The relationships of suicidal ideation with symptoms, neurocognitive function, and psychological factors in patients with first-episode psychosis.
Individuals with first-episode psychosis (FEP) have markedly elevated risk for suicide. Previous research on suicidality in early psychosis mainly focused on attempted and completed suicide. Data regarding risk factors for suicidal ideation, which is a common antecedent and predictor of suicide attempt, were limited. This study aimed to examine the prevalence of suicidal ideation and its relationships with clinical, neurocognitive and psychological factors in FEP patients. Eighty-nine Chinese patients aged 15 to 25years presenting with FEP to specialized early intervention service were recruited. A comprehensive set of assessments examining pre-treatment illness characteristics, symptom severity, neurocognitive function, and psychological factors were administered. Current suicidal ideation and history of suicide attempt were systematically evaluated. Approximately 42% of patients expressed suicidal ideation after service entry. Univariate regression analyses found that suicidal ideation was significantly associated with past suicide attempt, depressive symptoms, emotion expressivity, hopelessness, future expectation, attentional impulsiveness, internal and external locus of control, and the likelihood of endorsing fear of social approval and survival and coping beliefs as reasons for living. Final multivariate model showed that previous suicide attempt, depression, less severe diminished expression, greater degree of hopelessness and lower level of internal locus of control independently predicted suicidal ideation. Suicidal ideation was prevalent in FEP patients. Our findings implied that close monitoring and prompt intervention of those potentially modifiable risk factors for suicidal ideation including depression, hopelessness and perceived inadequate personal control may reduce suicide risk in the early course of psychotic illness.


[Morphological characteristics of the rotaviruses and the structure of their genome].
The data on human and animal rotavirus reproduction in monkey kidney cell culture, their morphology, and genome structure are presented. Both viruses, simian rotavirus SA 11 and human rotavirus K1, did not differ morphologically, in both cases two-capsid and one-capsid particles were found. The genome structure was determined by electrophoresis in 6% PAG. The electrophoretic mobility of genome fragments of both viruses was similar.


Occipital artery bypass importance in unsuitable superficial temporal artery: Two case reports.
Superficial temporal artery-middle cerebral artery (STA-MCA) bypass helps treat cerebral ischemia. However, the STA is not available for bypass in some conditions. Therefore, with some technical tips, the authors introduced a bypass technique using the occipital artery (OA). Two female patients complained of hemiparesis. Brain magnetic resonance imaging (MRI) indicated contralateral infarction from the MCA steno-occlusion. On Diamox single photon emission computed tomography or perfusion MRI, the contralateral front parietotemporal reserve was diminished. On transfemoral cerebral angiography, the STA was thin with a weak flow; however, the OA was prominent. Direct OA-MCA end-to-side extracranial-intracranial bypass surgery was implemented instead of STA because the caliber was too narrow. The postoperative course was uneventful in both cases, with well-maintained bypass patency and neurological stability during follow-up. OA might be an acceptable alternative for MCA cerebral ischemic cases with an unsuitable STA.


Comparing early life nutritional sources and human milk feeding practices: personalized and dynamic nutrition supports infant gut microbiome development and immune system maturation.
Exclusive breastfeeding is recommended for the first six months of life, but many infants receive pumped milk, formula, donor human milk, or other nutritional sources during this critical period. Substantive evidence shows early nutrition influences development of the microbiome and immune system, affecting lifelong health. However, the underlying mechanisms are unclear and the nuances of human milk feeding are rarely considered. This review synthesizes evidence from human studies and model systems to discuss the impact of different nutritional sources on co-development of the gut microbiome, antigen tolerance, and immunity. We highlight two key mechanisms: epigenetics and the so-called "weaning reaction". Collectively, this evidence highlights i) the fundamental role of parents' own milk, fed directly at the breast, as a dynamic and personalized nutrition source that drives developmental programming, and ii) the deficiencies of alternative nutritional sources and priority research areas for improving these alternatives when direct breastfeeding is not possible.


Prone position ventilation and femoro-femoral veno-venous extracorporeal membrane oxygenation for COVID-19 treatment.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has resulted in significant morbidity and mortality worldwide. Approximately 5% of COVID-19 patients who suffer from pneumonia develop critical respiratory failure. Here, we report the case of a healthy 52-year-old man who had respiratory failure owing to SARS-CoV-2 infection and was treated using femoro-femoral veno-venous extracorporeal membrane oxygenation (VV-ECMO) and prone position ventilation (PPV). After this treatment, his blood oxygen levels, chest high-resolution computed tomography findings, and clinical parameters significantly improved. He was decannulated from VV-ECMO on day 6 and finally extubated on day 11. To our knowledge, this is the first reported case of SARS-CoV-2-associated acute respiratory distress syndrome that was successfully treated with a combination of femoro-femoral VV-ECMO and PPV.


Human exposure to polybrominated diphenyl ethers through the diet.
Polybrominated diphenyl ethers (PBDEs), a class of brominated flame retardants, are used in a variety of consumer products being produced in notable quantities. PBDEs have been detected in environmental samples. In recent years, a marked increase in the levels of PBDEs in human biological tissues and fluids, especially breast milk, has been observed in some countries. As for other persistent organic pollutants (POPs), dietary intake is very probably the main route of exposure to PBDEs for the general population. This paper reviews the state of the science regarding human exposure to PBDEs through the diet. Because of the scarce information about it, it is concluded that studies focused on determining PBDE exposure for the population of a number of countries are clearly required. The correlation of PBDE body burdens and dietary intake of PBDEs are also necessary.


Dynamic mode decomposition of dynamic MRI for assessment of pulmonary ventilation and perfusion.
To introduce dynamic mode decomposition (DMD) as a robust alternative for the assessment of pulmonary functional information from dynamic non-contrast-enhanced acquisitions. Pulmonary fractional ventilation and normalized perfusion maps were obtained using DMD from simulated phantoms as well as in vivo dynamic acquisitions of healthy volunteers at 1.5T. The performance of DMD was compared with conventional Fourier decomposition (FD) and matrix pencil (MP) methods in estimating functional map values. The proposed method was evaluated based on estimated signal amplitude in functional maps across varying number of measurements. Quantitative assessments performed on phantoms and in vivo measurements indicate that DMD is capable of successfully obtaining pulmonary functional maps. Specifically, compared to FD and MP methods, DMD is able to reduce variations in estimated amplitudes across different number of measurements. This improvement is evident in the fractional ventilation and normalized perfusion maps obtain from phantom simulations with frequency variations and noise, as well as in the maps obtained from in vivo measurements. A robust method for accurately estimating pulmonary ventilation and perfusion related signal changes in dynamic acquisitions is presented. The proposed method uses DMD to obtain functional maps reliably, while reducing amplitude variations caused by differences in number of measurements.


Epidermal growth factor receptor-mediated selective cytotoxicity of antitumor agents toward human xenografts and murine syngeneic solid tumors.
Severe toxic side effects of antiproliferative agents limit their clinical usefulness as antitumor drugs. Recently we observed that the antitumor efficacy of various antitumor agents (5-fluorouracil, tegafur, adriamycin, mitomycin C, cyclophosphamide, and cisplatin) against experimental solid tumors was enhanced by prior or simultaneous administration of human epidermal growth factor (EGF). However, coadministration of EGF did not enhance the toxicity of antitumor agents as measured by LD50 and body weight loss. The above selective potentiation of efficacy of the antitumor agents by human EGF can be characterized as follows. In a dose-dependent manner, human EGF enhanced the efficacy of an antitumor agent (5-FU) treatment against human epidermoid carcinoma A431 transplanted sc in athymic nude mice [ED50 = 2.9 (0.2-49.7, 95% confidence interval) microgram/kg, sc]. Various degrees of enhancement were also observed against other experimental tumors transplanted sc. The degrees of enhancement were directly proportional to the numbers of human EGF binding sites present on tumor cell plasma membrane (threshold of binding site density = 1.5 X 10(3) sites/cell) using 5-FU or cisplatin as an antitumor agent, thus suggesting that the binding of EGF to the receptors on tumor cells is an essential process in enhancing the susceptibility of tumor cells to antitumor agents. Normal cells including intestinal epithelial and bone marrow cells are endowed with fewer EGF binding sites (less than 10(3) sites/cell). This may explain partially the absence of EGF-enhanced cytotoxicity by antitumor agents toward normal cells.


The influence of orchiopexy on serum inhibin B level: relationship with histology.
Since inhibin B is the endocrine marker of spermatogenesis, basal inhibin B levels may reflect germ cell status in children. The aims of this study were to determine the changes in endocrine parameters after orchiopexy in patients with cryptorchidism and to compare these findings with testicular biopsy parameters. A total of 27 boys with undescended testis were included in this study. Inguinal orchiopexy was performed in all patients and 15 underwent testicular biopsy at orchiopexy. Spermatogonia per tubular transverse section and fertility index values were determined. Before and 6 months after orchiopexy serum basal inhibin B and other serum hormone levels were measured in all patients. Mean serum basal inhibin B levels significantly increased 6 months after successful orchiopexy (p = 0.001). However, inhibin B level did not increase in patients who had a low testicular biopsy score. Other reproductive hormone levels did not change after orchiopexy. Basal inhibin B level could be used as a followup parameter after orchiopexy. If basal inhibin B level does not increase in the postoperative period, the amount of germ cells in the testis may be too low or the orchiopexy might not have been implemented appropriately.


Effect of the accumulation of risk factors on the risk of oral squamous cell carcinoma
the causative factors of oral squamous cell carcinoma are not necessary and not sufficient causes, even the most accepted ones, such as tobacco and alcohol. Little is known about the cumulative effect of all risk factors for oral cancer. The objective of this work was to analyze whether the sum of oral cancer risk factors is associated with an increase in its risk. a case-control study was carried out to determine the risk factors for oral cancer in the population under study, and then correlate the number of risk factors in each individual with the risk of oral cancer. the accumulation of oral cancer risk factors, analyzed using different strategies, was always associated with a significant increase in the risk of oral cancer. Having 3 or more risk factors was associated with an increased risk of oral cancer (OR 110, p <0.0001) the main risk factor for oral cancer is the accumulation of its risk factors. The accumulation of risk factors could be considered a necessary cause for the development of oral cancer.


A scanning electron microscope study of the interstitial tissue of the canine testis.
Scanning electron microscopy (SEM) is a potent tool that is especially valuable in interpreting the three-dimensional relationships of cells within tissues. This type of information is obtainable from thin sections in transmission electron microscopy (TEM) only by reconstructions of serial sections. The arrangement of the interstitial cells of the testis in relation to the capillaries and lymphatic channels, in particular, is easier to visualize in SEM than in TEM. Cytoplasmic constituents, as well as cell surface modifications, are demonstrable by this technique. The presence of droplets, presumably lipid droplets, both within and on the Leydig cells and the lymphatic endothelial cells, is quite evident. Other cytoplasmic structures are also apparent. For example, the possible functional significance of "openings" that are seen by SEM on the septa that surround lipid droplets is discussed relative to the appearance of the same area as seen in thin sections or in freeze-fracture replicas. SEM should become a very useful method for studying cytological and morphological alterations that occur in testicular tissue that is subjected to physical or chemical manipulation.


The endothelium-derived contracting factor uridine adenosine tetraphosphate induces P2Y(2)-mediated pro-inflammatory signaling by monocyte chemoattractant protein-1 formation.
It is very well established that purinergic signaling plays a relevant role in vascular physiology and pathophysiology. Recently, a new purinoceptor agonist uridine adenosine tetraphosphate (Up(4)A) has been identified as a highly potent endothelial-derived contracting factor (EDCF). The purpose of the study was to investigate Up(4)A's influence on pro-inflammatory mechanisms. An early component of the inflammatory response in atherogenesis is the oxidative stress-induced formation of monocyte chemoattractant protein-1 (MCP-1). Here, we investigated the influence of Up(4)A on MCP-1 formation and characterized the underlying signaling transduction mechanisms in rat vascular smooth muscle cells (VSMCs). Up(4)A induced MCP-1 expression and secretion in VSMCs via the activation of P2Y(2) in a concentration-dependent manner. MCP-1 formation depends on generation of reactive oxygen species (ROS). To determine whether the predominant source of ROS in the vasculature, the NAD(P)H oxidase (Nox), is involved, we used different approaches. The ROS scavenger, tiron, the Nox inhibitor, apocynin and diphenyl-iodonium, as well as Nox1 knockdown, diminished the Up(4)A-induced MCP-1 formation. Rac1 activation and p47(phox) translocation from cytosol to the plasma membrane-both required for assembling and activation of Nox, were stimulated by Up(4)A. ERK1/2 and p38 activation is essential for the intracellular signal transduction. In summary, Up(4)A induced Nox1-dependent ROS generation, which further stimulated MCP-1 formation via MAPK phosphorylation in VSMCs. This process requires the activation of the G-protein coupled receptor P2Y(2). Therefore, Up(4)A is not only a potent EDCF but also a potent inductor of pro-inflammatory response in the vascular wall.


Rapid changes in transcriptomic profile and mitochondrial function in human soleus muscle after 3-day dry immersion.
We aimed to explore the effect of the 3-day dry immersion, a model of physical unloading, on mitochondrial function, transcriptomic and proteomic profiles in a slow-twitch soleus muscle of six healthy females. We registered that a marked reduction (25-34%) in the ADP-stimulated respiration in permeabilized muscle fibers was not accompanied by a decrease in the content of mitochondrial enzymes (mass spectrometry-based quantitative proteomics), hence, it is related to the disruption in regulation of respiration. We detected a widespread change in the transcriptomic profile (RNA-seq) upon dry immersion. Downregulated mRNAs were strongly associated with mitochondrial function, as well as with lipid metabolism, glycolysis, insulin signaling, and various transporters. Despite the substantial transcriptomic response, we found no effect on the content of highly abundant proteins (sarcomeric, mitochondrial, chaperon, and extracellular matrix-related, etc.) that may be explained by long half-life of these proteins. We suggest that during short-term disuse the content of some regulatory (and usually low abundant) proteins such as cytokines, receptors, transporters, and transcription regulators is largely determined by their mRNA concentration. These mRNAs revealed in our work may serve as putative targets for future studies aimed at developing approaches for the prevention of muscle deconditioning induced by disuse.NEW & NOTEWORTHY Three-day dry immersion (a model of physical unloading) substantially changes the transcriptomic profile in the human soleus muscle, a muscle with predominantly slow-twitch fibers and strong postural function; despite this, we found no effect on the muscle proteome (highly abundant proteins). Dry immersion markedly reduces ADP-stimulated respiration; this decline is not accompanied by a decrease in the content of mitochondrial proteins/respiratory enzymes, indicating the disruption in regulation of cellular respiration.


Microtubule disruption changes endothelial cell mechanics and adhesion.
The interest in studying the mechanical and adhesive properties of cells has increased in recent years. The cytoskeleton is known to play a key role in cell mechanics. However, the role of the microtubules in shaping cell mechanics is not yet well understood. We have employed Atomic Force Microscopy (AFM) together with confocal fluorescence microscopy to determine the role of microtubules in cytomechanics of Human Umbilical Vein Endothelial Cells (HUVECs). Additionally, the time variation of the adhesion between tip and cell surface was studied. The disruption of microtubules by exposing the cells to two colchicine concentrations was monitored as a function of time. Already, after 30 min of incubation the cells stiffened, their relaxation times increased (lower fluidity) and the adhesion between tip and cell decreased. This was accompanied by cytoskeletal rearrangements, a reduction in cell area and changes in cell shape. Over the whole experimental time, different behavior for the two used concentrations was found while for the control the values remained stable. This study underlines the role of microtubules in shaping endothelial cell mechanics.


A study of the histochemical changes in mucus from patients with benign and malignant pathological conditions of the colon and rectum.
This study has shown the presence of an abnormal mucus pattern in premalignant and malignant conditions of the colon and rectum. This abnormal mucus pattern extended as a field change around colorectal tumors into the adjacent apparently normal mucosa. Presence of this premalignant field in patients undergoing apparently curative surgery was associated with an increased risk of local tumor recurrence or metachronous primary tumors.


Chronic nausea and morphine-6-glucuronide.
Morphine-6-glucuronide is an active metabolite of morphine that has analgesic properties and is measurable in the plasma and cerebrospinal fluid of patients treated with this opioid. Decreased clearance of the compound has been observed in patients with renal insufficiency, and this has been associated with an increase in the ratio of morphine-6-glucuronide to morphine. Clinical effects from accumulation of morphine-6-glucuronide have not been described with the exception of case reports in which patients with renal failure were noted to develop opioid toxicity with high plasma levels of the metabolite and low levels of the parent drug. We describe a patient who experienced chronic nausea and an episode of confusion while treated with a small, stable dose of oral morphine in the setting of mild renal insufficiency. Relatively high levels of morphine-6-glucuronide were measured and all symptoms resolved promptly as the concentration of this metabolite declined. This case provides suggestive evidence that morphine-6-glucuronide can produce clinically significant effects in patients with mild renal insufficiency.


Predictors of serostatus disclosure to partners among young people living with HIV in the pre- and post-HAART eras.
Predictors of serostatus disclosure were identified among youth living with HIV pre- and post-introduction of highly active antiretroviral therapy (HAART). Two cohorts of HIV-positive youth, aged 13-24, in 1994-1996 (n = 351) and 1999-2000 (n = 253) in Los Angeles, New York, San Francisco, and Miami were sampled through medical providers and a variety of social service agencies. Data were collected on demographic, social, medical, and behavioral topics. Men who had sex with men were more likely to disclose serostatus to their partners. Moreover, a positive association with length of time since diagnosis and the likelihood of disclosure exists; across time, youth were less likely to disclose serostatus to casual partners or HIV-negative partners. Post-HAART, number of sex acts with a partner was associated with increased likelihood of disclosure. Interventions for HIV-positive youth must improve disclosure to casual and serodiscordant sexual partners.


Myocardial performance after contusion with concurrent hypovolemia.
Myocardial contusion may present as a benign nonclinical event or a life-threatening emergency. Although cardiac output is recognized to be decreased with major contusion, the contribution of hypovolemic shock to myocardial dysfunction is unclear. This study was designed to evaluate the relationship between myocardial contusion and hypovolemic shock. After Sprague-Dawley rats were anesthetized, contusions were administered at either 80 psi or 120 psi. Half of each group then underwent hypovolemic shock. After 24 hours of recovery, cardiac hemodynamics were studied in each subgroup using the Neely-Langendorff apparatus. Isoenzymes and histology were evaluated as well. The data showed that rats undergoing hypovolemic shock in each subgroup had a significant decrease in cardiac output when compared with their controls. This decrease was more pronounced in the 120-psi group. Cardiac isoenzyme levels were elevated in all groups. Microscopic evaluations showed contusion in the controls and necrosis in the shock groups. Patients whose injuries are compatible with myocardial contusion and hypovolemic shock should be resuscitated quickly and evaluated for myocardial dysfunction secondary to infarction.


The evolution of parental care diversity in amphibians.
Parental care is extremely diverse across species, ranging from simple behaviours to complex adaptations, varying in duration and in which sex cares. Surprisingly, we know little about how such diversity has evolved. Here, using phylogenetic comparative methods and data for over 1300 amphibian species, we show that egg attendance, arguably one of the simplest care behaviours, is gained and lost faster than any other care form, while complex adaptations, like brooding and viviparity, are lost at very low rates, if at all. Prolonged care from the egg to later developmental stages evolves from temporally limited care, but it is as easily lost as it is gained. Finally, biparental care is evolutionarily unstable regardless of whether the parents perform complementary or similar care duties. By considering the full spectrum of parental care adaptations, our study reveals a more complex and nuanced picture of how care evolves, is maintained, or is lost.


The rules of variation: amino acid exchange according to the rotating circular genetic code.
General guidelines for the molecular basis of functional variation are presented while focused on the rotating circular genetic code and allowable exchanges that make it resistant to genetic diseases under normal conditions. The rules of variation, bioinformatics aids for preventative medicine, are: (1) same position in the four quadrants for hydrophobic codons, (2) same or contiguous position in two quadrants for synonymous or related codons, and (3) same quadrant for equivalent codons. To preserve protein function, amino acid exchange according to the first rule takes into account the positional homology of essential hydrophobic amino acids with every codon with a central uracil in the four quadrants, the second rule includes codons for identical, acidic, or their amidic amino acids present in two quadrants, and the third rule, the smaller, aromatic, stop codons, and basic amino acids, each in proximity within a 90 degree angle. I also define codifying genes and palindromati, CTCGTGCCGAATTCGGCACGAG.


Direct causality between single-Purkinje cell activities and motor learning revealed by a cerebellum-machine interface utilizing VOR adaptation paradigm.
A cerebellum-machine interface (CMI) was developed to test direct causality between single-unit cerebellar Purkinje cell activities and motor learning. The CMI converts Purkinje cell simple spike firing rates into a pulse width modulation signal that drives a single-joint robot arm. The CMI has no adaptive capability, thus any changes observed in the robot arm motion can be attributed directly to changes in the Purkinje cell's firing activities. We employed a vestibuloocular reflex (VOR) adaptation paradigm in goldfish as an example of motor learning where desired motion and control error signal of the robot arm were given to the fish as its head rotation and retinal slip, respectively. It is demonstrated that the control error of the robot arm decreased gradually, but not monotonically and in many cases only in one direction. This is the first direct evidence that a single Purkinje cell is capable of adaptive motor control. The results also suggest that a single Purkinje cell can be responsible for directional selective VOR motor learning previously reported in goldfish by Yoshikawa et al. (Conf Proc IEEE Eng Med Biol Soc 1:478-481, 2004) and monkeys by Hirata et al. (J Neurophysiol 85(5):2267-2288, 2002).


3D time-lapse microscopy paired with endpoint lineage analysis in mouse blastocysts.
Determining how signaling dynamics relate to gene expression and cell fate is essential to understanding multicellular development. We present a unified live imaging and lineage analysis method that allows integrated analysis of both techniques in the same mouse embryos. This protocol describes the embryo isolation, confocal imaging, immunofluorescence, and in silico alignment required to connect time-lapse and endpoint measurements. By utilizing different biosensors and fixed readouts, this method allows interrogation of signaling dynamics that specify cell fates in developing embryos. For complete details on the use and execution of this protocol, please refer to Pokrass et al. (2020).


[Evolution of bacterial resistance to antibiotics in México, 1973-2013].
Bacterial resistance to antibiotics is a worldwide public health concern. Research priorities for the study and control of this emerging problem include country-wide surveillance. To review and comment on the contributions by Mexican investigators towards a greater understanding of the mechanisms of bacterial antibiotic resistance. A comprehensive search of the medical literature on Medline/PubMed between 1973 and July 2013 was performed. The contributions of Mexican investigators have included descriptions of resistance in enteric pathogens, such as Salmonella Typhi, publications on the production of extended spectrum beta-lactamases, metallo-beta-lactamases, and carbapenemases, resistance mechanisms of Pseudomonas aeruginosa , and the evolution of resistance in Gram-positive pathogens, including Streptococcus pneumoniae , Staphylococcus aureus , and Enterococcus spp. The Mexican literature on mechanisms of bacterial resistance is relevant for the development of plans to control the antibiotic resistance crisis.


Morphological plasticity in Chlamydomonas reinhardtii and acclimation to micropollutant stress.
Phytoplankton are characterized by a great phenotypic plasticity and amazing morphological variability, both playing a primary role in the acclimation to changing environments. However, there is a knowledge gap concerning the role of algal morphological plasticity in stress responses and acclimation to micropollutants. The present study aims at examining palmelloid colony formation of the green alga Chlamydomonas reinhardtii upon micropollutants exposure. Cells were exposed to four micropollutants (MPs, copper, cadmium, PFOS and paraquat) with different modes of action for a duration of 72 h. Effects of MPs on palmelloid formation, growth and physiological traits (chlorophyll fluorescence, membrane integrity and oxidative stress) were monitored by flow cytometry and fluorescence microscopy. Palmelloid formation was observed upon treatment with the four micropollutants. Number of palmelloid colonies and their size were dependent on MP concentration and exposure duration. Cells reverted to their unicellular lifestyle when colonies were harvested and inoculated in fresh medium indicating that palmelloid formation is a plastic response to micropollutants. No physiological effects of these compounds were observed in cells forming palmelloids. Palmelloid colonies accumulated lower Cd concentration than unicellular C. reinhardtii suggesting that colony formation protects the cells from MPs stress. The results show that colony formation in Chlamydomonas reinhardtii is a stress response strategy activated to face sub-lethal micropollutant concentrations.


Etoposide and carbo-or cisplatin combination therapy in refractory or relapsed Ewing sarcoma: a large retrospective study.
Patients with Ewing sarcoma (EWS) who develop refractory or relapsed disease have limited treatment options. In some sarcoma centres in Europe the combination of etoposide with carbo- or cisplatin is being used for these patients, however, there are no published data available yet. Here we investigated the outcome of the combination treatment for patients with advanced Ewing sarcoma in progression after standard treatment. All patients diagnosed with EWS between 1980 and 2012 in one of six major sarcoma centres in Europe and treated with either carboplatin and etoposide or cisplatin and etoposide were included and data were retrospectively collected for analysis. A total of 107 patients enrolled in this study of which 61 received the combination of etoposide and carboplatin and 46 received etoposide and cisplatin. The median overall survival (OS) was 23 months for both patient groups and the 5-year OS was 24.5% for the patients who received carboplatin and etoposide and 20% for those who received cisplatin and etoposide. The progression free survival was better in patients treated with the combination of carboplatin and etoposide (14.5 vs. 6.3 months P = 0.023). This is a retrospective study on the combination treatment of etoposide and carbo- or cisplatin in refractory Ewing sarcoma. The results justify exploring the combination in a prospective study with relapsed patients.


Radiation-induced extracellular vesicle (EV) release of miR-603 promotes IGF1-mediated stem cell state in glioblastomas.
Recurrence after radiation therapy is nearly universal for glioblastomas, the most common form of adult brain cancer. The study aims to define clinically pertinent mechanisms underlying this recurrence. microRNA (miRNA) profiling was performed using matched pre- and post-radiation treatment glioblastoma specimens from the same patients. All specimens harbored unmethylated O6-methylguanine-DNA methyltransferase promoters (umMGMT) and wild-type isocitrate dehydrogenase (wtIDH). The most altered miRNA, miR-603, was characterized. While nearly all miRNAs remained unchanged after treatment, decreased levels of few, select miRNAs in the post-treatment specimens were observed, the most notable of which involved miR-603. Unbiased profiling of miR-603 targets revealed insulin-like growth factor 1 (IGF1) and IGF1 receptor (IGF1R). Ionizing radiation (IR) induced cellular export of miR-603 through extracellular vesicle (EV) release, thereby de-repressing IGF1 and IGF1R. This de-repression, in turn, promoted cancer stem-cell (CSC) state and acquired radiation resistance in glioblastomas. Export of miR-603 additionally de-repressed MGMT, a DNA repair protein responsible for detoxifying DNA alkylating agents, to promote cross-resistance to these agents. Ectopic miR-603 expression overwhelmed cellular capacity for miR-603 export and synergized with the tumoricidal effects of IR and DNA alkylating agents. Profiling of matched pre- and post-treatment glioblastoma specimens revealed altered homeostasis of select miRNAs in response to radiation. Radiation-induced EV export of miR-603 simultaneously promoted the CSC state and up-regulated DNA repair to promote acquired resistance. These effects were abolished by exogenous miR-603 expression, suggesting potential for clinical translation. NIH 1R01NS097649-01, 9R44GM128223-02, 1R01CA240953-01, the Doris Duke Charitable Foundation Clinical Scientist Development Award, The Sontag Foundation Distinguished Scientist Award, the Kimmel Scholar Award, and BWF 1006774.01 (C.C.C).


Peripheral subcutaneous field stimulation for the treatment of spinal cord injury at-level pain: case report, literature review, and 5-year follow-up.
Spinal cord injury (SCI) frequently engenders chronic pain which may be classified as occurring above, at, or below the level of injury. Since patients with SCI may have a complex combination of nociceptive and neuropathic pain, pharmacological interventions often fail. Peripheral subcutaneous field stimulation (PSFS) is a novel neuromodulation surgery for pain in which subcutaneous electrodes designed for spinal cord stimulation are placed subcutaneously in a region of pain. We report the case of a 26-year-old man who was an unrestrained driver in a motor vehicle accident and suffered a complete ASIA A spinal cord injury with paraplegia due to a T4 three-column burst fracture. He underwent successful surgical fixation of the fracture (7/27/12) and developed severe at-level SCI-associated pain which failed all conservative measures. After a successful trial, two octrode leads (Abbott Medical, Plano, TX, USA) were placed for PSFS under general anesthesia and were connected to a right flank rechargeable pulse generator (11/6/13). At 60 months postoperative, the patient continues to use the peripheral field stimulation system on a daily basis and reports near complete relief of his at-level spinal cord injury pain. He noted instantaneous relief of his pain once ideal stimulation programming was achieved and has tolerated complete cessation of all narcotic use. His current programming settings are: Frequency of 50 Hz (Hz), Pulse Width of 350 μs (μsec), Amplitude of 0.00 miliamps (mA), Comf of 7.70 mA, and Perc of 4.50 mA. Chronic pain is a challenging and expensive sequela to manage in SCI patients and newer therapies are needed. Our case suggests that SCI at-level pain may respond durably to PSFS and provides the longest published follow-up on a case of PSFS. Peripheral subcutaneous field stimulation remains an investigational treatment for chronic pain syndrome and larger, long-term follow up studies are needed for the FDA and payers to approve this modality.


Developmentally regulated cell-cell adhesion in Dictyostelium purpureum is mediated by a glycoprotein synthesized in nonadhesive cells.
Upon starvation the cellular slime mold, Dictyostelium purpureum, develops a form of cell-cell adhesion aiding in the formation of large multicellular aggregates, which are capable of further differentiation. The molecule that mediates this adhesion is a glycoprotein of Mr approximately 40,000. The protein shares a common carbohydrate epitope with another well-characterized cell adhesion molecule from Dictyostelium discoideum, contact sites A, but the polypeptides to which it is attached differ for each species. Although mediating a developmental form of adhesiveness, the protein is synthesized in vegetative cells at a time when they do not adhere. Most of the vegetative protein is associated with cell membranes and appears to be on the surface of these cells. The protein is compared to other cell adhesion molecules from other species of cellular slime molds, and possible explanations for its inability to function in vegetative cells are discussed.


Melatonin does not inhibit hypothalamic-pituitary-adrenal activity in waking young men.
The pineal hormone melatonin is mainly secreted during night-time which, in humans, is the normal time of sleep. It has been proposed that, during this period, melatonin exerts an inhibitory influence on secretory activity of the hypothalamic-pituitary-adrenal (HPA) system, although there is little evidence for this view in humans. In blind humans, a single oral dose of melatonin at bed time suppressed nocturnal cortisol secretion. However, suppression could have been secondary to an improved sleep after melatonin in these experiments. In the present study, we examined whether melatonin exerts a similar inhibitory effect on HPA activity in waking subjects. Fourteen healthy young men were tested at bed time, but kept awake throughout the experimental epoch. Thirty minutes after oral ingestion of 5 mg melatonin, activity of the HPA-system was stimulated through a standard insulin-induced hypoglycaemia. Adrenocorticotrophin hormone and cortisol concentrations under basal conditions before insulin injection, as well as in response to insulin-induced hypoglycaemia, were almost identical for the melatonin and placebo control conditions (P > 0.5). However, melatonin increased plasma prolactin concentrations (P < 0.01) and reduced systolic blood pressure in the time interval following hypoglycaemia (P < 0.05). Based on a review of the literature and our results, we conclude that melatonin per se has no substantially suppressing effect on HPA secretory activity, although such an effect can be gated by sleep-related processes.


Heterotopic autotransplantation of the pancreas segment after pylorus-preserving total pancreatectomy: a case report of successful surgical treatment for chronic pancreatitis.
A 38-year-old man who had suffered for 5 years from persistent abdominal pain caused by alcoholic chronic pancreatitis, presented with diffuse calcification of the entire pancreas with cystic formation of the pancreatic head. After a pylorus-preserving total pancreatectomy, the pancreatic head, including the cyst, was removed extracorporeally by bench surgery, and the remaining segment of the body and tail autotransplanted heterotopically to the iliac vessels with a pancreaticojejunostomy. Total resolution of the pain was achieved postoperatively, and dietary intake has been satisfactory. Both endocrine and exocrine pancreatic functions have been well preserved, and no insulin has been needed. Three months after his operation, the patient has returned to leading a normal life.


Differential expression of ethylene biosynthetic and receptor genes in pollination-induced senescence of Dendrobium flowers.
Following successful pollination, Dendrobium orchid flowers rapidly undergo senescence. In Dendrobium cv. Khao Chaimongkol, compatible pollination resulted in faster ethylene production and more rapid development of senescence symptoms, such as drooping, epinasty, venation and yellowing, compared with non-pollinated controls or pollination with incompatible pollinia. The DenACS1 and DenACO1 genes in the perianth of florets that had been pollinated with compatible pollinia were expressed more highly than those in non-pollinated open florets. Incompatible pollinia reduced the expression of DenACS1 and DenACO1 genes in the perianth. Transcript levels of the ethylene receptor gene DenERS1 and signaling genes DenEIL1 and DenERF1 showed differential spatial regulation with greater expression in the perianth than in the column plus ovary following compatible pollination. Compatible pollinia increased ethylene production concomitant with premature senescence and the increased expression of the DenACS1 and DenACO1 genes, and suppressed the ethylene receptor gene DenERS1, whereas incompatible pollinia did not stimulate ethylene production nor induce premature senescence but induced higher expression of DenERS1 both in the perianth and in the column plus ovary. These results suggest that the increased ethylene production in open florets pollinated with compatible pollen was partially due to an increase in the expression of DenACS1 and DenACO1 genes. The compatible pollinia induced a negative regulation of DenERS1 which may play an important role in ethylene perception and in modulating ethylene signaling transduction during pollinia-induced flower senescence.


Estimation of daily risk of neonatal death, including the day of birth, in 186 countries in 2013: a vital-registration and modelling-based study.
The days immediately after birth are the most risky for human survival, yet neonatal mortality risks are generally not reported by day. Early neonatal deaths are sometimes under-reported or might be misclassified by day of death or as stillbirths. We modelled daily neonatal mortality risk and estimated the proportion of deaths on the day of birth and in week 1 for 186 countries in 2013. We reviewed data from vital registration (VR) and demographic and health surveys for information on the timing of neonatal deaths. For countries with high-quality VR we used the data as reported. For countries without high-quality VR data, we applied an exponential model to data from 206 surveys in 79 countries (n=50,396 deaths) to estimate the proportions of neonatal deaths per day and used bootstrap sampling to develop uncertainty estimates. 57 countries (n=122,757 deaths) had high-quality VR, and modelled data were used for 129 countries. The proportion of deaths on the day of birth (day 0) and within week 1 varied little by neonatal mortality rate, income, or region. 1·00 million (36.3%) of all neonatal deaths occurred on day 0 (uncertainty range 0·94 million to 1·05 million), and 2·02 million (73.2%) in the first week (uncertainty range 1·99 million to 2·05 million). Sub-Saharan Africa had the highest risk of neonatal death and, therefore, had the highest risk of death on day 0 (11·2 per 1000 livebirths); the highest number of deaths on day 0 was seen in southern Asia (n=392,300). The risk of early neonatal death is very high across a range of countries and contexts. Cost-effective and feasible interventions to improve neonatal and maternity care could save many lives. Save the Children's Saving Newborn Lives programme.


Genetic variant within CDK6 regulates immune response to palbociclib treatment.
Everyone carries a set of genetic variants that contribute to regulation of the levels of blood cells, with unknown clinical impact. One of them, rs445 within the cell-cycle checkpoint gene CDK6, reduces the levels of myeloid cell types including granulocytes. We treated CD3+ T cells and whole blood with palbociclib in 41 individuals, who were stratified by genotype for analyses. In T cells we assessed cell cycle and apoptosis, whereas in whole blood, apoptosis in activated (CD11b+), unactivated (CD11b-) granulocytes, cytotoxic (CD8 + CD4-), and helper (CD8-CD4+) T cells. We find that rs445 modulates the immune response of CD8+ T cells. It also increases the level of apoptotic CD11b + activated granulocytes after palbociclib treatment, which, in synergy with neutropenia, may affect drug related adverse events. These results suggest that the effect of palbociclib treatment may depend on underlying genetically encoded individual immune response as well as the direct response to the drug.


Inter-brain synchrony in mother-child dyads during cooperation: An fNIRS hyperscanning study.
Coordinated brain activity between individuals, or inter-brain synchrony, has been shown to increase during cooperation and correlate with cooperation success. However, few studies have examined parent-child inter-brain synchrony and whether it is associated with meaningful aspects of the parent-child relationship. Here, we measured inter-brain synchrony in the right prefrontal (PFC) and temporal cortices in mother-child dyads while they engaged in a cooperative and independent task. We tested whether inter-brain synchrony in mother-child dyads (1) increases during cooperation, (2) differs in mother-son versus mother-daughter dyads, and (3) is related to cooperation performance and the attachment relationship. Overall inter-brain synchrony in the right hemisphere, and the right dorsolateral and frontopolar PFC in particular, was higher during cooperation. Mother-son dyads showed less inter-brain synchrony during the independent task and a stronger increase in synchrony in response to cooperation than mother-daughter dyads. Lastly, we did not find strong evidence for links between inter-brain synchrony and child attachment. Mother-child cooperation may increase overall inter-brain synchrony, although differently for mother-son versus mother-daughter dyads. More research is needed to better understand the potential role of overall inter-brain synchrony in mother-child cooperation, and the potential link between inter-brain synchrony and attachment.


Porous ZrO2 encapsulated perovskite composite oxide for organic pollutants removal: Enhanced catalytic efficiency and suppressed metal leaching.
Cobalt-based perovskite material, an effective activator of PMS, is widely employed for wastewater remediation, but still affected by the leakage of the cobalt ions. In this study, a porous core-shell structured perovskite LaFe0.1Co0.9O3-λ/SiO2 core @ZrO2 shell (LFCS@ZrO2) was fabricated and partially etched to enlarge channels to further enhance mass transfer ability. The well-designed core-shell structure can not only restrain metal ion leaching by changing the surface microenvironment but also provide an additional driving force attributed to the enriched concentration gradient, thus enhancing the catalytic oxidation performance. Results showed that the partially etched LFCS@ZrO2 (eLFCS@ZrO2) particles exhibited an increased pore size and showed an attractive catalytic performance as well as a suppressed cobalt ion leaching (3.61 to 0.67 mg/L). Over 99% of tetracycline hydrochloride (20 mg/L) could be degraded in 15 min, and the reaction rate increased 2 folds compared with pristine LaFe0.1Co0.9O3-λ. Besides, quenching test and electron paramagnetic resonance analysis proved that sulfate radicals and singlet oxygen were the two predominant reactive oxygen species during the catalytic oxidation. This work provides a novel perspective for the fabrication of an environmentally friendly perovskite catalyst, which has a great potential application in organic pollutant degradation.


Spiderweb Nanomechanical Resonators via Bayesian Optimization: Inspired by Nature and Guided by Machine Learning.
From ultrasensitive detectors of fundamental forces to quantum networks and sensors, mechanical resonators are enabling next-generation technologies to operate in room-temperature environments. Currently, silicon nitride nanoresonators stand as a leading microchip platform in these advances by allowing for mechanical resonators whose motion is remarkably isolated from ambient thermal noise. However, to date, human intuition has remained the driving force behind design processes. Here, inspired by nature and guided by machine learning, a spiderweb nanomechanical resonator is developed that exhibits vibration modes, which are isolated from ambient thermal environments via a novel "torsional soft-clamping" mechanism discovered by the data-driven optimization algorithm. This bioinspired resonator is then fabricated, experimentally confirming a new paradigm in mechanics with quality factors above 1 billion in room-temperature environments. In contrast to other state-of-the-art resonators, this milestone is achieved with a compact design that does not require sub-micrometer lithographic features or complex phononic bandgaps, making it significantly easier and cheaper to manufacture at large scales. These results demonstrate the ability of machine learning to work in tandem with human intuition to augment creative possibilities and uncover new strategies in computing and nanotechnology.


Cortisol and behavioral responses of working dogs to environmental challenges.
This paper's primary objective is to analyse the physiological (cortisol) and behavioral responses of military working dogs (MWD). Dogs (N=27) were submitted twice to environmental challenges (challenge 1 and 2, 20 days in-between) composed of social (training), visual (mobile toy car) and auditory (air blast) stimuli. Cortisol levels decreased back to the baseline after the second challenge. The behavioral observations showed that these MWD were more active, and presented less stereotypic behaviors (pacing, manipulation of the environment) during both visual challenges, whereas half low posture was observed during the first but not during the second visual challenge. The present study shows that this group of MWD still has an adaptation capacity to an environmental challenge (return to baseline of the cortisol levels, a higher posture during the second than at the first challenge). These results are encouraging and indicate that the dogs might have a diminished welfare (i.e. stereotypic behaviors), but are not chronically stressed.


Recovery of microbial DNA by agar-containing solution from extremely low-biomass specimens including skin.
Recovering a sufficient amount of microbial DNA from extremely low-biomass specimens, such as human skin, to investigate the community structure of the microbiome remains challenging. We developed a sampling solution containing agar to increase the abundance of recovered microbial DNA. Quantitative PCR targeting the 16S rRNA gene revealed a significant increase in the amount of microbial DNA recovered from the developed sampling solution compared with conventional solutions from extremely low-biomass skin sites such as the volar forearm and antecubital fossa. In addition, we confirmed that the developed sampling solution reduces the contamination rate of probable non-skin microbes compared to the conventional solutions, indicating that the enhanced recovery of microbial DNA was accompanied by a reduced relative abundance of contaminating microbes in the 16S rRNA gene amplicon sequencing data. In addition, agar was added to each step of the DNA extraction process, which improved the DNA extraction efficiency as a co-precipitant. Enzymatic lysis with agar yielded more microbial DNA than conventional kits, indicating that this method is effective for analyzing microbiomes of low-biomass specimens.


Bone-derived serum enzymes and bone density in perimenopausal Caucasian women.
Serum levels of bone-origin alkaline phosphatase and of tartrate-resistant acid phosphatase were measured in Caucasian women aged 41-69 years who had volunteered for bone densitometry. Bone alkaline phosphatase and tartrate-resistant acid phosphatase were inversely correlated with vertebral bone density and with femoral neck bone density. Bone alkaline phosphatase and acid phosphatase were also significantly correlated, consistent with the concept of 'coupling' between osteoblast and osteoclast activity.


Atrial cholangiocarcinoma diagnosed by cardiac magnetic resonance imaging.
In this rare case of intrahepatic cholangiocarcinoma (ICC) tumor thrombus with right atrial (RA) invasion, we describe its diagnostic workup based on cardiac magnetic resonance imaging (cMRI). An 85-year-old man underwent transthoracic echocardiography due to dyspnea, revealing a RA mass. Comprehensive cMRI evaluation, including cine bright blood, T1- and T2-weighed, fat-suppressed, and contrast-enhanced imaging, was performed and diagnosis of ICC tumor thrombus with RA invasion was made. This first description of cMRI-guided diagnosis of RA invasion by ICC tumor thrombus points out the usefulness of cMRI for the diagnostic approach of RA masses suggestive of tumor thrombus.


Studies on heterologous expression of Rhizobium meliloti nifA gene and oxygen sensitivity of its product.
When the R. meliloti (Rm) nifA'-lacZ fusion-carrying plasmids were introduced into the strains of Agrobacterium tumefaciens, R. trifolii and R. astragalus, beta-galactosidase activity was demonstrated. However, activity was not induced by microaerobiosis. Furthermore, R. meliloti nifA'-lacZ fusion was also not expressed in the nodule bacteroids of R. trifolii and R. astragalus. We speculate that some factor(s) important for the induction of Rm nifA presumed to be the fixLJ regulatory system would not be operative in these bacteria. Experiments using R. meliloti nifH'-lacZ/K. Pneumoniae nifH'-lacZ fusion and the constitutive Rm nifA system to test the nifA-dependent expression of nifH'-lacZ under aerobic and microaerobic conditions in E. coli were performed. The inhibition of the Rm nifA activation of nifH'-lacZ expression in the bacteria grown in the aerobic condition was shown. Assays on the Rm nifA-m RNA produced by the constitutive Rm nifA in E. coli under aerobic and microaerobic conditions with the cloned nifA as a probe for dot blot hybridization showed a marked decrease of Rm nifA mRNA when the bacteria were grown under aeration.


Evaluation of the effect of UGT1A1 polymorphisms on the pharmacokinetics of oral and long-acting injectable cabotegravir.
Cabotegravir is an HIV integrase inhibitor in clinical development with both oral and long-acting (LA) injectable formulations. Cabotegravir is primarily metabolized by uridine 5'-diphospho-glucuronosyltransferase (UGT) 1A1, a known polymorphic enzyme with functional variants that can affect drug metabolism and exposure. To investigate the pharmacogenetic effects of the reduced-function alleles UGT1A1*6, UGT1A1*28 and/or UGT1A1*37 on steady-state pharmacokinetics (PK) and safety of oral cabotegravir (30 mg/day) and intramuscular cabotegravir LA (400 mg every 4 weeks or 600 mg every 8 weeks). Plasma cabotegravir PK was assessed in 346 UGT-genotyped participants with and without UGT1A1 functional variants across six studies (four Phase I and two Phase II) of oral cabotegravir, including 215 HIV-infected participants who received oral cabotegravir followed by cabotegravir LA. Changes from baseline in total bilirubin and ALT were assessed in one study (LATTE; NCT01641809). Statistically significant (P < 0.05) associations were observed between UGT1A1 genotype and plasma cabotegravir PK parameters, with 28%-50% increases following oral cabotegravir [plasma cabotegravir concentration at the end of the dosing interval (Ctau), 1.50-fold; AUCtau, 1.41-fold; and Cmax, 1.28-fold] and 16%-24% increases following cabotegravir LA administration (48 week Ctau, 1.24-fold; AUCtau, 1.16-fold; and Cmax, 1.18-fold) among those with low-versus-normal genetically predicted UGT1A1 activity. A statistically significant (P < 10-5) association between predicted UGT1A1 activity and maximum change in total bilirubin was also observed (2.45-fold asymptomatic increase for low versus normal) without a corresponding change in ALT. This modest increase in oral and parenteral cabotegravir exposure associated with a reduced function of UGT1A1 is not considered clinically relevant based on accumulated safety data; no dose adjustment is required.


Elimination of transient dendritic spines in ipsilaterally projecting retinal ganglion cells in rats with neonatal unilateral thalamotomy.
Using the DiI and intracellular Lucifer Yellow labeling techniques in the rat, we have demonstrated that the unilateral neonatal thalamotomy does not result in retention of transient dendritic spines of ipsilaterally projecting retinal ganglion cells (IPRGCs), although the thalamotomy is known to retain the normally transient IPRGCs (Chan et al., Dev. Brain Res., 49 (1989) 265-274). These results suggest that the process of elimination or retraction of transient dendritic spines occurs in retinal ganglion cells during development regardless of whether they make connections with appropriate or inappropriate loci in the visual targets, and/or a decrease in interactions with neighboring retinal ganglion cells.


The impact of electronic health record implementation and use on performance of the Surgical Care Improvement Project measures.
To examine the impact of electronic health record (EHR) deployment on Surgical Care Improvement Project (SCIP) measures in a tertiary-care teaching hospital. SCIP Core Measure dataset from the CMS Hospital Inpatient Quality Reporting Program (March 2010 to February 2012). One-group pre- and post-EHR logistic regression and difference-in-differences analyses. Statistically significant short-term declines in scores were observed for the composite, postoperative removal of urinary catheter and post-cardiac surgery glucose control measures. A statistically insignificant improvement in scores for these measures was noted 3 months after EHR deployment. The transition to an EHR appears to be associated with a short-term decline in quality. Implementation strategies should be developed to preempt or minimize this initial decline.


Assessment of Anterior Cruciate Ligament Tibial Footprint Sagittal Diameter and Orientation of the Ligament in the Intercondylar Notch in Indian Population: A Magnetic Resonance Imaging (MRI) Analysis.
To study the relevant anatomy of anterior cruciate ligament tibial footprint and orientation of the ligament in the intercondylar roof in Indian population the using MRI. A total of 70 knee MRI with intact anterior cruciate ligament (ACL) was assessed for intercondylar roof angle, ACL inclination angle, ACL-bluemensaat angle, ACL sagittal center, and tibial insertion size. The ACL tibial sagittal center was found to be at 43.5% of the anteroposterior tibial length. Tibial insertion size averaged 15.40 (±1.29) mm with no significant difference in males and females (p > 0.05). The roof angle was 36.29 (± 4.02) ˚ and the ACL inclination angle and ACL-bluemensaat angle were 51.22 (± 3.39) ˚ and 4.70 (±3.35) ˚ respectively with no significant sex difference (p > 0.05). The ACL tibial insertion size averaged 15.40 mm and its center was at 43.51% along the Staubli and Rauschning line. The mean roof angle was 36.29 degrees and the ACL-bluemensaat angle was 4.70 degrees. Understanding of the tibial footprint morphology and the relation of the ligament to the roof of the intercondylar notch helps in anatomical graft placement during reconstruction.


Nitrogen-doped ordered mesoporous carbon with a high surface area, synthesized through organic-inorganic coassembly, and its application in supercapacitors.
A new nitrogen-doped ordered mesoporous carbon (N-doped OMC) is synthesized by using an organic-inorganic coassembly method, in which resol is used as the carbon precursor, dicyandiamide as the nitrogen precursor, silicate oligomers as the inorganic precursors, and F127 as the soft template. The N-doped OMC possesses a surface area as high as 1374 m(2) g(-1) and a large pore size of 7.4 nm. As an electrode material for supercapacitors, the obtained carbon exhibits excellent cycling stability and delivers a reversible specific capacitance as high as 308 F g(-1) in 1 mol L(-1) H(2)SO(4) aqueous electrolyte, of which 58 % of the capacity is due to pseudo-capacitance. The large specific capacitance is attributed to proper pore size distributions, large surface area, and high nitrogen content.


Electrospray tandem mass spectrometry for structural characterization of aporphine- benzylisoquinoline alkaloids.
Electrospray mass spectrometry and tandem mass spectrometry techniques were utilized to elucidate the structures of ten aporphine-benzylisoquinoline alkaloids, consisting of monoether link between aporphine and benzyltetrahydroisoquinoline units, which were isolated and identified previously from a variety of Thalictrum sp. (Ranunculaceae family) based mainly on the UV, IR, CD, NMR, EI-MS, CI-MS, derivatization, and chemical degradation techniques. In this investigation, protonated molecules, [M+H]+ ions, for nine tertiary alkaloids, a molecular ion, [M+'] ion, for a quaternary alkaloid, and very intense doubly- protonated molecules, [M+2H]2+ ions (100% of relative abundance) in Q1 Scan MS spectra, and prominent as well as diagnostic product ions for structural information in the tandem MS/MS spectra were observed for all investigated alkaloids each in nanogram quantities. More than 10 microg quantities of each investigated alkaloid or other isoquinoline and aporphine analogs needed for the CI-MS, EI-MS and FAB-MS analysis from the previous studies.


Mycoplasma hyosynoviae in joints with arthritis in abattoir baconers.
The occurrence of Mycoplasma hyosynoviae in synovial fluid of baconers with chronic arthritis was studied at an abattoir. Cultural examination of synovial fluid samples from diseased tarsal joints of 50 animals from 42 herds yielded M. hyosynoviae in 10 cases from 8 herds. Streptococci were found in 6 cases from 6 other herds. M. hyosynoviae antigen was found in 1 of 47 of the samples, and antibody to the mycoplasma was found in 14 of 40 of the samples by ELISA test. The presence of M. hyosynoviae in a joint was usually accompanied by the corresponding antibody. In joints with streptococcal infection antibody to M. hyosynoviae could not be found.


South African Jewish Responses to COVID-19.
Although the death rate caused by the COVID-19 pandemic in South Africa has thus far been much lower than initially feared, the economic and social impact has been severe. The country's Jewish community, constituting 0.1% of the population with a median age of 45 years, has not escaped its effects. Organizations and individuals have nonetheless been able to mobilize a rapid and wide-reaching series of responses directed towards those most in need both inside and outside the community. The uniquely coordinated, energetic, and multipronged nature of these responses are attributed to robust communal infrastructure, strong community social capital, and the history of the Jewish community's positioning in post-apartheid South Africa, alongside the perceived importance of health to collective well-being.


Unrelieved symptoms of female cancer patients during their last months of life and long-term psychological morbidity in their widowers: a nationwide population-based study.
To investigate if a cancer patient's unrelieved symptoms during the last 3 months of life increase the risk of long-term psychological morbidity in the surviving widower. Men (n=907) younger than 80 years and living in Sweden, who had lost their wives due to cancer, were asked 4-5 years after their loss to answer an anonymous postal questionnaire that included questions about their current psychological morbidity and their wives' unrelieved symptoms during the last 3 months of life. If the wife suffered unrelieved anxiety or pain during the last 3 months of her life, then the widowers had a higher risk of sleep-related problems 4-5 years after the loss. When the wife had suffered from anxiety, the relative risks (RR) for the widowers' sleep-related problems were: difficulty falling asleep (RR 1.7, 95% CI 1.0-3.0) and waking up at night with anxiety (RR 4.9, 95% CI 1.5-15.7). When the wife had unrelieved pain, the widowers years later had an increased risk of difficulty falling asleep at night (RR 1.8, 95% CI 1.0-3.3). The unrelieved patients' end-of-life problems increase the risk of widowers' long-term mental suffering. Efficient and effective diagnoses and treatment of pain and anxiety in terminally ill cancer patients are critical for both patients and their surviving widowers.


Deregulated miRNA clusters in ovarian cancer: Imperative implications in personalized medicine.
Ovarian cancer (OC) is one of the most common and fatal types of gynecological cancer. OC is usually detected at the advanced stages of the disease, making it highly lethal. miRNAs are single-stranded, small non-coding RNAs with an approximate size ranging around 22 nt. Interestingly, a considerable proportion of miRNAs are organized in clusters with miRNA genes placed adjacent to one another, getting transcribed together to result in miRNA clusters (MCs). MCs comprise two or more miRNAs that follow the same orientation during transcription. Abnormal expression of the miRNA cluster has been identified as one of the key drivers in OC. MC exists both as tumor-suppressive and oncogenic clusters and has a significant role in OC pathogenesis by facilitating cancer cells to acquire various hallmarks. The present review summarizes the regulation and biological function of MCs in OC. The review also highlights the utility of abnormally expressed MCs in the clinical management of OC.


In vivo photoacoustic assessment of the oxygen saturation changes in the human radial artery: a preliminary study associated with age.
We demonstrate the potential of probing the sO2 change under blood flow in vivo using photoacoustic (PA) imaging and sheds light on the complex relationship between RBC aggregation and oxygen delivery. To conduct in vivo assessments of the sO2 in the radial artery of healthy volunteers and simultaneously probe the relation between the sO2 and hemodynamic behavior such as red blood cell (RBC) aggregation. The effects of PA-based measurements of blood hemodynamics were studied as a function of the subjects' age (20s, 30s, and 40s). The pulsatile blood flow in the human radial artery of 12 healthy subjects was imaged in the 700 to 900 nm optical wavelength range using a linear array-based PA system. The PA power when blood velocity is minimum (Pamax) was larger than the one attained at maximum blood velocity (Pamin), consistent with predictions based on the cyclical variation of RBC aggregation during pulsatile flow. The difference between Pamin and Pamax at 800 nm (ΔPa800) increased with age (1.7, 2.2, and 2.6 dB for age group of 20s, 30s, and 40s, respectively). The sO2 computed from Pamax was larger than the one from Pamin. The ΔPa800 increased with participant age. The ΔPa800 metric could be a surrogate of noninvasively monitoring the age-induced changes in RBC aggregation. The sO2 change during a cycle of pulsatile blood flow also increased with age, demonstrating that RBC aggregation can affect the sO2 change.


Locked-in syndrome with bilateral ventral midbrain infarcts.
We report a patient who was quadriplegic and mute, but retained consciousness and communicated by eye movements and blinks. EEG and SEPs were normal. BAEPs showed slight prolongation of latencies for waves IV and V. MRI showed bilateral infarcts only in the middle and lateral portions of the cerebral peduncles.


Elevated serum tumor necrosis factor-alpha levels in patients with systemic sclerosis: association with pulmonary fibrosis.
To determine whether serum tumor necrosis factor-alpha (TNF-alpha) levels are elevated, and whether they correlate with clinical features in patients with systemic sclerosis (SSc). Serum samples from patients with limited cutaneous SSc (ISSc) (n = 51), diffuse cutaneous SSc (dSSc) (n = 30), and control subjects (n = 30) were examined by ELISA. Serum TNF-alpha levels were elevated in patients with ISSc and dSSc and correlated with the presence of pulmonary fibrosis and with the decreased vital capacity of the patients. Serum TNF-alpha may be one of the cytokines that contribute to the disease process, especially to pulmonary fibrosis in patients with SSc.


Engineering Multi-Cellular Spheroids for Tissue Engineering and Regenerative Medicine.
Multi-cellular spheroids are formed as a 3D structure with dense cell-cell/cell-extracellular matrix interactions, and thus, have been widely utilized as implantable therapeutics and various ex vivo tissue models in tissue engineering. In principle, spheroid culture methods maximize cell-cell cohesion and induce spontaneous cellular assembly while minimizing cellular interactions with substrates by using physical forces such as gravitational or centrifugal forces, protein-repellant biomaterials, and micro-structured surfaces. In addition, biofunctional materials including magnetic nanoparticles, polymer microspheres, and nanofiber particles are combined with cells to harvest composite spheroids, to accelerate spheroid formation, to increase the mechanical properties and viability of spheroids, and to direct differentiation of stem cells into desirable cell types. Biocompatible hydrogels are developed to produce microgels for the fabrication of size-controlled spheroids with high efficiency. Recently, spheroids have been further engineered to fabricate structurally and functionally reliable in vitro artificial 3D tissues of the desired shape with enhanced specific biological functions. This paper reviews the overall characteristics of spheroids and general/advanced spheroid culture techniques. Significant roles of functional biomaterials in advanced spheroid engineering with emphasis on the use of spheroids in the reconstruction of artificial 3D tissue for tissue engineering are also thoroughly discussed.


Do childhood cognitive ability or smoking behaviour explain the influence of lifetime socio-economic conditions on premature adult mortality in a British post war birth cohort?
Poor childhood and adult socio-economic conditions, lower childhood cognitive ability and cigarette smoking are all associated with adult mortality risk. Using data on 4458 men and women aged 60 years from a British birth cohort study, we investigated the extent to which these risk factors are part of the same pathway linking childhood experience to adult survival. Compared with women from non-manual origins, men from non-manual origins, women and men from manual origins, and those with missing data on father's social class had about double the risk of mortality between 26 and 60 years. Cox proportional hazards models showed that these differences were reduced but remained significant after adjusting for childhood cognitive ability, adult socio-economic conditions and smoking. Higher childhood ability increased survival chances by securing better adult socio-economic conditions, such as home ownership, which was strongly associated with survival. These findings were similar for cardiovascular and cancer mortality.


Retinal, NPY- and 5ht- inputs to the aged suprachiasmatic nucleus in common marmosets (Callithrix jacchus).
The circadian timing system (CTS) anticipates optimal physiological patterns in response to environmental fluctuations, such as light-dark cycle. Since age-related disruption of circadian synchronization is linked to several pathological conditions, we characterized alterations of neurochemical constituents and retinal projections to the major pacemaker of CTS, the suprachiasmatic nucleus (SCN), in adult and aged marmosets. We used intraocular injections of neural tracer Cholera toxin b (CTb) to report age-related reductions in CTb, neuropeptide Y and serotonin immunoreactivities. Considering these projections arise in SCN from nuclei that relay environmental information to entrain the circadian clock, we provide important anatomical correlates to age-associated physiological deficits.


Capitate shortening osteotomy and vascularized bone grafting for Kienböck's disease in ulnar positive or neutral wrists.
We report the short- to medium-term outcomes for patients with Kienböck's disease and ulnar positive or neutral wrists treated by capitate shortening osteotomy combined with a 4 + 5 extensor compartmental artery vascularized bone graft placed in the lunate. This is a retrospective study of seven consecutive patients with Lichtman Stage 2 to 3B. Radiological and clinical outcomes were evaluated. Six patients maintained their Lichtman stage, one progressed. Mean time to union of the capitate was 10 weeks. Five of six lunates were completely revascularized on MRI scans, with one partial revascularization. Mean follow-up for functional scores was 40 months (range 15 to 62). Mean pain score improved significantly from 7.4/10 preoperatively to 1.9/10 postoperatively, and patient satisfaction was 9.2/10. Mean postoperative Quick Disabilities of Arm, Shoulder and Hand, Patient Evaluation Measure and Patient-Rated Wrist Evaluation scores were improved. All patients returned to their previous work. We conclude that this procedure has good short- to medium-term outcomes.Level of evidence: IV.


Measurement of Water Holdup in Vertical Upward Oil-Water Two-Phase Flow Pipes Using a Helical Capacitance Sensor.
Oil-water two-phase flows widely exist in industrial production, especially in the petroleum industry. The liquid holdup is significant for understanding reservoir production characteristics and improving oil recovery. This paper focuses on the helical capacitance sensor for the measurement of water holdup of oil-water two-phase flows. A new double helix capacitance sensor with an electrode rotation angle of 360° is designed. The sensitivity field distribution of the sensor with different parameters is simulated by the finite element analysis method, and the optimal geometric size of the sensor is obtained. The measurement characteristics of the sensor under different flow conditions are investigated by dynamical experiments of vertical oil-water flows. By analyzing the response signal of the helical capacitance sensor, the flow pattern can be identified, and the apparent water holdup can be calculated. The results show that the proposed sensor is suitable to measure the water holdup in a wide range of water cuts. Even in flow conditions of a high water cut, the sensor still retains good resolution in the D O/W flow pattern. This study expands the water holdup measurement of a capacitance sensor in the case of an oil-water two-phase flow with a high water cut.


Ovarian-independent fluctuations of estradiol receptor levels in mammalian tissues.
Three types of periodic fluctuation in tissue concentrations of estradiol receptor protein have been observed. A seasonal variation is described in the uteri of 12-16-week-old calves and of ovariectomized pigs, and in mammary tumor tissue obtained from postmenopausal women. A circadian rhythm has been demonstrated in uteri of ovariectomized rats. An irregular periodic fluctuation has been found in uteri of ovariectomized and of ovariectomized/hypophysectomized rats, with the period varying from 9 to 15 days. These observations establish that a substantial turnover of receptor occurs in the absence of hormone and that 'normal' baseline values of receptor concentration do not exist.


Use of heparinoids to treat acute ischemic stroke.
Low molecular weight heparinoids (LMWHs) offer a new treatment option to patients experiencing acute ischemic stroke. These heparin sub-fractions provide an increased risk/benefit ratio when compared to standard heparin, and allow patients to achieve better functional outcomes with fewer neurologic deficits. Because LMWHs separate the antithrombotic activity of standard heparin from its anticoagulant and antiplatelet-aggregating effects, they are safer, but equally or more effective than heparin.


Assessing PAHs pollution in Qingdao coastal area (China) by the combination of chemical and biochemical responses in scallops, Chlamys farreri.
The PAHs concentrations in seawater and tissues from the scallop Chlamys farreri were detected in three sites in Qingdao, China in 2011. The PAHs concentrations in seawater ranged from 25.32 ng/L to 314.62 ng/L. There were significant differences (p<0.05) between the residual levels among scallop tissues. The highest concentrations of PAHs in seawater and tissues were found in S2. The ethoxyresorufin-O-deethylase (EROD) activity of the digestive gland and the malondialdehyde (MDA) contents of the digestive gland and gill were sensitive to PAHs (p<0.05). This study integrated the PAHs concentrations in seawater, residual levels, the variation of biochemical response and the correlation coefficient analysis, and concluded that Qingdao is a medium PAH-contaminated area on a global scale. The highest PAHs were accumulated in the digestive gland followed by the gill, soft tissue and adductor muscle. The EROD activity of the digestive gland and the MDA contents of the digestive gland and gill could be applied to assess the PAHs pollution status in Qingdao, China.


Release of interleukin 2 and gamma interferon by peripheral mononuclear cells in human Schistosoma mansoni infection normalizes after chemotherapy.
Interleukin 2 (IL-2) and gamma interferon (IFN-gamma) were determined in supernatants of mitogen- and antigen-driven cell cultures from patients with hepatosplenic or intestinal schistosomiasis. Skin reactivity was tested using a panel of eight recall antigens. Results were compared with those of uninfected local controls. In both schistosomiasis groups, IL-2 activity was reduced before treatment. In less than one third of the patients, schistosomal antigens elicited detectable IL-2 activity. IFN-gamma production was reduced more severely in hepatosplenic cases, in particular after stimulation by anti-CD3 monoclonal antibodies. After anti-schistosomal therapy with praziquantel, mitogen-induced IL-2 and IFN-gamma activities became normal within 3 months in intestinal schistosomiasis, and within 6 months in the hepatosplenic patient group. Results of in vivo delayed-type hypersensitivity tests paralleled those of in vitro lymphokine production. In conclusion, evidence is presented for severe, antigen-unspecific suppression of lymphokine production and skin reactivity against recall antigens. Anti-parasitic chemotherapy is shown to reverse the impairment of cell-mediated immune responses at the cytokine level.


Correction: Examination of oestrus-dependent alterations of bovine cervico-vaginal mucus glycosylation for potential as optimum fertilisation indicators.
Correction for 'Examination of oestrus-dependent alterations of bovine cervico-vaginal mucus glycosylation for potential as optimum fertilisation indicators' by Marie Le Berre et al., Mol. Omics, 2021, 17, 338-346, DOI: 10.1039/D0MO00193G.


Anti-inflammatory and Immunomodulatory Potency of Selenium-Enriched Probiotic Mutants in Mice with Induced Ulcerative Colitis.
Selenium-enriched Lactobacillus plantarum and Bifidobacterium longum mutants were used as a protector against Piroxicam-induced ulcerative colitis (UC). In this study, 32 BALB/c male mice were distributed to four groups: the control group, the Piroxicam group which was given 0.8 mg Piroxicam, SP and SB groups which were given 0.8 mg Piroxicam, and plus Lactobacillus plantarum and Bifidobacterium longum selenium-enriched mutants, respectively. Bodyweight; serum content of IgG, IgM, TNF-α, IL-2, IL-6, and IL-10; CBC; myeloperoxidase enzyme activity; histopathological examination of colon and spleen; and expression of TNF-α, IL-2, IL-6, and IL-10 genes in colon and spleen with qRT-PCR were determined. Bodyweight was found to reduce in the Piroxicam group and then recovery in the SB group. Serum content of IgG, IL-2, and IL-10 reduced in the Piroxicam group, whereas IgG, TNF-α, and IL-6 increased in the Piroxicam group in comparison to the other groups. Myeloperoxidase activity witnessed a significant increase in the Piroxicam group compared with the other groups. No significant differences were observed between all groups in measurements of red cells, hemoglobin, neutrophil, monocyte, eosinophil, and basophil in blood. Meanwhile, the white blood cells and platelets recorded the highest and lowest value, respectively, in the Piroxicam group. The colon of the Piroxicam group showed a noticeably massive infiltration of inflammatory cells in the lamina propria. These inflammations were mildly reduced in the SP group, while the reduction in the SB group was significant. In the Piroxicam group, splenic parenchyma saw an increase in the number of melanomacrophages, while hypertrophic plasma cells were observed in the SP group. The spleen of the SB group exhibits a nearly normal form. TNF-α and IL-6 genes had significantly upregulated in the colon of the Piroxicam group compared to the control group, while they were significantly downregulated in the SB group. In contrast, IL-2 and IL-10 genes had upregulated in the colon of the SB group compared to the control groups, while they had downregulated in the Piroxicam group. The expression of these genes had not recorded significant differences between all groups in the spleen. Therefore, this study recommends Bifidobacterium longum selenium-enriched mutants as anti-inflammatory and immunomodulatory supplements.


Pregnancy-specific responses to COVID-19 revealed by high-throughput proteomics of human plasma.
Pregnant women are at greater risk of adverse outcomes, including mortality, as well as obstetrical complications resulting from COVID-19. However, pregnancy-specific changes that underlie such worsened outcomes remain unclear. Plasma samples were collected from pregnant women and non-pregnant individuals (male and female) with (n = 72 pregnant, 52 non-pregnant) and without (n = 29 pregnant, 41 non-pregnant) COVID-19. COVID-19 patients were grouped as asymptomatic, mild, moderate, severe, or critically ill according to NIH classifications. Proteomic profiling of 7,288 analytes corresponding to 6,596 unique protein targets was performed using the SOMAmer platform. Herein, we profile the plasma proteome of pregnant and non-pregnant COVID-19 patients and controls and show alterations that display a dose-response relationship with disease severity; yet, such proteomic perturbations are dampened during pregnancy. In both pregnant and non-pregnant state, the proteome response induced by COVID-19 shows enrichment of mediators implicated in cytokine storm, endothelial dysfunction, and angiogenesis. Shared and pregnancy-specific proteomic changes are identified: pregnant women display a tailored response that may protect the conceptus from heightened inflammation, while non-pregnant individuals display a stronger response to repel infection. Furthermore, the plasma proteome can accurately identify COVID-19 patients, even when asymptomatic or with mild symptoms. This study represents the most comprehensive characterization of the plasma proteome of pregnant and non-pregnant COVID-19 patients. Our findings emphasize the distinct immune modulation between the non-pregnant and pregnant states, providing insight into the pathogenesis of COVID-19 as well as a potential explanation for the more severe outcomes observed in pregnant women.


Staphylococcus aureus in dairy products in the Bologna area.
A study was carried out to evaluate the extent of contamination by Staphylococcus spp. and in particular by Staphylococcus aureus in dairy products on sale in the Bologna area. Staphylococcus aureus was found in 16.30% of the 135 cheese samples examined: 8.3% in soft cheese, 17.60% in blue cheese, 18.9% in semi-soft cheese and 25.0% in mozzarella-type cheese. The mean concentration was 2699 CFU/g in the 22 positive samples. The most commonly found species were Staphylococcus epidermidis (14.8%), Staphylococcus hominis (19.5%), Staphylococcus xylosus 2 (19.2%) and Staphylococcus cohnii (16.3%). Staphylococcus aureus was found mostly during the hot months while the other common species were found mostly in the period October-March.


Effects of total and regional fat loss on plasma CRP and IL-6 in overweight and obese, older adults with knee osteoarthritis.
To describe associations between total and regional body fat mass loss and reduction of systemic levels of inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)) in obese, older adults with osteoarthritis (OA), undergoing intentional weight loss. Data come from a single-blind, 18-month, randomized controlled trial in adults (age: 65.6 ± 6.2; Body mass index (BMI): 33.6 ± 3.7) with knee OA. Participants were randomized to diet-induced weight loss plus exercise (D + E; n = 150), diet-induced weight loss-only (D; n = 149), or exercise-only (E; n = 151). Total body and region-specific (abdomen and thigh) fat mass were measured at baseline and 18 months. High-sensitivity CRP and IL-6 were measured at baseline, six and 18 months. Intervention effects were assessed using mixed models and associations between inflammation and adiposity were compared using logistic and mixed linear regression models. Intentional total body fat mass reduction was associated with significant reductions in log-adjusted CRP (β = 0.06 (95% CI = 0.04, 0.08) mg/L) and IL-6 (β = 0.02 (95% CI = 0.01, 0.04) pg/mL). Loss of abdominal fat volume was also associated with reduced inflammation, independent of total body fat mass; although models containing measures of total adiposity yielded the best fit. The odds of achieving clinically desirable levels of CRP (<3.0 mg/L) and IL-6 (<2.5 pg/mL) were 3.8 (95% CI = 1.6, 8.9) and 2.2 (95% CI = 1.1, 4.6), respectively, with 5% total weight and fat mass loss. Achievement of clinically desirable levels of CRP and IL-6 more than double with intentional 5% loss of total body weight and fat mass. Global, rather than regional, measures of adiposity are better predictors of change in inflammatory burden. NCT00381290.


A deviant comes of age.
Reflecting on 30 years of sociopolitical and professional changes in health care, the cofounder of the nurse practitioner movement compares and contrasts enabling environments, past and present, with the introduction and growth of the nurse practitioner. Differing responses of individual groups and institutions and research thrusts are reported as health care reforms offer new opportunities for the introduction of the nurse practitioner in acute care services.


Similarities and differences between actigraphy and parent-reported sleep in a Hispanic and non-Hispanic White sample.
Despite concerns about the inaccuracy of parents' reports of children's sleep, it remains unclear whether the bias of parents' reports varies across racial/ethnic groups. To address this limitation, the current study systematically investigated the concordance among parent-reported sleep questionnaires, sleep diaries, and actigraphy-based sleep in a sample of Hispanic and non-Hispanic White children. Parents of 51 Hispanic and 38 non-Hispanic White children (N = 89; Mage = 6.46, SD = 0.62; 50.6% male) reported their child's bedtime and wake time on school days using sleep diaries and questionnaires. Children's sleep also was assessed with actigraphy for five consecutive school days. Parents reported longer sleep duration, earlier bedtime, and later wake time using sleep diaries and questionnaires compared to actigraphy-based assessments. Larger discrepancies between diaries and actigraphy of sleep duration, and between questionnaires and actigraphy of wake time were found in non-Hispanic White children, compared to Hispanic children. Although parents tended to overestimate their child's sleep as compared to actigraphy, parents of Hispanic children may be more accurate in some estimates of children's sleep than parents of non-Hispanic White children. Researchers, clinicians, and parents should be aware of the potential biases in parents' reports and estimates of their child's sleep and that the degree of bias could vary across racial/ethnic groups.


Effect of different types of adhesive systems on the bond strength and marginal integrity of composite restorations in cavities prepared with the erbium laser-a systematic review.
There are inconclusive results regarding etching and bonding protocol to achieve optimal bond strength and marginal integrity of adhesive composite resin restorations in erbium laser prepared cavities. This systematic review aimed to consider which adhesive system protocol may be optimal in achieving the bond strength and marginal integrity in erbium laser-prepared cavities, comparable to that obtained with conventional method of cavity preparation. This review was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement with literature search based on all publications during the period January1, 2000-October 10, 2020, in three databases: MEDLINE, Google Scholar and ScienceDirect. The necessary information was extracted by two independent authors. The search resulted in 139 articles from all databases, and a total of thirty-one articles met the inclusion criteria. The results indicated that the selection of adhesives depending on their pH and composition and the laser pulse duration and pulse energy used plays an important role in predicting the adhesion and marginal integrity. The 10-MDP containing moderate self-etch adhesives has demonstrated predictable outcomes. Longer pulse durations used for cavity preparations may indicate the use of etch-and-rinse (EnR) or moderate self-etch adhesives (SEA) to allow better resin infiltration in deep craters formed due to laser irradiation. However, further studies with more standardizations in relation to adhesives and laser parameters are needed.


Automated planning stage tracking and analysis through an integrated whiteboard system.
One of the common challenges in delivering complex healthcare procedures such as radiation oncology is the organization and sharing of information in ways that facilitate workflow and prevent treatment delays. Within the major vendors of Oncology Information Systems (OIS) is a lack of tools and displays to assist in task timing and workflow processes. To address this issue, we developed an electronic whiteboard integrated with a local OIS to track, record, and evaluate time frames associated with clinical radiation oncology treatment planning processes. We developed software using an R environment hosted on a local web-server at Seattle Cancer Care Alliance (SCCA) in 2017. The planning process was divided into stages, and time-stamped moves between planning stages were recorded automatically via Mosaiq (Elekta, Sweden) Quality Check Lists (QCLs). Whiteboard logs were merged with Mosaiq-extracted diagnostic factors and evaluated for significance. Interventional changes to task time expectations were evaluated for 6 months in 2021 and compared with 6 month periods in 2018 and 2019. Whiteboard/Mosaiq data from the SCCA show that treatment intent, number of prescriptions, and nodal involvement were main factors influencing overall time to plan completion. Contouring and Planning times were improved by 2.6 days (p<10-14) and 2.5 days (p<10-11), respectively. Overall time to plan completion was reduced by 33% (5.1 days; p<10-11). This report establishes the utility of real-time task tracking tools in a radiotherapy planning process. The whiteboard results provide data-driven evidence to add justification for practice change implementations.


Fine-Grained Video Captioning via Graph-based Multi-Granularity Interaction Learning.
Learning to generate continuous linguistic descriptions for multi-subject interactive videos in great details has particular applications in team sports auto-narrative. In contrast to traditional video caption, this task is more challenging as it requires simultaneous modeling of fine-grained individual actions, uncovering of spatio-temporal dependency structures of frequent group interactions, and then accurate mapping of these complex interaction details into long and detailed commentary. To explicitly address these challenges, we propose a novel framework Graph-based Learning for Multi-Granularity Interaction Representation (GLMGIR) for fine-grained team sports auto-narrative task. A multi-granular interaction modeling module is proposed to extract among-subjects' interactive actions in a progressive way for encoding both intra- and inter-team interactions. Based on the above multi-granular representations, a multi-granular attention module is developed to consider action/event descriptions of multiple spatio-temporal resolutions. Both modules are integrated seamlessly and work in a collaborative way to generate the final narrative. In the meantime, to facilitate reproducible research, we collect a new video dataset from YouTube.com called Sports Video Narrative dataset (SVN). It is a novel direction as it contains 6K team sports videos (i.e., NBA basketball games) with 10K ground-truth narratives(e.g., sentences). Furthermore, as previous metrics such as METEOR (i.e., used in coarse-grained video caption task) DO NOT cope with fine-grained sports narrative task well, we hence develop a novel evaluation metric named Fine-grained Captioning Evaluation (FCE), which measures how accurate the generated linguistic description reflects fine-grained action details as well as the overall spatio-temporal interactional structure. Extensive experiments on our SVN dataset have demonstrated the effectiveness of the proposed framework for fine-grained team sports video auto-narrative.


Cutaneous receptive fields of somatic and viscerosomatic neurones in the thoracic spinal cord of the cat.
Extracellular single-unit recordings were made from 121 neurones in the thoracic spinal cord of the cat. All neurones could be driven by electrical stimulation of dorsal root afferent fibres. The neurones were classified, according to the absence or presence of inputs from the ipsilateral splanchnic nerve, as "somatic" or "viscerosomatic", respectively. Cutaneous receptive fields were identified for 75 of the neurones: 31 were somatic and 44 viscerosomatic. Only two of the somatic cells received cutaneous nociceptive inputs, compared with 33 of the viscerosomatic cells. Sixty-four percent of the whole sample of neurones had receptive fields which included three or more dermatomes. Viscerosomatic cells tended to have larger receptive fields than the somatic neurones, and six of them had fields which did not include the corresponding (T11) dermatome. Neurones with receptive fields in the dorsal one-third of the dermatome tended to be located in the lateral one-third of the dorsal horn, but those with receptive fields in the ventral two-thirds of the dermatome showed no differential distribution within the gray matter. This is discussed with respect to the results of anatomical studies on the dorsal horn projections of cutaneous afferent fibres from different regions of the dermatome. Preliminary results from intracellular staining with horseradish peroxidase reveal extensive branching of primary afferents in the dorsal horn, and large dendritic fields of dorsal horn neurones. Our physiological and morphological results indicate that the somatotopic organisation of the thoracic spinal cord is less well defined than that of the lumbosacral region.


Reproducibility of stress redistribution thallium-201 SPECT quantitative indexes of hypoperfused myocardium secondary to coronary artery disease.
To determine the reproducibility of quantitative indexes of hypoperfused myocardium by exercise thallium-201 single-photon emission computed tomography, duplicate studies were performed in 16 stable patients within 1 month. Twenty-three other patients, with intervals up to 13 months between studies, were retrospectively identified from medical records. Symptoms, weight, heart rate achieved and peak systolic blood pressure during the 2 studies were similar. Maximal counts circumferential profiles' polar maps were generated and divided into 3 vascular territories. The hypoperfused myocardium was defined as the percent stress profile points below the normal level. The observed values were compared between the 2 studies for each patient. Defect size ranged from 0 to 73%. The concordance correlation coefficient (a measure of the closeness of the data points to the line of identity) and mean absolute deviation were 0.94 and 4.5%, respectively, when all patients were considered together, 0.93 and 3.2%, respectively in the reproducibility group, and 0.94 and 5.1%, respectively, in the retrospective group. Inter- and intraobserver reproducibility were also very high. For individual vessels, the concordance correlation coefficients were all > or = 0.89 and the mean absolute deviations between 3.7 and 9%. Thus, in stable patients with repeat thallium studies within a year, the percent hypoperfused myocardium is highly reproducible.


Formation of amino acids by cobalt-60 irradiation of hydrogen cyanide solutions.
Aqueous solutions of hydrogen cyanide (0.004-0.1 M) were exposed to cobalt-60 gamma rays. Among the products formed on hydrolysis of the irradiated solution; glycine, alanine, valine, serine, threonine, aspartic acid, and glutamic acid have been identified.


Students' self-confidence and perceived quality of prosthodontics education: A study in the Faculty of Dental Medicine of the University of Porto.
Oral rehabilitation with removable dentures (RDs) is still a viable choice for the edentulous population. Fostering students' confidence in prosthodontic procedures should be a major concern in dental schools. This study has three purposes: (a) to measure the self-reported confidence levels of undergraduate dental students when performing removable prosthodontic treatments; (b) to evaluate the students' perceived quality of removable prosthodontics education; and (c) to assess the students' suggestions to improve removable prosthodontics education. An anonymous questionnaire was delivered to third-, fourth- and fifth-year students of the Faculty of Dental Medicine of the University of Porto (FMDUP) (n = 176). Data from quantitative questions were statistically analysed with IBM SPSS Statistics for Windows (V.24.0), whilst qualitative data were clustered into topics and analysed in Excel. With a 100% response rate, most students felt "confident" and "very confident" in RD clinical procedures. Overall, the 5th-year students had higher confidence than 4th-year ones, except when surveying diagnostic casts. Our findings also revealed that students considered the removable prosthodontics education "Good" and "Very good," and their main suggestions were related to increasing the time allocated to clinical practice. Students' confidence in carrying out removable prosthodontic procedures grew as they progressed through the course. Overall, the students' evaluation of the quality of prosthodontics education was positive, and their main suggestion to improve their confidence levels was increasing the clinical experience.