Immunohistochemical studies in diagnosis of the uncommon cases of tumours of the central nervous system.
There is a growing evidence that tumoursof the central nervous system (CNS) exhibit some immunophenotypic aberrations pointing to the multipotential cell differentiation. However, the immunohistochemistry remains still very helpful in differential diagnosis and nosologic classification of the CNS neoplasms. The purpose of this paper is to present the immunomorphological pattern of some rare neoplasms of neuroepithelial origin that over last years were recognised and classified as new clinico-pathological entities. Histological and immuniohistochemical features of three cases including pleomorphic xanthoastrocytoma, chordoid glioma and central neurocytoma are reported with special references to immunohistochemical differentiation of these neoplasmswith other tumours of similar morphology but different histogenesis.


[Management of children with heart murmurs. Diagnostic importance of noninvasive complementary tests].
To determine the benefits of noninvasive tests in the characterization of heart disease in children referred due to heart murmur. Two hundred and thirty three consecutive children were fully examined with the aid of the electrocardiograma (ECG), chest X-ray and echocardiogram (ECHO). The patients were divided in 2 groups according to the initial diagnosis of innocent murmur (n = 23) and pathological murmur (n = 210). A comparison was made between the initial and final diagnosis after the noninvasive tests. Statistical analysis was employed through the qui-square test. The initial diagnosis did not change after ECG. The chest X-ray induced the diagnosis of idiopathic dilatation of the main pulmonary artery in one case and of cardiomyopathy in 8 cases, confirmed in only one. After ECHO, the initial diagnosis of innocent murmur was maintained in 70% of the cases, while 30% had some form of heart disease. In 80% of the pathologic murmur group, the diagnosis did not change after ECHO, while 20% were considered as having an innocent murmur. In the 2 groups together, the concordance index between initial and final diagnosis after ECHO reached 90%. Statistically, a non-significant difference was found between the 2 groups. Careful clinical examination is mandatory in the initial evaluation of children with heart murmur. ECG and chest X-ray does not change the initial clinical diagnosis. After ECHO, the diagnosis changing was low (10%), as long as clinical mistakes are eliminated. The initial diagnosis of innocent murmur excludes the necessity of noninvasive tests with a small possibility of error. EKG, chest X-ray and ECHO should be reserved to cases with obvious or persistent suspicious heart disease after clinical examination.


Design issues for the Michaelis-Menten model.
We discuss design issues for the Michaelis-Menten model and use geometrical arguments to find optimal designs for estimating a subset of the model parameters, or a linear combination of the parameters. We propose multiple-objective optimal designs when the parameters have different levels of interest to the researcher. In addition, we compare six commonly used sequence designs in the biological sciences for estimating parameters and, propose optimal choices for the parameters for geometric designs using closed-form efficiency formulas.


Review of risk from potential emerging contaminants in UK groundwater.
This paper provides a review of the types of emerging organic groundwater contaminants (EGCs) which are beginning to be found in the UK. EGCs are compounds being found in groundwater that were previously not detectable or known to be significant and can come from agricultural, urban and rural point sources. EGCs include nanomaterials, pesticides, pharmaceuticals, industrial compounds, personal care products, fragrances, water treatment by-products, flame retardants and surfactants, as well as caffeine and nicotine. Many are relatively small polar molecules which may not be effectively removed by drinking water treatment. Data from the UK Environment Agency's groundwater screening programme for organic pollutants found within the 30 most frequently detected compounds a number of EGCs such as pesticide metabolites, caffeine and DEET. Specific determinands frequently detected include pesticides metabolites, pharmaceuticals including carbamazepine and triclosan, nicotine, food additives and alkyl phosphates. This paper discusses the routes by which these compounds enter groundwater, their toxicity and potential risks to drinking water and the environment. It identifies challenges that need to be met to minimise risk to drinking water and ecosystems.


Cultivating Compassion and Reducing Stress and Mental Ill-Health in Employees-A Randomized Controlled Study.
Stress and mental ill-health carry considerable costs for both individuals and organizations. Although interventions targeting compassion and self-compassion have been shown to reduce stress and benefit mental health, related research in organizational settings is limited. We investigated the effects of a 6-week psychological intervention utilizing compassion training on stress, mental health, and self-compassion. Forty-nine employees of two organizations were randomly assigned to either the intervention (n = 25) or a physical exercise control condition (n = 24). Multilevel growth models showed that stress (p = 0.04) and mental ill-health (p = 0.02) decreased over 3 months in both groups (pre-intervention to follow-up: Cohen's d = -0.46 and d = 0.33, respectively), while self-compassion only increased in the intervention group (p = 0.03, between group d = 0.53). There were no significant effects on life satisfaction in any of the groups (p > 0.53). The findings show promising results regarding the ability of compassion training within organizations to decrease stress and mental ill-health and increase self-compassion.


Effects of Exercise Interventions on Depressive Symptoms Among Community-Dwelling Older Adults in the United States: A Systematic Review.
Depression is the most prevalent mental health problem among older adults. Exercise has been found to have a protective and treatable effect on depression in this population. A systematic review of literature published between 2006 and 2015 was performed to examine the influence of exercise interventions in reducing depressive symptoms among community-dwelling older adults in the United States. Ten studies were identified for inclusion. Exercise interventions have positive effects on clinical depression and depressive symptoms among older adults. In addition, exercise interventions alleviated the depressive symptoms among older adults with a diagnosis of chronic disease. Future studies should include a randomized controlled trial with a larger sample, longitudinal design, and culturally sensitive intervention. For long-term benefits, incorporating motivational strategies into community exercise programs and collaborating with community health care providers are recommended to enhance the maintenance of exercise behavior among community-dwelling older adults. [Journal of Gerontological Nursing, 44(3), 31-38.].


Fostering healthy work environments through nursing education initiatives.
In this era of value-based health care, the knowledge, competence, and professionalism of the front-line nurse and other clinical staff are paramount. Everyone involved in patient care must maximize their skill set and drive high performance in the clinical arena. Healthy work environments will be key to achieving and sustaining quality outcomes and developing and retaining high-performing teams.


[Application experience of attain ® select II catheter delivery system for left ventricular lead implantation in cardiac resynchronization therapy].
To summarize application experience of attain ® select II catheter delivery system for left ventricular lead implantation in cardiac resynchronization therapy (CRT). CRT/CRT-D was applied for 86 patients with congestive heart failure and left bundle-branch block. Left ventricular lead implantation was applied without use of attain ® select II catheter delivery system in 42 patients without coronary vein anatomy variation (group A). Coronary sinus and cardiac vein angiography detected coronary vein anatomy variations in 44 patients and attain ® select II catheter delivery system was not used in 21 patients (group B) and used in 23 patients (group C). Total procedure time, LV lead implantation time, X-ray exposure time and complications were compared among groups. The optimal LV lead location were observed at the end of procedure. Patients were followed up to 245 days (160 - 368 days). Total procedure time [(119 ± 18) min vs. (142 ± 17) min; (119 ± 18) min vs. (143 ± 17) min], LV lead implantation time [(32 ± 7) min vs. (49 ± 8) min;(32 ± 7) min vs. (51 ± 7) min]and X-ray exposure time [(27 ± 6) min vs. (46 ± 84) min;(27 ± 6) min vs. (45 ± 7) min] were significant reduced in group C compared to group A and B. Procedure-related complications were similar among the 3 groups. The rate of optimal LV lead location was significantly higher in group C than in group B (96% vs. 71%). It is feasible and safe to implant LV lead through coronary sinus with attain ® select II catheter delivery system. Applying Attain ® select II catheter delivery system can improve the rate of optimal LV lead location with coronary venous anatomy variation.


Long-term duration of reduced serum complement level following burn injury.
We report the case of a boy whose serum CH50 was below the detection limit following burn injury and skin transplantation. The APCH50 level was slightly decreased, although C3, C4, and the other complements were within the normal range. Cold activation was not detected in his plasma. His peripheral blood monocyte ratio slightly elevated to 19% and then decreased to 5.9%. In this case, burn injury caused the depletion of the complement, particularly in the alternative pathway, and resulted in the reduced CH50 level, although C3 did not show the typical pattern of alternative pathway depletion. In previously reported cases of burn injury, the CH50 level returned to the normal range within 2 weeks. In this patient the reduced level of CH50 continued for 4 months. We should consider burn injury one of the causes of complement deficiency even in cases with a duration of more than 1 month.


Preharvest and Postharvest Applications of a Pomegranate Peel Extract to Control Citrus Fruit Decay During Storage and Shelf Life.
Green and blue molds are the most important postharvest diseases affecting citrus in storage. These diseases are commonly controlled with fungicides, but legislative restrictions, consumer concerns, and the development of resistant strains of the pathogens have increasingly led to the search for alternative methods of control. A pomegranate peel extract (PGE) was very effective in controlling Valencia orange and clementine postharvest rot under commercial conditions. After cold storage and 7 days of shelf life, the incidence of decay on oranges sprayed before harvest with PGE at 12, 6, and 3 g/liter was reduced by 78.9, 76.0, and 64.6%, respectively. Similarly, postharvest dipping treatments with PGE reduced rot by 90.2, 84.3, and 77.6%, respectively. Comparable levels of protection were also achieved on clementines. On both oranges and clementines, the extract provided a significantly higher level of protection compared with imazalil, a fungicide commonly used for postharvest treatments. The high level of efficacy and the consistent results on different fruit species (clementines and oranges) and with different application methods (preharvest and postharvest) were evidence of reliability and flexibility. PGE also showed a strong antimicrobial activity against fungi and bacteria, suggesting its possible use in sanitizers to reduce the microbial contamination of recirculated water in packinghouses. The results of the present study encourage the integration of conventional chemical fungicides and sanitizers with PGE to control citrus postharvest rot.


Clinical characteristics of lacrimal drainage pathway disease-associated keratopathy.
To report the clinical characteristics of 13 cases of noninfectious corneal ulceration related to lacrimal drainage pathway disease. Medical records of 13 patients with lacrimal drainage pathway disease-associated keratopathy who were examined at Ehime University Hospital between April 2007 and December 2021 were analyzed. The predisposing lacrimal drainage pathway diseases for corneal ulceration were chronic dacryocystitis in seven patients and lacrimal canaliculitis in six patients. The corneal ulcers were located at the peripheral cornea in 10 patients and the paracentral cornea in three patients. All patients indicated few cellular infiltrations of the ulcerated area at the slit-lamp examination. Corneal perforation was found in seven patients. The primary identified organisms were Streptococcus spp. in chronic dacryocystitis and Actinomycetes spp. in lacrimal canaliculitis. All patients showed rapid healing of the epithelial defects after treatment of the lacrimal drainage pathway disease. The mean time elapsed between treatment of the lacrimal drainage pathway disease and re-epithelialization of corneal ulcer was 14.5 ± 4.8 days. Lacrimal drainage pathway disease-associated keratopathy may be characterized by peripheral corneal ulcer with few cellular infiltrations, occasionally leading to corneal perforation. Treatment of the lacrimal drainage pathway disease could be the most effective treatment for lacrimal drainage pathway disease-associated keratopathy.


Does Low-Carbon City Construction Improve Total Factor Productivity? Evidence from a Quasi-Natural Experiment in China.
Low-carbon city construction (LCC) is an important strategy for countries desiring to improve environmental quality, realize cleaner production, and achieve sustainable development. Low-carbon cities have attracted widespread attention for their attempts to coordinate the relationship between environmental protection and economic development. Using the panel data from 2006 to 2017 of prefecture-level cities in China, this study applied the difference-in-differences (DID) method to analyze the effects of LCC on the total factor productivity (TFP) of the cities and its possible transmission mechanism. The results show significantly positive effects on TFP, but the effects on each component of TFP are different. Although the LCC has promoted technical progress and scale efficiency, it has inhibited technical efficiency. The accuracy of the results has been confirmed by several robustness tests. Mechanism analysis showed that the pilot policy of low-carbon cities has promoted technical progress and scale efficiency by technological innovation and the upgrading of industrial structure, but resource mismatches among enterprises have been the main reason for reduced technical efficiency. Regional heterogeneity analysis showed that the effects on TFP in the eastern region have been more significant than in the central and western regions. In the eastern region, they have promoted technical progress, while in the central and western regions, they have promoted technical progress and scale efficiency but hindered technical efficiency. This paper presents our findings for the effects of LCC on economic development and provides insightful policy implications for the improvement of technical efficiency in low-carbon cities.


Anti-AIDS agents, 21. Triterpenoid saponins as anti-HIV principles from fruits of Gleditsia japonica and Gymnocladus chinensis, and a structure-activity correlation.
Gleditsia saponin C [1] and gymnocladus saponin G [2] were isolated from Gleditsia japonica and Gymnocladus chinensis, respectively, as anti-HIV principles. Compounds 1 and 2 demonstrated inhibitory effects against HIV replication in H-9 cells with EC50 values of 1.1 and 2.7 microM, respectively. Evaluation of the anti-HIV activities of the prosapogenins of 1 and 2 suggested that the unusual monoterpenyl moieties in 1 and 2 are essential for their anti-HIV activity. Derivatives of echinocystic acid [8], the aglycone of compound 1, were also prepared and evaluated for inhibitory activity against HIV replication. 3,16-Di-O-acetylechinocystic acid [12] was shown to be an anti-HIV agent with an EC50 value of 2.3 microM.


[Dermatomyositis: successful therapy with high dosage intravenous 7S immunoglobulins].
This report describes the successful administration of high dose, intravenous 7S immunoglobulins (IG) to an 11 year-old girl with corticosteroid-resistant dermatomyositis. Clinical symptoms improved immediately and the pathological laboratory findings normalized within 10 days of commencement of immunoglobulin therapy. After three cycles of IG the patient showed complete remission of the muscular and dermatological findings. On follow-up examination after one year the patient remained symptom-free in the absence of any therapy and was leading a normally active life. The efficacy of IG therapy in this case is reviewed in the light of the literature.


Methylprednisolone up-regulates annexin A1 (ANXA1) to inhibit the inflammation, apoptosis and oxidative stress of cigarette smoke extract (CSE)-induced bronchial epithelial cells, a chronic obstructive pulmonary disease in vitro model, through the formyl peptide receptor 2 (FPR2) receptors and the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway.
Chronic obstructive pulmonary disease (COPD) is a progressive degenerative disease, of which smoking is the main causer. We carried out this study with the aim of exploring the underlying mechanism of methylprednisolone (MP) treating the COPD. To stimulate COPD in vitro, cigarette smoke extract (CSE)was employed to induce human bronchial epithelial cells BEAS-2B. With the help of MTT and Tunel assays, the viability and apoptosis of BEAS-2B cells after indicated treatment were assessed. The levels of inflammatory response and oxidative stress were determined by the changes of markers basing on their commercial kits. Additionally, annexin A1 (ANXA1) expressions at both protein and mRNA levels were assessed with Western blot and Reverse transcription‑quantitative PCR (RT-qPCR). Moreover, the expressions of apoptosis- and formyl peptide receptor 2 (FPR2) receptors and the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway-related proteins were determined with Western blot., related proteins and proteins. As a result, MP up-regulated the ANXA1 expression in CSE-induced BEAS-2B cells. MP enhanced the viability but suppressed the apoptosis, inflammatory response and oxidative stress of CSE-induced BEAS-2B cells via regulating FPR2/AMPK pathway, while ANXA1 knockdown exhibited oppositive effects on them. In conclusion, MP up-regulated ANXA1 to inhibit the inflammation, apoptosis and oxidative stress of BEAS-2B cells induced by CSE, alleviating COPD through suppressing the FPR2/AMPK pathway.


[Association between primary tumor regression and lymph node status after neoadjuvant chemoradiotherapy in mid and low rectal cancer].
To analyze the association between the response of primary tumor to neoadjuvant chemoradiotherapy (CRT) and lymph node status in mid and low rectal cancer. Seventy-one patients with locally advanced mid and low rectal cancer underwent preoperative CRT followed by surgery. Surgical specimens were examined by surgeons and pathologists to obtain more lymph nodes and the histological sections were examined. Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and tumor regression. Statistical analyses were performed to investigate the relationship between tumor regression and lymph node status. All the patients completed the neoadjuvant CRT. Twelve patients achieved pathological complete response, of whom one was not operated and on surveillance. Pathological examination of the remaining 70 patients showed that the tumor was downstaged to T 0-2 group in 39 patients, among whom 5 patients (12.8%) had positive lymph nodes. Tumor was not downstaged in 31 patients, of whom 10 patients (32.3%) had positive nodes. The difference between the two groups was statistically significant (P=0.029). Tumor regression is consistent with the reduction of lymph node metastasis after preoperative CRT.


Cell-based immunotherapy of glioblastoma multiforme.
Glioblastoma multiforme (GBM) is the most aggressive and lethal primary glial brain tumor. It has an unfavorable prognosis and relatively ineffective treatment protocols, with the median survival of patients being ~15 months. Tumor resistance to treatment is associated with its cancer stem cells (CSCs). At present, there is no medication or technologies that have the ability to completely eradicate CSCs, and immunotherapy (IT) is only able to prolong the patient's life. The present review aimed to investigate systemic solutions for issues associated with immunosuppression, such as ineffective IT and the creation of optimal conditions for CSCs to fulfill their lethal potential. The present review also investigated the main methods involved in local immunosuppression treatment, and highlighted the associated disadvantages. In addition, novel treatment options and targets for the elimination and regulation of CSCs with adaptive and active IT are discussed. Antagonists of TGF-β inhibitors, immune checkpoints and other targeted medication are also summarized. The role of normal hematopoietic stem cells (HSCs) in the mechanisms underlying systemic immune suppression development in cases of GBM is analyzed, and the potential reprogramming of HSCs during their interaction with cancer cells is discussed. Moreover, the present review emphasizes the importance of the aforementioned interactions in the development of immune tolerance and the inactivation of the immune system in neoplastic processes. The possibility of solving the problem of systemic immunosuppression during transplantation of donor HSCs is discussed.


The Heterogeneity of Atopic Dermatitis.
Recent advances were made in characterizing the clinical heterogeneity of atopic dermatitis (AD). To review the clinical domains contributing to AD heterogeneity and describe their importance in clinical practice. We conducted a focused review of the published literature, including retrospective, observational, and prospective studies, clinical trials, and consensus guidelines. AD is associated with heterogeneous skin manifestations, symptoms, lesional severity, lesional extent, longitudinal course, burden of signs and symptoms, and comorbidities. Each of these domains characterizes a different aspect of AD and should be used to guide overall severity assessment and clinical management. Primary focus on any one specific clinical domain of AD is insufficient to describe the full burden of disease. Heterogeneity should be routinely considered during AD clinical encounters. J Drugs Dermatol. 2022;21(2):172-176. doi:10.36849/JDD.6408.


Immune stimulation following dermal exposure to unsintered indium tin oxide.
In recent years, several types of pulmonary pathology, including alveolar proteinosis, fibrosis, and emphysema, have been reported in workers in the indium industry. To date, there remains no clear understanding of the underlying mechanism(s). Pulmonary toxicity studies in rats and mice have demonstrated the development of mediastinal lymph node hyperplasia and granulomas of mediastinal lymph nodes and bronchus-associated lymphoid tissues following exposure to indium tin oxide. Given the association between exposure to other metals and the development of immune-mediated diseases, these studies were undertaken to begin to investigate the immuno-modulatory potential of unsintered indium tin oxide (uITO) in a mouse model. Using modifications of the local lymph node assay, BALB/c mice (five animals/group) were exposed topically via intact or breached skin or injected intradermally at the base of the ear pinnae with either vehicle or increasing concentrations 2.5-10% uITO (90:10 indium oxide/tin oxide, particle size <50 nm). Dose-responsive increases in lymphocyte proliferation were observed with a calculated EC3 of 4.7% for the intact skin study. Phenotypic analysis of draining lymph node cells following intradermal injection with 5% uITO yielded a profile consistent with a T-cell-mediated response. These studies demonstrate the potential for uITO to induce sensitization and using lymphocyte proliferation as a biomarker of exposure, and demonstrate the potential for uITO to penetrate both intact and breached skin.


A pretibial plaque in a five and a half year-old girl.
A five and a half year-old girl presented with a reddish-brown plaque on her right anterior tibia, first observed 1 year previously and without any history of injury or insect bite. Histological examination showed a dense dermal infiltrate composed of plasma cells and small lymphocytes, combined with lymphocytic exocytosis in the epidermis and interface dermatitis. In addition, a second biopsy found small epithelioid granulomas within the lymphoplasmocytic infiltrate. Infection was ruled out. No clonality was found. None of the treatments attempted was successful (antibiotics and steroids), and the lesion was stable but did not improve for 4 years. The same features typical of lymphoplasmocytic pseudolymphoma were observed on a third biopsy. A diagnosis of "pretibial lymphoplasmocytic plaque" was made on the basis of clinical and histological findings. Recently, 3 other cases of this type of lymphocytic and plasma cell cutaneous infiltrate with very distinctive clinical and histopathological features have been reported in children. Our case is instructive because it presents new and as yet undocumented histopathologic features including a lichenoid reaction with vacuolization of the basal cell layer and numerous apoptotic bodies, apparent in 2 of the 3 biopsies, and hypervascularity with thick-walled blood vessels lined with plump endothelial cells in the upper dermis. The clinicopathological presentation of these cases, including ours, is homogenous suggesting a specific entity described as "pretibial lymphoplasmocytic plaque in children". This seems to be a benign, chronic, reactive process, probably arising secondary to a local response to an unknown antigen.


Effect of Heel Heights on Female Postural Control During Standing on a Dynamic Support Surface With Sinusoidal Oscillations.
The authors aimed to investigate female balance or stability control with comparative analysis of the center of pressure trajectory and plantar pressure distribution with different high-heeled shoes while standing on a dynamic surface with multidirectional perturbations. College females with at least 2 years' history of wearing high-heel shoes voluntarily participated in the test with a Novel Pedar insole (Novel, GmBH, Munich, Germany. With heels height increasing, the pressure time integral obviously transfer to the medial forefoot region, with center of pressure trajectory medially deviated significantly, either under anteroposterior or mediolateral perturbations. The passive plantarflexion position of ankle incurred by high heel increased the range of motion in the frontal plane but decreased ankle stability, thus increasing the challenge of body balance maintenance.


Surgical management of macular holes - indications and complications.
Macular hole surgery is very demand surgery performed due to fullthickness macular rupture characterized by abscence of all retinal layers. Indications for surgery includes stages 3 and 4 regarding to Gass classification. Some authors sugest surgery for stage 2 but results are promissing only in anatomical reconstruction. Complications are evident such as cataract, late macular reopening, retinal tears and detachment, visual field defect etc. With improving surgical techniques, the rate of complications became lower.


Gross Efficiency and The Relationship with Maximum Oxygen Uptake in Young Elite Cyclists During the Competitive Season.
This study assessed gross efficiency (GE) during a single competitive season and determined the relationship between GE and maximum oxygen uptake (V̇O2max) in young elite cyclists (n = 15, 20.1 ± 1.4 yrs, 177.5 ± 5.7 cm, 68.3 ± 6.2 kg, 45.2 ± 7.5 mm of six skinfolds) during a competitive season. Participants completed at two occasions (T1 = April; T2 = July), a progressive bike protocol (initial intensity = 100 W, 35 W increments every 3 min) until volitional exhaustion to assess V̇O2max and submaximal variables. A single capillary blood sample was drawn from the left earlobe immediately after completion of each exercise load to determine lactate thresholds. Cyclists' GE was calculated as ([work accomplished/energy expended] x 100). No significant differences were obtained in GE at any workload between T1 and T2 or in the mean GE between T1 (19.3%) and T2 (19.4%) testing (p = 0.93). No significant association was found between mean GE and V̇O2max at either T1 (r = -0.28, p = 0.30), or T2 (r = -0.27, p = 0.32). GE of young elite cyclists might not vary during the most important phase of the training season and GE was not related to V̇O2max. A lower accumulated volume and intensity of training of these cyclists may account for their lower GE in comparison to older professional cyclists and might not have been enough to foster higher increases of GE in cyclists with lower V̇O2max.


[The expression of Rb, p16 and cyclin D1 in 41 esophageal cancers].
D-type cyclins being considered as oncogenes promote progression of the cell through the G1 phase of the cell cycle by CDK4 mediated phosphorylation of the retinoblastoma protein. The activities of CDK4 is constrained by inhibitors such as p16, the product of the CDKN2 in tumor cells and primary tumors suggests that p16 acts as a tumor suppressor. We examined these proteins and genes by immunohistochemistry and in situ hybridization techniques in 41 primary esophageal cancers. Overexpression of cyclin D1 was revealed in 26/41 samples (63.4%) and also in the mucosa adjacent to the cancers in 10 of 26 cyclin D1 overexpression samples, which also have high levels of cyclin D1. P16 was undetectable in 13 of 41 samples. Interestingly, 17 of 24 Rb positive cancers had no or low p16, while 9 Rb-negative cancers showed high levels of p16. These results suggest that the overexpression of cyclin D1 may be a common molecular abnormality and an early molecular event in esophageal cancer, followed either by Rb loss, as occurred in Rb negative samples, or by loss of p16, as occurred in p16 negative samples. Cyclin D1 overexpression and Rb inactivation can coexist in esophageal cancer. However, there is a reciprocity between Rb inactivation and p16 expression in esophageal cancer. Thus, abnormality in the negative feedback regulatory pathway of cyclin D1/CDK4, Rb and p16 may be involved in the molecular mechanism of esophageal cancer.


Impact of an Interprofessional Health Student Education Program on Older Adult Participants.
Training health professional students to work with older adults will improve future workforce capacity to meet growing needs. Additionally, older adults may benefit from health education and interactions with health professional students. We analyzed survey responses from older adults who had participated in an interprofessional health student education program regarding their experiences. Qualitative data were summed and averaged, and quantitative survey data were analyzed with Fisher's Exact Test. At least 60% of participants reported receiving information for health needs or making changes to physical activity, dental care, or diet. The most significant differences in lifestyle modifications were noted among racial and ethnic minorities and among speakers of different primary languages. 64% of the qualitative responses reflected positive affirmation of the program. Our data suggest that interactions with health students are meaningful experiences for older adults, are associated with healthy habit changes, and reflect demographic differences in response to health education.


A new gravity-driven microfluidic-based electrochemical assay coupled to magnetic beads for nucleic acid detection.
In this work, the characterisation and the optimisation of hybridisation assays based on a novel, rapid and sensitive micro-analytical, gravity-driven, flow device is reported. This device combines a special chip containing eight polymer microchannels, with a portable, computer-controlled instrument. The device is used as a platform for affinity experiments using oligonucleotide-modified paramagnetic particles. In our approach, both hybridisation and labelling events are performed on streptavidin-coated paramagnetic microparticles functionalized with a biotinylated capture probe. Modified particles, introduced in the microchannel inlet of the chip, accumulate near the electrode surface by virtue of a magnetic holder. After hybridisation with the complementary sequence, the hybrid is labelled with an alkaline phosphatase conjugate. The electrochemical substrate for alkaline phosphatase revelation is p-aminophenyl phosphate. Solutions and reagents are sequentially passed through the microchannels, until enzyme substrate is added for in situ signal detection. Upon readout, the magnet array is flipped away, beads are removed by addition of regeneration buffer, and the so-regenerated chip is ready for further analysis. This protocol has been applied to the analytical detection of specific DNA sequences of Legionella pneumophila, with an RSD=8.5% and a detection limit of 0.33 nM.


Development of Insert Condition Classification System for CNC Lathes Using Power Spectral Density Distribution of Accelerometer Vibration Signals.
Insert conditions significantly influence the product quality and manufacturing efficiency of lathe machining. This study used the power spectral density distribution of the vibration signals of a lathe machining accelerometer to design an insert condition classification system applicable to different machining conditions. For four common lathe machining insert conditions (i.e., built-up edge, flank wear, normal, and fracture), herein, the insert condition classification system was established with two stages-insert condition modeling and machining model fusion. In the insert condition modeling stage, the magnitude features of the segmented frequencies were captured according to the power spectral density distributions of the accelerometer vibration signals. Principal component analysis and backpropagation neural networks were used to develop insert condition models for different machining conditions. In the machining model fusion stage, a backpropagation neural network was employed to establish the weight function between the machining conditions and insert condition models. Subsequently, the insert conditions were classified based on the calculated weight values of all the insert condition models. Cutting tests were performed on a computer numerical control (CNC) lathe and utilized to validate the feasibility of the designed insert condition classification system. The results of the cutting tests showed that the designed system could perform insert condition classification under different machining conditions, with a classification rate exceeding 80%. Using a triaxial accelerometer, the designed insert condition classification system could perform identification and classification online for four common insert conditions under different machining conditions, ensuring that CNC lathes could further improve manufacturing quality and efficiency in practice.


Treatment considerations for the hypertensive patient over age 55.
The prevalence of hypertension increases with age. The majority of the hypertensive population is over age 55. Although the treatment of systolic hypertension remains incompletely understood, the reduction of diastolic hypertension with pharmacotherapy has been shown to reduce complications from hypertension in persons over age 55. The older hypertensive patient is at risk for the same complications as the younger patient: angina, myocardial infarction, arteriosclerosis obliterans, stroke, myocardial hypertrophy, congestive heart failure, and renal failure; the risk of sudden death and multi-infarct dementia in the older patient may be somewhat higher. The older hypertensive individual may have reduced plasma volume and defective salt and water conservation, reduced renal function, impairment of baroreceptor reflexes and sympathetic reactivity, and altered drug pharmacokinetics, or may have arteriosclerosis leading to pseudohypertension. Many circumstances interfere with adequate compliance with therapeutic regimens among the elderly. Concomitant medical conditions increase the possibility of drug interactions and require that the practitioner be able to adjust the antihypertensive program to the patient.


B-MYB is required for recovery from the DNA damage-induced G2 checkpoint in p53 mutant cells.
In response to DNA damage, several signaling pathways that arrest the cell cycle in G(1) and G(2) are activated. The down-regulation of mitotic genes contributes to the stable maintenance of the G(2) arrest. The human LINC or DREAM complex, together with the B-MYB transcription factor, plays an essential role in the expression of G(2)-M genes. Here, we show that DNA damage results in the p53-dependent binding of p130 and E2F4 to LINC and the dissociation of B-MYB from LINC. We find that B-MYB fails to dissociate from LINC in p53 mutant cells, that this contributes to increased G(2)-M gene expression in response to DNA damage in these cells, and, importantly, that B-MYB is required for recovery from the G(2) DNA damage checkpoint in p53-negative cells. Reanalysis of microarray expression data sets revealed that high levels of B-MYB correlate with a p53 mutant status and an advanced tumor stage in primary human breast cancer. Taken together, these data suggest that B-MYB/LINC plays an important role in the DNA damage response downstream of p53.


Myocardial release of endothelin (ET) and enhanced ET(A) receptor-mediated coronary vasoconstriction after coronary thrombosis and thrombolysis in pigs.
We investigated changes in vascular reactivity to endothelin (ET) and local release of ET-like immunoreactivity (ET-LI) induced by myocardial ischemia and reperfusion in a pig model of coronary thrombosis and thrombolysis and studied the possible mechanisms producing the changed vascular reactivity to ET-1. We induced coronary thrombosis by inserting a copper coil into the left anterior descending coronary artery (LAD) and achieved thrombolysis with tissue plasminogen activator (t-PA). Vascular reactivity to ET-1 in the nonischemic and ischemic/reperfused LAD diagonal branches was evaluated in vitro. ET-LI was analyzed in plasma from the great cardiac vein and aorta for estimation of local release. The vasoconstrictor response to ET-1 was enhanced twofold (p < 0.01) in the ischemic/reperfused arteries as compared with the nonischemic arteries. The vasoconstriction induced by the ETB receptor agonist [Ala 1,3,11,15] ET-1 or serotonin was not significantly affected by ischemia/reperfusion. The ETA receptor antagonist BQ-123 reversed the ET-1-induced vascular contraction to a similar degree in ischemic/reperfused and control arteries. The ET-1-induced vasoconstriction of control arteries was not affected by inhibition of nitric oxide (NO) synthase with NG-nitro-L-arginine (L-NNA) or cyclooxygenase with indomethacin. During reperfusion, the myocardial venoarterial plasma concentration difference of ET-LI and blood flow increased, resulting in an increased overflow of ET-LI. Our results demonstrate that coronary thrombosis and thrombolysis evokes enhanced local release of ET-LI during the reperfusion period and increases the vasoconstrictor effects of ET-1 through a mechanism related to ETA receptor activation but unrelated to altered endothelial function. These changes may play a role in the development of ischemic/reperfusion injury and no-reflow phenomenon.


Clinical significance and applications of oscillometry.
Recently, "Technical standards for respiratory oscillometry" was published, which reviewed the physiological basis of oscillometric measures and detailed the technical factors related to equipment and test performance, quality assurance and reporting of results. Here we present a review of the clinical significance and applications of oscillometry. We briefly review the physiological principles of oscillometry and the basics of oscillometry interpretation, and then describe what is currently known about oscillometry in its role as a sensitive measure of airway resistance, bronchodilator responsiveness and bronchial challenge testing, and response to medical therapy, particularly in asthma and COPD. The technique may have unique advantages in situations where spirometry and other lung function tests are not suitable, such as in infants, neuromuscular disease, sleep apnoea and critical care. Other potential applications include detection of bronchiolitis obliterans, vocal cord dysfunction and the effects of environmental exposures. However, despite great promise as a useful clinical tool, we identify a number of areas in which more evidence of clinical utility is needed before oscillometry becomes routinely used for diagnosing or monitoring respiratory disease.


An in silico discovery of potential 3CL protease inhibitors of SARS-CoV-2 based upon inactivation of the cysteine 145-Histidine 41 catalytic dyad.
Coronavirus disease 19 (COVID19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, several countries are at risk of the pandemic caused by this virus. In the absence of any vaccine or virus-specific antiviral treatments, the need is to fast track search for potential drug candidates to combat the virus. Though there are known drugs that are being repurposed to fight against the SARS-CoV-2, there is a requirement for the virus-specific drugs at the earliest. One of the main drug targets of SARS-CoV-2 is an essential non-structural protein, 3CL protease, critical for the life cycle of the virus. We have used molecular docking studies to screen a chemically diverse set of small molecules to identify potential drug candidates to target this protein. Of the 22,630 molecules from varied small molecule libraries, based on the binding affinities and physicochemical properties, we finalized 30 molecules to be potential drug candidates. Eight of these molecules bind in a manner allowing for the scope of a nearly orthogonal backside nucleophilic attack on their suitably placed electrophilic carbonyl groups by the thiol group of cysteine residue 145, while remaining inside a 4 Ǻ distance range. It is interesting since carbonyl groups are known to be attacked in a similar fashion by external nucleophiles and can be relevant when considering these molecules as potential mechanism-based irreversible inhibitors of the 3CLPro. Further, ADMET analysis and Molecular dynamics simulations and available bioactive assays led to the identification of three molecules with high potential to be explored as drug candidates/lead molecules to target 3CLPro of SARS-CoV-2.Communicated by Ramaswamy H. Sarma.


CacyBP/SIP nuclear translocation regulates p27Kip1 stability in gastric cancer cells.
To investigate the mechanism of calcyclin binding protein/Siah-1 interacting protein (CacyBP/SIP) nuclear translocation in promoting the proliferation of gastric cancer (GC) cells. The effect of CacyBP/SIP nuclear translocation on cell cycle was investigated by cell cycle analysis. Western blot analysis was used to assess the change in expression of cell cycle regulatory proteins and proteasome-mediated degradation of p27Kip1. Co-immunoprecipitation (co-IP) analysis was performed to examine the binding of CacyBP/SIP with Skp1. A CacyBP/SIP truncation mutant which lacked the Skp1 binding site was constructed and fused to a fluorescent protein. Subsequently, the effect on Skp1 binding with the fusion protein was examined by co-IP, while localization of fluorescent fusion protein observed by confocal laser microscopy, and change in p27Kip1 protein expression assessed by Western blot analysis. CacyBP/SIP nuclear translocation induced by gastrin promoted progression of GC cells from G1 phase. However, while CacyBP/SIP nuclear translocation was inhibited using siRNA to suppress CacyBP/SIP expression, cell cycle was clearly inhibited. CacyBP/SIP nuclear translocation significantly decreased the level of cell cycle inhibitor p27Kip1, increased Cyclin E protein expression whereas the levels of Skp1, Skp2, and CDK2 were not affected. Upon inhibition of CacyBP/SIP nuclear translocation, there were no changes in protein levels of p27Kip1 and Cyclin E, while p27Kip1 decrease could be prevented by the proteasome inhibitor MG132. Moreover, CacyBP/SIP was found to bind to Skp1 by immunoprecipitation, an event that was abolished by mutant CacyBP/SIP, which also failed to stimulate p27Kip1 degradation, even though the mutant could still translocate into the nucleus. CacyBP/SIP nuclear translocation contributes to the proliferation of GC cells, and CacyBP/SIP exerts this effect, at least in part, by stimulating ubiquitin-mediated degradation of p27Kip1.


Lower lobe pulmonary tuberculosis in immunocompetent male.
We present a case of 23-year-old student misdiagnosed for two months. Radiological finding showed a pneumonial infiltrate of left lung lower lobe. Antibiotical therapy was not resulting in a radiological regression. Biopsy of the lung infiltrate by transthoracic computed tomography guided histology needle, showed granulomatous inflammation with necrosis. Bronchial aspirate received by bronchoscopy was positive in culture on Mycobacterium tuberculosis. After 6 months of antituberculotic therapy advance the complete regression of lung infiltrate. Tuberculosis of lower lung lobe is difficult to diagnose, particularly in persons who are not immunocompromised or without associated diseases. Lower lobe localization of tuberculosis is between 0.6 to 10.5% in all cases. Early diagnosis and therapy of pulmonary tuberculosis depends on bronchoscopic samples. The biopsy of the lung infiltrate by transthoracic computed tomography guided histology needle in histopathological and bacteriological diagnosis of tuberculosis was also useful.


Fluconazole versus amphotericin B in the treatment of esophageal candidiasis in cancer patients.
Thirty-one patients with malignancy and endoscopy-confirmed symptomatic esophageal candidiasis were randomly assigned to receive oral fluconazole, 200 mg once daily, or intravenous amphotericin B, 0.3 mg/kg, over 1-4 weeks. Clinical efficacy was determined weekly and follow-up esophageal endoscopy with biopsy and culture performed whenever possible. Both agents produced rapid resolution of symptoms, especially dysphagia and odynophagia. All 13 evaluable patients in the fluconazole group and 10/12 treated with amphotericin had clinical improvement. Endoscopy showed eradication of the fungus in all 11 patients undergoing repeat endoscopy, with cure or improvement of esophagitis. The incidence of adverse effects attributable to treatment was higher in the amphotericin group. The efficacy of oral fluconazole in esophageal candidiasis appears to be equivalent to that of amphotericin, with fewer adverse reactions.


The road to medical vibrational spectroscopy--a history.
The present Editorial chronicles the journey from classical infrared and Raman spectroscopy to medical vibrational spectroscopy, as experienced by a contemporary witness of the times. During the second half of the last century vibrational biospectroscopy became a topic of increasing global interest and has spawned a number of international conferences of which the most recent, SPEC 2012 - Shedding New Light on Disease, constitutes the basis of the present themed issue.


Complete heart block in late presentation of inferior STEMI successfully treated with percutaneous coronary intervention.
A 55-year-old female presented with 4-day history of fatigue and exertional shortness of breath. A late presentation inferior ST elevation myocardial infarction (STEMI) was diagnosed based on ST elevation in the inferior leads of electrocardiography and elevated cardiac troponin T (TnT). She developed complete heart block 1 day after admission to the hospital and remained hemodynamically stable. She was taken to the catheterization laboratory for a temporary pacing wire insertion. Coronary angiogram at the same time showed an occluded right coronary artery at the mid-section. The lesion was successfully opened. Within 24 hours, the patient's heart rhythm returned to sinus with first-degree atrioventricular block (AVB), thus avoiding the need for a permanent pacemaker. Current guidelines recommend medical management for late presentation hemodynamically stable STEMI of more than 72 H onset. Current ACC/AHA/HRS Pacemaker Guidelines recommend reperfusion strategy for acute presentation inferior STEMI associated with AVB. However, no clear strategy exists in the case of late presentation inferior STEMI with advanced AVB. Our case report suggests that late coronary intervention could be a management strategy in such a scenario in order to avoid a permanent pacemaker.


Genetics of congenital nemaline myopathy: a study of 10 families.
In order to investigate the inheritance in congenital nemaline myopathy (CNM), we studied the family histories and pedigrees of 13 patients with CNM from 10 families, and the 20 patients, by physical examination, single fibre electromyography, ultrasonography of muscles, measurement of serum creatine kinase, muscle biopsy, and electrophoresis of muscle proteins. None of the parents was affected. In three families there were two affected children. Of the parents, 15 showed deficiency of type 2B muscle fibres, and all except one father showed some other minor neuromuscular abnormality. These may represent heterozygous manifestations of recessive gene. Most of the ancestors came from sparsely populated rural communities in the west of Finland. We conclude that in the Finnish CNM patients, the mode of inheritance appears to be recessive. Apart from a few instances of dominant inheritance, most cases published also seem compatible with recessive inheritance.


[Three-dimensional (3D) transvaginal ultrasound--clinical implementation in benign gynecological disorders].
The implementation of three-dimensional (3D) transvaginal (TV) ultrasound (US) in gynecology increases progressively. The method is successfully used in the diagnosis and differential diagnosis of benign gynecological pathology--congenital anomalies of the female reproductive system, fibroids, endometriosis, adenomyosis, endometrial polyps, pelvic inflammatory disease, adnexal masses, ectopic pregnancy, etc. This review describes the current use of 3D TV US in gynecological practice.


Targeting IL-17A attenuates neonatal sepsis mortality induced by IL-18.
Interleukin (IL)-18 is an important effector of innate and adaptive immunity, but its expression must also be tightly regulated because it can potentiate lethal systemic inflammation and death. Healthy and septic human neonates demonstrate elevated serum concentrations of IL-18 compared with adults. Thus, we determined the contribution of IL-18 to lethality and its mechanism in a murine model of neonatal sepsis. We find that IL-18-null neonatal mice are highly protected from polymicrobial sepsis, whereas replenishing IL-18 increased lethality to sepsis or endotoxemia. Increased lethality depended on IL-1 receptor 1 (IL-1R1) signaling but not adaptive immunity. In genome-wide analyses of blood mRNA from septic human neonates, expression of the IL-17 receptor emerged as a critical regulatory node. Indeed, IL-18 administration in sepsis increased IL-17A production by murine intestinal γδT cells as well as Ly6G(+) myeloid cells, and blocking IL-17A reduced IL-18-potentiated mortality to both neonatal sepsis and endotoxemia. We conclude that IL-17A is a previously unrecognized effector of IL-18-mediated injury in neonatal sepsis and that disruption of the deleterious and tissue-destructive IL-18/IL-1/IL-17A axis represents a novel therapeutic approach to improve outcomes for human neonates with sepsis.


Suppression of immunoreactive macrophages in atheromatous lesions of rabbits by clodronate.
Bisphosphonates inhibit the development of experimental atherosclerosis and decrease the intima-media thickness of human carotid artery. Since arterial macrophages have a key role in atherogenesis, we studied whether clodronate, an antiatherogenic bisphosphonate, will suppress the appearance of macrophages generated by atheromatous process in the rabbit aorta. The atherosclerosis was caused in rabbits by means of a high-cholesterol (1%) diet, and the animals were treated simultaneously with saline (n = 11) or 25 mg/kg of clodronate disodium (n= 12) intravenously twice a week for 6 to 12 weeks. The cholesterol diet for 6 weeks caused no visible atheromatous plaques in the aorta, but feeding for 6 more weeks produced progressively atheromatous lesions. Immunohistochemistry with specific antimacrophage antibody showed an intensive accumulation of macrophages in the subendothelial layer of the aorta in cholesterol-fed rabbits treated with saline or clodronate for 6 weeks. In the aorta of rabbits treated with cholesterol diet + saline for 12 weeks, the area of immunoreactive macrophages extended from the internal elastic lamina up to the luminal surface of the aorta. However, far less immunoreactive macrophages were present in the atheromatous regions of the aorta of rabbits medicated with clodronate for 12 weeks; in the clodronate-treated animals the macrophages were located closer to the luminal surface of the aorta than in controls on saline. No atheromatous lesions and macrophages appeared in the aorta of rabbits on standard diet (n = 7). The results suggest that clodronate suppresses the appearance of cholesterol-phagocyting macrophages in arterial walls during atherogenesis.


Phylogeny and taxonomy of powdery mildew caused by Erysiphe species on Corylus hosts.
Erysiphe species (powdery mildews) on Corylus and Ostrya hosts (Betulaceae subfam. Coryloideae) in Asia and North America are widespread pathogens on these economically and ecologically valuable nut crops. An improved understanding of their phylogeny and taxonomy is of ecological and applied importance. Phylogenetic analyses and morphological reexaminations conducted in this study revealed a higher degree of diversity and cryptic speciation than reflected in earlier species concepts. North American collections on C. cornuta, which were previously assigned to E. corylacearum, proved to constitute a species of its own and are herein introduced as E. cornutae, sp. nov. Two additional North American species, E. coryli-americanae, sp. nov. and E. ostryae, sp. nov., have been detected on C. americana and O. virginiana and are described. They are morphologically similar to E. cornutae, but genetically distinct. Based on phylogenetic analyses, E. corylacearum is an Asian species confined to various Asian Corylus species. Sequence data retrieved from Japanese type material of E. corylicola revealed that this species clusters with sequences from E. elevata on Catalpa species, distant from all other Erysiphe species on Corylus. Morphologically similar, yet distinct, specimens on C. sieboldiana, which were previously assigned to E. corylicola, form a distinct, distant clade. The species involved is described herein as E. pseudocorylacearum, sp. nov. Additionally, an unusual infection of C. sieboldiana in Japan by E. syringae has been shown by means of sequence data. The phylogeny and taxonomy of Erysiphe species belonging to the Corylioideae are discussed in detail, and a key to the species concerned is provided.


Vincristine- and bortezomib-induced neuropathies - from bedside to bench and back.
Vincristine and bortezomib are effective chemotherapeutics widely used to treat hematological cancers. Vincristine blocks tubulin polymerization, whereas bortezomib is a proteasome inhibitor. Despite different mechanisms of action, the main non-hematological side effect of both is peripheral neuropathy that can last long after treatment has ended and cause permanent disability. Many different cellular and animal models of various aspects of vincristine and bortezomib-induced neuropathies have been generated to investigate underlying molecular mechanisms and serve as platforms to develop new therapeutics. These models revealed that bortezomib induces several transcriptional programs in dorsal root ganglia that result in the activation of different neuroinflammatory pathways and secondary central sensitization. In contrast, vincristine has direct toxic effects on the axon, which are accompanied by changes similar to those observed after nerve cut. Axon degeneration following both vincristine and bortezomib is mediated by a phylogenetically ancient, genetically encoded axon destruction program that leads to the activation of the Toll-like receptor adaptor SARM1 (sterile alpha and TIR motif containing protein 1) and local decrease of nicotinamide dinucleotide (NAD+). Here, I describe current in vitro and in vivo models of vincristine- and bortezomib induced neuropathies, present discoveries resulting from these models in the context of clinical findings and discuss how increased understanding of molecular mechanisms underlying different aspects of neuropathies can be translated to effective treatments to prevent, attenuate or reverse vincristine- and bortezomib-induced neuropathies. Such treatments could improve the quality of life of patients both during and after cancer therapy and, accordingly, have enormous societal impact.


Cryoprotective effect of the serine-rich repetitive sequence in silk protein sericin.
The silk proteins, fibroin and sericin, are produced in the silk gland of Bombyx mori, and hydrophilic sericin envelops fibroin with successive sticky layers in the formation of a cocoon. To study the biological functions of sericin, we focused on the serine-rich sericin peptide consisting of 38 amino acids, which is a highly conserved and internally repetitive sequence of a sericin protein. The corresponding gene was chemically synthesized, and the PCR-amplified gene was ligated to oligomerize sericin peptide and fused at the amino terminus to a His-tagged and proteolytic cleavage sequence in an inducible expression vector. When the dimers of sericin peptides were overexpressed in Escherichia coli, the transformants showed a prominent increase in cell viability after freezing in medium. Further, the purified dimeric sericin peptide from E. coli was found to be effective in protecting lactate dehydrogenase from denaturation caused by freeze-thaw. Both of these protective effects against freezing stress in cells and proteins were also observed with sericin hydrolysate. These results indicate that this unique sericin peptide, like sericin, has a high cryoprotective activity and will be valuable as a new biomaterial for industrial use.


Population attributable fraction of infection-related cancers in Korea.
A number of infectious agents have been classified as human carcinogens. The purpose of the current study was to provide an evidence-based assessment of the burden of infection-related cancers in the Korean population. The population attributable fraction was calculated using infection prevalence data from 1990 or earlier, relative risk estimates from meta-analyses using mainly Korean studies and national data on cancer incidence and mortality for the year 2007. The fractions of all cancers attributable to infection were 25.1% and 16.8% for cancer incidence in men and women, and 25.8% and 22.7% of cancer mortality in men and women, respectively. Among infection-related cancers, Helicobacter pylori was responsible for 56.5% of cases and 45.1% of deaths, followed by hepatitis B virus (HBV) (23.9% of cases and 37.5% of deaths) and human papillomavirus (HPV) (11.3% of cases and 6% of deaths) and then by hepatitis C virus (HCV) (6% of cases and 9% of deaths). Over 97% of infection-related cancers were attributable to infection with H. pylori, HBV, HCV and HPV. Up to one-quarter of cancer cases and deaths would be preventable through appropriate control of infectious agents in Korea.


Beyond blobs in percolation cluster structure: the distribution of 3-blocks at the percolation threshold.
The incipient infinite cluster appearing at the bond percolation threshold can be decomposed into singly connected "links" and multiply connected "blobs." Here we decompose blobs into objects known in graph theory as 3-blocks. A 3-block is a graph that cannot be separated into disconnected subgraphs by cutting the graph at two or fewer vertices. Clusters, blobs, and 3-blocks are special cases of k-blocks with k=1, 2, and 3, respectively. We study bond percolation clusters at the percolation threshold on two-dimensional (2D) square lattices and three-dimensional cubic lattices and, using Monte Carlo simulations, determine the distribution of the sizes of the 3-blocks into which the blobs are decomposed. We find that the 3-blocks have fractal dimension d(3)=1.2+/-0.1 in 2D and 1.15+/-0.1 in 3D. These fractal dimensions are significantly smaller than the fractal dimensions of the blobs, making possible more efficient calculation of percolation properties. Additionally, the closeness of the estimated values for d(3) in 2D and 3D is consistent with the possibility that d(3) is dimension independent. Generalizing the concept of the backbone, we introduce the concept of a "k-bone," which is the set of all points in a percolation system connected to k disjoint terminal points (or sets of disjoint terminal points) by k disjoint paths. We argue that the fractal dimension of a k-bone is equal to the fractal dimension of k-blocks, allowing us to discuss the relation between the fractal dimension of k-blocks and recent work on path crossing probabilities.


Evaluation of polymerase chain reaction for diagnosis of pneumococcal pneumonia.
To test the ability of the polymerase chain reaction (PCR) to detect Streptococcus pneumoniae in blood, we generated two sets of nested primers. The first defined 559-bp and 649-bp regions of the pneumolysin gene, and the second defined 445-bp and 553-bp regions of the autolysin gene. These nucleotide segments were detected in DNAs from isolates of all 20 pneumococcal serotypes tested, but they were not detected when used to test DNAs from 41 isolates of nonpneumococcal bacteria and fungi. The sensitivity was evaluated by using purified pneumococcal DNA. We were able to detect 10 fg of S. pneumoniae DNA, or 4.3 genome equivalents. Blood samples were obtained from 16 patients with culture-proven pneumococcal bacteremia and were subjected to PCR analysis. Of eight buffy coat fractions tested, six showed reactivity in the PCR with the pneumolysin primers, and five of the eight produced the expected products when tested with the autolysin primers (sensitivities, 75 and 63%, respectively). Of the eight whole-blood specimens tested, only three produced the expected products with either set of primers. Additionally, we tested 14 samples from patients with bacteremia that were culture positive for nonpneumococcal bacterial species, and 13 were negative (specificity, 93%). This combination of sensitivity and specificity may make detection of S. pneumoniae in blood by PCR in comparison with that by blood culture a very promising alternative for a means of definitive diagnosis.


Molecular role of ethylene in fruit ripening of Ziziphus jujube Mill.
The fruit of Chinese jujube (Ziziphus jujube) is widely consumed by human beings due to its high proteins, vitamins, and mineral nutrients. The harvest time of Chinese jujube fruit determines its quality, while ethylene plays a pivotal role in fruit ripening. Nevertheless, the relationship between ethylene biosynthesis/signal transduction and fruit ripening of Chinese jujube is still elusive. Here, the Chinese jujube fruit ripening with its fruit peel color change from cyan to dark red at seven different ripening stages (stage I-VII) and expression levels of genes related to ethylene synthesis and signal transduction were determined. Results showed that expression levels of ZjACO1-3, ZjETR2, ZjERF1, and ZjERF4 were increasingly upregulated, whereas the expression levels of ZjERS1, ZjETI, ZjERF2, and ZjERF3 were downregulated from green to red fruit ripening stages. Among them, ZjACO1-3 promoters contain ethylene response element. Taken together, Chinese jujube fruit ripening might be affected by the ethylene signaling which was mainly regulated by ZjACO, a gene involved in ethylene biosynthesis. This research supports theories and techniques for the storage, preservation and molecular breeding of Z. jujube.


Imprint cytology of strumal carcinoid of the ovary: A case report with immunocytochemical analysis.
Strumal carcinoid is a rare ovarian tumor defined as carcinoid associated with struma ovarii. We report here the second cytological case of strumal carcinoid and performed immunocytochemical analysis for the first time. A 68-year-old Japanese female was found to have a solid tumor with small cystic components in the left ovary, and bilateral salpingo-oophorectomy was performed. The Papanicolaou smear of the imprint cytological specimen of the left ovarian tumor revealed presence of two distinct components. The first component included thyroid follicles, which was composed of flat sheets of polygonal epithelial cells without nuclear groove and intranuclear inclusion. The other component was composed of trabecular clusters of columnar cells containing round to slender nuclei with "salt and pepper" chromatin. Immunocytochemical analysis revealed that synaptophysin was expressed in the latter component. Therefore, a cytodiagnosis of strumal carcinoid was made. Histopathological analyses confirmed the diagnosis of strumal carcinoid. Albeit rare, carcinoid tumor occurs in the ovary, and the recognition of characteristic nuclear features and cellular arrangement leads to correct cytodiagnosis. Presence of struma ovarii component suggests an ovarian origin. Moreover, immunocytochemical analysis for neuroendocrine markers aids its differential diagnosis from granulosa cell tumor and carcinoma arising from struma ovarii.


Nanoplatform-based cascade engineering for cancer therapy.
Various therapeutic techniques have been studied for treating cancer precisely and effectively, such as targeted drug delivery, phototherapy, tumor-specific catalytic therapy, and synergistic therapy, which, however, evoke numerous challenges due to the inherent limitations of these therapeutic modalities and intricate biological circumstances as well. With the remarkable advances of nanotechnology, nanoplatform-based cascade engineering, as an efficient and booming strategy, has been tactfully introduced to optimize these cancer therapies. Based on the designed nanoplatforms, pre-supposed cascade processes could be triggered under specific conditions to generate/deliver more therapeutic species or produce stronger tumoricidal effects inside tumors, aiming to achieve cancer therapy with increased anti-tumor efficacy and diminished side effects. In this review, the recent advances in nanoplatform-based cascade engineering for cancer therapy are summarized and discussed, with an emphasis on the design of smart nanoplatforms with unique structures, compositions and properties, and the implementation of specific cascade processes by means of endogenous tumor microenvironment (TME) resources and/or exogenous energy inputs. This fascinating strategy presents unprecedented potential in the enhancement of cancer therapies, and offers better controllability, specificity and effectiveness of therapeutic functions compared to the corresponding single components/functions. In the end, challenges and prospects of such a burgeoning strategy in the field of cancer therapy will be discussed, hopefully to facilitate its further development to meet the personalized treatment demands.


Liver transplantation for iatrogenic porta hepatis transection.
Iatrogenic porta hepatis transection is a rare but devastating surgical complication. There are no systematic studies examining the best treatment strategy in patients with this injury. We report two cases of transection of all three portal structures, one during an open right adrenalectomy and another during a laparoscopic cholecystectomy, both of which were transferred to our tertiary care center hours postinjury. Diagnostic imaging and exploration revealed nonsalvageable livers, and both patients underwent total hepatectomies and portocaval shunting. Donor livers were available 12 to 20 hours after United Network for Organ Sharing Status 1 listing and both patients survived their postoperative course with 2- and 6-year follow up to date. Two-stage total hepatectomy with portocaval shunting followed by liver transplantation should be considered for patients presenting with porta hepatis transection.


Blunt splenic injuries: nonsurgical treatment with CT, arteriography, and transcatheter arterial embolization of the splenic artery.
The management and outcome of blunt splenic injury diagnosed with computed tomography (CT) were studied in 44 consecutive patients who were hemodynamically stable or whose condition stabilized rapidly with resuscitation. Celiac and splenic arteriography was used in the triage of patients for nonsurgical treatment or for hemostasis. Patients without arterial extravasation of contrast material at arteriography were treated with bed rest only (group 1, n = 19); patients who had such extravasation were treated with bed rest after percutaneous transcatheter coil occlusion of the proximal splenic artery (group 2, n = 17). Abdominal exploration without angiography or embolotherapy was begun if the patient or attending surgeon did not agree with the treatment protocol (group 3, n = 8). Treatment with bed rest alone was successful in 18 patients. Clinical control of hemorrhage was accomplished in all patients in group 2 and one patient in group 1. Thus, exploratory laparotomy was avoided in 34 of 36 patients (94%) in whom nonoperative management was attempted; splenic salvage was achieved in 35 of 36 patients (97%).


Surgical and endovascular hybrid approach in peripheral arterial disease of the lower limbs.
Multilevel peripheral arterial disease is frequently observed in patients with intermittent claudication or critical limb ischemia. This report evaluates the efficacy of one-stage hybrid revascularization in patients with multilevel arterial peripheral disease. A retrospective analysis of a prospective database included all consecutive patients treated by a hybrid approach for a multilevel arterial peripheral disease. The primary outcome was the patency rate at 6 months and 1 year. Secondary outcomes were early and midterm complication rate, limb salvage and mortality rate. Statistical analysis, including a Kaplan-Meier estimate and univariate and multivariate Cox regression analyses were carried out with the primary, primary assisted and secondary patency, comparing the impact of various risk factors in pre- and post-operative treatments. 64 patients were included in the study, with a mean follow-up time of 428 days (range: 4 - 1140). The technical success rate was 100 %. The primary, primary assisted and secondary patency rates at 1 year were 39 %, 66 % and 81 %, respectively. The limb-salvage rate was 94 %. The early mortality rate was 3.1 %. Early and midterm complication rates were 15.4 % and 6.4 %, respectively. The early mortality rate was 3.1 %. The hybrid approach is a major alternative in the treatment of peripheral arterial disease in multilevel disease and comorbid patients, with low complication and mortality rates and a high limb-salvage rate.


Evaluation of radiation exposure from diagnostic radiology examination; availability of final recommendations--FDA. Notice.
The Food and Drug Administration (FDA) is announcing the availability of a document entitled "Recommendations for Evaluation of Radiation Exposure from Diagnostic Radiology Examinations". The recommendations, prepared by FDA's Center for Devices and Radiological Health (CDRH), encourage diagnostic radiology facilities to take voluntary action to: Become aware of the radiation levels experienced by patients undergoing the projections commonly given in the facility; compare their radiation levels to generally accepted levels for these projections; and bring the exposures back into line if their levels fall consistently outside these generally accepted levels.


Entropy-driven spatial organization of highly confined polymers: lessons for the bacterial chromosome.
Despite recent progress in visualization experiments, the mechanism underlying chromosome segregation in bacteria still remains elusive. Here we address a basic physical issue associated with bacterial chromosome segregation, namely the spatial organization of highly confined, self-avoiding polymers (of nontrivial topology) in a rod-shaped cell-like geometry. Through computer simulations, we present evidence that, under strong confinement conditions, topologically distinct domains of a polymer complex effectively repel each other to maximize their conformational entropy, suggesting that duplicated circular chromosomes could partition spontaneously. This mechanism not only is able to account for the spatial separation per se but also captures the major features of the spatiotemporal organization of the duplicating chromosomes observed in Escherichia coli and Caulobacter crescentus.


Antiemetic efficacy of cimetidine randomized, double-blind, crossover study with dexamethasone in cancer patients receiving emetogenic chemotherapy.
In a randomized, double-blind, crossover study the antiemetic effect of cimetidine was compared with that of dexamethasone in cancer patients receiving emetogenic chemotherapy. Thirty-two patients were evaluable and all were chemotherapy-naive. Eight patients (25%) received high doses of cisplatin, 17 (53%) had cyclophosphamide in combination treatment, 2 (6%) received adriamycin, and 1 another chemotherapy of less emetogenic potential. Complete protection (CR) rates of 59.4% and 62.5% were achieved with cimetidine and dexamethasone, respectively. In addition, three (9.4%) and 1 (3%) patients attained partial protection with cimetidine and dexamethasone, respectively. No significant difference was noted between the two antiemetic therapies (p = 0.07). Although CR has not been achieved in any of those patients who received cisplatin, a comparable antiemetic effect was attained. Both antiemetic regimens were well tolerated with minimal side effects. We conclude that the antiemetic potential of cimetidine and its safety deserve further investigation in a larger study, perhaps in combination with other antiemetic agents.


Quantitative Fluorescence In Situ Hybridization (FISH) and Immunofluorescence (IF) of Specific Gene Products in KSHV-Infected Cells.
Mechanistic insight arrives from careful study and quantification of specific RNAs and proteins. The relative locations of these biomolecules throughout the cell at specific times can be captured with fluorescence in situ hybridization (FISH) and immunofluorescence (IF). During lytic herpesvirus infection, the virus hijacks the host cell to preferentially express viral genes, causing changes in cell morphology and behavior of biomolecules. Lytic activities are centered in nuclear factories, termed viral replication compartments, which are discernable only with FISH and IF. Here we describe an adaptable protocol of RNA FISH and IF techniques for Kaposi's sarcoma-associated herpesvirus (KSHV)-infected cells, both adherent and in suspension. The method includes steps for the development of specific anti-sense oligonucleotides, double RNA FISH, RNA FISH with IF, and quantitative calculations of fluorescence intensities. This protocol has been successfully applied to multiple cell types, uninfected cells, latent cells, lytic cells, time-courses, and cells treated with inhibitors to analyze the spatiotemporal activities of specific RNAs and proteins from both the human host and KSHV.


Characterization of deletion and truncation mutants of the rat glucagon receptor. Seven transmembrane segments are necessary for receptor transport to the plasma membrane and glucagon binding.
Glucagon receptor mutants were characterized with the aim of elucidating minimal structural requirements for proper biosynthesis, ligand binding, and adenylyl cyclase coupling. One N-terminal deletion mutant and five truncation mutants with progressively shorter C termini were expressed in transiently transfected monkey kidney (COS-1) cells. Each truncation mutant was designed so that the truncated C-terminal tail would remain on the cytoplasmic surface of the receptor. In order to characterize the cellular location of the expressed receptor mutants, a highly specific, high affinity antipeptide antibody was prepared against the extracellular, N-terminal tail of the receptor. Immunoblot analysis and immunofluorescence microscopy showed that the presence of all seven putative transmembrane segments, but not not an intact N-terminal tail, was required for cell surface expression of the receptor. Membranes from cells expressing receptor mutants lacking a large portion of the N-terminal tail or any of the seven putative transmembrane segments failed to bind glucagon. Membranes from cells expressing the C-terminal tail truncation mutants, which retained all seven transmembrane segments, bound glucagon with affinities similar to that of the native receptor and activated cellular adenylyl cyclase in response to glucagon. These results indicate that all seven helices are necessary for the proper folding and processing of the glucagon receptor. Glycosylation is not required for the receptor to reach the cell surface, and it may not be required for ligand binding. However, the N-terminal extracellular portion of the receptor is required for ligand binding. Most of the distal C-terminal tail is not necessary for ligand binding, and the absence of the tail may increase slightly the receptor binding affinity for glucagon. The C-terminal tail is also not necessary for adenylyl cyclase coupling and therefore does not play a direct role in G protein (GS) activation by the glucagon receptor.


Ultrastructure of the membrana limitans interna after dye-assisted membrane peeling.
The purpose of this study was to investigate the ultrastructure of the membrana limitans interna (internal limiting membrane, ILM) and to evaluate alterations to the retinal cell layers after membrane peeling with vital dyes. Twenty-five patients (25 eyes) who underwent macular hole surgery were included, whereby 12 indocyanine green (ICG)- and 13 brilliant blue G (BBG)-stained ILM were analyzed using light, transmission electron and scanning electron microscopy. Retinal cell fragments on the ILM were identified in both groups using immunohistochemistry. Comparing ICG- and BBG-stained membranes, larger cellular fragments were observed at a higher frequency in the BBG group. Thereby, the findings indicate that ICG permits an enhanced separation of the ILM from the underlying retina with less mechanical destruction. A possible explanation might be seen in the known photosensitivity of ICG, which induces a stiffening and shrinkage of the ILM but also generates retinal toxic metabolites.


The ionic mechanism of gamma resonance in rat striatal fast-spiking neurons.
Striatal fast-spiking (FS) cells in slices fire in the gamma frequency range and in vivo are often phase-locked to gamma oscillations in the field potential. We studied the firing patterns of these cells in slices from rats ages 16-23 days to determine the mechanism of their gamma resonance. The resonance of striatal FS cells was manifested as a minimum frequency for repetitive firing. At rheobase, cells fired a doublet of action potentials or doublets separated by pauses, with an instantaneous firing rate averaging 44 spikes/s. The minimum rate for sustained firing was also responsible for the stuttering firing pattern. Firing rate adapted during each episode of firing, and bursts were terminated when firing was reduced to the minimum sustainable rate. Resonance and stuttering continued after blockade of Kv3 current using tetraethylammonium (0.1-1 mM). Both gamma resonance and stuttering were strongly dependent on Kv1 current. Blockade of Kv1 channels with dendrotoxin-I (100 nM) completely abolished the stuttering firing pattern, greatly lowered the minimum firing rate, abolished gamma-band subthreshold oscillations, and slowed spike frequency adaptation. The loss of resonance could be accounted for by a reduction in potassium current near spike threshold and the emergence of a fixed spike threshold. Inactivation of the Kv1 channel combined with the minimum firing rate could account for the stuttering firing pattern. The resonant properties conferred by this channel were shown to be adequate to account for their phase-locking to gamma-frequency inputs as seen in vivo.


Low-frequency hearing preceded the evolution of giant body size and filter feeding in baleen whales.
Living baleen whales (mysticetes) produce and hear the lowest-frequency (infrasonic) sounds among mammals. There is currently debate over whether the ancestor of crown cetaceans (Neoceti) was able to detect low frequencies. However, the lack of information on the most archaic fossil mysticetes has prevented us from determining the earliest evolution of their extreme acoustic biology. Here, we report the first anatomical analyses and frequency range estimation of the inner ear in Oligocene (34-23 Ma) fossils of archaic toothed mysticetes from Australia and the USA. The cochlear anatomy of these small fossil mysticetes resembles basilosaurid archaeocetes, but is also similar to that of today's baleen whales, indicating that even the earliest mysticetes detected low-frequency sounds, and lacked ultrasonic hearing and echolocation. This suggests that, in contrast to recent research, the plesiomorphic hearing condition for Neoceti was low frequency, which was retained by toothed mysticetes, and the high-frequency hearing of odontocetes is derived. Therefore, the low-frequency hearing of baleen whales has remained relatively unchanged over the last approximately 34 Myr, being present before the evolution of other signature mysticete traits, including filter feeding, baleen and giant body size.


[A case of sarcoidosis with diabetes insipidus].
A 23-year-old man was admitted because of polydipsia and polyuria. As chest radiographs and computed tomography showed mediastinal and bilateral hilary lymph node swelling, and diffuse small nodules in bilateral lung fields, we suspected sarcoidosis. Sarcoidosis was diagnosed by biopsy of a cervical lymph node, and central diabetes insipidus was diagnosed by fluid restriction test and vasopressin load test. A pituitary mass was also revealed by magnetic resonance imaging. Prednisolone therapy improved all of his clinical findings except diabetes insipidus. He had to continue intranasal 1-desamino-8-D-arginine vasopressin (DDAVP) therapy.


Vibrational dephasing in ionic liquids as a signature of hydrogen bonding.
Understanding both structure and dynamics is crucial for producing tailor-made ionic liquids (ILs). We studied the vibrational and structural dynamics of medium versus weakly hydrogen-bonded CH groups of the imidazolium ring in ILs of the type [1-alkyl-3-methylimidazolium][bis(trifluoromethanesulfonyl)imide] ([Cn mim][NTf2 ]), with n=1, 2, and 8, by time-resolved coherent anti-Stokes Raman scattering (CARS) and quantum-classical hybrid (QCH) simulations. From the time series of the CARS spectra, dephasing times were extracted by modeling the full nonlinear response. From the QCH calculations, pure dephasing times were obtained by analyzing the distribution of transition frequencies. Experiments and calculations reveal larger dephasing rates for the vibrational stretching modes of C(2)H compared with the more weakly hydrogen-bonded C(4,5)H. This finding can be understood in terms of different H-bonding motifs and the fast interconversion between them. Differences in population relaxation rates are attributed to Fermi resonance interactions.


Longitudinal analysis of chronic allograft nephropathy: clinicopathologic correlations.
Loss of the allograft from chronic allograft nephropathy and death of the patient from vascular, malignant, or infective disease are the major problems in renal transplantation today. Protocol biopsy of the long-term kidney has provided new data with which to develop strategies for prevention and treatment of chronic allograft nephropathy. Two series of long-term protocol biopsies are reviewed. In the first, renal biopsies were obtained at time 0, and at 3 months and 12 months, and the recipients of the renal allografts were followed up for up to 15 years. In the second, the kidneys of recipients of simultaneous pancreas kidney transplants were biopsied annually for 10 years, and the results correlated with clinical events. Chronic allograft nephropathy is caused by acute and chronic immune-mediated damage, as well as by chronic calcineurin inhibitor nephrotoxicity. Both immune and nonimmune mechanisms exacerbate pre-existing donor disease and ischemia-reperfusion injury. Established interstitial fibrosis and arteriolar hyalinosis lead to progressive glomerular sclerosis and eventual loss of the graft. Protocol biopsies have shown that clinical parameters of renal function underestimate the severity of chronic graft damage. Strategies for preventing or treating chronic renal allograft dysfunction and subsequent graft loss must better control rejection and simultaneously avoid nephrotoxicity.


Pathogenesis of slipped capital femoral epiphysis: current concepts.
Since Ambrose Paré in 1572 initially described what is believed to be the first case of slipped capital femoral epiphysis (SCFE), a virtual plethora of unproven theories has evolved in the ensuing years. The most currently popular theories embrace a framework of biomechanical events versus biochemical events having impact at the time of puberty. The zone of slipping always occurs primarily through the zone of hypertrophy in a corrugated undulating fashion. All investigative studies show that the growth plate at the time of puberty is weakened in SCFE. The final common pathway appears to be a mechanical failure of the growth plate, due to a weakened state, to resist displacement. The commonly encountered large body mass coupled with an increasingly oblique physis lying in a relative degree of retroversion creates a mechanical environment that, coupled with delicate alterations in the hormonal balance of thyroid hormone, growth hormone, testosterone, and estrogen, render the plate intrinsically suspectible to displacement by rather innocuous forces occurring in a shear plane. Ultrastructure studies of SCFE demonstrate a significant alteration in anatomy and physiology in all active metabolic areas of the growth plate. It is the author's concept that SCFE is a generalized metabolic disorder of puberty resulting from a series of pubertal mishaps with a multifactorial basis ordinarily caused by a relative imbalance of hormones, coupled with biomechanical events.


A randomized study to evaluate the efficacy and safety of adding topical therapy to etanercept in patients with moderate to severe plaque psoriasis.
Few clinical trials have evaluated the combination of topical corticosteroids plus systemic therapies for psoriasis. We sought to evaluate efficacy and safety of etanercept plus topical clobetasol propionate (CP) foam versus etanercept monotherapy for treatment of moderate to severe plaque psoriasis. Adults with Psoriasis Area and Severity Index (PASI) score greater than or equal to 10 and psoriasis-affected body surface area greater than or equal to 10% were randomized to etanercept with CP as needed to clear (2 up-to-2-week courses, weeks 11-12 and 23-24) or etanercept alone (each arm at 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks). A total of 592 patients enrolled (295 etanercept + CP arm; 297 etanercept arm). At week 12, significant differences were observed for response of 75% improvement in PASI score (primary end point, 65.2% vs 48.3% in the etanercept + CP vs etanercept arms, respectively; P < .001), response of 90% improvement in PASI score (29.7% vs 19.4%; P = .009), percentage PASI score improvement (76.5% vs 68.2%; P < .001), static physician global assessment of clear/almost clear (63.1% vs 47.3%; P < .001), and patient satisfaction with treatment (P = .006). Response of 75% improvement in PASI score and static physician global assessment of clear/almost clear were not significantly different between arms at week 24. Patient satisfaction with treatment (P = .001) and percentage improvement in PASI score (P = .031) were also greater in the etanercept + CP arm compared with etanercept only at week 24. Comparable numbers of adverse events occurred in each arm. No placebo for CP foam was provided in the etanercept arm. Addition of CP to etanercept yielded increased efficacy compared with etanercept alone at week 12 without an increase in treatment-related adverse events.


A centrifuge-less plasma separation method from whole blood anticoagulated with EDTA-2K for the use of clinical laboratory tests.
In the modern medical laboratory system, simple and rapid processing of specimens are required. In the current system with the transportation line, its centrifugation part would disturb smooth flow of the testing because it needs much time for the centrifugation. To solve the problems, a serum separation method was tried for the whole blood specimen using poly-L-lysine, concanavalin A and phyto-hemoagglutinin. Ploy-L-lysine with molecular weight 130,000 to 210,000 in a final concentration of 0.1% could accelerate blood sedimentation, although its supernatant contaminated platelets. Concanavalin and phytohemoagulutinin could accelerate the sedimentation and obtained plasma, but the method could yield enough amount of supernatant by 1 hour standing. As the purpose of this study is to develop a centrifugeless method, a sieve method using a steel mesh and a magnet was applied to the mixture of EDTA blood, red-cell adhesives and thrombin. The method was unique to separate plasma, but the yield was not so high and chemistry data were not fitted with serum data in some of tests. Thus, the trial would be a new technology, but it was judged that some further improvement will be needed technically.


Sleep quality varies as a function of 5-HTTLPR genotype and stress.
To test the hypothesis that allelic variation in 5HTT gene-linked polymorphic region (5-HTTLPR) genotype was associated with sleep quality (Pittsburgh Sleep Quality Index, PSQI) as a main effect and as moderated by the chronic stress of caregiving. Serotonin (5HT) is involved in sleep regulation and the 5HT transporter (5HTT) regulates 5HT function. A common 44-base pair deletion (s allele) polymorphism in the 5-HTTLPR is associated with reduced 5HTT transcription efficiency and 5HT uptake in vitro. Subjects were 142 adult primary caregivers for a spouse or parent with dementia and 146 noncaregiver controls. Subjects underwent genotyping and completed the PSQI. Variation in 5-HTTLPR genotype was not related to sleep quality as a main effect (p > .36). However, there was a caregiver X 5-HTTLPR interaction (p < .009), such that the s allele was associated with poorer sleep quality in caregivers as compared with controls. Findings suggest that the s allele may moderate sleep disturbance in response to chronic stress.


When legislation precedes the state of the art in teacher training: problems and implications.
Passage of Public Law 94-142, the Education for all Handicapped Children Act requires the development of an Individualized Education Program (IEP) for each handicapped child served. While administration are inclined to view the IEP as a document intended to monitor the provision of special services, teachers focused on the potential instructional value of the IEP. Professionals agree that this has been one of the most difficult components of the law to implement. Policymakers designing the law posited that training technology was adequate to support the instructional requirements outlined in the legislation. The present study challenges that assumption. It is also argued that studies which attempt to integrate multiple operations to clarify findings can provide more accurate and consequently more useful data of critical value in the beginning stages of policy formation. The multiple data collection strategies employed in this study yielded increasingly specific information on the status of present training technology--particularly in relation to teacher skills related to the instructional aspects of the IEP planning process. Teacher perceptions of their training needs were compared with actual skill performances on selected IEP tasks. Data reveal the inadequacy of essential skills in formulating required goal and objective statements. Special education and regular classroom teachers show similar patterns in specific skills which are problematic. Statements from teacher interviews corroborated deficits in past training. Suggestions for future training are offered as are emphases for needed research. Implications for implementation of the IEP are also discussed.


Structural Failure Sites in Anterior Vaginal Wall Prolapse: Identification of a Collinear Triad.
To test the null hypothesis that six factors representing potential fascial and muscular failure sites contribute equally to the presence and size of a cystocele: two vaginal attachment factors (apical support and paravaginal defects), two vaginal wall factors (vaginal length and width), and two levator ani factors (hiatus size and levator ani defects). Thirty women with anterior-predominant prolapse (women in a case group) and 30 women in a control group underwent three-dimensional stress magnetic resonance imaging. The location of the anterior vaginal wall at maximal Valsalva was identified with the modified Pelvic Inclination Coordinate System and the six factors measured. Analysis included repeated-measure analysis of variance, logistic regression, and stepwise linear regression. We identified a collinear triad consisting of apical location, paravaginal location, and hiatus size that were not only the strongest predictors of cystocele size, but were also highly correlated with one another (r=0.84-0.89, P<.001) for the presence and size of the prolapse. Together they explain up to 83% of the variation in cystocele size. Among the less significant vaginal factors, vaginal length explained 19% of the variation in cystocele size, but no significant difference in vaginal width existed. Women in the case group were more likely to have abnormalities in collinear triad factors (up to 80%) than vaginal wall factors (up to 23.3%). Combining the strongest collinear triad with the vaginal factors, the model explained 92.5% of the variation in cystocele size. Apical location, paravaginal location, and hiatus size are highly correlated and are strong predictors of cystocele presence and size.


Organic Photovoltaic Cells Based on Nonhalogenated Polymer Donors and Nonhalogenated A-DA'D-A-Type Nonfullerene Acceptors with High VOC and Low Nonradiative Voltage Loss.
Compared with other all-inorganic/organic-inorganic hybrid solar cells, the large voltage loss (Vloss) of organic photovoltaic (OPV) cells, especially the nonradiative voltage loss (ΔVnonrad), limited the further improvement of performance. Although A-DA'D-A-type Y-series nonfullerene acceptors (NFAs) largely improve the power conversion efficiencies (PCEs) to 18%, the open-circuit voltage (VOC) of this kind of material was still restricted to below 1.0 V. Herein, we designed and synthesized a narrow bandgap (Eg = 1.41 eV) acceptor BTA77 with an A-DA'D-A-type backbone containing a nonhalogenated terminal group to achieve high electroluminescence efficiency and high VOC. Combined with the nonhalogenated polymer PBDB-T with a conjugated thiophene side chain, BTA77 realized a VOC of 0.944 V, a Vloss of 0.552 V, and a PCE of 13.75%, which is one of the highest PCEs based on nonhalogenated A-DA'D-A-type acceptors with VOC > 0.9 V. After further blending with the nonhalogenated donor polymer PBT1-C with a conjugated phenyl side chain, the VOC increases to 1.021 V with a super low ΔVnonrad of 0.14 V owing to the greatly improved electroluminescence external quantum efficiency (EQEEL) of 4.42 × 10-3. Our results indicate that there is still a large room to decrease the ΔVnonrad and increase VOC by synergistic molecular engineering of p-type polymers and n-type small molecules.


Xanthones from Securidaca inappendiculata antagonized the antirheumatic effects of methotrexate in vivo by promoting its secretion into urine.
This study was designed to characterize the interaction between Securidaca inappendiculata Hassk. derived xanthones and methotrexate (MTX). Collagen-induced arthritis (CIA) was induced in rats, which were treated with MTX, a xanthone-rich fraction (XRF), or MTX+XRF by gavage for 30 days. Clinical efficacy was assessed based on arthritis scores, serological analysis, and histological examination. Protein expression was investigated by either immunohistochemical or immunoblotting methods. MTX concentrations were determined by HPLC or LC-MS methods. Obtained results were further validated by in vitro assays using 1,7-dihydroxy-3,4-dimethoxyxanthone and HEK 293 T cells. XRF antagonized the antirheumatic effects of MTX in vivo, suggested by higher levels of proinflammatory cytokines, and severer swelling and deformation of joints in CIA rats in the MTX+XRF group compared with MTX monotherapy. XRF reduced MTX concentration in plasma and promoted its excretion into urine. As a result, XRF attenuated MTX-induced edema of the proximal tubule. Furthermore, XRF restored the decreased expression of organic anion transporter three (OAT3), which accounts for MTX secretion in the kidney. Consistently, 1,7-dihydroxy-3,4-dimethoxyxanthone promoted the cellular intake of MTX by increasing OTA3 expression. It is suggested that the combined use of S. inappendulata with MTX should be optimized to avoid the antagonistic effects and improve the safety of the MTX regimen.