Influence of some antirheumatic drugs and cytostatics on urinary enzyme level.
In experiments with rats, the influence of the treatment with sodium salicylate (350 mg/kg), phenylbutazone (100 mg/kg), cyclophosphamide (5 mg/kg), 6-mercaptopurine (25 mg/kg) and D-penicillamine (50 mg/kg), on urinary lactate dehydrogenase, leucine aminopeptidase and alanine aminopeptidase was investigated. All these drugs caused an increase in the enzyme levels in urine. In the case of sodium salicylate, the increase occurred only after the first administration of the drug; phenylbutazone caused a gradual increase of the enzymes. Cytostatic drugs caused an increase in the level of the investigated enzymes in urine with a maximum after 1 week of treatment.


MicroRNA regulation of MDM2-p53 loop in pterygium.
The pathogenesis of pterygium has been linked to limbal stem cell damage, abnormal apoptosis and cellular proliferation. In this study, we investigated the epigenetic regulation through microRNA expression in the pathogenesis of pterygium. Human full-length primary pterygia were microdissected into head and body regions. Specific microRNA and mRNA expression was assayed by TaqMan® real-time quantitative polymerase chain reaction (qPCR). Tissue localization of target microRNAs was performed by LNA-based in situ hybridization. MicroRNA-145 (miR-145) mimics were transfected to primary culture of human pterygial cells, followed by analyses of cell cycle changes, apoptosis, p53 and MDM2 expression using flow cytometry and qPCR. The expression of miR-145 was markedly higher in primary human pterygium than in limbus and conjunctiva. Both miR-143 and miR-145 were predominantly expressed in the basal pterygial epithelium. Oncogene MDM2 expression was abundant in pterygial epithelium and stroma, while the expression pattern was opposite to that of miR-145. Ectopic expression of miR-145 in pterygial cells induced G1 arrest, down-regulated MDM2 and elevated p53 expression. Our study showed that miR-145 suppressed MDM2 expression, which subsequently influenced the p53-related cell growth pattern in pterygial epithelium. The regulatory miR-145/MDM2-p53 loop can serve as a potential target for treatment of pterygium.


Binding of zinc(II) to beta-D-fructose 2,6-bisphosphate.
The formation of a complex between Zn(II) and beta-D-fructose 2,6-bisphosphate was shown because the latter compound: activated bis(5'-guanosyl)tetraphosphatase (EC 184.108.40.206) and dinucleoside triphosphatase (EC 220.127.116.11) only to the extent that they could be inhibited by Zn(II); increased the consumption of Zn(II) necessary to titrate to an end point a solution of the metallochromic indicator eriochrome black T; coeluted with Zn(II) in a gel filtration column capable of resolving them if unbound. Neither of those effects was shown by D-fructose 1,6-bisphosphate under the same conditions.


In vitro studies of nuclear volume of rat adrenocortical cells: lace of ACTH effect.
The effect of ACTH on nuclear volume of adrenocortical cells in the zona fasciculata of rat adrenal cortex was examined in vitro. Sections of adrenal gland were incubated for 60 or 90 min in Krebs-Ringer's solution with 1% glucose in the presence of ACTH, actinomycin D, cycloheximide and aminoglutethimide. ACTH, despite its clear effect in stimulating steroidogenesis, did not exert a direct effect on the nuclear volume of cells studied. This phenomenon is not dependent upon the stimulation of steroidogenesis, since aminoglutethimide does not influence the nuclear volume of adrenocortical cells studied; rather, ACTH in the presence of aminoglutethimide leads to a decrease in their volume. Actinomycin D does not influence nuclear volume while after incubation with cycloheximide nuclei were larger than the control. The presence of ACTH did not alter this effect. These results indicate no relationship between the degree of corticosterone output and nuclear volume in rat adrenocortical cells of the zona fasciculata in vitro.


MiR-429 suppresses the progression and metastasis of osteosarcoma by targeting ZEB1.
MiR-429 functions as a tumor suppressor and has been observed in multiple types of cancer, but the effects and mechanisms of miR-429 in osteosarcoma are poorly understood. This study is performed to evaluate the functions of miR-429 in the progression of osteosarcoma. Firstly, the miR-429 expression in osteosarcoma tissues and osteosarcoma cells was detected using real time PCR, and the relationship between miR-429 expression and overall survival of osteosarcoma was analyzed. Secondly, the effects of miR-429 on the migration, invasion, proliferation and apoptosis of osteosarcoma cells were evaluated using transwell assay, wound-healing assay, CCK-8 assay and flow cytometry, respectively. Proteins related to epithelial-mesenchymal transition (EMT), E-cadherin, Vimentin, N-cadherin and Snail, were also detected using Western blot. Finally, the target gene of miR-429 in osteosarcoma was predicted and verified using dual luciferase assay and the expression correlation between them was analyzed using Pearson's correlation. MiR-429 was down-regulated in osteosarcoma tissues and osteosarcoma cells; the expression level of miR-429 was associated with the prognosis of osteosarcoma. High level of miR-429 in osteosarcoma cells significantly suppressed the migration, invasion and proliferation of cells but induced cells apoptosis. Furthermore, high level of miR-429 in osteosarcoma cells obviously increased the expression of E-cadherin protein but decreased the expression of Vimentin, N-Cadherin and Snail proteins. EMT inducer ZEB1 was the target gene of miR-429 and the expression of ZEB1 was negatively related to the miR-429 expression in osteosarcoma. In conclusion, miR-429 may functions as a tumor suppressor and be down-regulated in osteosarcoma. MiR-429 may suppress the progression and metastasis of osteosarcoma by down-regulating the ZEB1 expression.


Filling out phenomenon with technetium-99m HM-PAO brain SPECT at the site of mild cerebral ischemia.
Although the distribution of [99mTc]hexamethylpropyleneamine oxime (HM-PAO) in the brain is said to be in a flow-related manner without temporal change, we present cases with leakage of [99mTc]HM-PAO (filling out phenomenon) in the delayed image of brain single photon emission computed tomography (SPECT) and clarify its clinical significance. The filling out phenomenon was observed in seven out of 21 cases of cerebrovascular disease and four cases of arteriovenous malformation. The leakage of [99mTc]HM-PAO was also confirmed by visual and semiquantitative analysis. In the pharmacokinetics of [99mTc]HM-PAO in the blood, the percent dose of plasma fraction at 4 hr was reduced to 54% of activity at 30 min. The percent dose of brain blood could be predicted as 3.36%/1 at 30 min and 2.35%/1 at 4 hr after correction with the hematocrit of the brain. The filling out phenomenon of [99mTc]HM-PAO was attributed to a significant reduction of blood activity of [99mTc]HM-PAO in the plasma. Since the initial image might mask reduced rCBF with an increase of rCBV, the late image would have an advantage in accurately evaluating rCBF from the clearance of [99mTc] HM-PAO bound to the plasma. Therefore, the filling out phenomenon of [99mTc]HM-PAO in late images of brain SPECT could show the area of mild cerebral ischemia accompanying cerebral vascular reserve.


Engaging patients, clinicians and health funders in weight management: the Counterweight Programme.
The Counterweight Programme provides an evidence based and effective approach for weight management in routine primary care. Uptake of the programme has been variable for practices and patients. Aim. To explore key barriers and facilitators of practice and patient engagement in the Counterweight Programme and to describe key strategies used to address barriers in the wider implementation of this weight management programme in UK primary care. All seven weight management advisers participated in a focus group. In-depth interviews were conducted with purposeful samples of GPs (n = 7) and practice nurses (n = 15) from 11 practices out of the 65 participating in the programme. A total of 37 patients participated through a mixture of in-depth interviews (n = 18) and three focus groups. Interviews and focus groups were analysed for key themes that emerged. Engagement of practice staff was influenced by clinicians' beliefs and attitudes, factors relating to the way the programme was initiated and implemented, the programme content and organizational/contextual factors. Patient engagement was influenced by practice endorsement of the programme, clear understanding of programme goals, structured proactive follow-up and perception of positive outcomes. Having a clear understanding of programme goals and expectations, enhancing self-efficacy in weight management and providing proactive follow-up is important for engaging both practices and patients. The widespread integration of weight management programmes into routine primary care is likely to require supportive public policy.


IL-17 induces the proliferation and migration of glioma cells through the activation of PI3K/Akt1/NF-κB-p65.
Interleukin 17 (IL-17), as a pro-inflammatory cytokine, is up-regulated in the sera and tumor tissues of glioma patients; however the effects of IL-17 on glioma proliferation and migration remain unclear. In this study, the roles of IL-17 in the proliferation and migration of glioma cells and their potential mechanisms were determined. The results showed that IL-17 could not only enhance the proliferation and migration of cultured glioma cells (in vitro), but also promote the tumor formation of glioma cells in BALB/c nude mice (in vivo). Mechanical exploration revealed that IL-17 stimulation could increase the phosphorylation levels of Akt1 and NF-κB-p65 in glioma cells, and knockdown or inhibition of PI3K, Akt1 and NF-κB-p65 could also reduce the IL-17-induced proliferation and migration of the glioma cells. Moreover, PI3K/Akt1 was the upstream regulator of NF-κB-p65 activation in IL-17-incubated glioma cells. Furthermore, the inhibition of PI3K, Akt1 and NF-κB-p65 markedly suppressed the tumor formation of glioma cells induced by IL-17. Together, these data indicate that IL-17 can promote the proliferation and migration of glioma cells via PI3K/Akt1/NF-κB-p65 activation, and these findings might provide a new insight into glioma pathogenesis.


How was the Earth-Moon system formed? New insights from the geodynamo.
The most widely accepted scenario for the formation of the Earth-Moon system involves a dramatic impact between the proto-Earth and some other cosmic body. Many features of the present-day Earth-Moon system provide constraints on the nature of this impact. Any model of the history of the Earth must account for the physical, geochemical, petrological, and dynamical evidence. These constraints notwithstanding, there are several radically different impact models that could in principle account for all the evidence. Thus, in the absence of further constraints, we may never know for sure how the Earth-Moon system was formed. Here, we put forward the idea that additional constraints are indeed provided by the fact that the Earth is strongly magnetized. It is universally accepted that the Earth's magnetic field is maintained by a dynamo operating in the outer liquid core. However, because of the rapid rotation of the Earth, this dynamo has the peculiar property that it can maintain a strong field but cannot amplify a weak one. Therefore, the Earth must have been magnetized at a very early epoch, either preimpact or as a result of the impact itself. Either way, any realistic model of the formation of the Earth-Moon system must include magnetic field evolution. This requirement may ultimately constrain the models sufficiently to discriminate between the various candidates.


A prospective study of the demographics, management and outcome of patients with acute kidney injury in Cape Town, South Africa.
To study the demographics and outcome of acute kidney injury (AKI) at Groote Schuur Hospital, Cape Town, South Africa. A prospective observational study of AKI fulfilling the Kidney Disease: Improving Global Outcomes definition, from 8 July 2012 to 8 July 2013. Ethics approval was granted by the University of Cape Town Human Research Ethics Committee. Consent was waived because patient data was de-identified and patient management was not adversely affected by the study. A clerking sheet was used for data collection. Patients were reassessed after 3 months. Main outcomes were renal recovery and 3 month mortality. Descriptive statistics and multivariate logistic regression were carried out for risk factors. Over this period there were 10,750 hospital admissions and 366 patients with AKI giving an incidence of 3.4%. Median age was 44 years (IQR 14-82) and 214 (58.5%) were male, with 152 (41.5%) female. Most, 265 (72.4%), had community acquired AKI. Common underlying comorbidities were hypertension (n = 152, 41.5%), diabetes mellitus (n = 65, 17.8%) Human immunodeficiency virus (HIV) (n = 75, 20.6%), heart disease (n = 58, 16.1%), and chronic kidney disease (n = 37, 10.1%). Renal biopsies were performed in 36 (9.8%) patients. In total, 202 (55.2%) patients were in the intensive care unit, and of the whole study population 204 (55.7%) were dialysed. Those admitted to ICU who required dialysis amounted to 145 (39.6%). The overall 3 month mortality was 38.8%. Among the 145 patients dialysed in ICU, there were 71 deaths (49%) at 3 month follow up. Of the 119 patients with follow up serum creatinine, 95 (79.8%) had full renal recovery, and 4 (3.4%) had end-stage renal disease. On multivariate analysis, mechanical ventilation was associated with 3 month mortality (OR 2.46, p-value 0.019, 95% CI 1.41-4.03). Sepsis had a borderline significant association (OR 1.83, P-value 0.066, 95%CI 1.02-3.27), as did prolonged time to dialysis (OR 1.93, p-value 0.08, 095% CI 0.93-4.03). HIV status did not affect outcome. The main study limitations were the large numbers of patients with AKI stage 3, reflecting the fact that the institution is a tertiary referral centre and that patients with earlier stages of AKI tended not to be referred. Another study limitation was the low number of patients who were available for follow up for 3 month serum creatinine. The incidence of AKI in the population studied is 3.4% of hospital admissions and carries a high mortality risk, most significant in mechanically ventilated patients. Sepsis and late dialysis initiation may carry a risk of mortality, but HIV infection did not affect outcome. Follow up of patients at least 3 months after an episode of AKI is essential to detect and appropriately manage those with incomplete renal recovery. In this study 36 patients underwent a kidney biopsy, and in many of these the results guided patient management. This study demonstrates finally that it remains imperative that clinicians actively pursue underlying causes of acute decline in renal function, including urine analysis, renal ultrasonography and if indicated and safe, a renal biopsy.


Passenger effects on teenage driving and opportunities for reducing the risks of such travel.
To review the research evidence concerning the effects of passengers on teenage driving and crash involvement, and to explore ways to reduce negative effects. Review of the international literature on these topics. Passenger presence increases crash risk for teenage drivers, especially when the passengers are other teenagers and especially when they are male. Female passengers do not have the same effects. Teenagers are more susceptible to peer influences than adults. The combination of passenger-induced distraction and driving inexperience can disrupt driving behavior, and there is evidence that teenage driver risk taking increases in vehicles with multiple teenagers. Possible ways to reduce the resulting crash problem include altering the in-vehicle behavior of teenagers or influencing their selection of travel partners. Legal restrictions on passengers with teenage drivers have been found effective in reducing the crash problem. Parental monitoring of teenage driving behavior, and programs aimed at teenagers themselves, could be other options but their efficacy is unproven. It currently is unknown why female passengers have a different effect than males or if that might offer clues about future interventions. Despite passenger restrictions in the majority of states, 42% of 16- and 17-year-old drivers in fatal crashes in 2005 were transporting teenagers with no adults in the vehicle; 61% of teenage passenger deaths (1,222 in 2005) occurred in vehicles driven by other teenagers. Wider application of passenger restrictions is indicated. Ways to make passenger restrictions more effective are needed, and other techniques for reducing this major problem need development and testing.


Clinical relevance of serum-derived exosomal messenger RNA sequencing in patients with non-Hodgkin lymphoma.
Background: The clinical utility of mRNA cargo in exosomes is unclear, although exosomes have potential as non-invasive biomarkers. This study aimed to investigate the feasibility of exosomal mRNA sequencing for monitoring disease status and predicting outcomes in non-Hodgkin lymphoma (NHL) patients. Methods: Exosomes were isolated from archived serum samples of 33 patients with NHL who were registered into our prospective cohort: diffuse large B-cell lymphoma (DLBCL, n = 17), intravascular B-cell lymphoma (IVL, n = 1), primary mediastinal large B-cell lymphoma (PMBL, n = 4), follicular lymphoma (FL, n = 3), mantle cell lymphoma (MCL, n = 3), and extranodal NK/T-cell lymphoma (ENKTL, n = 5). Exosomal mRNA sequencing was performed, and its concordance with clinical course was analyzed and compared with those of circulating tumor DNA (ctDNA) mutations. Results: Exosomal mRNA sequencing was performed successfully in 26 cases (79%, 26/33), whereas the remaining seven cases were not completed due to their small amount of RNA. The exosomal mRNA sequencing of DLBCL showed gene expression profiles consistent with activated B-cell-like and germinal center type. The longitudinal assessment of exosomal mRNA sequencing results in accordance with the clinical course showed that the post-treatment changes of exosomal mRNA expression were more consistent with treatment outcome than were those of ctDNA mutations. In particular, the exosomal mRNA expression of genes such as BCL2 and BCL6 was increased at the time of disease progression in DLBCL and FL patients. Conclusions: This study demonstrated the feasibility of exosomal mRNA expression profiles as a biomarker for NHL patients. Our results might provide the rationale for studies to explore the potential of exosomal mRNA as a biomarker in NHL patients.


Diastereoselective Spirocyclization: Entry to Spirocyclic Diketopiperazines.
We report a novel approach to access spirocyclic compounds containing a diketopiperazine (DKP) motif fused on a pyrrolidine ring. The shared spirocyclic carbon is at the ketone oxidation state, bearing two carbon-nitrogen bonds, one of which is introduced stereoselectively during the cyclization event. The reaction proceeds through an acid-catalyzed cyclization of a pendent chiral aminoamide unit onto a 2,3-dehydroproline amide moiety with up to >98:2 diastereoselectivity. We have demonstrated the generality of this methodology and its applicability to access chemically diverse DKP-containing structures. The extent of stereoinduction and how it varies according to the bulkiness of the substituent on the pendent aminoamide is demonstrated through a diverse substrate set. This methodology gives access to an underexplored spirocyclic diketopiperazine motif that may be useful in identifying new bioactive molecules.


Effects of local anesthetics on mechanical characteristics of lipid bilayers and on the ion transport dynamics.
Bilayer lipid membranes (BLM) of various composition were used to study the effects of local anesthetics (LA) carbisocaine and lidocaine on mechanical membrane characteristics and on the transport dynamics of ions across gramicidin D ionic channels. Carbisocaine concentrations of 20 mumols/l-0.1 mmol/l caused a considerable decrease (by 15-40%) in modulus of elasticity E1 in direction perpendicular to membrane surface. The effect of lidocaine was approx. one order of magnitude weaker. LA-induced changes in E1 were shown to depend on both the lipid composition of the membrane and the electrolyte pH. Neutral forms of LA induce marked changes in E1. An analysis of current-voltage (I-V) characteristics of BLM modified by the channel forming agent gramicidin D revealed that carbisocaine significantly affects the superlinear segment of the I-V relationship; this suggests a strong effect on the transport dynamics of ions through the internal channel region. The results of the study suggest that the action of both carbisocaine and lidocaine may be non-specific. The effectivity of the non-specific action of LA is determined by the hydrophobic moiety of the local anesthetic molecule.


Indomethacin-enhanced immunotherapy of pulmonary metastases using IL-2 and IFN-alpha.
In a murine pulmonary metastases model, interleukin-2 (IL-2), a lymphokine capable of expanding all classes of T lymphocytes, synergizes with interferon-alpha (IFN-alpha) to reduce established metastases and prolong survival. We tested whether indomethacin (INDO), which inhibits synthesis of prostaglandin E2 (a potent immunosuppressor), could further augment the antitumor efficacy of these lymphokines. Age-matched C57BL/6 mice bearing pulmonary micrometastases of a weakly immunogenic fibrosarcoma MCA-106 were treated intraperitoneally for 6 consecutive days, starting on day 3 with (1) saline solution, (2) IL-2 (50,000 units twice a day), (3) IFN-alpha A/D (50,000 units per day), and (4) IL-2 and IFN-alpha A/D. Half of each treatment group was given plain water and the rest INDO-treated (14 micrograms/cc) drinking water throughout the duration of the experiment. Pulmonary metastases were enumerated on day 21. IFN or INDO alone had little effect, whereas IL-2 reduced metastases and prolonged survival. All combination treatments, including INDO/IFN, decreased metastases and prolonged survival except INDO/IL-2/IFN in which several early deaths negated any significant survival prolongation. Early mortality (less than 21 days) was seen with IFN/INDO (8.3%), IL-2/IFN (7.7%), and IL-2/IFN/INDO (8.3%) indicating toxicity of these treatments. Spontaneous proliferation of splenocytes from non-tumor-bearing mice treated for 5 days showed that INDO combined with IL-2 or IFN enhanced proliferation measured 3 days after cessation or treatments. A striking reduction in T-cell marker (Thy 1.2+) in groups treated with IL-2/IFN, INDO/IL-2, INDO/IFN, and INDO/IL-2/IFN 3 days after cessation of IL-2 and IFN suggests that a non-T-cell is amplified when INDO is combined with IL-2 or IFN. These results show that INDO can enhance efficacy of IL-2 or IL-2/IFN. Furthermore, INDO/IFN offers an equi-efficacious, albeit similarly toxic, alternative to IL-2 treatment of tumors and may be useful clinically.


Exploring the Use of information and communication technologies and social networks among university nursing faculty staff. An opinion survey.
This work sought to analyze the use of Information and Communication Technologies (ICTs) and social networks among the university nursing faculty staff in Spain. This was a descriptive, cross-sectional study using a questionnaire on ICT skills designed to comply with the research objective, which was evaluated by experts and which was subjected to exploratory analysis of principal components; the reliability of this instrument measured with Cronbach's alpha was 0.85. The information technology tool used to publish the questionnaire on line was Limesurvey. The sample comprised 165 professors from 25 Nursing Faculties and Schools from universities in Spain. Seventy one percent of the total surveyed used internet services to look for information, 63% used the internet as a means for formation and learning, and 72% used it as a communication platform (e-mail and virtual platforms like Sakai and Moodle). Although 51% of the teaching staff surveyed had more than 120 students registered in their courses, hypothesis testing revealed that the number of students in class is not a determining factor for the teaching staff to have greater interest to update its knowledge in ICTs. Younger professors use new technologies more profusely and the most-valued advantage of using ICTs was quick access to information. Professors perceive that after the Bologna Declaration, which requires modifying their teaching-learning processes through the new teaching methodologies, a drop has been produced in their performance and that of their peers in their area of knowledge. The nursing teaching staff is making strong efforts to confront the new challenges posed by ICTs to train the professionals of the 21st century. It is fundamental to pay special attention to improving the university teaching staff's skills in managing ICTs, promoting the implementation of the knowledge acquired.


Effect of atorvastatin on cellular adhesion molecules on leukocytes in patients with normocholesterolemic coronary artery disease.
Expression of cellular adhesion molecules on leukocytes plays a key role in coronary artery disease (CAD). The aim of the present study was to assess whether atorvastatin therapy has an impact on the expression of cellular adhesion molecules on leukocytes in patients with normocholesterolemic CAD. In 54 patients with CAD and atorvastatin treatment and 54 CAD patients without atorvastatin therapy, expression of CD40L, CD11a, CD11b, CD54, CD62L and CD41 on leukocytes was measured using flow cytometry. All patients were normocholesterolemic. Atorvastatin treatment led to a significantly lower expression of CD40L, CD11b and CD54 on monocytes (p<0.05) and neutrophils (p<0.05). Expression of CD11a was significantly lower on monocytes (p<0.05) in atorvastatin-treated patients. The present results indicate that atorvastatin apparently improves chronic inflammation and may have a beneficial effect on hemostasis by reducing the expression of cellular adhesion molecules on leukocytes.


Cyclosporine-amiodarone interaction.
To report a possible interaction between cyclosporine (CsA) and amiodarone in a kidney transplant recipient. A 66-year-old kidney transplant recipient with a history significant for hypertension, moderate mitral valve insufficiency, and decreased left ventricular function developed ventricular tachycardia posttransplant and was eventually treated with amiodarone. Maintenance immunosuppression included prednisone, azathioprine, and CsA. CsA concentrations before amiodarone initiation were stable (range 100-150 ng/mL). After amiodarone initiation, the CsA concentration increased more than twofold. Following CsA dosage reduction, concentrations returned to the desired range. The patient did not experience any toxicity with the increased concentration of CsA. The possible mechanisms of an interaction between CsA and amiodarone are reviewed. Reports of this interaction in heart transplant recipients are also reviewed. Changes in protein binding, changes in metabolism, or both may explain the interaction. Both CsA and amiodarone are protein bound and metabolized by the cytochrome P-450 enzyme system. It is likely that there is an interaction between CsA and amiodarone. The exact mechanism of this interaction has not been fully determined. When CsA is administered concurrently with amiodarone, CsA concentrations should be monitored closely and the CsA dosage should be adjusted as necessary.


Canine hypoadrenocorticism: part I.
Hypoadrenocorticism (Addison's disease) has been referred to as "the great pretender," due to its ability to mimic other common diseases in the dog and thereby represent a diagnostic challenge. Naturally occurring hypoadrenocorticism is an uncommon canine disease. Young, female dogs are overrepresented. Hypoadrenocorticism typically results from immune-mediated destruction of all adrenocortical layers, resulting in deficiencies of min-eralocorticoids (aldosterone) and glucocorticoids (cortisol). A small number of dogs suffer from glucocorticoid deficiency only. Dogs suffering from hypoadrenocorticism may present in a variety of conditions, from a mildly ill dog to a shocky and recumbent dog. This review discusses etiology, pathophysiology, history, physical examination findings, and diagnostic findings in the Addisonian patient. A follow-up article (Part II) will discuss the definitive diagnosis and management strategies for these patients.


Effects of a moderate dietary fibre supplement on hunger rating, energy input and faecal energy output in young, healthy volunteers. A randomized, double-blind, cross-over trial.
The effects of moderate dietary-fibre supplementation on satiety, energy intake and faecal energy excretion were studied in 20 young healthy volunteers of normal body weight, mean body mass index 20.9, receiving a dietary fibre supplement of 7.3 g per day in a randomized, double-blind, cross-over study. Hunger feeling, energy intake, and defaecation pattern, were recorded daily during a 2-week control period and then, during two 4-week treatment periods. Furthermore, faecal energy output was determined during the last week of each treatment period. The fibre treatment, as compared to placebo, resulted in a significantly higher faecal energy excretion: 173 kcal/d (163-183 kcal/d) vs 153 kcal/d (135-171 kcal/d), respectively (P less than 0.05); a decrease in hunger rating (using a visual analogue scale) (P less than 0.05); an increase in number of bowel movements (P less than 0.05), and a softer consistency of the stools (P less than 0.05). There was no significant difference in mean energy intake between the two treatment periods. This study demonstrated that moderate dietary fibre supplementation in normal man increases faecal energy excretion with simultaneously decreased hunger feeling. These beneficial effects may have therapeutic value in the management of obesity.


Development of a machine learning-based real-time location system to streamline acute endovascular intervention in acute stroke: a proof-of-concept study.
Delivery of acute stroke endovascular intervention can be challenging because it requires complex coordination of patient and staff across many different locations. In this proof-of-concept paper we (a) examine whether WiFi fingerprinting is a feasible machine learning (ML)-based real-time location system (RTLS) technology that can provide accurate real-time location information within a hospital setting, and (b) hypothesize its potential application in streamlining acute stroke endovascular intervention. We conducted our study in a comprehensive stroke care unit in Melbourne, Australia that offers a 24-hour mechanical thrombectomy service. ML algorithms including K-nearest neighbors, decision tree, random forest, support vector machine and ensemble models were trained and tested on a public WiFi dataset and the study hospital WiFi dataset. The hospital dataset was collected using the WiFi explorer software (version 3.0.2) on a MacBook Pro (AirPort Extreme, Broadcom BCM43x×1.0). Data analysis was implemented in the Python programming environment using the scikit-learn package. The primary statistical measure for algorithm performance was the accuracy of location prediction. ML-based WiFi fingerprinting can accurately predict the different hospital zones relevant in the acute endovascular intervention workflow such as emergency department, CT room and angiography suite. The most accurate algorithms were random forest and support vector machine, both of which were 98% accurate. The algorithms remain robust when new data points, which were distinct from the training dataset, were tested. ML-based RTLS technology using WiFi fingerprinting has the potential to streamline delivery of acute stroke endovascular intervention by efficiently tracking patient and staff movement during stroke calls.


Tunable photonic defect modes in a cholesteric liquid crystal induced by optical deformation of helix.
We have demonstrated, based on numerical analyses, that the introduction and tuning of photonic defect modes in a cholesteric liquid crystal (CLC) can be realized by the local deformation of its one-dimensional periodic helical structure. The defect modes appear in transmission spectra only when incident circularly polarized light has the same handedness as CLC's. The tuning of defect modes position can be performed upon both local elongation and shortening of the helix; however, the direction of the shift of the defect mode wavelength is opposite. By controlling the degree of the deformation of helix, a continuous shift of the defect modes can be realized. Our results will open the way for the optical introduction and tuning of defect modes in CLC's.


The CTCF insulator protein is posttranslationally modified by SUMO.
The CTCF protein is a highly conserved zinc finger protein that is implicated in many aspects of gene regulation and nuclear organization. Its functions include the ability to act as a repressor of genes, including the c-myc oncogene. In this paper, we show that the CTCF protein can be posttranslationally modified by the small ubiquitin-like protein SUMO. CTCF is SUMOylated both in vivo and in vitro, and we identify two major sites of SUMOylation in the protein. The posttranslational modification of CTCF by the SUMO proteins does not affect its ability to bind to DNA in vitro. SUMOylation of CTCF contributes to the repressive function of CTCF on the c-myc P2 promoter. We also found that CTCF and the repressive Polycomb protein, Pc2, are colocalized to nuclear Polycomb bodies. The Pc2 protein may act as a SUMO E3 ligase for CTCF, strongly enhancing its modification by SUMO 2 and 3. These studies expand the repertoire of posttranslational modifications of CTCF and suggest roles for such modifications in its regulation of epigenetic states.


Demonstration of tuning to stimulus orientation in the human visual cortex: a high-resolution fMRI study with a novel continuous and periodic stimulation paradigm.
Cells in the animal early visual cortex are sensitive to contour orientations and form repeated structures known as orientation columns. At the behavioral level, there exist 2 well-known global biases in orientation perception (oblique effect and radial bias) in both animals and humans. However, their neural bases are still under debate. To unveil how these behavioral biases are achieved in the early visual cortex, we conducted high-resolution functional magnetic resonance imaging experiments with a novel continuous and periodic stimulation paradigm. By inserting resting recovery periods between successive stimulation periods and introducing a pair of orthogonal stimulation conditions that differed by 90° continuously, we focused on analyzing a blood oxygenation level-dependent response modulated by the change in stimulus orientation and reliably extracted orientation preferences of single voxels. We found that there are more voxels preferring horizontal and vertical orientations, a physiological substrate underlying the oblique effect, and that these over-representations of horizontal and vertical orientations are prevalent in the cortical regions near the horizontal- and vertical-meridian representations, a phenomenon related to the radial bias. Behaviorally, we also confirmed that there exists perceptual superiority for horizontal and vertical orientations around horizontal and vertical meridians, respectively. Our results, thus, refined the neural mechanisms of these 2 global biases in orientation perception.


A tragedy of the commons case study: modeling the fishers king crab system in Southern Chile.
Illegal fishing in small-scale fisheries is a contentious issue and resists a straightforward interpretation. Particularly, there is little knowledge regarding cooperative interactions between legal and illegal fishers and the potential effects on fisheries arising from these interactions. Taking the Chilean king crab (Lithodes santolla; common name centolla) fishery as a case study, our goal is twofold: (i) to model the effect of illegal-legal fishers' interactions on the fishery and (ii) analyze how management and social behavior affect fishery's outcomes. We framed the analysis of this problem within game theory combined with network theory to represent the architecture of competitive interactions. The fishers' system was set to include registered (legal) fishers and unregistered (illegal) fishers. In the presence of unregistered fishers, legal fishers may decide to cooperate (ignoring the presence of illegal fishers) or defect, which involves becoming a "super fisher" and whitewashing the captures of illegal fishers for a gain. The utility of both players, standard fisher and super fisher depend on the strategy chosen by each of them, as well as on the presence of illegal fishers. The nodes of the network represent the legal fishers (both standard and super fishers) and the links between nodes indicate that these fishers compete for the resource, assumed to be finite and evenly distributed across space. The decision to change (or not) the adopted strategy is modeled considering that fishers are subjected to variable levels of temptation to whitewash the illegal capture and to social pressure to stop doing so. To represent the vital dynamics of the king crab, we propose a model that includes the Allee effect and a term accounting for the crab extraction. We found that the super fisher strategy leads to the decrease of the king crab population under a critical threshold as postulated in the tragedy of the commons hypothesis when there are: (i) high net extraction rates of the network composed of non-competing standard fishers, (ii) high values of the extent of the fishing season, and (iii) high density of illegal fishers. The results suggest that even in the presence of super fishers and illegal fishers, the choice of properly distributed fishing/closure cycles or setting an extraction limit per vessel can prevent the king crab population from falling below a critical threshold. This finding, although controversial, reflects the reality of this fishery that, for decades, has operated under a dynamic in which whitewashing and super fishers have become well established within the system.


Francisella tularensis as a potential agent of bioterrorism?
Francisella tularensis is a category A bioterrorism agent. It is the etiological agent of tularemia, a zoonotic disease found throughout the northern hemisphere. The intentional spread of F. tularensis aerosols would probably lead to severe and often fatal pneumonia cases, but also secondary cases from contaminated animals and environments. We are not ready to face such a situation. No vaccine is currently available. A few antibiotics are active against F. tularensis, but strains resistant to these antibiotics could be used in the context of bioterrorism. We need new therapeutic strategies to fight against category A bioterrorism agents, including development of new drugs inhibiting F. tularensis growth and/or virulence, or enhancing the host response to infection by this pathogen.


SP100 expression modulates ETS1 transcriptional activity and inhibits cell invasion.
The ETS1 transcription factor is a member of the Ets family of conserved sequence-specific DNA-binding proteins. ETS1 has been shown to play important roles in various cellular processes such as proliferation, differentiation, lymphoid development, motility, invasion and angiogenesis. These diverse roles of ETS1 are likely to be dependent on specific protein interactions. To identify proteins that interact with ETS1, a yeast two-hybrid screen was conducted. Here, we describe the functional interaction between SP100 and ETS1. SP100 protein interacts with ETS1 both in vitro and in vivo. SP100 is localized to nuclear bodies and ETS1 expression alters the nuclear body morphology in living cells. SP100 negatively modulates ETS1 transcriptional activation of the MMP1 and uPA promoters in a dose-dependent manner, decreases the expression of these endogenous genes, and reduces ETS1 DNA binding. Expression of SP100 inhibits the invasion of breast cancer cells and is induced by Interferon-alpha, which has been shown to inhibit the invasion of cancer cells. These data demonstrate that SP100 modulates ETS1-dependent biological processes.


Effects of the dietary ratio of ruminal degraded to undegraded protein and feed intake on intestinal flows of endogenous nitrogen and amino acids in goats.
This study was conducted to evaluate the effects of the dietary ratio of ruminal degraded protein (RDP) to ruminal undegraded protein (RUP) and the dry matter intake (DMI) on the intestinal flows of endogenous nitrogen (N) and amino acids (AA) in goats. The experiment was designed as a 4×4 Latin square using four ruminally, duodenally and ileally cannulated goats. The treatments were arranged in a 2×2 factorial design; two ratios of RDP to RUP (65:35 and 45:55, RDP1 and RDP2, respectively) and two levels at 95% and 75% of voluntary feed intake (DMI1 and DMI2, respectively) were fed to the goats. There were no significant differences in the N intake, duodenal flow of total N, undegraded feed N, microbial N, endogenous N or ileal flow of endogenous N, but the duodenal and ileal flow of endogenous N numerically decreased by approximately 22% and 9%, respectively, when the feed intake changed from DMI1 (0.63 kg/d) to DMI2 (0.50 kg/d). The dietary ratio of RDP to RUP had significant effects (p<0.05) on the ileal flows of endogenous leucine, phenylalanine and cysteine. The present results implied that the duodenal flows of endogenous N and AA decreased when the dietary RDP to RUP ratio and DMI decreased, and the flow of endogenous AA at the ileum also decreased when the DMI decreased but increased with decreasing RDP to RUP ratios.


Preparation of semi-conducting polymeric nanoparticles by supercritical carbon dioxide RESOLV process.
The rapid expansion of supercritical carbon dioxide solutions into a liquid solvent (RESOLV) technique with environmentally benign supercritical carbon dioxide was used to produce semi-conducting polymeric nanoparticles of fluoroalkyl ester substituted thiophenes. When the supercritical solutions of the conjugated polymer, poly[2-(3-thienyl) acetyl-3,3,4,4,5,5,6,6,7,7,8,8,8,tridecafluoro-1-octanate] (PSFTE) were expanded into aqueous solutions through a small capillary nozzle (150 microm), spherical nanoparticles in the range of 50-100 nm were obtained. However, after 15 min of expansion, the particles tended to aggregate to form larger objects due to the high surface energy of the polymeric nanoparticles. In order to prevent the agglomeration of particles, a relatively low concentration of sodium dodecyl sulphate (SDS) or NaCI was used as a stabilizing agent in aqueous solution. While NaCI did not give enough stabilization to the system, uniform spherical nanoparticles of PSFTE having an average size of 45 nm were successfully obtained by SDS stabilization.


B-type natriuretic peptide modulates ghrelin, hunger, and satiety in healthy men.
Chronic heart failure is accompanied by anorexia and increased release of B-type natriuretic peptide (BNP) from ventricular cardiomyocytes. The pathophysiological mechanisms linking heart failure and appetite regulation remain unknown. In this study, we investigated the impact of intravenous BNP administration on appetite-regulating hormones and subjective ratings of hunger and satiety in 10 healthy volunteers. Participants received in a randomized, placebo-controlled, crossover, single-blinded study (subject) placebo once and 3.0 pmol/kg/min human BNP-32 once administered as a continuous infusion during 4 h. Circulating concentrations of appetite-regulating peptides were measured hourly. Subjective ratings of hunger and satiety were evaluated by visual analog scales. BNP inhibited the fasting-induced increase in total and acylated ghrelin concentrations over time (P = 0.043 and P = 0.038, respectively). In addition, BNP decreased the subjective rating of hunger (P = 0.009) and increased the feeling of satiety (P = 0.012) when compared with placebo. There were no significant changes in circulating peptide YY, glucagon-like peptide 1, oxyntomodulin, pancreatic polypeptide, leptin, and adiponectin concentrations. In summary, our results demonstrate that BNP exerts anorectic effects and reduces ghrelin concentrations in men. These data, taken together with the known cardiovascular properties of ghrelin, support the existence of a heart-gut-brain axis, which could be therapeutically targeted in patients with heart failure and obesity.


The chemical ligation of selectively S-acylated cysteine peptides to form native peptides via 5-, 11- and 14-membered cyclic transition states.
Cysteine and C-terminal cysteine peptides are selectively S-acylated at 0-20 degrees C by N-(Pg-alpha-aminoacyl)benzotriazoles to give N-Pg-S-acyl-isodi-, -isotri-, and -isotetra-peptides isolated in good yields. N-Fmoc-S-acyl-isopeptides are Fmoc deprotected to afford free S-acyl-isopeptides isolated in high yields. S-Acyl-isodi-, S-acyl-isotetra-, and S-acyl-isopentapeptides undergo chemical ligation; migration of the cysteine S-acyl groups to the N-terminal amino acids via 5-, 11-, and 14-membered transition states giving the corresponding native di-, tetra-, and penta-peptides. By contrast, the Sacyl-isotripeptide prefers intermolecular acylation from one molecule to another over an 8-membered intramolecular transition state. The developed methodology allows convenient isolation of stable, unprotected S-acyl cysteine peptides including the first isolation of S-acyl-isopeptides, which should facilitate the investigation of ligation by physical organic chemistry techniques.


Highly enantioselective [3+2] cycloaddition of vinylcyclopropane with nitroalkenes catalyzed by palladium(0) with a chiral bis(tert-amine) ligand.
An enantioselective [3+2] cycloaddition of vinyl cyclopropane derived from 1,3-indanedione with nitroalkenes catalyzed by palladium(0) with a chiral bis(tert-amine) ligand was developed in high yields with good diastereoselectivities and excellent enantioselectivities. The resulting bis(tert-amine)-palladium complex proved to be a highly efficient catalyst for this cycloaddition.


Ischemic preconditioning by unstable angina reduces the release of CK-MB following CABG and stimulates left ventricular HSP-72 protein expression.
Whether the CK-MB reducing effect of ischemic preconditioning (IP) by unstable angina within 24 to 48 hours before CABG is achieved by early or by delayed preconditioning of left ventricular myocardium in humans is unknown. We investigated whether IP is associated with phosphorylation of p38 MAPK (characteristic for early preconditioning) or with increased protein expression of HSP-72 (characteristic for delayed preconditioning) at the time of CABG in patients. Nineteen patients were grouped according to the occurrence of ischemic episodes within 48 hours before CABG. The patients without angina were assigned to the control group (CON, n = 10) whereas patients who had experienced angina within 48 hours before CABG were assigned to the preconditioned group (IP, n = 9). The effect of IP on the CABG induced maximal release of creatine kinase (CK) and CK-MB was examined. Left ventricular biopsy specimens taken immediately before cross clamping from ischemic (ISCH) and from reference (REF) areas were processed to analyze p38 MAPK phosphorylation and HSP-72-protein expression. While IP significantly reduced CK-MB (18.7 +/- 1.3 vs. 13.8 +/- 1.5 U/L, mean +/- SEM, p < 0.05), it only tended to reduce CK (292.7 +/- 32.8 vs. 274.1+/-31.1 U/L, p = NS, mean +/- SEM). CK-MB release for any given cross-clamp time was significantly reduced by IP (regression lines: CON, y= 0.4x+ 2, r= 0.8; IP, y= 0.1x+ 10, r= 0.2; p < 0.01, ANCOVA). There was no effect of IP on left ventricular p38 MAPK phosphorylation. IP increased left ventricular HSP-72-protein expression in ischemic areas when compared to reference areas (1.78 +/- 0.35 vs. 2.58 +/- 0.65, REF vs. ISCH, PhosphorImager units x10(6), mean +/- SEM, p < 0.05, ANCOVA). Thus, in the human left ventricular myocardium there is a second window of protection lasting for at least 48 hours, while at that time the early phase of preconditioning has already gone.


Predicting undergraduates' intentions to drink.
Sex-linked differences in motivation to drink were studied with Fishbein's model of the relationship between attitudes and behavior. Fishbein's model was revised so that personal normative beliefs were seen as measuring ideal behavioral intentions (what the person intended given real-world constraints) rather than personal norms. A total of 101 college students (53 women) completed a questionnaire. Also, 10 additional students (five women) were interviewed to determine referents whose expectations were salient for the present sample. Both attitudes and social normative beliefs (SNB) correlated significantly with ideal behavioral intentions (IBI); IBI was able to be predicted from the weighted sum of attitudes and SNB. IBI correlated significantly with actual behavioral intentions and accounted for the majority of the variance in actual intentions to drink. Support for the revision of Fishbein's model was shown by the direct effect of attitude on women's intentions to drink. The lack of mediation of attitudes by IBI showed that IBI function differently from actual intentions. The revised model was shown to be very successful in predicting intentions to drink, and in exploring gender and cultural differences therein.


A Promising Method for Repairing Low-Level Biliary Strictures After Cholecystectomy.
The purpose of this study is to introduce and evaluate a new technique of repairing bile ducts by the tubular gastric wall with a vascularized pedicle. Both the end-to-end bile duct repair and Roux-en-Y hepatoenterostomy have limitations in the treatment of benign bile duct strictures after cholecystectomy. There are no other good choices to manage these cases, especially the bile duct transection injuries or partly missing common bile duct or hepatic duct. Eleven patients with partly missing common bile ducts in the Chinese People's Liberation Army General Hospital between January 2007 and December 2012 were retrospectively analyzed. The study comprised 8 females and 3 males, whose age ranged from 29 to 56 years. All patients underwent successful bile duct repair. The time of operations ranged from 210 minutes to 240 minutes. The maximal blood loss was less than 220 ml. There was no perioperative mortality and no case of gastric fistula. Postoperative complications occurred in 3 patients, including wound infection, bile leakage, and erosive gastritis. All complications were cured by conservative treatment. The mean follow-up time was 42 months. One patient was classified as Terblanche's grade II and 10 patients were classified as Terblanche's grade I. The observations indicate that this technique is a feasible and effective choice to manage low level biliary stricture after cholecystectomy, especially suitable to repair bile duct transection injuries or partly missing common bile duct or hepatic duct.


The effectiveness of shockwave therapy on patellar tendinopathy, Achilles tendinopathy, and plantar fasciitis: a systematic review and meta-analysis.
Tendinopathy is a growing global concern affecting many people, like athletes, workers, and the elderly. Despite its commonality among the sporting population, there is no practical clinical guideline for patellar tendinopathy (PT). Furthermore, there is conflicting evidence between clinical guidelines on shockwave therapy's application and clinical utility for Achilles tendinopathy (AT) and plantar fasciitis (PF). Thus, our aim of this study is to evaluate the evidence for shockwave therapy; to provide a Grading of Recommendation, Assessment, Development and Evaluation (GRADE) level of the evidence and effectiveness of shockwave therapy for patellar tendinopathy, Achilles tendinopathy, and Plantar fasciitis. Medical Literature Analysis and Retrieval System Online (Medline), Embase, The Cumulative Index to Nursing and Allied Health Literature (CINAHL), Physiotherapy Evidence Database (PEDro) and China National Knowledge Infrastructure database (CNKI) were searched to find relevant studies published before December 14th, 2022. Our study showed that for PT in the short term, extracorporeal shockwave therapy (ESWT) or ESWT + eccentric exercise (EE) has a negligible effect on pain and function compared to a placebo or placebo + EE. On the contrary, ESWT significantly affects pain compared to conservative treatment (CT). For AT, ESWT has a small inconclusive effect on pain and function in the short term compared to EE. On the other hand, a placebo outperformed ESWT in improving function for AT but not pain outcomes. PF showed that ESWT significantly affects short- and long-term pain and function. When ESWT was compared to other interventions such as low laser therapy (LLLT), corticosteroid injection (CSI), or CT, there was a small inconclusive effect on pain and function in the short term. There is low-moderate evidence that ESWT has a negligible effect on pain and function for PT and AT. However, high-quality evidence suggests ESWT has a large effect on pain and function for PF. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023396835, identifier CRD42023396835.


Regional and genotypic differences in stromal-vascular cells from obese and lean Zucker rats.
LPL activity, total lipogenesis and rates of growth were determined for stromal-vascular cells derived from epididymal and inguinal depots of 13 1/2-week-old obese and lean Zucker rats. LPL activity, in cells of both depots, was found to increase between days 4 and 6 and decrease by day 8 in the presence of insulin. Inguinal derived fatty cell LPL activity increased between days 4 and 8 in contrast to lean cells which peaked at day 6 under basal growth conditions. LPL activity was elevated in fatty versus lean cells at days 6 and 8 in inguinal derived stromal vascular cells while in epididymal derived stromal vascular cells, LPL activity was elevated in lean versus fatty derived cells at day 4 and 6 but by day 8 the genotypic effect was reversed. Lipogenesis was elevated in lean versus fatty derived epididymal and inguinal cells at all concentrations of insulin and lean cells showed a dose-dependent response to insulin in contrast to fatty cells. There were no effects of genotype on the proliferative capacity of cells from either depot but some regional differences in growth were observed. These data illustrate that fa gene effects can be studied in primary cell culture.


Impact of donor-recipient MHC matching on experimental islet allotransplant survival in naïve and presensitized Lewis rats.
In human islet transplantation (ITX), the impact of donor-recipient major histocompatibility complex (MHC) matching on transplant survival is currently unknown. Utilizing defined MHC mismatches, we have investigated the outcome of ITX in naïve and presensitized congenic Lewis rats. ITX into streptozotocin diabetic Lewis rats was performed under the kidney capsule. Presensitization by skin transplantation was performed on days 1, 28, and 56, followed by ITX on day 84. Survival was greatest in isolated MHC class I mismatches, followed by isolated MHC class II mismatches. The shortest transplant survival was observed following full MHC mismatched ITX (P<0.05 vs. isolated MHC class I or II). Following recipient presensitization, islets in general showed reduced survival compared to naïve recipients. In this congenic rat model, islet transplant survival was significantly influenced by the degree of donor-recipient MHC matching, as well as by recipient presensitization. These data suggest that MHC matching might be useful in human islet transplantation.


Self-doped N, S porous carbon from semi-coking wastewater-based phenolic resin for supercapacitor electrodes.
Contamination of phenolic compounds has devastating effects on the environment. Therefore, its harmless treatment and recycling have received extensive attention. Herein, a novel method for preparing N-S doped phenolic resin (NSPR) from phenols, N and S groups in semi-coking wastewater, and formaldehyde are developed. The KOH is consequently incorporated into the NSPR through simultaneous carbonization and activation in a single step to produce porous carbon material (NSPC). The as-obtained NSPC exhibits a high specific capacitance of 182 F g-1 at 0.5 A g-1, a high energy density of 9.1 Wh kg-1 at a power density of 0.15 kW kg-1, and remarkable cycling stability in aqueous KOH electrolyte. This outstanding electrochemical performance is attributed to its ultrahigh specific surface area (SSA, 2,523 m2 g-1), enormous total pore volume (Vt, 1.30 cm3 g-1), rational pore structure, and N-S heteroatom self-doping (0.76 at% N and 0.914 at% S), which ensures adequate charge storage, rapid electrolyte ion diffusion, and contributed pseudo-capacitance. This work not only provides a facile method for transforming phenolic wastewater into high-value products but also offers a cost-effective and high-performance porous carbon material for supercapacitors.


Hesperetin-loaded lipid-core nanocapsules in polyamide: a new textile formulation for topical drug delivery.
Chronic venous insufficiency is characterized by chronic reflux disorder of blood from the peripheral to the central vein, with subsequent venous hypertension and resulting changes in the skin. Traditionally, nonsurgical treatments relied on the use of compression therapy, and more recently a variety of flavonoids have been shown to have positive effects. There have also been developments of more effective drug delivery systems using various textiles and nanotechnology to provide new therapeutic options. Our objective was to use nanotechnology to develop a new formulation containing hesperetin (Hst), a substance not previously used in the treatment of chronic venous insufficiency, impregnated into textile fibers as a possible alternative treatment of venous diseases. We prepared the nanocapsules using the interfacial deposition of preformed polymer method with an Hst concentration of 0.5 mg/mL and then characterized the size and distribution of particles. To quantify the Hst in the samples, we developed an analytical method using high-performance liquid chromatography. Studies of encapsulation efficiency (98.81%±0.28%), microscopy, drug release (free-Hst: 104.96%±12.83%; lipid-core nanocapsule-Hst: 69.90%±1.33%), penetration/permeation, drug content (0.46±0.01 mg/mL) and the effect of washing the textile after drug impregnation were performed as part of the study. The results showed that nanoparticles of a suitable size and distribution with controlled release of the drug and penetration/permeation into the skin layers were achieved. Furthermore, it was established that polyamide was able to hold more of the drug, with a 2.54 times higher content than the cotton fiber; after one wash and after five washes, this relation was 2.80 times higher. In conclusion, this is a promising therapeutic alternative to be further studied in clinical trials.


CORRELATED RESPONSE IN THE DEVELOPMENTAL CHOREOGRAPHIES OF THE MOUSE MANDIBLE TO SELECTION FOR BODY COMPOSITION.
The correlated response to 13 generations of selection for percent fatness and leanness is investigated in 11 mandible traits in mice. Five selection lines are examined including high fat (HF), low fat (LF), high lean (HL), low lean (LL) and a randomly selected control strain (RC. The ontogenetic patterns of growth in the RC strain serve as a model to evaluate the developmental consequences of directional selection. Selection has systematically altered the patterns of mandible growth in selection lines relative to the control strain. Further, selection has significantly altered the age-specific phenotypic covariance among these traits. In the HF strain, growth in the mandible is completed by 12 weeks of age for most traits. In other selected strains, notably LF and LL, there is a significant growth spurt that occurs between 12 and 15 weeks of age. Changes in the patterns of mandibular growth produce significant differences among strains in the final form of the mandible. Because of the changes in the patterns of growth, the differences among strains are themselves shown to vary at different postnatal ages. The phenotypically similar strains, i.e., HF and LL or LF and HL, show different but correlated patterns of divergence. Multivariate statistical analyses suggest that the temporal strain differences in these traits are multidimensional.


Sleep patterns and insomnia among internationally adopted adolescents.
Sleep is essential for adolescent development. We aimed to investigate sleep patterns and insomnia among internationally adopted adolescents compared with their nonadopted peers. Cross-sectional. Data stem from the population-based youth@hordaland-survey, conducted during winter/spring 2012, in Hordaland, Norway. Of the 9846 adolescents who responded to the sleep measures in the youth@hordaland-survey, 44 were identified as international adoptees by linkage to the Central Adoption Registry. The adolescents provided self-report information on demographic characteristics, mental health problems, and a range of sleep measures. There were no significant differences between the adoptees and nonadopted peers regarding how much time they spent in bed, but the internationally adopted adolescents reported significantly shorter sleep duration, both on weekdays (d=0.37, P = .014) and weekends (d=0.37, P = .015). The difference was due to the adoptees spending longer time awake after sleep onset (d=0.78, P > .001). Furthermore, 32% of the adopted adolescents fulfilled the DMS-5 criteria for insomnia, compared with 18% of their nonadopted peers (odds ratio 2.06, 95% CI: 1.09-3.90). However, this association was no longer significant after adjusting for symptoms of depression. Adolescents adopted after 12 months of age reported more sleep problems than those who were adopted earlier. The short sleep duration and high occurrence of insomnia among the internationally adopted adolescents suggest both a problem area that should receive more focus and a potential avenue for intervention. The results further suggest that assessing both mental health problems and sleep problems among internationally adopted adolescents who are experiencing difficulties could help target interventions.


A Pilot Study Examining Feasibility and Initial Efficacy of Remotely Delivered Cognitive Adaptation Training.
Cognitive Adaptation Training (CAT) is an evidence-based treatment that uses environmental supports including signs, text messages, checklists, smart pill containers, and the organization of belongings to bypass cognitive and motivational impairments and to cue adaptive behavior in the home or work environment. We developed and tested a remote version of CAT to make the treatment available more broadly. Because CAT is focused on working with the individual in their home environment to establish supports, CAT may not be as easy to translate into an effective virtual treatment as talk-therapies. Fifty-six members of managed care were assigned to or given their treatment preference for CAT or Remote CAT (R-CAT) for 6 months. In-person or virtual pill counts were conducted monthly and assessments of habit-formation, symptoms, functioning, and satisfaction were administered every 2 months by independent raters. Analyses using mixed models with repeated measures focused on pre-planned evaluations of within-group change. Adherence improved significantly in R-CAT, functioning improved significantly in CAT and both groups improved significantly on measures of habit-formation and symptoms across 6 months. Higher functioning individuals appeared to choose R-CAT. Satisfaction with treatment was very high in both groups. R-CAT appears to be a potentially effective treatment, particularly for medication follow-though. However, in contrast to decades of previous research, fewer than 20% of eligible Medicaid recipients agreed to participate in the study. This may have been due to recruitment during and immediately post-pandemic.


Forced Kramers escape in single-molecule pulling experiments.
The pulling-induced rupture of noncovalent bonds is studied by the overdamped Kramers theory with full account of a time-varying barrier. Mechanic pulling reduces the energy barrier and leads to loading-rate dependence of the rupture force F(u)(F(t)). Tested against Langevin dynamics, four distinct regimes are identified, including kinetic dominant, weak pulling, strong pulling, and mechanic pulling dominant. Asymptotic analyses show that F(u) approximately ln F(t) in weak pulling regime and becomes 1-(F(u)F(c)) approximately [ln(F(t))E(b)](23) in strong pulling regime. Kinetic informations such as activation energy E(b) and critical force F(c) were extracted from pulling experiments for biotin-streptavidin complex.


Influence of multifrequency vibration on the optical performance of diamond-turned optics and its elimination method.
In this work, to reveal the underlying mechanism of the influence of multifrequency vibration on the optical performance of diamond-turned optics, a systematic simulation investigation is performed using Fourier modal method and fast Fourier transformation based on a well-established surface topography model. Both the simulation results and the experimental observations demonstrate that the center area is the most heavily influenced region on the machined surface, which is closely associated with the distribution of the surface roughness under multifrequency vibration. The vibration amplitude has a visible impact on the specular reflectivity, and with an increase in vibration amplitude, the specular reflectivity in the center area obviously decreases, while the specular reflectivity in remote areas basically remains invariant. To eliminate the negative effect in relation to the vibration, a two-step process technology is developed that includes a strict spindle balance and the optimization of process parameters, particularly the depth of cut and the spindle speed. The cutting experiments further validate the effectiveness of the proposed technology for elimination of the negative effect concerning multifrequency vibration.


Performances of VITEK 2 colorimetric cards for identification of gram-positive and gram-negative bacteria.
The purpose of this study was to evaluate the new VITEK 2 identification cards that use colorimetric reading to identify gram-positive and gram-negative bacteria (GP and GN cards, respectively) in comparison to fluorimetric cards (ID-GPC and ID-GNB, respectively). A total of 580 clinical isolates and stock collection strains belonging to 116 taxa were included in the study. Of the 249 gram-positive strains tested with both the ID-GPC and GP cards, 218 (87.5%) and 235 (94.4%) strains were correctly identified (to the genus and species level), respectively. Of the 331 gram-negative strains tested with the ID-GNB and GN cards, 295 (89.1%) and 321 (97%) strains were correctly identified, respectively. Another focus of the study was to apply the percentages of correct identifications obtained in this study to the list of bacteria isolated in our laboratory (32,739 isolates) in the year 2004. We obtained 97.9% correct identifications with the colorimetric cards and 93.9% with fluorescent cards.


Measurement of red blood cell mechanics during morphological changes.
The human red blood cell (RBC) membrane, a fluid lipid bilayer tethered to an elastic 2D spectrin network, provides the principal control of the cell's morphology and mechanics. These properties, in turn, influence the ability of RBCs to transport oxygen in circulation. Current mechanical measurements of RBCs rely on external loads. Here we apply a noncontact optical interferometric technique to quantify the thermal fluctuations of RBC membranes with 3 nm accuracy over a broad range of spatial and temporal frequencies. Combining this technique with a new mathematical model describing RBC membrane undulations, we measure the mechanical changes of RBCs as they undergo a transition from the normal discoid shape to the abnormal echinocyte and spherical shapes. These measurements indicate that, coincident with this morphological transition, there is a significant increase in the membrane's shear, area, and bending moduli. This mechanical transition can alter cell circulation and impede oxygen delivery.


Response to sulfasalazine in rheumatoid arthritis: life table analysis of a 5-year followup.
Eighty-six patients with rheumatoid arthritis treated with sulfasalazine were followed for 5 years, or until treatment was discontinued. At the end of 5 years, there was a 22% probability of successfully continuing treatment. Most adverse effects developed in the first 3 months of treatment. In 38 patients treatment was discontinued because of inefficacy. In 18 of these, a brief period of improvement was followed by clinical relapse. Twenty were regarded as having no useful response to sulfasalazine. The treatment continuation rate of 22% at 5 years is in marked contrast to the pessimistic longterm evaluations of second line drugs that have recently been reported.


[The relationship between LDL-C and ischemic stroke in 2 470 patients with nonvalvular atrial fibrillation in Xinjiang region].
Objective: To evaluate the association between LDL-C and ischemic stroke in patients with nonvalvular atrial fibrillation (AF). Method: A total of 2 470 patients with nonvalvular AF were included in the present study. The clinical data and laboratory examination results of the patients in the hospital were collected. The subjects were either divided into the ischemic stroke history (n=560), and non- ischemic stroke history groups (n=1 910), or divided into the low-middle risk (n=566) and high risk groups (n=1 904) based on CHA(2)DS(2) - VASc score. Results: There were significant differences in the proportion of Han, the ratio of gender, age, hemoglobin, hematocrit, ALT, serum uric acid, HDL-C and LDL-C between the patients with ischemic stroke history and without (all P<0.05). Similarly, there were significant differences in the proportion of Han, the ratio of gender, age, white blood cell count, hemoglobin, hematocrit, platelet count, ALT, albumin, TG and LDL-C between subjects in the low-middle risk group and those in the high risk group (all P<0.05). A logistical regression analysis showed that LDL-C was an independent risk factor for both the ischemic stroke history (OR 2.089, 95% CI 1.860-2.347, P<0.05), and future ischemic stroke risk (OR 1.270, 95% CI 1.079-1.494, P<0.05) in patients with nonvalvular AF. Conclusion: LDL-C is associated with ischemic stroke in patients with nonvalvular AF, and it is also an independent risk factor for future ischemic stroke in these patients.


Pock-forming plasmids isolated from streptomyces roseochromogenus.
A series of high copy number plasmids designated pSRC were isolated from Streptomyces roseochromogenus S264. The pSRC series were found to be self-transmissible by conjugation and to elicit lethal zygosis (Ltz). Using the Ltz phenotype to detect plasmid transformants, the pSRC plasmids were shown to have a wide host range. Among them pSRC1 consisted of two different plasmids with the same molecular weight, pSRC1a and 1b. Information regarding restriction sites suitable for the insertion of DNA was obtained by cloning the thiostrepton resistance gene from pIJ702 into pSRC1b. The single Bgl II site of pSRC1b was nonessential for replication and pock-formation. The pSRC plasmids may be suitable as cloning vectors in Streptomyces.


Algorithm to identify frequent coupled modules from two-layered network series: application to study transcription and splicing coupling.
Current network analysis methods all focus on one or multiple networks of the same type. However, cells are organized by multi-layer networks (e.g., transcriptional regulatory networks, splicing regulatory networks, protein-protein interaction networks), which interact and influence each other. Elucidating the coupling mechanisms among those different types of networks is essential in understanding the functions and mechanisms of cellular activities. In this article, we developed the first computational method for pattern mining across many two-layered graphs, with the two layers representing different types yet coupled biological networks. We formulated the problem of identifying frequent coupled clusters between the two layers of networks into a tensor-based computation problem, and proposed an efficient solution to solve the problem. We applied the method to 38 two-layered co-transcription and co-splicing networks, derived from 38 RNA-seq datasets. With the identified atlas of coupled transcription-splicing modules, we explored to what extent, for which cellular functions, and by what mechanisms transcription-splicing coupling takes place.


Steroidogenesis patterns in common trisomies.
By determining the early patterns of steroidogenesis in the most common aneuploidies, we have shown that there are differences between aneuploid and euploid pregnancy steroidogenesis patterns. We hypothesize that there are differences in steroidogenesis between specific trisomies, as well. The records of all patients with a cytogenetic diagnosis of aneuploidy were studied. Serial data on progesterone(P), estradiol(E2) and beta-HCG(bHCG) was collected in the first trimester of aneuploid pregnancies. A matched group of normals at the same gestational ages was used as a control group. The specific trisomies of the above group were catalogued. 31 aneuploid pregnancies were reviewed for progesterone, estradiol and beta-HCG in the first trimester. Data was available for three or more patients with trisomy 16, 18, 21 and 22. Serial measurements between 5 and 10 weeks of pregnancy were obtained for P, E2, and bHCG. Gestational age was determined by LMP and serial sonograms. The progesterone, estradiol and beta-HCG levels were evaluated by calculating the rates of change between 5 and 10 weeks, rather than threshold values. The natural log of the values was used to plot serial data and reduce scatter due to the large natural variation in values between patients. The rates of change of P, E2 and b-HCG in the trisomic pregnancy groups were compared to matched normal pregnancies. The slopes of the curves for the trisomies and euploid pregnancies were calculated and compared. We determined that the rate of change of HCG for each of the trisomies was no different from euploid pregnancies, which is consistent with earlier data. In examining estradiol, trisomy 22 did not have a statistically different pattern of steroidogenesis, where trisomies 16, 18 and 21 were different than euploid (p < 0.05). With progesterone, trisomies 16, 18 and 22 had statistically different rates of change (p < 0.05), however trisomy 21 did not. As we have shown, in pregnancies with aneuploidy, there is a different pattern of steroidogenesis from euploid pregnancies. The difference is detectable in the first trimester by serial measurements of P and E2. In determining steroidogenesis in trisomies 16, 18, 21, and 22, we demonstrate that there is a difference in progesterone and estradiol levels over 5 to 10 weeks among the trisomies that can assist in the diagnosing of abnormal pregnancies in the first trimester. Furthermore, by looking at the rates of change of the individual steroids, the specific aneuploidy may be suspected. A large prospective study may reveal the clinical utility of these observations for early prenatal diagnosis of aneuploidy or probable spontaneous abortion.


How to make the most of NE dictionaries in statistical NER.
When term ambiguity and variability are very high, dictionary-based Named Entity Recognition (NER) is not an ideal solution even though large-scale terminological resources are available. Many researches on statistical NER have tried to cope with these problems. However, it is not straightforward how to exploit existing and additional Named Entity (NE) dictionaries in statistical NER. Presumably, addition of NEs to an NE dictionary leads to better performance. However, in reality, the retraining of NER models is required to achieve this. We chose protein name recognition as a case study because it most suffers the problems related to heavy term variation and ambiguity. We have established a novel way to improve the NER performance by adding NEs to an NE dictionary without retraining. In our approach, first, known NEs are identified in parallel with Part-of-Speech (POS) tagging based on a general word dictionary and an NE dictionary. Then, statistical NER is trained on the POS/PROTEIN tagger outputs with correct NE labels attached. We evaluated performance of our NER on the standard JNLPBA-2004 data set. The F-score on the test set has been improved from 73.14 to 73.78 after adding protein names appearing in the training data to the POS tagger dictionary without any model retraining. The performance further increased to 78.72 after enriching the tagging dictionary with test set protein names. Our approach has demonstrated high performance in protein name recognition, which indicates how to make the most of known NEs in statistical NER.


Stille type P-C coupling polycondensation towards phosphorus-crosslinked polythiophenes with P-regulated photocatalytic hydrogen evolution.
Recently, exploring new type polymerization protocols has been a major driving force in advancing organic polymers into highly functional materials. Herein we report a new polycondensation protocol to implant the phosphorus (P) atom in the main backbone of crosslinked polythiophenes. The polycondensation harnesses a Stille phosphorus-carbon (P-C) coupling reaction between phosphorus halides and aryl stannanes that has not been reported previously. Mechanistic studies uncovered that the P-electrophile makes the reactivity of a catalytic Pd-center highly sensitive towards the chemical structures of aryl stannanes, which is distinct from the typical Stille carbon-carbon coupling reaction. The efficient P-C polycondensation afforded a series of P-crosslinked polythiophenes (PC-PTs). Leveraging on the direct P-crosslinking polymerization, solid-state 31P NMR studies revealed highly uniform crosslinking environments. Efficient post-polymerization P-chemistry was also applied to the PC-PTs, which readily yielded the polymers with various P-environments. As a proof of concept, new PC-PTs were applied as the photocatalysts for H2 evolution under visible light irradiation. PC-PTs with an ionic P(Me)-center exhibit a H2 evolution rate up to 2050 μmol h-1 g-1, which is much higher than those of PC-PTs with a P(O)-center (900 μmol h-1 g-1) and P(iii)-center (155 μmol h-1 g-1). For the first time, the studies reveal that regulating P-center environments can be an effective strategy for fine tuning the photocatalytic H2 evolution performance of organic polymers.


Combinatorial materials research applied to the development of new surface coatings X: a high-throughput electrochemical impedance spectroscopy method for screening organic coatings for corrosion inhibition.
The objective of the study was to develop a high-throughput electrochemical impedance spectroscopy (HT-EIS) method for rapid and quantitative evaluation of corrosion protective coatings. A 12-element, spatially addressable electrochemical platform was designed, fabricated, and validated. This platform was interfaced to a commercial EIS instrument through an automated electronic switching unit. The HT-EIS system enables four parallel EIS measurements to be run simultaneously, which significantly reduces characterization time compared to that of serial EIS measurements using a multiplexer. The performance of the HT-EIS system was validated using a series of model systems, including a Randles equivalent circuit, an electrochemical reaction (Ti/K4FeCN6, K3FeCN6), a highly uniform polymer film, and several polymer coatings. The results of the validation studies showed that the HT-EIS system enables a major reduction in characterization time and provides high quality data comparable to data obtained with conventional, single-cell EIS measurement systems.


Antioxidant enzymatic systems in pigment tissue of amphibia.
Superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities in pigmented and unpigmented liver tissues of frog and albino rat, respectively, were studied. Our results show that pigmented tissue is lacking in manganese superoxide dismutase activity and that the main enzymatic activity utilized in the cytosol by pigmented cells to reduce the hydrogen peroxide to water is represented by catalase; on the contrary, for the same reaction, the cells of albino rat liver primarily utilize the glutathione peroxidase activity. Both a low glutathione peroxidase activity and a low glutathione reductase activity were found in pigmented tissue of frog liver when compared with unpigmented tissue of rat liver. In light of our results, we also report a hypothetical interrelationship between melanin and reduced glutathione: We believe that in pigmented cells the melanin could act as a reducing physiological agent replacing the glutathione in the reduction of hydrogen peroxide. This reducing action of melanin could cause a diminished need for GSH and therefore could provoke the low glutathione peroxidase and reductase activities in pigmented tissue.


Analysis of strategy and efficacy clinical treatments of Kümmell disease: a cohort study.
Most clinical reports on the surgical treatment of kümmell disease lack consistency between classification and treatment protocol. In this study, we investigate the most appropriate and effective clinical treatment strategies according to the characteristics of different types of Kümmell disease. A retrospective analysis was performed of 48 patients with Kümmell disease treated in Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China for which complete follow-up data were available. All cases were classified into six types: type I, vertebral body height loss less than 20% and no intervertebral disc degeneration from adjacent segments; type II, vertebral body height loss more than 20% and accompanied by degeneration or mild instability of intervertebral discs at adjacent segments; type III, posterior vertebral cortical rupture and dural sac compression, and some accompanied by spinal cord nerve injury. Type III includes type IIIA (recoverable stable type), type IIIB (recoverable unstable type), type IIIC (spinal stenosis type), and type IIID (kyphosis type). Methods of surgery: patients of types I, II, and IIIA were treated with percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP), type IIIB were treated with posterior fixation and fusion, type IIIC were treated with posterior decompression and fixation fusion, and type IIID were treated with posterior osteotomy, orthopedic fixation, and fusion. All patients were followed up for 10-44 months (mean, 20.5±4.5 months). The preoperative and postoperative visual analog scale (VAS) scores, Owestry disability index (ODI) scores, secondary height loss and kyphosis, and neurological improvement were followed up and statistically analyzed. The VAS and ODI scores of all cases were improved compared with those pre-surgery (P<0.05). A total of 8 cases showed loss of vertebral height or secondary kyphosis. The American Spinal Injury Association (ASIA) grades of patients with neural impairment were all improved at the last follow-up. According to the characteristics of different types of Kümmell disease, appropriate clinical treatment strategies can achieve satisfactory curative effects and reduce the occurrence of complications. This study is only a retrospective study, lacks a control group, and the sample size is small. Therefore, it has limitations and does not provide guidance.


Blood level of cadmium and lead in occupationally exposed persons in Gwagwalada, Abuja, Nigeria.
This study was designed to assess the blood levels of cadmium and lead in some occupationally exposed individuals and compare the values with non-exposed individuals, with the aim of increasing the awareness of health risk caused by these heavy metals. A total of 120 subjects (64 occupationally exposed and 56 non-exposed subjects) with the age range of 15-40 years were studied in cross-sectional study conducted between September 2012 and February 2013 in Gwagwalada area of Abuja, Nigeria. Blood cadmium and lead were analyzed using an atomic absorption spectrophotometer (AAS). The respective mean blood levels of cadmium and lead were 11.63±1.73 μg/dl and 45.43±6.93 μg/dl in occupationally-exposed subjects, while in non-exposed subjects 2.03±0.55 μg/dl and 12.08±2.87 μg/dl. The results show that occupational exposure increases the blood level of cadmium and lead, which consequently increases the health risk of the exposed individuals.


Rapid Detection of the mt3243A > G Mutation Using Urine Sediment in Elderly Chinese Type 2 Diabetic Patients.
In this study, we aimed to identify mt3243A > G mutation carriers in a group of Chinese elderly type 2 diabetic patients by a rapid and noninvasive diagnostic system. DNA was extracted from blood, saliva, and urine sediment samples. The mutation screening and quantitation of heteroplasmy were performed by high-resolution melting (HRM) curve and pyrosequencing, respectively. Patients with mt3243A > G mutation underwent a detailed audiometric, ophthalmologic, neurological, and cardiac examination. Two patients (2/1041) carrying the mt3243A > G mutation were detected among all type 2 diabetic patients. In patient 1, the heteroplasmy was 0.8%, 2.8%, and 14.7% in peripheral blood leukocytes, saliva, and urine sediment, respectively. In patient 2, the heteroplasmy was 5.3%, 8.4%, and 37.7% in peripheral blood leukocytes, saliva, and urine sediment, respectively. Both of the two patients showed hearing impairment. Abnormal ophthalmologic conditions and hyperintensity on T2-weighted magnetic resonance images were showed in patient 1. The occurrence of mt3243 A > G mutation was 0.2% in Chinese elderly type 2 diabetic patients. Moreover, detection of mt3243 A > G mutation in urine sediment with high-resolution melting (HRM) curve and pyrosequencing is feasible in molecular genetic diagnosis.


New clinical investigations with selective angiotensin II receptor blocker therapy in diabetes and renal disease.
Halting the reduction in glomerular filtration rate (GFR) is the primary aim of any treatment of patients presenting with progressive chronic renal failure, a very common corollary to diabetes. To improve GFR, the high blood pressure (BP) and proteinuria often seen in these patients must both be controlled. These symptoms lead not only to progressive loss of renal function, but also to an increase in cardiovascular risk. Use of angiotensin-converting enzyme (ACE) inhibitors in these patients has been reported to control BP and reduce protein excretion and cardiovascular risk. Complete blockade of angiotensin II (Ang II) action with the highly selective Ang II receptor blocker (ARB) valsartan, both as monotherapy and in combination with ACE inhibitors, is well-tolerated and efficacious in patients with renal failure. Unlike ACE inhibition, ARB treatment leads to no initial reduction in GFR, thus valsartan may be a better agent for the control of BP, with greater renal protection.


Influence of forest fragmentation on community structure of frogs and lizards in northeastern Costa Rica.
To better understand responses of reptiles and amphibians to forest fragmentation in the lowland Neotropics, we examined community and population structure of frogs and lizards in the fragmented landscape surrounding La Selva Biological Station in the Sarapiquí region of northeastern Costa Rica. We used diurnal quadrats and nocturnal transects to sample frogs and lizards in nine forest fragments (1-7 ha each) and La Selva (1100 ha). Species richness in all fragments combined was 85% of that found in La Selva with comparable sampling effort. Richness varied from 10 to 24 species among forest fragments, compared with 36 species at La Selva. Lizard density was higher and frog density was lower in forest fragments than in La Selva. Community composition varied among sites and by fragment size class, and species occurrence was nested with respect to fragment area. Isolation and habitat variables did not significantly affect species richness, composition, or nestedness. We classified 34% of species as fragmentation sensitive because they were absent or occurred at low densities in fragments. Nevertheless, the relatively high diversity observed in the entire set of fragments indicates that preserving a network of small forest patches may be of considerable conservation value to the amphibians and reptiles of this region.


The role of metabolic reprogramming in T cell fate and function.
T lymphocytes undergo extensive changes in their metabolic properties during their transition through various differentiation states, from naïve to effector to memory or regulatory roles. The cause and effect relationship between metabolism and differentiation is a field of intense investigation. Many recent studies demonstrate the dependency of T cell functional outcomes on metabolic pathways and the possibility of metabolic intervention to modify these functions. In this review, we describe the basic metabolic features of T cells and new findings on how these correlate with various differentiation fates and functions. We also highlight the latest information regarding the main factors that affect T cell metabolic reprogramming.


Superconducting Continuous Graphene Fibers via Calcium Intercalation.
Superconductors are important materials in the field of low-temperature magnet applications and long-distance electrical power transmission systems. Besides metal-based superconducting materials, carbon-based superconductors have attracted considerable attention in recent years. Up to now, five allotropes of carbon, including diamond, graphite, C60, CNTs, and graphene, have been reported to show superconducting behavior. However, most of the carbon-based superconductors are limited to small size and discontinuous phases, which inevitably hinders further application in macroscopic form. Therefore, it raises a question of whether continuously carbon-based superconducting wires could be accessed, which is of vital importance from viewpoints of fundamental research and practical application. Here, inspired by superconducting graphene, we successfully fabricated flexible graphene-based superconducting fibers via a well-established calcium (Ca) intercalation strategy. The resultant Ca-intercalated graphene fiber (Ca-GF) shows a superconducting transition at ∼11 K, which is almost 2 orders of magnitude higher than that of early reported alkali metal intercalated graphite and comparable to that of commercial superconducting NbTi wire. The combination of lightness and easy scalability makes Ca-GF highly promising as a lightweight superconducting wire.


African Swine Fever Virus NP868R Capping Enzyme Promotes Reovirus Rescue during Reverse Genetics by Promoting Reovirus Protein Expression, Virion Assembly, and RNA Incorporation into Infectious Virions.
Reoviruses, like many eukaryotic viruses, contain an inverted 7-methylguanosine (m7G) cap linked to the 5' nucleotide of mRNA. The traditional functions of capping are to promote mRNA stability, protein translation, and concealment from cellular proteins that recognize foreign RNA. To address the role of mRNA capping during reovirus replication, we assessed the benefits of adding the African swine fever virus NP868R capping enzyme during reovirus rescue. C3P3, a fusion protein containing T7 RNA polymerase and NP868R, was found to increase protein expression 5- to 10-fold compared to T7 RNA polymerase alone while enhancing reovirus rescue from the current reverse genetics system by 100-fold. Surprisingly, RNA stability was not increased by C3P3, suggesting a direct effect on protein translation. A time course analysis revealed that C3P3 increased protein synthesis within the first 2 days of a reverse genetics transfection. This analysis also revealed that C3P3 enhanced processing of outer capsid μ1 protein to μ1C, a previously described hallmark of reovirus assembly. Finally, to determine the rate of infectious-RNA incorporation into new virions, we developed a new recombinant reovirus S1 gene that expressed the fluorescent protein UnaG. Following transfection of cells with UnaG and infection with wild-type virus, passage of UnaG through progeny was significantly enhanced by C3P3. These data suggest that capping provides nontraditional functions to reovirus, such as promoting assembly and infectious-RNA incorporation.IMPORTANCE Our findings expand our understanding of how viruses utilize capping, suggesting that capping provides nontraditional functions to reovirus, such as promoting assembly and infectious-RNA incorporation, in addition to enhancing protein translation. Beyond providing mechanistic insight into reovirus replication, our findings also show that reovirus reverse genetics rescue is enhanced 100-fold by the NP868R capping enzyme. Since reovirus shows promise as a cancer therapy, efficient reovirus reverse genetics rescue will accelerate production of recombinant reoviruses as candidates to enhance therapeutic potency. NP868R-assisted reovirus rescue will also expedite production of recombinant reovirus for mechanistic insights into reovirus protein function and structure.


Pure Motor Stroke Secondary to Cerebral Infarction of Recurrent Artery of Heubner after Mild Head Trauma: A Case Report.
The recurrent Heubner's artery is the distal part of the medial striate artery. Occlusion of the recurrent artery of Heubner, classically contralateral hemiparesis with fasciobrachiocrural predominance, is attributed to the occlusion of the recurrent artery of Heubner and is widely known as a stroke syndrome in adults. However, isolated occlusion of the deep perforating arteries following mild head trauma also occurs extremely rarely in childhood. Here we report the case of an 11-year-old boy with pure motor stroke. The brain MRI showed an acute ischemia in the recurrent artery of Heubner supply area following mild head trauma. His fasciobrachial hemiparesis and dysarthria were thought to be secondary to the stretching of deep perforating arteries leading to occlusion of the recurrent artery of Heubner. Post-traumatic pure motor ischemic stroke can be secondary to stretching of the deep perforating arteries especially in childhood.


Nitric Oxide Has a Concentration-Dependent Effect on the Cell Cycle Acting via EIN2 in Arabidopsis thaliana Cultured Cells.
Ethylene is known to influence the cell cycle (CC) via poorly characterized roles whilst nitric oxide (NO) has well-established roles in the animal CC but analogous role(s) have not been reported for plants. As NO and ethylene signaling events often interact we examined their role in CC in cultured cells derived from Arabidopsis thaliana wild-type (Col-0) plants and from ethylene-insensitive mutant ein2-1 plants. Both NO and ethylene were produced mainly during the first 5 days of the sub-cultivation period corresponding to the period of active cell division. However, in ein2-1 cells, ethylene generation was significantly reduced while NO levels were increased. With application of a range of concentrations of the NO donor, sodium nitroprusside (SNP) (between 20 and 500 μM) ethylene production was significantly diminished in Col-0 but unchanged in ein2-1 cells. Flow cytometry assays showed that in Col-0 cells treatments with 5 and 10 μM SNP concentrations led to an increase in S-phase cell number indicating the stimulation of G1/S transition. However, at ≥20 μM SNP CC progression was restrained at G1/S transition. In the mutant ein2-1 strain, the index of S-phase cells was not altered at 5-10 μM SNP but decreased dramatically at higher SNP concentrations. Concomitantly, 5 μM SNP induced transcription of genes encoding CDKA;1 and CYCD3;1 in Col-0 cells whereas transcription of CDKs and CYCs were not significantly altered in ein2-1 cells at any SNP concentrations examined. Hence, it is appears that EIN2 is required for full responses at each SNP concentration. In ein2-1 cells, greater amounts of NO, reactive oxygen species, and the tyrosine-nitrating peroxynitrite radical were detected, possibly indicating NO-dependent post-translational protein modifications which could stop CC. Thus, we suggest that in Arabidopsis cultured cells NO affects CC progression as a concentration-dependent modulator with a dependency on EIN2 for both ethylene production and a NO/ethylene regulatory function.


Rapid, long-range molecular haplotyping of thiopurine S-methyltransferase (TPMT) *3A, *3B, and *3C.
Haplotyping is an important technique in molecular diagnostics because haplotypes are often more predictive for individual phenotypes than are the underlying single-nucleotide polymorphisms (SNPs). Until recently, methods for haplotyping SNPs separated by kilobase distances were laborious and not applicable to high-throughput screening. In the case of thiopurine S-methyltransferase (TPMT*), differentiating among TPMT*3A, *3B, and *3C alleles is sometimes necessary for predictive genotyping. The genomic region including the two SNPs that define TPMT*3A, *3B, and *3C alleles was amplified by long-range PCR. The resulting PCR product was circularized by ligation and haplotyped by allele-specific amplification PCR followed by product identification with hybridization probes. Critical points were the long-range PCR conditions, including choice of buffer and primers, optimization of the ligation reaction, and selection of primers that allowed for strict allele-specific amplification in the second-round PCR. Different underlying TPMT haplotypes could then be differentiated. Results from the haplotyping method were in full agreement with those from our standard real-time PCR method: TPMT*1/*3A (n = 20); TPMT*1/*3C (n = 4); TPMT*1/*1 (n = 6); and TPMT*3A/*3A (n = 6). One TPMT*1/*3A sample failed to amplify, and no whole blood was available for repeat DNA isolation. This method for rapid-cycle real-time, allele-specific amplification PCR-assisted long-range haplotyping has general application for the haplotyping of distant SNPs. The procedure is simpler and more rapid than previous methods. With respect to TPMT, haplotyping has the potential to discriminate the genotypes TPMT*1/*3A (intermediate metabolizer) and TPMT*3B/*3C (poor metabolizer).