[Comparison of the Wechsler Memory Scale-III and the Spain-Complutense Verbal Learning Test in acquired brain injury: construct validity and ecological validity].
To perform an in-depth examination of the construct validity and the ecological validity of the Wechsler Memory Scale-III (WMS-III) and the Spain-Complutense Verbal Learning Test (TAVEC). The sample consists of 106 adults with acquired brain injury who were treated in the Area of Neuropsychology and Neuropsychiatry of the Complejo Hospitalario de Navarra and displayed memory deficit as the main sequela, measured by means of specific memory tests. The construct validity is determined by examining the tasks required in each test over the basic theoretical models, comparing the performance according to the parameters offered by the tests, contrasting the severity indices of each test and analysing their convergence. The external validity is explored through the correlation between the tests and by using regression models. According to the results obtained, both the WMS-III and the TAVEC have construct validity. The TAVEC is more sensitive and captures not only the deficits in mnemonic consolidation, but also in the executive functions involved in memory. The working memory index of the WMS-III is useful for predicting the return to work at two years after the acquired brain injury, but none of the instruments anticipates the disability and dependence at least six months after the injury. We reflect upon the construct validity of the tests and their insufficient capacity to predict functionality when the sequelae become chronic.


Cell-free DNA, inflammation, and the initiation of spontaneous term labor.
Hypomethylated cell-free DNA from senescent placental trophoblasts may be involved in the activation of the inflammatory cascade to initiate labor. To determine the changes in cell-free DNA concentrations, the methylation ratio, and inflammatory markers between women in labor at term vs women without labor. In this prospective cohort study, eligible participants carried a nonanomalous singleton fetus. Women with major medical comorbidity, preterm labor, progesterone use, aneuploidy, infectious disease, vaginal bleeding, abdominal trauma, or invasive procedures during the pregnancy were excluded. Maternal blood samples were collected at 28 weeks, 36 weeks, and at admission for delivery. Total cell-free DNA concentration, methylation ratio, and interleukin-6 were analyzed. The primary outcome was the difference in methylation ratio in women with labor vs without labor. Secondary outcomes included the longitudinal changes in these biomarkers corresponding to labor status. A total of 55 women were included; 20 presented in labor on admission and 35 presented without labor. Women in labor had significantly greater methylation ratio (P = .001) and interleukin-6 (P < .001) on admission for delivery than women without labor. After we controlled for body mass index and maternal age, methylation ratio (adjusted relative risk, 1.38; 95% confidence interval, 1.13 to 1.68) and interleukin-6 (adjusted relative risk, 1.12, 95% confidence interval, 1.07 to 1.17) remained greater in women presenting in labor. Total cell-free DNA was not significantly different in women with labor compared with women without. Longitudinally, total cell-free DNA (P < .001 in labor, P = .002 without labor) and interleukin-6 (P < .001 in labor, P = .01 without labor) increased significantly across gestation in both groups. The methylation ratio increased significantly in women with labor from 36 weeks to delivery (P = .02). Spontaneous labor at term is associated with a greater cell-free DNA methylation ratio and interleukin-6 compared with nonlabored controls. As gestation advances, total cell-free DNA concentrations and interleukin-6 levels increase. A greater methylation ratio reflects a greater maternal contribution (vs placental) in women with labor, likely resulting from greater levels of neutrophils, lymphocytes, and uterine activation proteins at the time of labor. Although not significant, women in labor had a greater total cell-free DNA concentration and thus could theoretically have more hypomethylated DNA available for interaction with the inflammatory cascade. Larger studies are needed to investigate this theory.


Distinct features of the regenerating heart uncovered through comparative single-cell profiling.
Adult humans respond to heart injury by forming a permanent scar, yet other vertebrates are capable of robust and complete cardiac regeneration. Despite progress towards characterizing the mechanisms of cardiac regeneration in fish and amphibians, the large evolutionary gulf between mammals and regenerating vertebrates complicates deciphering which cellular and molecular features truly enable regeneration. To better define these features, we compared cardiac injury responses in zebrafish and medaka, two fish species that share similar heart anatomy and common teleost ancestry but differ in regenerative capability. We used single-cell transcriptional profiling to create a time-resolved comparative cell atlas of injury responses in all major cardiac cell types across both species. With this approach, we identified several key features that distinguish cardiac injury response in the non-regenerating medaka heart. By comparing immune responses to injury, we found altered cell recruitment and a distinct pro-inflammatory gene program in medaka leukocytes, and an absence of the injury-induced interferon response seen in zebrafish. In addition, we found a lack of pro-regenerative signals, including nrg1 and retinoic acid, from medaka endothelial and epicardial cells. Finally, we identified alterations in the myocardial structure in medaka, where they lack embryonic-like primordial layer cardiomyocytes, and fail to employ a cardioprotective gene program shared by regenerating vertebrates. Our findings reveal notable variation in injury response across nearly all major cardiac cell types in zebrafish and medaka, demonstrating how evolutionary divergence influences the hidden cellular features underpinning regenerative potential in these seemingly similar vertebrates.


Work-related olfactory disorder: a case series and review.
The olfactory bulb is anatomically exposed and thus can be directly damaged by external stimulation. This can occur as an occupational injury owing to contact with organic solvents or other causes. We present cases of eight patients who sustained occupation-related exposure to potentially toxic substances and later presented with signs and symptoms of anosmia. We examined the occupational and medical characteristics of the patients and evaluated their work-relatedness. Case 1: A 50-year-old man performed high-frequency heat treatments for approximately 11 years. He experienced decreased senses for olfaction and taste during the later years culminating in the diagnosis of anosmia after 3 years (high work-relatedness). Case 2: A 54-year-old man whose work involved exposure to various organic solvents, such as spray painting and application of paint and thinners for approximately 4 years, was subsequently diagnosed with anosmia based on rhinorrhea, headache, and loss of olfaction (high work-relatedness). Case 3: A 44-year-old-man who performed spray painting for approximately 17 years developed anosmia (high work-relatedness). Case 4: A 44-year-old man was involved in ship engine cleaning once a month, for approximately 7 h per cleaning session; he was diagnosed with anosmia based on loss of olfaction (low work-relatedness). Case 5: A 41-year-old man worked in ship building block construction for approximately 13 years; anosmia diagnosis was based on loss of olfaction (low work-relatedness). Case 6: A 47-year-old woman performed product inspection and labeling at a plant manufacturing automobile parts; anosmia diagnosis was based on decreased olfaction and taste (low work-relatedness). Case 7: A 50-year-old woman performed epoxy coating in a plant manufacturing automobile parts; anosmia diagnosis was based on diminishing olfaction (low work-relatedness). Case 8: A 57-year-old woman performed cleaning of the area where mobile phone parts were manufactured; anosmia diagnosis was based on diminishing olfaction (low work-relatedness). The study results confirmed work-relatedness when the subject was young, and the duration of exposure was long without any other cause of anosmia. Regarding compensation for occupational diseases, work-relatedness can be recognized as a relative concept.


Chemical and biological threat-agent detection using electrophoresis-based lab-on-a-chip devices.
The ability to separate complex mixtures of analytes has made capillary electrophoresis (CE) a powerful analytical tool since its modern configuration was first introduced over 25 years ago. The technique found new utility with its application to the microfluidics based lab-on-a-chip platform (i.e., microchip), which resulted in ever smaller footprints, sample volumes, and analysis times. These features, coupled with the technique's potential for portability, have prompted recent interest in the development of novel analyzers for chemical and biological threat agents. This article will comment on three main areas of microchip CE as applied to the separation and detection of threat agents: detection techniques and their corresponding limits of detection, sampling protocol and preparation time, and system portability. These three areas typify the broad utility of lab-on-a-chip for meeting critical, present-day security, in addition to illustrating areas wherein advances are necessary.


Widespread gene flow following range expansion in Anna's Hummingbird.
Anthropogenic changes have altered the historical distributions of many North American taxa. As environments shift, ecological and evolutionary processes can combine in complex ways to either stimulate or inhibit range expansion. Here, we examined the role of evolution in a rapid range expansion whose ecological context has been well-documented, Anna's Hummingbird (Calypte anna). Previous studies have suggested that the C. anna range expansion is the result of an ecological release facilitated by human-mediated environmental changes, where access to new food sources have allowed further filling of the abiotic niche. We examined the role of gene flow and adaptation during range expansion from their native California breeding range, north into Canada and east into New Mexico and Texas, USA. Using low coverage whole genome sequencing we found high genetic diversity, low divergence, and little evidence of selection on the northern and eastern expansion fronts. Additionally, there are no clear barriers to gene flow across the native and expanded range. The lack of selective signals between core and expanded ranges could reflect (i) an absence of novel selection pressure in the expanded range (supporting the ecological release hypothesis), (ii) swamping of adaptive variation due to high gene flow, or (iii) limitations of genome scans for detecting small shifts in allele frequencies across many loci. Nevertheless, our results provide an example where strong selection is not apparent during a rapid, contemporary range shift.


A novel compact three-dimensional laser-sintered collimator for neutron scattering.
Improvements in the available flux at neutron sources are making it increasingly feasible to obtain refineable neutron diffraction data from samples smaller than 1 mm(3). The signal is typically too weak to introduce any further sample environment in the 30-50 mm diameter surrounding the sample (such as the walls of a pressure cell) due to the high ratio of background to sample signal, such that even longer count times fail to reveal reflections from the sample. Many neutron instruments incorporate collimators to reduce parasitic scattering from the instrument and from any surrounding material and larger pieces of sample environment, such as cryostats. However, conventional collimation is limited in the volume it can focus on due to difficulties in producing tightly spaced neutron-absorbing foils close to the sample and in integrating this into neutron instruments. Here we present the design of a novel compact 3D rapid-prototyped (or "printed") collimator which reduces these limitations and is shown to improve the ratio of signal to background, opening up the feasibility of using additional sample environment for neutron diffraction from small sample volumes. The compactness and ease of customisation of the design allows this concept to be integrated with existing sample environment and with designs that can be tailored to individual detector geometries without the need to alter the setup of the instrument. Results from online testing of a prototype collimator are presented. The proof of concept shows that there are many additional collimator designs which may be manufactured relatively inexpensively, with a broad range of customisation, and geometries otherwise impossible to manufacture by conventional techniques.


A Rare Case of Fractured Posterior Facet of the Talus in Association With Open Medial Subtalar Dislocation.
Subtalar or peritalar dislocation is the loss of contact between the articular surface of the talus distally and the calcaneum and navicular. In this paper, a case of open medial type of subtalar dislocation associated with fractured posterior facet of the talus in a 27-year-old man with a history of road traffic accident was reported. Immediate wound irrigation and open reduction under general anesthesia at the emergency room operation theater was successful followed by cast immobilization. At one-year follow-up, the patient was walking and carrying out his daily activities with mild restriction of inversion and eversion movements. Extensive wound debridement followed by immediate reduction and, when required, stabilization are the principal features of management. Open subtalar dislocation is an extremely rare injury and often poses a treatment dilemma. Early debridement and open reduction of the dislocation like in our case can give good functional outcome for an open medial subtalar dislocation at one-year follow-up. Temporary stabilization of dislocation in the form of Kirschner wires maybe needed in some cases only.


Evaluation of Chêneau brace in the treatment of thoracic and lumbar adolescent idiopathic scoliosis with apical vertebral rotation.
Adolescent idiopathic scoliosis (AIS) is a common structural disorder of the spine in adolescents, often associated with structural deformities in both coronal and axial positions. Apical vertex rotation (AVR) is one of the main indicators of axial deformity in patients with scoliosis. Currently, there are few studies on the impact of AVR in the treatment of AIS. This study examined the influence of different AVR on AIS after brace treatment. Data were collected from 106 AIS participants aged 11-16 years from the orthopedic outpatient clinic of the Second Hospital of Lanzhou University. Two orthopaedic professionals measured the Cobb angle, AVR and spinal mid-line offset before and after brace treatment, and descriptive and linear correlation analyses were used to determine the correlation between AVR and AIS measured parameters. (1) In AIS volunteers with the same AVR, the treatment effect of AIS with lumbar predominant curvature was higher than that of AIS with thoracic predominant curvature. The treatment effect tended to decrease with increasing AVR. (2) Spinal mid-line deviation was associated with AVR. For patients with AIS with I and II degrees of AVR, the treatment effect of spinal mid-line offset after bracing is better. For AIS patients with AVR III degrees and above, the degree of correction of spinal mid-line offset decreases with the continuous correction of Cobb angle. The efficacy of AIS was found to be related to the severity of AVR. The efficacy of AIS with predominantly lumbar curvature was significantly higher than that of AIS with predominantly thoracic curvature. The efficacy of treatment of mid-line spinal deviation also decreased with increasing AVR.


Growth of a vortex polycrystal in type II superconductors.
We discuss the formation of a vortex polycrystal in type II superconductors from the competition between pinning and elastic forces. We compute the elastic energy of a deformed grain boundary, which is strongly nonlocal, and obtain the depinning stress for weak and strong pinning. Our estimates for the grain size dependence on the magnetic field strength are in good agreement with previous experiments on NbMo. Finally, we discuss the effect of thermal noise on grain growth.


Surveillance of Otitis Media With Effusion in Thai Children With Cleft Palate: Cumulative Incidence and Outcome of the Management.
To study the incidence and outcome of management of otitis media with effusion in Thai children with cleft palate. Retrospective cohort study in the tertiary care center. Ninety-five children with cleft palate were referred for ear evaluation, from June 1997 to January 2015. Fifteen children (15.8%) had associated craniofacial syndromic anomalies. Cumulative incidence of otitis media with effusion, rate of ventilation tube insertion, duration of indwelling tubes, hearing outcome, and complications of ventilation tubes. Ear examinations were done every 8 to 12 weeks throughout the study. Cumulative incidence of otitis media with effusion was 53.7% in children within 12 months of age and 81.1% within 24 months of age. At the end of the study, all of the patients had at least 1 episode of otitis media with effusion. Eighty-eight children (92.6%) had palatoplasty, and there was no significant difference in the incidence of otitis media before and after palatoplasty. The mean hearing level at recruitment was 40.8 ±18.4 dB. Ventilation tube insertion was done in 76 patients (80%). The median time for indwelling tubes was 11.7 months. Rate of ventilation tube insertion was 0.5/year. The mean hearing level at last follow-up was 23.5 ± 14 dB. Otorrhea through tube was found in 24 cases (31.6%). Otitis media with effusion was common in Thai children with cleft palate. Surveillance of middle ear effusion and ventilation tube insertion contributed to a favorable hearing outcome.


Social determinants of depression in systemic lupus erythematosus: A systematic scoping review.
Social determinants of health (SDOH) influence inequities in systemic lupus erythematosus (SLE). While these inequities contribute to overall disease experience, there is little consensus guiding our understanding of the psychological implications of SDOH in SLE. Given the paucity of evidence in this area, the aim of this scoping review was to systematically assess the volume and features of available research literature on associations of SDOH with depression in SLE over the past 20 years, from 1 January 2000 to 16 November 2021. We developed a search strategy for PubMed and EMBASE that included keywords for depression and lupus. After screening 2188 articles, we identified 22 original articles that met our inclusion criteria. At least one SDOH was associated with depression in two of the six studies with unadjusted estimates and 13 of the 16 studies with adjusted estimates. Results provide consistent but sparse evidence that SDOH are associated with depression in SLE. Additionally, depression epidemiology in SLE may differ from the general population such that depression risk is more similar across genders and racial/ethnic groups. More work is needed to identify the SDOH that have the greatest impact on depression and mental health among SLE patients, as well as how and when to intervene.


Human granulosa and thecal cells secrete distinct protein profiles.
Granulosa and thecal cells were isolated from follicles of ovaries removed from premenopausal women who underwent salpingo-oophorectomy. The electrophoretic profiles of the [35S]methionine-radiolabeled proteins secreted by the two cell types were quite distinct and showed different major proteins. Untreated granulosa cells secreted a major radiolabeled protein with a molecular weight of 220,000, identified as fibronectin by immunoprecipitation. This protein comprised 21% of the total secreted protein; however, the intensity of labeling was reduced after treatment with 0.5 mM dibutyryladenosine 3':5'-cyclic monophosphate ([Bu]2 cAMP). Fibronectin secretion by control cultures measured by a competitive enzyme-linked immunoadsorbant assay ranged from 15.1 to 16.8 micrograms/mg cellular protein/24 hours and was reduced to 30% after treatment with 0.5 mM (Bu)2 cAMP. In contrast, untreated thecal cells secreted only low levels of fibronectin and a 25,000-dalton protein contributed 20% of the total secreted radiolabeled proteins.


Protein Phosphorylation is a Key Mechanism in Alzheimer's Disease.
Altered protein phosphorylation states of several proteins are closely associated with Alzheimer's disease (AD). Among these are the amyloid-β protein precursor (AβPP) and the tau protein. In fact, altered protein phosphorylation states already provide strong biomarkers for AD diagnosis, as is the case with hyperphosphorylated tau. It follows that modulating signaling cascades provides an attractive avenue for exploring novel therapeutic strategies. This review focuses on some of the major protein kinases and protein phosphatases relevant to AD. Of particular relevance, posttranslational modifications dynamically regulate protein activity, subcellular localization, and stability. Protein phosphorylation states can mediate complex formation as well as regulate protein function, and this is important for cellular physiology but can likewise contribute to the development of neuropathological conditions. Furthermore, applying a system approach provides a more comprehensive understanding of the signaling events associated with AD and highlights possible convergence points that may contribute to the different AD pathological hallmarks.


Gypsins A-D from Gypsophila arabica.
Four new cyclopeptides, named gypsins A-D (1- 4), together with one known oleanane saponin, were isolated from the roots of Gypsophila arabica. The structures of cyclo(-Leu(1)-Pro(2)-Leu(3)-Trp(4)-Pro(5)-Gly(6)-) (1), cyclo(-Leu(1)-Pro(2)-Tyr(3)-Phe(4)-Pro(5)-Gly(6)-) (2), cyclo(-Ala(1)-Pro(2)-Tyr(3)-Leu(4)-Leu(5)-Pro (6)-Pro(7)-Ala(8)-) (3), and cyclo(-Leu(1)-Trp(2)-Pro(3)-Gly(4)-Gly(5)-Ser(6)-Ser(7)-) (4) were elucidated by 1D and 2D NMR spectroscopy including 1D-TOCSY, DQF-COSY, 2D-ROESY, HSQC, and HMBC experiments, as well as ESI tandem mass spectrometric fragmentation analysis and chemical evidence.


Thromboelastography for Evaluation of Coagulopathy in Nonbleeding Patients with Sepsis at Intensive Care Unit Admission.
Thromboelastography (TEG) is a global test of coagulation which analyzes the whole coagulation process. TEG is popular in trauma, liver transplant, and cardiac surgeries, but studies in sepsis are limited. We have assessed the utility of TEG for evaluating coagulopathy in nonbleeding patients with sepsis. A prospective, observational study was done in 12-bedded Intensive Care Unit (ICU) of a tertiary care hospital in North India, during May 2014-November 2014. After ethical clearance, all patients at ICU admission with sepsis were included in the study. Exclusion criteria were age <18 years, plasma/platelet transfusion before admission, patients on oral antiplatelets/anticoagulants, or with underlying hematological disorders. At admission, blood samples for TEG were analyzed by kaolin-based TEG analyzer within an hour of collecting 2.7 ml citrated blood from arterial line. TEG parameters included reaction time (R), K time (K), alpha angle (a), maximum amplitude (MA), coagulation index (CI), and lysis index (LY 30). In TEG, mean values of R, K, a, MA, CI, and LY30 were 6.45 ± 2.59 (min), 1.67 ± 0.96 (min), 66.37 ± 10.44 (0), 67.08 ± 10.33 (mm), 0.63 ± 3.46, and 2.23 ± 4.08 (%), respectively. In conventional coagulation assay (CCA), mean values of international normalized ratio (INR), platelet, and fibrinogen were 1.63 ± 0.57, 153.96 ± 99.16 (×103 /mm3), and 301.33 ± 112.82 (mg/dl), respectively. In those with deranged INR (INR ≥1.6), 60% were normocoagulable and 20% were hypercoagulable. Similarly, 81% patients with thrombocytopenia (platelet count <1,00,000/mL) were normocoagulable. TEG could differentiate among normocoagulant, hypocoagulant, hypercoagulant states (unlike CCAs). Patients with septic shock had trend toward hypocoagulant state while those without shock had trend toward hypercoagulant state.


The epileptic network and cognition: What functional connectivity is teaching us about the childhood epilepsies.
Our objective was to summarize and evaluate the rapidly expanding body of literature studying functional connectivity in childhood epilepsy. In the self-limited childhood epilepsies, awareness of cognitive comorbidities has been steadily increasing, and recent advances in our understanding of the network effects of these disorders promise insights into the underlying neurobiology. We reviewed publications addressing functional connectivity in children with epilepsy with an emphasis on studies of children with self-limited childhood epilepsies. The majority of studies have been published in the past 10 years and predominantly examine childhood epilepsy with centrotemporal spikes and childhood absence epilepsy. Cognitive network alterations are commonly observed across the childhood epilepsies. Some of these effects appear to be nonspecific to epilepsy syndrome or even to category of neurological disorder. Other patterns, such as changes in the connectivity of cortical language areas in childhood epilepsy with centrotemporal spikes, provide clues to the underlying cognitive deficits seen in affected children. The literature to date is dominated by general observations of connectivity patterns without a priori hypotheses. These data-driven studies build an important foundation for hypothesis generation and are already providing useful insights into the neuropathology of the childhood epilepsies. Future work should emphasize hypothesis-driven approaches and rigorous clinical correlations to better understand how the knowledge of network alterations can be applied to guidance and treatment for the children in our clinics.


The delayed southern migration of a transcatheter aortic valve.
Transcatheter aortic valve replacement has emerged as a favourable alternative in patients with severe symptomatic aortic stenosis who are at intermediate and/or high risk for open aortic valve replacement. While transcatheter aortic valve replacement has been shown to be a safe alternative to surgical aortic valve replacement in those populations, the procedure is not without risks. Transcatheter heart valve migration can occur, albeit rarely, in an acute, subacute and delayed fashion. This complication can have fatal consequences if not managed appropriately. We describe a patient who underwent a transcatheter aortic valve replacement and had evidence of transcatheter heart valve subacute migration into the left ventricular outflow tract.


Accuracy of trans-abdominal ultrasound pregnancy diagnosis in sows using a linear or sector probe.
The assessment of an early and reliable pregnancy diagnosis in sows is very important for limiting the number of non-productive days in sow herds. The aim of the present study was to investigate the accuracy of trans-abdominal ultrasound detection for early pregnancy diagnosis in sows under field conditions. Particular attention was paid to the time when a reliable diagnosis can be made, and to possible differences between two commonly used types of scanners. In total, 202 sows from two herds were tested daily with scanners A (linear transducer of 5 MHz) and B (sector transducer of 3.5 MHz) from day 16 until 25 after insemination. Ninety-three percentage of the sows were pregnant 36 days after insemination. Using ultrasound, the first pregnancy could be detected already 18 days after insemination. The sensitivity, specificity and overall accuracy were higher than 95% from day 24 (scanner A) or day 23 (scanner B) post-insemination onwards. The positive predictive values from day 19 onwards were consistently higher than 95% with both types of scanners, whereas the negative predictive values were consistently low for both scanners during the entire period. The sensitivity of testing tended to be slightly lower in sows with a litter size of <10 total born piglets, compared to sows with 10 or more piglets. In conclusion, pregnancy diagnosis in sows using trans-abdominal ultrasound testing can be assessed quickly and reliably under field conditions from day 23 of gestation onwards. Predictive values of positive test results were high in these herds, whereas those of negative test results were low. This implies that sows with a negative test result early in pregnancy should be retested later.


Cinnamaldehyde in diabetes: A review of pharmacology, pharmacokinetics and safety.
Cinnamaldehyde, one of the active components derived from Cinnamon, has been used as a natural flavorant and fragrance agent in kitchen and industry. Emerging studies have been performed over the past decades to evaluate its beneficial role in management of diabetes and its complications. This review highlights recent advances of cinnamaldehyde in its glucolipid lowering effects, its pharmacokinetics, and its safety by consulting the Pubmed, China Knowledge Resource Integrated, China Science and Technology Journal, National Science and Technology Library, Wanfang Data, and the Web of Science Databases. For the inquiries, keywords such as Cinnamon, cinnamaldehyde, property, synthesis, diabetes, obesity, pharmacokinetics, and safety were used in various combinations. Accumulating evidence supports the notion that cinnamaldehyde exhibits glucolipid lowering effects in diabetic animals by increasing glucose uptake and improving insulin sensitivity in adipose and skeletal muscle tissues, improving glycogen synthesis in liver, restoring pancreatic islets dysfunction, slowing gastric emptying rates, and improving diabetic renal and brain disorders. Cinnamaldehyde exerts these effects through its action on multiple signaling pathways, including PPARs, AMPK, PI3K/IRS-1, RBP4-GLUT4, and ERK/JNK/p38MAPK, TRPA1-ghrelin and Nrf2 pathways. In addition, cinnamaldehyde seems to regulate the activities of PTP1B and α-amylase. Furthermore, cinnamaldehyde has the potential of metalizing into cinnamyl alcohol and methyl cinnamate and cinnamic acid in the body. Finally, there is a potential toxicity concern about this compound. In summary, cinnamaldehyde supplementation is shown to improve glucose and lipid homeostasis in diabetic animals, which may provide a new option for diabetic intervention. To this end, further scientific evidences are required from clinical trials on its glucose regulating effects and safety.


Secreted frizzled-related protein 4 exerts anti-atherosclerotic effects by reducing inflammation and oxidative stress.
Atherosclerosis and its sequelae, such as coronary artery disease (CAD), are the most common diseases worldwide and the leading causes of morbidity and mortality in most countries. Our previous studies have shown that circulating secreted frizzled-related protein 4 (SFRP4) levels are increased in patients with CAD. However, the role of SFRP4 in the development of atherosclerosis remains unclear; thus, the purpose of this study was to determine the effect of SFRP4 on high-fat diet (HFD)-induced atherosclerosis and explore the possible mechanisms. In this study, we found for the first time that administration of recombinant SFRP4 alleviates atherosclerosis in ApoE-/- mice by reducing inflammation and oxidative stress. In addition, the anti-atherosclerotic effect of SFRP4 was associated with inhibition of the Wnt/β-catenin signaling pathway, and Wnt1 overexpression abolished the anti-atherosclerotic effects of SFRP4. Taken together, our results highlight the potential beneficial effect of SFRP4 as a therapeutic agent for atherosclerosis and CAD.


Update: Non-Invasive Positive Pressure Ventilation in Chronic Respiratory Failure Due to COPD.
Long-term non-invasive positive pressure ventilation (NPPV) has widely been accepted to treat chronic hypercapnic respiratory failure arising from different etiologies. Although the survival benefits provided by long-term NPPV in individuals with restrictive thoracic disorders or stable, slowly-progressing neuromuscular disorders are overwhelming, the benefits provided by long-term NPPV in patients with chronic obstructive pulmonary disease (COPD) remain under question, due to a lack of convincing evidence in the literature. In addition, long-term NPPV reportedly failed in the classic trials to improve important physiological parameters such as arterial blood gases, which might serve as an explanation as to why long-term NPPV has not been shown to substantially impact on survival. However, high intensity NPPV (HI-NPPV) using controlled NPPV with the highest possible inspiratory pressures tolerated by the patient has recently been described as a new and promising approach that is well-tolerated and is also capable of improving important physiological parameters such as arterial blood gases and lung function. This clearly contrasts with the conventional approach of low-intensity NPPV (LI-NPPV) that uses considerably lower inspiratory pressures with assisted forms of NPPV. Importantly, HI-NPPV was very recently shown to be superior to LI-NPPV in terms of improved overnight blood gases, and was also better tolerated than LI-NPPV. Furthermore, HI-NPPV, but not LI-NPPV, improved dyspnea, lung function and disease-specific aspects of health-related quality of life. A recent study showed that long-term treatment with NPPV with increased ventilatory pressures that reduced hypercapnia was associated with significant and sustained improvements in overall mortality. Thus, long-term NPPV seems to offer important benefits in this patient group, but the treatment success might be dependent on effective ventilatory strategies.


Improving the quality and safety of frozen muscle foods by emerging freezing technologies: A review.
Freezing is one of the most widespread used preservation methods for meats including fish meat. Traditional freezing methods such as air blast freezing and cryogenic freezing could induce some quality deterioration such as damage to cell structure, increased drip loss, and poor sensory value. Therefore, novel freezing methods have been developed to minimize the disadvantages of traditional freezing methods. This review describes the enhancement of quality attributes of muscle tissues frozen by novel freezing technologies, including high pressure freezing, electrically and magnetically assisted freezing, ultrasound assisted freezing and antifreeze protein. These quality attributes include microstructure, moisture loss, color, tenderness, protein denaturation, lipid and protein oxidation, and microbial counts. In this review, the principles of these emerging freezing technologies are introduced, and the impacts of these technologies on controlling the formation and growth of ice crystals and on complex changes of protein are also discussed. The current review shows that the novel freezing methods have positive effects on promoting the quality of frozen muscle. At a micro level, the majority of the novel methods have some certain ability on controlling the formation and growth of ice crystals, thus creating smaller, and more homogeneous and regular distribution of ice crystals, leading to better microstructure and enhanced quality attributes of frozen meats. Meanwhile, complex changes of protein take place under some of these novel freezing processes, and therefore the possible negative effect of the changes of protein should also be considered for commercial applications of these technologies in the frozen food industry.


Dark matter, constrained minimal supersymmetric standard model, and lattice QCD.
Recent lattice measurements have given accurate estimates of the quark condensates in the proton. We use these results to significantly improve the dark matter predictions in benchmark models within the constrained minimal supersymmetric standard model. The predicted spin-independent cross sections are at least an order of magnitude smaller than previously suggested and our results have significant consequences for dark matter searches.


The application and research progress of bacteriophages in food safety.
The abuse of antibiotics and the emergence of drug-resistant bacteria aggravate the problem of food safety. Finding safe and efficient antibiotic substitutes is an inevitable demand for ensuring the safety of animal-derived food. Bacteriophages are a kind of virus that can infect bacteria, fungi or actinomycetes. They have advantages of simple structure, strong specificity and nontoxic side effects for the human body. Bacteriophages can not only differentiate live cells from dead ones but also detect bacteria in a viable but nonculturable state. These characteristics make bacteriophages more and more widely used in the food industry. This paper describes the concept and characteristics of bacteriophages, and introduces the application of bacteriophages in preharvest production, food processing, storage and sales. Several methods of using bacteriophages to detect foodborne pathogens are listed. Finally, the advantages and limitations of bacteriophages in the food industry are summarized, and the application prospect of bacteriophages in the food industry is discussed.


Uptake and barriers for implementation of the resect and discard strategy: an international survey.
Background and study aims Optical real-time diagnosis (= resect-and-discard strategy) is an alternative to histopathology for diminutive colorectal polyps. However, clinical adoption of this approach seems sparse. We were interested in evaluating potential clinical uptake and barriers for implementation of this approach. Methods We conducted an international survey using the "Google forms" platform. Nine endoscopy societies distributed the survey. Survey questions measured current clinical uptake and barriers for implementing the resect-and-discard strategy , perceived cancer risk associated with diminutive polyps and potential concerns with using CT-colonography as follow-up, as well as non-resection of diminutive polyps. Results Eight hundred and eight endoscopists participated in the survey. 84.2 % (95 % CI 81.6 %-86.7 %) of endoscopists are currently not using the resect-and-discard strategy and 59.9 % (95 % CI 56.5 %-63.2 %) do not believe that the resect-and-discard strategy is feasible for implementation in its current form. European (38.5 %) and Asian (45 %) endoscopists had the highest rates of resect-and-discard practice, while Canadian (13.8 %) and American (5.1 %) endoscopists had some of the lowest implementation rates. 80.3 % (95 % CI 77.5 %-83.0 %) of endoscopists believe that using the resect-and-discard strategy for diminutive polyps will not increase cancer risk. 48.4 % (95 % CI 45.0 %-51.9 %) of endoscopists believe that leaving diminutive polyps in place is associated with increased cancer risk. This proportion was slightly higher (54.7 %; 95 % CI 53.6 %-60.4 %) when asked if current CT-colonography screening practice might increase cancer risks. Conclusion Clinical uptake of resect-and-discard is very low. Most endoscopists believe that resect-and-discard is not feasible for clinical implementation in its current form. The most important barriers for implementation are fear of making an incorrect diagnosis, assigning incorrect surveillance intervals and medico-legal consequences.


Delayed activation of HNF-3 beta upon retinoic acid-induced teratocarcinoma cell differentiation.
We have investigated the retinoic acid-mediated activation of the transcriptional regulator HNF-3 beta during differentiation of mouse F9 embryonal carcinoma cells. Using gel shifts, HNF-3 beta DNA binding activity was clearly detected in differentiated cells, while F9 stem cells were devoid of this activity. We also demonstrated that HNF-3 beta mRNA is specific for differentiated cells. Addition of retinoic acid to F9 stem cells results in delayed activation of HNF-3 beta mRNA which can be detected 1-2 days after the initiation of differentiation. HNF-3 beta mRNA concentrations are maximal at approximately 4 days postdifferentiation and stay at elevated levels for at least 4 additional days. Nuclear run-on experiments clearly show that HNF-3 beta is activated at the level of transcriptional initiation, suggesting that the increases of beta-specific DNA binding activity and mRNA concentration are merely a reflection of this activation mechanism. F9 cells can give rise to three distinct differentiated cell types, visceral endoderm, parietal endoderm, and primitive endoderm, and we have observed HNF-3 beta stimulation during the formation of all three tissues. HNF-3 beta stimulation upon visceral endoderm differentiation is accompanied by the activation of HNF-3 target genes such as transthyretin, suggesting that HNF-3 beta is involved in the developmental activation of this gene. In contrast, HNF-3 beta target genes in parietal and primitive endoderm have yet to be identified. However, the stimulation of HNF-3 beta during primitive endoderm formation, which is an extremely early event during murine embryogenesis, points toward a role for the factor in crucial determination processes that occur early during development.


When does prior knowledge disproportionately benefit older adults' memory?
Material consistent with knowledge/experience is generally more memorable than material inconsistent with knowledge/experience - an effect that can be more extreme in older adults. Four experiments investigated knowledge effects on memory with young and older adults. Memory for familiar and unfamiliar proverbs (Experiment 1) and for common and uncommon scenes (Experiment 2) showed similar knowledge effects across age groups. Memory for person-consistent and person-neutral actions (Experiment 3) showed a greater benefit of prior knowledge in older adults. For cued recall of related and unrelated word pairs (Experiment 4), older adults benefited more from prior knowledge only when it provided uniquely useful additional information beyond the episodic association itself. The current data and literature suggest that prior knowledge has the age-dissociable mnemonic properties of (1) improving memory for the episodes themselves (age invariant), and (2) providing conceptual information about the tasks/stimuli extrinsically to the actual episodic memory (particularly aiding older adults).


Antibiogram profile of uropathogens isolated at Bahir Dar Regional Health Research Laboratory Centre, Northwest Ethiopia.
Antimicrobial resistance among bacteria that cause urinary tract infection (UTI) has been increasing since the introduction of chemotherapy. This study was aimed to assess the types of isolates from patients with UTI and to determine their current antimicrobial susceptibility profile. A record based retrospective analysis of bacterial uropathogens processed in the period of January 2012 to December 2014 at Bahir Dar Health Research Laboratory Center (BRHRLC) was determined. According to standard microbiological procedures, midstream urine samples were collected and processed with conventional culture and biochemical tests. Isolates were tested against commonly used antibiotics by Kirby-Bauer disc diffusion methods. Chi-square test was calculated to compare the proportion of bacterial isolates between sex and age and statistical significance was set at p value < 0.05. Out of 446 patients, female constituted at 299 (67%). Significant bacteriuria was reported on 30.5% (95% CI: 26.4-34.9%) cultures. Of these, 78% (95% CI: 71.0-84.7%) were from females. Age and sex were found associated with significant bacteriuria at p=0.046 and p=0.001 respectively. The most commonly identified isolates were Escherichia coli, at 72 (49 %) followed by Klebshella pneumonia at 20 (13.6%) and Pseudomonas aureginosa at 11 (7.5%). The overall antimicrobial susceptibility profile showed that Trimetoprim-sulphamethoxazole, amoxicillin/clavulanate and ampicillin revealed high level of resistance, at 84(66.7%), 61(79.2%), 106(91.4% respectively. Conversely, 64.2-100% sensitivity rate was documented for ciprofloxacin, gentamycin and pepracillin. UTI associated with multiple drug resistant bacteria is an important health concern of the study population. Therefore, ongoing surveillance of the types of uropathogens and their up-to-date antimicrobial resistance profile is crucial for better management of patients.


Transcription termination and RNA processing in the 3'-end spacer of mouse ribosomal RNA genes.
The 3' termini of ribosomal RNA precursors from mouse FM3A cultured cells are mapped to eight sites within 625 bp downstream from the 3' terminus of 28 S rRNA. Three additional sites are mapped in liver RNA from C3H/He strain mice. Two of them, the sites at 570 bp and 625 bp are assumed to be termination sites in vivo, because they correspond to in vitro termination sites of RNA polymerase I, and 45 S RNAs having these 3' termini decay with kinetics distinct from others. The amount of 45 S RNA having the 3' terminus at other sites is variable among several mouse strains, despite their having the same DNA sequence in these regions. The ability to produce 3' termini in these sites seems to follow Mendel's law of inheritance. Therefore, we postulate that these nine sites are RNA processing sites which are controlled genetically.


Downregulation of CXCR4 by SDF-KDEL in SBC-5 cells inhibits their migration in vitro and organ metastasis in vivo.
Metastasis is the principal cause of morbidity and mortality in cancer patients. The master genes that govern organ-selective metastasis remain elusive. We compared the expression levels of C-X-C chemokine receptor type 4 (CXCR4) in the human small cell lung cancer (SCLC) cells, SBC-5 and SBC-3, by flow cytometric analysis and found that CXCR4 was expressed at markedly higher levels in the SBC-5 cells which can produce multiple organ metastasis, particularly bone metastasis compared to the SBC-3 cells. Stromal-derived-factor-1 (SDF-1)-CXCR4 has been shown to regulate cell migration and metastasis in a various types of cancer; however, the roles of SDF-1-CXCR4 in the organ-selective metastasis of SCLC in vivo remain to be elucidated. Thus, in this study, we constructed a phenotype of SBC-5 cells in which CXCR4 was knocked out using the intrakine strategy and found that the downregulation of CXCR4 inhibited cell migration and invasion, but did not affect cell proliferation or apoptosis in vitro. In in vivo experiments, the knockout of CXCR4 suppressed the development of metastastic lesions in the lungs, liver and bone, but did not decrease metastasis to the kidneys. Our data demonstrate that CXCR4 is a candidate gene involved in the development of metastastic lesions in specific organs, such as the lungs, bone and liver, which can secrete high concentrations of SDF-1, the sole ligand of CXCR4. Thus, CXCR4 may prove to be a promising target for the prevention and effective treatment of metastastic lesions due to SCLC.


Quantification of human myeloperoxidase in oral fluids.
Peroxidase activity in human whole saliva is derived from salivary peroxidase and myeloperoxidase. Present spectrophotometric assays are relatively non-specific and influenced by ions present in salivary secretions, resulting in an over and/or underestimation of peroxidase activities. Specific polyclonal or monoclonal antibodies would greatly simplify the identification of salivary peroxidase and myeloperoxidase in human saliva and determine the relative contribution of each enzyme to the total peroxidase activity in human saliva. In the present study, a highly purified preparation of myeloperoxidase was used to raise polyclonal antibodies against the antigen. The antibodies were purified and extensively characterized in terms of their ability to interact with the antigen, with other mammalian peroxidases, and with other proteins present in salivary fluids. The antibodies recognized only myeloperoxidase and did not cross-react with any of the substances tested, showing that these antibodies can be used to detect and differentiate myeloperoxidase from other peroxidases in saliva. We have also developed and tested a sandwich ELISA which can be used in a clinical setting to quantify myeloperoxidase in whole saliva and gingival crevicular fluid.


[Cross-reactivity in immunotherapy].
Side effects of allergen-specific immunotherapy beyond the well-known local and systemic allergic reactions are rare. Cross-reactivity between some groups of inhaled and oral allergens has been documented but not sufficiently explained. Some trials and clinical observations indicate the similarity of allergen subunits and clinical manifestations of this phenomenon.


Docosapentaenoic acid (DPA, 22:5n-3) ameliorates inflammation in an ulcerative colitis model.
The anti-inflammatory profile of DPA was investigated via a dextran sulphate sodium (DSS)-induced colitis model, and was also compared with those of EPA and DHA. The results showed that DPA could significantly reduce (stronger than EPA and DHA) the disease activity index score, macroscopic appearance score, colon shortening, histological assessment, and myeloperoxidase accumulation in the colon. In addition, DPA also inhibited the abnormal production and mRNA expression of pro-inflammatory cytokines, namely tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 and improved the production and expression of an anti-inflammatory cytokine, IL-10. Furthermore, the molecular mechanisms underlying these effects were also explored through the synthesis pathway of eicosanoids. DPA could inhibit the synthesis of leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) more greatly while differences of cyclooxygenase (COX) and 5-lipoxidase (LOX) contents in these three groups were not significant. We ascribed these effects to the easier incorporation of DPA into inflammatory cells leading to the decrease in the substrate for the synthesis of pro-inflammatory eicosanoids (PGE2 and LTB4). Besides, DPA-derived mediators might also be involved.


[Intervention of Qi-activating and Spleen-strengthening Herbs on Ca2+/CaMK II Signaling Pathways Key Factors in Skeletal Muscle Tissue of Rats with Spleen-qi Deficiency].
To observe changes of [Ca2+]i concentration and CaM, CaMK II and p-CaMK II of Ca2+/CaMK II signaling pathways in skeletal muscle tissue of rats with spleen-qi deficiency and intervention of Sijunzi decoction and extract of Hedysarum polybotrys. Rats were randomized into four groups: normal control group, spleen-qi deficient model group, extract from Hedysarum polybotrys group and Sijunzi decoction group, ten rats in each group. After the spleen-qi deficient models were built by comprehensive application of rhubarb, exhaustive and hungry methods, and treatment groups were treated with extract from Hedysarum polybotrys at 6 g/(kg . d) or Sijunzi decoction at 20 g/(kg . d) for 21 d. Then, general existence,gastrointestinal hormones GAS and MOT levels, and activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase of skeletal muscle were evaluated. Also, confocal laser technology was used to test cellular[Ca2+]i concentrations in skeletal muscle and Western blotting technique was used to test CaM, CaMK II and p-CaMK 11 expression in intestinal tissue of spleen-qi deficient model rats. Compared with normal group, general condition was poor, levels of GAS and MOT decreased (P <0. 01), activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase, [Ca2+]i concentration as well as expression of CaM, CaMK II and p-CaMK II in skeletal muscle decreased significantly (P < 0. 01) in spleen-qi deficienct model rats. Compared with model group, general condition improved significantly, as well as level of MOT in intestinal increased (P <0. 05) in the rats of extract from Hedysarum polybotrys group and Sijunzi decoction group,while level of GAS increased in intestinal(P <0. 05) in the rats of Sijunzi decoction group; Moreover, activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase as well as [Ca2+]i concentration and expression of CaM and CaMK II in skeletal muscle tissue increased (P < 0. 05) in the rats of extract from Hedysarum polybotrys group and Sijunzi decoction group, while p-CaMK II in skeletal muscle tissue increased in the rats of Sijunzi decoction group (P < 0. 05). Sijunzi decoction and extract of Hedysarum polybotrys can be applied to treat spleen-qi deficiency syndrome through the mechanism of regulating GAS and MOT secretion and raising expression of Ca2+ /CaM signaling pathways key factors in skeletal muscle tissue. Sijunzi decoction has the better effect


Verapamil-sensitive idiopathic left ventricular tachycardia in a 6-month-old: unique considerations in diagnosis and management in an infant.
Idiopathic left ventricular tachycardia of the Belhassen type is rare in infants. We present a 6-month-old infant girl with a wide-complex tachycardia with right bundle branch block QRS morphology, a superior axis, and atrioventricular dissociation, consistent with a left anterior fascicular tachycardia. Initial echocardiogram revealed depressed ventricular function. The tachycardia was unresponsive to therapeutic trials of adenosine, esmolol, procainamide, and lidocaine. There was brief conversion of the tachycardia to sinus rhythm with transesophageal atrial overdrive pacing, suggesting a reentrant mechanism of the arrhythmia. Ultimately, the judicious administration of intravenous verapamil resulted in termination of the arrhythmia, which has been sustained on oral therapy.


The spin and orbital moment of Fe(n) (n = 2-20) clusters.
Complementary to the recent experimental finding that the orbital magnetic moment is strongly quenched in small Fe clusters [M. Niemeyer, K. Hirsch, V. Zamudio-Bayer, A. Langenberg, M. Vogel, M. Kossick, C. Ebrecht, K. Egashira, A. Terasaki, T. Möller, B. v. Issendorff, and J. T. Lau, Phys. Rev. Lett. 108, 057201 (2012)], we provide the theoretical understanding of the spin and orbital moments as well as the electronic properties of neutral and cation Fen clusters (n = 2-20) by taking into account the effects of strong electronic correlation, spin-orbit coupling, and noncollinearity of inter-atomic magnetization. The generalized gradient approximation (GGA)+U method is used and its effluence on the magnetic moment is emphasized. We find that without inclusion of the Coulomb interaction U, the spin (orbital) moments have an average value between 2.69 and 3.50 μB/atom (0.04 and 0.08 μB/atom). With inclusion of U, the magnetic value is between 2.75 and 3.80 μB/atom (0.10 and 0.30 μB/atom), which provide an excellent agreement with the experimental measurements. Our results confirm that the spin moments are less quenched, while the orbital moments are strongly quenched in small Fe clusters. Both GGA and GGA+U functionals always yield collinear magnetic ground-state solutions for the fully relaxed Fe structures. Geometrical evolution, as a function of cluster size, illustrates that the icosahedral morphology competes with the hexagonal-antiprism morphology for large Fe clusters. In addition, the calculated trends of ionization potentials, electron affinities, fragment energies, and polarizabilities generally agree with respective experimental observations.


Young and heavy patients with a cementless TKA do as well as older and lightweight patients.
Given concerns about long term implant loosening in young, heavy patients, we asked whether these patients would fare as well as older, lightweight patients with bone-ingrowth fixation. Cementless total knee arthroplasty was performed consecutively in 1328 patients (1556 knees) using a total knee system designed for porous-ingrowth fixation. A consecutive series of 122 patients (167 knees) whose age was younger than 55 years and whose weight was greater than 90 kg was compared with a gender-matched consecutive series of 122 patients (167 knees) who were 65 years of age or older and who weighed less than 80 kg. The minimum followup was 5 years (mean 7.3 years; range 5-10 years). The mean Knee Society scores and pain scores were similar at each interval for both groups. Function scores were better for the young, heavy patients at each interval. None of the knees in either group loosened. One patient in the young, heavy group underwent polyethylene component revision for wear. These results indicate young, heavy patients fare as well as older, lightweight patients when this implant is used with the osteointegration technique. Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.


The Role of Ultrasound Semi-Quantitative Scoring in the Diagnosis and Assessment of Gout and Hyperuricemia.
To develop an ultrasound semi-quantitative scoring system for the diagnosis and evaluation of gout and hyperuricemia. This study included 348 male patients: 81 patients with asymptomatic hyperuricemia, 182 patients with gout, and 85 patients with other arthritis. Clinical data were collected, ultrasound was detected, gout activity score was calculated to assess disease activity, and statistical analysis was performed. Monosodium urate crystal deposition and subclinical arthritis were detected in 17 patients with asymptomatic hyperuricemia, with lesions concentrated in the metatarsophalangeal joint, ankle and peroneus-longus and brevis at rate of 91.8%. Gout was significantly higher than non-gouty arthritis in crystal scores (sum scores of double contour, aggregates, and tophi), but not in inflammation scores (sum scores of synovial hypertrophy, power Doppler [PD] activity, and tenosynovitis) and bone erosion. The optimal cut-off score for the diagnosis of gout by the crystal score was 2. The sensitivity, specificity, and AUC were 95.4%, 97.1%, and .965, respectively. Gout flare had higher inflammation scores than intercritical gout, while bone erosion scores were lower than intercritical gout. The active gout patients had higher ultrasound scores of tophi, bone erosion, and PD activity than the remission group (P < .001). The sensitivity, specificity and area under the receiver operating characteristic curve (AUC) for the identification with high disease activity gout by ultrasound semi-quantitative composite score were 76.2%, 84.2%, and .812, respectively. Ultrasound helps early identification of patients at risk in asymptomatic hyperuricemia. Ultrasound semi-quantitative scoring allows for more objective and accurate assessment of gout lesions, correlates with disease activity, and helps in the diagnosis and assessment of gout.


Role of 18F-Flurodeoxyglucose Positron-Emission Tomography/Computed Tomography in the Evaluation of Early Response to Neoadjuvant Chemotherapy in Patients with Locally Advanced Triple-Negative Breast Cancer.
Response evaluation in locally advanced breast cancer is done through different methods ranging from clinical examination to magnetic resonance imaging, however evaluation with positron-emission tomography/computed tomography (PET/CT) in now being incorporated for the response evaluation. The aim of the present study is to correlate response to neoadjuvant chemotherapy (NACT) with PET/CT scan. The present study is a retrospective analysis of 30 locally advanced, triple-negative breast cancer patients. PET/CT scan was done pretreatment and post three and six cycles of NACT and was correlated with pathologic complete response (pCR). Responding disease was considered when there was at least a 50% reduction in the longest diameter. The median pretreatment size of the breast lesion in CT scan was 3.9 ± 2.3 cm (2-12 cm) and maximum standardized uptake value (SUVmax) on PET/CT was 8.5 ± 5.5 (2.9-24). Among the responders, the median decrease in size of lesion was 3.2 ± 1.3 cm and median reduction in SUV of the tumor among was -8.1 ± 5.4 and was statistically significant when compared with nonresponders (P < 0.001). CT scan has 66% accuracy and PET has 82% accuracy at post three cycles NACT in predicting the pathological response. PET/CT had higher sensitivity and specificity when compared with CT findings alone in response evaluation. PET/CT scan can be considered as a sensitive tool for predicting pCRs and further larger trials are required to establish these findings.


Protein Profile Analysis of Two Australian Snake Venoms by One- Dimensional Gel Electrophoresis and MS/MS Experiments.
The Pseudechis colletti and Pseudechis butleri venoms were analyzed by 1-D gel electrophoresis, followed by mass spectrometric analysis of tryptic peptides obtained from the protein bands. Both venoms contain highly potent pharmacologically active components, which were assigned to the following protein families: basic and acidic phospholipases A2 (PLA2s), L-amino acid oxidases (LAAOs), P-III metalloproteinases (P-III SVMPs), 5'- nucleotidases (5'-NTDs), cysteine-rich secretory proteins (CRISPs), venom nerve growth factors (VNGFs) and post-synaptic neurotoxins. Considerable predominance of PLA2s over other toxins is a characteristic feature of both venoms. The major differences in the venom compositions are the higher concentration of SVMPs and CRISPs in the P. butleri venom, as well as the presence of post-synaptic neurotoxins. Furthermore, the analysis revealed a high concentration of proteins with myotoxic, coagulopathic and apoptotic activities. PLA2s are responsible for the myotoxic and anticoagulant effects observed in patients after envenomation (4). The other protein families, encountered in the two venoms, probably contribute to the major symptoms described for these venoms. These results explain the observed clinical effects of the black snake envenomation. The analyzed venoms contain group P-III metalloproteinases of medical importance with the potency to be used for diagnostic purposes of von Willebrand factor (vWF) disease, for regulation of vWF in thrombosis and haemostasis, for studying the function of the complement system in host defense and in the pathogenesis of diseases. Comparison of venomic data showed similarities in the major venom components of snakes from the genus Pseudechis, resulting in common clinical effects of envenomation, and demonstrating close relationships between venom toxins of Elapidae snakes.


[SPECT radiopharmaceuticals -- novelties and new possibilities].
Actual state of affairs and future perspectives of SPECT radiopharmaceuticals regarding local and international data were summarized. Beyond conventional gamma-emitting radioisotopes, localization studies with beta emitting therapeutic radiopharmaceuticals hold increasing importance. Extension of hybrid (SPECT/CT) equipments has modified conventional scintigraphic and SPECT methods as well but more important changes come into the world through novel ligands for specific diagnoses and therapy.


Enzymatic debridement after mobile phone explosion: a case report.
It is estimated that over 90% of people own a mobile phone. Although rare, lithium-ion battery explosions can cause varying degrees of thermal burn injury. Recently, selective enzymatic debridement has gained importance in the management of burn patients, thanks to its simplicity, minimum invasiveness and safety. In this work, we describe a case of a burn injury caused by the explosion of a lithium-ion battery and treated with selective enzymatic debridement in a paediatric patient.


Anti-Ro/SS-A and anti-La/SS-B antibodies associated with cardiac involvement in childhood systemic lupus erythematosus.
To determine the frequency and type of cardiac manifestations in children with systemic lupus erythematosus (SLE) and investigate whether cardiac involvement of SLE in children was associated with any autoantibody pattern. Retrospective analysis of the medical records of all children with SLE (31 patients) seen between January 1984 and January 1994 by the paediatric rheumatology service at Children's Hospital in New Orleans. All patients satisfied the American College of Rheumatology criteria for the diagnosis of SLE. Paediatric SLE patients with cardiac manifestations based on echocardiogram were identified. Autoantibody tests at diagnosis were identified retrospectively by chart review, and the correlation between autoantibodies and cardiac involvement was analysed using the two tailed Fisher's exact test. Thirteen (42%) of 31 SLE patients had cardiac manifestations of SLE. Seven (22%) had pericarditis without myocarditis, five (16%) had pericarditis and myocarditis, and one (3%) had myocarditis without pericarditis. Two patients (6%) with pericarditis had cardiac tamponade. Cardiac manifestations of SLE usually occurred at the time of diagnosis or within six months. Anti-Ro/SS-A antibodies were present in serum samples of nine of 11 (82%) patients with cardiac involvement and in five of 15 (33%) without cardiac involvement (p = 0.02). Anti-La/SS-B antibodies were present in serum samples of six of 10 (60%) patients with cardiac involvement and two of 15 (13%) without cardiac involvement (p = 0.03). Anti-Sm and anti-RNP antibodies showed no correlation with the presence of cardiac disease. Cardiac involvement in our paediatric SLE population was frequently found and correlated significantly with the presence of anti-Ro/SS-A and anti-La/SS-B antibodies.


The effect of sleep duration on exhaled nitric oxide levels in U.S. adults.
Poor sleep quality and duration are associated with systemic endothelial dysfunction. However, an association between poor sleep and pulmonary endothelial dysfunction has not been elucidated. We sought to determine if there is a relationship between sleep duration and fractional exhaled nitric oxide (FeNO) concentrations as a surrogate for pulmonary endothelial function. We used three National Health and Nutrition Examination Survey (NHANES) cycles (2007-2012). Linear regression models were built with and without adjustment for age, sex, race, BMI, asthma/bronchitis, CRP, smoking, folate, renal function, respiratory infections, and steroid use. To examine a non-linear relationship, we introduced a spline, with single knot at mean sleep duration (7 h). Of 13,173 participants (50.8% male, 44.2% Caucasian), 78% slept 6-8 hours (h). FeNO was significantly higher in the group sleeping 6-8 h (17.3 ± 14.9 ppb) than in the other two groups (16.0 ± 13.0 ppb, 15.9 ± 12.7 ppb for <6 and >8 h respectively; P < 0.001). In unadjusted linear regression, FeNO increased by 1.1 ppb for each hour increase in sleep up to 7 h (P < 0.001). Increased sleep duration beyond 7 h saw a 0.96 ppb decrease in FeNO (P < 0.001). After adjustment for confounders, FeNO increased by 1.09 ppb for each hour of sleep up to 7 h (P = 0.001) and decreased by 0.71 ppb for each hour after (P = 0.02). Sleeping less or more than 7 h is associated with pulmonary endothelial dysfunction as measured by FeNO. Further study is needed to evaluate mechanism(s) of this association and validity of FeNO as a marker of endothelial function.


Comparison of Sedentary Behaviors in Office Workers Using Sit-Stand Tables With and Without Semiautomated Position Changes.
We compared usage patterns of two different electronically controlled sit-stand tables during a 2-month intervention period among office workers. Office workers spend most of their working time sitting, which is likely detrimental to health. Although the introduction of sit-stand tables has been suggested as an effective intervention to decrease sitting time, limited evidence is available on usage patterns of sit-stand tables and whether patterns are influenced by table configuration. Twelve workers were provided with standard sit-stand tables (nonautomated table group) and 12 with semiautomated sit-stand tables programmed to change table position according to a preset pattern, if the user agreed to the system-generated prompt (semiautomated table group). Table position was monitored continuously for 2 months after introducing the tables, as a proxy for sit-stand behavior. On average, the table was in a "sit" position for 85% of the workday in both groups; this percentage did not change significantly during the 2-month period. Switches in table position from sit to stand were, however, more frequent in the semiautomated table group than in the nonautomated table group (0.65 vs. 0.29 hr-1; p = .001). Introducing a semiautomated sit-stand table appeared to be an attractive alternative to a standard sit-stand table, because it led to more posture variation. A semiautomated sit-stand table may effectively contribute to making postures more variable among office workers and thus aid in alleviating negative health effects of extensive sitting.


TCA-phospholipid-glycolysis targeted triple therapy effectively suppresses ATP production and tumor growth in glioblastoma.
Rationale: Glioblastoma (GBM) displays a complex metabolic reprogramming in cancer cells. Adenosine triphosphate (ATP) is one of the central mediators of cell metabolism and signaling. GBM cells generate ATP by glycolysis and the tricarboxylic acid (TCA) cycle associated with oxidative phosphorylation (OXPHOS) through the breaking-down of pyruvate or fatty acids to meet the growing energy demand of cancer cells. Therefore, it's urgent to develop novel treatments targeting energy metabolism to hinder tumor cell proliferation in GBM. Methods: Non-targeted metabolomic profiling analysis was utilized to evaluate cell metabolic reprogramming using a small molecule inhibitor (SMI) EPIC-0412 treatment. Cellular oxygen consumption rate (OCR) and the total proton efflux rate (PER), as well as ATP concentration, were tracked to study metabolic responses to specifically targeted inhibitors, including EPIC-0412, arachidonyl trifluoromethyl ketone (AACOCF3), and 2 deoxy-D-glucose (2-DG). Cancer cell proliferation was assessed by CCK-8 measurements and colony formation assay. Additionally, flow cytometry, immunoblotting (IB), and immunofluorescence (IF) analyses were performed with GBM cells to understand their tumorigenic properties under treatments. Finally, the anticancer effects of this combination therapy were evaluated in the GBM mouse model by convection-enhanced delivery (CED). Results: We found that SMI EPIC-0412 could effectively perturb the TCA cycle, which participated in the combination therapy of cytosolic phospholipase A2 (cPLA2)-inhibitor AACOCF3, and hexokinase II (HK2)-inhibitor 2-DG to disrupt the GBM energy metabolism for targeted metabolic treatments. ATP production was significantly declined in glioma cells when treated with monotherapy (EPIC-0412 or AACOCF3), dual therapy (EPIC-0412 + AACOCF3), or triple therapy (EPIC-0412 + AACOCF3 +2-DG) regimen. Our experiments revealed that these therapies hindered glioma cell proliferation and growth, leading to the reduction in ATP production and G0/G1 cell cycle arrest. We demonstrated that the combination therapy effectively extended the survival of cerebral tumor-bearing mice. Conclusion: Our findings indicate that the TCA-phospholipid-glycolysis metabolism axis can be blocked by specific inhibitors that significantly disrupt the tumor energy metabolism and suppress tumor proliferation in vitro and in vivo, suggesting that targeting ATP synthesis inhibition in cancer cells might be an attractive therapeutic avenue in GBM management.


Paracrine calcitonin in prostate cancer is linked to CD44 variant expression and invasion.
Calcitonin (CT) exerts an autocrine/paracrine influence on prostatic tumor invasion through coupling to transduction protein Gsalpha. Cell adhesion glycoprotein CD44 variant v7-v10 also faciliates invasion, but its modulation by the CT-Gsalpha system was unexplored. LnCaP, PC-3 and metastasis-derived PC-3M cell lines were studied, including cells modified therefrom: Gsalpha-QL, expressing mutant constitutively active Gsalpha protein, and CT+, overexpressing CT. CD44 variant expression was evaluated in vivo after orthotopic implantion into nude mice, and in vitro by real-time RT-PCR and Western blotting. Both mRNA and protein levels of the CD44 variant were minimal in PC-3M tumor implants, but elevated in Gsalpha-QL. Exogenous CT stimulated invasion into Matrigel strongly in LnCaP and CT+, and less in PC-3 and Gsalpha-QL. By Western blot analysis, untreated Gsalpha-QL and CT+ cells overexpressed CD44 variant compared with LnCaP or PC-3. By quantitative RT-PCR, exogenous CT dose-dependently increased CD44 variant mRNA to seven-fold. Pharmacologic agents that stimulated or inhibited Gsalpha activity or stimulated adenylyl cyclase produced proportionate dose-dependent effects on both CD44 variant expression and Matrigel invasion. This paracrine factor, acting though cyclic AMP, regulates the expression of CD44v7-10, which modulates the tumor phenotype.


Antropometric measurements and body composition of English and Malaysian footballers.
This comparative study was conducted to determine the anthropometric measurements and body composition of football teams in the UK and Malaysia. A total of 32 footballers from two teams were studied. The teams were the St Mary's University team (UK) and the Selangor Reserved League team. The height and body weight of the subjects were measured using SECA digital balance with height attachment. Skinfold thickness measurements were taken using Harpenden skinfold callipers at four sites (biceps, triceps, subscapular and suprailiac) and the VO2max of the subjects was estimated by participation in a multi-stage 20m shuttle-run test. The UK team were significantly heavier (p<0.05), taller (p<0.05) and had a higher body fat content (p<0.05) than their Malaysian counterpart. There was no significant difference in VO2 max between the two teams, with the Malaysians recording a slightly higher VO2 max. With regard to playing position, the defenders were found to be the most physically robust and yet had the highest VO2 max, whilst the midfielders had the lightest body weights. More data on the body composition and nutritional status of Malaysian footballers would allow adjustments to be made to dietary intakes and training levels in order to obtain maximum performance throughout the football season.


Tendon avulsion as a cause of lameness in turkeys.
Avulsion of the lateral intertarsal tendon is a common cause of hock deformity and lameness in turkeys. The clinical and pathological features of this condition are described.


Unexplained recurrent pregnancy loss and markers of arterial vascular health: An experimental case-control study.
To investigate whether women with unexplained recurrent pregnancy loss have impaired arterial vascular health compared with controls, and to evaluate whether this is modifiable by exercise. Experimental case-control pilot study. University medical centre in the Netherlands. Twelve women with unexplained recurrent pregnancy loss, 11 nulliparous women and 19 primiparous women with a history of uncomplicated pregnancies. In all three groups we measured baseline characteristics, metabolic components and arterial vascular health, and repeated this in women with unexplained recurrent pregnancy loss after 1 month of protocolled and supervised cycle training. Differences in arterial vascular health between women with unexplained recurrent pregnancy loss and controls, and the effect of exercise on arterial vascular health in women with unexplained recurrent pregnancy loss. Women with unexplained recurrent pregnancy loss have a significantly increased carotid intima media thickness in comparison with both controls (both P < 0.01), a significantly decreased brachial endothelial dependent flow-mediated vasodilation in comparison with both controls (nulliparous: P < 0.01; primiparous: P = 0.05) and a significantly decreased femoral endothelial dependent flow-mediated vasodilation in comparison with primiparous women (P = 0.01). The endothelium independent glyceryl trinitrate response was similar in all groups. With 1 month of exercise, the carotid intima media thickness decreased significantly by 7% (P = 0.05) and the femoral FMD increased significantly by 10% (P = 0.01) in women with unexplained recurrent pregnancy loss. Women with unexplained recurrent pregnancy loss have an impaired vascular health in comparison with controls. This impaired arterial vascular health can be improved by exercise.


Molecular Self-Assembly in a Poorly Screened Environment: F4TCNQ on Graphene/BN.
We report a scanning tunneling microscopy and noncontact atomic force microscopy study of close-packed 2D islands of tetrafluorotetracyanoquinodimethane (F4TCNQ) molecules at the surface of a graphene layer supported by boron nitride. While F4TCNQ molecules are known to form cohesive 3D solids, the intermolecular interactions that are attractive for F4TCNQ in 3D are repulsive in 2D. Our experimental observation of cohesive molecular behavior for F4TCNQ on graphene is thus unexpected. This self-assembly behavior can be explained by a novel solid formation mechanism that occurs when charged molecules are placed in a poorly screened environment. As negatively charged molecules coalesce, the local work function increases, causing electrons to flow into the coalescing molecular island and increase its cohesive binding energy.


Rescuing the emergency--multiple expertise and IT in the emergency field.
The rapid growth, both in technical and social approaches to the innovation phenomenon in health care suggests that profound changes are occurring. The focus of the project was to evaluate these changes through the case study of the French emergency field. The consequences of information technology implementations in the Emergency Services are presented as models to investigate the importance of technical expertise, with both the involvement of all the stakeholders from the beginning of the design and the test of the new tool in real settings. A new form of work resulted for the management of the crisis, which questioned the status of the actors and their actions, and the characteristics of the protocols of rescue. The outcome of this project was a new model built for the rescue of the emergency field which encompasses alternative forms of expertise.


[The sternotomy and thoracotomy approaches in the treatment of differentiated thyroid cancer in an advanced phase].
The authors report their experience in the treatment of well-differentiated thyroid cancer. The analysis of 5 cases treated with extensive surgery give the opportunity to discuss about the use of sternotomy or thoracotomy to eradicate mediastinal lymph nodes. The importance of preoperative assessment, especially by histological examination is stressed as well as the role of surgery in the multidisciplinary approach for the treatment of the disease.


Kangaroo position during neonatal ground ambulance transport: Parents' experiences.
Kangaroo mother care including skin-to-skin care aims to overcome the negative effects of separating parents and infants and to increase the quality of care for infants and parents in need of neonatal care. In most cases where inter-hospital transport is needed, the infant is placed in a transport incubator, which increases the risk of separation due to ambulance service restrictions that imply that parents are not allowed to accompany these transport trips. To illuminate parents' experiences of holding their infant in a kangaroo position during neonatal ground ambulance transport. A qualitative design with an inductive approach. A total of 11 open interviews with Swedish parents were conducted two to seven days after their infant had been transferred in a kangaroo position between hospitals. The transcribed interviews were analysed using qualitative content analysis. The emerged overarching category was "an uninterrupted closeness chain." The parents experienced that holding their infant during the transport extended the time they were close to their infant. Using the kangaroo position during ground ambulance transport also created a feeling of being important as a parent, as their participation during transport was appreciated. Parents' experiences were allocated into three categories: "Strengthen the feeling of being important as a parent," "promote security and create a positive environment for the baby" and "the professionals' attitude promotes security." This knowledge about parents' experiences is important in the continued work to develop interventions that focus on promoting zero separation in neonatal care. Using kangaroo position in a safety harness during ambulance transport enhances zero separation and closeness. To encourage the implementation of kangaroo position during ambulance transport, further research is needed to address parents' experiences of zero separation during transport of infants to a higher level of care.


Non-invasive assessment of negative pressure wound therapy using high frequency diagnostic ultrasound: oedema reduction and new tissue accumulation.
Tissue oedema plays an important role in the pathology of chronic and traumatic wounds. Negative pressure wound therapy (NPWT) is thought to contribute to active oedema reduction, yet few studies have showed this effect. In this study, high frequency diagnostic ultrasound at 20 MHz with an axial resolution of 60 µm was used to assess the effect of NPWT at - 80 mmHg on pressure ulcers and the surrounding tissue. Wounds were monitored in four patients over a 3-month period during which changes in oedema and wound bed thickness (granulation tissue) were measured non-invasively. The results showed a rapid reduction of periwound tissue oedema in all patients with levels falling by a mean of 43% after 4 days of therapy. A 20% increase in the thickness of the wound bed was observed after 7 days due to new granulation tissue formation. Ultrasound scans through the in situ gauze NPWT filler also revealed the existence of macrodeformation in the tissue produced by the negative pressure. These preliminary studies suggest that non-invasive assessment using high frequency diagnostic ultrasound could be a valuable tool in clinical studies of NPWT.


Experimental cholelithiasis in the rabbit induced by cholestanol feeding: effect of neomycin treatment on bile composition and gallstone formation.
Fed cholestanol is converted by the rabbit to 5alpha-bile acids which coprecipitate with the normally occurring 5beta-bile acids to form gallstones composed of calcium and sodium glycoallodeoxycholate and glycodeoxycholate. The present study shows that oral administration of large doses of neomycin prevents gallstone formation in the cholestanol-fed rabbit and reduces the elevated concentration of allodeoxycholic acid in bile, with a reciprocal increase in allocholic acid concentration. The reduction in the concentration of allodeoxycholic acid and in the incidence of gallstones is proportional to the dose of neomycin; at a concentration of allodeoxycholic acid below about 20% of total bile acids, gallstone formation does not occur. Neomycin probably exerts its action by modifying the anerobic intestinal flora which dehydroxylate allocholic acid to allodeoxycholic acid; if so, this suggests that both hepatic and bacterial transformations are essential steps in the pathogenesis of cholestanol-induced cholelithiasis. The bile of rabbits on a normal diet contains allodeoxycholic acid (5% of total bile acids). A similar decrease in allodeoxycholic acid concentration and reciprocal increase in allocholic acid concentration is observed when neomycin is administered to rabbits on a normal diet.


CBCT Evaluation of Lingual Foramen and its Anatomic Variations in Northeast Indian Population.
The identification of nearby neurovascular structures is a vital part of dental implant treatment planning. Commonly two implants are placed in the mandibular inter foraminal region to support the overdenture. Placing dental implants in this region is considered relatively safe. The purpose of this study was to employ cone beam computed tomography (CBCT) on a representative sample of Northeast Indians to find out the location and distribution of lingual foramen in the anterior mandible. A total of 104 CBCT scans were performed using the Cranex 3D CBCT system. Three Oral and Maxillofacial Radiologists agreed on a visibility grade for assessing the lingual foramen using a 3-point scale. The number and presence of foramina were noted. On cross-sectional pictures, the distance in millimeters between the crest of the alveolar ridge and the superior cortical margin of the foramen was determined. Furthermore, the analysis of the distribution of lingual foramina in terms of frequency and percentages was performed. Scan results showed that the lingual foramen was clearly visible in 65.4% of cases, somewhat visible in 12.5% of scans, and not visible at all in 22.1% of cases. Half of the people in the study had two foramina, whereas 27.9 percent had one and 22.1 percent had none. The mean distance from the crest of the alveolar ridge was 10.84 mm in males whereas 9.91 mm in females. The Northeast Indian population exhibits an unusually high prevalence of lingual foramen in the anterior portion of the mandible. This research will aid in the precise pre-operative identification of the position and number of lingual foramina prior to surgical treatments involving the midline of the mandible.


GABAB receptor expression and function in olfactory receptor neuron axon growth.
Neurotransmitters have been implicated in regulating growth cone motility and guidance in the developing nervous system. Anatomical and electrophysiological studies show the presence of functional GABAB receptors on adult olfactory receptor neuron (ORN) nerve terminals. Using antisera against the GABAB R1a/b receptor isoforms we show that developing mouse olfactory receptor neurons express GABAB receptors from embryonic day 14 through to adulthood. GABAB receptors are present on axon growth cones from both dissociated ORNs and olfactory epithelial explants. Neurons in the olfactory bulb begin to express glutamic acid decarboxylase (GAD), the synthetic enzyme for GABA, from E16 through to adulthood. When dissociated ORNs were cultured in the presence of the GABAB receptor agonists, baclofen or SKF97541, neurite outgrowth was significantly reduced. Concurrent treatment of the neurons with baclofen and the GABAB receptor antagonist CGP54626 prevented the inhibitory effects of baclofen on ORN neurite outgrowth. These results show that growing ORN axons express GABAB receptors and are sensitive to the effects of GABAB receptor activation. Thus, ORNs in vivo may detect GABA release from juxtaglomerular cells as they enter the glomerular layer and use this as a signal to limit their outgrowth and find synaptic targets in regeneration and development.


Epidemiology and genetics of Meniere's disease.
This review discusses the recent developments on the understanding of epidemiology and genetics of Meniere's disease. Meniere's disease has been shown to be associated with several comorbidities, such as migraine, anxiety, allergy and immune disorders. Recent studies have investigated the relationship between environmental factors and Meniere's disease such as air pollution, allergy, asthma, osteoporosis or atmospheric pressure, reporting specific comorbidities in East Asian population. The application of exome sequencing has enabled the identification of genes sharing rare missense variants in multiple families with Meniere's disease, including OTOG and TECTA and suggesting digenic inheritance in MYO7A. Moreover, knockdown of DTNA gene orthologue in Drosophila resulted in defective proprioception and auditory function. DTNA and FAM136A knockout mice have been studied as potential mouse models for Meniere's disease. While it has attracted emerging attention in recent years, the study of Meniere's disease genetics is still at its early stage. More geographically and ethnically based human genome studies, and the development of cellular and animal models of Meniere's disease may help shed light on the molecular mechanisms of Meniere's disease and provide the potential for gene-specific therapies.


Docetaxel-resistant triple-negative breast cancer cell-derived exosomal lncRNA LINC00667 reduces the chemosensitivity of breast cancer cells to docetaxel via targeting miR-200b-3p/Bcl-2 axis.
Development of docetaxel (TXT) resistance is a major obstacle for triple-negative breast cancer (TNBC) treatment. Additionally, chemoresistant cell-derived exosomes were able to change the chemo-response of chemosensitive recipient cells via transportation of lncRNAs. It has been shown that lncRNA LINC00667 level was significantly elevated in breast cancer tissues. Therefore, we explored whether LINC00667 level is increased in TXT-resistant TNBC cell-derived exosomes. In addition, whether exosomal LINC00667 derived from TXT-resistant TNBC cell could affect TXT sensitivity in TXT-sensitive TNBC cells was investigated as well. In the present study, exosomes were isolated from the TXT-resistant TNBC cells and from TXT-sensitive TNBC cells. Next, the level of LINC00667 in the isolated exosomes was detected with RT-qPCR. We found that LINC00667 expression was obviously elevated in TXT-resistant TNBC cell-derived exosomes compared to that in TXT-sensitive TNBC cell-derived exosomes. In addition, LINC00667 could be transferred from TXT-resistant TNBC cells to TNBC cells via exosomes. Moreover, TXT-resistant TNBC cell secreted exosomal LINC00667 markedly reduced the sensitivity of TNBC cells to TXT via upregulation of Bcl-2. Meanwhile, downregulation of LINC00667 notably enhanced the sensitivity of TXT-resistant TNBC cells to TXT through downregulation of Bcl-2. Additionally, LINC00667 was considered to be a ceRNA to sponge miR-200b-3p, thereby elevating Bcl-2 expression. Collectively, TXT-resistant TNBC cell-derived exosomal LINC00667 could decrease the chemosensitivity of TNBC cells to TXT via regulating miR-200b-3p/Bcl-2 axis. These findings suggested that LINC00667 might serve as a promising target for enhancing sensitivity of TNBC cells to TXT therapy.


IV tPA is associated with increase in rates of intracerebral hemorrhage and length of stay in patients with acute stroke treated with endovascular treatment within 4.5 hours: should we bypass IV tPA in large vessel occlusion?
Endovascular treatment (EVT) is a widely proved method to treat patients diagnosed with intracranial large vessel occlusions (LVOs); however, there has been controversy about the safety and efficacy of incorporating intravenous tissue plasminogen activator (IV tPA) as pretreatment for EVT. To compare the outcomes of all patients with LVO treated with IV tPA +EVT versus EVT alone within 4.5 hours of stroke onset. A prospectively collected endovascular database at a comprehensive stroke center between 2012 and 2019 was used to examine variables such as demographics, comorbid conditions, symptomatic/asymptomatic intracerebral hemorrhage (ICH), mortality rate, and good/poor outcomes as shown by the modified Thrombolysis in Cerebral Infarction score and modified Rankin Scale (mRS) assessment at discharge. The outcomes between patients receiving IV tPA+EVT on admission and patients who underwent EVT alone were compared. Of 588 patients with acute ischemic stroke treated with EVT, a total of 189 met the criteria for the study (average age 70.44±12.90 years, 42.9% women). Analysis of 109 patients from the group receiving EVT+IV tPA (average age 68.17±14.28 years, 41.3% women), and 80 patients from the EVT alone group was performed (average age 73.54±9.84 years, 45.0% women). Four patients (5.0%) in the EVT alone group experienced symptomatic ICH versus 15 patients (13.8%) in the IV tPA+EVT group (p=0.0478); significant increases were also noted in the length of stay for patients treated with IV tPA (8.2 days vs 11.0 days; p=0.0056). IV tPA in addition to EVT was associated with an increase in the rate of ICH in patients with LVO treated within 4.5 hours and in patients' length of stay. Further research is required to determine whether EVT treatment alone in patients with LVO treated within 4.5 hours is a more effective option.


A long history of breakdowns: A historiographical review.
The introduction to this special issue argues that network breakdowns play an important and unacknowledged role in the shaping and emergence of scientific knowledge. It focuses on transnational scientific networks from the early modern Republic of Letters to 21st-century globalized science. It attempts to unite the disparate historiography of the early modern Republic of Letters, the literature on 20th-century globalization, and the scholarship on Actor-Network Theory. We can perceive two, seemingly contradictory, changes to scientific networks over the past four hundred years. At the level of individuals, networks have become increasing fragile, as developments in communication and transportation technologies, and the emergence of regimes of standardization and instrumentation, have made it easier both to create new constellations of people and materials, and to replace and rearrange them. But at the level of institutions, collaborations have become much more extensive and long-lived, with single projects routinely outlasting even the arc of a full scientific career. In the modern world, the strength of institutions and macro-networks often relies on ideological regimes of standardization and instrumentation that can flexibly replace elements and individuals at will.


Acute otitis media in an era of increasing antimicrobial resistance and universal administration of pneumococcal conjugate vaccine.
The last decade has witnessed a shift in the epidemiology of acute otitis media (AOM) with an earlier onset of disease and a greater proportion of children with recurrent episodes before 1 year of age. In addition antimicrobial resistance to beta-lactams, macrolides and trimethoprim-sulfamethoxazole among otopathogens has increased significantly. Most recently universal administration of a seven valent pneumococcal conjugate vaccine has been endorsed by the American Academy of Pediatrics and the Advisory Committee on Immunization Practices. Earlier onset of disease and the decrease in antimicrobial susceptibility among pediatric respiratory bacterial pathogens is likely to increase the risk of failure among young children with AOM. A seven valent pneumococcal conjugate vaccine (PCV7) has demonstrated efficacy for prevention of serotype-specific pneumococcal otitis; however, increase in disease caused by nonvaccine serotypes and Haemophilus influenzae has been reported. With these events as the background, I have reviewed the strategies most likely to be successful for the treatment of AOM in 2002.


Magnetic resonance neurography of peripheral nerve following experimental crush injury, and correlation with functional deficit.
In a number of clinical studies magnetic resonance (MR) neurography has been used to examine patients with peripheral nerve damage, but little is understood about the sequence of imaging changes following nerve injuries, and how they correlate with functional deficit. The goal of this study was to further understanding of these changes and their implications. Using the rat sciatic nerve crush model, the sciatic nerve was imaged at intervals over 70 days in 12 rats. Sham-operated contralateral nerves served as controls. A 4.7-tesla MR imager with a custom-made surface coil was used. The T2 maps were calculated from images obtained at four echo times and from regions of interest designated on the nerve at three sites. Walking-track analysis was performed at the same intervals as imaging. Magnetic resonance neurography revealed a mean T2 of normal sciatic nerve of 36 msec (standard deviation [SD] 1.2 msec). Crushed nerves demonstrated a sequence of changes in signal intensity that were maximal at 14 days, with a mean T2 of 64 msec (SD 5.2 msec), then falling to a T2 of 53 msec (SD 3.7 msec). Sham-operated nerves had a short and nonsustained rise in signal at 7 days. Walking-track analysis revealed maximum deficit immediately postinjury, with an improvement in function approaching that of control nerves at 30 days. In this study the authors demonstrate that quantitative assessment of nerve signals with MR neurography allows the sequence of events following nerve crush injury to be followed in vivo, and that a return toward a normal signal correlates with functional improvement. Assessment of peripheral nerve injury in patients by using MR neurography has the potential to confirm acute nerve injury as well as to monitor the recovery process.


Identification of functional epitopes of Pseudomonas aeruginosa exotoxin A using synthetic peptides and subclone products.
The structure-function relationship of P. aeruginosa exotoxin A (ETA) was examined using synthetic peptides and genetically engineered ETA deletion mutants. Antibodies directed against synthetic peptides have allowed the identification of three ETA epitopes, two within domain I and one within the last 33 amino acids of domain III. In addition two distinct neutralizing determinants have been identified by antibodies directed against subclone products. One was associated with the amino-terminal half of ETA, the proposed receptor binding region. The second was associated with the carboxy-terminal half of ETA, a region previously not associated with receptor-binding. The amino-terminal subclone also offers potential as an ETA vaccine, since it produces a stable, non-enzymatically active product, effective in inducing ETA neutralizing antibodies. Data derived from these studies were used in a re-evaluation of structure-function relationships between ETA and diphtheria toxin.