Miracle-dz/UniFAR-FTUs huggingface dataset:
TGF-β1 protects intestinal integrity and influences Smads and MAPK signal pathways in IPEC-J2 after TNF-α challenge

The aim of this study was to investigate the protective effects of TGF-β1 on intestinal epithelial barrier, as well as canonical Smad and MAPK signal pathways involved in these protection processes by a IPEC-J2 model stimulated with TNF-α. IPEC-J2 monolayers were treated without or with TNF-α in the absence or presence of TGF-β1. The results showed that TGF-β1 pretreatment ameliorated TNF-α-induced intestinal epithelial barrier disturbances as indicated by decrease of transepithelial electrical resistance (TER) and increase of paracellular permeability. TGF-β1 also dramatically alleviated TNF-α-induced alteration of TJ proteins ZO-1 and occludin. Moreover, TGF-β1 pretreatment increased TβRII protein expression in IPEC-J2 monolayers challenged with TNF-α. In addition, a significant increase of Smad4 and Smad7 mRNA was also observed in the TGF-β1 pretreatment after TNF-α challenge compared with the control group. Furthermore, TGF-β1 pretreatment enhanced smad2 protein activation. These results indicated that the canonical Smad signaling pathway was activated by TGF-β1 pretreatment. Finally, TGF-β1 pretreatment decreased the ratios of the phosphorylated to total JNK and p38 (p-JNK/JNK and p-p38/p38) and increased the ratio of ERK (p-ERK/ERK). Anti-TGF-β1 Abs reduced these TGF-β1 effects. These results indicated that TGF-β1 protects intestinal integrity and influences Smad and MAPK signal pathways in IPEC-J2 after TNF-α challenge.
Lack of protection of N-acetylcysteine (NAC) in acute renal failure related to elective aortic aneurysm repair-a randomized controlled trial.

BACKGROUND N-acetylcysteine (NAC) is an antioxidant drug largely tested in different clinical situations. Recently, NAC has been employed with variable success in the prevention of radiocontrast nephropathy. Since aortic aneurysm surgical repair is a condition that is frequently accompanied by acute renal failure (ARF), we sought to investigate whether NAC has any role in preventing ARF in this scenario. METHODS A randomized, placebo-controlled, double-blind trial with the following inclusion criteria: elective aortic aneurysm repair in patients with stable renal function. The groups were randomly matched for age, gender, presence of diabetes and pre-existent renal failure. NAC or placebo (control) was administered p.o. for 24 h before operation and maintained i.v. for 48 h after operation. The dose of NAC was 1200 mg b.i. d. the day before surgery and 600 mg b.i. d. after. The primary endpoint was the development of ARF up to the third post-operative day, defined as an increase in SCr > or = 25% from baseline. Secondary endpoints were: ICU mortality and ICU length of stay. RESULTS Forty-two patients (n = 18 for NAC group and n = 24 for control) were studied. The baseline SCr and calculated GFR did not differ between the groups (1.19 +/- 0.33 vs 1.37 +/- 0.49 mg/dl; and 64.6 +/- 26.22 vs 65.7 +/- 28.32 ml/min, NAC vs control, respectively, P = 0.17 and P = 0.90). Need for suprarenal aortic cross-clamping and its duration, occurrence of major bleeding, intra-operative hypotension and the post-operative peak of CPK did not differ between NAC and control groups. The overall incidence of ARF in the study was 36% (13/36), but it was not significantly different between groups (7/14, 50% in NAC vs 6/22, 27.3% in control, P = 0.16). The overall mortality was 23% (10/42) and was not different (P = 0.209) in NAC group (33.3%) when compared with control (16.7%), the same occurring with the length of ICU stay (2.93 +/- 1.53 vs 2.52 +/- 1.36 days, P = 0.40). CONCLUSION This study suggests that the putative beneficial effects of NAC on radiocontrast nephropathy might not be applicable to other situations, such as ARF associated with elective aortic aneurysm repair.
Implant Site Under-Preparation to Compensate the Remodeling of an Autologous Bone Block Graft

AbstractAutologous bone block grafting is an efficient technique to thicken an atrophied residual alveolar ridge. A variable degree of resorption, however, occurs due to graft remodeling. In this study, we hypothesize that under-preparation of implant socket would permit the dental implant to act as a bone expansor and thus compensate for the contraction in the augmented ridge width. For that reason, 10 patients received an autologous bone block graft that was obtained from the ramus of the mandible. Residual alveolar ridge width was measured on CBCT scans obtained before surgery (T0), after 2 months of healing (T1), after 4 months of healing just before implant placement (T2), and after 4 months of implant placement (T3). The thickness of the alveolar ridge was initially increased from 2.5 ± 1.4 to 6.1 ± 2.0 mm. Before implant insertion, this width was decreased to 5.6 ± 2.1 mm. The last measurement after implant insertion indicated an increase to 7.3 ± 1.8 mm. In comparison to the measurements at T1, a loss of about 0.5 mm of the augmented width occurred. But, this loss was compensated by an increment of 1.2 mm at T3 (after implant insertion) if related to the measurement at T1. Neither gingival dehiscence nor block exposure was observed. Within the limitations of this study, under-preparation of implant socket could make the ridge expansion possible during implant insertion and thus to compensate the remodeling of autologous bone block graft.
Perspective on Translating Biomaterials Into Glioma Therapy: Lessons From in vitro Models

Glioblastoma (GBM) is the most common and malignant form of brain cancer. Even with aggressive standard of care, GBM almost always recurs because its diffuse, infiltrative nature makes these tumors difficult to treat. The use of biomaterials is one strategy that has been, and is being, employed to study and overcome recurrence. Biomaterials have been used in GBM in two ways: in vitro as mediums in which to model the tumor microenvironment, and in vivo to sustain release of cytotoxic therapeutics. In vitro systems are a useful platform for studying the effects of drugs and tissue-level effectors on tumor cells in a physiologically relevant context. These systems have aided examination of how glioma cells respond to a variety of natural, synthetic, and semi-synthetic biomaterials with varying substrate properties, biochemical factor presentations, and non-malignant parenchymal cell compositions in both 2D and 3D environments. The current in vivo paradigm is completely different, however. Polymeric implants are simply used to line the post-surgical resection cavities and deliver secondary therapies, offering moderate impacts on survival. Instead, perhaps we can use the data generated from in vitro systems to design novel biomaterial-based treatments for GBM akin to a tissue engineering approach. Here we offer our perspective on the topic, summarizing how biomaterials have been used to identify facets of glioma biology in vitro and discussing the elements that show promise for translating these systems in vivo as new therapies for GBM.
[A prospective study on body mass index and mortality].

OBJECTIVE To assess the relationship between body mass index (BMI, weight in kilograms divided by the square of height in meters) and both all-causes mortality and mortality from specific cause. METHODS Cardiovascular disease (CVD) risk factors were studied in 1982 - 1985 on more than 30 thousands participants aged 35 - 59 from 10 Chinese populations. 30 560 participants (15 723 for men, 148 837 for women) without known myocardial infraction, stroke or cancer was followed from 1999 to 2000. All-causes of death were documented. RESULTS Three thousand two hundred and twelve death cases occurred during follow-up of average 15.2 years, including 676 CVD (coronary heart disease and stroke) deaths, 1 281 cancer deaths and 1 255 deaths for other reasons. Cox proportional hazards model adjusting age and gender showed that the relative risks of all causes of death in groups of low BMI (BMI < 18.5), normal BMI (BMI from 18.5 to 23.9), overweight (BMI from 24 to 27.9) and obesity (BMI >/= 28) which were defined according to the strata of BMI for Chinese were 1.21 (95% CI: 1.10 - 1.33), 1.00, 0.91 (95% CI: 0.82 - 1.01) and 1.12 (95% CI: 0.93 - 1.37), respectively ("U" shaped relation). The relative risk of low BMI group (RR = 1.01, 95% CI: 0.84 - 1.21) was not significant different and the relative risk of obesity significantly increased (RR = 1.36, 95% CI: 1.04 - 1.80) while the lowest relative risk was in normal BMI group. The relative risks increased for CVD death, but decreased for cancer death with increased levels of BMI and a "U" shaped relationship was found between BMI groups and mortality for other reasons, which remained after excluding the early death and smokers. CONCLUSION BMI in normal level was not only related to low risk of all causes of death, but also with relative low risk of CVD, cancer and other deaths. Data were important to public health.
ABO-incompatible hearts for infant transplantation

Purpose of reviewThe practice of offering ABO-incompatible (ABOi) heart transplantation during infancy was initiated based on the rationale that infants are at the highest risk of dying while waiting for a transplant, yet are at low risk of hyperacute antibody-mediated rejection due to immunologic immaturity. Since the first report of intentional ABOi heart transplantation a decade ago, its success has been corroborated in numerous reports and the practice has been widely adopted. This review summarizes clinical results in reports of ABOi transplantation and the evolution of ABOi listing strategies, as well as evidence of immune tolerance after ABOi transplantation. Recent findingsRecent reports have documented comparable midterm and long-term clinical outcomes in ABOi and ABO-compatible (ABOc) heart transplant recipients in terms of survival and posttransplant complications. Despite successful outcomes, however, there are obstacles to widespread implementation of ABOi transplantation in the USA and in some European centers. The notable deficiency in development of antibody production to donor A/B antigens following ABOi transplantation described in early reports has been corroborated, with some exceptions. Potential advantages of ABOi transplantation are emerging as well as innovative strategies that may allow ABOi heart transplantation beyond the age of infancy. SummaryABOi heart transplantation is one example in which immunologic immaturity has been exploited to the advantage of pediatric transplant recipients. In-depth exploration of transplant-related immunobiology in the young may reveal further opportunities.
Is the Thoracolumbar Injury Classification and Severity Score (TLICS) Superior to the AO Thoracolumbar Injury Classification System for Guiding the Surgical Management of Unstable Thoracolumbar Burst Fractures without Neurological Deficit?

AIM To determine whether the Thoracolumbar Injury Classification and Severity Score (TLICS) and the Arbeitsgemeinschaft für Osteosynthesefragen (AO) Spine Thoracolumbar Injury Classification System have any superiority to each other regarding the reliability of their recommendations in the surgical management of unstable thoracolumbar burst fractures. MATERIAL AND METHODS Fifty-five consecutive patients with thoracolumbar burst fractures undergoing instrumentation between 2010 and 2015 were analyzed retrospectively. TLICS and AO systems were compared based on patients" American Spinal Injury Association (ASIA) scores and they were analyzed for their safety and reliability. RESULTS A total of 55 patients were studied. Neurological deficits were detected in 18 patients and the remaining 37 patients had normal neurological functions. All the patients with neurological deficits received > 4 points according to TLICS. There were 14 patients with incomplete spinal cord injury and all of them received > 4 points according to TLICS (p < 0.01). On the other hand; 8 of these 14 patients received 4 points according to the AO system. None of the 37 patients without neurological deficit received < 4 points of TLICS whereas 18 of these 37 patients received 3 AO points, to whom AO recommends conservative treatment despite the fact that they had unstable burst fractures (p < 0.01). CONCLUSION Recommendations of TLICS might be more reliable than those of AO particularly for guiding the surgical management of unstable thoracolumbar burst fractures without neurological deficit. However, this conclusion needs to be verified with further multicenter prospective studies.
The MicroRNA390/TRANS-ACTING SHORT INTERFERING RNA3 Module Mediates Lateral Root Growth under Salt Stress via the Auxin Pathway1

The miR390/TAS3/ARF4 module is involved in the regulation of lateral root development under salt stress in poplar by auxin signaling. Salt-induced developmental plasticity in a plant root system strongly depends on auxin signaling. However, the molecular events underlying this process are poorly understood. MicroRNA390 (miR390), trans-actin small interfering RNAs (tasiRNAs), and AUXIN RESPONSE FACTORs (ARFs) form a regulatory module involved in controlling lateral root (LR) growth. Here, we found that miR390 expression was strongly induced by exposure to salt during LR formation in poplar (Populus spp.) plants. miR390 overexpression stimulated LR development and increased salt tolerance, whereas miR390 knockdown caused by a short tandem target mimic repressed LR growth and compromised salt resistance. ARF3.1, ARF3.2, and ARF4 expression was inhibited significantly by the presence of salt, and transcript abundance was decreased dramatically in the miR390-overexpressing line but increased in the miR390-knockdown line. Constitutive expression of ARF4m harboring mutated trans-acting small interfering ARF-binding sites removed the salt resistance of the miR390 overexpressors. miR390 positively regulated auxin signaling in LRs subjected to salt, but ARF4 inhibited auxin signaling. Salinity stabilized the poplar Aux/IAA repressor INDOLE-3-ACETIC ACID17.1, and overexpression of an auxin/salt-resistant form of this repressor suppressed LR growth in miR390-overexpressing and ARF4-RNA interfering lines in the presence of salt. Thus, the miR390/TAS3/ARFs module is a key regulator, via modulating the auxin pathway, of LR growth in poplar subjected to salt stress.
A Comparative Study Between Total Contact Cast and Pressure-Relieving Ankle Foot Orthosis in Diabetic Neuropathic Foot Ulcers

Background: Off-loading of the ulcer area is extremely important for the healing of plantar ulcers. Off-loading with total contact cast (TCC) may be superior to other off-loading strategies studied so far, but practical limitations can dissuade clinicians from using this modality. This study was conducted to evaluate the efficacy of TCC compared with that of a pressure-relieving ankle foot orthosis (PRAFO) in healing of diabetic neuropathic foot ulcers and their effect on gait parameters. Methods: Thirty adult diabetic patients attending the foot clinic with neuropathic plantar ulcers irrespective of sex, age, duration and type of diabetes were randomly assigned to 1 of 2 off-loading modalities (TCC and PRAFO). Main outcome measures were ulcer healing after 4 weeks of randomization and effect of each of the modalities on various gait parameters. Results: The percentage reduction of the ulcer surface area at 4 weeks from baseline was 75.75 ± 9.25 with TCC and 34.72 ± 13.07 with PRAFO, which was significantly different (P < .001). The results of this study however, showed that most of the gait parameters were better with PRAFO than with TCC. Conclusions: This study comprehensively evaluated the well known advantages and disadvantages of a removable (PRAFO) and a nonremovable device (TCC) in the treatment of diabetic neuropathic foot ulcer. Further studies are needed involving larger subjects and using 3D gait analysis to collect more accurate data on gait parameters and wound healing with different off-loading devices.
Cortisol secretion, bone health, and bone loss: a cross-sectional and prospective study in normal non-osteoporotic women in the early postmenopausal period.

OBJECTIVE The aim of the study was to evaluate the relationship between cortisol secretion, bone health, and bone loss in a cohort of normal women in the early postmenopausal period. METHODS We measured lumbar and hip bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) and heel ultrasound parameters in 82 healthy, nonosteoporotic (lumbar T-score ≥-2.0) women (median age 52.5 years, range 42-61). These women were examined in two sessions, 1 year apart, in the early postmenopausal period (onset of menopause between 6 and 60 months). Parameters of the hypothalamic-pituitary-adrenal (HPA) axis function were morning serum cortisol, morning and midnight salivary cortisol, 24-h urinary free cortisol (UFC), serum cortisol after 0.5 and 1 mg overnight dexamethasone, and DHEA-S. RESULTS In multiple regression analyses, the following significant inverse correlations were found: i) lumbar BMD and either 24-h UFC (P<0.005) or morning serum cortisol (P<0.05), ii) total femur and femoral neck BMD with morning serum cortisol (P=0.05 and P<0.05), and iii) heel ultrasound stiffness index and midnight salivary cortisol (P<0.005). The annual rate of change in lumbar and femoral BMD did not correlate with any of the above-mentioned hormonal variables. No difference was found in the parameters of HPA axis function in slow (loss of BMD <1%) vs fast (loss of BMD ≥3%) bone losers. CONCLUSIONS HPA axis may contribute to postmenopausal bone health, but differences in cortisol secretion do not influence the differential rate of bone loss between slow and fast bone losers in the early postmenopausal period, at least in healthy women.
Bio-Guided Isolation of the Cytotoxic Terpenoids from the Roots of Euphorbia kansui against Human Normal Cell Lines L-O2 and GES-1

The dried roots of Euphorbia kansui (kansui) have been used for centuries in China as a herbal medicine for edema, ascites, and asthma. The 95% ethanol extract showed a significant inhibition of cell proliferation against human normal cell lines L-O2 and GES-1. Bioassay-guided separation of the 95% ethanol extract from the roots of E. kansui led to the isolation of 12 diverse terpenoids whose structures were identified by 1H, 13C NMR spectroscopy and ESI-MS as kansuinine A (1), kansuinine B (2), kansuinine C (3), kansuiphorin C (4), 3-O-(2′E,4′Z-decadienoyl)-20-O-acetylingenol (5), 3-O-(2′E,4′Edecadienoyl)-20-O-acetylingenol (6), 3-O-(2′E,4′Z-decadienoyl)-20-deoxyingenol (7), 3-O-benzoyl-20-deoxyingenol (8), 5-O-benzoyl-20-deoxyingenol (9), kansenone (10), epi-kansenone (11), euphol (12). All these 12 terpernoids were evaluated in vitro for cytotoxicity on L-O2 and GES-1 cell lines. Most ingenane-type diterpenoids and 8-ene-7-one triterpenoids (5–11) exhibited a relatively lower IC50 value; therefore, these compounds had stronger cytotoxicity against human normal cell lines L-O2 and GES-1 with dose-dependent relationships. These results will be significantly helpful to reveal the mechanism of toxicity of kansui and to effectively guide safer clinical application of this herb.
[Toxocariasis: clinical and laboratory features in 54 patients].

OBJECTIVE To describe the clinical and laboratory findings in children with toxocariasis. METHODS Fifty-four children with reactive serology to Toxocara determined by ELISA were prospectively identified between January 1998 and September 2000. The patients were divided into three groups: asymptomatic children (n 24), those with visceral larva migrans (n 16) and those with ocular larva migrans (n 14). Age, serology titers, and eosinophil count at diagnosis were compared among the groups. The patients received treatment with albendazole 10-15 mg/kg/day for 15 days or thiabendazole 25 mg/kg/day in two series of 7 days. RESULTS The clinical features were as follows: 24 children (44.4 %) were asymptomatic, pneumonitis was found in 9 (16.7 %), hepatomegaly in 6 (11.1 %), acute posterior uveitis in 5 (9.3 %), strabismus in 5 (9.3 %), leukocoria in 4 (7.4 %), fever in 3 (5.6 %). There was 1 case of keratitis, 1 of cataracts, 1 of myocarditis and 1 case of pneumonia with pleural effusion. Some patients showed more than one clinical feature. Four children experienced loss of vision in the affected eye. No differences in age or serology titers were found among the groups. Eosinophil count was lower in the group with ocular larva migrans than in the other groups (p < 0.001). Children with active disease showed clinical improvement and a 70.4 % decrease in eosinophilic count one year after treatment. Serological titers showed an unpredictable pattern during the follow-up. CONCLUSIONS Most of the infected children were asymptomatic. In the post-treatment follow-up, clinical improvement and a decrease in eosinophilic count were observed. Further studies are needed to evaluate the efficacy of treatment, especially in asymptomatic children.
The behavioral spectrum of tic disorders: A community-based study

BackgroundTourette syndrome (TS) and related tic disorders are commonly associated with obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD). It has been argued, however, that any observed association between TS and these and other psychopathologies may be due to ascertainment bias in that individuals with multiple problems are more likely to be referred for medical evaluation. MethodsIn order to overcome the potential confounding by ascertainment bias, the authors conducted a community-based study of school children using direct interviews to determine the prevalence of tic disorders and any comorbid psychopathology. A standard psychiatric interview and standardized rating scales were utilized to diagnose childhood behavioral disorders. ResultsOf the 1,596 children interviewed, 339 were identified as having tics. The following psychopathologies were found more commonly (p < 0.05) in the children with tics: OCD, ADHD, separation anxiety, overanxious disorder, simple phobia, social phobia, agoraphobia, mania, major depression, and oppositional defiant behavior. ConclusionThe behavioral spectrum of tic disorders includes OCD, other anxiety disorders, a mood disorder, and attention-deficit and disruptive behavior disorders.
Prenatal exposure to TAK242 affects the childhood autism in offspring in animal models of autism spectrum disorder

Objective(s): To evaluate whether prenatal exposure to TAK242 affects childhood autism in the offspring in animal models of autism spectrum disorder (ASD). Materials and Methods: The pregnant rats were pseudo-randomly divided into three groups, the ASD model group, the TAK242 treatment group, and the control group. The ASD model was constructed by injecting IP with LPS. The blood samples from 1-month-old offspring were collected for cytokine evaluation and the social interaction test was used in the offspring of ASD rats. Rats were killed and the hippocampus, cerebral cortex, and cerebellum were used for the immunohistochemical study. Results: As compared to the control, the levels of IFN-γ, IL-1β, IL-2, and IL-6 were significantly increased (P<0.05), and the levels of IL-4, IL-10, and TGF-β were significantly decreased (P <0.05) in the offspring of ASD rats; whereas those cytokines were significantly reversed after prenatal exposure to TAK242 (P<0.05). The hesitation time and none-social interaction time were significantly increased as compared to the control (P<0.05); whereas they were both decreased after prenatal exposure to TAK242 (P<0.05). This was contrary to the social interaction time (P<0.05). The expression of GFAP and IBA1 in the cortex, hippocampus, and cerebellum were stronger in the LPS group as compared to control group, and this effect was reversed after prenatal exposure to TAK242. Conclusion: Prenatal exposure to TAK242 affects serum cytokines levels and the social interaction time in rat offspring in animal models of ASD.