Electrocardiographic exercise test in patients with abnormal T waves at rest.
The results of submaximal ECG exercise test were evaluated in six leads recorded simultaneously in two groups of patients with T-wave abnormalities in one or more of Leads I, II, and V4-6. Group I included 185 patients with documented ischemic heart disease (IHD) and Group II 28 patients in whom IHD appeared unlikely. The test was positive in 88 per cent of patients in Group I and in 4 per cent of patients in Group II. In the majority of patients in both groups the T wave either did not change or became more positive or less negative after exercise. The pattern of exercise-induced T-wave changes was similar in patients with and without IHD, and was influenced predominantly by the physiologic effects of exercise. T-wave normalization after exercise occurred frequently in patients with and without IHD, and in patients with positive and negative exercise tests. Our results suggest that T-wave abnormalities, not caused by hypertrophy, conduction disturbances, drugs, or electrolyte imbalance, do not modify the results of submaximal ECG stress test, and that behavior of T wave after exercise does not alter the interpretation of the postexercise ECG. The independent behavior of the S-T segment and T wave after exercise in consistent with the theory that the S-T segment and the T wave are generated by different components of the ventricular action potential.


Severe microcytic anemia but increased erythropoiesis in mice lacking Hfe or Tfr2 and Tmprss6.
Cell surface proteins Hfe, Tfr2, hemojuvelin and Tmprss6 play key roles in iron homeostasis. Hfe and Tfr2 induce transcription of hepcidin, a small peptide that promotes the degradation of the iron transporter ferroportin. Hemojuvelin, a co-receptor for bone morphogenic proteins, induces hepcidin transcription through a Smad signaling pathway. Tmprss6 (also known as matriptase-2), a membrane serine protease that has been found to bind and degrade hemojuvelin in vitro, is a potent suppressor of hepcidin expression. In order to examine if Hfe and Tfr2 are substrates for Tmprss6, we generated mice lacking functional Hfe or Tfr2 and Tmprss6. We found that double mutant mice lacking functional Hfe or Tfr2 and Tmprss6 exhibited a severe iron deficiency microcytic anemia phenotype mimicking the phenotype of single mutant mice lacking functional Tmprss6 (Tmprss6msk/msk mutant) demonstrating that Hfe and Tfr2 are not substrates for Tmprss6. Nevertheless, the phenotype of the mice lacking Hfe or Tfr2 and Tmprss6 differed from Tmprss6 deficient mice alone, in that the double mutant mice exhibited much greater erythropoiesis. Hfe and Tfr2 have been shown to play important roles in the erythron, independent of their role in regulating liver hepcidin transcription. We demonstrate that lack of functional Tfr2 and Hfe allows for increased erythropoiesis even in the presence of high hepcidin expression, but the high levels of hepcidin levels significantly limit the availability of iron to the erythron, resulting in ineffective erythropoiesis. Furthermore, repression of hepcidin expression by hypoxia was unaffected by the loss of functional Hfe, Tfr2 and Tmprss6.


Vulnerability of coronary arteries in surgery for transposition of the great arteries.
A detailed anatomic study of 82 hearts from patients operated upon for complete or congenitally corrected transposition of the great arteries revealed 12 instances of intraoperative injury to a major coronary artery. Because the coronary arterial anatomy is so variable in transposition of the great arteries, there is a significant risk of injury to them during operation. This is especially so if epicardial adhesions and scarring from previous operations obscure the surface anatomy of the heart. The most common site of injury was adjacent to incisions in the anterior surface of the right-sided ventricle, particularly in congenitally corrected transposition. Without a meticulous examination, these complications of cardiac surgery may be easily overlooked even when the hearts are examined at autopsy.


Teaching and learning pathology: a critical review of the English literature.
There are few publications summarising the main issues concerning pathology teaching and learning within undergraduate medical degrees. This article examines the themes that have emerged from the literature over the last 2 decades. A literature search was performed using PubMed, which identified 86 relevant papers in the English language. The themes discussed in the literature included the timing and duration of pathology courses, the appropriate pathology teacher for medical students, the teaching strategies used for pathology, and the methods used to assess learning. With the gradual increase of integrated medical curricula, it is important for pathology teachers to engage in the change process and help to shape the new-style courses. One of the positive aspects of change is that it can provide an opportunity to rethink current practice. It is hoped that this paper might stimulate discussion about how pathology is taught and learnt, leading to further developments in this area.


The pattern and spread of invasion can predict late cervical lymph node metastasis in early tongue squamous cell carcinoma.
To determine the predictive indexes of late cervical lymph node metastasis in early tongue squamous cell carcinoma (TSCC). We retrospectively analyzed the cases of 25 patients with stage I/II TSCC who had undergone surgical treatment without elective neck dissection. We evaluated the relationships between clinicopathologic factors and the occurrence of late cervical lymph node metastasis. Of the 25 cases, metastasis to the cervical lymph nodes was observed in nine cases (36.0%). The clinicopathological factors associated with late cervical lymph node metastasis were the mode of invasion (MOI, p = 0.032), depth of invasion (DOI, p = 0.004), and perineural invasion (PNI, p = 0.040). A multivariate analysis revealed that only the DOI was an independent predictor of late cervical lymph node metastasis. The combination of the DOI and MOI or the PNI and MOI was significantly correlated with late cervical lymph node metastasis (p = 0.004 and p = 0.012, respectively). Our findings suggest that combinations of the MOI, DOI, and PNI could be used as an index for predicting late cervical lymph node metastasis in early TSCC.


Codesigned framework for organisational culture reform in South Australian older persons' mental health services after the Oakden Report.
The Oakden Report documented failures in governance, clinical practice and organisational culture occurring at the Oakden Older Persons' Mental Health Service and drew national attention to the care of older people with complex clinical needs. Responding to the recommendations of the Report, a working group brought together stakeholders to engage in a codesign process involving literature review, gallery walks and focus groups, under the governance of the Oakden Response Oversight Committee. The working group developed a framework as a blueprint for organisational culture reform built around a central philosophy of compassionate relationship-centred care, supported by four priorities: developing a values-based workforce, cultivating psychological safety, facilitating excellence in care and providing transparent accountability. The purpose of the framework was to provide a way forward for South Australian older persons' mental health services after The Oakden Report, and it may provide insight into similar processes of codesign and culture change in other service contexts.


Effects of naloxone on stress-induced analgesia after hemorrhagic shock.
To investigate whether endogenous opioids might be involved in the mechanisms that underlie hemorrhagic shock-induced analgesia, formalin tests were performed after hemorrhage and reinfusion in naloxone pretreated and untreated rats. Twenty-four adult male Sprague-Dawley rats were divided into control (n = 6), saline (n = 6), naloxone 10 mg/kg (n = 6), and naloxone 100 mg/kg (n = 6) groups. The mean blood pressure (mBP) was kept at 50 to 60 mm Hg for 30 minutes by draining arterial blood in the saline group and the naloxone groups. After 15 minutes of returning mBP to normal levels by reinfusion of the drained shed blood, 10% formalin (3.7% formaldehyde solution, 0.1 mL) was injected into the left rear paw. Nociceptive behaviors were observed for 1 hour after the formalin injection. Nociceptive behaviors of the posthemorrhagic shock groups were significantly lower than those of the control group. No significant difference was seen in nociceptive behaviors among the saline and naloxone groups. Naloxone did not reverse the hemorrhagic shock-induced analgesia, which suggests that endogenous opioids might not be a major factor that governs stress-induced analgesia (SIA) after hemorrhagic shock.


Intrauterine adhesions after conservative and surgical management of spontaneous abortion.
To determine the frequency of intrauterine adhesions (IUA) after conservative management, medical evacuation, and surgical evacuation for spontaneous abortion. Prospective follow-up study (Canadian Task Force classification II-2). Gynecology unit in a teaching hospital. Eighty-two women who had been treated with conservative management, medical evacuation, or surgical evacuation of retained products of conception after spontaneous abortions in a randomized, controlled trial. Hysteroscopic diagnosis of IUA 6 months after initial treatment was the primary outcome measure. No cases of IUA were found in patients managed conservatively or by medical evacuation, whereas two cases (7.7%) of filmy IUA were detected in those managed by surgical evacuation. There was no statistical significant difference in the rate of self-reported reduced menstrual flow 6 months after initial treatment by any method. The prevalence of IUA was low after each modality of treatment for spontaneous abortion. Conservative management and medical evacuation are both acceptable alternatives to standard surgical evacuation.


Re-affirmation of a Preliminary Live with Love Conceptual Framework for cancer couple dyads: A couple-based complex intervention study.
The relational dynamics of couples may be under great strain due to the diagnosis and treatment of cancer. A complex "Caring for Couples Coping with Cancer" (4Cs) intervention program, guided by a Preliminary Live with Love Conceptual Framework (P-LLCF) for Cancer Couple Dyads, was developed to support couples going through such hardship. The purpose of this paper is to present a re-analysis of the results of the 4Cs intervention program to determine whether the findings provide evidence to support the constructs in the P-LLCF. The 4Cs intervention was provided to support cancer patients and their spousal caregivers. The pre- and post-intervention findings of the 4Cs intervention program were re-analyzed using descriptive-correlational analysis and structural equation modeling (SEM) to test whether the findings provide evidence to support the constructs in the P-LLCF. A total of 92 out of the 117 dyads at baseline (T0) were successfully followed-up at 6 weeks (T1). The re-analysis of the findings from the 4Cs program (T1 outcomes) showed inter-relationships among the components included in the P-LLCF: dyadic mediators, dyadic coping, dyadic appraisal, and dyadic outcomes. The SEM of all six models resulted in convergence and showed goodness of fit to the data and variables, which is supportive of the constructs in the P-LLCF. The present analysis of the T1 outcome measures of the 4Cs program provides evidence to support the constructs in the P-LLCF. Multiple mutual effects existed between couples in the process of living and coping with cancer as dyads.


Aminoglycoside antibiotics in clinical use.
Aminoglycosides are among the most used antibiotics despite competitive pressure from newer beta-lactam agents. The activity profile, pharmacology, toxicity potential, and methods of toxicity prevention of aminoglycosides are well appreciated after three decades. Nephrotoxicity, ototoxicity, and the added costs of drug level monitoring limit wider usage, but great activity against highly antibiotic resistant gram negative bacteria often outweigh these disadvantages and will likely keep aminoglycosides available for the foreseeable future.


Imaging individual spindle microtubule dynamics in fission yeast.
Microtubules exhibit dynamic instability, stochastically switching between infrequent phases of growth and shrinkage. In the cell, microtubule dynamic instability is further modulated by microtubule-associated proteins and motors, which are specifically tuned to cell cycle stages. For example, mitotic microtubules are more dynamic than interphase microtubules. The different parameters of microtubule dynamics can be measured from length versus time data, which are generally obtained from time-lapse acquisition using the optical microscope. The typical maximum resolution of the optical microscope is ~λ/2 or ~300 nm. This scale represents a challenge for imaging fission yeast microtubule dynamics specifically during early mitosis, where the bipolar mitotic spindle contains many short dynamic microtubules of ~1-μm scale. Here, we present a novel method to image short fission yeast mitotic microtubules. The method uses the thermosensitive reversible kinesin-5 cut7.24(ts) to create monopolar spindles, where asters of individual mitotic microtubules are presented for imaging and subsequent analysis.


Left to right: representational biases for numbers and the effect of visuomotor adaptation.
Adaptation to right-shifting prisms improves left neglect for mental number line bisection. This study examined whether adaptation affects the mental number line in normal participants. Thirty-six participants completed a mental number line task before and after adaptation to either: left-shifting prisms, right-shifting prisms or control spectacles that did not shift the visual scene. Participants viewed number triplets (e.g. 16, 36, 55) and determined whether the numerical distance was greater on the left or right side of the inner number. Participants demonstrated a leftward bias (i.e. overestimated the length occupied by numbers located on the left side of the number line) that was consistent with the effect of pseudoneglect. The leftward bias was corrected by a short period of visuomotor adaptation to left-shifting prisms, but remained unaffected by adaptation to right-shifting prisms and control spectacles. The findings demonstrate that a simple visuomotor task alters the representation of space on the mental number line in normal participants.


Inhibition of MMTV transcription by HDAC inhibitors occurs independent of changes in chromatin remodeling and increased histone acetylation.
Increased histone acetylation has been associated with activated gene transcription and decreased acetylation with repression. However, there is a growing number of genes known, which are downregulated by histone deacetylase (HDAC) inhibitors through unknown mechanisms. This study examines the mechanism by which the mouse mammary tumor virus (MMTV) promoter is repressed by the HDAC inhibitor, trichostatin A (TSA). We find that this repression is transcriptional in nature and that it occurs in the presence and absence of glucocorticoids. TSA decreases MMTV transcription at a rapid rate, reaching maximum in 30-60 min. In contrast with previous reports, the repression does not correlate with an inhibition of glucocorticoid-induced nuclease hypersensitivity or NF1-binding at the MMTV promoter. Surprisingly, TSA does not induce sizable increases in histone acetylation at the MMTV promoter nor does it inhibit histone deacetylation, which accompanies deactivation of the glucocorticoid-activated MMTV promoter. Repression of MMTV transcription by TSA does not depend on the chromatin organization of the promoter because a transiently transfected MMTV promoter construct with a disorganized nucleoprotein structure was also repressed by TSA treatment. Mutational analysis of the MMTV promoter indicates that repression by TSA is mediated through the TATA box region. These results suggest a novel mechanism that involves acetylation of nonhistone proteins necessary for basal transcription.


Clinical and laboratory characteristics of 19 patients with Churg-Strauss syndrome from a single South Australian centre.
Churg-Strauss syndrome (CSS) is a rare, idiopathic systemic vasculitis. There is emerging evidence of an association between the presence or absence of antineutrophil cytoplasmic antibodies (ANCA) and clinical phenotype. Thromboembolism is an increasingly recognised complication of the disease. Given the paucity of Australian data, the aim of this study was to examine the clinical and laboratory features of CSS in a single Australian centre. We performed a retrospective review of all patients who fulfilled the American College of Rheumatology classification criteria for CSS managed at the Department of Immunology, Royal Adelaide Hospital between 2002 and 2008. Nineteen patients were included. All patients had asthma and most had upper airway involvement. Peripheral nerve, musculoskeletal, gastrointestinal and cutaneous involvement was common. Renal and cardiac involvement was uncommon in this series. Histological confirmation was obtained in 15 patients (78.9%). Ten patients (52.6%) were ANCA+, and these were more likely to have musculoskeletal involvement, such as arthralgia or myalgia (odds ratio 57, P = 0.005). Thrombosis was a feature at diagnosis in six patients (31.6%); two of these recurred with relapse. Sixteen patients (84.2%) were followed up; five died, and mean survival was 8.9 years. This is the first Australian study to focus on CSS. Our results demonstrate similar presentation and prognosis of CSS to previous descriptions; however, we noted that musculoskeletal involvement was more common in ANCA+ patients. In our series, thrombosis was a significant complication and we suggest that thromboprophylaxis may be warranted.


Patterns of livestock activity on heterogeneous subalpine pastures reveal distinct responses to spatial autocorrelation, environment and management.
In order to understand the impact of grazing livestock on pasture ecosystems, it is essential to quantify pasture use intensity at a fine spatial scale and the factors influencing its distribution. The observation and analysis of animal activity is greatly facilitated by remote tracking technology and new statistical frameworks allowing for rapid inference on spatially correlated data. We used these advances to study activity patterns of GPS-tracked cows in six summer-grazing areas in the Swiss Alps that differed in environmental conditions as well as livestock management. Recorded GPS positions were assigned to the activities of grazing, resting, and walking, and were discretized on a regular grid. Regression models with spatially structured effects were fitted to the spatial activity patterns using Integrated Nested Laplace Approximation. They indicated that terrain slope, forage quality, and stocking rate were the primary factors determining cow activity in the six study areas. Terrain slope significantly reduced livestock activity in five of the six areas and sparse forage availability significantly reduced grazing in all areas. In three areas, grazing pressure imposed by the pasture rotation was observable in the grazing pattern. Insolation, distance to the shed, and distance to water were less important for cow activity. In addition to the main factors identified across all study areas, we found effects operating only in individual areas, which were partly explained by specific environmental and management characteristics. In study areas with few paddocks, environmental variables exerted a stronger control on livestock activity than in areas with a short stocking period per paddock. The data demonstrated that a strict pasture rotation with short stocking periods is necessary to influence livestock activity, and hence potential effects on ecosystem processes. Without grazing management, livestock activity is primarily determined by the environment. Such insight is indispensable for studying relationships between grazing animals and ecosystem characteristics, and for developing management strategies to optimize ecosystem services. The analysis also highlighted the need for an appropriate statistical treatment of bio-logging data, since various estimates were biased if spatial autocorrelation was ignored.


COVID-19 and resultant restrictions on gambling behaviour.
Since the onset of COVID-19, studies suggest a significant increase in online gambling, potentially facilitated by increased time at home, social isolation and boredom. This study aimed to address what is known about the impact of the pandemic on gambling behaviour by conducting a mapping review. A systematic literature search was conducted using four online databases. Additional studies were identified using reference lists. Relevant studies were quality scored and their findings synthesised in terms of overall changes at the population level and potentially vulnerable groups. The weight of evidence from 35 relevant reports across 12 countries indicated reductions of gambling during the pandemic at the level of the general population. However, marked increases in gambling amongst vulnerable sub-populations including amongst young adults and people with pre-existing at-risk gambling were also noted. The impact of COVID-19 on gambling is highly contingent on context. If policy makers examine only population level data, this could overlook profound negative effects identified in those with at-risk gambling, gambling disorder, and amongst young adults.


Identification of a Stress-Sensitive Anorexigenic Neurocircuit From Medial Prefrontal Cortex to Lateral Hypothalamus.
A greater understanding of how the brain controls appetite is fundamental to developing new approaches for treating diseases characterized by dysfunctional feeding behavior, such as obesity and anorexia nervosa. By modeling neural network dynamics related to homeostatic state and body mass index, we identified a novel pathway projecting from the medial prefrontal cortex (mPFC) to the lateral hypothalamus (LH) in humans (n = 53). We then assessed the physiological role and dissected the function of this mPFC-LH circuit in mice. In vivo recordings of population calcium activity revealed that this glutamatergic mPFC-LH pathway is activated in response to acute stressors and inhibited during food consumption, suggesting a role in stress-related control over food intake. Consistent with this role, inhibition of this circuit increased feeding and sucrose seeking during mild stressors, but not under nonstressful conditions. Finally, chemogenetic or optogenetic activation of the mPFC-LH pathway is sufficient to suppress food intake and sucrose seeking in mice. These studies identify a glutamatergic mPFC-LH circuit as a novel stress-sensitive anorexigenic neural pathway involved in the cortical control of food intake.


Deliberate acquisition of competence in physiological breech birth: A grounded theory study.
Research suggests that the skill and experience of the attendant significantly affect the outcomes of vaginal breech births, yet practitioner experience levels are minimal within many contemporary maternity care systems. Due to minimal experience and cultural resistance, few practitioners offer vaginal breech birth, and many practice guidelines and training programmes recommend delivery techniques requiring supine maternal position. Fewer practitioners have skills to support physiological breech birth, involving active maternal movement and choice of birthing position, including upright postures such as kneeling, standing, squatting, or on a birth stool. How professionals learn complex skills contrary to those taught in their local practice settings is unclear. How do professionals develop competence and expertise in physiological breech birth? Nine midwives and five obstetricians with experience facilitating upright physiological breech births participated in semi-structured interviews. Data were analysed iteratively using constructivist grounded theory methods to develop an empirical theory of physiological breech skill acquisition. Among the participants in this research, the deliberate acquisition of competence in physiological breech birth included stages of affinity with physiological birth, critical awareness, intention, identity and responsibility. Expert practitioners operating across local and national boundaries guided less experienced practitioners. The results depict a specialist learning model which could be formalised in sympathetic training programmes, and evaluated. It may also be relevant to developing competence in other specialist/expert roles and innovative practices. Deliberate development of local communities of practice may support professionals to acquire elusive breech skills in a sustainable way.


An application of stereo matching algorithm based on transfer learning on robots in multiple scenes.
Robot vision technology based on binocular vision holds tremendous potential for development in various fields, including 3D scene reconstruction, target detection, and autonomous driving. However, current binocular vision methods used in robotics engineering have limitations such as high costs, complex algorithms, and low reliability of the generated disparity map in different scenes. To overcome these challenges, a cross-domain stereo matching algorithm for binocular vision based on transfer learning was proposed in this paper, named Cross-Domain Adaptation and Transfer Learning Network (Ct-Net), which has shown valuable results in multiple robot scenes. First, this paper introduces a General Feature Extractor to extract rich general feature information for domain adaptive stereo matching tasks. Then, a feature adapter is used to adapt the general features to the stereo matching network. Furthermore, a Domain Adaptive Cost Optimization Module is designed to optimize the matching cost. A disparity score prediction module was also embedded to adaptively adjust the search range of disparity and optimize the cost distribution. The overall framework was trained using a phased strategy, and ablation experiments were conducted to verify the effectiveness of the training strategy. Compared with the prototype PSMNet, on KITTI 2015 benchmark, the 3PE-fg of Ct-Net in all regions and non-occluded regions decreased by 19.3 and 21.1% respectively, meanwhile, on the Middlebury dataset, the proposed algorithm improves the sample error rate at least 28.4%, which is the Staircase sample. The quantitative and qualitative results obtained from Middlebury, Apollo, and other datasets demonstrate that Ct-Net significantly improves the cross-domain performance of stereo matching. Stereo matching experiments in real-world scenes have shown that it can effectively address visual tasks in multiple scenes.


Regulation of Microtubule Growth and Catastrophe: Unifying Theory and Experiment.
Recent studies have found that microtubule-associated proteins (MAPs) can regulate the dynamical properties of microtubules in unexpected ways. For most MAPs, there is an inverse relationship between their effects on the speed of growth and the frequency of catastrophe, the conversion of a growing microtubule to a shrinking one. Such a negative correlation is predicted by the standard GTP-cap model, which posits that catastrophe is due to loss of a stabilizing cap of GTP-tubulin at the end of a growing microtubule. However, many other MAPs, notably Kinesin-4 and combinations of EB1 with XMAP215, contradict this general rule. In this review, we show that a more nuanced, but still simple, GTP-cap model, can account for the diverse regulatory activities of MAPs.


Pilot study with technosphere/PTH(1-34)--a new approach for effective pulmonary delivery of parathyroid hormone (1-34).
Sequential subcutaneous PTH injection therapy (repeated 14 days of PTH administration and a subsequent treatment pause for a few weeks) is known to increase bone mineral density in patients with osteopenic disorders. Alternative methods of drug delivery may be beneficial in increasing compliance. A pilot study was performed in 10 healthy volunteers (4 female/6-male, age: 25.6 +/- 3.5 years, BMI: 22.3 +/- 2.4 kg/m 2, mean +/- SD) to assess the pharmacokinetic profiles of 1600 IU of PTH(1 - 34) using the pulmonary Technosphere drug delivery system in comparison to a subcutaneous injection of 400 IU. The treatments were administered in the morning after an overnight fast and blood samples for measurement of PTH(1 - 34), PTH(1 - 84), and calcium and calcitonin were taken over a period of 6 hours. Both injection and pulmonary application of PTH(1 - 34) were well tolerated. After pulmonary administration of Technosphere/PTH(1 - 34), PTH(1 - 34) appeared in the serum with a faster concentration increase (T max: pulmonary 10 +/- 5 min vs. subcutaneous 28 +/- 8 min, p < 0.001) and with higher maximal concentrations (C max : pulmonary 309 +/- 215 pmol/l vs. subcutaneous 102 +/- 45 pmol/l, p < 0.05) as compared to the subcutaneous injection. The relative bioavailability of pulmonary Technosphere/PTH(1 - 34) was calculated to be 48 %. No differences were seen between pulmonary and subcutaneous application with regard to the PTH(1 - 84), calcitonin and calcium concentrations. In conclusion, pulmonary application of Technosphere/PTH(1 - 34) appears to be an effective and thus attractive candidate for PTH substitution therapy in osteoporosis and other conditions leading to a decrease in bone mineral density.


Interleukin-1β in hypothalamic paraventricular nucleus mediates excitatory renal reflex.
Chemical stimulation of kidney causes sympathetic activation and pressor responses in rats. The excitatory renal reflex (ERR) is mediated by angiotensin type 1 receptor (AT1R) and superoxide anions in hypothalamic paraventricular nucleus (PVN). The aim of this study is to determine whether interleukin-1β (IL-1β) in the PVN mediates the ERR, and whether the IL-1β production in the PVN is dependent on the AT1R-superoxide anion signaling. Experiments were performed in adult rats under anesthesia. The ERR was induced by renal infusion of capsaicin, and evaluated by the responses of the contralateral renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP). Inhibition of IL-1β production with MCC950 in the PVN dose-dependently inhibited the capsaicin-induced ERR and sympathetic activation. The PVN microinjection of IL-1 receptor antagonist IL-1Ra or specific IL-1β antibody abolished the capsaicin-induced ERR, while IL-1β enhanced the ERR. Renal infusion of capsaicin promoted p65-NFκB phosphorylation and IL-1β production in the PVN, which were prevented by PVN microinjection of NADPH oxidase inhibitor apocynin or the superoxide anion scavenger tempol. The PVN microinjection of NFκB inhibitor BMS-345541 abolished the capsaicin induced-ERR and IL-1β production, but not the NADPH oxidase activation and superoxide anion production. Furthermore, capsaicin-induced p65-NFκB phosphorylation and IL-1β production in the PVN were prevented by AT1R antagonist losartan, or angiotensin converting enzyme inhibitor captopril. These results indicate that capsaicin-induced ERR and sympathetic activation are mediated by IL-1β in the PVN. The IL-1β production in the PVN is dependent on the AT1R-mediated superoxide anion generation and NFκB activation.


Current knowledge on pancreaticobiliary reflux in normal pancreaticobiliary junction.
Knowledge on pancreaticobiliary reflux in normal pancreaticobiliary junction and their pathologic implications has experienced tremendous progress during the last few years. This article reviews the current knowledge on this condition and its pathological implications on gallbladder diseases. Many publications with different levels of evidence were found supporting biliary carcinogenesis associated with pancreaticobiliary reflux in normal and abnormal pancreaticobiliary junction. Also, there are many publications supporting the common occurrence of pancreaticobiliary reflux in normal pancreaticobiliary junction, and sphincter of Oddi dysfunction as the most plausible cause of this condition. Although an important body of research has been published regarding pancreaticobiliary reflux in normal pancreaticobiliary junction and their clinical significance, the current evidence does not fully support what has been suggested. The reflux of pancreatic enzymes into the bile tract and gallbladder is a fascinating subject of study which is open to active research. The final demonstration of the pathophysiology and consequences of PBR in NPBL and support by evidence level type I would constitute a major breakthrough in the understanding and eventually in the treatment of gallbladder diseases.


Demonstration of sugar residues in the ultimobranchial tubule and thyroid C-cells of the rat using peroxidase labelled lectins.
The distribution of various sugars, that contribute to the composition of the carbohydrate components of the glycoprotein in the ultimobranchial tubule and the thyroid C-cells has been studied, using eight peroxidase-labelled lectins (Dolichos biblorus, Glycine max, Bauhinia purpurea, Helix pomatia, Arachis hipogaea, Ulex europaeus I, Limax flavus and Sophora japonica). The results obtained seem to show that there are receptors for Dolichos biflorus, Glycine max, Bauhinia purpurea, Helix pomatia, Arachis hipogaea, Ulex europaeus I and Limax flavus in the ultimobranchial tubule, suggesting the existence of N-acetylgalactosamine, galactose, L-fucose and sialic acid. However, the C-cells show only a positive reaction with Ulex europaeus I indicating the existence of fucosyl residues in those cells. All these findings support the contention that the ultimobranchial body might contribute decisively not only to the formation of C-cells but also, partially, to the constitution of certain follicular cells.


Optimal surgical approach for digestive neuroendocrine neoplasia primaries: Oncological benefits versus short and long-term complications.
The rising incidence and the accumulating prevalence of neuroendocrine neoplasia (NEN) in the population makes this a common, prevalent and a clinically relevant disease group. Surgical resection represents the only potentially curative treatment for digestive NENs. Thus, resection should in principle be considered for all patients with NEN, although taking the patients age, relevant comorbidity, and performance status into account for operability. Patients with insulinomas, NEN of the appendix and rectal NENs are usually cured by surgery alone. However, less than a third of patients are amendable to curative surgery alone at time of diagnosis. Furthermore, recurrence is common and may occur years after primary surgery, hence the long follow-up time recommended in most NENs (>10 years). As many patients with NENs present with locoregional or metastatic disease, there is considerable debate regarding the role of debulking surgery in these settings. However, good long-term survival can be achieved in a considerable proportion of patients, with 50-70% alive up to 10 years after surgery. Location and grade are the main determinants of long-term survival. Here we present considerations to surgery for primary neuroendocrine tumors in the digestive tract.


Adults with a more extensive body involvement, moderate to extremely severe vitiligo and a prolonged clinical course have an early onset in childhood in addition to other prognostic factors as compared to individuals with later-onset vitiligo.
The extent and disease severity, duration and other associated prognostic cofactors in vitiligo in adults may vary with the age of onset (before or after 10 years of age). To compare extent and disease severity, duration and other cofactors in adults with early-onset and late-onset vitiligo. The medical records of 408 (M:F 1:1.1) adults aged 20-75 years diagnosed with vitiligo between January 2016 and December 2019 were examined retrospectively. The extent and severity of vitiligo were defined. Characteristics of vitiligo with early onset and late onset were compared statistically and odds ratios calculated for risk assessment. 31 (7.6%, M:F 1:2.4) patients had early-onset vitiligo, and 377 (92.4%, M:F 0.8:1) patients had later-onset vitiligo. Compared to late onset, patients with early-onset vitiligo had a significant number of males (71% vs 45.9%), higher percentages of body surface area involvement and moderate to extremely severe disease (29% vs 10.6%), longer duration of disease (41.9% vs 9%), Koebner's phenomenon (48.4% vs 15.6%) and halo nevus (9.7% vs 1.9%). Differences between the two groups were not significant for types of vitiligo, family history of vitiligo and presence of cutaneous and systemic/autoimmune diseases. The adults, males in particular, with generalised vitiligo (>10% BSA involvement) appear to have an early onset and a prolonged clinical course. The presence of Koebner's phenomenon and halo nevus in patients with early-onset vitiligo was other poor prognostic factors compared to patients with late-onset vitiligo. The retrospective, hospital-based cross-sectional design and small sample size for stratification remain major limitations.


Vision and hearing deficits and associations with parent-reported behavioral and developmental problems in international adoptees.
To determine the occurrence of vision and hearing deficits in international adoptees and their associations with emotional, behavioral and cognitive problems. The Minnesota International Adoption Project (MnIAP) was a 556-item survey that was mailed to 2,969 parents who finalized an international adoption in Minnesota (MN) between January 1990 and December 1998 and whose children were between 4 and 18 years-old at the time of the survey. Families returned surveys for 1,906 children (64%); 1,005 had complete data for analyses. The survey included questions about the child's pre-adoption experiences and post-placement medical diagnoses, and the Child Behavior Checklist (CBCL). Multivariate logistic regression assessed associations between hearing and vision problems and problems identified by the CBCL. Information on hearing and vision screening and specific vision and hearing problems was also collected via a telephone survey (HVS) from 96/184 children (52%) seen between June 1999 and December 2000 at the University of Minnesota International Adoption Clinic. In both cohorts, 61% of children had been screened for vision problems and 59% for hearing problems. Among those children screened, vision (MnIAP = 25%, HVS = 31%) and hearing (MnIAP = 12%, HVS = 13%) problems were common. For MnIAP children, such problems were significant independent predictors for T scores >67 for the CBCL social problems and attention subscales and parent-reported, practitioner-diagnosed developmental delay, learning and speech/language problems, and cognitive impairment. Hearing and vision problems are common in international adoptees and screening and correction are available in the immediate post-arrival period. The importance of identifying vision and hearing problems cannot be overstated as they are risk factors for development and behavior problems.


Iris metastasis from endometrial carcinoma: A challenging diagnosis and individualized eye-sparing treatment.
A woman in her 70's with a history of recurrent oral aphthosis and two years earlier of resected stage IA low risk endometrial adenocarcinoma, presented with blurred vision and a painful mass of the right eye that had developed in two months. PET/CT imaging detected a nodule in the right lung. Because of diagnostic uncertainties between inflammatory disease (Behçet syndrome) or cancer, a biopsy of iris and pulmonary lesions were performed and lead to histologically documented metastases from endometrial adenocarcinoma in both sites. After a multidisciplinary team discussion excluding disfiguring local therapies (radiation therapy or surgery), systemic chemotherapy with carboplatin and paclitaxel was performed, leading to radiological complete response that is sustained at 12 months after the end of treatment. This case shows that chemotherapy should be considered as a valid organ-sparing treatment in the management of these uncommon metastatic sites.


Medial temporal atrophy in preclinical dementia: Visual and automated assessment during six year follow-up.
Medial temporal lobe (MTL) atrophy is an important morphological marker of many dementias and is closely related to cognitive decline. In this study we aimed to characterize longitudinal progression of MTL atrophy in 93 individuals with subjective cognitive decline and mild cognitive impairment followed up over six years, and to assess if clinical rating scales are able to detect these changes. All MRI images were visually rated according to Scheltens' scale of medial temporal atrophy (MTA) by two neuroradiologists and AVRA, a software for automated MTA ratings. The images were also segmented using FreeSurfer's longitudinal pipeline in order to compare the MTA ratings to volumes of the hippocampi and inferior lateral ventricles. We found that MTL atrophy rates increased with CSF biomarker abnormality, used to define preclinical stages of Alzheimer's Disease. Both AVRA's and the radiologists' MTA ratings showed similar longitudinal trends as the subcortical volumes, suggesting that visual rating scales provide a valid alternative to automatic segmentations. Our results further showed that it took more than 8 years on average for individuals with mild cognitive impairment, and an Alzheimer's disease biomarker profile, to increase the MTA score by one. This suggests that discrete MTA ratings are too coarse for tracking individual MTL atrophy in short time spans. While the MTA scores from each radiologist showed strong correlations to subcortical volumes, the inter-rater agreement was low. We conclude that the main limitation of quantifying MTL atrophy with visual ratings in clinics is the subjectiveness of the assessment.


Kinematic specificity of cortical reorganization associated with motor training.
Motor training consisting of repetition of directionally specific voluntary thumb movements elicits a short-term memory trace that encodes the kinematic details of the practiced motions in the primary motor cortex. Here, we studied activation patterns associated with this form of training using functional magnetic resonance imaging under careful monitoring of motor training kinematics and electromyography. We identified task-specific reductions in activation in contralateral motor cortex, a region that controls executive motor output, as well as somatosensory cortex and inferior parietal lobule, regions in charge of monitoring motor training kinematics. Our findings are consistent with the hypothesis that a short training period consisting of repetition of finger motions leads to cortical reorganization characterized by a smaller and more efficient network that is specific for the trained movement direction.


Genetic diversity within Theileria orientalis parasites detected in Sri Lankan cattle.
In the present study, we investigated the genetic diversity of Theileria orientalis parasites circulating among Sri Lankan cattle. Nucleotide sequence analysis of the major piroplasm surface protein (MPSP) gene fragments amplified from T. orientalis-positive DNA samples (from bovine blood) revealed the presence of 4 parasite genotypes. The genotypes consisted of types 1, 3, 5, and 7. Phylogenetic analysis indicated that the Sri Lankan MPSP sequences were closely related to those reported from Vietnam (types 3 and 5), Mongolia (types 1 and 5), Thailand (types 1, 5, and 7), and Japan (type 7). Subsequently, genotype-specific PCR assays determined that the most common genotype was type 7, followed by types 5, 3, and 1. Genotype 7 has been reported to be involved in disease outbreaks in India. Therefore, preventive and control measures are essential to avoid potential economic losses due to T. orientalis infection in Sri Lanka. This is the first report that describes the genetic diversity of T. orientalis circulating among Sri Lankan cattle.


Inability to clonally expand fetal progenitors from maternal blood.
To confirm the recent report of the culture of single clones of fetal progenitor cells from maternal blood. Hemopoietic progenitor cells were cultured from 16 blood samples obtained from women pregnant with a male singleton fetus. Single colonies were isolated by micro-manipulation and examined by multiplex real-time PCR. Of a total of 1,674 colonies examined, 1,648 were identified as being maternal. No colonies were detected of fetal origin. The clonal expansion of single fetal colonies from the maternal circulation is not feasible by current methods.


Enzyme catalyzed hydrolysis of inorganic pyrophosphate. Current view of problems in characterization of PP1-phosphohydrolytic activity associated with alkaline phosphatases (EC 18.104.22.168).
A survey of the hydrolytic activity of alkaline phosphatase (EC 22.214.171.124) reveals that PP1, like phosphomonoesters, can serve as substrate in vitro. This pp1-phosphohydrolytic activity can be distinguished from PP1-phosphohydrolytic activities of inorganic pyrophosphatases (EC 220.127.116.11) and glucose-6-phosphatase (EC 22.214.171.124) by several criteria. Discrimination among these hydrolytic enzymes is possible by their dependence on variation of pH and of magnesium to PP1 ratios in the assay solutions. The true substrates and modifiers are not simply PP1 and magnesium, but the equilibrium species in mixtures of these two. The physiological significance of each of the three enzymes is not predictable from their differential efficiency as catalysts of PP1-hydrolysis in vitro.


Physicochemical parameters, sensory profile and concentration of volatile compounds and anthocyanins in beers brewed using potato variety with purple flesh.
In the recent years, beer brewers are experimenting with using various substrates, other than traditional barley malt, water, hops, and yeast for beer production, because new adjuncts to the beer brewing can add new sensory and functional properties to this beverage. Novel potatoes with purple or red-colour flesh are a good and cheap starch source and are rich in bioactive components, which could increase the nutritive value of the produced beer. The aim of the study was to determine whether some part of barley malt can be replaced by the potatoes of purple-colour flesh and assessment of properties of such beer. Beer samples showed increased antioxidant activity, higher concentration of anthocyanins and polyphenol compounds, as well as modified composition of volatiles and lower ethanol content. Beer produced with the addition of 30% of purple potatoes showed acceptable organoleptic qualities in the sensory analysis.


Cognitive profile in adult women with turner syndrome: IQ split and associations with ADHD and ASD.
The behavioural phenotype in Turner syndrome (TS) is associated with an uneven cognitive profile and social and executive difficulties. Still, studies in adult populations of TS are scarce, and the interactions between different behavioural domains are unclear. The aim of this study was to examine the cognitive profile in relation to measures of ADHD and ASD in a Swedish sample of 30 adult women with TS. Standardized psychological tests and questionnaires were used for behavioural assessments in a sample of adult women with a diagnosis of TS (n = 30). Both frequentist and Bayesian statistics were applied. The cognitive profile was characterized by a verbal > non-verbal intelligence quotient (IQ) split, and 77% of the sample displayed a split exceeding cut-off for clinical significance. Symptoms on screening measures reaching thresholds for ADHD were reported in two of the 30 participants (7%) and thresholds for autism spectrum disorders (ASD) in one participant (3%). Bayesian statistics gave substantial evidence for no association between the IQ split and symptoms of ADHD/ASD. These results show that the TS phenotype in adulthood is associated with a clinically significant uneven cognitive profile, and particular impairments in integrative executive functions.


Combinatorial perturbation sequencing on single cells using microwell-based droplet random pairing.
Combinatorial drug therapy reduces drug resistance and disease relapse, but informed drug combinations are lacking due to the high scale of possible combinations and the relatively simple phenotyping strategies. Here we report combinatorial perturbation sequencing (CP-seq) on single cells using microwell-base droplet random pairing. CP-seq uses oligonucleotides to barcode drugs, encapsulates drugs and cells in separate droplets, and pairs cell droplets with two drug droplets randomly on a microwell array chip to complete combinatorial drug treatment and barcode-tagging on cells. The subsequent single-cell RNA sequencing simultaneously detects the single-cell transcriptomes and drug barcodes to demultiplex the corresponding drug treatment. The microfluidic droplet operations had robust performance, with the overall utilization rate of the microwells being up to 83%. We then progressively validated the CP-seq by performing single-drug treatments and then combinatorial-drug treatments, confirming the CP-seq's capability in the collection and analysis of drug-perturbed transcriptomes. Leveraging the advantage of droplet microfluidics in massive multiplexing, the CP-seq represents a great technology for combinatorial perturbation screening with high throughput and comprehensive profiling.


Long-term outcome of patients with drug-refractory atrial flutter and fibrillation after single- and dual-site right atrial pacing for arrhythmia prevention.
An initial crossover study comparing dual- and single-site right atrial pacing was performed followed by a long-term efficacy and safety evaluation of dual-site right atrial pacing in patients with drug-refractory atrial fibrillation (AF). Also examined was the efficacy of two single-site right atrial pacing modes (high right atrium and coronary sinus ostium) and the long-term need for cardioversion, antithrombotic and antiarrhythmic drug therapies during dual-site atrial pacing. Thirty consecutive patients with drug-refractory symptomatic AF and documented primary or drug-induced bradycardia were implanted with a dual chamber rate-responsive pacemaker and two atrial leads. Single-site atrial pacing was performed at the high right atrium or the coronary sinus ostium. Continuous atrial pacing was maintained. Mean arrhythmia-free intervals increased from 9+/-10 days in the control period preceding implant to 143+/-110 days (p < 0.0001) in single-site right atrial pacing and 195+/-96 days in dual-site right atrial pacing (p < 0.005 versus single-site pacing and p < 0.0001 versus control). Dual-site right atrial pacing significantly increased the proportion of patients free of AF recurrence (89%) as compared to single-site right atrial pacing (62%, p = 0.02). High right atrial pacing and coronary sinus ostial pacing had similar efficacy for AF prevention. Effective rhythm control was achieved in 86% of patients during dual right atrial pacing. Seventy-eight percent of patients at 1 year and 56% at 3 years remained free of symptomatic AF. The need for cardioversion was reduced after pacemaker implant (p < 0.05) and antithrombotic therapy was reduced (p < 0.06) without any thromboembolic event. Coronary sinus ostial lead dislodgement was not observed after discharge. Atrial pacing in combination with antiarrhythmic drugs eliminates or markedly reduces recurrent AF. Prevention of AF is enhanced by dual-site right atrial pacing. High right atrial and coronary sinus ostial pacing do not differ in efficacy. Dual-site right atrial pacing is safe, achieves long-term rhythm control in most patients, decreases the need for cardioversion, and antithrombotic therapy can be selectively reduced.


The influence of AMH on IVF success.
Anti-Müllerian hormone has a regulative function in the activation of folliculogenesis and an influence on atresia rate. It is considered a marker for the ovarian reserve. We know that a relationship exists between AMH levels and oocyte retrieval numbers, antral follicle count, pregnancy rates and birth rates. The role of AMH as an efficient prognostic factor in determining the probability of pregnancy has been largely discussed in the literature. The aim of this study is to determine the role age and AMH levels play in success rates of IVF/ICSI therapies. To date, the sample group we examined was one of the biggest ever included in a single study of the subject. All patients who underwent an IVF/ICSI treatment with FSH stimulation in the Wiesbaden Kinderwunschzentrum between 2003 and 2010, were no older than 44 years old, and had an evaluation of serum AMH levels before treatment were included in this study. In total, 1287 patients were analysed retrospectively. Statistical analysis was performed with SPSS. Females' mean age was 34.89, ranging from 21 to 44 years. The patients underwent between 1 and 11 IVF cycles. Younger women had significantly higher AMH levels (p = 0.001). Patients with higher AMH levels had significantly lower break-off rates (p < 0.0005) and a significantly higher number of oocytes retrieved (p < 0.0005). Higher levels of AMH corresponded to higher pregnancy rates (p = 0.017). AMH levels do not influence pregnancy rates in younger patients (<36 years). AMH is a useful parameter that should be measured before performing an IVF/ICSI treatment. In younger patients, AMH levels do not predict pregnancy outcomes. In patients older than 36 years, AMH can be used as a prognostic factor. Even when a woman's AMH levels are too low to be detected, she still an acceptable chance of becoming pregnant.


Effects of zeranol on protein turnover in L6 myotubes.
Protein synthesis and degradation were measured in cultures of L6 myotubes to determine the direct anabolic activity of zeranol on muscle. Zeranol, dexamethasone, insulin and zeranol-dexamethasone combination, at various concentrations from 10(-8) to 10(-6) M, were added to cultures at either 18 hr prior to or at the beginning of a 6 hr synthesis or degradation measuring period. Protein synthesis was measured by determining the incorporation of radioactivity into trichloraoacetic acid precipitable cell protein following incubation with [3H] leucine. Protein synthesis was expressed as cpm incorporated in 6 hr per mg protein. Protein degradation was measured by a pulse-chase procedure using [3H] leucine. Protein degradation was expressed as the percent labeled protein degraded in 6 hr. Results from the study indicate that zeranol did not stimulate protein synthesis or inhibit proteolysis (P greater than .01). Stimulation of proteolysis observed with 10(-8) M dexamethasone was 13% and 18% (P less than .01) at the 6 hr and 24 hr incubation period, respectively. Dexamethasone-stimulated protein degradation was not altered appreciably by zeranol. In contrast, 10(-6) M insulin significantly (P less than .01) stimulated protein synthesis (16%) and inhibited protein degradation (15%). These results suggest that the anabolic action of zeranol does not occur by directly regulating muscle protein synthesis or degradation, or by altering the glucocorticoid-induced catabolic response in muscle.


Monoclonal antibodies prepared against PAS-I butyrophilin and GP-55 from guinea-pig milk-fat-globule membrane bind specifically to the apical pole of secretory-epithelial cells in lactating mammary tissue.
Monoclonal antibodies to the three major glycoproteins of guinea-pig milk-fat-globule membrane were isolated. The specificity of these antibodies was determined by solid-phase immunoassays and by immunoblotting and autoradiographic techniques after one- and two-dimensional gel electrophoresis. The antibodies bound to PAS-I, a sialoglycoprotein of Mr greater than or equal to 200 000 and the glycoproteins butyrophilin and GP-55, of Mr 63 000 and 55 000, respectively. Immunolocalization studies showed that all three proteins were highly concentrated in the apical pole of secretory-epithelial cells in mammary tissue during lactation. PAS-I, butyrophilin or GP-55, were not detected in either the basal cytoplasm of mammary epithelial cells or in myoepithelial cells, capillary endothelial cells or other cells found in the mammary gland. These proteins were either present in small amounts or were absent from mammary tissue taken in late pregnancy. The monoclonal antibodies characterized in this study will therefore be useful as probes for studies of the biogenesis of apical membrane proteins in mammary epithelial cells during lactation.


Design and preparation of amino-functionalized core-shell magnetic nanoparticles for photocatalytic application and investigation of cytotoxicity effects.
The goal of the current paper was a synthesis of Amino-functionalized Fe3O4@SiO2 core-shell magnetic nanoparticles as a unique efficient photocatalyst for removing organic dyes from aqueous environments. The magnetic Fe3O4@SiO2 core-shell was produced by a silica source to avoid aggregation by the co-precipitation method. Next, functionalized by using 3-Aminopropyltriethoxysilane (APTES) via a post-synthesis link. The chemical structure, magnetic properties, and shape of the manufactured photocatalyst (Fe3O4@SiO2-NH2) were described by XRD, VSM, FT-IR, FESEM, EDAX, and DLS/Zeta potential analyses. The XRD findings approved the successful synthesis of nanoparticles. The photocatalytic activity of Fe3O4@SiO2-NH2 nanoparticles was examined for MB degradation and the degradation performance was about 90% in the optimum conditions. Also, the cytotoxicity of Fe3O4, Fe3O4@SiO2 core-shell, and Fe3O4@SiO2-NH2 nanoparticles was examined on CT-26 cells using an MTT assay, the finding has shown that nanoparticles can be used for inhibiting cancer cells.


An efficient method for smoothing indicator-dilution and other unimodal curves.
A mathematical function has been developed for approximating unimodal functions, particularly those which are non-Gaussian, skewed, and incomplete. It is useful as an alternative to cubic splines in smoothing noisy experimental data. Particular applications are to indicator-dilution curves and probability density functions of varied form. In its Fortran implementation, SMOEX, it is computationally inexpensive compared to standard cubic spline smoothing routines and requires less storage to preserve the smoothed function for retrieval or interpolation.


Aflatoxin detection technologies: recent advances and future prospects.
Aflatoxins have posed serious threat to food safety and human health. Therefore, it is important to detect aflatoxins in samples rapidly and accurately. In this review, various technologies to detect aflatoxins in food are discussed, including conventional ones such as thin-layer chromatography (TLC), high performance liquid chromatography (HPLC), enzyme linked immunosorbent assay (ELISA), colloidal gold immunochromatographic assay (GICA), radioimmunoassay (RIA), fluorescence spectroscopy (FS), as well as emerging ones (e.g., biosensors, molecular imprinting technology, surface plasmon resonance). Critical challenges of these technologies include high cost, complex processing procedures and long processing time, low stability, low repeatability, low accuracy, poor portability, and so on. Critical discussion is provided on the trade-off relationship between detection speed and detection accuracy, as well as the application scenario and sustainability of different technologies. Especially, the prospect of combining different technologies is discussed. Future research is necessary to develop more convenient, more accurate, faster, and cost-effective technologies to detect aflatoxins.


Layered Co doped MnO2 with abundant oxygen defects to boost aqueous zinc-ion storage.
Zinc Manganese oxide (Zn/MnO2)-based aqueous battery is favored due to their high specific capacity, security and cost performance. Nevertheless, they usually problems of unstable cyclic structure and slow diffusion kinetics, restricting their practical application. Here, we have successfully synthesized a Co doped MnO2 cathode material with abundant defects on a carbon cloth substrate. Through a simple hydrothermal method, the Co element can be lightly intercalated in the two-dimensional (2D) layered α-MnO2 nanowires, inhibiting the structural transformation during the cycle and improve the stability of the material. Meanwhile, plasma technology facilitates the formation of oxygen vacancies in the electrode material, which not only accelerate electron diffusion but also improve the conductivity. Therefore, Zn/Co-MnO2 battery can reach a specific capacity of 511 mAh g-1 at 0.5A g-1 and the retention rate accomplish 98% at high current density. This research puts forward a strategy of element doping and physical preparation of oxygen vacancies, which provides the possibility to develop reversible Zn/MnO2-based aqueous battery cathode materials with high-performance.


Indirect photodegradation of sulfadimidine and sulfapyridine: Influence of CDOM components and main seawater factors.
This study investigated the indirect photodegradation of sulfadimidine (SM2) and sulfapyridine (SP) in the presence of chromophoric dissolved organic matter (CDOM), and studied the influences of main marine factors (salinity, pH, NO3- and HCO3-). Reactive intermediate (RI) trapping experiments demonstrated that triplet CDOM (3CDOM*) played a major role in the photodegradation of SM2 with a 58% photolysis contribution, and the contributions to the photolysis of SP were 32%, 34% and 34% for 3CDOM*, hydroxyl radical (HO·) and singlet oxygen (1O2), respectively. Among the four CDOMs, JKHA, with the highest fluorescence efficiency, exhibited the fastest rate of SM2 and SP photolysis. The CDOMs were composed of one autochthonous humus (C1) and two allochthonous humus (C2 and C3). C3, with the strongest fluorescence intensity, had the strongest capacity to generate RIs and accounted for approximately 22%, 11%, 9% and 38% of the total fluorescence intensity of SRHA, SRFA, SRNOM and JKHA, respectively, indicating the predominance of CDOM fluorescent components in the indirect photodegradation of SM2 and SP. These results demonstrated the photolysis mechanism: The photosensitization of CDOM occurred after its fluorescence intensity decreased, and a large number of RIs (3CDOM*, HO· and 1O2, etc.) were generated by energy and electron transfer, then these RIs reacted with SM2 and SP to cause photolysis. The increase in salinity stimulated the photolysis of SM2 and SP consecutively. The photodegradation rate of SM2 first increased and then decreased with increasing pH, whereas the photolysis of SP was remarkably promoted by high pH but remained stable at low pH. NO3- and HCO3- had little effect on the indirect photodegradation of SM2 and SP. This research may contribute to a better understanding of the fate of SM2 and SP in the ocean and provide new insights into the transformation of other sulfonamides (SAs) in marine ecological environments.


3D seismic model of faulting systems of a Jurassic - Cretaceous sedimentary packages in Merjan_West Kifl Oil fields - Central Iraq.
Study of three dimension seismic data of Merjan survey, central Iraq has showed that the Jurassic - Cretaceous succession is affected by faulting system. Seven major normal faults were identified and mapped. Synthetic traces calculated from sonic and density logs of the well Me-1. Two exploration wells were drilled in the area Me-1 and Wkf-1 wells. The area is characterized by extension phase led to graben system forms rift sub-basin. The structural components of rift sub-basin has identified and visualized in three dimensions. Discussion about the effect of this system on the sedimentary package has been presented. Faulting framework can be divided into two groups: the first affects the Jurassic and lower Cretaceous rocks and the second affects the upper Cretaceous and lower Tertiary rocks. The first group is associated with the post rift thermal sag, passive margin progradation and gravitational collapse (lower Jurassic - mid Turonian 190-92 ma); approximately during the Sargelu - NahrUmr depositional time. The second group is limited and is associated with the rifting creating the Euphrates graben as collision wanes (Late Turonian - Maastrichtian 90-70 Ma) approximately during the Tanuma shale/Sadi - Shiranish depositional time.


Strategies to address structural and institutional barriers to success among students of color in nursing programs.
The COVID-19 pandemic and the significant disparities experienced by Black, Indigenous, and people of color (BIPOC) in infections, hospitalizations, and deaths associated with the Coronavirus have underscored the imperative to increase the size and diversity of the healthcare workforce, including nursing. Academically focused pipeline development programs have led to some advances in minority recruitment and retention; however, emerging research highlights the importance of extra-academic factors that reduce the sense of belonging and persistence among underrepresented and minority students. The purpose of this manuscript is to describe the diversity, equity, and inclusion goals and activities of a college of nursing located in a minority-serving institution. Here, we emphasize the description of a range of activities aimed at meeting our diversity goals. Further, we highlight the actions initiated in response to emergent "extra-academic" student needs over the past year related to the COVID-19 pandemic and police brutality. The strategies described have implications for improving diversity, equity, and inclusion among higher education institutions in nursing.


Degradation from the endoplasmic reticulum: disposing of newly synthesized proteins.
We have characterized a pre-Golgi, proteolytic pathway for rapid degradation of newly synthesized T cell receptor (TCR) subunits which is insensitive to drugs that block lysosomal proteolysis. The site of degradation in this pathway is either part of or closely related to the endoplasmic reticulum (ER). This "ER" degradative pathway very likely plays an important role in many cells in the removal of unassembled or incompletely assembled membrane protein complexes from the secretory pathway. It is the sole pathway followed by TCR alpha chains and alpha-beta complexes in transfected fibroblasts. In T cells treated with ionophores, which disrupt transport of the TCR from the ER to the Golgi, all newly synthesized alpha, beta, and delta chains are destroyed by this pathway. A variety of biochemical and morphological techniques have been used to distinguish the "ER" degradative pathway from an alternative, lysosomal pathway.


Frequent methylation of p16INK4A/p14ARF promoters in tumorigenesis of Epstein-Barr virus transformed lymphoblastoid cell lines.
The data that the p16INK4A gene is frequently inactivated in Burkitt lymphoma (BL) and that this event often accompanies the inactivation of p14ARF in several tumours prompted us to examine the genetic and methylation status of both genes in BL and B-lymphoblastoid cell lines (LCLs). The existence of gene deletion, mutation and promoter methylation was investigated by single-strand conformational polymorphism, direct sequencing and methylation-specific PCR (MSP) analysis, respectively. Sequencing of each exon of both tumour suppressor genes revealed p16INK4A mutation only in 3 out of 11 BL, but 1 of them also affected the p14ARF gene. MSP analysis of promoters showed p16INK4A to be methylated and p14ARF not to be methylated in each Epstein-Barr virus-positive BL cell line. Primary B-cells and de novo established LCLs had no genetic changes or methylated promoter of either gene. LCLs achieving the stage of immortalization usually showed methylation of both p16INK4A and p14ARF promoters. Our results suggest that, in contrast to p161NK4A, inactivation of p14ARF by either genetic change or promoter methylation has no importance in the development of BL cell lines, while its methylation has a central role in the immortalization of LCLs.


[Genetic counselling].
'Genetic counselling is the process by which patients or relatives at risk of a disorder that may be hereditary are advised of the consequences of the disorder, the probability of developing and transmitting it and of the ways in which this may be prevented or ameliorated.' The genetic counsellor will discuss the genetic basis and medical facts and also possible personal, familial, social and insurance implications of the respective disorder with the consultand. Further diagnostic investigations, such as genetic tests, may be helpful or necessary for risk predictions or may be required to reach a firm diagnosis. In asymptomatic individuals at risk for a late-onset genetic disorder genetic counselling is obligatory for predictive genetic testing. Genetic counselling also should be offered to symptomatic patients before a diagnostic test is performed. Thereby the patients might become aware in time about the personal, familial and social consequences of the test result that may exceed that of their actual illness. Due to medical confidentiality the geneticist is not allowed to contact other family members and to inform them about a familial disorder and warn them about their own genetic risk. This is the concern of the consultand. Various aspects make up genetic counselling as a specific process which concerns genetic diagnosis, risk estimation and accurate information on medical and genetic facts, but also has a supportive role ensuring that consultands may benefit from given advice and possible preventive measures.


A Social Ecological Model of Syndemic Risk affecting Women with and At-Risk for HIV in Impoverished Urban Communities.
Syndemic risk is an ecological construct, defined by co-occurring interdependent socio-environmental, interpersonal and intrapersonal determinants. We posited syndemic risk to be a function of violence, substance use, perceived financial hardship, emotional distress and self-worth among women with and at-risk for HIV in an impoverished urban community. In order to better understand these interrelationships, we developed and validated a system dynamics (SD) model based upon peer-reviewed literature; secondary data analyses of a cohort dataset including women living with and at-risk of HIV in Bronx, NY (N = 620); and input from a Bronx-based community advisory board. Simulated model output revealed divergent levels and patterns of syndemic risk over time across different sample profiles. Outputs generated new insights about how to effectively explore multicomponent multi-level programs in order to strategically develop more effective services for this population. Specifically, the model indicated that effective multi-level interventions might bolster women's resilience by increasing self-worth, which may result in decreased perceived financial hardship and risk of violence. Overall, our stakeholder-informed model depicts how self-worth may be a major driver of vulnerability and a meaningful addition to syndemic theory affecting this population.


Validation of a continuous penile blood-flow measurement by pulse-volume-plethysmography.
Today, in the assessment of cavernous artery blood-flow, the most commonly used technique is Doppler ultrasound velocimetry (continuous, pulsed, color-coded or power), which is often considered as the gold standard. Plethysmographic techniques and radioactive tracers have been widely used for the assessment of global penis flow variations but are not adequate for continuous blood-flow measurement. A new pulse-volume plethysmographic (PVP) device using a water-filled penile cuff was employed to assess continuous blood-flow measurement in the penis. Simultaneously Doppler velocity was recorded and served as a gold standard. A penile water-cuff is connected through a pressure tube to a three-way tap. The pulse-volume changes in the penile water-cuff are measured by means of a latex membrane placed over one of the three-way taps. The displacements of the latex are recorded by a photoplethysmograph. The third tap is connected to a 5 l perfusion bag placed 30 cm above the penis so as to maintain constant pressure in the whole device whatever the penis volume. Twenty-four volunteers were tested. The Doppler velocity signal and pulse volume of cavernous arteries were measured simultaneously after PGE1 intra-cavernous injection. Blood-flow variations were induced by increasing penis artery compression with a second penile water-cuff used as a tourniquet fitted onto the penis root, and the pressure of which could be modified by a water-filled syringe. The amplitude of the plethysmographic pulse-volume signal and the area under the Doppler velocity signal were correlated. The inter-patient (n=24) correlation ranged from 0.455 to 0.904, with a mean correlation of 0.704 and P<0.0001. PVP measurement by a water-filled cuff was validated by ultrasound velocimetry. This new continuous, non-invasive and easy-to-use technique enables physiological and physiopathological flow-measurement during sleep, under visual sexual stimulation (VSS), or following artificial erection. Simultaneous recording of penile blood-flow by PVP and intra-cavernous pressure (ICP) measured by a non-invasive device will provide fundamental inflow and outflow information in both physiological and pathophysiological conditions, and further enable venous leakage to be assessed by a mathematical model.


Distinct patterns of gene expression in hepatocellular carcinomas and adjacent non-cancerous, cirrhotic liver tissues in rats fed a choline-deficient, L-amino acid-defined diet.
Gene expression profiles of HCC and surrounding non-cancerous tissues in rats fed a CDAA diet for 70 weeks, as well as normal liver tissues, were explored using an oligonucleotide microarray for 3757 genes. A total of 146 genes were identified as differentially expressed; the affected functions including metabolism, apoptosis, cell cycling, RNA splicing, Wnt signaling, reactive oxygen species-induced stress, and fibro/cirrhogenesis. The genes were found to fit into four distinct expression patterns after classification by hierarchical and k-means clustering procedures. Notably, genes within the same functional category tended to be found within the same cluster, thus gene functions appeared to be related to their expression patterns. For example, genes encoding receptors (Fisher's exact test, P < 0.01) and cytokines (Fisher's exact test, P < 0.05) were both enriched in a cluster characterized by low expression in HCC compared to their surrounding tissues. While some of the receptors in this cluster had cell-proliferative potential, others are known to be growth-suppressive. It was noted, however, that four of the 10 receptor genes encode G-protein-coupled receptors, for which growth-suppressive potential has been reported. The seven growth factors in the same cluster included two fibroblast growth factors. The current findings suggest the possibility that genes differentially expressed in this multistep carcinogenic model may be classified into relatively few clusters according to their expression patterns, and that these clusters may be associated with gene functional categories.


Hexyl (E)-3-(3,4-dihy-droxy-phen-yl)acrylate.
The title mol-ecule, C(15)H(20)O(4), has an E conformation about its C=C bond and is almost planar (r.m.s. deviation of all non-H atoms = 0.04 Å). The crystal structurere features O-H⋯O and C-H⋯O hydrogen bonds.


Iron deficiency, but not underfeeding reduces the secretion of interferon-gamma by mitogen-activated murine spleen cells.
Interferon-gamma (IFN-γ), a cytokine primarily secreted by T and natural killer cells regulates cell-mediated and innate immunity. Iron deficiency, a public health problem in children impairs immune function. To determine whether reduced IFN-γ contributes to impaired immunity, we measured IFN-γ in supernatants of activated (2.5 μg/ml concanavalin A, 50 ng/ml anti-CD3 antibody) spleen cells from control (C), iron-deficient (ID), pair-fed (PF), and iron-replete mice for 3 (R3) and 14 days (R14) (11-12/group). Except for iron content, the low iron (5 ppm) and control (50 ppm) diets had identical composition. Mean indices of iron status after 51 days of feeding were as follows: C=PF≈R14>R3>ID (p<0.01). Iron deficiency, but not pairfeeding reduced IFN-γ concentration in mitogen-treated cells by 30-43% (p<0.05); iron repletion improved it. Reduced IFN-γ was not simply due to differences in IL-12 (IFN-γ inducer), percentage of CD3+ T cells, or impaired cell proliferation because these indices were not always decreased. It was likely due to a defect in T cell activation that leads to IFN-γ gene expression. IFN-γ positively correlated with indicators of iron status, body, and thymus weights (r=0.238-0.472; p<0.05). Reduced IFN-γ secretion during iron deficiency may affect response to infections.


Effects of antimutagenic flavourings on SCEs induced by chemical mutagens in cultured Chinese hamster cells.
Effects of antimutagenic flavourings such as vanillin, ethylvanillin, anisaldehyde, cinnamaldehyde, coumarin and umbelliferone on the induction of SCEs by MMC were investigated in cultured Chinese hamster ovary cells. None of these 6 flavourings showed any SCE-inducing activity by themselves. However, an obvious increase in the frequencies of SCEs was observed when MMC-pretreated cells were cultured in the presence of each flavouring. All these compounds have either an alpha, beta-unsaturated carbonyl group or a carbonyl functionality neighbouring the phenyl group which may react with an enzyme SH-group and cause higher-order structure changes. SCE-enhancing effects of vanillin were further investigated on 6 other kinds of mutagens. Vanillin was also effective on SCEs induced by EMS, ENNG, ENU or MNU. On the other hand, MMS- or MNNG-induced SCEs were not influenced at all by vanillin. SCE-enhancing effects of vanillin seemed to be dependent on the quality of lesions in DNA.


The Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer Screening and Diagnosis, 2018 Edition.
This article updates readers as to what is new in the Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer Screening and Diagnosis, 2018 Edition. Breast cancer screening issues are covered, including matters of breast density and possible supplemental modalities, along with appropriate pre-operative/follow-up diagnostic breast imaging tests. Up-to-date clinical practice guidelines for breast cancer screening and diagnosis should help to provide patients and clinicians with not only evidence-based breast imaging options, but also accurate and balanced information about the benefits and harms of intervention, which ultimately enables shared decision making about imaging test plans.


Rational collaborative ablation of bacterial biofilms ignited by physical cavitation and concurrent deep antibiotic release.
Bacteria biofilm has extracellular polymeric substances to protect bacteria from external threats, which is a stubborn problem for human health. Herein, a kind of gasifiable nanodroplet is fabricated to ablate Staphylococcus aureus (S. aureus) biofilm. Upon NIR pulsed laser irradiation, the nanodroplets can gasify to generate destructive gas shockwave, which further potentiates initial acoustic cavitation effect, thus synergistically disrupting the protective biofilm and killing resident bacteria. More importantly, the gasification can further promote antibiotic release in deep biofilm for residual bacteria eradication. The nanodroplets not only exhibit deep biofilm penetration capacity and high potency to ablate biofilms, but also good biocompatibility without detectable side effects. In vivo mouse implant model indicates that the nanodroplets can accumulate at the S. aureus infected implant sites. Upon pulsed laser treatment, the nanodroplets efficiently eradicate bacteria biofilm in implanted catheter by synergistic contribution of gas shockwave-enhanced cavitation and deep antibiotic release. Current phase changeable nanodroplets with synergistic physical and chemical therapeutic modalities are promising to combat complex bacterial biofilms with drug resistance, which provides an alternative visual angle for biofilm inhibition in biomedicine.


Response of the seated human body to whole-body vertical vibration: biodynamic responses to sinusoidal and random vibration.
The dependence of biodynamic responses of the seated human body on the frequency, magnitude and waveform of vertical vibration has been studied in 20 males and 20 females. With sinusoidal vibration (13 frequencies from 1 to 16 Hz) at five magnitudes (0.1-1.6 ms(-2) r.m.s.) and with random vibration (1-16 Hz) at the same magnitudes, the apparent mass of the body was similar with random and sinusoidal vibration of the same overall magnitude. With increasing magnitude of vibration, the stiffness and damping of a model fitted to the apparent mass reduced and the resonance frequency decreased (from 6.5 to 4.5 Hz). Male and female subjects had similar apparent mass (after adjusting for subject weight) and a similar principal resonance frequency with both random and sinusoidal vibration. The change in biodynamic response with increasing vibration magnitude depends on the frequency of the vibration excitation, but is similar with sinusoidal and random excitation.


Scilla maderensis, TLC screening and positive inotropic effect of bulb extracts.
Scilla maderensis Menezes (Hyacinthaceae) is endemic to the Portuguese Archipelago of Madeira. The taxonomic proximity between Scilla L. and Urginea Steinh. genus, and also the knowledge that bulbs of Urginea maritima (L.) Baker (Scilla maritima L.) contain cardiac glycosides of the bufadienolide type, led us to a phytochemical and pharmacological study of S. maderensis. Extracts obtained from the bulbs were screened by TLC and tested in the isolated frog heart preparation. The TLC screening revealed spots with colours and R(f) values similar to those obtained for proscillaridin and scillaren A. In the frog heart preparation the extracts showed a positive inotropic effect and toxic doses induced the arrest of the heartbeat in systole. We can conclude that the bulbs of S. maderensis contain substances exerting pharmacological effects on the heart.


Understanding the relationships among individual-based momentary measured noise, perceived noise, and psychological stress: A geographic ecological momentary assessment (GEMA) approach.
This study aims to understand how the relationship between individual-based noise exposure and psychological stress is influenced by perceived noise and context. Using geographic ecological momentary assessment, along with activity-travel diaries, GPS tracking, and portable noise sensors, this study collected real-time data of individuals' daily movement, noise exposure, and self-reported noise perception and psychological stress. Structural equation modeling was used to examine the direct and indirect pathways among context, momentary measured noise, perceived noise, and psychological stress. The study finds that momentary measured noise influences psychological stress through the mediating effect of perceived noise. Further, different activity and travel, social, and temporal contexts significantly influence people's momentary measured noise, perceived noise, and psychological stress. These findings advance our understanding of specific contexts, individual-based objectively measured and subjectively perceived environmental exposures, and their effects on psychological health at a high spatiotemporal resolution.


Primary carcinoma of the gallbladder: review of 25 cases.
The records of 25 patients with carcinoma of the gallbladder occurring during a 5 year period were reviewed. The frequent relation of the disease with cholelithiasis and benign tumors has been widely recognized. Stones were present in the gallbladder in 92 per cent of the patients. In the majority of cases, a diagnosis of carcinoma of the gallbladder was not made clinically. The most common preoperative diagnosis was benign biliary tract disease. The mean survival time after operation was 7 months, and only five patients had a curative resection. The best hope for reducing the mortality from this disease lies in earlier cholecystectomy in patients with benign gallbladder disease.


Comparative trial of cefuroxime axetil in recurrent urinary tract infections illustrating importance of 6-week follow-up.
Women with recurrent urinary tract infections treated with cefuroxime axetil (500 or 250 mg twice daily) for 7 days had a higher relapse rate when tested 6 weeks after the start of treatment than those given amoxycillin (250 mg three times daily). The poor performance of cefuroxime axetil is explained by variable bioavailability.


Multicenter Palmaz stent renal artery stenosis revascularization registry report: four-year follow-up of 1,058 successful patients.
Palmaz-Schatz stent revascularization of renal artery stenosis was successfully performed on 1,058 patients who were entered into a voluntary, multicenter registry. The revascularization procedures were performed because of poorly controlled hypertension, preservation of renal function, and congestive heart failure. All 1,058 patients were eligible for > or =6-month clinical follow-up, which focused on subsequent renal function, blood pressure, number of antihypertensive medications, and survival. At 4-year follow-up, systolic and diastolic blood pressures had significantly decreased (168 +/- 27 mm Hg to 147 +/- 21 mm Hg, and 84 +/- 15 to 78 +/- 12 mm Hg; P < 0.05) and the blood pressure appeared to be more facilely controlled as indicated by the concomitant decrease in number of antihypertensive medications (2.4 +/- 1.1 to 2.0 +/- 1.0; P < 0.05). Serum creatinine had also significantly decreased (1.7 +/- 1.1 to 1.3 +/- 0.8 mg/dl; P < 0.05). The cumulative probability of survival was 74% +/- 3% at 4 years. Survival was good for patients with normal (85% +/- 3%) baseline renal function, fair (78% +/- 5%) with mildly impaired renal function, and poor (49% +/- 5%) with severely impaired renal function (baseline creatinine > or =2.0 mg/dl). The combination of impaired renal function and bilateral disease adversely effected survival (unilateral 55% +/- 6% vs. bilateral 36% +/- 11%; P < 0.05). Renal artery stent revascularization, in the presence of normal or mildly impaired renal function, had a beneficial effect on blood pressure control and on renal function (through stabilization or improvement). Survival was adversely effected by renal dysfunction despite adequate revascularization. Perhaps early diagnosis of renal artery stenosis and adequate revascularization prior to the onset of renal dysfunction could beneficially impact blood pressure control, preserve or prevent deterioration of renal function, and improve patient survival.


Quantitative monitoring of single nucleotide mutations by allele-specific quantitative PCR can be used for the assessment of minimal residual disease in patients with hematological malignancies throughout their clinical course.
Monitoring of minimal residual disease (MRD) in patients with hematological malignancies is important for evaluating the patients' therapeutic response and risk of relapse. Single nucleotide mutations associated with leukemogenesis can be considered as applicable MRD markers. We developed an allele-specific quantitative polymerase chain reaction (AS-qPCR) for FLT3 2503G>T, KIT 2446G>T, and KIT 2447A>T and compared the change in the expression levels of the FLT3 or KIT mutations assessed by AS-qPCR to those of the RUNX1-RUNX1T1 fusion gene and WT1 by conventional quantitative PCR. The AS-qPCR using primers including template-mismatched nucleotide or template-mismatched nucleotide plus locked nucleic acid substituted nucleotide provided higher selectivity for mutant nucleotides. The change in the expression levels of the FLT3 or KIT mutations at the time of relapse and just after hematopoietic stem cell transplantation correlated well with that of the RUNX1-RUNX1T1 fusion gene and WT1. Moreover, during complete remission, only AS-qPCR could detect low-level expression of residual mutations. The AS-qPCR for analyzing single nucleotide mutations contributes to the monitoring of MRD in patients without recurrent fusion gene throughout the clinical course and thus broadens the spectrum of patients in whom MRD can be monitored.


The association between frailty and incident cardiovascular disease events in community-dwelling healthy older adults.
This study examined the association between frailty and incident cardiovascular disease (CVD) events, major adverse cardiovascular events (MACE), and CVD-related mortality. Longitudinal cohort study. The ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial in Australia and the United States. 19,114 community-dwelling older adults (median age 74.0 years; 56.4 % females). Pre-frailty and frailty were assessed using a modified Fried phenotype and a deficit accumulation Frailty Index (FI) at baseline. CVD was defined as a composite of CVD death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for heart failure; MACE included all except heart failure. Cox proportional hazards regression was used to analyze the association between frailty and CVD outcomes over a median follow-up of 4.7 years. Baseline pre-frail and frail groups had a higher risk of incident CVD events (Hazard Ratio (HR): 1.31; 95 % Confidence Interval (CI): 1.14-1.50 for pre-frail and HR: 1.63; 95 % CI: 1.15-2.32 for frail) and MACE (pre-frail HR: 1.26; 95 % CI: 1.08-1.47 and frail HR: 1.51; 95 % CI: 1.00-2.29) than non-frail participants according to Fried phenotype after adjusting for traditional CVD risk factors. Effect sizes were similar or larger when frailty was assessed with FI; similar results for men and women. Frailty increases the likelihood of developing CVD, including MACE, in community-dwelling older men and women without prior CVD events. Screening for frailty using Fried or FI method could help identify community-dwelling older adults without prior CVD events who are more likely to develop CVD, including MACE, and may facilitate targeted preventive measures to reduce their risk.


Integrated genome-centric metagenomic and metaproteomic analyses unravel the responses of the microbial community to ammonia stress.
Ammonia is a major inhibitor in anaerobic digestion of nitrogen-rich organic wastes. In this study, integrated genome-centric metagenomic and metaproteomic analyses were used to identify the key microorganisms and metabolic links causing instability by characterizing the process performance, microbial community, and metabolic responses of key microorganisms during endogenous ammonia accumulation. The identification of 89 metagenome-assembled genomes and analysis of their abundance profile in different operational phases permitted the identification of key taxa (Firmicutes and Proteobacteria) causing poor performance. Metabolic reconstruction indicated that the key taxa had the genetic potential to participate in the metabolism of C2C5 volatile fatty acids (VFAs). Further investigation suggested that during Phase I, the total ammonia nitrogen (TAN) level was maintained below 2000 mg N/L, and the reactor showed a high methane yield (478.30 ± 33.35 mL/g VS) and low VFAs concentration. When the TAN accumulated to > 2000 mg N/L, acid accumulation, mainly of acetate, began to occur, and the methane yield gradually decreased to 330.44 mL/g VS (Phase II). During this phase, the VFA degradation functions of the community were mainly mediated by Firmicutes. Approximately 61.54% of significant differentially expressed proteins (DEPs) related to acetate metabolism in Firmicutes were down-regulated, which led to an increase in acetate concentration to 4897.91 ± 1558.96 mg/L. However, the reactor performance showed spontaneous recovery without any interference (Phase III), during which Firmicutes gradually adapted to the high ammonia conditions. Approximately 75% of the significant DEPs related to acetate metabolism of Proteobacteria were also up-regulated in Phase III compared with Phase II; thus, VFA-related metabolic functions of the community were enhanced, which resulted in a decrease in the total VFA concentration to 195.39 mg/L. When the TAN increased above 4000 mg N/L, the system gradually showed acid accumulation dominated by propionate, accompanied by a second decrease in methane yield (Phase IV). During this phase, the number of up-regulated and down-regulated proteins related to acetate metabolism of Firmicutes and butyrate/valerate metabolism of Proteobacteria was comparable with that of Phase III, indicating that the metabolic functions related to acetate, butyrate, and valerate of the microbial community were not significantly affected. However, for propionate metabolism, the expression activity of fumarate hydratase from Firmicutes and Proteobacteria was severely inhibited by ammonia, as shown by down-regulation ratios of 63.64% and 85.71%, respectively. No protein with the same function that was not inhibited by ammonia could be detected, and the fumarate degradation function of the microbial community was severely damaged, leading to blocked propionate metabolism and irreversible deterioration of reactor performance. This study has provided a new perspective on the microecological mechanisms of ammonia inhibition.


A self-assemble aptamer fragment/target complex based high-throughput colorimetric aptasensor using enzyme linked aptamer assay.
Enzyme linked aptamer assay (ELAA) uses an aptamer as recognition element and enzyme as signal readout element for establishing different kinds of aptasensors. We reported herein a high-throughput colorimetric aptasensor based on ELAA only requiring a single aptamer sequence for cocaine detection. An anti-cocaine aptamer was cleaved into two fragments, one of which was immobilized on a DNA-BIND 96-well plate via 5'-labeled primary amine and the other one was biotin labeled. The presence of two aptamer fragments and the target molecule led to the formation of aptamer fragments/target complexes. Streptavidin-horseradish peroxidase (SA-HRP) was used to react with biotin in order to obtain quantitative signals. A linear response towards cocaine concentration in the range of 5-200 μM and a detection limit down to 2.8 μM (S/N=3) were achieved. The specificity and application in real sample were validated. Furthermore, a verification test of thrombin detection in the same strategy illustrated its feasibility for not only small molecule but also biomacromolecule. With the advantage of high-throughput, easy operation, high specificity, the colorimetric assay based on ELAA requiring a single aptamer sequence opens up a new approach for detecting different kinds of targets via specific affinity recognition among target and suitably cleaved aptamer fragments.


Transcatheter intra-arterial infusion of doxorubicin loaded porous magnetic nano-clusters with iodinated oil for the treatment of liver cancer.
A promising strategy for liver cancer treatment is to deliver chemotherapeutic agents with multifunctional carriers into the tumor tissue via intra-arterial (IA) transcatheter infusion. These carriers should release drugs within the target tissue for prolonged periods and permit intra-procedural multi-modal imaging of selective tumor delivery. This targeted transcatheter delivery approach is enabled via the arterial blood supply to liver tumors and utilized in current clinical practice which is called chemoembolization or radioembolization. During our study, we developed Doxorubicin (Dox) loaded porous magnetic nano-clusters (Dox-pMNCs). The porous structure and carboxylic groups on the MNCs achieved high-drug loading efficiency and sustained drug release, along with magnetic properties resulting in high MRI T2-weighted image contrast. Dox-pMNC within iodinated oil, Dox-pMNCs, and Dox within iodinated oil were infused via hepatic arteries to target liver tumors in a rabbit model. MRI and histological evaluations revealed that the long-term drug release and retention of Dox-pMNCs within iodinated oil induced significantly enhanced liver cancer cell death.


Automated method for the determination of total arsenic and selenium in natural and drinking water by HG-AAS.
A multicommutated flow system was designed and evaluated for the determination of total arsenic and selenium by Hydride Generation Atomic Absorption Spectrometry (HG-AAS). It was applied to the determination of arsenic and selenium in samples of natural and drinking water. Detection limits were 0.46 and 0.08 μg l(-1) for arsenic and selenium, respectively; sampling frequency was 120 samples h(-1) for arsenic and 160 samples h(-1) for selenium. Linear ranges found were 1.54-10 μg l(-1) (R = 0.999) for arsenic and 0.27-27 μg l(-1) (R = 0.999) for selenium. Accuracy was evaluated by spiking various water samples and using a reference material. Recoveries were in the range 95-116%. Analytical precision (s ( r ) (%), n = 10) was 6% for both elements. Compared with the Standard Methods, APHA, 3114B manual method, the system consumes at least 10 times less sample per determination, and the quantities of acid and reducing agent used are significantly lower with a reduction in the generation of pollutants and waste. As an additional advantage, the system is very fast, efficient and environmentally friendly for monitoring total arsenic and selenium levels in waters.