Mechanistic Pathways in Amide Activation: Flexible Synthesis of Oxazoles and Imidazoles.
The preparation of substituted aminooxazoles and aminoimidazoles from α-arylamides and α-aminoamides through triflic anhydride-mediated amide activation is reported. These reactions proceed via the intermediacy of nitrilium adducts and feature N-oxide-promoted umpolung of the α-position of amides as well as a mechanistically intriguing sequence that results in sulfonyl migration from nitrogen to carbon. Quantum-chemical mechanistic analysis sheds light on the intricacies of the process.


Fluorophore-NanoLuc BRET Reporters Enable Sensitive In Vivo Optical Imaging and Flow Cytometry for Monitoring Tumorigenesis.
Fluorescent proteins are widely used to study molecular and cellular events, yet this traditionally relies on delivery of excitation light, which can trigger autofluorescence, photoxicity, and photobleaching, impairing their use in vivo. Accordingly, chemiluminescent light sources such as those generated by luciferases have emerged, as they do not require excitation light. However, current luciferase reporters lack the brightness needed to visualize events in deep tissues. We report the creation of chimeric eGFP-NanoLuc (GpNLuc) and LSSmOrange-NanoLuc (OgNLuc) fusion reporter proteins coined LumiFluors, which combine the benefits of eGFP or LSSmOrange fluorescent proteins with the bright, glow-type bioluminescent light generated by an enhanced small luciferase subunit (NanoLuc) of the deep-sea shrimp Oplophorus gracilirostris. The intramolecular bioluminescence resonance energy transfer that occurs between NanoLuc and the fused fluorophore generates the brightest bioluminescent signal known to date, including improved intensity, sensitivity, and durable spectral properties, thereby dramatically reducing image acquisition times and permitting highly sensitive in vivo imaging. Notably, the self-illuminating and bifunctional nature of these LumiFluor reporters enables greatly improved spatiotemporal monitoring of very small numbers of tumor cells via in vivo optical imaging and also allows the isolation and analyses of single cells by flow cytometry. Thus, LumiFluor reporters are inexpensive, robust, noninvasive tools that allow for markedly improved in vivo optical imaging of tumorigenic processes.


Transmitting false memories in social groups.
In 2 experiments, subjects studied word lists drawn from Roediger and McDermott (1995) and then participated in perceived group recall (PGR) tests that were intended to lead each subject to believe that she or he was participating in collaborative recall in a 4-person group. Some of the lists were followed by PGR tests containing the nonpresented critical word, some lists were followed by PGR tests not containing the nonpresented critical word, and some lists were not followed by PGR tests. Subjects then completed individually administered recall tests and subsequent immediate or delayed recognition tests that required remember or know judgments. The major finding was that critical words contained within PGR tests were as likely to be falsely recalled, recognized, and consciously remembered as original list items. These findings show that false memories can be socially transmitted.


New Surface Modification Method To Develop a PET-Based Membrane with Enhanced Ion Permeability and Organic Fouling Resistance for Efficient Production of Marine Microalgae.
This paper presents a new surface modification strategy to develop a poly(ethylene terephthalate) (PET)-based membrane having a hydrophilic surface, high nutrient ion permeability, sufficient mechanical strength, and organic fouling resistance, using an anthracene (ANT)-attached polyethylene glycol (PEG) surface modification agent (SMA) synthesized in this work. During the modification process, the ANT parts of the SMAs poke through and anchor to the surface of a commercial PET woven fabric via physical interactions and mechanical locking. The PEG chain parts coat the surface in the brush and arch forms, which generates a hydration layer on the fabric surface. The consequently obtained surface property and unique structure of the modified PET-based membrane result in higher nitrate ion permeability, organic fouling resistance, and microalgae production compared to those of the unmodified one. These are also affected by the molecular weight of the PEG and the number density of the anchored SMAs. The study demonstrates that this new surface modification method has the potential to allow the development of a desirable PET-based membrane for the efficient massive production of marine microalgae.


Improvement of muscle strength in familial hypokalaemic periodic paralysis with acetazolamide.
A double blind cross-over study of eight patients with familial hypokalaemic periodic paralysis was made to assess the influence of acetazolamide on muscle strength. All patients had a reduced interictal muscle fibre conduction velocity. Five patients had no attacks at the time of the study. One patient withdrew from the study because of an adverse reaction. The muscle strength of 11 muscle groups was measured with a hand-held dynamometer. The sum of force improved significantly in the seven patients (mean increase: 17%, p less than 0.05; 95% confidence interval: 7.2-26.8%). Endurance tests showed an improvement in the performance of 30 full kneebends. Surface EMG measurement showed no change in the muscle fibre conduction velocity or power spectra during treatment. The integrated EMG showed a (non significant) mean increase of 21%.


Ultrasonographic Validation of Anatomical Landmarks for Localization of the Tendon of the Long Head of Biceps Brachii.
Objectives. To establish anatomical landmarks for biceps tendon groove localization based on intrinsic anatomical relations and to validate the localization with ultrasonographic measurement. Design. Perspective, observational, single-blinded pilot study. Participants. 25 healthy male and female volunteers ages 24-50 years. Methods. We used two anatomical landmarks, the medial epicondyle vertical line related landmark and the coracoid process landmark. The distance from the groove skin mark to the medial epicondyle vertical line and the coracoid process was measured horizontally and was measured at 0° and 45° of shoulder external rotation, respectively. Results. Medial epicondyle vertical lines were 9.3 mm/21.5 mm medial to the groove at 0°/45° of shoulder external rotation, respectively. Correlation coefficients were 0.04/0.10, 0.32/0.42, and 0.26/0.37 for weight, height, and BMI in 0°/45° of shoulder external rotation, respectively. The distance between the coracoid process and the groove was 44.0 mm/62.2 mm in 0°/45° of shoulder external rotation, respectively. Correlation coefficients were 0.36/0.41, 0.36/0.54, and 0.18/0.12 for weight, height, and BMI in 0°/45° of shoulder external rotation, respectively. Conclusions. The medial epicondyle vertical line and the coracoid process landmark are both useful anatomical landmarks to localize the biceps groove. The anatomical landmark based localization is essentially not correlated with subject's weight, height, or BMI.


An Injectable Hydrogel for Treatment of Chronic Neuropathic Pain.
Current treatments for chronic neuropathic pain often fall short. A small-molecular compound ZL006 can suppress N-Methyl-d-aspartate receptor (NMDAR)-mediated neuropathic pain behaviors without blocking essential NMDAR function and brings new hope for neuropathic pain therapy. The persistent nature of neuropathic pain mandates the long-term treatment. However, similar to existing analgesics, ZL006 has only a short duration of action. To unleash the therapeutic potential of ZL006, the stability of ZL006 in aqueous solutions is investigated, and a ZL006-incorporated P407-based thermoresponsive injectable hydrogel is developed. The computational analysis is performed to help achieve the desired ZL006-loaded hydrogel system and elucidate the gelation mechanism. The hydrogel matrix can be loaded with ZL006 in an aqueous phase at room temperature without costly specialized equipment and no organic solvent, where the sol is formed and injectable. On subcutaneous administration and subsequent rapid warming to physiological temperature, the sol is converted to a gel. The thermoresponsive hydrogel at body temperature enables the extended release of encapsulated ZL006, and therefore a single subcutaneous injection of ZL006-hydrogel produces a prolonged and stable analgesic action in mice with spinal nerve ligation. The study provides a practical chronic neuropathic pain therapy and a new perspective on future applications of ZL006.


The Central Role of IFI204 in IFN-β Release and Autophagy Activation during Mycobacterium bovis Infection.
Mycobacterium bovis (M. bovis) is the pathogen of animals and humans that can replicate in the phagosomes of myeloid cells. Cytosolic detection of bacterial products plays a crucial role in initiating the innate immune response, including autophagy activation and interferon-β (IFN-β) release. Although IFN-β release and autophagy activation have been reported during mycobacterium infection, the mechanisms underlying remains poorly defined. Here, we demonstrated that IFN-β release increases in macrophages exposed to M. bovis and this requires the activation of the DNA sensor of interferon-γ inducible protein 204 (IFI204). Knockdown of the IFI204 in immortalized and primary murine macrophages blocked IFN-β production and autophagy marker LC3 expression. Thus, our results indicate that the IFI204 is an important sensor for innate immune responses of M. bovis infection.


Constructing Two-Dimensional Distorted Kagome Lattices on Ag(111).
Two-dimensional (2D) tessellation of organic species acquired increased interest recently because of their potential applications in physics, biology, and chemistry. Herein, we successfully synthesized the chiral distorted Kagome lattice p3 (333) with bicomponent precursors on Ag(111). Scanning tunneling microscopy and density functional calculation studies reveal that the networks are formed by multiple intermolecular hydrogen bonds. The network structures can be rationally tuned by adjusting the stoichiometric ratio of the reaction precursors. Our study provides new strategies to synthesize complex low-dimensional nanostructures on metal surfaces.


Treating diabetes: cardiovascular benefits of antidiabetes drugs.
Type 2 diabetes is a metabolic disorder that, if untreated, can result in macrovascular and microvascular complications. Lowering blood glucose levels primarily reduces microvascular risk; other treatment strategies are necessary to lower the risk for macrovascular disease. Because most patients with diabetes die of macrovascular disease, it is vitally important that patients with diabetes receive aggressive therapies to lessen this risk. It has been found that the risk for macrovascular complications begins even earlier than the risk for microvascular complications. Therefore, patients with insulin resistance (now called prediabetes) should be identified and treated to lower their risk of cardiovascular disease and reduce their risk for progression to diabetes. Two cases are reviewed--a patient with prediabetes and the metabolic syndrome, and a second patient with type 2 diabetes and advanced cardiovascular disease. A review of potential cardiovascular therapies is included.


The evaluation of the outcome in myelodysplastic patients by using non-cytogenetic prognostic scores.
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders; they are characterized by ineffective hematopoiesis and a predilection to the development of acute myeloid leukemia (AML). For a rapid evaluation of the outcome in myelodysplastic patients non-cytogenetic prognostic scores can be used. This study proposed to demonstrate that age and gender are important factors in the outcome of the patients diagnosed with myelodysplastic syndrome. This study was conducted in the Department of Hematology of the Emergency University Hospital Bucharest during October 2008 and October 2012. Male sex and age higher than 60 years are associated with high risk in the studied cases by using the Spanish prognostic score. According to Goasguen score: male sex and age, patients older than 60 years, present characteristics associated with an intermediate risk. Based on the Dusseldorf score, age over 60 years and female gender were associated with pronounced risk in the examined group. By examining the Bournemouth score in our group, we found that age > 60 years correlated with a higher frequency of risk, but no significant differences regarding the sex of patients were observed. We concluded that age > 60 years and male gender are important predisposing factors in the survival.


Evaluation of Axilla With Sentinel Lymph Node Biopsy (Using Methylene-Blue) and Reverse Axillary Mapping (Using Fluorescein) to Validate Optimum and Safe Axillary Dissection in Breast Cancer.
Introduction Sentinel lymph node biopsy (SLNB) has replaced routine axillary lymph node dissection (ALND) in node-negative axillae. In cases where the axilla needs to be dissected, one must dissect below the uppermost intercostobrachial nerve (ICBN) to avoid damaging arm lymphatics. Methods One milliliter of methylene blue dye was injected around the areola. Fluorescein dye (1 ml) was injected into the upper arm. After SLNB and ALND, the axilla was visualized under blue light. The location of fluorescent lymphatics was mapped with respect to the uppermost ICBN. Results The identification rate of sentinel lymph nodes and arm lymphatics was 100%. Arm lymphatics were above ICBN in 86.7%. The false negative rate of SLNB was 13%, with sensitivity and specificity of 87% and 100%, respectively. Conclusions SLNB using the single-dye technique has results comparable to dual agent studies that utilize blue dye and radioactive colloid. The uppermost ICBN could define the superior limit of axillary dissection.


Lung vital capacity and oxygen saturation in adults with cerebral palsy.
Individuals with infantile cerebral palsy have multiple disabilities. The most conspicuous syndrome being investigated from many aspects is motor movement disorder with a spastic gait pattern. The lung function of adults with spasticity attracts less attention in the literature. This is surprising because decreased thoracic mobility and longstanding scoliosis should have an impact on lung function. With increasing age and the level of disability, individuals become susceptible to lung infections and reflux illness, and these are accompanied by increased aspiration risk. This study examined, with different methods, to what extent adults with congenital cerebral palsy and acquired spastic paresis - following traumatic brain injury - showed restriction of lung function. It also assessed the contribution of disability level on this restriction. The oxygen saturation of 46 adults with a diagnosis of cerebral palsy was measured with an oximeter. Lung vital capacity was measured with a mobile spirometer and excursion of the thorax was clinically registered. The gross motor function levels and the presence or absence of scoliosis were determined. A significantly positive correlation between lung vital capacity and chest expansion was established. Both the lung vital capacity and the thorax excursion decreased with increases in gross motor function level. Oxygen saturation remained within the normal range in all persons, in spite of reduced values of the measured lung parameters. No statistically significant dependency between lung vital capacity and oxygen saturation, and between chest expansion and oxygen saturation was found. The scoliotic deformities of the spine were associated with an additional decrease in the vital capacity, but this did not affect blood oxygen supply. Despite the decreased chest expansion and the significantly reduced lung volume in adults with cerebral palsy, sufficient oxygen supply was registered.


When Core Self-Evaluation Leads to Career Adaptability: Effects of Ethical Leadership and Implications for Citizenship Behavior.
Drawing upon the career construction theory and the trait activation theory, the present study first aims to uncover the interactive effect of core self-evaluation (CSE) and ethical leadership on career adaptability. In addition, the authors examined how career adaptability mediates the interaction effect of CSE and ethical leadership on organizational citizenship behavior (OCB). Two-wave data from 156 employees were collected in a manufacturing company over a one-month interval. Results showed that ethical leadership moderated the relationship between CSE and career adaptability. Specifically, the positive relationship between CSE and career adaptability was stronger when ethical leadership was low. Moreover, career adaptability mediated the relationship between CSE and OCB, and ethical leadership moderated this indirect relationship. We discuss implications for career adaptation and organizational effectiveness.


Influence of Ca2+ cations on low pH-induced DNA structural transitions.
A confocal Raman microspectrometer was used to investigate the influence of Ca2+ cations on low pH-induced DNA structural changes. The effects of Ca2+ cations on the protonation mechanism of opening AT and changing the protonation of GC base pairs in DNA are discussed. Based on the observation that the midpoint of the transition of Watson-Crick GC base pairs to protonated GC base pairs lies at around pH 3 (analyzing the 681 cm(-1) line), measurements were carried out on calf thymus DNA at neutral pH and pH 3 in the presence of low and high concentrations of Ca2+ cations. Raman spectra show that low concentrations of Ca2+ cations partially protect DNA against protonation of cytosine (characteristic line at 1262 cm(-1)) and do not protect adenine (characteristic line at 1304 cm(-1)) and the N(7) of guanine (line at 1488 cm(-1)) against binding of H+. High Ca2+ concentrations can prevent protonation of cytosine and protonation of adenine (little disruption of AT pairs). Analyzing the line at 1488 cm(-1), which obtains most of its intensity from a guanine vibration, high salt was also found to protect the N(7) of guanine against protonation.


Contemporary Outcomes of Pulmonary Valve Endocarditis: A 16-Year Single Centre Experience.
Limited data exist regarding the clinical characteristics and contemporary outcomes of patients with pulmonary valve (PoV) infective endocarditis (IE). This is a retrospective cohort study of patients with a confirmed diagnosis of IE affecting the PoV at our centre between January 2002 and October 2018. Electronic medical records were reviewed to gather the clinical and echocardiographic variables. The population was subdivided according to risk factor profiles: group 1: miscellaneous risk factors; group 2: patients with congenital heart disease (CHD); and group 3: patients who inject drugs (PWID). The primary outcome was all-cause mortality. Out of 2,124 cases of IE during the study period, 24 (1.1%) patients had PoV IE. The majority of cases of PoV IE occurred in patients with prosthetic valves (54.2%). Coagulase-negative Staphylococci species were the most common micro-organisms. Seventy-five per cent (75%) of the patients required surgical management. The median follow-up was 2.8 years (interquartile range: 0.2-5.3 years). Patients with miscellaneous risk factors were older (p<0.01), and had higher rates of hypertension (p=0.01) and hyperlipidaemia (p=0.04). There was a statistically significant difference in survival between the groups (p=0.03), mainly driven by better outcomes of patients with CHD, compared to those with miscellaneous risk factors. In a contemporary 16-year series, a high proportion of patients with PoV IE required surgical management. Patients with PoV IE and CHD had better survival, compared to patients with miscellaneous risk factors at a median follow-up of 2.8 years.


Imaging of Brain Structural and Functional Effects in People With Human Immunodeficiency Virus.
Before the introduction of antiretroviral therapy, human immunodeficiency virus (HIV) infection was often accompanied by central nervous system (CNS) opportunistic infections and HIV encephalopathy marked by profound structural and functional alterations detectable with neuroimaging. Treatment with antiretroviral therapy nearly eliminated CNS opportunistic infections, while neuropsychiatric impairment and peripheral nerve and organ damage have persisted among virally suppressed people with HIV (PWH), suggesting ongoing brain injury. Neuroimaging research must use methods sensitive for detecting subtle HIV-associated brain structural and functional abnormalities, while allowing for adjustments for potential confounders, such as age, sex, substance use, hepatitis C coinfection, cardiovascular risk, and others. Here, we review existing and emerging neuroimaging tools that demonstrated promise in detecting markers of HIV-associated brain pathology and explore strategies to study the impact of potential confounding factors on these brain measures. We emphasize neuroimaging approaches that may be used in parallel to gather complementary information, allowing efficient detection and interpretation of altered brain structure and function associated with suboptimal clinical outcomes among virally suppressed PWH. We examine the advantages of each imaging modality and systematic approaches in study design and analysis. We also consider advantages of combining experimental and statistical control techniques to improve sensitivity and specificity of biotype identification and explore the costs and benefits of aggregating data from multiple studies to achieve larger sample sizes, enabling use of emerging methods for combining and analyzing large, multifaceted data sets. Many of the topics addressed in this article were discussed at the National Institute of Mental Health meeting "Biotypes of CNS Complications in People Living with HIV," held in October 2021, and are part of ongoing research initiatives to define the role of neuroimaging in emerging alternative approaches to identifying biotypes of CNS complications in PWH. An outcome of these considerations may be the development of a common neuroimaging protocol available for researchers to use in future studies examining neurological changes in the brains of PWH.


Vincristine, Irinotecan, and Temozolomide in Patients With Relapsed/Refractory Neuroblastoma.
The combination of irinotecan, temozolomide and vincristine has been proposed as an effective salvage regimen for some pediatric malignancies. Thus, we sought to evaluate this combination for patients with relapsed and refractory neuroblastoma (NB). In this retrospective study, forty-six patients with relapsed or refractory NB were treated with the combination of vincristine (1.5 mg/m2 i.v. day 1), irinotecan (50 mg/m2/day i.v. days 1-5) and temozolomide (100 mg/m2/day p.o. days 1-5) (VIT) during the period 2011-2019. All toxicities were documented. A total of 251 cycles (median 6 cycles/patient) were administered. A complete response (CR) was achieved in 5 patients, partial response (PR) in 27 patients, stable disease (SD) in 8 patients, and progression disease (PD) in 6 patients, with an overall objective response rate (CR+PR) of 69.6%. Eighteen patients developed diarrhea with Grade 3 or less. Grade 1-2 hematologic toxicity occurred in 10 patients. Grade 3-4 hematologic toxicity developed in 32 patients. VIT was an effective regimen for different metastatic sites. UGT1A*28 genotyping performed in 7 patients revealed wild type. Diarrhea occurred in 4 of them. The shorter, 5-day VIT regimen is an active and well-tolerated salvage regimen in relapse/refractory NB.


Contrast enhanced endoscopic ultrasound: More than just a fancy Doppler.
Contrast enhanced endoscopic ultrasound (CEUS) is a new modality that takes advantage of vascular structure and blood flow to distinguish different clinical entities. Contrast agents are microbubbles that oscillate when exposed to ultrasonographic waves resulting in characteristic acoustic signals that are then converted to colour images. This permits exquisite imaging of macro- and microvasculature, providing information to help delineate malignant from non-malignant processes. The use of CEUS may significantly increase the sensitivity and specificity over conventional endoscopic ultrasound. Currently available contrast agents are safe, with infrequent adverse effects. This review summarizes the theory and technique behind CEUS and the current and future clinical applications.


[Development of a psychoanalytic memory theory].
A theory of memory for biographical material is proposed. This theory consists in the following central assumptions: a symbol formation process, which on the one hand maps affectively experienced object relations into inner propositions (representations) and on the other hand transforms representations into communicable symbols; repression which may affect representations and which thus establishes an unconsciousness which is rooted in object relations; defense mechanisms, which are part of the symbol formation process and which transform unconscious representations into conscious but distorted symbols. This theory is supposed to explain remembering, distorted remembering, and phenomena of compulsive repetition.


Irradiated Graphene Loaded with SnO₂ Quantum Dots for Energy Storage.
Tin dioxide (SnO2) and graphene are unique strategic functional materials with widespread technological applications, particularly in the areas of solar batteries, optoelectronic devices, and solid-state gas sensors owing to advances in optical and electronic properties. Versatile strategies for microstructural evolution and related performance of SnO2 and graphene composites are of fundamental importance in the development of electrode materials. Here we report that a novel composite, SnO2 quantum dots (QDs) supported by graphene nanosheets (GNSs), has been prepared successfully by a simple hydrothermal method and electron-beam irradiation (EBI) strategies. Microstructure analysis indicates that the EBI technique can induce the exfoliation of GNSs and increase their interlayer spacing, resulting in the increase of GNS amorphization, disorder, and defects and the removal of partial oxygen-containing functional groups on the surface of GNSs. The investigation of SnO2 nanoparticles supported by GNSs (SnO2/GNSs) reveals that the GNSs are loaded with SnO2 QDs, which are dispersed uniformly on both sides of GNSs. Interestingly, the electrochemical performance of SnO2/GNSs indicates that SnO2 QDs supported by a 210 kGy irradiated GNS shows excellent cycle response, high specific capacity, and high reversible capacity. This novel SnO2/GNS composite has potential practical applications in SnO2 electrode materials during Li(+) insertion/extraction.


Personal-protection measures against mosquitoes: a study of practices and costs in a district, in the Indian state of Orissa, where malaria and lymphatic filariasis are co-endemic.
In a study undertaken among rural and urban communities in a district of Orissa, India, the personal-protection measures used against mosquitoes, and the household costs of these measures, were investigated. Most people living in the study communities perceived mosquitoes as a problem, both as a biting nuisance and as vectors of human disease. Almost all (99%) of the urban households investigated and most (84%) of the rural each reported the use of at least one measure against mosquitoes. Most of the study households (92% of the urban and 64% of the rural) used a 'modern' chemical method (coils, vaporizing mats, liquid vaporizers or sprays), with mosquito coils used more frequently than any other personal-protection measure. Untreated bednets were also used by most of the households investigated (76% of the urban and 58% of the rural) and some households (about 10% of the urban and 8% of the rural) still used the more traditional method of burning dried dung or vegetation indoors, specifically to create smoke to drive away mosquitoes. Setting, house type, as indicated by the material used as roofing, and number of people in the household were each a significant predictor of the use of personal protection, with households in an urban setting, large households, and households occupying a concrete-roofed building relatively more likely to use some form of personal protection. Although 'modern', chemical-based methods were frequently employed, about one in every two interviewees (57% of the urban and 43% of the rural) considered the use of such methods to be harmful to their health. The mean monthly expenditures on personal-protection measures were 101 Indian rupees (U.S.$2.20)/urban household and 72 Indian rupees (U.S.$1.60)/rural household. Setting, family income, family size and number of sleeping rooms in the house each affected such expenditure significantly. As a proportion of household income, expenditure on controlling mosquitoes was surprisingly high.


Anomalous origin of the right coronary artery from the left coronary sinus: case report and literature review.
A 41-year-old man with no relevant cardiac history presented for evaluation of episodic syncope. Electrocardiography showed sinus rhythm with right bundle-branch block and Q waves in leads II, III, and aVF. Subsequent exercise treadmill testing and technetium 99m sestamibi study revealed a reversible posterior defect. Coronary angiography later showed a right coronary artery that arose from the left coronary sinus--an anomaly that has been associated with angina, myocardial infarction, and sudden cardiac death. After being informed of the potential risks and options associated with this anomaly, the patient chose long-term beta-blocker medical therapy. At follow-up, this treatment appeared to have resolved his episodic syncope.


Enhanced growth of neural networks on conductive cellulose-derived nanofibrous scaffolds.
The problem of recovery from neurodegeneration needs new effective solutions. Tissue engineering is viewed as a prospective approach for solving this problem since it can help to develop healthy neural tissue using supportive scaffolds. This study presents effective and sustainable tissue engineering methods for creating biomaterials from cellulose that can be used either as scaffolds for the growth of neural tissue in vitro or as drug screening models. To reach this goal, nanofibrous electrospun cellulose mats were made conductive via two different procedures: carbonization and addition of multi-walled carbon nanotubes. The resulting scaffolds were much more conductive than untreated cellulose material and were used to support growth and differentiation of SH-SY5Y neuroblastoma cells. The cells were evaluated by scanning electron microscopy and confocal microscopy methods over a period of 15 days at different time points. The results showed that the cellulose-derived conductive scaffolds can provide support for good cell attachment, growth and differentiation. The formation of a neural network occurred within 10 days of differentiation, which is a promising length of time for SH-SY5Y neuroblastoma cells.


[Genotype-phenotype correlations in multiple endocrine neoplasia type 2].
To evaluate the relationship between different RET mutations and the aggressiveness of hereditary medullary thyroid cancer (HMTC) or the presentation of other endocrine disorders in patients with multiple endocrine neoplasia type 2 (MEN2). A total of 73 thyroid medullary carcinoma patients from 22 Chinese kindreds who were treated in our center from 2010 to 2015 were enrolled. RET genes in the patients and their relatives were screened. According to the clinical data and 2015 American Thyroid Association (ATA) guidelines, patients were classified into 3 RET mutation risk groups: Modest, 24 cases; High, 48 cases; and Highest, 1 case. Multivariate analysis showed an increased likelihood of MTC stage III or IV at diagnosis with increasing of age and risk. The likelihood increased 11.6% per year of age at surgery (95% confidence interval, 1.040-1.198; P=0.002). The likelihood in patients with high risk was 7.9 times higher than patients with modest risk (95% confidence interval, 1.607-38.717; P=0.003). Aside from one patient with MEN2B, other 72 patients were MEN2A, of them, 28 cases from 7 kindreds with classical MEN2A (codon 634 & 618), 14 cases from 3 kindreds with cutaneous lichen amyloidosis (codon 634), 4 cases from 1 kindred with Hirschsprung's disease (codon 620), and 26 cases from 10 kindreds with familial MTC. The aggressiveness of HMTC and the presentation of other endocrine diseases are related to specific RET mutations. For RET mutation carriers, MTC and other endocrine diseases should be diagnosed and treated early based on the RET genotypes.


Maximizing utility of nondirected living liver donor grafts using machine learning.
There is an unmet need for optimizing hepatic allograft allocation from nondirected living liver donors (ND-LLD). Using OPTN living donor liver transplant (LDLT) data (1/1/2000-12/31/2019), we identified 6328 LDLTs (4621 right, 644 left, 1063 left-lateral grafts). Random forest survival models were constructed to predict 10-year graft survival for each of the 3 graft types. Donor-to-recipient body surface area ratio was an important predictor in all 3 models. Other predictors in all 3 models were: malignant diagnosis, medical location at LDLT (inpatient/ICU), and moderate ascites. Biliary atresia was important in left and left-lateral graft models. Re-transplant was important in right graft models. C-index for 10-year graft survival predictions for the 3 models were: 0.70 (left-lateral); 0.63 (left); 0.61 (right). Similar C-indices were found for 1-, 3-, and 5-year graft survivals. Comparison of model predictions to actual 10-year graft survivals demonstrated that the predicted upper quartile survival group in each model had significantly better actual 10-year graft survival compared to the lower quartiles (p<0.005). When applied in clinical context, our models assist with the identification and stratification of potential recipients for hepatic grafts from ND-LLD based on predicted graft survivals, while accounting for complex donor-recipient interactions. These analyses highlight the unmet need for granular data collection and machine learning modeling to identify potential recipients who have the best predicted transplant outcomes with ND-LLD grafts.


A plasmid cassette system that allows optimization of primers for use in the amplification refractory mutation system.
A plasmid "cassette" system is presented that allows the development of amplification refractory mutation system (ARMS) primers. Primer development may be accomplished even in the absence of appropriate clinical material from patients demonstrating mutated alleles. The use of such cassettes is demonstrated here in the assessment of primers prepared for ARMS analysis of the gene coding for the normal and Z variant alleles of the human serine protease inhibitor alpha-1-antitrypsin.


Reactive cavity optical force on microdisk-coupled nanomechanical beam waveguides.
We demonstrate spectrally tuned dispersive and reactive optical force in a cavity optomechanics system that comprises a microdisk and a vibrating nanomechanical beam waveguide. The waveguide coupled to the microdisk acts as a bosonic dissipation channel and its motion modulates the cavity's damping rate. As a result a reactive optical force arises in addition to the normal dispersive force. The cavity enhanced force is not observed at zero detuning but shows asymmetric behavior with a maximum at red-detuned offset. Such reactive cavity backaction force points to new avenues in cavity optomechanics.


Enhanced efficacy with reduced toxicity of tripterygium glycoside tablet by compatibility with total glucosides of paeony for rheumatoid arthritis therapy.
Drug-induced liver injury remains a critical issue to hinder clinical application of Tripterygium Glycosides Tablets (TGTs) for rheumatoid arthritis (RA) therapy. Combination of TGTs with Total Glucosides of Peony (TGP) may be the most common therapeutic strategy for enhancing TGTs' efficacy and reducing its toxicity. Herein, we aimed to investigate the efficacy-enhancing and toxicity-reducing properties and mechanisms of TGT-TGP combination. Both TGT-induced acute and chronic liver injury animal models were established. ELISA, transmission electron microscopy, immunohistochemistry, western blot and quantitative PCR were performed to determine the efficacy, toxicity and regulatory mechanisms of TGT-TGP combination. The compatibility of TGP significantly reduced the abnormal serum ALT and AST levels, and improved liver histopathological changes in both acute and chronic DILI animal models induced by TGTs, with the most effective dosage of TGP-M (medium-dose TGP, 450 mg/kg). Additionally, TGP and TGT synergistically alleviated joint swelling and improved the elevation of serum inflammatory factors, in line with the positive changes in joint histopathological features of collagen induced arthritis mice, with the same effective dosage of TGP-M following 5 weeks' drug combination treatment. Mechanically, TGT significantly increased the number of autophagosomes and the expression of LC3II protein while reducing p62 protein expression in the liver tissues, which were significantly reversed by the compatibility with TGP, similar to the findings based on the inflamed joint tissues. These findings suggest an enhanced efficacy with reduced toxicity of TGT by the compatibility with TGP for RA therapy, possibly through regulating various autophagy-related proteins.


Pediatric pancreatic hemangioma: a case report and literature review.
The pancreas is an unusual site for a hemangioma in an infant. A child with obstructive jaundice caused by a pancreatic hemangioma is presented and management strategies for this benign tumor are discussed. A 5-month-old girl presented with a 2-week history of jaundice, pale stools and dark urine. Liver function tests confirmed obstructive jaundice. An abdominal ultrasound scan and magnetic resonance imaging showed an enhancing mass in the head of the pancreas. At laparotomy, a wedge biopsy of the pancreatic tumor was taken and a tube cholecystostomy inserted. Histological examination of the specimen revealed a pancreatic hemangioma with sclerotic features. The high volume of bile loss from the cholecystostomy proved problematic and biliary diversion with a Roux-en-y hepaticojejunostomy was therefore performed. The tumor subsequently regressed spontaneously and was no longer visible on follow-up imaging two years later. The child has since thrived. Pancreatic hemangiomas are rare and may cause diagnostic confusion. Pancreatic resection should be avoided since the natural history of these benign tumors is that of spontaneous involution. Various strategies can be used to manage any associated obstructive jaundice.


The Role of Caregivers in the Management of Alzheimer's disease: Examples from Asian Countries.
The demographic profile of the Asian population is rapidly changing, with a fast increasing ageing population, owing to an increase in longevity and a decreasing birth rate. Moreover, due to improved medical facilities and the increased aged population, Alzheimer's disease (AD) is fast emerging as a major health problem in many Asian countries. As curative treatment for AD is still elusive, care giving is an important component of the management of AD. While Western countries have recognised this issue, besides highly industrialized Japan, the Asian initiative has been relatively slow. This article aims to address issues involved in caregiving in AD in some Asian countries.


Risk and maintenance factors for young women's DSM-5 eating disorders.
Recent research with young women attending colleges, who are at the average age of eating disorder (ED) onset, established that the ED symptoms are not only prevalent but also relatively stable over the college period. Nonetheless, our knowledge regarding the course and modifiable factors associated with both the onset and maintenance of diagnosable (DSM-5) EDs in this population is limited. The objective of this report was to address these key research gaps. Data were examined from 2713 women who completed assessments of potential vulnerability factors and EDs in the autumn semester of the first (baseline) and fourth (follow-up) college years. A total of 13.1% of the sample met DSM-5 criteria for an ED diagnosis at baseline. At 4-year follow-up, 7.6% of the sample met DSM-5 criteria for an ED, with 67.5% of these cases representing women who had maintained an ED diagnosis from baseline, and 32.5% representing new onset EDs. Elevated appearance-ideal internalization, body dissatisfaction, self-objectification, dieting, and negative affectivity at baseline as well as changes in these factors between assessments all predicted onset and maintenance of DSM-5 EDs at 4-year follow-up. Self-objectification (thinking about and monitoring the body's appearance from an external observer's perspective) was the largest contributor to both ED onset and maintenance. In addition to enhancing our knowledge about the course of young women's (DSM-5) EDs during college, this work highlights potentially similar psychological foci for prevention and treatment efforts. Implications for improving existing preventive and treatment approaches are outlined.


Development of polyetherurethane sheet embedded with powdered charcoal for use in hemoperfusion.
This article describes the development of a polyetherurethane sheet embedded with powdered charcoal ( UPC ) for use in a hemoperfusion system. The UPC was 200 micron thick and the release of microparticles could be limited. The powdered charcoal used was selected for optimum pore size distribution and particle size (10-40 micron) to provide a maximum adsorption of bilirubin. The results of an in vitro adsorption test with this material showed an adsorption of bilirubin approximately 14 and 6 times higher than those by bead-type charcoal and XAD-7, respectively. Jaundiced dogs were subjected to direct hemoperfusion through a UPC column containing 36 g powdered charcoal. Effective decreases in bilirubin were observed, giving the maximum removal amounts of 78% in conjugated bilirubin and 76% in unconjugated bilirubin.


Modulation of lymphocyte motility by beta-endorphin and met-enkephalin.
The opioid peptides, beta-endorphin and met-enkephalin, have been shown to affect the immune system, resulting in either enhancement or suppression of immune response. However, the mechanism of the immunomodulatory effects and the immune cells that are affected by the opioid peptides are unclear. Early studies have provided evidence for their influence on granulocytes, monocytes and lymphocytes. In this study, the effect of beta-endorphin and met-enkephalin on the motility of lymphocyte subpopulations was examined. beta-Endorphin, depending on the concentration tested, has only slight enhancing or inhibitory effect on the motility of spleen lymphocytes; interestingly, met-enkephalin inhibited their motility. However, both beta-endorphin and met-enkephalin have a similar effect on the motility of separated spleen T and B lymphocytes, in that the motility of B lymphocytes was enhanced by both opioid peptides whereas the motility of T lymphocytes was inhibited. In contrast to the inhibitory effect of beta-endorphin and met-enkephalin on mature spleen T lymphocytes, the motility of thymocytes was enhanced by both opioid peptides. The results from this study suggest that the interaction of beta-endorphin and met-enkephalin with lymphocytes is complex and intricate.


Aquaporin 4 in Astrocytes is a Target for Therapy in Alzheimer's Disease.
Current experimental evidence points to the conclusion that aquaporin 4 (AQP4), which is an important water-channel membrane protein found in the brain, could play major roles in various brain conditions pathologically including pathogenesis of Alzheimer's disease (AD). In this paper, we review how AQP4 and altered astrocyte functions interact in AD, and provide experimental evidence highlighting the importance of this topic for the future investigations. The interactions of AQP4 are as follows: (i) AQP4 could influence astrocytic calcium signaling and potassium homeostasis. (ii) AQP4 is linked with the removal of interstitial β-amyloid and glutamate transmission. (iii) Furthermore, AQP4 modulates the reactive astrogliosis and neuroinflammation mechanisms. (iv) To add to this, AQP4 could participate in the AD pathogenesis through affecting neurotrophic factor production. It is therefore possible to identify certain functional molecules that regulate astrocyte make-up and functions. However, making crucial efforts to develop specific agents or drugs that target AQP4 function and test their therapeutic efficiency will be a breakthrough for addressing AD in that AQP4 controls the various physiological as well as pathophysiological features of astrocytes.


Retraction notice to "Long-Term Trends (1986-2003)in the Use of Coronary Reperfusion Strategies in Patients Hospitalized With Acute Myocardial Infarction in Central Massachusetts" [Int. J Cardiol. 131 (2008) (83-89)].
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief and Author. This article is a duplicate of a paper that has already been published in the Journal of Thrombosis and Thrombolysis, 23 (2007) 163-71. http://dx.doi.org/10.1007/s11239-006-9029-0. One of the conditions of submission of a paper for publication is that authors declare explicitly that the paper is not under consideration for publication elsewhere. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.


Babesia canis canis and Babesia canis vogeli infections in dogs from northern Portugal.
Canine babesiosis represents an important veterinary medical problem. This study describes the molecular characterization of babesial parasites detected in eight clinically suspected dogs from northern Portugal, affected by lethargy, muscle tremors, weight loss, pale mucous membranes, hyperthermia or red-coloured urine. Microscopic examination of peripheral blood smears showed large intraerythrocytic piroplasms morphologically compatible with Babesia canis in all eight animals. DNA was extracted from blood on filter paper, and a Babesia spp. infection confirmed by polymerase chain reaction (PCR) amplification of a 408bp fragment of the 18S rRNA gene. Analysis of PCR-derived sequences revealed that seven dogs were infected with B. canis canis and one with B. canis vogeli. This is the first molecular identification report of both the species B. canis and the subspecies B. canis canis and B. canis vogeli in dogs from Portugal.


A Parameterized Ultrasound-Based Finite Element Analysis of the Mechanical Environment of Pregnancy.
Preterm birth is the leading cause of childhood mortality and can lead to health risks in survivors. The mechanical functions of the uterus, fetal membranes, and cervix have dynamic roles to protect the fetus during gestation. To understand their mechanical function and relation to preterm birth, we built a three-dimensional parameterized finite element model of pregnancy. This model is generated by an automated procedure that is informed by maternal ultrasound measurements. A baseline model at 25 weeks of gestation was characterized, and to visualize the impact of cervical structural parameters on tissue stretch, we evaluated the model sensitivity to (1) anterior uterocervical angle, (2) cervical length, (3) posterior cervical offset, and (4) cervical stiffness. We found that cervical tissue stretching is minimal when the cervical canal is aligned with the longitudinal uterine axis, and a softer cervix is more sensitive to changes in the geometric variables tested.


Assessment of facial reinnervation by use of chronic electromyographic monitoring.
The study of muscle reinnervation has been difficult because of lack of an accurate, reproducible method to monitor return of function. Visual assessment relies on subjective interpretation. Histology provides anatomic, not functional, information. Electromyography and anatomic tracing have been most effective in evaluating physiologic return of muscle function. It has been difficult to assess the timing of functional return electromyographically because measurements are intermittent and electrode placement varies. A method was designed to allow long-term monitoring of electromyographic (EMG) activity in the facial musculature of the rabbit. Sixteen rabbits were monitored for at least 1 month or until return of normal EMG activity was identified. Various levels of injury (nerve crush, transection without repair, and transection with immediate end-to-end anastomosis) were evaluated. EMG evidence of reinnervation was seen in all animals with nerve crush injuries as well as those with anastomoses. Physiologic continuity of the nerves was then evaluated by retrograde transport of horseradish peroxidase. All muscles showing return of EMG activity had uptake of HRP into the appropriate brain stem motor neurons. The denervated muscles showed no HRP uptake. The information gained in this study shows potential for use of this technique in comparing functional return of muscle activity between different reinnervation methods.


Perioperative complications of robot-assisted partial nephrectomy: analysis of 886 patients at 5 United States centers.
To review complications of robot-assisted partial nephrectomy (RAPN) at 5 centers, as classified by the Clavien system. A multi-institutional analysis of prospectively maintained databases assessed RAPN complications. From June 2007 to November 2011, 886 patients at 5 United States centers underwent RAPN. Patient demographics, perioperative outcomes, and complications data were collected. Complication severity was classified by Clavien grade. Mean (standard deviation) data were patient age, 59.4 (11.4) years; age-adjusted Charlson Comorbidity Index, 3.0 (1.9); radiographic tumor size, 3.0 (1.6) cm; nephrometry score, 6.9 (2.0); and warm ischemia time, 18.8 (9.0) minutes. Median blood loss was 100 mL (interquartile range, 100-250 mL). Of the 886 patients, intraoperative complications occurred in 23 patients (2.6%) and 139 postoperative complications occurred in 115 patients (13.0%) for a total complication rate of 15.6%. Among the 139 postoperative complications, 43 (30.9%) were classified as Clavien 1, 64 (46.0%) were Clavien 2, 21 (15.1%) were Clavien 3, and 11 (7.9%) were Clavien 4. No complication-related deaths occurred. Intraoperative hemorrhage occurred in 9 patients (1.0%) and postoperative hemorrhage in 51 (5.8%). Forty-one patients (4.6%) required a perioperative blood transfusion, 10 (1.1%) required angioembolization, and 2 (0.2%) required surgical reexploration for postoperative hemorrhage. Urine leaks developed in 10 patients (1.1%): 3 (0.3%) required ureteral stenting, and 2 (0.2%) required percutaneous drainage. Acute postoperative renal insufficiency or renal failure developed in 7 patients (0.8%), 2 of whom required hemodialysis. The RENAL (radius, exophytic/endophytic properties of the tumor, nearness of tumor deepest portion to the collecting system or sinus, anterior/posterior descriptor and the location relative to polar lines) nephrometry scoring system accurately predicted RAPN complication rates. Complication rates in this large multicenter series of RAPN appear to be acceptable and comparable with other nephron-sparing modalities. Most complications (77.0%) are Clavien 1 and 2 and can be managed conservatively.


Eph/ephrin signaling maintains the boundary of dorsal forerunner cell cluster during morphogenesis of the zebrafish embryonic left-right organizer.
The Kupffer's vesicle (KV) is the so-called left-right organizer in teleost fishes. KV is formed from dorsal forerunner cells (DFCs) and generates asymmetrical signals for breaking symmetry of embryos. It is unclear how DFCs or KV cells are prevented from intermingling with adjacent cells. In this study, we show that the Eph receptor gene ephb4b is highly expressed in DFCs whereas ephrin ligand genes, including efnb2b, are expressed in cells next to the DFC cluster during zebrafish gastrulation. ephb4b knockdown or mutation and efnb2b knockdown cause dispersal of DFCs, a smaller KV and randomization of laterality organs. DFCs often dynamically form lamellipodium-like, bleb-like and filopodium-like membrane protrusions at the interface, which attempt to invade but are bounced back by adjacent non-DFC cells during gastrulation. Upon inhibition of Eph/ephrin signaling, however, the repulsion between DFCs and non-DFC cells is weakened or lost, allowing DFCs to migrate away. Ephb4b/Efnb2b signaling by activating RhoA activity mediates contact and repulsion between DFCs and neighboring cells during gastrulation, preventing intermingling of different cell populations. Therefore, our data uncover an important role of Eph/ephrin signaling in maintaining DFC cluster boundary and KV boundary for normal left-right asymmetrical development.


Biphasic alteration in the trigeminal nociceptive neuronal responses after intracerebroventricular injection of prostaglandin E2 in rats.
To investigate the role of prostaglandin E2 (PGE2) in the brain in nociception electrophysiologically, we injected PGE2 (0.1 fmol(-1) nmol) into the lateral cerebroventricle (LCV) of anesthetized rats and observed the changes of the responses of the wide dynamic range (WDR) neurons in the trigeminal nucleus caudalis to noxious pinching of facial skin. The LCV injection of PGE2 at 1 fmol and 10 fmol enhanced the responses of the majority of WDR neurons to noxious stimuli, whereas that of PGE2 at 100 pmol and 1 nmol suppressed them. The enhancement and suppression of the nociceptive responses of WDR neurons were observed 15-25 min and 5-15 min after injection of PGE2 at 10 fmol (3.53 pg) and 1 nmol (353 ng), respectively. On the other hand, the LCV injection of PGE2 at both 10 fmol and 1 nmol had no effect on the responses of the low threshold mechanoreceptive neurons to skin brushing. These results provide electrophysiological evidence that brain-derived PGE2 has biphasic effects on nociception, i.e., it induces mechanical hyperalgesia at lower doses and hypoalgesia at higher doses in rats.


Near-miss and hazard reporting: promoting mindfulness in patient safety education.
Patient safety efforts advocate for transforming healthcare from a culture of blame to a non-punitive "culture of safety." One of the most challenging hurdles is to encourage healthcare practitioners to be mindful about their activities. To promote mindfulness during clinical education for entry-level nurses, we developed a web-based dangerous situation and near miss reporting system for a cohort of baccalaureate nursing students (N=156). For this curricular innovation project, we provided wireless handheld devices to students who were required to submit one report for each of their clinical days in the medical-surgical, pediatric, psychiatric, obstetrics and community settings. During a ten-week period, students submitted 1487 reports. Of these, 63% were dangerous situations and 37% were near misses. The most frequently occurring dangerous situations were poor infection control practices. The most commonly reported near misses were medication errors. Free text comments from students identified inadequate patient identification and poor documentation as commonly occurring dangerous situations observed.


Informing patients of the teratogenic potential of mood stabilizing drugs: a case note review of the practice of psychiatrists.
Lithium, carbamazepine and valproate are established human teratogens. Women of childbearing potential who are prescribed these drugs should be informed of their teratogenic potential and advised of the need for adequate contraception and the protective role of folate. We reviewed the clinical records of all women of childbearing age in long-term contact with one specialist mental health Trust providing services for a total population of 750,000. One hundred and thirty eight (16%) of 837 women of childbearing age were prescribed one or more of these drugs. There was documented evidence that 29 (21%) of these women had been informed about teratogenicity and that 33 (24%) had been advised about contraception. Fourteen women (10%) had a confirmed pregnancy while taking lithium, carbamazepine or valproate; eight had a complication of pregnancy. If prescribing practice in this large mental health Trust were typical of the UK, between 7000 and 11 000 women of childbearing potential would be prescribed lithium, carbamazepine or valproate by psychiatrists without documented discussion of the risks.


[Identification of prognostic factors in post-transplantation lymphoproliferative disorders].
Post-transplantation lymphoproliferative disorders (PTLD) represent a severe complication of organ transplantation, so the determination of prognostic factors for the response and the survival is of major interest. Studies on PTLD are hindered by the small number of cases, explaining the conflicting published results. In order to identify, prognostic factors in this kind of disease, 61 patients have been analyzed in a retrospective multicenter study. A new index is proposed to assess the survival probability, it is composed of two factors: the performance status (PS < or = 1 versus 2-3) and the number of involved sites (1 versus > 1). This index seems to be more accurate in PTLD than the IPI, the reference in immunocompetent patients with non Hodgkin lymphomas. However, a similar analysis in a more homogeneous population remains necessary.


Advances in Stereoselective 1,2-cis Glycosylation using C-2 Auxiliaries.
The control of stereoselectivity in a glycosylation reaction remains one of the most challenging aspects of oligosaccharide synthesis. Especially the synthesis of 1,2-cis-glycosides is challenging and generally applicable methodology to prepare this linkage is needed to standardize oligosaccharide synthesis. This review highlights the recent development of an elegant strategy employing a C-2 auxiliary to control the anomeric stereoselectivity in glycosylations. The various auxiliaries developed to date, their compatibility with protecting groups and monosaccharide types as well as mechanistic aspects are summarized. Furthermore, the application, advantages and limitations of C-2 auxiliaries in oligosaccharide synthesis are discussed.


Prophylaxis of infection and effects on osseointegration using a tobramycin-periapatite coating on titanium implants--an experimental study in the rabbit.
No options are available for local antibiotic delivery from uncemented implants. By loading a porous titanium implant with a biomimetic HA-coating (PeriApatite, PA) with antibiotics, we could obtain adequate local antibiotic concentrations and reduce infection susceptibility. This study investigated the efficacy of a tobramycin-loaded PA-coated titanium foam implant in preventing infection, as well as the effects on osseointegration. In 72 New Zealand White rabbits, an uncoated (Ti), PA-coated (PA), or Tobramycin-PA-coated (PA-tobra) titanium foam rod was implanted intramedullary in the left tibiae after contamination of the implant bed with none (control), 10(3), 10(4) or 10(5) CFU Staphylococcus aureus. PA-tobra implants were loaded with 2.4 mg tobramycin. After 28 days analysis was done by bacteriology, histopathology and histomorphometry. Six percent of the contaminated PA-tobra rabbits were infected, whereas this was 53 and 67% for PA and Ti, respectively (p < 0.001). Quantitative cultures were also significantly lower in the PA-tobra group (p = 0.003). None of the control rabbits were infected. Histopathological and histomorphometrical scores were both better for the PA-tobra group, although only significant compared to Ti. No significant differences were observed between PA and Ti rabbits. We conclude that the application of tobramycin to PA-coated titanium foam implants appears to be an effective local antibiotic strategy for uncemented implants for infection prophylaxis and has a beneficial effect on implant fixation, which will result in improved long-term implant survival.


Post-disaster psychosocial support and quality improvement: A conceptual framework for understanding and improving the quality of psychosocial support programs.
This article is original in that it addresses post-disaster psychosocial support programs from a quality-improvement perspective, not from the traditional viewpoint of mental health services. Based on a combination of renowned quality models, a framework is sketched that offers chances to better understand and optimize the quality of post-disaster psychosocial service delivery. The quality is reflected in the program's structure, process, and outcome. Moreover, quality can be expressed in scores per criterion (i.e. need centeredness, effectiveness, safety, timeliness, efficiency, and equity) that are proposed to be related to the "attitude" (more passive or active) toward affected people. When quality and attitude are combined in a 2-D parabolic model, psychosocial support is preferably found in the middle of the attitude-axis (high quality); extremely passive or active positions are to be avoided (low quality). Well-timed assessments of structure, process, and outcome aspects, and associations between them, will help planners, providers, and evaluators understand if the optimum is reached, as well as provide guidance for quality improvement.


Interval timing behavior in Pallas's long-tongued bat (Glossophaga soricina).
Timing behavior in animals and its underlying mechanisms have been investigated extensively in the peak procedure, a variant of fixed interval procedures. In such experiments, individuals typically start responding with high frequency after an initial inactive time interval and continue their responses after peak time if rewards are omitted. This begs the so far unexplored question as to how timing behavior is influenced when such continuous responses are suppressed. Here, we present results from a nectar-feeding bat species, Glossophaga soricina, that was tested in a modified version of the peak procedure at three fixed time intervals (5 s, 11 s, 20 s). In contrast to standard peak procedures we imposed metabolic costs on individual responses which effectively suppressed trains of rapid responses during trials. Under this manipulation, bats' aggregated responses showed clear peaks around the peak time in the 5-s and 11-s schedules. Bats' responses in the 20-s schedule, however, did not peak around the fixed interval time. Crucially, an analysis of time intervals between successive revisits in all schedules revealed that bats revisited feeders at accurately timed intervals in all three conditions. The individual within trial behavioral responses showed clear oscillatory patterns throughout nonrewarded trials. These findings follow predictions from mechanistic timing models, like the striatal beat frequency model, and are discussed with regard to these models.


Tumor-induced thymic atrophy: alteration in interferons and Jak/Stats signaling pathways.
The thymus is the major site of T cell differentiation and a key organ of the immune system. Thym atrophy has been observed in several model systems including aging, and tumor development. Previous results from our laboratory have reported that the thymic atrophy seen in mammary tumor bearers is associated with a severe depletion of CD4+CD8+ double positive immature cells and changes in the levels of cytokines expressed in the thymus microenvironment. Cytokines regulate numerous aspects of hematopoiesis via activation of the Jak/Stat pathways. In the present study we have used our mammary tumor model to investigate whether changes in the levels of cytokines in the thymus could affect the normal expression of the aforementioned pathways. RNA and protein analysis revealed an overexpression of the different members of interferons, a downregulation of most of the Jak/Stat pathways, and an increased expression of several suppressors of cytokine signaling (SOSC) in the thymuses of tumor bearers. Together, our data suggest that the impaired Jak/Stat signaling pathways observed in the whole thymus of tumor-bearing mice could be contributing to the abnormal T cell development and apoptosis observed during the tumor-induced thymic atrophy.


[Bone marrow transplantation at the Essen University Clinic].
From December 1975 until October 1988 292 bone marrow transplantations (bmt) have been performed at the Center for Tumor Research and Tumor Therapy, University Hospital Essen; 251 of these transplantations were allogeneic, 30 autologous and 11 syngeneic. The main indications were ALL (n = 39), AML (n = 132), CML (n = 75) and severe aplastic anemia (n = 26). Now the transplantation rate is one bmt per week. Early transplantation during a controlled stage of disease provides the best chance of cure. Important prerequisites of a successful allotransplantation are patient age under 45-50 years, good general condition and a histocompatible donor. In case of autologous bmt, being mainly tested in acute leukemias and malignant lymphomas, the age limit is 50-55 years. If the allogeneic transplantation is performed during an early stage of disease, the cure expectancy is about 50% for acute leukemia in first remission and CML in chronic phase. In the case of severe aplastic anemia the cure rates are even higher, provided that the transplant is grafted before multiple blood transfusions have been given. In AML the risk of relapse after autologous bmt is higher than after allogeneic transplantation, but the preliminary data are promising. The question of whether or not autologous bmt is superior to conventional chemotherapy of AML, has to be investigated.


Evaluation of the ABA-100 procedure for total and direct bilirubin in serum or plasma.
We present a modified Evelyn-Malloy method, adapted to the Abbott Biochromatic Analyzer (ABA-100) for the determination of both total and direct bilirubin. It requires less than 25 mul of serum or plasma. At least 50 samples can be assayed per hour with economy of reagent consumption and the precision compares favorably with that for conventional manual methods.


Off-line and in-line determination of catechol- O-methyltransferase activity in a capillary electrophoretic system.
The use of capillary electrophoresis for the determination of catechol-O-methyltransferase (COMT) activity with dihydroxybenzoic acid as a substrate was investigated. Both an off-line and in-line capillary electrophoresis determination of COMT activity was developed and the two approaches are discussed. In the presented methods, substrate and reaction products are monitored at the same time. The initial velocity of the reaction is quantified spectrophotometrically by the corrected peak area of the products at 200 nm. In the off-line setup, capillary zone electrophoresis is used to separate and quantify the different reaction compounds. Each electrophoretic run required only 37 nL of the enzymatic reaction solution. Based on the off-line assay, an in-line determination of COMT activity was developed by a methodology known as electrophoretically mediated microanalysis (EMMA). All the different steps (i.e. mixing, incubation, separation and in-line quantitation) are combined in the capillary, which is used as a microreactor for the enzymatic reaction. Full automation of the assay is achieved with this microscale approach.


[Descriptive analysis of 660 cases of upper digestive hemorrhage: relation of emergency endoscopy and mortality].
A study was made of 660 patients admitted for upper gastrointestinal bleeding in which the endoscopic findings were analyzed, excluding patients with esophageal varices and cases in which the lesions responsible for bleeding were not appreciated (5.7% diagnostic failure). 71.7% were males and 38.3% females, average age was 59.9 +/- 17.5 years and average hematocrit on admission was 27.4 +/- 8.2. 58.3% were over 60 years-old. There was a history of ingestion of gastro-erosive drugs in 56.8%. Gastroscopy was performed within 24 hours of admission in 77.4%, the first clinical symptom of bleeding being melenas in 50%. Peptic ulcer was the most common cause of upper gastrointestinal bleeding. Eighty-one patients required surgery, 30 early and 51 delayed. The global mortality was 3.6% and surgical mortality, 13.5%. After relating the endoscopic groups of upper gastrointestinal bleeding and individual risk with mortality rates, emphasis is placed on the need for early endoscopy as a diagnostic tool of prognostic value.


Inherited dental anomalies: a review and prospects for the future role of clinicians.
Inherited dental anomalies such as hypodontia, supernumerary teeth, enamel defects, and diastema are evident in large segments of most populations. Although treatment options for many of these conditions are ever improving, much remains to be understood about their etiology and pathophysiology. In this review, the authors hope to enthuse dental professionals into aiding the human geneticist by collaborating in studies seeking the underlying genetic cause of dental anomalies and referring patients presenting these conditions to the human geneticist.


Parenting and social anxiety: fathers' versus mothers' influence on their children's anxiety in ambiguous social situations.
The role of parenting in child social anxiety was examined in an information processing experiment. We tested the relative weight that children in general, and high versus low socially anxious children in particular, put on fathers' versus mothers' signal about whether a social situation is safe or a threat. Children aged 8-12 (n = 144) varying in social anxiety were presented scripts of ambiguous social situations in which either the father or the mother acted anxious or confident. Children indicated how anxious or confident they would be. Fathers' behaviour influenced high socially anxious children's confidence or anxiety more than mothers' behaviour. In contrast, in normal and low socially anxious children, mothers' behaviour was more influential than fathers'. Mothers might have the role of teaching social wariness to their low socially anxious children, whereas fathers may teach social confidence to socially anxious children.


Inhibitory Effects of Thai Essential Oils on Potentially Aflatoxigenic Aspergillus parasiticus and Aspergillus flavus.
The antiaflatoxigenic and antifungal activities of essential oils (EOs) of finger root (Boesenbergia rotunda (L.) Mansf.), pine (Pinus pinaster), rosewood (Aniba rosaedora), Siam benzoin (Styrax tonkinensis), Thai moringa (Moringa oleifera), and ylang ylang (Cananga odorata) were tested for Aspergillus parasiticus and Aspergillus flavus in potato dextrose broth. Aflatoxin B1 (AFB1) was extracted from culture using a QuEChERS-based extraction procedure and analyzed with high performance liquid chromatography (HPLC) coupled to a fluorescence detector. EO of pine showed the greatest inhibition of growth and AFB1 production of A. parasiticus, followed by EOs of rosewood, finger root, Siam benzoin, and ylang ylang. EO of finger root gave the best inhibitory effects on A. flavus, followed by EOs of rosewood, pine, ylang ylang, and Siam benzoin. EO of Thai moringa did not show any significant inhibition of aflatoxigenic fungi. The antiaflatoxigenic activities of EOs correlated with their antifungal activities in the dosedependent manner. Comparison of the application of the five selected EOs in peanut pods by direct and vapor exposure indicated that the AFB1 production inhibitory effects of the five EOs by direct exposure were faster and more effective than by vapor exposure. EO of finger root showed the best inhibition of AFB1 production of A. flavus in peanut pods by direct exposure, followed by EOs of pine, rosewood, ylang ylang, and Siam benzoin.


Anemia and stroke: Where do we stand?
Anemia seems to have a clear relationship with cerebrovascular events (CVEs), as there is a direct connection between central nervous system, blood supply, and tissue oxygen delivery. Anemia is considered a hyperkinetic state which disturbs endothelial adhesion molecule genes that may lead to thrombus formation. Furthermore, blood flow augmentation and turbulence may result in the migration of this thrombus, thus producing artery-to-artery embolism. It is for this reason that anemia is characterized as "the fifth cardiovascular risk factor." Anemia is consistently present in patients with acute stroke, ranging from 15% to 29%, while the mortality rate was significantly higher in patients suffering from anemia at the time of admission. Different types of anemia (sickle cell disease, beta thalassemia, iron deficiency anemia [IDA]) have been associated with increased cardiovascular and CVE risk. The relation between hemoglobin level and stroke would require further investigation. Unfortunately, treatment of anemia in cardiovascular and cerebrovascular disease still lacks clear targets and specific therapy has not developed. However, packed red blood cell transfusion is generally reserved for therapy in patients with CVEs. What is more, treatment of IDA prevents thrombosis and the occurrence of stroke; although iron levels should be checked, chronic administration favors thrombosis. Regarding erythropoietin (EPO), as there is lack of studies in anemic stroke patients, it would be desirable to utilize both neuroprotective and hematopoietic properties of EPO in anemic stroke patients. This review aims to clarify the poorly investigated and defined issues concerning the relation of anemia and CVEs.


O-GlcNAc modification of Sp3 and Sp4 transcription factors negatively regulates their transcriptional activities.
The addition of O-linked N-acetylglucosamine (O-GlcNAc) on serine or threonine modifies a myriad of proteins and regulates their function, stability and localization. O-GlcNAc modification is common among chromosome-associated proteins, such as transcription factors, suggesting its extensive involvement in gene expression regulation. In this study, we demonstrate the O-GlcNAc status of the Sp family members of transcription factors and the functional impact on their transcriptional activities. We highlight the presence of O-GlcNAc residues in Sp3 and Sp4, but not Sp2, as demonstrated by their enrichment in GlcNAc positive protein fractions and by detection of O-GlcNAc residues on Sp3 and Sp4 co-expressed in Escherichia coli together with O-GlcNAc transferase (OGT) using an O-GlcNAc-specific antibody. Deletion mutants of Sp3 and Sp4 indicate that the majority of O-GlcNAc sites reside in their N-terminal transactivation domain. Overall, using reporter gene assays and co-immunoprecipitations, we demonstrate a functional inhibitory role of O-GlcNAc modifications in Sp3 and Sp4 transcription factors. Thereby, our study strengthens the current notion that O-GlcNAc modification is an important regulator of protein interactome.


Effects of imipramine on cancer patients over-expressing Fascin1; description of the HITCLIF clinical trial.
Tumor invasion and metastasis are responsible for the majority of cancer-related deaths. The identification of molecules involved in these processes is crucial to design effective treatments that can halt the progression of cancer. To spread and metastasize, tumor cells must restructure their cytoskeleton and emit protrusions. A key molecule in this process of creating these invading structures is Fascin1, the main protein involved in the formation of actin cytoskeleton bundles and a consistent marker of bad prognosis in several types of cancer. Recent studies have shown that imipramine, an FDA- and EMA-approved antidepressant, can block Fascin1and prevent the formation of actin bundles, making it a promising candidate for the treatment of Fascin1-expressing cancers. As a result, a clinical trial will be conducted to assess the efficacy of imipramine being the first experimental clinical study selecting patients based on Fascin1 expression. The HITCLIF trial is a multicenter, double-blind, placebo-controlled, randomized and non-commercial phase II clinical trial conducted in parallel groups to evaluate the effectiveness of the tricyclic antidepressant imipramine as anti-invasive agent in the treatment of localized colon, rectal and triple negative breast cancer patients with overexpression of Fascin1. Eligible patients will be randomly assigned, in a 1:1 ratio, to receive imipramine or placebo. Patients will be stratified into 2 groups according to whether administration of imipramine is concomitant with neoadjuvant chemotherapy regimen. Group A will receive imipramine alone without neoadjuvant chemotherapy, while Group B will receive imipramine treatment along with the standard neoadjuvant chemotherapy regimen. The primary endpoint of the trial is the grade of alteration in the prognostic histopathological features at invasive margins (tumor budding, cytoplasmic pseudo-fragments, tumor growth pattern, and peritumoral lymphocytic infiltration). Fascin1 is an interesting therapeutical target as it plays a causative role in the invasion and metastasis of cancer cells. Moreover, its expression is virtually absent in normal epithelia but highly expressed in cancer with bad prognosis. In silico, in vitro and in vivo studies by our group have demonstrated that the antidepressant imipramine has Fascin1-dependant anti-invasive and anti-metastatic effects in colorectal cancer cells. Now we are recruiting patients in a clinical trial based on Fascin1 over-expression in which administration of imipramine will be carried out during the period between the diagnosis biopsy and surgical resection to explore the drug effects on tumor invasive front. https:///www.clinicaltrialsregister.eu/ctr-search/trial/2021-001328-17/ES, identifier 2021-001328-17.


Effect of mRNA COVID-19 vaccine on ovarian reserve of women of reproductive age.
To evaluate the effect of messenger ribonucleic acid (mRNA) vaccines developed for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) on the ovarian reserve of women of reproductive age. This prospective study was conducted between July and December 2022 in a tertiary care hospital affiliated with a university. A total of 117 patients were included in the study. The patients were divided into two groups. The first group (n = 62) consisted of women of reproductive age who received two doses of Pfizer-BioNTech COVID-19 vaccine administered 21 days apart. The control group (n = 55) included women with the same demographic characteristics who did not plan to be vaccinated. Hormonal values and basal antral follicle count were compared between two groups. The mean age of the study group was 26.3 ± 3.6 years, and the mean age of the control group was 25.4 ± 6.2 years (p = 0.332). In the vaccinated group, mean follicular stimulating hormone (FSH) on day 2 was 5.29 ± 2.28; luteinizing hormone (LH): 5.18 ± 1.3; E2: 46.43 ± 24.51; anti-Mullerian hormone (AMH): 4.17 ± 2.1; antral follicle count: 16.23 ± 8.04; right ovarian volume: 6.4 ± 1.7; left ovarian volume: 6.2 ± 2.1. FSH measured at D2 in the control group was 5.68 ± 1.89; LH: 5.22 ± 2.2; E2: 48.41 ± 27.12; AMH: 4.30 ± 1.74; number of antral follicles: 15.64 ± 9.04; right ovarian volume: 6.1 ± 1.8; left ovarian volume: 6.3 ± 1.4. There were no statistically significant differences for FSH, LH, E2, AMH, ovarian volume, and number of antral follicles on the second day of menstruation between the groups. According to the results of the present study, the mRNA SARS-CoV-2 vaccine does not affect the ovarian reserve of patients.


Single-cell qPCR facilitates the optimization of hematopoietic differentiation in hPSCs/OP9 coculture system.
Human pluripotent stem cells (hPSCs)/OP9 coculture system is a widely used hematopoietic differentiation approach. The limited understanding of this process leads to its low efficiency. Thus, we used single-cell qPCR to reveal the gene expression profiles of individual CD34+ cells from different stages of differentiation. According to the dynamic gene expression of hematopoietic transcription factors, we overexpressed specific hematopoietic transcription factors (Gata2, Lmo2, Etv2, ERG, and SCL) at an early stage of hematopoietic differentiation. After overexpression, we generated more CD34+ cells with normal expression level of CD43 and CD31, which are used to define various hematopoietic progenitors. Furthermore, these CD34+ cells possessed normal differentiation potency in colony-forming unit assays and normal gene expression profiles. In this study, we demonstrated that single-cell qPCR can provide guidance for optimization of hematopoietic differentiation and transient overexpression of selected hematopoietic transcription factors can enhance hematopoietic differentiation.


Influence of methanol and its metabolites on the activity of alpha1-antitrypsin.
Among methanol and its metabolites, formaldehyde was found to have the strongest inactivating effect on the activity of alpha1-antitrypsin preparation and inhibitor existing in blood serum. The influence of formaldehyde on the activity of serum alpha1-antitrypsin is lower in comparison with purified inhibitor. alpha1-Antitrypsin modified by formaldehyde inactivates the trypsin in its action on the BAPA to a smaller degree than on the hemoglobin. The effective formaldehyde concentration in the case of the BAPA is about 64 mM and in the case of the hemoglobin is about 256 mM. The significant inhibitory effect of methanol on alpha1-antitrypsin appears only at a high concentration of this compound. Formate does not decrease alpha1-antitrypsin activity. In people intoxicated with methanol, alpha1-antitrypsin activity decreases, whereas the content of this inhibitor does not change.


Cloning and expression of the mouse glomerular podoplanin homologue gp38P.
Puromycin aminonucleoside nephrosis (PAN) is a rat model for human minimal change nephropathy. During PAN, severe proteinuria is induced that is paralleled by a reduced expression of a rat podocyte protein, named podoplanin. The protein probably plays a role in maintaining the unique shape of podocytes. Recently, attenuated amino acid transport has been observed in cultured mouse glomerular epithelial cells treated with puromycin aminonucleoside (PA). In the present study, gp38P, a protein homologous to rat podoplanin was cloned from mouse glomerular epithelial cells and was found to be down-regulated by PA. A role for gp38P in membrane transport in mouse podocytes has been suggested. Based on homology to rat podoplanin, the protein gp38P was cloned from mouse glomerular epithelial cells by RT-PCR. Mouse glomerular epithelial cells, mouse cortical collecting duct cells, and Xenopus oocytes were treated with PA and the expression of gp38P was examined by RT-PCR and western blot analysis. Expression of gp38P in other mouse tissues was demonstrated by RT-PCR. The possible impact of gp38P on amino acid transport and folic acid uptake was examined in Xenopus oocytes. gp38P cloned from mouse glomerular epithelial cells showed strong homologies to rat podoplanin and gp38, a protein expressed in the thymus and other tissues. RT-PCR analysis demonstrated ubiquitous expression of gp38P in epithelial and non-epithelial tissues. Quantitative RT-PCR and western blot analysis indicated down-regulation of gp38P in PA-treated glomerular epithelial cells along with loss of cell shape and cell lysis, which was not observed in other cell types. When expressed in Xenopus oocytes, gp38P had no impact on folic acid uptake or transport activity of the amino acid co-transporters CAT1, EAAC1, and rBAT. Cultured mouse glomerular epithelial cells express the podoplanin homologue gp38P, which is down-regulated by PAs. gp38P is ubiquitously expressed and is likely to control specifically the unique shape of podocytes.


Extent of polytene in the pericentric heterochromatin of polytene chromosomes of pseudonurse cells of otu (ovarian tumor) mutants of Drosophila melanogaster.
In the polytene nuclei of germ-line cells (ovarian pseudonurse cells) of Drosophila melanogaster females mutant for otu11 (ovarian tumor), the pericentric heterochromatin is much more abundant than in somatic salivary gland cells. This is due to the degree of heterochromatin compaction (and consequently the level of underreplication) being lower in the nurse cells than in the salivary gland cells. The lower level of compaction probably results in a very low degree of position effect gene inactivation in the ovarian nurse cells.


The views and values of community nurses and their managers: research in progress--one person's pain, another person's vision.
This paper presents preliminary findings from research being carried out into how community nurses in three first-wave community trusts are responding to changes stemming from recent legislation. A Measure of Job Satisfaction was devised for the study for administration to the entire nursing workforce in the participating trusts and semi-structured interviews were carried out with managers at all levels in each of the trusts. This paper concentrates on the textual data arising from the study dealing with how nurses understood the values of managers and how managers viewed nurses' values. Nurses tended to express their beliefs about managers as a series of us-them oppositions while the comments of managers can be seen within a rational/irrational dualism. Some possible theoretical frameworks in which these texts can be further explored are briefly discussed, including Foucault's power/knowledge concept and the literature of 'colonization'.


End-stage kidney disease probably due to reflux nephropathy with segmental hypoplasia (Ask-Upmark kidney) in young Boxer dogs in Norway. A retrospective study.
This paper is a retrospective morphologic study of 7 young Boxer dogs, showing end-stage kidney lesions compatible with chronic pyelonephritis with severe segmental cortical atrophy and fibrosis, associated with chronic tubulointerstitial inflammation of varying degree. Azotemia was observed in 6 of the 7 cases. The gross kidney lesions were as follows: bilateral small kidneys with numerous segmental cortical scars causing depression of the renal cortical surface. Histologic examination revealed salient atrophy of nephrons, including paucity of glomeruli, glomerulocystic lesions, colloid-filled tubular microcysts, and a conspicuously increased occurrence of arteries with narrowed lumina caused by intimal thickening. These segmental abnormalities were accompanied by pronounced interstitial fibrosis. All but 1 dog showed salient tubulointerstitial lympho-plasmacytic infiltration, which in 3 cases also included diffuse infiltration of polymorphonuclear neutrophilic leukocyte (PMN)-cells and occurrence of tubular PMN-casts. Morphologic signs of abnormal metanephric differentiation (renal dysplasia) were observed in all cases in the form of atypical tubules or asynchronous nephronic development (immature glomeruli) or both. However, other morphologic primary dysplastic features were absent. Based on the morphologic features, it is concluded that the end-stage kidney disease in these young Boxer dogs was the result of chronic atrophic nonobstructive pyelonephritis, most probably caused by vesico-ureteral reflux, compatible with reflux nephropathy causing segmental hypoplasia (Ask-Upmark kidney) in man. It is proposed that atypical tubular epithelium in the form of adenomatoid proliferation of collecting duct epithelial cells should be considered an acquired compensatory lesion, rather than the result of disorganized metanephric development.


[Abnormalities of meiotic recombination in Han Chinese azoospermic patients].
To analyze defective homologous chromosomal recombination in Han Chinese azoospermic patients. Testicular biopsy samples from 7 healthy controls and 7 Han Chinese azoospermic patients including 2 obstructive azoospermia (OA group) and 5 non-obstructive azoospermia (NOA group) were analyzed. Immunofluorescence staining was performed to categorize early stage cells at meiosis prophase and to analyze chromosome pairing and recombination of pachytene spermatocyte. Newly developed meiotic proteins antibodies (anti-SCP3, anti-synaptonemal complex proteins 3, anti-MLH1, anti-Mut-L Homolog 1, anti-CREST, chromosome centromere antibody) were used to identify synaptonemal complex (anti-SCP3), recombination sites (anti-MLH1) and centromere (anti-CREST), respectively. Staging of spermatocyte was determined according to SCP3 formation progression. Qualitative data were compared by a Chi-square test, and ANOVA was used to analyze quantitative data. Respectively, 2346 and 2932 spermatocytes were categorized in the controls and azoospermic patients. The proportions of zygotene cells in both OA group and NOA group were significantly higher than that of the control group. Investigation of 1967 pachytene cells from the controls and 354 pachytene cells from azoospermic patients indicated that the mean MLH1 foci per pachytene cell of NOA group was statistically lower than that of the controls. Compared with the controls, incomplete synaptonemal complexes cells (containing gap and/or split) were significantly increased in the NOA group. Delayed meiosis prophase is relatively common in azoospermic patients, and changes in quantity and distribution of recombination foci may be the cause for spermatogenesis arrest in Han Chinese population.


Essential Thrombocythemia in a Two-year-old Child, Responsive to Hydroxyurea but Not Aspirin.
Essential thrombocythemia (ET) is a myeloproliferative neoplasm that occurs mostly in patients above the age of 50 years. Its incidence in children is very rare, with around 100 cases reported in the literature. High-risk patients are defined by previous life threatening major thrombotic or severe hemorrhagic complication or age > 60. Those patients probably benefit from cytoreductive therapy. On the other hand, antiplatelet drugs are recommended for patients with low risk group. Although rare, ET should be considered in the differential diagnosis of persistent thrombocytosis in children, even at a very young age. A constellation of clinical, pathologic, and molecular testing are essential for diagnosis. Given the rarity of these cases, there is currently no consensus for treatment guidelines in children, especially in asymptomatic patients. We describe a case of a two-year old girl who presented with unexplained, isolated thrombocytosis which persisted for eight years. Bone marrow biopsy demonstrated typical features of ET. Over the course of the disease, hydroxyurea, but not aspirin, showed better control of symptoms and lowered the platelets level.


DNA repair protein biomarkers associated with time to recurrence in triple-negative breast cancer.
To evaluate the prognostic utility of immunohistochemical assessment of key proteins in multiple DNA repair pathways in triple-negative breast cancer (TNBC; estrogen receptor negative, progesterone receptor negative, and HER2/neu negative by immunohistochemistry). Archived clinically annotated tumor specimens from 112 women with TNBC were immunostained with antibodies against DNA repair proteins and scored using digital image analysis. The cohort was divided into training and test sets for development of a multiantibody model. Scores were combined with clinical data to assess association with outcome. Low XPF (P = 0.005), pMK2 (P = 0.01), MLH; P = 0.002), and FANCD2 (P = 0.001) were each associated with shorter time to recurrence (TTR) in univariate analysis. A 4-antibody model could segregate high-risk and low-risk groups on the basis of TTR in both the training (relative risk [RR] = 3.52; P = 9.05E-07) and test (RR 2.67; P = 0.019) cohorts. DNA repair proteins may be useful as prognostic markers in TNBC. Further study in larger, uniformly treated cohorts with additional clinical parameters is warranted.


Hyperoside pre-treatment prevents glomerular basement membrane damage in diabetic nephropathy by inhibiting podocyte heparanase expression.
Glomerular basement membrane (GBM) damage plays a pivotal role in pathogenesis of albuminuria in diabetic nephropathy (DN). Heparan sulfate (HS) degradation induced by podocyte heparanase is the major cause of GBM thickening and abnormal perm-selectivity. In the present study, we aimed to examine the prophylactic effect of hyperoside on proteinuria development and GBM damage in DN mouse model and the cultured mouse podocytes. Pre-treatment with hyperoside (30 mg/kg/d) for four weeks could significantly decrease albuminuria, prevent GBM damage and oxidative stress in diabetes mellitus (DM) mice. Immunofluorescence staining, Real time PCR and Western blot analysis showed that decreased HS contents and increased heparanase expression in DN mice were also significantly improved by hyperoside pre-treatment. Meanwhile, transmission electron microscope imaging showed that hyperoside significantly alleviated GBM thickening in DN mice. In addition, hyperoside pre-treatment inhibited the increased heparanase gene (HPR1) promoter activity and heparanase expression induced by high glucose or reactive oxidative species (ROS) in cultured podocytes. Our data suggested that hyperoside has a prophylactic effect on proteinuria development and GBM damage in DM mice by decreasing podocyte heparanase expression.


Local direction change of surface gliding microtubules.
In vitro gliding assay, microtubule translocation by kinesin motor proteins on a surface, has been used as an engineering tool in analyte detection, molecular cargo transport, and other applications. Although controlling the moving direction is often necessary to realize these applications, current direction control methods focus largely on lithographic microfabrication of tracks or external fields on the microtubules. These methods are effective, but are relatively complicated. In addition, they cannot target particular microtubules without affecting others. In this study, we propose a facile approach that can make local direction changes for selected microtubules using a polystyrene particle as a circular motion center and a DNA double helix with streptavidin as a capture arm. The DNA arm captures a microtubule in the close proximity of the immobilized particle via biotin-streptavidin interaction and changes the moving direction ~10° on average. In contrast, no significant direction changes are observed other than random variations with streptavidin-less DNA arms (normal distribution centered at 0°), similar to regular motility assay. The particle-assisted local direction change scheme is compared with a flow field-based ensemble method. The combination of flow and kinesin interactions with each microtubule exerts a force to change the direction, ultimately aligning it to the flow field, regardless of its initial direction. A simple model based on the force balance predicts the time needed for such an alignment. Overall, the particle-based local scheme is distinct and different from ensemble methods such as crossflow that changes directions of all microtubules in the field, thus offering unique utility in engineering applications.


Peach Kernel Oil Downregulates Expression of Tissue Factor and Reduces Atherosclerosis in ApoE knockout Mice.
Atherosclerosis is the pathological process in arteries due to the plaque formation that is responsible for several diseases like heart disease, stroke and peripheral arterial disease. In this study, we performed in vitro and in vivo assays to evaluate the potential anti-atherosclerosis activity of peach kernel oil. For the in vitro assay, we incubated human umbilical vein endothelial cells (HUVEC) with tumor necrosis factor-α (TNF-α) to induce tissue factors (TF, an essential mediator of hemostasis and trigger of thrombosis) elevation. We found that TNF-α-induced TF elevation was suppressed by peach kernel oil in a dose-dependent manner at both mRNA and protein levels. Peach kernel oil can significantly improve HUVEC viability, protect the endothelial cells, which achieved the goal of prevention of thrombotic diseases. For the in vivo assay, we investigated the effect and mechanism of peach kernel oil on preventing atherosclerotic lesion formation in ApoE knockout mice. Results show that peach kernel oil could reduce total cholesterol, triglyceride, low-density lipoprotein cholesterol levels, elevate the high-density lipoprotein cholesterol level in serum, and reduce the area of the aortic atherosclerotic lesions in high-fat diet fed ApoE knockout mice. Moreover, peach kernel oil treatment can significantly down regulate the expression of TF protein to inhibit the formation of atherosclerotic plaque. In conclusion, peach kernel oil may be a potential health food to prevent atherosclerosis in cardiovascular diseases.


Clarification of fast metal sphere movement in glass.
In this study, metal spheres were implanted into glass by continuous-wave (CW) laser illumination, which manipulated the metal sphere inside the glass. The spheres moved at approximately 100 mm/s, which is 100 times faster compared to conventional movement. The movement mechanism was clarified by in situ, cross-sectional, and microscopic observations. With a high laser power density, the metal spheres moved fast with plasma emission, and their trajectory contained fine iron particles. The temperatures of the metal sphere with slow (<0.1 mm/s) and fast (>1 mm/s) speeds were 1,900 and 2,900 K, respectively.