Modulation of c-kit expression in pancreatic adenocarcinoma: a novel stem cell marker responsible for the progression of the disease.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers because of late symptoms and resistance to chemotherapy and radiation therapy. We have investigated the appearance of c-kit, a stem cell marker, in both normal adult pancreatic tissue and in cancerous tissue. Apart from some very pale staining of islets of Langerhans, normal pancreas was devoid of staining with antibodies to c-kit. In contrast, in cancerous tissue that still preserves the overall integrity of the pancreatic tissue, there was a clear labeling in islets of Langerhans, which seemed to be co-localized with insulin containing β cells. In other cases, where the pancreatic tissue was completely deteriorated, intensive labeling was clearly evident in remnants of both the exocrine and the endocrine tissues. The duct cells of the adenocarcinoma were moderately but clearly labeled with antibodies to c-kit. In contrast, in metastasis of PDAC, very intensive labeling of c-kit was evident. The location of KRAS, which is strongly associated with PDAC, was also analyzed at the initial stages of the disease, when islets of Langerhans still preserve their integrity to a large extent. KRAS was found exclusively in islets of Langerhans and overlapped in its location with insulin and c-kit expressing cells. It is suggested that the modulation of the expression of c-kit, visualized by antibodies to the oncogene molecule, may play an important role in the formation and progression of PDAC. The absence of c-kit in normal pancreas and its appearance in PDAC is probably due to a mutational event, which probably allows conversion of the β cells into cancer stem cells (CSC). Co-expression of both c-kit and KRAS, typical markers for CSC with overlapping with insulin in islets of Langerhans, strongly support the notion that β-cells play a central role in the development of PDAC. The use of specific drugs that can attenuate the kinase activity of c-kit or target KRAS expressing cancer cells should be tested in order to attenuate the progression of this lethal disease.


Two-dimensional CT measurements enable assessment of body composition on head and neck CT.
The aim of this study was to evaluate whether simple 2D measurements in axial slices of head and neck CT examinations correlate with generally established measurements of body composition in abdominal CT at the height of the third lumbar vertebra and thus allow for an estimation of muscle and fat masses. One hundred twenty-two patients who underwent concurrent CT of the head and neck and the abdomen between July 2016 and July 2020 were retrospectively included. For a subset of 30 patients, additional bioelectrical impedance analysis (BIA) was available. Areas of paraspinal muscles at the height of the third (C3) and fifth cervical vertebrae (C5) as well as the total cross-sectional area at the height of C3 and at the submandibular level were correlated with the results of abdominal measurements and BIA. Furthermore, intra- and interreader variabilities of all measurements were assessed. Regarding adipose tissue, good correlations were found between the total cross-sectional area of the patient's body at the submandibular level and at the height of C3 between both abdominal measurements and BIA results (r = 0.8-0.92; all p < 0.001). Regarding muscle, the total paraspinal muscle area at the height of C3 and C5 showed strong correlations with abdominal measurements and moderate to strong correlations with BIA results (r = 0.44-0.80; all p < 0.001), with the muscle area on C5 yielding slightly higher correlations. Body composition information can be obtained with comparable reliability from head and neck CT using simple biplanar measurements as from abdominal CT. • The total paraspinal muscle area at the height of C3 and C5 correlates strongly with abdominal muscle mass. • The total cross-sectional area at the submandibular level and at the height of C3 shows good correlations with abdominal fat mass. • The described measurements facilitate a rapid, opportunistic assessment of relevant body composition parameters.


E65 K polymorphism in KCNMB1 gene is not associated with ischaemic heart disease in Spanish patients.
Hypertension is a main risk factor for atherosclerosis through vascular wall hyperplasia. A recent study reported a new polymorphism (E65 K) in the beta(1) subunit (KCNMB1) gene of the Ca(2+)-dependent potassium channel with a protective effect against the severity of diastolic hypertension, but further data have lead to conflicting results. In order to ascertain the involvement of the E65 K variant in cardiovascular system regulation, the potential association between this mutation and ischaemic heart disease was assessed through a family-based association study (n=302 individuals). Transmission disequilibrium analysis failed to detect any association between this polymorphism and ischaemic heart disease. Although a minor effect cannot be discarded, sample analytical power and negative results do not support a major role for E65 K polymorphism in atherogenic pathologies.


The emerging role of lncRNAs in the regulation of cancer stem cells.
Tumors contain a functional subpopulation of cells that exhibit stem cell properties. These cells, named cancer stem cells (CSCs), play significant roles in the initiation and progression of cancer. Long non-coding RNAs (lncRNAs) can act at the transcriptional, posttranscriptional and translational level. As such, they may be involved in various biological processes such as DNA damage repair, inflammation, metabolism, cell survival, cell signaling, cell growth and differentiation. Accumulating evidence indicates that lncRNAs are key regulators of the CSC subpopulation, thereby contributing to cancer progression. The aim of this review is to overview current knowledge about the functional role and the mechanisms of action of lncRNAs in the initiation, maintenance and regulation of CSCs derived from different neoplasms. These lncRNAs include CTCF7, ROR, DILC, HOTAIR, H19, HOTTIP, ATB, HIF2PUT, SOX2OT, MALAT-1, CUDR, Lnc34a, Linc00617, DYNC2H1-4, PVT1, SOX4 and ARSR Uc.283-plus. Furthermore, we will illustrate how lncRNAs may regulate asymmetric CSC division and contribute to self-renewal, drug resistance and EMT, thus affecting the metastasis and recurrence of different cancers. In addition, we will highlight the implications of targeting lncRNAs to improve the efficacy of conventional drug therapies and to hamper CSC survival and proliferation. lncRNAs are valuable tools in the search for new targets to selectively eliminate CSCs and improve clinical outcomes. LncRNAs may serve as excellent therapeutic targets because they are stable, easily detectable and expressed in tissue-specific contexts.


Kinetic properties and functional role of creatine phosphokinase in glycerinated muscle fibers--further evidence for compartmentation.
The following phenomena were observed when relative contraction and relaxation effects of ATP and creatine phosphate (CP) were studied in rabbit psoas muscle glycerinated fiber bundles containing native creatine phosphokinase (CPK) and ATPase activities: (1) nucleotide was absolutely necessary for contraction; (2) in the presence of a small amount of ADP (250 microM), physiological concentration of CP (10 mM) produced faster and stronger contraction and faster, more complete, relaxation than equimolar or higher concentrations of ATP; (3) if the nucleotide was in the form of ATP, the nucleotide Km for contraction was about 1.5 mM; (4) if the nucleotide was in the form of ADP, the nucleotide Km for contraction at physiological concentration of CP (10 mM) was 0.076 to 1.18 mM depending upon the order of addition of ADP and CP; (5) the apparent Km for CP for contraction was 2.67 mM independent of sequence of addition of ADP and CP.


Transcriptome analysis reveals functional roles of nacreous protein N16 in prednisolone-induced osteoporotic zebrafish.
N16 is an active protein isolated and screened from nacre proteins. Our previous studies have shown that N16 exerted a good effect on osteoporosis caused by dexamethasone on female rats. In order to further confirm the action of N16 against glucocorticoid-induced osteoporosis (GIOP) and clarify its possible mechanisms, prednisolone-treated larval zebrafish (Danio rerio) model was adopted. Administration of N16 resulted in a significant increase of vertebral bone density of osteoporotic zebrafish, indicating a good effect of N16 against GIOP. Transcriptomic sequencing analysis was then performed to investigate the mechanisms of the action of N16 against GIOP. It was observed that N16 modulated the osteoporotic phenotype by up-regulating the osteoblastic characteristic genes and down-regulating the osteoclastic characteristic genes in zebrafish.


The effect of long-term radiofrequency exposure on cognition in human observational studies: A protocol for a systematic review.
The long term effects of exposure to radiofrequency (RF) electromagnetic fields (EMF) for frequencies from 100 kHz to 300 GHz on cognitive performance are best assessed using observational studies. In recent years, the use of mobile (cell) phones has been the main source of RF EMF exposure to the brain, although other sources of exposure may be significant. Cognitive function includes various mental and psychological abilities, which can be measured in a range of domains, such as learning, memory, reasoning, problem solving, decision making and attention. Although effects on cognitive function may be most evident later in life, in the experimental setting acute and immediate effects can only be studied. Observational studies are needed when effects are observed after months or years following short or long-term exposure. The importance of the effects of exposure on children has also been recently identified. To assess the long-term effects of RF EMF local and whole-body exposure compared to no or a lower level of exposure on indicators of cognition, including complex attention, executive function, learning and memory, perceptual motor ability and social cognition, but excluding cognitive effects caused by neurodegenerative diseases or neurodevelopmental disorders, and to assess if there is evidence of a dose response relationship. We will include observational studies that have evaluated cognitive effects of RF energy including a comparator group with a different level of exposure. Studies must report at least one validated measure of cognitive function, including global or domain specific measures, or cognitive impairment, with a minimum follow-up of 6 months. Cohort or case-control studies published in the peer review literature in any language are eligible. We will exclude cross-sectional studies and any that only report brain structure or biomarkers. We will conduct searches of PubMed, Embase, PsycINFO and the EMF-Portal. At least two authors will independently screen the titles/abstracts of all records, with any conflicts resolved by a third reviewer. Full-text screening will also be conducted independently by two authors with conflicts resolved by consensus. Data will be extracted from the studies included, such as identifiers and characteristics of the study design, exposure and comparator groups, participants, outcomes assessed and results. Risk of bias will be assessed with the Office of Health Assessment and Translation (OHAT) tool. We will conduct a meta-analysis of similar studies with a random effects model in STATA or similar software, if two or more studies are available for a given exposure-outcome combination. Confidence in the body evidence will be judged using GRADE methods as adapted by OHAT for reviews of environmental exposures.


Standard subcutaneous dosing of unfractionated heparin for venous thromboembolism prophylaxis in surgical ICU patients leads to subtherapeutic factor Xa inhibition.
To assess coagulation status and factor Xa inhibition in surgical intensive care unit (ICU) patients administered prophylactic unfractionated heparin for venous thromboembolism (VTE) prophylaxis. We conducted a randomized, single-blind study at a tertiary academic medical center. Included were patients 18 years and older admitted to the surgical ICU directly after major abdominal surgery. Exclusion criteria included significant bleeding risk, preoperative anticoagulation, or history of heparin-induced thrombocytopenia. Patients were randomized to two regimens for VTE prophylaxis: standard of care unfractionated heparin, 5,000 units subcutaneously three times daily (SQH) versus unfractionated heparin via intravenous infusion, titrated to an activated partial thromboplastin time of 40-45 s (IVH). Blood samples were taken prior to surgical incision on day 0 and daily for 5 days after surgery. Samples were analyzed for factor Xa inhibition and viscoelastic whole blood clotting parameters (Sonoclot analyzer). A total of 50 patients were randomized to either SQH or IVH. The majority of patients had cancer. Patients in the SQH group had no detectable peak anti-factor Xa (aFXa) activity for 5 days after surgery, while patients in the IVH group had statistically elevated levels compared to the SQH group on days 3-5. SQH patients demonstrated a hypercoagulable profile on Sonoclot, while IVH patients displayed a normal profile. Standard of care subcutaneous dosing of unfractionated heparin for VTE prophylaxis in surgical ICU patients leads to subtherapeutic levels of factor Xa inhibition.


Immigrant generation status and its association with pubertal timing and tempo among Hispanic girls and boys.
In the United States, Hispanic-Latino children reach puberty earlier on average than non-Hispanic white children. Yet among U.S. Hispanic/Latino children, pubertal timing comparisons between immigrant generations have not been made, hence we examined whether pubertal timing differs by immigrant generational status, independent of BMI and acculturation measures. Cross-sectional data on 724 boys and 735 girls, aged 10-15 years, from the Hispanic Community Children's Health Study/Study of Latino (SOL) Youth, were used to predict the median ages of thelarche, pubarche, and menarche in girls, and pubarche and voice change in boys, using Weibull survival models, while adjusting for SOL center, BMI, and acculturation. In girls, the first generation began thelarche earlier than second and third generations (median age [years] [95% confidence interval]: 7.4 [6.1, 8.8] vs. 8.5 [7.3, 9.7] and 9.1 [7.6, 10.7], respectively), but began menarche later (12.9 [12.0,137] vs. 11.8 [11.0, 12.5] and 11.6 [10.6, 12.6], respectively). Pubertal timing and tempo for boys did not differ by generational status. First-generation U.S. Hispanic/Latino girls had the earliest thelarche, latest menarche and longest pubertal tempo, compared to second and third generations. Factors beyond BMI and acculturation may account for the differences in pubertal timing by generational status of U.S. Hispanic/Latino girls.


[Influence of Different Growing Years on Accumulation of Flavonoids and Saponins in Astragali Radix].
To study the effects of different growing years on the accumulation of flavonoids and saponins in Astragali Radix, in order to offer evidence to determine the most appropriate harvest time. HPLC method was developed for the determination of the contents of flavonoids and saponins. The contents of flavonoids and saponins in different growing years of Astragali Radix existed obvious differences, the longer growing, the content was relatively higher. With the increase of growing years, the contents of flavonoids and saponins are roughly rising year by year, the harvest time has a great influence on the accumulation of the compositions.


Bioinformatics analysis of different candidate genes involved in hepatocellular carcinoma induced by HepG2 cells or tumor cells of patients.
Hepatocellular carcinoma (HCC) is a common cancer with a high mortality rate; the molecular mechanism involved in HCC remain unclear. We aimed to provide insight into HCC induced with HepG2 cells and identify genes and pathways associated with HCC, as well as potential therapeutic targets. Dataset GSE72581 was downloaded from the Gene Expression Omnibus, including samples from mice injected in liver parenchyma with HepG2 cells, and from mice injected with cells from patient tumor explants. Differentially expressed genes (DEGs) between the two groups of mice were analyzed. Then, gene ontology and Kyoto Encyclopedia of Gene and Genomes pathway enrichment analyses were performed. The MCODE plug-in in Cytoscape was applied to create a protein-protein interaction (PPI) network of DEGs. We identified 1,405 DEGs (479 upregulated and 926 downregulated genes), which were enriched in complement and coagulation cascades, peroxisome proliferator-activated receptor signaling pathway, and extracellular matrix-receptor interaction. The top 4 modules and top 20 hub genes were identified from the PPI network, and associations with overall survival were determined using Kaplan-Meier analysis. This preclinical study provided data on molecular targets in HCC that could be useful in the clinical treatment of HCC.


Monitoring regional astrocyte diversity by cell type-specific proteomic labeling in vivo.
Astrocytes exhibit regional heterogeneity in morphology, function and molecular composition to support and modulate neuronal function and signaling in a region-specific manner. To characterize regional heterogeneity of astrocytic proteomes of different brain regions we established an inducible Aldh1l1-methionyl-tRNA-synthetaseL274G (MetRSL274G ) mouse line that allows astrocyte-specific metabolic labeling of newly synthesized proteins by azidonorleucine (ANL) in vivo and subsequent isolation of tagged proteins by click chemistry. We analyzed astrocytic proteins from four different brain regions by mass spectrometry. The induced expression of MetRSL274G is restricted to astrocytes and identified proteins show a high overlap with proteins compiled in "AstroProt," a newly established database for astrocytic proteins. Gene enrichment analysis reveals a high similarity among brain regions with subtle differences in enriched biological processes and in abundances of key astrocytic proteins for hippocampus, cortex and striatum. However, the cerebellar proteome stands out with proteins being highly associated with the calcium signaling pathway or with bipolar disorder. Subregional analysis of single astrocyte TAMRA intensities in hippocampal layers indicates distinct subregional heterogeneity of astrocytes and highlights the applicability of our toolbox to study differences of astrocytic proteomes in vivo.


Deep learning and cognitive science.
In recent years, the family of algorithms collected under the term "deep learning" has revolutionized artificial intelligence, enabling machines to reach human-like performances in many complex cognitive tasks. Although deep learning models are grounded in the connectionist paradigm, their recent advances were basically developed with engineering goals in mind. Despite of their applied focus, deep learning models eventually seem fruitful for cognitive purposes. This can be thought as a kind of biological exaptation, where a physiological structure becomes applicable for a function different from that for which it was selected. In this paper, it will be argued that it is time for cognitive science to seriously come to terms with deep learning, and we try to spell out the reasons why this is the case. First, the path of the evolution of deep learning from the connectionist project is traced, demonstrating the remarkable continuity, and the differences as well. Then, it will be considered how deep learning models can be useful for many cognitive topics, especially those where it has achieved performance comparable to humans, from perception to language. It will be maintained that deep learning poses questions that cognitive sciences should try to answer. One of such questions is the reasons why deep convolutional models that are disembodied, inactive, unaware of context, and static, are by far the closest to the patterns of activation in the brain visual system.


Platelet aggregation in relationship to plasma catecholamines in patients with hypertension.
Plasma catecholamine concentration and platelet aggregation were studied in 22 patients with uncomplicated primary hypertension and 13 age-matched normotensive, healthy subjects at rest and in some during isometric handgrip exercise. The effect of norepinephrine (NE) infusion upon platelet aggregation was also examined. Plasma catecholamine concentration was slightly higher in the hypertensive than the normotensive group, but the difference was not significant. However, platelet aggregation to ADP was significantly greater in the hypertensive than the normotensive subjects. Exercise increased significantly both catecholamines and aggregation in both groups. Platelet aggregation was correlated with age (r = 0.62, P less than 0.01) and plasma NE (r = -0.34, P less than 0.05 for the total group of subjects). The infusion of NE increased significantly plasma NE and platelet aggregation and there was an inverse correlation between NE increase and threshold decrease (r = -0.69, P less than 0.05). Thus, plasma catecholamines and important determinants of platelet aggregation. However, in our study, uncomplicated primary hypertension was not associated with abnormal plasma catecholamine concentration. It is likely that the observed abnormal platelet aggregability to ADP represents a secondary phenomenon, possibly related to more advanced atherosclerotic vascular changes in hypertensive than normotensive subjects.


The effects of oxprenolol on ambulatory intra-arterial blood pressure in essential hypertension.
Continuous intra-arterial blood pressure recording using the "Oxford" technique has been used to study the antihypertensive effects of oxprenolol taken three times daily in fully ambulatory patients with essential hypertension, outside hospital. During the first 24 h of treatment there was a reduction in daytime heart rate and a small reduction in daytime blood pressure. After 10 weeks treatment there was a more substantial fall in daytime blood pressure from the hour of waking, but no effect on sleeping nighttime blood pressure or heart rate. Twenty-four hour variation, as assessed by the amplitude of a fitted regression curve, showed a reduction in heart rate but not blood pressure variation. In 4 patients restudied after 11 weeks treatment with oxprenolol (tid) and cyclopenthiazide at 9 a.m. there was some evidence of an antihypertensive effect occurring during both the daytime and nighttime.


Association between serum vitamin D status and health-related quality of life (HRQOL) in an older Korean population with radiographic knee osteoarthritis: data from the Korean national health and nutrition examination survey (2010-2011).
Vitamin D is important in bone health and its relationship with osteoarthritis has recently been reported. Both vitamin D deficiency and knee osteoarthritis are age dependent and are known to affect quality of life (QOL) in older populations. In this study, we aimed to determine the association between vitamin D status and health-related quality of life (HRQOL) in an older Korean population with knee osteoarthritis. A total of 2,165 participants aged ≥50 years with radiographic knee osteoarthritis defined as Kellgren-Lawrence (KL) grade ≥2 were selected from data from the 5th Korean National Health and Nutrition Examination Survey (KNHANES V), a representative cross-sectional nationwide survey conducted in 2010-2011. They stratified into two levels by vitamin D status (deficiency <10 ng/dL and normal ≥10 ng/dL). HRQOL was measured using the EuroQOL visual analogue scale (EQ-VAS) and the five dimensions and summary index of the EuroQOL-5 dimension (EQ-5D). The vitamin D deficiency group was more likely to report problems with mobility, self-care, and usual activities. Vitamin D deficiency was significantly associated with poor HRQOL indicated by the lowest quartile of EQ-VAS (unadjusted odds ratio [OR] =1.832, p = 0.006) and the lowest quartile of the EQ-5D index (unadjusted OR = 1.992, p = 0.003). Theses associations of vitamin D status with EQ-VAS and EQ-5D index were maintained after adjustment for age and sex (Model 1: OR = 1.677, p = 0.022 and OR = 1.701, p = 0.021, respectively). The significant associations of vitamin D status with EQ-VAS were maintained after adjustment for other possible covariates (Model 3: OR = 1.562, p = 0.044). Also, a trend of associations between vitamin D status and EQ-5D index were shown after adjustment for other covariates (Model3: OR = 1.681, p = 0.056). This is the first study to reveal that vitamin D status is independently associated with HRQOL in an older Korean population with knee osteoarthritis. Our results suggest that the maintenance of sufficient vitamin D status may be important to prevent QOL decline in older populations with knee osteoarthritis.


A rare case of deep cerebral venous thrombosis secondary to traumatic epidural hematoma: Case report.
Deep cerebral venous thrombosis (DCVT) is a rare disease, but always results in poor prognosis. We reported a 79-year-old female with coma after traumatic brain injury (TBI). The epidural hematoma was first diagnosed on non-contrast computerized tomography (CT). The hypodense areas in bilateral thalami and basal ganglia on reexamination CT highly indicated the suspicion of DCVT. Finally, the appearance of thrombosis of the vein of Galen on the computed tomography venography (CTA) and digital subtraction angiography (DSA) confirmed the diagnosis. The patients received surgery to remove the epidural hematoma. After that, she was treated with oral anticoagulation agent (low molecular weight heparin (LMWH), 180 Axal U/kg 24 h) for 4 weeks, shifted by oral warfarin (2.5 mg qd) for 4 weeks. The hypodense areas in bilateral thalami and basal ganglia have been largely reversed. At the time of 6 months after surgery, the patient could take care of herself. If the CT shows hypodense areas in bilateral thalami and basal ganglia, a diagnosis of DCVT should be suspected once the patients could not recover from the treatment of primary diseases.


Development of the pattern of dentition and dental laminae of Costa Rican plethodontid salamanders (Amphibia: Urodela).
The pattern of development of teeth and dental laminae of three Costa Rican plethodontids (Amphibia, Urodela, Plethodontidae) was investigated using transparent preparations, light microscopy and scanning electron microscopy. The teeth of the jaws are monostichously positioned, those of the posterior vomeral parts are polystichously arranged. The anterior vomeral parts carry monostichously positioned teeth at the caudal margin; yet, the adult Bolitoglossa subpalmata possesses two lines. As a sex dimorphism adult males display long monocuspid premaxillary teeth which protrude to the outside of the mouth cavity. All species studied possess paired dental laminae in the lower jaw. Nototriton abscondens possesses an unpaired dental lamina in the upper jaw, which is constricted between the unpaired premaxillary and the maxillaries. In contrast, the dental laminae in the upper jaw of B. subpalmata and Oedipina uniformis are segmented into a premaxillary and two maxillary laminae. All species possess a pair of anterior vomeral and a pair of posterior vomeral dental laminae in the adults, whereas the vomeral dental laminae of the subadults are unsegmented. The pattern of dentition is compared with that of Gyrinophilus and Eurycea.


RNA regulatory networks diversified through curvature of the PUF protein scaffold.
Proteins bind and control mRNAs, directing their localization, translation and stability. Members of the PUF family of RNA-binding proteins control multiple mRNAs in a single cell, and play key roles in development, stem cell maintenance and memory formation. Here we identified the mRNA targets of a S. cerevisiae PUF protein, Puf5p, by ultraviolet-crosslinking-affinity purification and high-throughput sequencing (HITS-CLIP). The binding sites recognized by Puf5p are diverse, with variable spacer lengths between two specific sequences. Each length of site correlates with a distinct biological function. Crystal structures of Puf5p-RNA complexes reveal that the protein scaffold presents an exceptionally flat and extended interaction surface relative to other PUF proteins. In complexes with RNAs of different lengths, the protein is unchanged. A single PUF protein repeat is sufficient to induce broadening of specificity. Changes in protein architecture, such as alterations in curvature, may lead to evolution of mRNA regulatory networks.


ChREBP binding and histone modifications modulate hepatic expression of the Fasn gene in a metabolic syndrome rat model.
Although the expression of hepatic lipogenic genes is enhanced in insulin resistance, the underlying mechanism is unclear. To reveal the details, the aim of this study was to investigate whether the expression of hepatic lipogenic genes are mediated by epigenetic regulation and specific transcription factors in an insulin resistance model of rats. Using a rat model of insulin resistance (SHR/NDmc-cp), we investigated the relationship between hepatic expression of the lipogenic gene fatty-acid synthase (Fasn), binding of the transcription factor carbohydrate-responsive element-binding protein (ChREBP) to the Fasn gene, and histone modifications in the region of the Fasn gene by real-time reverse transcriptase polymerase chain reaction, immunoblotting, and chromatin immunoprecipitation assay. Compared with control rats, Fasn mRNA expression and protein levels were higher in the livers of SHR/NDmc-cp rats, as were protein expression levels and Fasn binding of ChREBP and RNA polymerase II. Moreover, compared with the livers of control rats, levels of mono-methylated histone H3 lysine (K) 4 and acetylated histone H4 were higher in the promoter/enhancer region of the Fasn gene in the livers of SHR/NDmc-cp rats. Levels of trimethylated histone H3K4 and acetylated histone H3 were higher in the transcribed region. The results of this study indicate that expression of the Fasn gene in the livers of insulin-resistant rats is associated with increased H3K4 methylation, increased histone H3 acetylation, and increased H4 acetylation, and also, binding levels of ChREBP to promoter/enhancer region of Fasn gene is involved in the Fasn gene expression caused by hyperglycemia.


Correlations between peripapillary retinal nerve fiber layer thickness and macular thickness in different various stages of primary open-angle glaucoma.
To determine the relationship between macular thickness and peripapillary retinal nerve fiber layer (RNFLp) thickness in different stages of primary open-angle glaucoma (POAG). Ninety prospectively selected patients with different stage POAG underwent spectral domain optical coherence tomography (SD-OCT) to determine macular and RNFLp thicknesses in different regions and sectors respectively. Correlations were then established through Pearson's correlation coefficient between RNFLp and macular thicknesses in the different disease stages. Greatest correlation was observed between the inferior RNFLp sector and the internal inferior macula both in the whole patient population and in the subset of patients with incipient glaucoma. When the optic nerve disc is affected by another condition, macular thickness determination may help detect POAG and monitor its progression.


Structure-function relationship between galactomannans and their effects on freeze-thaw stability, retrogradation, and texture of corn starch gels during cold storage.
In this study, structural characteristics of Fenugreek (FG), Guar (GG), Locust bean (LBG), and Tara gums (TG) and their influence on physicochemical properties of corn starch (CS) gels were investigated. Results showed that FG presented a rigid rod structure, and GG, LBG, and TG showed an extended structure. The Mannose/Galactose (Man/Gal) ratio of FG, GG, LBG, and TG was 1.37, 1.96, 2.99, and 3.46, respectively. The molecular weight (Mw) of FG, GG, LBG, and TG was 0.89 × 106, 2.71 × 106, 3.61 × 106, and 2.77 × 106 Da, respectively. The structure-function relationship indicated that galactomannans with a high Man/Gal ratio and extended structure presented a higher apparent viscosity, formed gel more easily, and could limit retrogradation and improve freeze-thaw stability and textural profile of CS gels. Consequently, the results could be beneficial for the application of galactomannans in starch-based foods to improve their sensory characteristics and storage quality.


Characterization of the action of S 21403 (mitiglinide) on insulin secretion and biosynthesis in normal and diabetic beta-cells.
S 21403 (mitiglinide) is a new drug for type 2 diabetes mellitus (T2DM). Its action on insulin release and biosynthesis was investigated in several experimental systems utilizing pancreas from normal and T2DM animals. At high concentrations (10 microM), S 21403, like classical sulphonylurea, induced insulin release in the absence of glucose. In contrast, at therapeutic (0.1-1.0 microM) concentrations, S 21403 amplified insulin secretion glucose dose-dependently and with similar magnitude in normal and diabetic GK rat islets. In perfused GK rat pancreas, S 21403 induced normal kinetics of insulin secretion including first-phase response. The effect of S 21403 was strongly modulated by physiological factors. Thus, 0.1 microM adrenaline inhibited S 21403-induced insulin release. There was marked synergism between S 21403 and arginine in GK rat islets, combination of the two normalizing insulin secretion. In primary islet cultures from normal rats or prediabetic Psammomys obesus, prolonged exposure to S 21403 did not induce further depletion of insulin stores under normal or 'glucotoxic' conditions. Proinsulin biosynthesis was not affected by 2-h exposure of rat or prediabetic P. obesus islets to 1 microM S 21403. Yet, 24-h exposure of rat islets to S 21403 resulted in 30% increase in proinsulin biosynthesis at 8.3 mM glucose. Amplification by S 21403 of glucose-induced insulin secretion in diabetic GK beta-cells with restoration of first-phase response, a strong synergistic interaction with arginine and marked inhibition by adrenaline, make it a prime candidate for successful oral antidiabetic agent.


Neutral lipid transfer protein does not regulate alpha-tocopherol transfer between human plasma lipoproteins.
Vitamin E has no known plasma carrier protein and is transported by plasma lipoproteins. The site of association of vitamin E in the lipoprotein particle and the mode of transfer of vitamin E between plasma lipoproteins have not been ascertained. Since neutral lipids (triglycerides and cholesterol esters) exchange between plasma lipoproteins by processes mediated by neutral lipid transfer protein, we questioned that if vitamin E, a hydrophobic molecule, is carried in the core of the lipoprotein particle then its transfer between plasma lipoproteins may be mediated by neutral lipid transfer protein. Transfer of D-alpha(5-methyl-3H)tocopherol from in vitro-labeled human plasma lipoprotein fractions to other plasma lipoproteins was measured under incubation conditions that were designed to yield markedly differing degrees of neutral lipid exchange. Despite the presence of the d greater than 1.21 g/ml lipoprotein-poor plasma fraction or purified lipid transfer protein that resulted in up to a 10-fold increase in neutral lipid transfer, vitamin E transfer between very low density lipoproteins, low density and high density lipoproteins remained constant. Even excess amounts of lipid transfer protein, which caused triglyceride transfer between very low density and high density lipoproteins to reach saturation, failed to affect significantly vitamin E transfer. Vitamin E distribution between lipoprotein fractions did correlated with lipoprotein mass ratios. Vitamin E transfer was higher as the protein ratio of acceptor lipoproteins to donor lipoproteins increased.(ABSTRACT TRUNCATED AT 250 WORDS)


Sexual health knowledge and health practices of female sex workers in Liuzhou, China, differ by size of venue.
We conducted qualitative interviews with 48 female sex workers (FSW) recruited from entertainment venues in Liuzhou, China. Analyses found that HIV knowledge and sexual health seeking strategies differed by size of venue: (1) Women in smaller venues said they douched before/after sex and used condoms with all but their regular partners and clients. Most found the brochures distributed by Chinese CDC workers "irrelevant" or "boring" and relied on friends for health advice. (2) FSW in middle and large venues were less concerned about prevention, claiming their clients were "healthy." They relied more on the Internet for health information and were less concerned about the cost of seeing a doctor. (3) Pregnancies and abortions were frequent, especially among the younger women in large venues. This research documents the need to develop tailored HIV-related messages and prevention strategies with the help of FSW to address differences among FSW working in venues of different sizes.


Ex vivo and in vitro antiplasmodial activity and toxicity of Caesalpinia decapetala (Roth) Alston (Fabaceae).
Malaria is among the most prevalent and devastating parasitic diseases globally with most cases reported in Sub-Saharan Africa. One of the major reasons for the high malaria prevalence is the ever-increasing emergence of resistant strains of malaria-causing parasites to the currently used antimalarial drugs. This, therefore, calls for the search for antimalarial compounds with alternative modes of action. Plants used in traditional medicine for the treatment of malaria offer possible sources of such compounds. Caesalpinia decapetala has been used traditionally for the treatment of various diseases including malaria. However, the antiplasmodial activity of the plant has never been reported. To determine the ex vivo and in vitro antiplasmodial activities of the extracts of the roots, stem bark and leaves of Caesalpinia decapetala. The roots, stem bark and leaves of Caesalpinia decapetala (Roth) Alston (Caesalpiniaceae) were collected and air-dried under a shade then extracted consecutively with dichloromethane and methanol (1:1 (v/v) (4 × 0.8 L). The extracts were tested for antiplasmodial activities against four strains of Plasmodium falciparum (W2, DD2, 3D7, and D6) and fresh P. falciparum field isolates using the SYBR green I assay. The mean fifty percent inhibition concentration (IC50) was determined for each assay. An acute oral toxicity test was done based on the Organization for Economic Cooperation and Development (OECD 425) guidelines using Swiss albino mice. The leaves and stem bark extracts showed good antiplasmodial activities with IC50 values of 4.54 and 4.86 μg/mL, respectively, when tested against the fresh field isolates ex vivo. Similarly, the roots extract showed an IC50 value of 6.49 μg/mL when tested against field isolates ex vivo. The roots extract showed the highest antiplasmodial activities among the samples when tested against W2 (IC50 = 6.12 μg/mL), DD2 (IC50 = 8.17 μg/mL), and D6 (IC50 = 16.02 μg/mL) strains of P. falciparum whereas the leaves showed the highest activity (IC50 = 9.3 μg/mL) when tested against the 3D7 strain of P. falciparum. No mortality was observed for the mice treated with 2000 mg/kg of the leaves and stem bark extracts. The mouse treated with 2000 mg/kg of the roots extracts regained weight by day 12 of the observation period. Caesalpinia decapetala has the potential to suppress the growth of P. falciparum thereby contributing to combating the recurrent emergence of antimalarial drug resistance.


Endotracheal suction in term non vigorous meconium stained neonates-A pilot study.
To evaluate the effect of 'No endotracheal suction' on occurrence of meconium aspiration syndrome (MAS) and/or all-cause mortality in non-vigorous neonates born through meconium stained amniotic fluid (MSAF). This pilot randomized controlled trial enrolled term non-vigorous neonates (≥37 weeks) born through MSAF. Neonates randomized to 'No Endotracheal suction group' ('No ET' Group; n=88) did not undergo endotracheal suction before the definitive steps of resuscitation. Neonates randomized to 'Endotracheal suction group' ('ET' Group; n=87) underwent tracheal suction as part of the initial steps as per the current NRP recommendations. The primary outcome was occurrence of MAS and/or death. Secondary outcome variables were duration and severity of respiratory distress, need for respiratory support, development of hypoxic ischemic encephalopathy (HIE) and duration of oxygen therapy and hospitalization. Baseline characters including birth weight and gestational age were similar between the two groups. MAS was present in 23 (26.1%) vs. 28 (32.2%) neonates in 'No ET' and 'ET' groups respectively (OR 0.4 (0.12-1.4); p=0.14) with 4 (4.6%) and 9 (10.34%) deaths amongst these neonates with MAS in respective groups (OR 0.75 (0.62-1.2); p=0.38). Other parameters like severity and duration of respiratory distress, need for respiratory support, incidence of HIE, duration of oxygen therapy and duration of hospitalization were comparable. This study demonstrates that it is feasible to randomize non-vigorous infants born through meconium stained liquor to receive on not receive endotracheal suction. There is a need for a multi-center trial to address whether the current practices and guidelines can be justified.


Intraocular lenses: secondary membranes; cystoid macular edema.
In 650 consecutive Binkhorst lens implants, secondary membrane surgery was required more than eight times as frequently after an extracapsular than after an intracapsular cataract extraction. The visual acuity results after discussion were uniformly good. Transpars plana vitrectomy was reserved for more severe cases. The pupils were cleared, but the visual acuity results were mixed. A fluorescein angiographic study revealed little difference in the incidence of cystoid macular edema in implant and nonimplant cases. There was a lower incidence after extracapsular than intracapsular extractions in implant cases.


Okra polysaccharide-2 plays a vital role on the activation of RAW264.7 cells by TLR2/4-mediated signal transduction pathways.
Polysaccharide is the main active component of okra (Abelmoschus esculentus L.) and it can effectively stimulate the activation of macrophages. However, the immune regulatory mechanism is still not clear. Therefore, the present study aimed to reveal the possible mechanism by investigating the effect of okra polysaccharide-2 (RPS-2) on Toll-like receptor (TLR) 2/4-mediated signal transduction pathways in RAW264.7 murine macrophage cells. In order to confirm whether RPS-2 stimulated macrophages activation via TLR2 or TLR4, RAW264.7 murine macrophage cells were pretreated with TLR2/4 inhibitors for 1 h before RPS-2 treatment, and then the NO, IL-10, TNF-α levels were tested. The results indicated that both TLR2 and TLR4 were the keys of immune regulatory effect of RPS-2. Afterwards, the effect of RPS-2 on NF-κB and MAPKs signaling pathways were studied by western blot analysis. It showed RPS-2 induced the phosphorylation of p65, IκBα, p38, ERK1/2 and JNK. At the same time, the specific inhibitors reduced these phosphorylation levels as well as NO, IL-10 and TNF-α amounts. In a word, RPS-2 activated macrophages by NF-κB and MAPKs signal transduction pathways.


Sensing with tools extends somatosensory processing beyond the body.
The ability to extend sensory information processing beyond the nervous system1 has been observed throughout the animal kingdom; for example, when rodents palpate objects using whiskers2 and spiders localize prey using webs3. We investigated whether the ability to sense objects with tools4-9 represents an analogous information processing scheme in humans. Here we provide evidence from behavioural psychophysics, structural mechanics and neuronal modelling, which shows that tools are treated by the nervous system as sensory extensions of the body rather than as simple distal links between the hand and the environment10,11. We first demonstrate that tool users can accurately sense where an object contacts a wooden rod, just as is possible on the skin. We next demonstrate that the impact location is encoded by the modal response of the tool upon impact, reflecting a pre-neuronal stage of mechanical information processing akin to sensing with whiskers2 and webs3. Lastly, we use a computational model of tactile afferents12 to demonstrate that impact location can be rapidly re-encoded into a temporally precise spiking code. This code predicts the behaviour of human participants, providing evidence that the information encoded in motifs shapes localization. Thus, we show that this sensory capability emerges from the functional coupling between the material, biomechanical and neural levels of information processing13,14.


The development and validation of the protective factors survey: a self-report measure of protective factors against child maltreatment.
The objective of this study was to evaluate the internal structure of a self-report measure of multiple family-level protective factors against abuse and neglect and explore the relationship of this instrument to other measures of child maltreatment. For the exploratory factor analysis, 11 agencies from 4 states administered the Protective Factors Survey (PFS), the Brief Child Abuse Potential Inventory (Ondersma et al., 2005), and another measure to establish content validity (N=249 participants). Exploratory factor analyses were conducted to obtain a small, integrated set of items that tap the targeted protective factors correlated with other theoretically important constructs. Correlations were computed to explore PFS criterion-related validity. Confirmatory factor analyses were conducted on an additional sample of 689 participants from 19 agencies across the United States. Exploratory and confirmatory factor analyses yielded a 4-factor solution, consisting of Family Functioning, Emotional Support, Concrete Support, and Nurturing and Attachment. Four measures were administered to assess constructs that were predicted to correlate negatively with the protective factors: child abuse potential, depression, stress, and maladaptive coping. The PFS was also predicted to correlate positively with adaptive coping such as use of emotional and instrumental social support and positive reframing. Overall, the PFS subscales were significantly related to these measures in the directions predicted. The PFS is a valid and reliable instrument to measure individual differences in multiple protective factors in families. The measure is an easily administered tool that offers programs an alternative to costly, time-intensive measures. The PFS offers community-based prevention programs a valid and reliable survey instrument that measures multiple protective factors. The subscales-Family Functioning, Emotional Support, Concrete Supports, and Nurturing and Attachment-can be used by practitioners to understand the service population more fully, inform services, and contribute to the evidence base of a protective factors approach. Practitioners can build on the strengths or protective factors in parents and select services to address areas that are less developed.


Physiological variation of the vertebral bone marrow water T2 relaxation time.
The aim of this study was to investigate physiological variations of the water T2 relaxation time in vertebral bone marrow with respect to age, body mass index (BMI), sex and proton density fat fraction (PDFF) based on single-voxel magnetic resonance spectroscopy (MRS) at 3 T. Multi-TE single-voxel STEAM MRS data of a single lumbar vertebra (L4 or L5) from 260 subjects (160/100 female/male, age: 0.7/37.1/77.7 years, BMI: 13.6/26.2/44.5 kg/m2 [min./median/max.]) with no history of vertebral bone marrow pathologies were retrospectively included. All data were processed using a joint series T2-constrained time domain-based water-fat model. Water T2 and PDFF data were analyzed using (a) Pearson's correlation r and (b) multiple linear regression without interactions of the independent variables. Min./median/max. water T2 and PDFF were 11.2/21.1/42.5 ms and 4.0%/36.8%/82.0%, respectively. Pearson's correlation coefficients were significant (P < .05) for water T2 versus age (r = -0.429/-0.210 female/male) and for water T2 versus PDFF (r = -0.580/-0.546 female/male) for females and males, respectively. Females showed significant higher water T2 values compared with males (P < .001). Multiple linear regression for water T2 without interactions revealed a R2 = 0.407 with PDFF (P < .001) and sex (P < .001) as significant predictors. The current study suggests that under physiological conditions vertebral bone marrow water T2 is negatively correlated with age and PDFF and shows significant differences between females and males. The observed systematic trends are of relevance for the evaluation of T2 values and T2-weighted bone marrow parameters. Further research on the exact mechanisms and drivers of the observed water T2 behavior is required.


Flow-cytometric evaluation of oxidative burst in phagocytic cells of children with cystic fibrosis.
The objective of this study was to assess the dye 2', 7'-dichlorofluorescein (DCF) assay in screening for alterations in polymorphonuclear cell (PMN) and monocyte (MC) oxidative burst of cystic fibrosis (CF) patients. 56 CF patients aged between 2 and 20 years were investigated. Purified cells were stimulated with phorbolmyristate acetate (PMA) and zymosan (ZX). A range for DCF fluorescence for PMA- and ZX-stimulated and non-stimulated cells was established based on data from 60 healthy controls. PMNs showed both enhancement and impairment. A deficient oxidative burst was detected in a total of 14 CF patients caused by abnormally high mean fluorescence intensity (MFI) of resting cells. Enhanced oxidative burst was seen in 6 CF patients. CF patients responded differently to PMA or ZX stimulation. Pseudomonas aeruginosa colonization significantly enhanced (p<0.005) the MFI of resting PMNs. MCs of CF patients showed a significantly (p<0.05) enhanced oxidative burst after stimulation with PMA compared to healthy controls, but no differences could be observed after stimulation with ZX. Serum concentrations of interleukin-6 were elevated in all CF patients, in particular in those with activation of both PMNs and MCs. The DCF assay shows for the first time the heterogeneity of the oxidative burst reaction in CF patients. In our opinion, the DCF assay is a reliable method for detecting pathological oxidative burst in CF patients.


Stat3 is involved in control of MASP2 gene expression.
Little is known about determinants regulating expression of Mannan-binding lectin associated serine protease-2 (MASP-2), the effector component of the lectin pathway of complement activation. Comparative bioinformatic analysis of the MASP2 promoter regions in human, mouse, and rat, revealed conservation of two putative Stat binding sites, termed StatA and StatB. Site directed mutagenesis specific for these sites was performed. Transcription activity was decreased 5-fold when StatB site was mutated in the wildtype reporter gene construct. Gel retardation and competition assays demonstrated that proteins contained in the nuclear extract prepared from HepG2 specifically bound double-stranded StatB oligonucleotides. Supershift analysis revealed Stat3 to be the major specific binding protein. We conclude that Stat3 binding is important for MASP2 promoter activity.


Centromeres organize (epi)genome architecture.
In some plants and animals, microtubules attach across the length of the chromosome in mitosis, forming a holocentromere instead of a single centromeric locus. A new study in Cell shows that in the holocentric beak sedge Rhynchospora, holocentromeres also impact genomic architecture, epigenome organization, and karyotype evolution.


Correction to: Presynaptic Ethanol Actions: Potential Roles in Ethanol Seeking.
The Acknowledgements unfortunately went missing to be included in the chapter.


Kinematic priming of action predictions.
The ability to anticipate what others will do next is crucial for navigating social, interactive environments. Here, we develop an experimental and analytical framework to measure the implicit readout of prospective intention information from movement kinematics. Using a primed action categorization task, we first demonstrate implicit access to intention information by establishing a novel form of priming, which we term kinematic priming: subtle differences in movement kinematics prime action prediction. Next, using data collected from the same participants in a forced-choice intention discrimination task 1 h later, we quantify single-trial intention readout-the amount of intention information read by individual perceivers in individual kinematic primes-and assess whether it can be used to predict the amount of kinematic priming. We demonstrate that the amount of kinematic priming, as indexed by both response times (RTs) and initial fixations to a given probe, is directly proportional to the amount of intention information read by the individual perceiver at the single-trial level. These results demonstrate that human perceivers have rapid, implicit access to intention information encoded in movement kinematics and highlight the potential of our approach to reveal the computations that permit the readout of this information with single-subject, single-trial resolution.


Gated intracoronary thallium201 scintigraphy: feasibility and potential clinical advantages.
Visualization of ventricular walls with true global motion and myocardial thickening is not possible with use of present scintigraphic techniques. When thallium 201 (201TI) is injected intravenously (IV), only about 5% reaches the myocardium. However, if 201TI is injected intracoronarily, 100% reaches, and approximately 88% localizes in, the myocardium, which results in higher count rates than when given IV, permitting acceptable acquisition times for gated true wall motion studies. The authors describe a new technique using intracoronary (IC) 201TI to acquire high count rate, high contrast, and short acquisition time in gated true wall motion studies. Thirteen patients were studied at rest with gated IC thallium. Six of these patients also had resting IV 201TI myocardial studies. After routine coronary angiography, 0.75 mCi of 201TI was injected into each coronary artery. Multiple sequential one-minute gated studies were obtained in LAO and RAO projections, followed by sequential five-minute images for two hours to determine 201TI redistribution kinetics. Regions of interest over segments of left and right ventricles and background permitted definition of temporal and spatial distributions. Three one-minute gated studies were summed with a total count of 2,100 K for a three-minute acquisition. Myocardium-to-background ratios were as high as 13:1 with a mean of 11.4:1 in the IC study compared with 2.3:1 in the IV studies. Washout half-time in normal myocardium was 95 +/- 5 min. The detectability and size of perfusion defects were different on gated diastolic and systolic, nongated, and IV studies. Questionable defects seen on nongated studies or after IV administration were easily noted on gated diastolic images.(ABSTRACT TRUNCATED AT 250 WORDS)


Odontonia kerangcaris sp. nov., a new bivalve-associated shrimp (Crustacea, Decapoda, Palaemonidae) from East Kalimantan, revealing intrageneric host switching.
A new species of bivalve mollusk dwelling palaemonid shrimp of the genus Odontonia is described from the Berau Islands, East Kalimantan, Indonesia. This is the only Odontonia species recorded as a symbiont of a bivalve mollusk, all other congeners are known to associate with solitary ascidians. The new species belongs to the group wherein the dactylus of the ambulatory pereiopods has an accessory tooth. It differs from these species in the absence of a forward directed proximal tooth on the flexor margin of the corpus of the ambulatory dactyli. It also lacks the small denticles posterior to the distoventral accessory tooth on the dactylar corpus.


Tailoring chemotherapy in advanced colorectal cancer.
In this post-genomic era, the individualization of chemotherapy through the study of pharmacogenetics is becoming an ever attainable reality. Keys to individual variations in drug response and toxicity are being identified through the study of drug targets, metabolizing enzymes, efflux and DNA repair systems at the genomic, mRNA and protein levels. Several promising pharmacogenetic candidates with predictive and/or prognostic value have been identified. These candidates, along with others yet to be identified, could in the near future allow for the tailoring of therapy with an ever increasing chemotherapeutic armamentarium. Well-designed and large prospective analyses, which include relevant pharmacogenetic parameters, are needed to confirm the initial clinical associations reported thus far.


Changes in long-term glycemic control and performance indicators in a cohort of type 2 diabetic patients cared for by general practitioners: findings from the "Modena Diabetes Project".
General practitioners (GPs) are being increasingly asked to play a key role in the shared care of people with diabetes mellitus, but data concerning the effects of this in Italy are still scarce. We therefore evaluated the 4-year follow-up changes in outcomes and performance indicators in type 2 diabetic patients cared for by GPs in the framework of the "Modena Diabetes Project". Seventy-four percent of the local GPs participating in the project (387 out of 521) sent 5260 paired baseline and follow-up datasheets. The baseline characteristics of the type 2 diabetic patients (49.6% male) were a mean age of 67.3+/-11.2 years, a mean disease duration of 10.9+/-7.4 years, a mean BMI of 28.7+/-4.8 kg/m2, and a mean HbA1c level 7.56+/-1.52%. After four years follow-up, the individual before/after match-paired outcomes revealed an improvement in glycemic control: HbA1c levels significantly decreased to 7.39+/-1.31%, and the percentage of patients with HbA1c level of <6.5% significantly increased from 15.7% to 22.1%. There was also a significant decrease in body weight (from 78.3+/-14.8 to 77.6+/-14.6 kg) and BMI (from 28.8+/-4.8 to 28.5+/-4.9 kg/m2). The time trends of glycemic control significantly improved during the 4-year follow up, but those of the body weight and BMI values did not. Furthermore, the percentages of performance indicators matching the expected rate of recurrence per each year of follow-up significantly improved during the study period. Long-term glycemic control and the performance indicators relating to the type 2 diabetic patients participating in our shared care programme progressively improved.


Effect of calcium cation on lipid vesicle deposition on silicon dioxide surface under various thermal conditions.
Calcium cation (Ca(2+)) is a key element to the cell membrane functions. Its effects on liquid crystal vesicle deposition have already been learnt. In this study, it is found that Ca(2+) can also influence the gel vesicle deposition by controlling the vesicle rupture and fusion on SiO(2) at temperatures lower than the main transition temperature. Particular analyses were given to the vesicle-SiO(2) and inter-vesicle attractions that are originated from the Ca(2+) bridging effect. It is concluded that the aggregate condition of vesicles should be taken into consideration when dealing with vesicle deposition on a solid substrate.


Woman battering.
Woman battering is a common phenomenon in our society. The number of women effected means that most obstetrician-gynecologists have patients in their practice who are victims. When the diagnosis is suspected, it is necessary to question the patient directly. Therapy involves the use of resources mostly outside of the office. Therefore, the physician assumes the role of (1) permission giving through mutual acknowledgement that the problem exists and is deserving of remedial action and (2) information giving by providing the patient sources of relief from the abuse.


Food questionnaire for the assessment of gluten intake by children 1 to 4 years old.
A food questionnaire (FQ) to assess gluten intake in infants 0 to 12 months old has been developed and validated (FQ-gluten), but an instrument to assess gluten intake in children 1 to 4 years is not available. Development and validation of such an instrument (FQ-gluten4) was the aim of the present study. The FQ-gluten was adapted according to age-related food consumption. The results of this FQ-gluten4 were compared with the results of a 2-day food record. Seventy-one parents filled in both instruments. The mean amount of gluten consumption calculated from the FQ-gluten4 was comparable with that of the food record, but significant differences were found in the amount of gluten intake in 1- to 2-year-old children and in the percentage of gluten from porridge among the 1- to 3-year-olds. The Blant-Altman limits of agreement with standard deviation of 2600 mg were -5118 to 5630 mg. The new, short, standardized, validated, and easy-to-use FQ-gluten4 may be a useful instrument in the assessment of gluten intake in young children. Using this standardized method provides opportunity for better comparison of the results of gluten consumption in studies throughout the world. Furthermore, such an instrument can be used to quantify the gluten intake in individuals suspected to have celiac disease but in whom the diagnoses cannot be confirmed.


Harris Heel View is Inadequate to Visualize Screw Prominence of the Medial Calcaneus: A Case Report and Cadaveric Evaluation.
A 58-year-old man sustained multiple right foot injuries during a motor vehicle accident that included a calcaneus fracture requiring open reduction and internal fixation (ORIF). The procedure was complicated by a prominent implant inferior to the sustentaculum, which necessitated a return to the operating room. Commonly used fluoroscopic views do not adequately image this area. A cadaveric study was undertaken to identify the optimal 2-dimensional fluoroscopic view that evaluates prominent implants at the medial calcaneus. The sustentaculum tunnel view gives a reliable image of prominent medial implants, and use of this technique may limit complications after calcaneus ORIF.


A web-based e-learning programme for training external post-mortem examination in curricular medical education.
In Germany, the external post-mortem examination is considered a medical duty and may be performed by any licensed physician. Concerning legal medicine as a curricular subject in teaching medical students, the external post-mortem examination is regarded a core area. At the University of Müenster, 15 virtual cases of death have been developed by using the web-based Inmedea Simulator. The programme allows performing all relevant steps in executing a complete external post-mortem examination. A particular importance was attached to the aspect of training users in approaching the subject in a systematic way to interpret significant forensic findings correctly and to comprehend their medico-legal implications. The programme was used for the first time in the academic term of 2010/2011. The overall reception of the programme by the medical students resulted to be positive in a first evaluation.


A wearable sweat electrochemical aptasensor based on the Ni-Co MOF nanosheet-decorated CNTs/PU film for monitoring of stress biomarker.
Monitoring cortisol, a hormone released by the adrenal cortex in response to stress, is essential to evaluate the endocrine response to stress stimuli. While the current cortisol sensing methods require large laboratory settings, complex assay, and professional personnel. Herein, a novel flexible and wearable electrochemical aptasensor based on a Ni-Co metal-organic frameworks (MOF) nanosheet-decorated carbon nanotubes (CNTs)/polyurethane (PU) film is developed for rapid and reliable detection of cortisol in sweat. First, the CNTs/PU (CP) film was prepared by a modified wet spinning technology, and the CNTs/polyvinyl alcohol (PVA) solution was thermally deposited on the surface of CP film to form the highly flexible CNTs/PVA/CP (CCP) film with excellent conductivity. Then aminated Ni-Co MOF nanosheet prepared by a facile solvothermal method was conjugated with streptavidin and modified on the CCP film. Biofunctional MOF can effectively capture cortisol aptamer due to its excellent specific surface area. In addition, the MOF with peroxidase activity can catalytic oxidization of hydroquinone (HQ) by hydrogen peroxide (H2O2), which could amplify the peak current signal. The catalytic activity of Ni-Co MOF was substantially suppressed in the HQ/H2O2 system due to the formation of the aptamer-cortisol complex, which reduced the current signal, thereby realizing highly sensitive and selective detection of cortisol. The sensor has a linear range of 0.1-100 ng/mL and a detection limit of 0.032 ng/mL. Meanwhile, the sensor showed high accuracy for cortisol detection under mechanical deformation conditions. More importantly, the prepared MOF/CCP film based three-electrode was assembled with the polydimethylsiloxane (PDMS) substrate, and the sweat-cloth was used as the sweat collection channel to fabricate a wearable sensor patch for monitoring of cortisol in volunteers' sweat in the morning and evening. This flexible and non-invasive sweat cortisol aptasensor shows great potential for quantitative stress monitoring and management.


The fate of the messenger is pre-determined: a new model for regulation of gene expression.
Recent years have seen a rise in publications demonstrating coupling between transcription and mRNA decay. This coupling most often accompanies cellular processes that involve transitions in gene expression patterns, for example during mitotic division and cellular differentiation and in response to cellular stress. Transcription can affect the mRNA fate by multiple mechanisms. The most novel finding is the process of co-transcriptional imprinting of mRNAs with proteins, which in turn regulate cytoplasmic mRNA stability. Transcription therefore is not only a catalyst of mRNA synthesis but also provides a platform that enables imprinting, which coordinates between transcription and mRNA decay. Here we present an overview of the literature, which provides the evidence of coupling between transcription and decay, review the mechanisms and regulators by which the two processes are coupled, discuss why such coupling is beneficial and present a new model for regulation of gene expression. This article is part of a Special Issue entitled: RNA Decay mechanisms.


The implementation of the Medical Regulation Office and Mobile Emergency Attendance System and its impact on the gravity profile of non-traumatic afflictions treated in a University Hospital: a research study.
The public health system of Brazil is structured by a network of increasing complexity, but the low resolution of emergency care at pre-hospital units and the lack of organization of patient flow overloaded the hospitals, mainly the ones of higher complexity. The knowledge of this phenomenon induced Ribeirão Preto to implement the Medical Regulation Office and the Mobile Emergency Attendance System. The objective of this study was to analyze the impact of these services on the gravity profile of non-traumatic afflictions in a University Hospital. The study conducted a retrospective analysis of the medical records of 906 patients older than 13 years of age who entered the Emergency Care Unit of the Hospital of the University of São Paulo School of Medicine at Ribeirão Preto. All presented acute non-traumatic afflictions and were admitted to the Internal Medicine, Surgery or Neurology Departments during two study periods: May 1996 (prior to) and May 2001 (after the implementation of the Medical Regulation Office and Mobile Emergency Attendance System). Demographics and mortality risk levels calculated by Acute Physiology and Chronic Health Evaluation II (APACHE II) were determined. From 1996 to 2001, the mean age increased from 49 +/- 0.9 to 52 +/- 0.9 (P = 0.021), as did the percentage of co-morbidities, from 66.6 to 77.0 (P = 0.0001), the number of in-hospital complications from 260 to 284 (P = 0.0001), the mean calculated APACHE II mortality risk increased from 12.0 +/- 0.5 to 14.8 +/- 0.6 (P = 0.0008) and mortality rate from 6.1 to 12.2 (P = 0.002). The differences were more significant for patients admitted to the Internal Medicine Department. The implementation of the Medical Regulation and Mobile Emergency Attendance System contributed to directing patients with higher gravity scores to the Emergency Care Unit, demonstrating the potential of these services for hierarchical structuring of pre-hospital networks and referrals.


Expression of human telomerase catalytic subunit gene in cancerous and precancerous gastric conditions.
Telomerase activity is thought to be necessary for cellular immortality and carcinogenesis. The mRNA that encodes the telomerase catalytic subunit (hTERT) has recently been identified, and expression of hTERT mRNA is thought to regulate activation of telomerase. To determine at what stage of carcinogenesis cells begin to express hTERT, we analysed hTERT mRNA expression in gastric carcinoma and precancerous conditions, focusing on chronic gastritis with or without intestinal metaplasia. Using reverse transcription-polymerase chain reaction, hTERT gene expression was investigated in 18 gastric cancers and 60 specimens of chronic gastritis. Telomerase activity was evaluated using telomeric repeat amplification protocol. Sixteen of 18 (89%) gastric carcinomas expressed hTERT mRNA, and this expression was unrelated to histological type or depth of invasion. Telomerase activity was found in seven of eight (88%) gastric cancer tissues, all of which expressed hTERT mRNA. Expression of hTERT mRNA was positive in 14 of 60 (23%) specimens of chronic gastritis, and was most prominent in seven of 15 (47%) specimens of gastric mucosa with intestinal metaplasia. Expression of the hTERT gene was significantly more frequent in chronic gastritis with intestinal metaplasia than in gastritis without intestinal metaplasia (P=0.030). In addition, hTERT gene expression was not correlated with age, sex, biopsy site, histological grade of inflammatory cells, glandular atrophy and lymph follicles, or infection with Helicobacter pylori. None of eight normal gastric mucosa expressed hTERT mRNA. Our results indicate that hTERT mRNA is expressed in precancerous conditions as well as in gastric cancer, and that hTERT gene expression is induced at an early stage of gastric carcinogenesis.


Cost-effectiveness analysis of empagliflozin versus sitagliptin as second-line therapy for treatment in patients with type 2 diabetes in the United States.
To estimate the cost-effectiveness of sequential addition of empagliflozin versus sitagliptin after metformin in patients with type 2 diabetes (T2D) with or without cardiovascular disease (CVD) from the perspective of the US healthcare payer. An individual simulation model predicted lifetime diabetes-related complications, using UKPDS-OM2 equations in patients without CVD, and EMPA-REG OUTCOME equations in patients with CVD. Additional US-based sources informed inputs for population characteristics, adverse events, non-CV death, treatment escalation, quality of life and costs. Costs and quality-adjusted life-years (QALYs) were discounted 3.0% annually. The incremental cost-effectiveness ratio (ICER) for second-line empagliflozin versus sitagliptin in the overall T2D population was $6967/QALY. Empagliflozin led to longer CVD-free survival (0.07 years) and an 11% reduction in CV death in patients with CVD compared with sitagliptin. Empagliflozin resulted in greater benefits with greater costs in patients with versus without baseline CVD, yielding ICERs of $3589/QALY versus $12 577/QALY, respectively. Results were consistent across a range of deterministic and probabilistic sensitivity analyses and scenarios. Compared with sitagliptin, empagliflozin was cost-effective (at $50 000/QALY US threshold) as a second-line treatment to metformin for T2D patients with or without CVD in the United States. Our findings lend additional support for more widespread adoption of guidelines by healthcare decision-makers for T2D treatment.


Improving the enzymatic hydrolysis of dilute acid pretreated wheat straw by metal ion blocking of non-productive cellulase adsorption on lignin.
Eleven salts were selected to screen the possible metal ions for blocking the non-productive adsorption of cellulase onto the lignin of dilute acid pretreated wheat straw. Mg(2+) was screened finally as the promising candidate. The optimal concentration of MgCl2 was 1 mM, but the beneficial action was also dependent on pH, hydrolysis time and cellulase loading. Significant improvement of glucan conversion (19.3%) was observed at low cellulase loading (5 FPU/g solid). Addition of isolated lignins, tannic acid and lignin model compounds to pure cellulose hydrolysis demonstrated that phenolic hydroxyl group (Ph-OH) was the main active site blocked by Mg(2+). The interaction between Mg(2+) and Ph-OH of lignin monomeric moieties followed an order of p-hydroxyphenyl (H)>guaiacyl (G)>syringyl (S). Mg(2+) blocking made the lignin surface less negatively charged, which might weaken the hydrogen bonding and electrostatically attractive interaction between lignin and cellulase enzymes.


5alpha-androstane-3alpha,17beta-diol supports human prostate cancer cell survival and proliferation through androgen receptor-independent signaling pathways: implication of androgen-independent prostate cancer progression.
Androgen and androgen receptor (AR) are involved in growth of normal prostate and development of prostatic diseases including prostate cancer. Androgen deprivation therapy is used for treating advanced prostate cancer. This therapeutic approach focuses on suppressing the accumulation of potent androgens, testosterone and 5alpha-dihydrotestosterone (5alpha-DHT), or inactivating the AR. Unfortunately, the majority of patients with prostate cancer eventually advance to androgen-independent states and no longer respond to the therapy. In addition to the potent androgens, 5alpha-androstane-3alpha,17beta-diol (3alpha-diol), reduced from 5alpha-DHT through 3alpha-hydroxysteroid dehydrogenases (3alpha-HSDs), activated signaling may represent a novel pathway responsible for the progression to androgen-independent prostate cancer. Androgen sensitive human prostate cancer LNCaP cells were used to compare 5alpha-DHT and 3alpha-diol activated androgenic effects. In contrast to 5alpha-DHT, 3alpha-diol regulated unique patterns of beta-catenin and Akt expression as well as Akt phosphorylation in parental and in AR-silenced LNCaP cells. More significantly, 3alpha-diol, but not 5alpha-DHT, supported AR-silenced LNCaP cells and AR negative prostate cancer PC-3 cell proliferation. 3alpha-diol-activated androgenic effects in prostate cells cannot be attributed to the accumulation of 5alpha-DHT, since 5alpha-DHT formation was not detected following 3alpha-diol administration. Potential accumulation of 3alpha-diol, as a result of elevated 3alpha-HSD expression in cancerous prostate, may continue to support prostate cancer growth in the presence of androgen deprivation. Future therapeutic strategies for treating advanced prostate cancer might need to target reductive 3alpha-HSD to block intraprostatic 3alpha-diol accumulation.


Renal vascular disease: pathology of large blood vessel disease.
Lesions of the extrarenal arteries which are associated with hypertension are described. Included are descriptions of the development, stages, and complications of atherosclerotic plaques; intimal fibroplasia and the medial fibromuscular dysplasias; Takayasu's aortitis; radiation injury; and a newly described arterial disease, medial agenesis. Also described is the development of atherosclerosis in saphenous vein bypass grafts and the effects of transluminal angioplasty.


External validation of pulmonary radiotherapy toxicity models for ultracentral lung tumors.
Pulmonary toxicity is dose-limiting in stereotactic body radiation therapy (SBRT) for tumors that abut the proximal bronchial tree (PBT), esophagus, or other mediastinal structures. In this work we explored published models of pulmonary toxicity following SBRT for such ultracentral tumors in an independent cohort of patients. The PubMed database was searched for pulmonary toxicity models. Identified models were tested in a cohort of patients with ultracentral lung tumors treated between 2008 and 2017 at one large center (N = 88). This cohort included 60 % primary and 40 % metastatic tumors treated to 45 Gy in 5 fractions (fx), 50 Gy in 5 fx, 60 Gy in 8 fx, or 60 Gy in 15 fx prescribed as 100 % dose to PTV. Seven published NTCP models from two studies were identified. The NTCP models utilized PBT max point dose (Dmax), D0.2 cm3, V65, V100, and V130. Within the independent cohort, the ≥ grade 3 toxicity and grade 5 toxicity rates were 18 % and 7-10 %, respectively, and the Dmax models best described pulmonary toxicity. The Dmax to 0.1 cm3 model was better calibrated and had increased steepness compared to the Dmax model. A re-planning study minimizing PBT 0.1 cm3 to below 122 Gy in EQD23 (for a 10 % ≥grade 3 pulmonary toxicity) was demonstrated to be completely feasible in 4/6 patients, and dose to PBT 0.1 cm3 was considerably lowered in all six patients. Pulmonary toxicity models were identified from two studies and explored within an independent ultracentral lung tumor cohort. A modified Dmax to 0.1 cm3 PBT model displayed the best performance. This model could be utilized as a starting point for rationally constructed airways constraints in ultracentral patients treated with SBRT or hypofractionation.


Routine measurement of plasma chromogranin B has limited clinical utility in the management of patients with neuroendocrine tumours.
Chromogranin A (CgA) and B (CgB) are markers for monitoring disease status in patients with gastroenteropancreatic neuroendocrine tumours (NETs). These are specialized diagnostic tests often necessitating referral of specimens to a supraregional assay service (SAS) laboratory for analysis. The aim of this audit was to assess whether measurement of either plasma CgA or CgB alone provides sufficient clinical information in comparison with the current practice of measuring both markers together. A retrospective analysis was undertaken for all chromogranin tests requested for patients with a known NET diagnosis. Results were categorized based on whether plasma concentrations were elevated for one or both CgA and CgB. A total of 325 sequential patients with a NET diagnosis had plasma chromogranin levels measured during the period of review. Baseline CgA was elevated in 60·9% of patients. Isolated elevations in CgA (with normal CgB) were found in 44·9% of patients, whilst combined elevations in both CgA and CgB were found in 16% of patients. Combined CgA and CgB concentrations within the normal range were observed for 38·5% of patients. Only two patients (0·6%) had an isolated elevation in CgB at baseline. Both patients had a diagnosis of pancreatic NET and were radiologically stable. Plasma CgA and CgB corresponded with disease stage (localized vs metastatic). CgB in addition to CgA did not provide any significant improvement in diagnostic performance for identification of metastatic disease compared to CgA alone. Based on this NET population and specific assay performance characteristics, CgA alone provides sufficient information for the management of NET patients; the routine estimation of CgB in all patients is not informative in clinical practice.


Bile acid pool changes and regulation of cholate synthesis in experimental diabetes.
The effect of alloxan-diabetes and insulin treatment in bile acid pool size and composition, bile acid secretion and cholic acid synthesis was investigated in the rat. The size of the cholate pool was significantly increased 4 days after diabetes induction. It reached a constant size three times that of control animals after 2 weeks of diabetes. Changes in bile acid pool size and secretion were directly dependent of the insulin deficiency state since they were reversed by insulin treatment and were not influenced by the caloric intake of the animal nor the pharmacologic effect of alloxan. Biliary cholate secretion was also 3-fold increased in diabetic rats and it accounted for more than 80% of the total bile acids compared to 60% in the control group. The calculated daily rate of cholate synthesis was increased in diabetic rats and the circadian rhythm of cholate synthesis was abolished in this condition. Therefore, it was shown that the negative feedback mechanism that regulates bile acid snythesis was deleted in diabetes. This mechanism was partially restored after 2 weeks of insulin treatment. These studies demonstrated that bile acid metabolism was profoundly changed in alloxan-diabetic rats and suggested that insulin may play an important role in the regulation of bile acid snythesis and intestinal absorption.


Temperature-jump studies on hemoglobin. Kinetic evidence for a non-quaternary isomerization process in deoxy- and carbonmonoxyhemoglobin.
Temperature jumps on mixtures of hemoglobin and pH indicators give rise to relaxation signals in the microsecond range. The pH and concentration dependences of the reciprocal relaxation time, 1/tau, may be rationalized on the basis of a reaction scheme in which a slow isomerization process in the protein moiety is coupled to a rapid co-operative ionization of two protons. At 11 degrees C the rate constants of the isomerization are kr = 4.2(+/- 1.8) x 10(4) s-1 and kf = 1.3(+/- 0.1) x 10(4) s-1 in deoxyhemoglobin; in carbonmonoxyhemoglobin they are kr = 3.9(+/- 1.3) x 10(4) s-1 and kf = 5.3(+/- 1.8) x 10(3) s-1. The pKa values of the coupled ionizing groups are 5.3 in deoxy- and 6.0 in carbonmonoxyhemoglobin. Modification of the CysF9(93) beta sulfhydryl group with iodoacetamide abolishes the pH dependence of 1/tau, suggesting that this sulfhydryl is involved in the isomerization process. Consideration of the X-ray structure of oxyhemoglobin allows a structural interpretation of the results. It is concluded that the isomerization may be important for the physiological function of hemoglobin, but that it is not identical with the quaternary structure transition.


Volitional modulation of optically recorded calcium signals during neuroprosthetic learning.
Brain-machine interfaces are not only promising for neurological applications, but also powerful for investigating neuronal ensemble dynamics during learning. We trained mice to operantly control an auditory cursor using spike-related calcium signals recorded with two-photon imaging in motor and somatosensory cortex. Mice rapidly learned to modulate activity in layer 2/3 neurons, evident both across and within sessions. Learning was accompanied by modifications of firing correlations in spatially localized networks at fine scales.


The use of standardized Brazilian green propolis extract (EPP-AF) as an adjunct treatment for hospitalized COVID-19 patients (BeeCovid2): a structured summary of a study protocol for a randomized controlled trial.
The 2019 coronavirus disease (COVID-19) pandemic continues to spread and affects large numbers of people with unprecedented impacts. Experimental evidence has already been obtained for use of the standardized extract of Brazilian green propolis (EPP-AF) against viral targets, and clinical rationality has been demonstrated for testing this extract as an adjunct to treatment in patients affected by COVID-19. The BeeCovid2 study aims to assess whether EPP-AF has an impact on the improvement of patients hospitalized with COVID-19 by reducing the length of hospital stay. BeeCovid2 is a randomized, double-blinded, placebo-controlled clinical study being conducted in Brazil to provide further evidence on the effectiveness of standardized green propolis extract as an adjunctive treatment for adults hospitalized with COVID-19. Hospitalized patients over 18 years of age with a confirmed diagnosis of COVID-19 and up to 14 days of symptoms were included. Patients under mechanical ventilation at randomization, pregnant women, cancer patients, transplanted or using immunosuppression, HIV patients, patients who used propolis in the last 30 days, bacterial or fungal infection at randomization, impossibility of using medication orally or enterally, and advanced chronic diseases (e.g., advanced heart failure, severe liver disease, and end-stage chronic kidney disease). Enrolled patients are randomized at a 1:1 ratio to receive placebo or standardized propolis extract (900 mg/day) for 10 days. The study treatments are administered in a double-blinded manner, and patients are followed for 28 days. The primary outcome is the difference in length of hospital stay in days between groups. Secondary outcomes include the need for mechanical ventilation, the rate of secondary infection, rate of acute kidney injury, the need for renal replacement therapy, the requirement for vasoactive drugs, the use of an intra-aortic balloon pump (IABP), and the use of extracorporeal membrane oxygenation (ECMO). This trial is very useful and will provide more data on the effectiveness of using the standardized Brazilian green propolis extract as an adjunctive treatment in association with standard care in adults hospitalized with moderate to severe acute COVID-19. ClinicalTrials.gov NCT04800224 . Registered on March 16, 2021.


Synthesis and antifungal activity of thiadiazole-functionalized chitosan derivatives.
A groups of novel water soluble chitosan derivatives containing 1,3,4-thiadiazole group were synthesized including 1,3,4-thiadiazole (TPCTS), 2-methyl-1,3,4-thiadiazole (MTPCTS), and 2-phenyl-1,3,4-thiadiazole (PTPCTS). Their antifungal activity against three kinds of phytopathogens was estimated by hypha measurement in vitro, and the fungicidal assessment shows that the synthesized chitosan derivatives have excellent activity against tested fungi. Of all the synthesized chitosan derivatives, MTPCTS inhibited the growth of the tested phytopathogens most effectively with inhibitory indices of 75.3%, 82.5%, and 65.8% against Colletotrichum lagenarium (Pass) Ell.et halst, Phomopsis asparagi (Sacc.) Bubak, and Monilinia fructicola (Wint.) Honey respectively at 1.0 mg/mL. These indices are higher than those of chitosan. These data also demonstrate that the hydrophobic moiety (alkyl and phenyl) and the length of alkyl substituent in thiadiazole tend to affect the antifungal activity of chitosan derivatives. It is hypothesized that thiadiazole groups enable the synthesized chitosan to possess obviously better antifungal activity and good solubility in water.


Characteristics of plasma exosomes in drug-resistant tuberculosis patients.
Increasing prevalence of drug-resistant tuberculosis (DR-TB) poses a major challenge to the early detection and effective control of tuberculosis (TB). Exosomes carrying proteins and nucleic acid mediate intercellular communication between host and pathogen including Mycobacterium tuberculosis. However, molecular events of exosomes indicating the status and development of DR-TB remain unknown. This study determined the proteomics of exosome in DR-TB and explored the potential pathogenesis of DR-TB. Plasma samples were collected from 17 DR-TB patients and 33 non-drug-resistant tuberculosis (NDR-TB) patients using grouped case-control study design. After exosomes of plasma were isolated and confirmed by compositional and morphological measurement for exosomal characteristics, a label-free quantitative proteomics of exosomes was performed and differential protein components were determined via bioinformatics analysis. Compared with the NDR-TB group, we identified 16 up-regulated proteins and 10 down-regulated proteins in the DR-TB group. The down-regulated proteins were mainly apolipoproteins and mainly enriched in cholesterol metabolism-related pathways. Apolipoproteins family including APOA1, APOB, APOC1 were key proteins in protein-protein interaction network. Differentially expressed proteins in the exosomes may indicate the status of DR-TB from NDR-TB. Apolipoproteins family including APOA1, APOB, APOC1 may be involved in the pathogenesis of DR-TB by regulating cholesterol metabolism via exosomes.


MRI to evaluate left atrial and ventricular reverse remodeling after restrictive mitral annuloplasty in dilated cardiomyopathy.
Data on reverse remodeling of the left atrium (LA) and left ventricle (LV) after restrictive annuloplasty in patients with dilated cardiomyopathy are scarce, and follow-up studies are performed with echocardiography. Twenty patients with dilated cardiomyopathy and severe mitral regurgitation selected for restrictive mitral annuloplasty underwent serial MRI studies (within 1 week before surgery, and 2 months [n =18] and 1 year [n =13] after surgery). Early mortality was 10%; all patients were free from endocarditis and thromboembolism. New York Heart Association class improved from 3.2+/-0.4 to 1.2+/-0.9. Only 1 patient developed recurrent severe mitral regurgitation during follow-up and it was re-repaired. LA end-systolic volumes decreased significantly over time (from 165+/-48 mL to 109+/-23 mL to 111+/-28 mL; P < 0.01), as did LA end-diastolic volumes (from 92+/-32 mL to 71+/-22 mL to 75+/-17 mL; P = 0.01). LV end-diastolic volumes decreased significantly (from 244+/-56 mL to 184+/-54 mL to 195+/-67 mL; P < 0.01), whereas end-systolic volumes did not change significantly. LV ejection fraction increased significantly (from 35+/-8% to 46+/-13% to 46+/-15%; P < 0.01) and LV mass decreased significantly (from 150+/-43 grams to 132+/-39 grams to 136+/-33 grams; P = 0.02). Restrictive annuloplasty in patients with dilated cardiomyopathy yielded excellent clinical results associated with significant LA and LV reverse remodeling over time as demonstrated by MRI.


Therapeutic Hypothermia in Patients with Malignant Ischemic Stroke and Hemicraniectomy-A Systematic Review and Meta-analysis.
Therapeutic hypothermia (TH) offers cerebral protection following ischemic stroke and may improve outcomes in conjunction with decompressive hemicraniectomy (DHC). We aimed to assess the effectiveness of TH in patients with malignant ischemic stroke and DHC. We performed a meta-analysis in patients with malignant ischemic stroke undergoing DHC comparing TH versus normothermia in studies published up to August 2019. Included studies had ≥10 adults with acute ischemic stroke. Primary outcome was functional independence, and secondary outcomes included complications. Effect size was pooled and described by relative risk (RR) ratios and 95% confidence intervals (CIs). Five studies (n = 269 patients; n = 130 TH, n = 139 controls) were included, 4 of which were prospective (n = 2 randomized controlled trials). Median achieved body temperature of TH was 33.6°C (range 33°C-35°C). Median modified Rankin Scale at the study completion was similar between TH and controls (RR 1.08, 95% CI 0.56-2.07, P = 0.8). Three studies reported individual patient modified Rankin Scale outcomes demonstrated a shift toward worse outcomes with TH (unadjusted common odds ratio 1.74; 95% CI 1.05-2.88, P = 0.01). Overall complications were similar between groups (RR 1.20, 95% CI 0.70-2.05, random effects P = 0.5). A suggestion of higher mortality was seen in TH (RR 1.50, 95% CI 0.97-2.32, P = 0.07). Clinical and functional outcomes were not overall different between patients undergoing systemic TH and controls following DHC despite the shift toward worse outcomes with TH observed in some studies.


Comparing Migratory and Mechanical Properties of Human Bone Marrow-Derived Mesenchymal Stem Cells with Colon Cancer Cells In Vitro.
Colon cancer cells can migrate and metastasize by undergoing epithelial-to-mesenchymal transition (EMT). Mesenchymal stem cells (MSCs) are non-cancerous, multipotent adult stem cells, which can also migrate. In this study, we wanted to compare the biological, physical, and functional properties of these migratory cells. HT-29 and HCT-116, two human colon carcinoma cell lines, represent less aggressive and more aggressive cancer cells, respectively. MSCs were isolated from human bone marrow. After confirming the identity of all the cell types, they were evaluated for E-cadherin, β1-integrin, Vimentin, ZEB-1, β-catenin, and 18S rRNA using Q-PCR. MMP-2 and MMP-9 activity were evaluated using gelatin zymography. Functional tests like wound healing assay, migration assay, and invasion assay were also done. Biomechanical properties like cell stiffness and non-specific adhesion (between indenter probe and cell membrane) were evaluated through nanoindentation using atomic force microscopy (AFM). Expression of EMT and stem cell markers showed typical expression patterns for HT-29, HCT-116, and MSCs. Functional tests showed that MSCs migrated faster than malignant cells. MMP-2 and MMP-9 activity reinforced this behavior. Interestingly, the migration/invasion capacity of MSCs was comparable to aggressive HCT-116, and more than HT-29. MSCs also showed the maximum cell stiffness and non-specific cell-probe adhesions, followed by HCT116 and HT29 cells. Our findings indicate that the migratory properties of MSCs is comparable or even greater than that of cancer cells and despite their high migration potential, they also have the maximum stiffness.


Dapsone induced cholangitis as a part of dapsone syndrome: a case report.
Dapsone can rarely cause a hypersensitivity reaction called dapsone syndrome, consisting of fever, hepatitis, exfoliative dermatitis, lymphadenopathy and hemolytic anemia. Dapsone syndrome is a manifestation of the DRESS (drug rash with eosinophilia and systemic symptoms) syndrome which is a serious condition that has been reported in association with various drugs. Cholangitis in dapsone syndrome has not been reported so far in the world literature. We report a patient who presented with fever, exfoliative dermatitis, jaundice and anemia within three weeks of starting of dapsone therapy. These features are typical of dapsone syndrome, which is due to dapsone hypersensitivity and is potentially fatal. Unlike previous reports of hepatitic or cholestatic injury in dapsone syndrome we report here a case that had cholangitic liver injury. It responded to corticosteroids. We conclude that cholangitis, though unusual, can also form a part of dapsone syndrome. Physicians should be aware of this unusual picture of potentially fatal dapsone syndrome.


Association Between β-Blockers and Outcome of Coronary Artery Bypass Grafting: Before and After 1 Year.
We evaluated the long-term outcomes of coronary artery bypass grafting (CABG) according to β-blocker therapy using landmark analysis. Although β-blockers have been shown to improve outcomes for ischemic heart disease, the long-term effects and optimal treatment duration of use after CABG remain unknown. From January 2001 to December 2014, 5382 CABG patients were stratified into 2 groups according to β-blocker therapy at discharge (β-blocker group: 3677 [68.3%], no β-blocker group: 1705 [31.7%]). The primary outcome was all-cause death during 48 months of follow-up. Using propensity score-matched analysis, β-blocker therapy was associated with all-cause death during the 48-month follow-up (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.41-0.95; P = .03). The landmark analysis demonstrated that the effect of β-blockers on all-cause death was particularly significant within the first 12 months of therapy (HR, 0.37; 95% CI, 0.19-0.80; P = .01) but not after 12 months (HR, 0.92; 95% CI, 0.56-1.53; P = .77). The benefits of postdischarge β-blockers may be limited to 1 year after CABG, but further studies are required to confirm this finding.