to address physical activity, nutrition promotion and weight loss in primary care settings, especially with underserved populations who are disproportionately affected by chronic illness. Group medical visits (GMVs) are one approach that can help overcome some of the barriers to behaviour change in underserved populations, including the amount of time required to care for these patients due to socio-economic stressors and psychosocial complexities (1). GMVs have been shown to improve care in coronary artery disease and diabetes, but more evidence is needed in underserved settings. OBJECTIVE This project sought to evaluate a GMV incorporating a physical activity component in an underserved patient population, measuring biometric and motivation outcome measures. METHODS This project used a pre-post intervention study design through patient surveys at baseline and 12 weeks. We included validated motivational measures along with self-reported demographic information. A GMV intervention promoting physical activity and nutrition to promote weight loss was delivered by an interdisciplinary primary care team and community partners in a Federally Qualified Health Center in Rochester, NY. The intervention consisted of six, 2-hour sessions that occurred every other week at the clinic site. RESULTS Participants lost a significant amount of weight and maintained the weight loss at 6 months. In addition, there was a significant improvement in motivation measures. CONCLUSION This study provides preliminary evidence that our GMV model can improve weight loss and autonomous motivation in an underserved population. This project has potential for scalability and sustainability. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.CONTEXT Impaired glucose homeostasis is a common finding in pheochromocytoma (PHEO), especially with adrenergic phenotype. The possible contribution of incretin dysfunction to dysglycemia in PHEO patients has not been studied. OBJECTIVE To compare changes in pancreatic endocrine function and gut hormones' production during a liquid meal test before and one year after adrenalectomy. METHODS In a prospective study, we included 18 patients with PHEO (13 females) with adrenergic biochemical phenotype. A liquid meal test with predefined isocaloric enteral nutrition was performed to evaluate dynamic changes in pancreatic hormones and incretins. RESULTS During the meal test, insulin levels were significantly lower before adrenalectomy only in the early phase of insulin secretion, but changes in AUC did not reach statistical significance (AUC = 0.07). Plasma glucagon (AUC less then 0.01) and pancreatic polypeptide levels (AUC less then 0.01) were suppressed in comparison with the postoperative state. Impaired response to the meal was found preoperatively for GLP-1 (AUC P less then 0.05), but not GIP (AUC P = 0.21). No significant changes in insulin resistance indices were found, except for the HOMA-beta index, an indicator of the function of islet beta cells, which negatively correlated with plasma metanephrine (R = -0.66, P less then 0.01). CONCLUSIONS Our study shows suppression of pancreatic alpha and beta cell function and impaired GLP-1 secretion during a dynamic meal test in patients with PHEO, that is improved after its surgical treatment. These data demonstrate a novel and potentially significant interconnection between excessive catecholamine production and the secretion of glucoregulatory hormones. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.INTRODUCTION Post-treatment relapse is a major roadblock to stemming the global epidemic of tobacco-related illness. This article presents results from a pilot trial evaluating the feasibility and initial efficacy of Mindfulness-Based Relapse Prevention (MBRP) as an adjunct to standard relapse prevention treatment (ST) for smoking cessation. METHODS Smokers (n = 86) in the maintenance phase of treatment were randomized to receive either ST plus MBRP (MBRP) (n = 44) or ST alone (ST) (n = 42). Data were collected at baseline and at four, twelve and twenty-four week follow up points. We evaluated the feasibility of the protocol with frequency analysis, and the efficacy with both intention to treat (ITT) and complete case (CC) analyses of the effects of MBRP on abstinence. https://www.selleckchem.com/products/brd3308.html Secondary outcomes included mindfulness, craving, depression, anxiety and positive/negative affect. RESULTS High adherence suggested MBRP is acceptable and feasible. Participants in the MBRP group reported increases in mindfulness (M = -7.833, and merits further research. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Response-adaptive randomization (RAR) has recently gained popularity in clinical trials. The intent is noble minimize the number of participants randomized to inferior treatments and increase the amount of information about better treatments. Unfortunately, RAR causes many problems, including 1) bias from temporal trends, 2) inefficiency in treatment effect estimation, 3) volatility in sample size distributions that can cause a nontrivial proportion of trials to assign more patients to an inferior arm, 4) difficulty of validly analyzing results, and 5) the potential for selection bias and other issues inherent from being unblinded to ongoing results. The problems of RAR are most acute in the very setting for which RAR has been proposed, namely long duration "platform" trials and infectious disease settings where temporal trends are ubiquitous. Response-adaptive randomization can eliminate the benefits that randomization, the most powerful tool in clinical trials, provides. Use of response adaptive randomization is discouraged.

In addition, the application of externally applied lower punch vibration led to a pronounced decrease of the capping or lamination tendency and improved mechanical stability of the manufactured tablets. Janus nanoparticles (JNP) are innovative nanocarriers with an interesting pharmaceutical and cosmetic potential. They are characterized by the presence of a lipid compartment associated with an aqueous compartment delimited by a phospholipid bilayer containing phospholipids and non-ionic surfactants. The hydrodynamic diameter of JNP varies between 150 and 300 nm. The purpose of this study was to answer the following questions after cutaneous application, are JNP penetrating? If so, how deep? And in which state, intact or degraded? It was essential to understand these phenomena in order to control the rate and kinetics of diffusion of active ingredients, which can be encapsulated in this vehicle for pharmaceutical or cosmetic purposes. An innovative technique called AFM-IR, was used to elucidate the behavior of JNP after cutaneous application. This instrument, coupling atomic force microscopy and IR spectroscopy, allowing to perform chemical analysis at the nanometer scale thanks to local absorption measurements. The identification of organic molecules at the nanoscale is possible without any labelling. Before cutaneous application of JNP, the nano-structure of untreated human skin was investigated with AFM-IR. Then, in vitro human skin penetration of JNP was studied using Franz cells, and AFM-IR allowed us to perform ultra-local information investigations. The epithelial permeation of water-soluble fluorescent PAMAM dendrons based on 7H-benz[de] benzimidazo [2,1-a] isoquinoline-7-one as a fluorescent core across epithelial cell models MDCK I and MDCK II has been quantified. Hydrodynamic radii have been derived from self-diffusion coefficients obtained via pulsed-gradient spin-echo Nuclear Magnetic Resonance (PGSE-NMR). Results indicate that these dendritic molecules are molecularly disperse, non-aggregating, and only slightly larger than their parent homologues. MDCK I permeability studies across epithelial barriers show that these dendritic molecules are biocompatible with the chosen epithelial in-vitro model and can permeate across MDCK cell monolayers. Permeability is demonstrated to be a property of dendritic size and cell barrier restrictiveness indicating that paracellular mechanisms play the predominant role in the transport of these molecules. Senicapoc (SEN), a potent antisickling agent, shows poor water solubility and poor oral bioavailability. https://www.selleckchem.com/products/finerenone.html To improve the solubility and cell permeation of SEN, self-nanoemulsifying drug delivery systems (SNEDDSs) were developed. Capryol PGMC®, which showed the highest solubilization capacity, was selected as the oil. The self-emulsification ability of two surfactants, viz., Cremophor-EL® and Tween® 80, was compared. Based on a solubility study and ternary phase diagrams, three optimized nanoemulsions with droplet sizes less than 200 nm were prepared. An in vitro dissolution study demonstrated the superior performance of the SNEDDS over the free drug. During in vitro lipolysis, 80% of SEN loaded in the SNEDDS remained solubilized. An in vitro cytotoxicity study using the Caco-2 cell line indicated the safety of the formulations at 1 mg/mL. The transport of SEN-SNEDDSs across Caco-2 monolayers was enhanced 115-fold (p  less then  0.01) compared to that of the free drug. According to these results, SNEDDS formulations could be promising tools for the oral delivery of SEN. Brain delivery of nanoparticles and macromolecular drugs depends on blood-brain barrier (BBB)-permeable carriers. In this study, we searched for cyclic heptapeptides facilitating BBB permeation of M13 phages by phage library screening using a transcellular permeability assay with hCMEC/D3 cell monolayers, a human BBB model. The M13 phage, which is larger than macromolecular drugs and nanoparticles, served as a model macromolecule. The screen identified cyclic heptapeptide SLSHSPQ (SLS) as a human BBB-permeable peptide. The SLS-displaying phage (SLS-phage) exhibited improved permeation across the cell monolayer of monkey and rat BBB co-culture models. The SLS-phage internalized into hCMEC/D3 cells via macropinocytosis and externalized via the exosome excretion pathway. SLS-phage distribution into brain parenchyma was observed in mice after intravenous administration. Moreover, liposome permeated across the BBB as cyclic SLS peptide conjugates. In conclusion, the cyclic SLS heptapeptide is a novel carrier candidate for brain delivery of macromolecular drugs and nanoparticles. The rapid dissemination of life-threatening multidrug-resistant bacterial pathogens calls for the development of new antibacterial agents and alternative strategies. The virulence factor secreted by bacteria plays a crucial role in the sophisticated processes during infections. Inspired by the unique capacity of many bacteria inducing clotting of plasma to initiate colonization, we propose a programmable antibiotic delivery system for precision therapy using methicillin-resistant S. aureus (MRSA) as a model. Coagulase utilized by MRSA to directly cleave fibrinogen into fibrin, is an ideal target not only for tracking bacterial status but for triggering the collapse of fibrinogen functionalized porous microspheres. Subsequently, staphylokinase, another virulence factor of MRSA, catalyzed hydrolysis of fibrin to further release the encapsulated antibiotics from microspheres. Our sequential triggered-release system exhibits high selectivity to distinguish live or dead MRSA from other pathogenic bacteria. Furthermore, such programmable microspheres clear 99% MRSA in 4 h, and show increased efficiency in a wound healing model in rats. Our study provides a programmable drug delivery system to precisely target bacterial pathogens using their intrinsic enzymatic cascades. This programmable platform with reduced selective stress of antibiotics on microbiota sheds light on the potential therapy for future clinical applications. Liver fibrosis leads to over one million deaths annually worldwide. Hepatic stellate cells (HSCs) have been identified as the main executors of liver fibrosis. Unfortunately, no drug has yet been approved for clinical use against liver fibrosis, largely because the tested drugs have been unable to access HSCs and efficiently remove the collagen accumulation involved in fibrogenesis. Here, we designed an efficient HSC-targeting lipid delivery system that carried dual siRNAs intended to both inhibit collagen synthesis and promote collagen degradation, with the goal of realizing enhanced anti-liver fibrosis by bidirectional regulation of collagen accumulation. The delivery system was constructed by using amphiphilic cationic hyperbranched lipoids (C15-PA) for siRNA complexation and helper lipoids (cholesterol-polyethylene glycol-vitamin A, Chol-PEG-VA) for HSCs targeting. The generated vitamin A-decorated and hyperbranched lipoid-based lipid nanoparticles (VLNPs) showed excellent gene-binding ability and transfection efficiency, and enhanced the delivery of siRNAs to HSCs.