Association of peroxisome proliferator-activated receptor and Hsp72.
In an effort to understand the relationship between a 72-kDa heat shock protein (Hsp72) and peroxisome proliferator-activated receptors (PPARs), we have characterized their interaction using clofibric acid-Sepharose chromatography and co-immunoprecipitation with antisera raised against either rat PPAR (rPPAR) or Hsp72. First, we observed that both rPPAR and Hsp72 elute in a clofibrate-dependent manner from the clofibric acid-Sepharose matrix. Second, we found that immunoprecipitation of either protein from solution resulted in the precipitation of the other. This result was obtained from rat liver cytosol, from Spodoptera frugiperda (Sf9) insect cells expressing rPPAR, and from reticulocyte lysate rPPAR expression systems. These results suggest that Hsp72 and rPPAR form a complex in vivo and that Hsp72 may play a role in the folding, subcellular localization, and/or signaling pathway of PPARs.


Hydrogen sulfide-linked sulfhydration of NF-κB mediates its antiapoptotic actions.
Nuclear factor κB (NF-κB) is an antiapoptotic transcription factor. We show that the antiapoptotic actions of NF-κB are mediated by hydrogen sulfide (H(2)S) synthesized by cystathionine gamma-lyase (CSE). TNF-α treatment triples H(2)S generation by stimulating binding of SP1 to the CSE promoter. H(2)S generated by CSE stimulates DNA binding and gene activation of NF-κB, processes that are abolished in CSE-deleted mice. As CSE deletion leads to decreased glutathione levels, resultant oxidative stress may contribute to alterations in CSE mutant mice. H(2)S acts by sulfhydrating the p65 subunit of NF-κB at cysteine-38, which promotes its binding to the coactivator ribosomal protein S3 (RPS3). Sulfhydration of p65 predominates early after TNF-α treatment, then declines and is succeeded by a reciprocal enhancement of p65 nitrosylation. In CSE mutant mice, antiapoptotic influences of NF-κB are markedly diminished. Thus, sulfhydration of NF-κB appears to be a physiologic determinant of its antiapoptotic transcriptional activity.


High-intensity physical activity is not associated with better cognition in the elder: evidence from the China Health and Retirement Longitudinal Study.
To evaluate the association of physical activity (PA) intensity with cognitive performance at baseline and during follow-up. A total of 4039 participants aged 45 years or above from the China Health and Retirement Longitudinal Study were enrolled in visit 1 (2011-2012) and followed for cognitive function in visit 2 (2013-2014), visit 3 (2015-2016), and visit 4 (2017-2018). We analyzed the association of PA intensity with global cognition, episodic memory, and mental intactness at baseline using adjusted regression methods and evaluated the long-term effect of PA intensity using multiple measures of cognition scores by mixed effect model. In cross-sectional analysis, mild and moderate PA, rather than vigorous PA, was associated with better cognitive performance. The results remained consistent in multiple sensitivity analyses. During the follow-up, participant with mild PA had a 0.56 (95% CI 0.12-0.99) higher global cognition, 0.23 (95% CI 0.01-0.46) higher episodic memory, and 0.33 (95% CI 0.01-0.64) higher mental intactness, while those with moderate PA had a 0.74 (95% CI 0.32-1.17) higher global score, 0.32 (95% CI 0.09-0.54) higher episodic memory, and 0.43 (95% CI 0.12-0.74) higher mental intactness, compared with individuals without PA. Vigorous PA was not beneficial to the long-term cognitive performance. Our study indicates that mild and moderate PA could improve cognitive performance, rather than the vigorous activity. The targeted intensity of PA might be more effective to achieve the greatest cognition improvement considering age and depressive status.


Mefunidone ameliorates lipopolysaccharide-induced acute lung injury through inhibiting MAPK signaling pathway and enhancing Nrf2 pathway.
Acute lung injury (ALI) is a life-threatening disease which has high mortality and lacks effective pharmacological treatments. Excessive inflammation and oxidative stress are the key pathogenesis of ALI. Mefunidone (MFD), a novel small molecule compound, displayed anti-inflammation and anti-oxidative stress effects on streptozocin (STZ) and db/db mice in our previous studies. In this study, we aimed to investigate the effects of MFD on lipopolysaccharide (LPS)-induced ALI and explore the potential molecular mechanisms. We investigated the effects of MFD on LPS-induced ALI mouse model and LPS-stimulated immortalized mouse bone marrow-derived macrophages (iBMDMs). MFD could alleviate pulmonary structure disorder and attenuate pulmonary neutrophils infiltration induced by LPS. MFD could also decreased proinflammatory cytokines release and reduce reactive oxygen species (ROS) generation stimulated by LPS. Further, MFD could significantly reduce LPS-induced phosphorylation levels of mitogen-activated protein kinase (MAPK), increase expression of nuclear factor-erythroid 2 related factor 2 (Nrf2) and restore the expressions of antioxidant enzymes. Our results firstly supported that MFD effectively protected LPS-induced ALI against inflammation and oxidative stress through inhibiting MAPK signaling pathway and activating Nrf2 pathway.


[Parry-Romberg syndrome: communication disorders in a 12-year old boy].
A case of a 12-year-old boy with Parry-Romberg syndrome was presented. Speech and hearing disorders impairing communicative process and abnormalities in the ENT examination, ultrasonography of parotid salivary glands, radiological changes of sella turcica were particularly considered.


Nucleotide sequence analysis of the C.AKR Lyt-2a gene: structural polymorphism in alleles encoding the Lyt-2.1 T-cell surface alloantigen.
The Lyt-2a allele of the C.AKR strain of mice (genotype Lyt-2a, Lyt-3a) was cloned, and its complete nucleotide sequence as well as that of 2 kb of 5' flanking DNA was determined. The sequence was compared with the partial sequence of the Lyt-2a allele of DBA/2 (genotype Lyt-2a, Lyt-3b) and the nearly complete sequence of the B10.CAS2 Lyt-2b allele reported by Liaw and coworkers (1986). The coding regions of the two Lyt-2a alleles differ from each other by two nucleotide substitutions in the three exons over which they could be compared, resulting in two amino acid substitutions in the leader and transmembrane segments. The coding region of the C.AKR Lyt-2a allele differs from the Lyt-2b allele by two nucleotide substitutions in the extracellular V-like domain, one of which is silent and the second of which leads to substitution of valine for methionine at amino acid position 78 giving rise to the Lyt-2.1 allotypic specificity. The coding region of the DBA/2 Lyt-2a allele shares with C.AKR the allotypic substitution at position 78 and differs from Lyt-2b by three additional nucleotide substitutions in the coding regions, two of which lead to amino acid substitutions in the leader and transmembrane segments. It would therefore appear that the Lyt-2 alleles of the three strains analyzed are distinct, and the nomenclature Lyt-2a1 and Lyt-2a2 is suggested to distinguish the alleles of C.AKR and DBA/2, respectively. These alleles share a common difference from the Lyt-2b gene product at position 78, and since the amino acid substitutions which distinguish them from each other are in the leader and transmembrane segments, their mature Lyt-2 gene products appear antigenically identical.


Result of the Physiologic Pacing Registry, an international multicenter prospective observational study of conduction system pacing.
Conduction system pacing (CSP), including both left bundle branch area pacing (LBBAP) and His-bundle pacing (HBP) has been proposed as an alternative therapy option for patients with indication for cardiac pacing to treat bradycardia or heart failure. The purpose of this study was to evaluate implant success, safety, and electrical performances of HBP and LBBAP in the multinational Physiological Pacing Registry. The international prospective observational registry included 44 sites from 16 countries globally between November 2018 and May 2021. Of 870 subjects enrolled, CSP lead implantation was attempted in 849 patients. Subjects with successful CSP lead implantation were followed for 6 months (5 ± 2 months). CSP lead implantation was successful in 768 patients (90.4%). Implant success was 95.2% (239/251) for LBBAP and 88.5% (529/598) for HBP (P = .002). Procedural duration and fluoroscopy duration were comparable between LBBAP and HBP (P = .537). Capture threshold at implant was 0.69 ± 0.39 V at 0.46 ± 0.15 ms in LBBAP and 1.44 ± 1.03 V at 0.71 ± 0.33 ms in HBP (P <.001). Capture threshold at 6 months was 0.79 ± 0.33 V at 0.44 ± 0.13 ms in LBBAP and 1.59 ± 0.97 V at 0.67 ± 0.31 ms in HBP (P <.001). Pacing threshold rise ≥1 V was observed at 6 months in 3 of 208 (1.4%) of LBBAP and 55 of 418 (13.2%) of HBP (P <.001). Serious adverse events related to implant procedure or CSP lead occurred in 5 of 251 (2.0%) with LBBAP and 25 of 598 (4.2%) with HBP (P = .115). This large prospective multicenter study demonstrates that CSP is technically feasible in most patients with relatively higher implant success and suggests that, with current technology, LBBAP may have better pacing parameters than HBP.


Epidemiology of malignant cutaneous granular cell tumors: A US population-based cohort analysis using the Surveillance, Epidemiology, and End Results (SEER) database.
Malignant cutaneous granular cell tumors (mcGCTs) are rare and associated with substantial morbidity and mortality. The literature includes single-institution studies. To examine the incidence, secondary malignancies, treatment, overall survival, and disease-specific survival (DSS) of patients with mcGCT. A population-based cohort analysis was conducted in the Surveillance, Epidemiology, and End Results database from 1973 to 2013 for patients with a diagnosis of mcGCT. Risk-adjusted associations between overall survival/DSS and patient characteristics and treatment modalities were assessed by Cox proportional hazard regression. Quantile regression was used to determine median survival times. The 5-year DSS rate was 62.8%. Patients demonstrated an increased risk for renal and pancreatic cancers. In risk-adjusted models, male sex (hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.06-0.82; P = .02), advanced cancer stage (HR, 2.29; 95% CI, 1.40-3.72; P < .01), and surgical resection (HR, 0.06; 95% CI, 0.01-0.59; P = .02) predicted DSS. Median survival time in years increased for males (1.39), earlier stage (0.60), and surgical intervention (5.34). Absent or incorrect reporting in retrospective Surveillance, Epidemiology, and End Results data is possible. The database is more likely to include academic centers. Some subanalyses may be underpowered because of the limited sample size for a rare cancer. Our study presents an in-depth assessment of factors that identify high-risk patients. Residency in a nonmetro area, black race, female sex, and no surgical resection were each associated with poorer DSS.


Graphene-based biomimetic materials targeting urine metabolite as potential cancer biomarker: application over different conductive materials for potentiometric transduction.
This works presents a novel surface Smart Polymer Antibody Material (SPAM) for Carnitine (CRT, a potential biomarker of ovarian cancer), tested for the first time as ionophore in potentiometric electrodes of unconventional configuration. The SPAM material consisted of a 3D polymeric network created by surface imprinting on graphene layers. The polymer was obtained by radical polymerization of (vinylbenzyl)trimethylammonium chloride and 4-styrenesulfonic acid (signaling the binding sites), and vinyl pivalate and ethylene glycol dimethacrylate (surroundings). Non-imprinted material (NIM) was prepared as control, by excluding the template from the procedure. These materials were then used to produce several plasticized PVC membranes, testing the relevance of including the SPAM as ionophore, and the need for a charged lipophilic additive. The membranes were casted over solid conductive supports of graphite or ITO/FTO. The effect of pH upon the potentiometric response was evaluated for different pHs (2-9) with different buffer compositions. Overall, the best performance was achieved for membranes with SPAM ionophore, having a cationic lipophilic additive and tested in HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) buffer, pH 5.1. Better slopes were achieved when the membrane was casted on conductive glass (-57.4mV/decade), while the best detection limits were obtained for graphite-based conductive supports (3.6×10-5mol/L). Good selectivity was observed against BSA, ascorbic acid, glucose, creatinine and urea, tested for concentrations up to their normal physiologic levels in urine. The application of the devices to the analysis of spiked samples showed recoveries ranging from 91% (± 6.8%) to 118% (± 11.2%). Overall, the combination of the SPAM sensory material with a suitable selective membrane composition and electrode design has lead to a promising tool for point-of-care applications.


A case report of image-based dosimetry of bone metastases with Alpharadin ((223)Ra-dichloride) therapy: inter-fraction variability of absorbed dose and follow-up.
A 70-year-old man affected by bone metastases from castration resistant prostate cancer underwent Alpharadin ((223)Ra-dichloride) therapy (6 administrations of 50 kBq per kg i.v., once every 4 weeks). The inter-fraction variability of the absorbed dose to lesions was evaluated for four injections. Dosimetric assessments were performed following the MIRD approach and a recently published methodology. The mean absorbed dose and standard deviation for 4 lesions [mean (σ %)] were: 434 mGy (15%) and 516 mGy (21%) for the right and left humeral head, 1205 mGy (14%) and 781 mGy (8%) for the right and left glenoid. The estimated total absorbed dose after the whole treatment, considering also the relative-biological effectiveness of alpha particles (RBE = 5), yielded a D RBE range of 13-36 Gy. A good correlation between (99m)Tc and (223)Ra uptake was obtained (R (2) = 0.7613). The tumour-non-tumour (TNT) ratio of 8 lesions (those above, plus 4 additional), monitored by six (99m)Tc-MDP bone scans over a period of about 10 months, evidenced a TNT reduction in two lesions (-42 and -48 %), but in most lesions the TNT remained fairly constant, evidencing that (223)Ra-dichloride therapy tends to prevent further progression of osseous disease, leading to chronicity of the metastatic status.


Comparative effectiveness of hyaluronic acid, platelet-rich plasma, and platelet-rich fibrin in treating temporomandibular disorders: a systematic review and network meta-analysis.
This study aims to compare the efficacy of intra-articular injections of hyaluronic acid (HA), platelet-rich plasma (PRP), and platelet-rich fibrin (PRF) for treating temporomandibular disorders (TMDs) and summarize their mechanisms of action. Randomized controlled trials (RCTs) published until November 13, 2021, were identified using electronic and manual searches. Each study was evaluated for the risk of bias using the Cochrane risk of bias tool. The studies found via searches were categorized by follow-up time (1, 3, or 6 months). Evidence quality was graded according to the GRADE system. Twelve RCTs were included that involved 421 patients with TMD. The network meta-analysis showed that all treatment groups improved compared to the placebo groups in terms of pain and maximal mouth opening (MMO). For pain evaluated via the visual analog scale, PRF exhibited better analgesic effects than PRP or HA after 1 and 3 months. PRP appeared to be more effective than PRF was after 6 months but there were no statistically significant differences between the two. For MMO, the effect of PRP was superior to those of PRF and HA after 1 month. However, after 3 and 6 months, PRF provided more encouraging results in improving MMO. PRP and PRF exhibited similar short-term efficacy in treating TMD, while PRF was more advantageous in terms of long-term efficacy. Therefore, PRF was recommended for treating TMD.


Comparison of Subthalamic Nucleus and Globus Pallidus Internus Deep Brain Stimulation Surgery on Parkinson Disease-Related Pain.
To analyze and compare the effects of subthalamic nucleus (STN) deep brain stimulation (DBS) and globus pallidus internus (GPi)-DBS on Parkinson disease (PD)-related pain. A retrospective study was performed of 64 patients (28 who underwent GPi-DBS and 36 who underwent STN-DBS) with PD-related pain in our hospital between January 2017 and July 2019. A numerical rating scale (NRS) was used to evaluate the degree of pain preoperatively and 4 months after operation, and the unified PD scale III (UPDRS-III) was completed simultaneously to assess motor symptoms. The average NRS score of all 64 patients after surgery was 1.09 ± 1.39, which was significantly lower than that before operation (4.44 ± 1.67; P < 0.0001). The improvement rate of NRS was 75 ± 27% in the 28 GPi-DBS patients and 79 ± 27% in the 36 STN-DBS patients, with no significant difference (P = 0.577). The improvements in NRS and UPDRS-III were significantly correlated in the STN-DBS group (r = 0.3707, P = 0.026) but not significantly correlated in the GPi-DBS group (P = 0.516). Both GPi-DBS and STN-DBS were effective for analyzing PD-related pain and seemed to have similar efficacy. This study provides an important first-step toward determining different DBS targets for controlling PD-related pain. Follow-up prospective research is an appropriate next step on the path to multicenter clinical trials.


Verification of Reliability and Validity of Trunk Forward Tilt Angle Measurement During Gait Using 2-Dimensional Motion Analysis.
The purpose of this study was to verify the reliability and validity of trunk forward tilt angle measurement during gait using the 2-dimensional motion analysis, open-source software Kinovea. The participants were 48 healthy people (23.3 ± 3.7 years of age), and the measurement task was normal gait. Two-dimensional motion analysis using Kinovea and measurement using a 3-dimensional motion analyzer were performed synchronously to calculate the forward tilt angle of the trunk during gait. The maximum and minimum values of the trunk forward tilt angle in 1 gait cycle were used as representative values. The intraclass correlation coefficient and the minimum detectable change amount in Kinovea were calculated. We also verified the correlation with the measured values using the 3-dimensional motion analyzer and the error by Bland-Altman analysis. The intraclass correlation coefficient for Kinovea was 0.925 (95% confidence interval, 0.866-0.958) at the maximum and 0.918 (95% confidence interval, 0.854-0.954) at the minimum. The maximum value of the minimum detectable change amount was 2.7°, and the minimum value was 2.9°. The correlation coefficient between the methods was the maximum value r = 0.964 (R² = 0.929) and the minimum value r = 0.970 (R² = 0.941). The average difference between the methods (d) was -0.55 to -0.51° and the standard deviation of the difference between the measured values was 0.66 to 0.84°, and the minimum value was d = -0.59 to -0.54° and SDd = 0.63 to 0.91°. The reliability and validity of the measurement by 2-dimensional motion analysis of the trunk forward tilt angle in young adults were confirmed.


A fluorescent artificial receptor with specific imprinted cavities to selectively detect colistin.
A novel and facile fluorescent artificial receptor on the basis of the molecularly imprinted polymer-coated graphene quantum dots was engineered successfully to detect colistin. The colistin imprinted graphene quantum dots (CMIP-GQDs) was synthesized by vinyl-based radical polymerization between functional monomers and crosslinker at around the template molecule on the surface of graphene quantum dots. The size of bare, CNIP-GQDs, and CMIP-GQDs was about 4.8 ± 0.6 nm, 18.4 ± 1.7 nm, and 19.7 ± 1.3 nm, respectively. The CMIP-GQDs, which showed the strong fluorescence emission at 440 nm with the excitation wavelength fixed at 380 nm, had excellent selectivity and specificity to rapidly recognize and detect colistin. The linear range of fluorescence quenching of this fluorescent artificial receptor for detection colistin was 0.016-2.0 μg mL-1 with a correlation coefficient (R2) of 0.99919, and the detection limit was 7.3 ng mL-1 in human serum samples. The designed receptor was successfully applied to detect colistin in human serum samples and it achieved excellent recoveries shifted from 93.8 to 105%. Graphical abstract.


[Control of hypertension refractory to medical management by means of short daily hemodialysis].
Hypertension is a very frequent complication in patients in hemodialysis. A high percentage of the patients on standard hemodialysis remain hypertense in spite of intensive pharmacologic treatment. We presented the case of a hypertense patient with difficult control in spite of antihypertensive treatment with five drugs and several secondary complications. The change to a short daily hemodialysis was successful to hypertension control and allowed a gradual suspension of drugs.


The role of alpha-synuclein in neurodegenerative diseases: a potential target for new treatment strategies?
Alpha-synuclein (AS) is the main constituent of Lewy bodies. There is an ongoing discussion if overexpression is already dangerous, or if toxicity is subjected to oligomers, protofibrils or mature aggregates. The facts that the central hydrophobic part of AS is also a constituent of amyloid plaques in Alzheimer's disease (AD) and that a majority of patients have Lewy bodies and Lewy neurites in specific brain areas raised our interest in the contribution of AS to AD pathogenesis. The N-terminal amino acid sequence 1-15 of beta-synuclein (BS) seems to be a natural antiaggregation factor for AS. We synthesized a library with different sequence variations. Several of these peptides displayed neuroprotective activity in tissue culture models of neurodegeneration induced by oxidative stress or beta-amyloid 1-42. In spite of the fact that these peptides have a short half-life, a significant in vivo reduction in brain plaque load and improvement of behavior was demonstrated in amyloid precursor protein transgenic mice after intranasal treatment for 2 months. KEGV, the shortest sequence, was also active after intraperitoneal application. The in vitro effects cannot be explained by the antiaggregatory potential, but most likely by interaction of BS derivates with antiapoptotic PI3/Akt or antioxidative pathways. The possibility that BS-derived peptidomimetics act as neuroprotectants and prevent protein misfolding suggests therapeutic usefulness.


Green synthesis of cerium oxide nanoparticles using zucchini peel extract for cytotoxic and photocatalytic properties.
The aim of this study is the green synthesis of cerium oxide nanoparticles (CeO2-NPs) using a natural capping agent and its application in water and wastewater treatment. This study presents the biosynthesis of CeO2-NPs by the exertion of a green method using zucchini (Cucurbita pepo) extract as a capping agent. Synthesized CeO2-NPs were distinguished through TGA/DTA, FT-IR, XRD, FESEM/TEM and EDX/PSA, and DRS procedures. According to the XRD pattern of NPs, the crystallinity structure was a face-centered cubic (fcc) with an Fm3m space group and the size was estimated at 30 nm. The spherical morphology of NPs was confirmed through FESEM/TEM images. In the following, the photocatalytic property of NPs was investigated by the decolorization of methylene blue (MB) dye within UV-A light. Also, the cytotoxicity of NPs on the CT26 cell line was evaluated through the MTT test, and no toxicity was observed in the results, which indicates their biocompatibility.


Regulatory properties of 14-day embryo and adult hen skeletal muscle AMP deaminase.
Chromatography on phosphocellulose column revealed changes in the elution profile of 14 day-old chicken embryo and adult hen skeletal muscle AMP deaminase. In the presence of 5 mM potassium the enzyme from embryo muscle exhibited a sigmoid-shaped plot of the reaction rate versus substrate concentration. The increase of KCl concentration up to 100 mM diminished distinctly sigmoidicity of the plot. Micromolar concentrations of ADP or ATP activated, whereas GTP at the same concentrations inhibited the embryo and hen skeletal muscle AMP deaminase while 5 mM KCl was present in the incubation medium. 100 mM potassium concentration diminished the effect of ADP and ATP but not of GTP. Palmitoyl-CoA inhibited strongly the embryo skeletal muscle adenylate deaminase but had no effect on the activity of the hen enzyme. Alanine inhibited only the adult hen enzyme. The embryo and hen AMP deaminase differed also in the specificity to adenylate analogues and exhibited a different dAMP/AMP ratio. The data presented indicate that kinetic and regulatory properties of the two developmental forms of AMP deaminase are different.


Repaired tetralogy of Fallot with coexisting unrepaired partial anomalous pulmonary venous connection is associated with diminished right ventricular ejection fraction and more severe right ventricular dilation.
There is an established association between tetralogy of Fallot and partial anomalous pulmonary venous connections. This association is important because surgically repaired tetralogy patients have increased risk of right heart failure. We hypothesize that partial anomalous venous connections increase right ventricular volumes and worsen right ventricular failure. We reviewed cardiac MRI exams performed at a tertiary pediatric hospital from January 2005 to January 2014. We identified patients with repaired tetralogy and unrepaired partial anomalous pulmonary venous connection. We used age- and gender-matched repaired tetralogy patients without partial anomalous pulmonary venous connection as controls. We analyzed the MRI results and surgical course and performed comparative statistics to identify group differences. There were eight patients with repaired tetralogy and unrepaired partial anomalous pulmonary venous connection and 16 controls. In all cases, the partial anomalous pulmonary venous connection was not detected on preoperative echocardiography. There were no significant differences in surgical course and body surface area between the two groups. Repaired tetralogy patients with unrepaired partial anomalous pulmonary venous connection showed significantly higher indexed right ventricular end diastolic volume (149 ± 33 mL/m(2) vs. 118 ± 30 mL/m(2)), right ventricle to left ventricle size ratios (3.1 ± 1.3 vs. 1.9 ± 0.5) and a higher incidence of reduced right ventricular ejection fraction compared to controls (3/8 vs. 0/16). Repaired tetralogy of Fallot with unrepaired partial anomalous pulmonary venous connection is associated with reduced right ventricular ejection fraction and more significant right ventricular dilation.


Low dose N, N-dimethylsphingosine is cardioprotective and activates cytosolic sphingosine kinase by a PKCepsilon dependent mechanism.
N, N-Dimethylsphingosine (DMS) is recognized as an inhibitor of sphingosine kinase (SphK), a key enzyme responsible for the formation of sphingosine-1-phosphate (S1P). We previously showed that S1P was cardioprotective and that SphK was critical for myocardial ischemic preconditioning. Although DMS is an endogenous sphingolipid, its effect on cardiac function and cardioprotection at low concentration has not been studied. In Langendorff-perfused wild-type and protein kinase C (PKC)epsilon-null mouse hearts, cardiac function, infarction size, and SphK activity were measured. Pretreatment with 0.3 microM and 1 microM DMS for 10 min protected against ischemia/reperfusion injury. Cardiac function (LVDP, +/-dP/dtmax) was improved and infarction size was reduced. The cardiac protection induced by DMS was abolished in PKCepsilon-null mouse hearts. Administration of 1 microM DMS ex vivo increased cytosolic SphK activity. This enhanced SphK activity was abolished in PKCepsilon-null mouse hearts. DMS also increased PKCepsilon translocation from the particulate to the cytosolic fraction with no effect on PKCalpha distribution. Co-immunoprecipitation showed that SphK1 interacted with PKCepsilon phosphorylated on Ser729. DMS also increased cytosolic Akt phosphorylation (Ser 473) and Akt translocation from a Triton-insoluble fraction to the cytosol. DMS has a biphasic effect on cardioprotection. Higher concentrations (10 microM) are inhibitory, whereas a low concentration (0.3 microM and 1 microM) of DMS protects murine hearts against ischemia/reperfusion injury. DMS activates SphK in the cytosol via a PKCepsilon dependent mechanism. The PKCepsilon-SphK-S1P-Akt pathway is involved in the cardiac protection induced by DMS.


Intrarenal vascular obstruction of superior ureteropelvic junction causing nephralgia in a woman with complete duplex kidney. (a case of Fraley's syndrome in duplex kidney).
A case of Fraley's syndrome in a Japanese woman was reported. This is believed to be the first case involved in a complete duplex kidney.


Thrombospondin is present in articular cartilage and is synthesized by articular chondrocytes.
Thrombospondin, a multifunctional adhesive glycoprotein originally identified in platelets, was isolated and identified from an extract of ovine articular cartilage. Immunoreactive material from a cartilage extract comigrated on gel electrophoresis with purified human platelet thrombospondin. When articular chondrocytes were cultured in the presence of 35S-methionine, metabolically labeled thrombospondin was immunoprecipitated from the culture medium and cell layer extract. These results demonstrate that thrombospondin is present in articular cartilage and is synthesized by articular chondrocytes.


[Clinical study on sodium hyaluronate intra-articular injection in treatment of degenerative osteoarthritis of knee].
To evaluate the clinical effect of sodium hyaluronate (SH) intra-articular injection in treatment of degenerative osteoarthritis (DOA) of knees. One hundred patients (116 knees) suffered from DOA were treated by SH injection intra-articularly once a week for three times. According to Lysholm scoring, clinical signs such as pain, swelling, excludes, range of movement (ROM), and the ability of walking, going upstairs and downstairs, squatting, running, were assessed before and after treatment. Ninety-six cases were followed up for 1 to 6 months. There were obvious improvements in the signs and function of knee in 39 patients (40.6%), only some improvements in 48 patients (50.0%), and no obvious improvements in other 9 patients (9.4%). The total effectiveness rate was 74.0%. No toxic or side effect was observed. Intraarticular injection of SH has a positive effect in relief of clinical symptoms and in improvement of articular function of DOA of knee.


Single origin of the Mascarene stick insects: ancient radiation on sunken islands?
The study of islands as model systems plays a key role in understanding many evolutionary processes. Knowledge of the historical events leading to present-day island communities is pivotal for exploring fundamental mechanisms of speciation and adaptation. The remote Mascarene archipelago (Mauritius, Réunion, Rodrigues), considered to be the product of an age-progressive trend of north-to-south volcanic activity in the Indian Ocean, hosts a remarkably diverse, endemic and threatened concentration of flora and fauna that has traditionally been considered to be biogeographically related to Madagascar and Africa. To explore the evolutionary diversity of the Mascarene stick insects (Phasmatodea), we constructed a global phylogeny from approximately 2.4 kb of mitochondrial and nuclear sequence data of more than 120 species representing all major phasmatodean lineages. Based on the obtained time-calibrated molecular tree we demonstrate that the current phasmid community of the Mascarene archipelago, which consists of members of four presumably unrelated traditional subfamilies, is the result of a single ancient dispersal event from Australasia and started radiating between 16-29 million years ago, significantly predating the age of Mauritius (8-10 million years). We propose that the Mascarene stick insects diversified on landmasses now eroded away, presumably to the north of Mauritius. In consequence, ancient islands have probably persisted in the Indian Ocean until the emergence of Mauritius and not only served as stepping stones for colonisation events during sea-level lowstands, but as long-lasting cradles of evolution. These ancient landmasses most likely allowed for adaptive speciation and served as significant sources of diversity that contributed to the biomes of the Mascarene archipelago and the megadiverse Madagascar.


The Parasternal Long Axis View in Isolation: Is it Good Enough?
Focused cardiac ultrasound (FOCUS) is a vital tool to evaluate patients at the bedside, but its use can be limited by patient habitus, sonographer skill, and time to perform the examination. Our primary goal was to determine the diagnostic accuracy of the parasternal long axis (PSLA) view in isolation for identifying pericardial effusion, left ventricular (LV) dysfunction, and right ventricular (RV) dilatation compared with a four-view FOCUS examination. This was a retrospective study looking at FOCUS images. Examinations were blinded and randomized for review by point-of-care ultrasound faculty. The primary objective was measured by comparing ultrasound findings on PSLA view in isolation with findings on a full four-view FOCUS examination, which served as the criterion standard. Sensitivity and specificity were calculated. Of 100 FOCUS examinations; 36% were normal, 16% had a pericardial effusion, 41% had an LV ejection fraction < 50%, and 7% had RV dilatation. Sensitivity and specificity for identifying pericardial effusion, LV dysfunction, and RV dilatation were 81% (confidence interval [CI] 0.54-0.95) and 98% (95% CI 0.91-0.99), 100% (95% CI 0.88-1) and 91% (95% CI 0.80-0.97), and 71% (95% CI 0.30-0.94) and 99% (95% CI 0.93-1), respectively. All moderate to large effusions were identified correctly. Overall, there were only four clinically significant disagreements between PSLA alone and the four-view interpretations. In isolation, the PSLA view was highly sensitive and specific for identifying LV ejection fraction and moderate to large pericardial effusions. It was highly specific for identifying RV dilatation, but had only moderate sensitivity.


Cytochromes P-450 in human hepatocyte plasma membrane: recognition by several autoantibodies.
Anti-cytochrome P-450 autoantibodies are present in several forms of autoimmune hepatitis. The possibility that cytochromes P-450 are present in the plasma membrane of human hepatocytes was examined. (1) Plasma membranes with microsomal contamination < 1%, as judged from the activities of glucose-6-phosphatase and NADH-cytochrome c reductase, were prepared. (2) After exposure of uncut, fixed hepatocytes to antibodies, immunofluorescence and immunoperoxidase studies were performed. (1) The specific content of cytochrome P-450 in plasma membrane was 9% of that in microsomes. Plasma membranes showed NADPH-cytochrome c reductase and mono-oxygenase activities; immunoblots showed the presence of cytochromes P-450 1A2, 2C, 2D6, 2E1, and 3A4; cytochromes P-450 1A2, 2D6, and 2C were also recognized by anti-liver microsome and anti-liver/kidney microsome type 1 and type 2 autoantibodies, respectively. (2) Immunofluorescence and immunoperoxidase labeling of the plasma membrane was observed with the three auto-antibodies and with anti-cytochrome P-450 1A2, 2C, 2E1, or 3A4. It is concluded that cytochromes P-450 are present and functional in the plasma membrane of human hepatocytes and that anti-cytochrome P-450 autoantibodies recognize epitopes expressed on the outer surface.


Hyperdiploid acute myeloid leukemia. Relationship between blast size and karyotype demonstrated by fluorescence in situ hybridization.
Hyperdiploidy is a rare finding in acute myeloid leukemia (AML), and the cases described so far showed characteristic large and bizarre blasts. We further demonstrate this morphologic/karyotypic relationship in a case of hyperdiploid AML by fluorescence in situ hybridization. Together with previous observations, we propose that in myeloid leukemias, increase in DNA content is accompanied by a corresponding increase in blast size. If large and bizarre blasts are shown on morphologic analysis, polyploid metaphases on cytogenetic preparations should also be analyzed, as they may be derived from these cells.


Near-total penile amputation secondary to hair Torniquet syndrome - Case of a staged repair with a satisfactory outcome.
Penile Hair Tourniquet Syndrome, a subtype of Penile Tourniquet Syndrome, is a rare condition and a pediatric surgical emergency seen in infants whereby a constricting hair coil strangulates the penis most often at the coronal sulcus, leading to edema, ischemia and necrosis, If untreated, it can potentially lead to development of a urethrocutaneous fistula or even urethral transection and penile amputation. Therefore, a well-timed intervention can prevent complications and lifelong unhappiness. Herein, we present a case of an 11-month-old boy who presented with near total amputation of the glans and underwent two-staged repair with a satisfactory outcome.


An isochore transition zone in the NF1 gene region is a conserved landmark of chromosome structure and function.
The mammalian genome is organized as a mosaic of isochores, stretches of DNA with a distinct sequence composition. Isochores form the basis of the chromosomal banding pattern, which is tightly correlated with a number of structural and functional features. We have recently demonstrated that the transition from a GC-poor isochore to a GC-rich one in the NF1 gene region occurs within 5 kb and demarcates genomic regions with high and low recombination frequency. We now report that the same transition zone separates early replicating from late replicating chromatin on the molecular level. At the isochore transition the replication fork is stalled in mid-S phase and can be visualized by fiber-FISH techniques as a Y-shaped structure. The switch in GC content and in replication timing is conserved between human and mouse, emphasizing the importance of the transition zones as landmarks of chromosome organization and function.


Beneficial effects of subcutaneous fat transplantation on metabolism.
Subcutaneous (SC) and visceral (VIS) obesity are associated with different risks of diabetes and the metabolic syndrome. To elucidate whether these differences are due to anatomic location or intrinsic differences in adipose depots, we characterized mice after transplantation of SC or VIS fat from donor mice into either SC or VIS regions of recipient mice. The group with SC fat transplanted into the VIS cavity exhibited decreased body weight, total fat mass, and glucose and insulin levels. These mice also exhibited improved insulin sensitivity during hyperinsulinemic-euglycemic clamps with increased whole-body glucose uptake, glucose uptake into endogenous fat, and insulin suppression of hepatic glucose production. These effects were observed to a lesser extent with SC fat transplanted to the SC area, whereas VIS fat transplanted to the VIS area was without effect. These data suggest that SC fat is intrinsically different from VIS fat and produces substances that can act systemically to improve glucose metabolism.


Atopic characteristics of wheezing children and responses to prednisolone.
We wanted to test the hypothesis that the efficacy of systemic corticosteroid is associated with atopic characteristics in wheezing children. A randomized controlled trial comparing oral prednisolone (2 mg/kg/day in 3 divided doses for 3 days) with placebo in hospitalized wheezing children (n = 266, median 1.6 years, range 3 months to 15.2 years) was conducted. In this post-hoc analysis, we assessed the link between the efficacy of prednisolone and several atopic characteristics, such as atopy, aeroallergen sensitization, total IgE level, number of sensitizations, eczema, atopic eczema, blood or nasal eosinophils, exhaled nitric oxide, positive modified asthma predictive index/asthma, inhaled corticosteroid medication and parental asthma/allergy. Virology was studied comprehensively. Our primary endpoint was the time until ready for discharge, and the most important secondary endpoint was the occurrence of relapses during the following 2 months. For statistics, we used interaction analyses in uni- and multivariate regression models. Overall, prednisolone did not decrease any of our predefined clinical endpoints. Neither was the efficacy of prednisolone associated with atopy. However, prednisolone significantly decreased the time until ready for discharge in children with positive modified asthma predictive index/asthma, inhaled corticosteroids, or rhinovirus infection and/or in children without azithromycin treatment. Prednisolone significantly decreased relapses in children with eczema, nasal eosinophilia and rhinovirus infection. The multiple clinical, inflammatory and viral markers associating with the efficacy of prednisolone should be confirmed in prospective trials. It is important that corticosteroid intervention trials have strict design for these potentially confounding factors.


Some applications of the law of evidence to the specialty of radiology.
Certain rules or laws of evidence are particularly applicable to diagnostic images in whatever form they are used in court as evidence. The legal principles and precedents of this subject, including opinion evidence, hearsay evidence rule, best evidence rule, and the role of the radiologist as a medical expert witness, are discussed.


Diabetes and the gastrointestinal tract.
Gastrointestinal motility disorders are common in patients with diabetes. The entire gastrointestinal tract may be involved from the esophagus to the anal sphincter. Before instituting therapy, people with diabetes first require a careful diagnostic evaluation. Treatment includes tight glucose control and the use of antiemetics and prokinetic agents.


Calcium in the diet: food sources, recommended intakes, and nutritional bioavailability.
Calcium nutritional status among some groups in the United States is suboptimal when judged by calcium intakes and the high prevalence of osteoporosis. Unfortunately, however, it is not clear that increases in calcium intake will have a significant impact on osteoporosis or other chronic diseases that have been linked to calcium nutriture. There is still considerable controversy surrounding the issue of calcium RDAs. The body's ability to adapt to varying levels of calcium intakes, the lack of sensitive indicators of calcium status, and the complexity and slow progression of chronic diseases such as osteoporosis make it very difficult to establish the role of diet in this regard. Great progress has been made in the study of calcium absorption. Much is known about the mechanisms involved in calcium absorption and its regulation. Thus, a rapidly advancing field and further developments will be invaluable to our understanding of the role of diet in calcium nutrition. Calcium bioavailability is affected by diet composition and the chemical form of calcium in foods. The calcium in dairy products is readily absorbed in the intestine. Lactose enhances calcium absorption efficiency under some conditions. Components of plants such as fiber, phytate, and oxalic acid may depress calcium absorption. High intakes of protein increase urinary losses of calcium but this effect may be partially offset by the phosphate association with most high-protein foods. Calcium absorption from salts used in supplement tablets is generally good. Absorption from salts such as calcium carbonate which require acid for dissolution may be poor in persons with achlorhydria unless the tablets are consumed with a meal. The practical significance of factors that may alter calcium bioavailability in normal mixed diets is difficult to assess. It may be a significant factor when calcium intakes are marginal or when absorption by the active transport, vitamin D-dependent process is impaired or not fully developed, i.e., it may be significant when vitamin D status is poor, in the elderly, and in young infants.


Cognitive functions in bipolar affective disorder and schizophrenia: comparison.
Earlier comparisons of cognitive impairment among patients with bipolar disorder and schizophrenia have found a largely similar profile of deficits, but results have varied between studies. This prompted the current attempt at another such comparison. Executive functions, memory, IQ, attention-concentration and perceptuomotor function were assessed in 48 bipolar disorder patients with operationally defined euthymia, and compared with 32 schizophrenia patients in remission, and 23 normal controls. Comparisons were re-attempted after controlling for years of schooling and residual affective symptoms. Uncontrolled comparisons indicated that, compared to controls, both bipolar disorder and schizophrenia patients were significantly impaired on different tests of executive function, memory, IQ and perceptuomotor functions. Controlling for years of schooling and residual affective symptoms, however, served to remove most of the differences between patients and controls, apart from some aspects of executive function in schizophrenia and memory impairment in both schizophrenia and bipolar disorder. Patients with schizophrenia consistently performed worse than patients with bipolar disorder, but none of the differences between schizophrenia and bipolar disorder were significant. Patients with bipolar disorder exhibit cognitive difficulties that are very similar to schizophrenia in terms of their profile, although patients with schizophrenia may have more severe and widespread impairments. The resemblance in cognitive profiles has important implications for the etiology and treatment of both disorders.


The CRH-R₁ receptor mediates luteinizing hormone, prolactin, corticosterone and progesterone secretion induced by restraint stress in estrogen-primed rats.
Acute stress has been shown to modify hypothalamus-pituitary-gonadal (HPG) axis activity. Corticotropin-releasing hormone (CRH), the principal regulator of the hypothalamus-pituitary-adrenal (HPA) axis, has been implicated as a mediator of stress-induced effects on the reproductive axis. The role of the specific CRH receptor subtypes in this response is not completely understood. In the current study, we investigated the role of the CRH-R(1) receptor on luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), progesterone (P) and corticosterone (CT) secretion in stress-induced responses under the influence of estrogen (E(2)). Estrogen-primed ovariectomized rats (estradiol cypionate, 10 μg sc) received an i.v. administration of antalarmin (0.1 or 1mg/kg), a selective CRH-R(1) antagonist, or vehicle before restraint stress for 40 min. Seven blood samples were collected from two experimental groups (one from 10:00 h to 14:00 h and the other from 10:00 h to 18:00 h). An increase of plasma LH induced by restraint acute-stress was followed by alteration of the secretion pattern in the estrogen-induced afternoon surge. In a similar manner, we observed a suppression of the afternoon surge in plasma FSH, a delay of E(2)-induced PRL secretion, and an increase in plasma P and CT. Antalarmin attenuated stress-induce LH increase, decreased CT and P secretion and blocked the stress effects on PRL secretion. These findings suggest that CRH-R(1) mediates, at least in part, the restraint stress effects on the HPA, PRL, and reproductive axes.


A novel and economical approach for the synthesis of short rod-shaped mesoporous silica nanoparticles from coal fly ash waste by Bacillus circulans MTCC 6811.
Coal fly ash (CFA) is an industrial byproduct produced during the production of electricity in thermal power plants from the burning of pulverized coal. It is considered hazardous due to the presence of toxic heavy metals while it is also considered valuable due to the presence of value-added minerals like silicates, alumina, and iron oxides. Silica nanoparticles' demands and application have increased drastically in the last decade due to their mesoporous nature, high surface area to volume ratio, etc. Here in the present research work, short rod-shaped, mesoporous silica nanoparticles (MSN) have been synthesized from coal fly ash by using Bacillus circulans MTCC 6811 in two steps. Firstly, CFA was kept with the bacterial culture for bioleaching for 25 days in an incubator shaker at 120 rpm. Secondly, the dissolved silica in the medium was precipitated with the 4 M sodium hydroxide to obtain a short rod-shaped MSN. The purification of the synthesized silica particle was done by treating them with 1 M HCl at 120 °C, for 90 min. The synthesized short rod-shaped MSN were characterized by UV-vis spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Particle size analyzer (PSA), Field emission scanning electron microscopy (FESEM), and transmission electron microscope. The microscopic techniques revealed the short rod-shaped mesoporous silica nanoparticles (MSN) for the final nano-silica, whose size varies from 40 to 80 nm, with an average size of 36 ± 5 nm. The XRD shows the crystalline nature of the synthesized MSN having a crystallite size of 36 nm. The FTIR showed the three characteristic bands in the range of 400-1100 cm-1, indicating the purity of the sample. The energy dispersive X-ray (EDX) showed 53.04 wt% oxygen and 43.42% Si along with 3.54% carbon in the final MSN. The particle size analyzer revealed that the average particle size is 368.7 nm in radius and the polydispersity index (PDI) is 0.667. Such a novel and economical approach could be helpful in the synthesis of silica in high yield with high purity from coal fly ash and other similar waste.


Long-term postpartum adherence to antiretroviral drugs among women in Latin America.
Antiretroviral adherence in the postpartum period is crucial for maternal health and decreasing the risk of mother-to-child HIV transmission and transmission to sexual partners. Self-reported antiretroviral adherence was examined between 6- to 12-weeks and 30 months postpartum among 270 HIV-infected women enrolled in a prospective cohort study from 2008 to 2010 at multiple sites in Latin America. Adherence data were collected at each study visit to quantify the proportion of prescribed antiretrovirals taken during the previous three days, assess the timing of the last missed dose, and identify predictors of adherence. Mean adherence rates were 89.5% at 6-12 weeks and 92.4% at 30 months; the proportions with perfect adherence were 80.3% and 83.6%, respectively. The overall trend for perfect adherence was not significant (p = 0.71). In adjusted regression modelling, younger age was associated with an increased probability of non-perfect adherence at 18 and 24 months postpartum. Other factors associated with increased probability of non-perfect adherence were higher parity, current use of alcohol and tobacco, and more advanced HIV disease. Women with perfect adherence had lower viral loads. Interventions for alcohol and tobacco use cessation, and support for young women and those with advanced HIV disease should be considered to improve postpartum adherence.


The role of radiotherapy and chemotherapy for curative management of medically inoperable and stage III nonsmall cell lung cancer, and radiotherapy for palliation of symptomatic disease.
Radiotherapy has an expanding role in all phases of treatment of nonsmall cell lung cancer. Evolutions in technique, such as three-dimensional conformal radiotherapy, hold the promise for more effective treatment of patients with early stage disease who are not candidates for surgical intervention. Multimodality therapy for patients with locally advanced disease is evolving rapidly, with evidence accruing as to the optimal schedules and doses of radiotherapy and combination chemotherapy. Palliative dose schedules are being refined that maximize patient comfort while providing substantial symptom relief.


Peritoneal dialysis in Dalmatian County, Croatia: 21 years of a single-center experience.
With end-stage renal disease becoming more prevalent, the importance of continuous ambulatory peritoneal dialysis (CAPD) is expected to rise even more. However, CAPD is associated with several infections with peritonitis being of the biggest importance. We collected data regarding acute peritonitis episodes (APEs), date of birth and CAPD start, BMI, diabetes mellitus (DM) prevalence, year of renal disease discovery, and details about renal replacement therapies. Primary outcomes included death, transplantation, and a switch to hemodialysis (HD). Hundred and twenty-nine men and 123 women were analyzed. 63 patients had DM. The median age at the start of CAPD was 56. The median length of CAPD treatment was 24 months. In the end, 147 patients were still alive of which 97 were transplanted, 33 were on CAPD, and 26 were switched to HD. A total of 327 APE were observed. Although the incidence is decreasing, efforts are required to enhance the prevention and treatment of APE.


Effect of milking efficiency on 99Tc content of 99mTc derived from 99mTc generators.
Calculation was made of the effect of milking efficiency on the 99Tc content of 99mTc derived from 99mTc-generators. Reduced milking efficiency was shown to lead to an increase in the 99Tc/99mTc ratio. Levels of 99Tc were determined in samples from both column and solvent extraction generators using a HPLC procedure. It is recommended that producers of 99mTc from solvent extraction generators should ensure that complete generator milking is performed daily.


High CYP2C19 phenotypic variability in gastrointestinal cancer patients.
CYP2C19 contributes to the metabolism of several chemotherapeutic agents. The CYP2C19 homozygous null function genotype strongly predicts activity phenotype in healthy populations. An additional acquired loss of function has been reported in up to one-third of cancer patients. It is not known whether this phenomenon also occurs in patients with earlier stage or in resected disease. This study investigated whether acquired loss of CYP2C19 function was detectable in patients with stage III-IV or resected gastrointestinal cancer. CYP2C19 genotype was determined in 49 patients, and subjects were probed for CYP2C19 activity on three test occasions. An acquired loss of CYP2C19 activity was observed in 20% of stage III-IV and 17% of resected patients at the first test. Significant (p < 0.01) genotype-phenotype discordance was observed in both groups. There were no direct associations between this discordance and inflammatory markers, tumour burden or chemotherapeutic history. Notably, hepatic CYP2C19 function was not stable over time and phenotype conversion occurred in 23 patients over the period of testing. Reliance on germ-line genotype to infer a poor metaboliser status could substantially underestimate the number of patients with deficient CYP2C19 function. This could compromise the interpretation of genotype-based clinical association studies.


Recessive mutations in the cancer gene Ataxia Telangiectasia Mutated (ATM), at a locus previously associated with metformin response, cause dysglycaemia and insulin resistance.
To investigate glucose and insulin metabolism in participants with ataxia telangiectasia in the absence of a diagnosis of diabetes. A standard oral glucose tolerance test was performed in participants with ataxia telangiectasia (n = 10) and in a control cohort (n = 10). Serial glucose and insulin measurements were taken to permit cohort comparisons of glucose-insulin homeostasis and indices of insulin secretion and sensitivity. During the oral glucose tolerance test, the 2-h glucose (6.75 vs 4.93 mmol/l; P = 0.029), insulin concentrations (285.6 vs 148.5 pmol/l; P = 0.043), incremental area under the curve for glucose (314 vs 161 mmol/l/min; P = 0.036) and incremental area under the curve for insulin (37,720 vs 18,080 pmol/l/min; P = 0.03) were higher in participants with ataxia telangiectasia than in the controls. There were no significant differences between groups in fasting glucose, insulin concentrations or insulinogenic index measurement (0.94 vs 0.95; P = 0.95). The Matsuda index, reflecting whole-body insulin sensitivity, was lower in participants with ataxia telangiectasia (5.96 vs 11.03; P = 0.019) than in control subjects. Mutations in Ataxia Telangiectasia Mutated (ATM) that cause ataxia telangiectasia are associated with elevated glycaemia and low insulin sensitivity in participants without diabetes. This indicates a role of ATM in glucose and insulin metabolic pathways.


Does talking about end of life with adults with intellectual disability cause emotional discomfort or psychological harm?
Caregivers often avoid involving people with intellectual disability in end-of-life discussions and activities. One reason is fear that the person may become upset or psychologically harmed. Pre and post a 6-month intervention about end of life, we assessed depression, anxiety, and fear of death among intervention (n = 24) and comparison (n = 20) participants with intellectual disability. End-of-life 'encounters' (conversations/activities about end of life) were monitored, including comfort ratings. Overall, 79% of encounters were rated very comfortable/somewhat comfortable. Participants initiated 69% of encounters. There was no significant pre-post change in depression or fear of death. Anxiety improved significantly. This is the first controlled, longitudinal study providing robust evidence about whether discussing end of life leads to emotional discomfort or psychological harm. Data showed adults with intellectual disability can safely engage in conversations/activities about end of life. The high percentage of participant-initiated encounters showed participants wanted to talk about end of life.


Unusual fistulae due to colonic diverticulitis.
Examples of diverticulitis of the colon associated with fistulae to the left hip, inferior mesenteric vein, and portal vein resulting in the demonstration of intrahepatic abscesses, the vermiform appendix, and the skin are presented with a review of the literature. A case of a fistula to the epidural space is included.


Stereotactic Body Radiotherapy for Localized Kidney Cancer.
Stereotactic body radiation therapy (SBRT) is increasingly utilized in the management of localized kidney cancers, particularly for patients who are not surgical candidates. Herein, we provide a narrative review of SBRT in the management of localized kidney cancers. Recent prospective studies and multi-institutional retrospective studies highlight the safety and efficacy of SBRT in the management of renal tumors, a disease previously thought to be radioresistant. Studies have shown that local control is greater than 90% with rare grade 3 or 4 toxicity and no grade 5 toxicity. SBRT can be utilized successfully in the treatment of large kidney tumors (> 5 cm). New techniques such as MRI-guided radiation therapy may further improve the therapeutic ratio. However, randomized clinical trials are necessary to confirm the optimal dosing schedule and compare outcomes with nephrectomy, which remains the standard of care in suitable patients. Advances in SBRT have made this modality a safe and effective treatment option in the management of localized kidney cancers.


A new computed tomography-based radiographic method to detect early loosening of total wrist implants.
Diagnosis of loosening of total wrist implants is usually late using routine radiographs. Switching modality to computed tomography (CT) should aid in early diagnosis. To propose and evaluate the accuracy of a new CT method for assessing loosening of the carpal component in total wrist arthroplasty. A protocol encompassing volume registration of paired CT scans of patients with unexplained pain in a prosthetically replaced wrist (used in clinical routine) is presented. Scans are acquired as a dynamic examination under torsional load. Using volume registration, the carpal component of the prosthesis is brought into spatial alignment. After registration, prosthetic loosening is diagnosed by a shift in position of the bones relative to the prosthesis. This study is a preclinical validation of this method using a human cadaverous arm with a cemented total wrist implant and tantalum markers. Seven CT scans of the arm were acquired. The scans were combined into 21 pairs of CT volumes. The carpal component was registered in each scan pair, and the residual mismatch of the surrounding tantalum markers and bone was analyzed both visually and numerically. The detection limit for prosthetic movement was less than 1 mm. The results of this study demonstrate that CT volume registration holds promise to improve detection of movement of the carpal component at an earlier stage than is obtainable with plain radiography.


Interpregnancy intervals in the United States: data from the birth certificate and the national survey of family growth.
To describe data on interpregnancy intervals (IPI), defined as the timing between a live birth and conception of a subsequent live birth, from a subset of jurisdictions that adopted the 2003 revised birth certificate. Because this information is available among revised jurisdictions only, the national representativeness of IPI and related patterns to the entire United States were assessed using the 2006-2010 National Survey of Family Growth (NSFG).


New homogeneous high-throughput assays for inhibitors of β-catenin/Tcf protein-protein interactions.
The transcriptional activator β-catenin is the primary mediator of the canonical Wnt/β-catenin signaling pathway. The aberrant formation of the β-catenin/T-cell factor (Tcf) complex leads to many cancers and organ fibroses. Selective inhibition of β-catenin/Tcf protein-protein interactions represents an appealing therapeutic strategy. In this study, two new robust, homogeneous high-throughput assays, AlphaScreen and fluorescence polarization, were established to study β-catenin/Tcf interactions. These two new assays reproduce native β-catenin/Tcf interactions, quantify inhibitory potency, and are complementary with each other. The establishment of these two high-throughput screenings enables quick identification of inhibitors of β-catenin/Tcf protein-protein interactions.


Initial evaluation of laparoscopic Roux-en-Y gastric bypass and adjustable gastric banding in Korea: a single institution study.
Obesity becomes a global epidemic disease, and bariatric surgery is increasing in Korea as well as in western countries. The first laparoscopic Roux-en-Y gastric bypass (LRYGBP) was performed in 2003, and the Lap Band was approved for use in Korea in 2004. There are no data regarding gastric bypass and adjustable gastric banding regarding weight loss as well as changing of pre-existing comorbidities up to date. St. Mary's Hospital Center, main leader of bariatric surgery in Korea, performed 76 weight loss operations [LRYGBP = 25, laparoscopic adjustable gastric banding (LAGB) = 51] for morbid obesity. We retrospectively reviewed a series of bariatric cases and examined changes of weight loss, postoperative complications, and pre-existing comorbidities between two procedures. There were no significant differences in age, BMI, sex distribution, pre-existing comorbidities in two procedures. Patients undergoing LRYGBP had longer operative times, more blood loss, and longer hospital stays. There is significant difference regarding postoperative complication (p < 0.05) but neither for mortality nor pulmonary embolism with both procedures. Percentage of excess weight loss (%EWL) of LRYGBP at 12, 24, and 36 months were 76.9%, 79.7%, and 85.8%, and %EWL of LAGB were 46.8%, 55.1%, 63.3%, respectively. The patients in the LRYGBP who has dyslipidemia, sleep apnea, degenerative joint disease, and diabetes mellitus were more likely to improve than the patients after LAGB at early postoperative period. The results of our initial study indicate that LRYGBP and LAGB are technically feasible and safe. It is a low rate of major postoperative complications without mortality. LRYGBP and LAGB are quite satisfactory and promising bariatric procedures with significant weight loss and improvement of obesity-related metabolic comorbidities in Korean.


Pyridoxamine protects human granulosa cells against advanced glycation end-products-induced steroidogenesis disturbances.
Ovarian advanced glycation end-products (AGEs) accumulation is associated with ovarian granulosa cells (GCs) dysfunction. Vitamin B6 derivatives positively affected reproduction. The current study was conducted to elucidate the AGEs effects on human luteinized mural GCs steroidogenesis in the presence or absence of pyridoxamine (PM). Isolated GCs of 50 healthy women were divided into four parts and treated with media alone (Control), PM alone, or human glycated albumin (HGA) with/without PM. Main steroidogenic enzymes and hormones were assessed by qRT-PCR and ELISA. The AGE receptor (RAGE) protein was also determined using Western blotting. The non-toxic concentration of HGA increased the expression of RAGE, StAR, 3β-HSD, and 17β-HSD (P < 0.0001 for all) but decreased the expression of CYP19A1 at mRNA levels. The increased RAGE protein expression was also confirmed by western blot analysis. These effects resulted in declined estradiol (E2), slightly, and a sharp rise in progesterone (P4) and testosterone (T) levels, respectively. PM, on its own, ameliorated the HGA-altered enzyme expression and, thereby, corrected the aberrant levels of E2, P4, and T. These effects are likely mediated by regulating the RAGE gene and protein expression. This study indicates that hormonal dysfunctions induced by the AGEs-RAGE axis in luteinized GCs are likely rectified by PM treatment. This effect is likely acquired by reduced expression of RAGE. A better understanding of how AGEs and PM interact in ovarian physiology and pathology may lead to more targeted therapy for treating ovarian dysfunction.


Nutritional patterns as machine learning predictors of liver health in a population of elderly subjects.
Non-alcoholic hepatic steatosis affects 25% of adults worldwide and its prevalence increases with age. There is currently no definitive treatment for NAFLD but international guidelines recommend a lifestyle-based approach, including a healthy diet. The aim of this study was to investigate the interactions between eating habits and the risk of steatosis and/or hepatic fibrosis, using a machine learning approach, in a non-institutionalized elderly population. We recruited 1929 subjects, mean age 74 years, from the population-based Salus in Apulia Study. Dietary habits and the risk of steatosis and hepatic fibrosis were evaluated with a validated food frequency questionnaire, the Fatty Liver Index (FLI) and the FIB-4 score, respectively. Two dietary patterns associated with the risk of steatosis and hepatic fibrosis have been identified. They are both similar to a "western" diet, defined by a greater consumption of refined foods, with a rich content of sugars and saturated fats, and alcoholic and non-alcoholic calorie drinks. This study further supports the concept of diet as a factor that significantly influences the development of the most widespread liver diseases. However, longitudinal studies are needed to better understand the causal effect of the consumption of particular foods on fat accumulation in the liver.


Time course of capillary regression and an expression balance between vascular endothelial growth factor-A and thrombospondin-1 in the soleus muscle of hindlimb unloaded rats.
Skeletal muscle capillaries regress with disuse; however, information on time-dependent changes in the expression of pro- and anti-angiogenic factors in disused muscle is limited. This study aimed to clarify time-dependent changes in skeletal muscle capillarization, pro-angiogenic vascular endothelial growth factor-A (VEGF-A), and anti-angiogenic thrombospondin-1 (TSP-1) in the soleus muscle of hindlimb unloaded rat. Eight-week-old male Sprague Dawley rats were randomly divided into four groups corresponding to different hindlimb unloading (HU) duration at 0, 1, 2, and 3 wk. Muscle atrophy and capillary regression worsened in the soleus muscle with longer periods of HU. The VEGF-A protein expression level was lower at week 1 than at week 0. In addition, the value at week 3 was also lower than those at weeks 0, 1, and 2. The TSP-1 protein expression level was higher at week 1 than that at week 0 but was similar at weeks 2 and 3. Moreover, reactive oxygen species, assessed by dihydroethidium fluorescence intensity on cryosection, were higher at weeks 2 and 3 than that at week 0. Depending on the HU period, VEGF-A and TSP-1 showed different expression patterns. In the early HU phase, TSP-1 may play an important role in capillary regression. However, when HU extends for a longer period, decreased VEGF-A, and/or increased oxidative stress may be more involved in capillary regression.


Cerebral hemodynamics and fetal behavioral states.
This study aimed to evaluate the hemodynamic patterns of the proximal (M1) and distal (M2) portions of the middle cerebral artery, during different fetal behavioral states. The study included 20 normal singleton pregnancies at between 36 and 40 weeks of gestation. After identification of the fetal behavioral state (FBS), flow velocity evaluation was performed on the proximal and distal segments of the middle cerebral artery during 'quiescence' (FBS-1F) and 'activity' (FBS-2F). A statistically significant decrease of pulsatility index, reflecting a decrease of impedance to flow values, was identified in both segments of the middle cerebral artery (MCA) during 'activity', with a more marked decrease in the MCA-M2 than in MCA-M1 (M1, P = 0.0028; M2, P = 0.00000085). The mean fetal heart rate during 'quiescence' was significantly lower than during 'activity' (P = 0.0047). However, there was no significant correlation between the pulsatility index of both segments of the middle cerebral artery and the fetal heart rate during different fetal behavioral states. The results of this study provide evidence of the influence of different fetal behavioral states on fetal cerebral hemodynamic patterns. We believe it is better to sample the proximal segment in clinical practice because it is less influenced by fetal behavioral state. This information should be considered when evaluating fetal cerebral hemodynamics.


External validation of the recommendations of the multidisciplinary consensus about inhaled therapies.
The understanding of physicians and the skill of patients in the use of inhalers continues to be inadequate. The external validation, by an expert panel, of practical clinical recommendations that had been developed in order to improve the knowledge and understanding of correct inhaled therapy use. After a bibliographic review about inhaled therapies, 40 clinical recommendations were proposed. A two-round modified Delphi consensus was used to compare the opinions of a panel of 59 experts about the recommendations, which were grouped into 8 areas: general aspects (4), inhaled drugs (9), pressurized metered-dose and spacer inhalers (6), powder inhalers (4), nebulizers (3), devices for mechanical ventilation (3), inhalers for children (5) and issues related with compliance and education (6). After the first round of the consensus panel, 35 of the 40 recommendations analyzed were accepted. At the end of round 2, agreement was reached in 39 (97.5%). In 8 (20%), the consensus was unanimous (100%). Item 14 was deleted from the recommendations as consensus was not reached. The external validation by experts in inhaled therapy found a high level of agreement with the clinical recommendations proposed. This consensus provides a tool that could contribute to the improved use of inhalers in our country in the future.


ULTRASOUND IMAGING MEASUREMENT OF THE TRANSVERSUS ABDOMINIS IN SUPINE, STANDING, AND UNDER LOADING: A RELIABILITY STUDY OF NOVICE EXAMINERS.
Military personnel and first responders (police and firefighters) often carry large amounts of gear. This increased load can negatively affect posture and lead to back pain. The ability to quantitatively measure muscle thickness under loading would be valuable to clinicians to assess the effectiveness of core stabilization treatment programs and could aid in return to work decisions. Ultrasound imaging (USI) has the potential to provide such a measure, but to be useful it must be reliable. To assess the intrarater and interrater reliability of measurements of transversus abdominis (TrA) and internal oblique (IO) muscle thickness conducted by novice examiners using USI in supine, standing, and with an axial load. Prospective, test-retest study. Healthy, active duty military (N=33) personnel were examined by two physical therapy doctoral students (primary and secondary ultrasound technicians) without prior experience in USI. Thickness measurements of the TrA and IO muscles were performed at rest and during a contraction to preferentially activate the TrA in three positions (hook-lying, standing, and standing with body armor). Percent thickness changes and intraclass correlation coefficients (ICC) were calculated. Using the mean of three measurements for each of the three positions in resting and contracted muscle states, the intrarater ICC (3,3) values ranged from 0.90 to 0.98. The interrater ICC (2,1) values ranged from 0.39 to 0.79. The ICC values of percent thickness changes were lower than the individual ICC values for all positions and muscle states. There is excellent intrarater reliability of novice ultrasound technicians measuring abdominal muscle thickness using USI in three positions during the resting and contracted muscle states. However, interrater reliability of two novice technicians was poor to fair, so additional training and experience may be necessary to improve reliability. 2b.


N.M.R. of 'oriented' monosubstituted amides--cis and trans N-methyl formamide.
The n.m.r. spectrum of N-methyl formamide oriented in a lyotropic liquid crystal solvent shows the presence of the cis as well as the trans forms. Analysis of the spectra due to both the species has been carried out. Possible non-planar distortions at the nitrogen atom for the trans species have been computed using the derived dipolar couplings and the available structural data.


The emerging role of microRNAs in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
The novel coronavirus disease 2019 (COVID-19) pandemic has imposed significant public health problems for the human populations worldwide after the 1918 influenza A virus (IVA) (H1N1) pandemic. Although numerous efforts have been made to unravel the mechanisms underlying the coronavirus, a notable gap remains in our perception of the COVID-19 pathogenesis. The innate and adaptive immune systems have a pivotal role in the fate of viral infections, such as COVID-19 pandemic. MicroRNAs (miRNAs) are known as short noncoding RNA molecules and appear as indispensable governors of almost any cellular means. Several lines of evidence demonstrate that miRNAs participate in essential mechanisms of cell biology, regulation of the immune system, and the onset and progression of numerous types of disorders. The immune responses to viral respiratory infections (VRIs), including influenza virus (IV), respiratory syncytial virus (RSV), and rhinovirus (RV), are correlated with the ectopic expression of miRNAs. Alterations of the miRNA expression in epithelial cells may contribute to the pathogenesis of chronic and acute airway infections. Hence, analyzing the role of these types of nucleotides in antiviral immune responses and the characterization of miRNA target genes might contribute to understanding the mechanisms of the interplay between the host and viruses, and in the future, potentially result in discovering therapeutic strategies for the prevention and treatment of acute COVID-19 infection. In this article, we present a general review of current studies concerning the function of miRNAs in different VRIs, particularly in coronavirus infection, and address all available therapeutic prospects to mitigate the burden of viral infections.


Metabolic profiling of transgenic adenocarcinoma of mouse prostate (TRAMP) tissue by 1H-NMR analysis: evidence for unusual phospholipid metabolism.
The TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mouse model has frequently been used in preclinical studies with chemotherapeutic/chemopreventive rationales. Here the hypothesis was tested using (1)H-NMR-based metabolic profiling that the TRAMP tumor metabolic phenotype resembles that reported for human prostate cancer. Aqueous extracts or intact tissues of normal prostate from 8- ("young") or 28-("old") week-old C57BL/6J wild-type mice or of prostate tumor from age-matched TRAMP mice were analyzed by (1)H-NMR. Results were compared with immunohistochemical findings. Expression of choline kinase was studied at the protein and mRNA levels. In young TRAMP mice presenting with zonal hyperplasia, the ratio of glycerophosphocholine (GPC) to phosphocholine (PC) was 22% below that in wild-type mice (P < 0.05). In old TRAMP mice with well-defined malignancy, reduced tumor levels of citrate (49%), choline (33%), PC (57%), GPC (66%), and glycerophosphoinositol (61%) were observed relative to normal prostate (P < 0.05). Hierarchical cluster analysis of metabolite levels distinguished between normal and malignant tissue in old but not young mice. While the reduction in tissue citrate resembles human prostate cancer, low levels of choline species in TRAMP tumors suggest atypical phospholipid metabolism as compared to human prostate cancer. TRAMP tumor and normal prostate tissues did not differ in expression of choline kinase, which is overexpressed in human prostate cancer. Although prostate cancer in TRAMP mice shares some metabolic features with that in humans, it differs with respect to choline phospholipid metabolism, which could impact upon the interpretation of results from biomarker or chemotherapy/chemoprevention studies.


Medical mistrust, culturally targeted message framing, and colorectal cancer screening among African Americans.
Mistrust in the information and treatment provided by medical professionals and organizations hinders cancer screening among African Americans. However, its impact on responses to health messaging aimed at bolstering screening uptake is unknown. The present study examined the effects of medical mistrust on message framing and culturally targeted health messaging about colorectal cancer (CRC) screening. Screening eligible African Americans (N = 457) completed the Group-Based Medical Mistrust scale and then viewed an informational video about CRC risks, prevention, and screening, during which all participants received either a gain or loss-framed message about screening. Half of participants received an additional culturally targeted screening message. After messaging, all participants completed Theory of Planned Behavior measures of CRC screening receptivity, as well as items assessing expectations about experiencing racism when obtaining CRC screening (i.e., anticipatory racism). Hierarchical multiple regressions showed that medical mistrust predicted lower screening receptivity and greater anticipatory racism. Additionally, effects of health messaging were moderated by medical mistrust. Among participants high in mistrust, targeted messaging-regardless of message frame-bolstered normative beliefs about CRC. Additionally, only targeted loss-framed messaging bolstered attitudes toward CRC screening. Although targeted messaging reduced anticipatory racism among participants with high mistrust, anticipatory racism did not mediate messaging effects. Findings indicate medical mistrust may be an important culturally-relevant individual difference to attend to in addressing CRC screening disparities, including its potential to impact responses to cancer screening messaging.


Effectiveness of seasonal influenza vaccine in adult Japanese workers, 2017-2020.
Previous studies have not estimated vaccine effectiveness (VE) against influenza in the working-age Japanese population. In this study, we determined VE in adult workers at a Japanese company. We estimated VE based on self-reported data regarding influenza infections and vaccinations in employees of an auto parts manufacturing company during three influenza seasons from 2017 to 2020. VE was estimated as 100% × [1 - odds ratio (the ratio of the odds of being diagnosed with influenza among enrollees with and without influenza vaccination)]. Odds ratios were estimated using logistic regression. We included 11,347 worker records [3,592 (2017-18), 3,663 (2018-19), and 4,092 (2019-20)] from employees who had worked with the company throughout each influenza season. The adjusted VE was moderate and significant in the 2019-20 season (VE = 53%; 95% confidence interval [CI] = 30% to 69%) but low or negative and non-significant during the 2017-18 (VE = 28%; 95% CI = -5% to 50%) and 2018-19 (VE = -11%; 95% CI = - 42% to 14%) seasons. Influenza vaccines were moderately effective during the 2019-20 season but showed low or negative effectiveness during the 2017-18 and 2018-19 seasons. Self-reports from worker records can successfully help determine VE against influenza.


Resonance assignments of sigma factor S binding protein Crl from Escherichia coli.
During bacterial transcription, sigma (σ) factors reversibly bind to RNA polymerase (RNAP) and recognize specific promoter sequences to initiate the process. While different sigma factors are utilized under different external conditions, Sigma S (RpoS, σS), a stress-responding sigma factor, is activated when bacteria face external threats. σS, which has a much lower affinity to RNAP compared with sigma D (RpoD, σ70), is controlled by a very complex network of regulatory factors. Crl protein, a transcriptional factor from Escherichia coli (E. coli, Ec), stimulates σS-dependent transcription by promoting the association of σS with core RNA polymerase. As an important regulator for σS, Crl is induced by low temperature, leading to an increased transcription rate of a subset of genes of the rpoS regulon under stress conditions or in stationary phase of growth. However, the underlying molecular mechanism for Crl/σS remains elusive. Here we describe the complete 1H, 13C and 15N chemical shift assignments of Crl as the basis for NMR structure determination and interaction studies.


Benzophenone derivatives as cysteine protease inhibitors and biological activity against Leishmania(L.) amazonensis amastigotes.
The leishmanicidal potential of benzophenones has been described, some of them highlighting their potential as cysteine protease inhibitors. Therefore, this work described leishmanicidal activity of nine benzophenone derivatives (1a-c;2a-c;3a-c) against intramacrophage amastigote forms of Leishmania(L.)amazonensis (IC50) and the cytotoxic effect on murine peritoneal macrophages (CC50). The derivative 1c exhibited a selectivity index SI (CC50/IC50) of 6.7, besides cytotoxicity lower than Amphotericin B (p< 0.05). Moreover it showed inhibitory activity against papain (42.8±0.3, p<0.05), and when tested on trypanosomatids cysteine proteases 1c also proved to be a potent inhibitor of rCPB2.8, rCPB3.0 and cruzain, showing non-competitive inhibition mechanism by enzymatic assays in vitro.So, benzophenone 1c is interesting drug candidate prototype, with a multi-target directed mode of action, inhibiting rCPB2.8, rCPB3.0 and cruzain.


Up-regulation of the G(q/11alpha) protein and protein kinase C during the development of sensitization to morphine-induced hyperlocomotion.
It has been recognized that protein kinase C (PKC) pathway is involved in the synaptic plasticity. The present study was then designed to examine the changes in G(q/11alpha) and G(betagamma) subunits and PKC activity on sensitization to the morphine-induced hyperlocomotion. Repeated subcutaneous administration of morphine every 72 h produced sensitization to the morphine-induced hyperlocomotion. In morphine-sensitized mice, the protein level of G(q/11alpha) subunit in the limbic forebrain including the nucleus accumbens, but not in the lower midbrain containing the ventral tegmental area, was markedly increased, whereas the levels of G(betagamma) subunit were not altered in either areas. Under these conditions, the levels of membrane-bound phosphorylated-PKC in the limbic forebrain was clearly up-regulated by intermittent morphine treatment. We also found the lack of changes in the level of the regulator of G protein signaling 4, which is a specific G(q/11alpha)-dependent GTPase activating protein, in the limbic forebrain obtained from morphine-sensitized mice. These results indicate that the up-regulation of membrane-bound PKC following intermittent morphine treatment results from the increase in levels of G(q/11alpha) protein. In order to investigate the direct involvement of PKC in the morphine-induced hyperlocomotion, the locomotion induced by acute morphine treatment in the presence or absence of a PKC inhibitor was measured. A specific PKC inhibitor Ro-32-0432 given intracerebroventricularly caused a dose-dependent inhibition of morphine-induced hyperlocomotion. These findings suggest that the up-regulation of G(q/11alpha)-dependent PKC activity in membranes of the limbic forebrain is implicated in the development of sensitization to morphine-induced hyperlocomotion in mice.


LncRNA XXYLT1-AS2 promotes tumor progression via autophagy inhibition through ubiquitinated degradation of TFEB in hepatocellular carcinoma.
There is compelling evidence that long-stranded non-coding RNAs (lncRNAs) play an important role in the progression of hepatocellular carcinoma (HCC). The aim of this study was to investigate the role of lncRNA XXYLT1 antisense-2 (XXYLT1-AS2) in HCC progression. Real-time PCR was used to assess the levels of XXYLT1-AS2 in plasma from HCC and normal patients. Cell proliferation, apoptosis, migration, and invasion were monitored, and tumor xenografts were established to investigate the biological functions of XXYLT1-AS2 by gain-of-function and loss-of-function studies in vitro and in vivo, the expression of autophagy biomarkers and transcriptional factor EB (TFEB) was examined by immunoprecipitation, ubiquitination assays, and western blotting. Autophagy inhibitor, 3-methyladenine (3MA), and proteasome inhibitor, MG132, were used to verify the role of autophagy in HCC progression and the effect of XXYLT1-AS2 on TFEB ubiquitination, respectively. In this study, we identified that lncRNA XXYLT1-AS2 is highly expressed in HCC plasma and promotes tumor growth in vivo. In functional studies, it was found that silent expression of XXYLT1-AS2 inhibited HCC proliferation, migration, invasion, and activated autophagy of HCC cells, which were attenuated by autophagy inhibitor, 3MA. Mechanistically, XXYLT1-AS2 decreased the protein level of TFEB through promoting its degradation by ubiquitin proteasome pathway. XXYLT1-AS2 plays an oncogenic role in HCC progression through inhibition of autophagy via promoting the degradation of TFEB, and thus could be a novel target for HCC treatment.


Evaluation of gravimetric assays of the H2O concentration in human serum and urine.
The oven-drying method and the combined freeze- and oven-drying method for gravimetrical measurement of human serum and urine H2O concentration, as well as two reported formulas for the calculation of the serum H2O concentration were evaluated. Day-to-day precision in serum and urine (coefficient of variation (CV) less than 0.95%), and recovery in serum (95-99%) were excellent. Storage at 4 degrees C and at -20 degrees C was safe at least for 3 wk and 2 mth, respectively. For the oven-drying method, which was the most practical, reference values after fasting overnight were determined (n = 47; 99% confidence interval; serum, 48.8-51.6 mol/l; urine, 51.2-53.8 mol/l). Patients in different disease categories were tested (n = 38), and had normal values mostly. Low serum values were found in a patient after hemodialysis with ultrafiltration (47.0 mol/l), and in two patients with an extreme hyperproteinemia (48.8 mol/l) and hypercholesterolemia (48.1 mol/l), respectively. Formulas for calculation of the serum H2O concentration proved unreliable. When direct measurement is impossible, a serum value of 50.5 mol/l can be substituted.


[Evaluation of the preoperative staging of rectal cancer by magnetic resonance imaging].
To evaluate the value of MRI in preoperative staging of rectal cancer. The data of 156 rectal cancer patients,undergone MRI scans from December 2004 to June 2006 in our hospital, were analyzed retrospectively. Findings of MRI were compared with postoperative pathological examinations. Intracavitary localized parenchyma tumors were seen in 72 cases, and intestinal wall abnormal incrassation or stricture in other 84 cases from MRI scan. Sixteen cases had rectal polyps simultaneously, 2 cases ovarian cysts, 13 cases anterior-sacral metastases and 2 cases bone metastases. The sensitivity and specificity of T(1-2), T(3) and T(4) rectal cancer by MRI examination were 25%(8/32), 93.3%(84/90), 94.1%(32/34) and 100%(124/124), 57.6%(38/66), 96.7%(118/122) respectively. In MRI imaging, metastatic para-rectal lymph node was diagnosed as the diameter >5 mm or abnormal border or mixed resonance, with a sensitivity of 85.1%(80/94) and specificity of 45.2%(28/62). MRI has high accuracy for preoperative staging of rectal cancer, and is useful to detect the serosal infiltration and lymph node metastasis.


Vulnerability to diet-induced obesity is associated with greater food priming-induced reinstatement of palatable food seeking.
We examined whether individual differences in weight gain during exposure to a "junk-food" diet were related to differences in later relapse-like behavior in a rat model. Following free access to a junk-food diet for 7 weeks, rats were trained to press a lever for palatable food pellets. Following extinction training, rats were tested for cue- and pellet priming-induced reinstatement. Results showed that rats prone to obesity while on the junk-food diet displayed greater pellet priming-, but not cue-, induced reinstatement relative to obesity-resistant rats, suggesting that obesity vulnerability is a factor determining one's chances for some types of relapse.


Observations of Forsythia koreana methanol extract on mast cell-mediated allergic reactions in experimental models.
To explore effects of Forsythia koreana methanol extract (FKME) on mast cell-mediated allergic and inflammatory properties, the effect of FKME was evaluated on compound 48/80-induced systemic anaphylaxis, ear swelling, and anti-dinitrophenyl (DNP) immunoglobulin E (IgE)-induced passive cutaneous anaphylaxis (PCA). In addition, the effect of FKME was investigated on the histamine release from rat peritoneal mast cells (RPMCs) stimulated by compound 48/80, which promotes histamine release. The human mast cell line HMC-1 was stimulated by phorbol 12-myristate 13-acetate plus calcium ionophore A23187. Activated HMC-1 can produce several proinflammatory and chemotactic cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8. Cytokine levels in the culture supernatant were measured by an enzyme-linked immunosorbent assay. Cytotoxicity by FKME was determined by a 3-(4,5-dimethylthiazol-2-yl)-diphenyl-tetrazolium bromide (MTT) assay. FKME inhibited compound 48/80-induced systemic anaphylactic shock and ear swelling in mice. When 1 g/kg FKME was pretreated or posttreated with mice, compound 48/80-induced mice morality was 50 and 66.7%, respectively. One gram per kilogram of FKME pretreatment inhibited ear-swelling responses derived from compound 48/80 by 29.75%. A PCA reaction was inhibited by 17.9%. In an in vitro model, FKME (1 mg/ml) inhibited histamine release from the RPMCs by 13.8% and TNF-alpha, IL-6, and IL-8 production from HMC-1 cells by 71.16% (P < 0.001), 86.72% (P < 0.001), and 44.6%, respectively. However, FKME had no cytotoxic effects on cell viability. In conclusion, FKME inhibited not only systemic anaphylaxis and ear swelling induced by compound 48/80 but also inhibited a PCA reaction induced by anti-DNP IgE in vivo. Treatment with FKME showed significant inhibitory effects on histamine, TNF-alpha, IL-6, and IL-8 release from mast cells.


Identification of secondary splenic lymphoma with contrast-enhanced ultrasound in the pediatric population. A case report.
Contrast-enhanced ultrasound scan (CEUS) is the application of ultrasound contrast agents (UCAs) to traditional ultrasound. Our aim is to report the use of CEUS for a prompt assessment of a suspected secondary splenic lymphoma in a child, which, in our experience, has allowed an accurate description of the parenchymal perfusion and vascularization pattern, leading to a confident diagnosis. We suggest that CEUS will replace Magnetic resonance imaging (MRI) or Computed tomography (CT) as standard imaging option for differential diagnosis of spleen lesions in pediatric population. As a result this will lead to decreasing the overall use of ionizing radiation and reducing the time interval to a certain diagnosis.


Dechlorination of polyvinyl chloride electric wires by hydrothermal treatment using K2CO3 in subcritical water.
Polyvinyl chloride (PVC) waste generation has significantly increased in recent years and their disposal is considered a major environmental concern. Removal techniques of chlorine from PVC waste are being studied to minimize a negative environmental impact. In this work, the use of K2CO3 as an alkaline additive to improve the dechlorination efficiency (DE) in the hydrothermal degradation of PVC wires was studied. Different experiments were carried out varying both temperature (175, 200, 225, 235 and 250 °C) and K2CO3 concentration (0.025, 0.050 and 0.125 M), using a solid/liquid ratio of 1:5 in order to determine the evolution of the dechlorination efficiency with time. About 4.66, 21.1, 24.4, 45.7 and 92.6 wt% of chlorine in PVC wire was removed during hydrothermal dechlorination (HTD) with an additive/chlorine ratio of 1:25 (K2CO3 solution of 0.050 M) at 175, 200, 225, 235 and 250 °C, respectively. Optimal additive/chlorine ratio decreased to 1:50 (K2CO3 solution of 0.025 M) at 250 °C, obtaining a dechlorination degree of 99.1% after 4 h without the need of metallic catalysts. Concerning the solid phase behavior during dechlorination, a linear correlation between the DE reached and the weight loss of PVC was found.


Relationship between non-photochemical quenching efficiency and the energy transfer rate from phycobilisomes to photosystem II.
The chromophorylated PBLcm domain of the ApcE linker protein in the cyanobacterial phycobilisome (PBS) serves as a bottleneck for Förster resonance energy transfer (FRET) from the PBS to the antennal chlorophyll of photosystem II (PS II) and as a redirection point for energy distribution to the orange protein ketocarotenoid (OCP), which is excitonically coupled to the PBLcm chromophore in the process of non-photochemical quenching (NPQ) under high light conditions. The involvement of PBLcm in the quenching process was first directly demonstrated by measuring steady-state fluorescence spectra of cyanobacterial cells at different stages of NPQ development. The time required to transfer energy from the PBLcm to the OCP is several times shorter than the time it takes to transfer energy from the PBLcm to the PS II, ensuring quenching efficiency. The data obtained provide an explanation for the different rates of PBS quenching in vivo and in vitro according to the half ratio of OCP/PBS in the cyanobacterial cell, which is tens of times lower than that realized for an effective NPQ process in solution.


Actions of orally administered organotin compounds on heme metabolism and cytochrome P-450 content and function in intestinal epithelium.
The gastrointestinal tract is a major route by which humans are exposed to environmental chemicals. We have examined in these studies the effects of oral administration of organotin compounds in the small intestinal epithelium, an organ which exhibits highly active drug and other chemical metabolism. A series of n-butyltin compounds was administered by gavage to male Sprague-Dawley rats (225-275 g) in single doses up to 250 mumol/kg body weight. Bis(tri-n-butyltin)oxide (TBTO) produced dose- and time-dependent decreases in the content and functional activity of intestinal cytochrome P-450, together with an elevation (3-fold) in the activity of microsomal heme oxygenase. The effects of di-n-butyltin dichloride on heme oxygenase and cytochrome P-450 were pronounced in the small intestine and extended to the liver and kidneys within 21 hr after oral-exposure, whereas TBTO did not affect the liver until much later (6 days), when cytochrome P-450 content was reduced markedly (30%). Furthermore, the effects produced by tetra-n-butyltin on cytochrome P-450 at 24 hr were localized in the intestinal epithelium. These studies indicate important pharmacological effects of organotin compounds in the gut, and raise the possibility that concurrent oral ingestion of organotins with other environmental pollutants may alter the cytochrome P-450-dependent metabolism of xenobiotics and natural substrates of this monooxygenase system in the small intestine.