Percutaneous Aspiration Thrombectomy for Arterial Thromboembolism during Infrainguinal Endovascular Recanalization.
To evaluate the efficacy of percutaneous aspiration thrombectomy (PAT) for infrainguinal arterial thromboembolism in patients undergoing endovascular recanalization (EVR) and to investigate the predictors for thromboembolic complications. In total, 23 patients (23 limbs) who underwent PAT for thromboembolism (PAT group, PG) during EVR and 237 patients (302 limbs) who underwent successful EVR without thromboembolic complications (control group, CG) were enrolled. Immediate post-operation and follow-up outcomes were compared between the two groups. Multivariate analysis was performed to identify the predictors of thromboembolic complications. Technical success of PAT was defined as achievement of <30% residual stenosis and restoration of mTIMI grade 3. The technical success rate was 95.7% in PG. After intervention, the ankle-brachial index (ABI), restoration of blood flow and improvement in dorsal/plantar arterial pulse score showed no significant differences between PG and CG. During follow-up in PG, a sustained ABI improvement was observed in 63.6% (70.9% in CG), an improvement in walking distance in 68.8% (79.9% in CG,), ulcer healing in 75.0% (71.7% in CG) and restenosis/occlusion in 31.8% (25.2% in CG). The limb salvage rate was 100% in PG (96.0% in CG), and pain relief was observed in 66.7% patients with critical limb ischaemia (81.6% in CG). Superficial femoral artery involvement [0.233; 95% confidence interval (CI), 0.108-0.461; P < 0.001], de-novo lesion occlusion (683.8; 95% CI, 36.5-12804.6; P < 0.001) and intraluminal angioplasty (118.4; 95% CI, 8.0-1758.0; P = 0.001) was associated with high incidence of thromboembolism. PAT is a safe and effective treatment for thromboembolism during infrainguinal arterial EVR. SFA involvement, de-novo lesion occlusion and intraluminal angioplasty may be predictors of thromboembolic complications.


Effect of Postoperative Radiation Therapy Timing on Survival in Pediatric and Young Adult Ependymoma.
Postoperative radiation therapy (RT) is commonly used for World Health Organization grade II-III intracranial ependymoma. Clinicians generally aim to begin RT ≤5 weeks after surgery, but postoperative recovery and need for second look surgery can delay the initiation of adjuvant therapy. On ACNS 0831, patients were required to enroll ≤8 weeks after initial surgery and begin adjuvant therapy within 3 weeks after enrollment. The purpose of this study was to determine the optimal timing of RT after surgery. The National Cancer Database was queried for patients (aged 1-39 years) with localized World Health Organization grade II-III intracranial ependymoma treated with surgery and postoperative RT. Overall survival (OS) curves were plotted based on RT timing (≤5 weeks, 5-8 weeks, and >8 weeks after surgery) and were compared by log-rank test. Factors associated with OS were identified by multivariate analysis. After 2009, complete data were available on whether patients underwent gross total resection or subtotal resection. Planned subset analysis was performed to examine the effect of RT timing on OS in patients with known extent of resection. In the final analytical data set of 1043 patients, no difference in 3-year OS was observed in patients who initiated RT ≤5 weeks, 5 to 8 weeks, and >8 weeks after surgery (89.8% vs 89.1% vs 88.4%; P = .796). On multivariate analysis, grade III tumors (hazard ratio, 2.752; 95% confidence interval, 1.969-3.846, P < .001) and subtotal resection (hazard ratio, 2.253; 95% confidence interval, 1.405-3.611, P < .001) were significantly associated with reduced OS. Timing of RT, total RT dose, age, and other factors were not significant. These findings were affirmed in the subset of patients treated between 2010 and 2016, when extent of resection was routinely recorded. Delayed postoperative RT was not associated with inferior survival in patients with intracranial ependymoma. Delayed RT initiation may be acceptable in patients who require longer postoperative recovery or referral to an appropriate RT center, but should be minimized whenever practical.


SIRT1 is a positive regulator of the master osteoblast transcription factor, RUNX2.
Activation of SIRT1 has previously been shown to protect mice against osteoporosis through yet ill-defined mechanisms. In this study, we outline a role for SIRT1 as a positive regulator of the master osteoblast transcription factor, RUNX2. We find that ex vivo deletion of sirt1 leads to decreased expression of runx2 downstream targets, but not runx2 itself, along with reduced osteoblast differentiation. Reciprocally, treatment with a SIRT1 agonist promotes osteoblast differentiation, as well as the expression of runx2 downstream targets, in a SIRT1-dependent manner. Biochemical and luciferase reporter assays demonstrate that SIRT1 interacts with and promotes the transactivation potential of RUNX2. Intriguingly, mice treated with the SIRT1 agonist, resveratrol, show similar increases in the expression of RUNX2 targets in their calvaria (bone tissue), validating SIRT1 as a physiologically relevant regulator of RUNX2.


Predicting hydration free energies using all-atom molecular dynamics simulations and multiple starting conformations.
Molecular dynamics simulations in explicit solvent were applied to predict the hydration free energies for 23 small organic molecules in blind SAMPL2 test. We found good agreement with experimental results, with an RMS error of 2.82 kcal/mol over the whole set and 1.86 kcal/mol over all the molecules except several hydroxyl-rich compounds where we find evidence for a systematic error in the force field. We tested two different solvent models, TIP3P and TIP4P-Ew, and obtained very similar hydration free energies for these two models; the RMS difference was 0.64 kcal/mol. We found that preferred conformation of the carboxylic acids in water differs from that in vacuum. Surprisingly, this conformational change is not adequately sampled on simulation timescales, so we apply an umbrella sampling technique to include free energies associated with the conformational change. Overall, the results of this test reveal that the force field parameters for some groups of molecules (such as hydroxyl-rich compounds) still need to be improved, but for most compounds, accuracy was consistent with that seen in our previous tests.


Possible link between ectopic pancreas and holoprosencephaly.
We report on the incidental observation of ectopic pancreas in a donor for islet cell transplantation. The donor's clinical and imaging presentation was definitive for holoprosencephaly. This case report discusses a possible link between ectopic pancreas and holoprosencephaly.


[Potential for developments in ulcer surgery].
Historically, surgery for peptic ulcer has seen the evolution of differing operative principles: resection, vagotomy (truncal, selective, highly selective), and a combination of vagotomy and resection (antrectomy). The long-term effects of the various operations can now be evaluated from several published studies. Though vagotomy and antrectomy is the most "efficient" operation (ulcer recurrence rate 1%), it has the highest morbidity (15-20%) and mortality (1.5-2%); while highly selective vagotomy is the least "efficient" operation (ulcer recurrence rate 10%), it has the lowest morbidity (5%) and mortality (less than 0.5%). In the future, reduced recurrence rates should be possible by improving surgical technique and by better selection of the operative procedure (on the basis of a better selection of the operative procedure (on the basis of a better understanding of ulcer pathogenesis), but without sacrificing the advantages of highly selective vagotomy--low morbidity and mortality--for the majority of patients. Intraoperative testing of the completeness of vagotomy, and addition of a drainage such as pyloroplasty or antrectomy for juxtapyloric ulcers, may help to achieve this goal.


[The prognostic value of the E.E.G. in premature infants (author's transl)].
The electroencephalograms of 82 infants (between 27 and 37 weeks of conceptional age) recorded during the neonatal period were analyzed and compared with the ultimate clinical evolution. Three groups of infants were identified according to their neurological state at 3 years of age or older: group A: normal (34 infants), group B: minor neurological sequellae (13 infants) and group C: major neurological sequellae (17 infants). A fourth group (group D: 18 infants) died during the neonatal period. The E.E.Gs were classified as: normal, questionably abnormal, moderately abnormal or grossly abnormal. The analysis revealed that E.E.Gs classified as grossly abnormal, were found only in groups B, C and D. Serial E.E.Gs were of more value in distinguishing these groups. Only infants in groups C and D (with I exceptional case in group B) had E.E.Gs which remained abnormal for several weeks or which deteriorated during the neonatal period. This study shows the prognostic value of the E.E.G. recorded during the neonatal period, particularly serial recordings obtained during and after a period of clinical deterioration. A detailed statistical analysis of the E.E.Gs is in progress.


Global regulatory roles of the cAMP/PKA pathway revealed by phenotypic, transcriptomic and phosphoproteomic analyses in a null mutant of the PKA catalytic subunit in Candida albicans.
The conserved cAMP-dependent protein kinase (PKA) plays critical roles in the regulation of morphological transitions and virulence in the human fungal pathogen Candida albicans. It has long been thought that the PKA catalytic subunit is essential for cell viability in this fungus. Paradoxically, the single adenylyl cyclase-encoding gene, CYR1, which is required for the production of cAMP in C. albicans, is not essential for cell growth. Here, a double mutant of TPK1 and TPK2 (tpk2/tpk2 tpk1/tpk1, t2t1), which encode two isoforms of the PKA catalytic subunit was successfully generated, suggesting that this subunit is not essential for cell viability. Inactivation of the PKA catalytic subunit blocked filamentation and dramatically attenuated white-to-opaque switching, but promoted sexual mating. Comparative transcriptomic analyses demonstrated that the t2t1 and cyr1/cyr1 mutants exhibited similar global gene expression profiles. Compared with the WT strain, the general transcriptional activity and metabolism were significantly decreased in both the t2t1 and cyr1/cyr1 mutants. Using combined phosphoproteomic and bioinformatic analyses, we identified 181 potential PKA phosphorylation targets, which represent 148 unique proteins involved in a wide spectrum of biological processes. The study sheds new insights into the global regulatory features of the cAMP/PKA pathway in C. albicans.


Comparison of the Berg Balance Scale and Fullerton Advanced Balance Scale to predict falls in community-dwelling adults.
[Purpose] The purpose of this study was to investigate and compare the predictive properties of Berg Balance Scale and Fullerton Advanced Balance Scales, in a group of independently-functioning community dwelling older adults. [Subjects and Methods] Ninety-seven community-dwelling older adults (male=39, female=58) who were capable of walking independently on assessment were included in this study. A binary logistic regression analysis of the Berg Balance Scale and Fullerton Advanced Balance Scale scores was used to investigate a predictive model for fall risk. A receiver operating characteristic analysis was conducted for each, to determine the cut-off for optimal levels of sensitivity and specificity. [Results] The overall prediction success rate was 89.7%; the total Berg Balance Scale and Fullerton Advanced Balance Scale scores were significant in predicting fall risk. Receiver operating characteristic analysis determined that a cut-off score of 40 out of 56 on the Berg Balance Scale produced the highest sensitivity (0.82) and specificity (0.67), and a cut-off score of 22 out of 40 on the Fullerton Advanced Balance Scale produced the highest sensitivity (0.85) and specificity (0.65) in predicting faller status. [Conclusion] The Berg Balance Scale and Fullerton Advanced Balance Scales can predict fall risk, when used for independently-functioning community-dwelling older adults.


An International Pilot Study of Self-Reported Quality of Life in Outpatient and Inpatient Mental Health Settings.
Introduction: Measuring quality of life (QoL) is essential to understand how clients perceive their care. In practice, many instruments are in place to identify mental health diagnoses and measure treatment outcomes, but there are fewer standardized instruments to routinely collect information about self-reported QoL, especially across different mental health settings. Moreover, existing tools have been criticized for being built from the perspective of care professionals rather than the users' perspective. The 23-item Self-Reported interRAI-QoL Survey for Mental Health and Addictions (interRAI SQoL-MHA) tackles these issues, as it is based on self-reported measures and has proven validity across settings and countries. Objective: The aim of this study is to assess and compare QoL across settings and explore associations between dimensions of self-reported QoL and some items from the interRAI SQoL-MHA in a multinational sample. Settings: Inpatient and community mental health services. Methods: Data were collected from organizations in Belgium, Finland, Russia, Brazil, Rwanda, Canada and Hong Kong. Logistic regression models were constructed using each domain scale of the interRAI SQoL-MHA (relationship, support, hope, activities and relationship with staff) as dependent variables. Results: A total of 2,474 people (51.2% female, 56.7% of age 45 or older) were included in the study. A benchmark analysis showed the samples that performed above the benchmark line or below. The models yielded significant odds ratios among the domain scales, as well as for the items of the interRAI SQoL-MHA, with positive associations for the items "work and education opportunities" and "satisfied with services", and inverse associations for the items "financial difficulties" and for the inpatient setting. Conclusion: The analysis of associations between the determinants offers relevant information to improve mental health care and clients' perceived quality of life. Information about the determinants can help policymakers to design interventions to improve care outcomes, as well as provide more possibilities for integration into the community. The interRAI SQoL-MHA is innovative, as it can be linked to the third generation interRAI MH and Community MH-instruments, to be used in different mental health care settings, combining the objective and subjective QoL domains.


Meningitis and epiglottitis: a new immunisation against haemophilus influenzae type b infections.
Since 1985 the number of cases of systemic haemophilus influenzae type b (Hib) disease in children in the Oxford region has been recorded. This study shows that a cumulative incidence of children suffering systematic Hib infections before their fifth birthday is 1:600, 71 per cent of sufferers having meningitis. Because the incidence of haemophilus infections may be increasing in the UK and there is increasing resistance of the organism to antimicrobial therapy, the need for primary prevention through immunisation is becoming increasingly attractive. We have therefore undertaken a safety and immunogenicity study of a haemophilus influenzae type b conjugate vaccine (HbO-C) as a first step towards introducing a routine immunisation programme for the UK.


Systemic Treatment for Gynecological Cancer Patients Undergoing Hemodialysis.
Gynecological cancer poses a serious threat to women's health. Chemotherapy-based systemic therapy plays a crucial role in the treatment of gynecological cancers. Many systemic therapeutic drugs are metabolized in the kidneys. Therefore, normal renal function is a prerequisite for gynecological tumor patients to complete the full course of systematic treatment and provide a guarantee for achieving an ideal prognosis. Chronic kidney disease often places restrictions on systematic treatment to different extents, such as influencing drug pharmacokinetics, increasing drug toxicity, and the risk of adverse drug reactions. Unfortunately, women undergoing renal replacement have a higher risk of developing gynecological cancers. This article summarizes the current knowledge on systemic treatment drugs for patients with gynecological cancer undergoing dialysis. We discuss the optimal choice of the systematic therapeutic protocol, administration of form and dosage, and window of chemotherapy during hemodialysis sessions to ensure both effectiveness and safety in gynecological cancer patients.


How do taxpayers respond to tax subsidy for long-term savings? Evidence from Thailand's tax return data.
This paper uses a panel of personal income tax return data for the population of Thai tax filers to examine how individuals respond to tax subsidy for long-term savings. We utilize the 2013 tax reform that lowered the price subsidy for long-term savings in order to obtain causal identification. Our difference-in-difference analysis illustrates that there is a considerable heterogeneity in the individual responses to the subsidy cut-with middle-income taxpayers responding much more than their high-income counterparts. Among the middle-income group, we also find that the subsidy reduction has larger effects on decisions of smaller contributors. Our findings shed light on the heterogeneity of individual responses which are crucial for policymakers who consider an incremental change in the existing tax incentive scheme. The online version contains supplementary material available at 10.1007/s10797-021-09687-w.


Telescopic Partial Dentures-Concealed Technology.
The ideal goal of good dentist is to restore the missing part of oral structure, phonetics, his look and the most important is restored the normal health of the patient, which is hampered due to less or insufficient intake of food. Removable partial denture (RPD) treatment option is considered as a notion, which precludes the inevitability of "floating plastic" in edentulous mouth, that many times fail to fulfill the above essential of the patients. In modern dentistry, though the dental implants or fixed partial denture is the better options, but they have certain limitations. However, overdentures and particularly telescopic denture is the overlooked technology in dentistry that would be a boon for such needy patients. Telescopic denture is especially indicated in the distal edentulous area with minimum two teeth bilaterally present with a good amount of periodontal support. This treatment modality is sort of preventive prosthodontics remedy, which in a conservative manner preserve the remaining teeth and helps in conservation of alveolar bone ultimately. There are two tenets related to this option, one is constant conservation edentulous ridge around the retained tooth and the most important is the endless existence of periodontal sensory action that directs and monitor gnathodynamic task. In this option the primary coping or inner coping are cemented on the prepared tooth, and a similar removable outer or inner telescopic crown placed tightly by using a mechanism of tenso-friction, this is firmly attached to a removable RPD in place without moving or rocking of the prosthesis, which is the common compliant of almost all patients of RPD. Copings are also protecting the abutment from tooth decay and also offers stabilization and maintaining of the outer crown. The outer crown engages the inner coping and gives as an anchor for the remainder of the dentition. This work is the review of telescopic prosthesis which is well supported by the case discussion, and designates the utilization of favorable retained tooth/teeth as abutment that drastically minimized alveolar bone resorption beneath the prosthesis and give the maximum tactile sensation of natural teeth to the patient, which is not possible with other type of RPD.


Expressions of irisin and urotensin II and their relationships with blood pressure in patients with preeclampsia.
The aims of this study are to observe irisin and urotensin II (UII) levels in serum and placenta in normal pregnant and preeclamptic women and investigate the relationship between expressions irisin and UII, and their association with blood pressure. A total of 67 pregnant subjects were recruited, including 31 healthy and 36 preeclamptic pregnant women. Serum irisin and UII concentrations were measured. Expressions of fibronectin type III domain-containing protein 5 (FNDC5) (irisin precursor) and UII in placenta specimens were performed. There was no significant difference of serum irisin levels between severe preeclamptic (SPE)) patients, mild preeclamptic (MPE) patients and normal controls, while serum UII was significantly higher in preeclamptic women than normal pregnancy. There was no relationship between serum UII and irisin levels. In patients with preeclampsia, serum irisin was negatively associated with systolic and diastolic blood pressure(r = -0.350, P = 0.004, r = -0.307, P = 0.011), while serum UII was positively associated with systolic blood pressure (r = 0.291, P = 0.031). Serum irisin, UII, urinary protein level, BMI and serum creatinine were the independent determinants of blood pressure in preeclampsia by multiple regression analysis. Protein expression of FNDC5 and UII was upregulated in placenta of patients with SPE and positively correlated with systolic blood pressure and urinary protein level. We firstly verify that serum irisin and placental irisin precursor expressions have differently correlated with blood pressure. Expressions of irisin and urotensin II have relationships with blood pressure in patients with preeclampsia.


Nail psoriasis.
Nail psoriasis affects nearly 80% of patients with plaque psoriasis and is even more prevalent in patients with psoriatic arthritis. Nail psoriasis is not simply a cosmetic problem but one that effects the structure and function of the nail, resulting in negative psychological effects. The first level in management of nail psoriasis is patient education. The hierarchy of nail psoriasis therapy begins with topical medication followed by devices, intralesional injections, and small molecules. For nail psoriasis patients unresponsive to these treatments, and especially in patients with severe plaque psoriasis, biologics are safe and effective options.


Correlation of fractalkine concentrations in serum and synovial fluid with the radiographic severity of knee osteoarthritis.
Fractalkine has been detected in synovial fluid (SF) from osteoarthritis (OA) patients. This study aims to examine the relation of fractalkine concentrations in serum and SF with the radiographic severity of OA. Fractalkine concentrations of serum and SF were measured using an enzyme-linked immunosorbent assay method in 223 patients with knee OA and 165 healthy controls. The progression of OA was classified according to the Kellgren-Lawrence grading system. Elevated concentrations of fractalkine in serum were found in knee OA patients compared with healthy controls [all results median (interquartile range) 226.25 (183.19-259.91) vs. 127.42 (99.54-154.98) pg/mL, P < 0.001]. The case group included 71 knee OA patients with grade 2, 98 with grade 3, and 54 with grade 4. Knee OA patients with KL grade 4 had significantly higher fractalkine concentrations in serum and SF compared with those with KL grade 2 and 3 [serum: 247.68 (215.05-278.64) vs. 212.45 (169.19-247.96) pg/mL, P < 0.001, and 247.68 (215.05-278.64) vs. 222.00 (179.80-254.98) pg/mL, P = 0.005, respectively; SF: 94.95 (76.46-106.68) vs. 74.31 (63.64-84.79) pg/mL, P < 0.001, and 94.95 (76.46-106.68) vs. 80.34 (68.84-96.39) pg/mL, P = 0.001, respectively]. Knee OA patients with KL grade 3 showed significantly elevated concentrations of fractalkine in SF compared with those with KL grade 2 [80.34 (68.84-96.39) vs. 74.31 (63.64-84.79) pg/mL, P = 0.004]. Fractalkine concentrations in serum and SF of knee OA patients were both significantly associated with the disease severity evaluated by KL grading criteria (r = 0.261, P < 0.001 and r = 0.366, P < 0.001, respectively). The fractalkine concentrations in serum and SF may serve as an effective biomarker for the severity of OA.


Ichthyosis hystrix. Report of a case.
An otherwise healthy 6-year-old girl, with lesions which clinically and histopathologically corresponded to the rare inherited disorder ichthyosis hystrix, is described. The classification of this disorder is briefly discussed.


Influence of prenatal administration of cadmium on postnatal development and inducibility of hepatic monooxygenases in rats.
Cadmium inhibits hepatic monooxygenases in rats of different ages. But also in the offspring of dams which had received cadmium during pregnancy changes in biotransformation activities and their inducibilities could be observed. In the 30- and 60-day-old offspring a decrease in the inducibility of ethoxyresorufin O-deethylation by the specific inducer beta-naphthoflavone could be demonstrated, whereas cytochrome P-450 concentration, ethylmorphine N-demethylation and ethoxycoumarin O-deethylation were not influenced.


Comparative proteomics of cucurbit phloem indicates both unique and shared sets of proteins.
Cucurbits are well-studied models for phloem biology but unusually possess both fascicular phloem (FP) within vascular bundles and additional extrafascicular phloem (EFP). Although the functional differences between the two systems are not yet clear, sugar analysis and limited protein profiling have established that FP and EFP have divergent compositions. Here we report a detailed comparative proteomics study of FP and EFP in two cucurbits, pumpkin and cucumber. We re-examined the sites of exudation by video microscopy, and confirmed that in both species, the spontaneous exudate following tissue cutting derives almost exclusively from EFP. Comparative gel electrophoresis and mass spectrometry-based proteomics of exudates, sieve element contents and microdissected stem tissues established that EFP and FP profiles are highly dissimilar, and that there are also species differences. Searches against cucurbit databases enabled identification of more than 300 FP proteins from each species. Few of the detected proteins (about 10%) were shared between the sieve element contents of FP and EFP, and enriched Gene Ontology categories also differed. To explore quantitative differences in the proteomes, we developed multiple reaction monitoring methods for cucumber proteins that are representative markers for FP or EFP and assessed exudate composition at different times after tissue cutting. Based on failure to detect FP markers in exudate samples, we conclude that FP is blocked very rapidly and therefore makes a minimal contribution to the exudates. Overall, the highly divergent contents of FP and EFP indicate that they are substantially independent vascular compartments.


Classification of Skin Disease using Ensemble Data Mining Techniques.
Objective: Skin diseases are a major global health problem associated with high number of people. With the rapid development of technologies and the application of various data mining techniques in recent years, the progress of dermatological predictive classification has become more and more predictive and accurate. Therefore, development of machine learning techniques, which can effectively differentiate skin disease classification, is of vast importance. The machine learning techniques applied to skin disease prediction so far, no techniques outperforms over all the others. Methods: In this research paper, we present a new method, which applies five different data mining techniques and then developed an ensemble approach that consists all the five different data mining techniques as a single unit. We use informative Dermatology data to analysis different data mining techniques to classify the skin disease and then, an ensemble machine learning method is applied. Results: The proposed ensemble method, which is based on machine learning was tested on Dermatology datasets and classify the type of skin disease in six different classes like include C1: psoriasis, C2: seborrheic dermatitis, C3: lichen planus, C4: pityriasis rosea, C5: chronic dermatitis, C6: pityriasis rubra. The results show that the dermatological prediction accuracy of the test data set is increased compared to a single classifier. Conclusion: The ensemble method used on Dermatology datasets give better performance as compared to different classifier algorithms. Ensemble method gives more accurate and effective skin disease prediction.


PHAGE-MEDIATED SELECTION AND THE EVOLUTION AND MAINTENANCE OF RESTRICTION-MODIFICATION.
Restriction-modification (R-M) was discovered because it provides bacteria with immunity to phage infection. But, is phage-mediated selection the sole mechanism responsible for the evolution and maintenance of these ubiquitous and multiply evolved systems? In an effort to answer this question, we have performed experiments with laboratory populations of E. coli and phage and computer simulations. We consider two ecological situations whereby phage-mediated selection could favor R-M immunity; i) when bacteria with a novel R-M system invade communities of phage-sensitive bacteria in which there are one or more species of phage, and ii) when bacteria colonize bacterial-free habitats in which phage are present. The results of our experiments indicate that in established communities of bacteria and phage, the advantage R-M provides an invading population of bacteria is ephemeral. Within short order, mutants resistant (refractory) to the phage evolve in the dominant population and subsequently in the invading population. The outcome of competition then depends on the relative fitness of the resistant states of these bacterial clones, rather than R-M. As a consequence of sequential selection for independent mutants, this rapid evolution of resistance occurs even when two and three species of phage are present. While in our experiments resistance also evolved when bacteria colonized new habitats in which phage were present, a novel R-M system greatly augmented the likelihood of their becoming established. We interpret the results of this study as support for the hypothesis that the latter, colonization selection, may play an important role in the evolution and maintenance of restriction-modification. However, we also see these results and other observations we discuss as questioning whether protection against phage is the unique biological role of restriction-modification.


Issues of malnutrition and bone disease in patients with cirrhosis.
Malnutrition is a frequent complication of cirrhosis, and many studies have demonstrated the adverse influence of malnutrition on clinical outcomes in patients with cirrhosis. The coexisting complications of fluid overload and ascites may mask the severity of malnutrition, particularly in the early stages of its development. During periods of decompensation, protein and energy requirements are higher, and many patients have inadequate nutritional intake at these times. Further, protein supplementation should not be restricted ad hoc in cirrhotic patients, as for the vast majority of patients dietary protein does not precipitate hepatic encephalopathy. The impairment of hepatic glycogen storage in cirrhotic patients effects a state of accelerated starvation with catabolism of fat and protein to provide substrates for gluconeogenesis. Recent studies have demonstrated the efficacy of nocturnal nutritional supplements in improving nitrogen balance. Resistance to the actions of the anabolic growth factors insulin and growth hormone (GH) is common in cirrhosis, and recent studies have shown that GH resistance, in particular, may be overcome with exogenous GH therapy. Hypermetabolism may be observed in up to one-third of cirrhotic patients. The recent exciting observation that beta-blocker therapy can decrease energy expenditure and catecholamine levels in these patients indicates the need for further intervention studies of beta-blockers as metabolic therapy in cirrhosis.


Altered activity of the medial prefrontal cortex and amygdala during acquisition and extinction of an active avoidance task.
Altered medial prefrontal cortex (mPFC) and amygdala function is associated with anxiety-related disorders. While the mPFC-amygdala pathway has a clear role in fear conditioning, these structures are also involved in active avoidance. Given that avoidance perseveration represents a core symptom of anxiety disorders, the neural substrate of avoidance, especially its extinction, requires better understanding. The present study was designed to investigate the activity, particularly, inhibitory neuronal activity in mPFC and amygdala during acquisition and extinction of lever-press avoidance in rats. Neural activity was examined in the mPFC, intercalated cell clusters (ITCs) lateral (LA), basal (BA) and central (CeA) amygdala, at various time points during acquisition and extinction, using induction of the immediate early gene product, c-Fos. Neural activity was greater in the mPFC, LA, BA, and ITC during the extinction phase as compared to the acquisition phase. In contrast, the CeA was the only region that was more activated during acquisition than during extinction. Our results indicate inhibitory neurons are more activated during late phase of acquisition and extinction in the mPFC and LA, suggesting the dynamic involvement of inhibitory circuits in the development and extinction of avoidance response. Together, these data start to identify the key brain regions important in active avoidance behavior, areas that could be associated with avoidance perseveration in anxiety disorders.


Effects of carbamazepine on the hypothalamic-pituitary-thyroid axis.
To evaluate the effects of treatment with carbamazepine on the hypothalamic-pituitary-thyroid axis and thyroid hormone concentrations in patients with epilepsy. We undertook a prospective study in seven subjects in whom the diagnosis of epilepsy had been established and a regimen of carbamazepine (200 mg three times a day) was initiated. All participants underwent 24-hour 123 I thyroid uptake studies, as well as assessment of the basal thyrotropin concentration and the thyrotropin response to intravenous administration of thyrotropin-releasing hormone. In addition, thyroxine (T(4)), free T(4) index, triiodothyronine (T(3)), free T(3) index, reverse T(3), and T(3) resin uptake were determined before initiation of carbamazepine treatment and again after 3 to 4 months of carbamazepine therapy. Serum T(4), T(3), and free T(4) index decreased significantly (P<0.05) after therapy with carbamazepine, whereas no significant alterations were noted in T(3) resin uptake, free T(3) index, and reverse T(3) concentrations. A significant increase occurred in basal serum thyrotropin level (P<0.05). Moreover, the peak thyrotropin concentration, the absolute change from the basal thyrotropin level, and an integrated thyrotropin response expressed as cumulative response to thyrotropin-releasing hormone stimulation were all significantly increased after carbamazepine therapy in comparison with values documented before initiation of therapy (P<0.05 for all comparisons). Finally, 24-hour 123 I uptake by the thyroid gland increased slightly after carbamazepine therapy, but the change was not statistically significant. All values determined both before and after carbamazepine therapy remained within normal ranges. Carbamazepine therapy induces significant alterations in serum thyroid hormone concentrations as well as in the hypothalamic-pituitary-thyroid axis. Nevertheless, patients receiving carbamazepine treatment continue to remain euthyroid despite these significant changes.


Multiple primary malignancies of laryngeal cancer, small cell lung cancer and squamous cell lung cancer in a patient: how to approach MPMs.
Lung malignancies presenting in association with head and neck cancers are well documented, while laryngeal cancers presenting with simultaneous small cell lung cancer and squamous cell lung cancer have been rarely reported. We report a case of a man aged 65 years with a triple primary malignancy of the lung and larynx. Without a meticulous approach, the patients may not receive curative aim treatment due to incomplete staging. The patient underwent concurrent chemoradiotherapy for locally advanced laryngeal cancer, small cell lung cancer and squamous cell lung cancer followed by combination chemotherapy with etoposide and cisplatin for synchronous double primary lung cancer. Following this therapy, he achieved a complete response of larynx cancer, but a partial response of small cell lung cancer and a stable disease of squamous cell lung cancer. A meticulous diagnostic approach should be encouraged to pursue the possibility of curative treatment and achieve better outcomes for such patients.


Morphologies, mechanical and in vitro behaviors of DLP-based 3D printed HA scaffolds with different structural configurations.
In the field of bone engineering, porous ceramic scaffolds are in great demand for repairing bone defects. In this study, hydroxyapatite (HA) ceramic scaffolds with three different structural configurations, including the body-centered cubic (BCC), the face-centered cubic (FCC), and the triply periodic minimal surface (TPMS), were fabricated through digital light processing (DLP) based 3D printing technologies. The effects of the structural configurations on the morphologies and mechanical properties of the DLP-based 3D printed HA scaffolds were characterized. Furthermore, in vitro evaluations, including in vitro cytocompatibility, bone alkaline phosphatase (ALP) activity assay, and protein expression, were conducted to assess HA scaffold behavior. Finally, we evaluated the effects of structural configurations from these aspects and selected the most suitable structure of HA scaffold for bone repair.


Co-segregation of HLA and rheumatoid arthritis in multicase families.
Inheritance of parental HLA haplotypes was examined in the offspring of 95 multicase rheumatoid arthritis (RA) families. Overall, in these families there was no evidence of preferential transmission of one parental haplotype, although this might have been expected given the loading of these families with RA cases. However, there was a difference in inheritance when the affected and non-affected offspring were compared. A co-segregation analysis showed that the inheritance of parental HLA haplotypes was different between the affected and the unaffected offspring. Unlike a previous report, no difference was demonstrated in this study between the offspring of affected and non-affected parents. Similarly, the affected offspring of HLA DR4 heterozygote parents were more likely to inherit HLA DR4 than the non-affected offspring. It is concluded first that linkage studies of RA using the affected sib-pair method are not invalidated, which would have been the case in the presence of preferential transmission of HLA to all offspring. Secondly, HLA and specifically HLA-DR4 does co-segregate with RA, and, finally, parental RA status, independent of DR4, has little influence in explaining the genetic susceptibility to RA.


Repeated alcohol intake changes circadian rhythm of ambulatory blood pressure.
The blood pressure of 7 clinically healthy volunteering social drinkers was studied while they consumed, with a crossover design for 5 days, either 40 g of alcohol by day or fruit juice, with the two spans on alcohol and juice being separated by a one-week washout. Whereas the rhythm-adjusted mean was not changed, a clear statistically significant increase in the circadian double amplitude was found. The study provides a model for a rapidly achieved circadian amplitude hypertension which may precede an elevation of the overall blood pressure mean in the natural course of the disease.


New Horizons in Diabetic Neuropathies: An Updated Review on their Pathology, Diagnosis, Mechanism, Screening Techniques, Pharmacological, and Future Approaches.
One of the largest problems for global public health is diabetes mellitus (DM) and its micro and macrovascular consequences. Although prevention, diagnosis, and treatment have generally improved, its incidence is predicted to keep rising over the coming years. Due to the intricacy of the molecular mechanisms, which include inflammation, oxidative stress, and angiogenesis, among others, discovering treatments to stop or slow the course of diabetic complications is still a current unmet need. The pathogenesis and development of diabetic neuropathies may be explained by a wide variety of molecular pathways, hexosamine pathways, such as MAPK pathway, PARP pathway, oxidative stress pathway polyol (sorbitol) pathway, cyclooxygenase pathway, and lipoxygenase pathway. Although diabetic neuropathies can be treated symptomatically, there are limited options for treating the underlying cause. Various pathways and screening models involved in diabetic neuropathies are discussed, along with their possible outcomes. Moreover, both medicinal and non-medical approaches to therapy are also explored. This study highlights the probable involvement of several processes and pathways in the establishment of diabetic neuropathies and presents in-depth knowledge of new therapeutic approaches intended to stop, delay, or reverse different types of diabetic complications.


Optimal radiotherapy target volumes in intracranial nongerminomatous germ cell tumors: Long-term institutional experience with chemotherapy, surgery, and dose- and field-adapted radiotherapy.
To evaluate patterns of failure after multimodality treatment of nongerminomatous germ cell tumors (NGGCTs). We retrospectively reviewed records of 34 patients diagnosed with primary intracranial NGGCT between 1988 and 2014. Thirty-four patients received induction chemotherapy followed by radiation with or without surgery. Median follow-up was 11.1 years (0.8-23.3). Outcomes were significantly improved in these 34 patients (5-year overall survival [OS]: 88% versus 50%, P = 0.0092), so analysis is restricted to that subset. Disease-free survival (DFS) was 67, 60, and 54% at 5, 10, and 15 years, respectively. Elevated cerebrospinal fluid-α-fetoprotein (CSF-AFP) at diagnosis was associated with poorer DFS (37 vs. 89% at 10 years; P = 0.01). There was no statistically significant difference in OS, or DFS, or patterns of failure for limited radiotherapy volumes versus larger volumes; however, patients receiving initial local radiotherapy had 32% distant central nervous system (CNS) recurrence at 10 years compared to 0% for those receiving initial larger field irradiation (P = 0.09). Fifteen patients recurred. All four patients who relapsed in the spine had received local radiotherapy and had elevated serum and CSF-AFP at baseline. All three patients with ventricular relapse received local radiation therapy. NGGCT patients continue to relapse beyond 5 years. Late ventricular relapse occurred even in patients without clear evidence of germinoma component. Elevated CSF-AFP at diagnosis is associated with poor DFS and risk for distant CNS relapse. Patients with residual radiographic disease after chemotherapy or residual malignant histologies after second-look surgery have inferior outcomes. Our data support consideration of treatment intensification for these patients.


Omental cyst presenting as tubercular ascites.
Cystic lymphangiomas are uncommon congenital benign tumours of vascular origin with a lymphatic differentiation originating across various anatomical locations. Large intrabdominal cysts may mimic ascites. We report the case of a one-and-a-half-year-old male child with a giant cystic lymphangioma originating in the greater omentum presenting as tubercular ascites. This report aims to highlight the limitations of biochemical investigations such as ascitic adenosine deaminase (ADA) in differentiating the epidemiologically prevalent tubercular ascites from an intrabdominal cyst, especially in a resource-poor nation as ours, where invasive diagnostic procedures pose an economic burden.


A multidirectional non-cell autonomous control and a genetic interaction restricting tobacco etch virus susceptibility in Arabidopsis.
Viruses constitute a major class of pathogens that infect a variety of hosts. Understanding the intricacies of signaling during host-virus interactions should aid in designing disease prevention strategies and in understanding mechanistic aspects of host and pathogen signaling machinery. An Arabidopsis mutant, B149, impaired in susceptibility to Tobacco etch virus (TEV), a positive strand RNA virus of picoRNA family, was identified using a high-throughput genetic screen and a counterselection scheme. The defects include initiation of infection foci, rate of cell-to-cell movement and long distance movement. The defect in infectivity is conferred by a recessive locus. Molecular genetic analysis and complementation analysis with three alleles of a previously published mutant lsp1 (loss of susceptibility to potyviruses) indicate a genetic interaction conferring haploinsufficiency between the B149 locus and certain alleles of lsp1 resulting in impaired host susceptibility. The pattern of restriction of TEV foci on leaves at or near the boundaries of certain cell types and leaf boundaries suggest dysregulation of a multidirectional non-cell autonomous regulatory mechanism. Understanding the nature of this multidirectional signal and the molecular genetic mechanism conferring it should potentially reveal a novel arsenal in the cellular machinery.


[Subjective assessment of voice functions among teachers taking part in the rehabilitation program].
In daily phoniatric practice, apart from laryngoscopy, another simple and useful method of examining the voice organ is perceptual voice assessment based on the GRBAS scale. An extension to this examination can be the Voice Handicap Index test (VHI). 79 female teachers taking part in a 7-week-long rehabilitation course on voice emission techniques. Before and after the course the participants were subject to phoniatric examination including laryngovideostroboscopy, GRBAS scale assessment and determining the voice handicap index (VHI). After the course, a substantial improvement has been observed in voice emission, perceptual assessment and the VHI test. It has been observed that there is a statistically significant correlation between GRBAS and VHI results and mean phonation time (MPT) measured before and after the course. The VHI test should be included in complex analysis of the effects of intensive rehabilitation.


Collocation based training of neural ordinary differential equations.
The predictive power of machine learning models often exceeds that of mechanistic modeling approaches. However, the interpretability of purely data-driven models, without any mechanistic basis is often complicated, and predictive power by itself can be a poor metric by which we might want to judge different methods. In this work, we focus on the relatively new modeling techniques of neural ordinary differential equations. We discuss how they relate to machine learning and mechanistic models, with the potential to narrow the gulf between these two frameworks: they constitute a class of hybrid model that integrates ideas from data-driven and dynamical systems approaches. Training neural ODEs as representations of dynamical systems data has its own specific demands, and we here propose a collocation scheme as a fast and efficient training strategy. This alleviates the need for costly ODE solvers. We illustrate the advantages that collocation approaches offer, as well as their robustness to qualitative features of a dynamical system, and the quantity and quality of observational data. We focus on systems that exemplify some of the hallmarks of complex dynamical systems encountered in systems biology, and we map out how these methods can be used in the analysis of mathematical models of cellular and physiological processes.


Prosthetic Complications Affecting Single-Tooth Morse-Taper Connection Implants.
To evaluate the long-term cumulative implant survival rate (CISR%) and cumulative implant-crown success rate (CICSR%) of single-tooth Morse-taper connection implants, with particular attention to documenting the incidence of prosthetic complications. The customized records of all patients who had been treated with single-tooth Morse-taper connection implants in 2 dental centers during the period between January 2002 and December 2012 were revisited. These records included patient-related (gender, age at surgery, smoking, bruxism), implant-related (date of insertion, site/location, and length/diameter of the implant, previous/concomitant bone regeneration), and restoration-related (date of delivery of the provisional and final crown) information. In addition, these records contained information about any implant failure and biologic and/or prosthetic complication that occurred during the follow-up period as well as the radiographic documentation. The follow-up period comprised between 5 and 15 years. The main outcomes were CISR% and CICSR%, with the latter being defined as the condition in which no complication had affected the surviving implant-supported crown during the entire follow-up. Life-table analysis was used for the analysis of CISR% and CICSR%. Peri-implant marginal bone resorption (PIMBR) at 5, 10, and 15 years was a secondary outcome of this study. In total, 578 patients who had received 612 implants were included in this study. The overall CISR% at 15 years was 94.8% (94.2% maxilla, 95.3% mandible). Among the surviving crowns, the overall CICSR% at 15 years was 94.5% (93.1% and 94.9% for anterior and posterior crowns, respectively), and the incidence of prosthetic complications was low (1.5%). The PIMBL amounted to 0.38 ± 0.29 mm, 0.49 ± 0.35 mm, and 0.94 ± 0.58 mm at the 5-, 10-, and 15-year follow-ups, respectively. Morse-taper connection implants represent a reliable treatment procedure for the restoration of single-tooth gaps in the long term, with high CISR% (94.8%) at 15 years, a very low incidence of complications, and a high CICSR% (94.5%).


Quadriceps muscle function after high tibial osteotomy for osteoarthritis of the knee.
In patients with osteoarthritis of the knees, quadriceps muscle dysfunction is an early and common clinical feature and an important determinant of disability. In the current study, changes in quadriceps muscle strength and voluntary quadriceps muscle activation after high tibial osteotomies for primary osteoarthritis of the knee in 19 patients were investigated. Quadriceps muscle function was assessed during different degrees of isometric maximum voluntary contraction using a specially built chair. One year after surgery all patients had reexamination of their surgically treated and contralateral knees. Voluntary activation and maximum voluntary contraction values of the followup assessment were significantly lower in the surgically treated knees compared with the preoperative assessment. In the contralateral knees, there were no differences between preoperative and followup measurements. High tibial osteotomy is an extraarticular operative therapeutic approach to treatment of osteoarthritis of the knee that does not lead to improvement of quadriceps muscle function. Because there is evidence that quadriceps sensorimotor dysfunction is important not only for the disability in osteoarthritis of the knee, but also for progression of the disease, knee function may be worsened by high tibial osteotomy in some patients.


ZNF32 prevents the activation of cancer-associated fibroblasts through negative regulation of TGFB1 transcription in breast cancer.
Breast cancer is the most frequently diagnosed malignancy and the leading cause of cancer-related deaths in women worldwide. Cancer-associated fibroblasts (CAFs) are one of the fundamental cellular components of the tumor microenvironment and play a critical role in the initiation, progression, and therapy resistance of breast cancer. However, the detailed molecular mechanisms of CAFs activation from normal fibroblasts (NFs) are still not well understood. In the present study, we reported that ZNF32 expression in breast cancer cells was negatively correlated with CAF-related markers (FSP1, α-SMA, and FAP) in stromal fibroblasts, and loss of ZNF32 promoted the activation of CAFs, as evidenced by the enhanced proliferation and contractility of CAFs. ZNF32 deficiency-mediated fibroblast activation promoted the growth and metastasis of breast cancer cells in vitro and in vivo. Mechanistically, we demonstrated that ZNF32 inhibited TGFB1 transcription by directly binding to the -1968/-1962 region of the TGFB1 promoter, leading to the prevention of fibroblast activation. Altogether, our findings reveal an important mechanism by which ZNF32 suppression increases the transcription of the TGFB1 gene in breast cancer cells, and subsequently, elevated levels of secretory TGF-β stimulate NFs transformation into CAFs, which in turn facilitates the malignant progression of breast cancer. Our data implicated ZNF32 as a potential therapeutic strategy against breast cancer.


Quinupristin/dalfopristin (RP 59500) therapy for vancomycin-resistant Enterococcus faecium aortic graft infection: case report.
A 46-year-old woman was admitted to the hospital with severe peripheral vascular disease, requiring multiple vascular surgical procedures. During the sixth hospital week, after prior therapy with multiple antibiotics, Enterococcus faecium was isolated as the only organism from an operating room culture of an infected aortic graft. Histological examination of the graft showed infiltration with polymorphonuclear leukocytes. Subsequently, cultures of an infected inguinal wound yielded Enterococcus faecium with mixed bacterial growth. Both isolates of Enterococcus faecium were resistant to all available antimicrobials, including ampicillin, vancomycin, tetracycline, chloramphenicol, and ciprofloxacin. Compassionate use therapy with quinupristin/dalfopristin (RP59500) was administered for 25 days, the patient's clinical condition improved, and wound healing occurred. Transient elevation of serum alkaline phosphatase was noted. This case demonstrates successful eradication of deep VREF infection by quinupristin/dalfopristin with good tolerance of prolonged therapy.


Expression of the serum opacity factor gene and the variation in its upstream region in Streptococcus dysgalactiae isolates from fish.
Group C Streptococcus dysgalactiae (GCSD) is a pathogen of farmed fish. Almost all GCSD isolates from Asian countries, including Japan, Taiwan, Malaysia, and China, have a serum opacity factor (SOF-FD). Although the SOF-FD sequences in different GCSD isolates are identical, different opacification activities are observed. Three types of variations were observed in the upstream sequence of the sof-FD gene in GCSD isolates with different SOF-FD activities. Type 1 was characterized by insertion of an IS981-like element into the upstream region of the sof-FD gene. In Type 2, an IS981-like element was inserted into the upstream region in a direction opposite to that in Type 1. In Type 3, no IS element was inserted. Type 1 was predominant among Japanese isolates (129 of 133). Isolates from other Asian countries were generally Type 3 (13 of 16). Except for 1 strain, Type 1 strains exhibited opacification activities with optical densities (ODs)>0.6, while Type 2 and Type 3 strains have low opacification activities (ODs >0.2). Only Type 1 strains have putative -10 and -35 promoter regions upstream of the sof-FD gene, and the expression level of the sof-FD gene was higher in Type 1 strains than in Type 2 and Type 3 strains.


Detecting envelope stress by monitoring β-barrel assembly.
The cell envelope protects bacteria from their surroundings. Defects in its integrity or assembly are sensed by signal transduction systems, allowing cells to rapidly adjust. The Rcs phosphorelay responds to outer membrane (OM)- and peptidoglycan-related stress in enterobacteria. We elucidated how the OM lipoprotein RcsF, the upstream Rcs component, senses envelope stress and activates the signaling cascade. RcsF interacts with BamA, the major component of the β-barrel assembly machinery. In growing cells, BamA continuously funnels RcsF through the β-barrel OmpA, displaying RcsF on the cell surface. This process spatially separates RcsF from the downstream Rcs component, which we show is the inner membrane protein IgaA. The Rcs system is activated when BamA fails to bind RcsF and funnel it to OmpA. Newly synthesized RcsF then remains periplasmic, interacting with IgaA to activate the cascade. Thus RcsF senses envelope damage by monitoring the activity of the Bam machinery.


[Establishment of a new combined enzyme immunoassay for detection of HBV preS1 and core antigens and the consistency with HBV DNA test].
In this study, a new combined enzyme immunoassay(NRAg ELISA) for detection of HBV PreS1 and core antigens which was highly consistent with serum HBV DNA test was established. The serial serum dilution test indicated that the average sensitivity of the assay was 10(3.2) genome copies/mL (95% CI: 10(2.2-4.2) genome copies/mL), which was notably higher than the test performed on Pre S1 or core antigen alone. The test with sera from 994 blood donors whose HBsAg were negative demonstrated that the specificity of this assay was 99.7% (95% CI: 99.1%-99.9%). 271 serum samples from chronic hepatitis patients were also examined and the result showed that the total consistent rate between NRAg ELISA and HBV DNA was 96.3% (95% CI: 93.3%-98.2%). The NRAg ELISA S/CO(signal/cutoff) was closely correlated with HBV genome copies (R = 0.9158, n=231). Furthermore,by using this assay,we found a patient whose HBsAg was negative but HBV DNA was positive. Sequencing result showed that HBV genome from this patient had a point mutation in the "a"epitope of S gene. Our results indicate that HBV NRAg ELISA has a high relativity with HBV DNA test, and can effectively detect the mutation of HBsAg,it is expected to be a potent tool for screening HBsAg mutant and is a convenient method for substituting HBV DNA test.


Neocortical activity tracks the hierarchical linguistic structures of self-produced speech during reading aloud.
How the human brain uses self-generated auditory information during speech production is rather unsettled. Current theories of language production consider a feedback monitoring system that monitors the auditory consequences of speech output and an internal monitoring system, which makes predictions about the auditory consequences of speech before its production. To gain novel insights into underlying neural processes, we investigated the coupling between neuromagnetic activity and the temporal envelope of the heard speech sounds (i.e., cortical tracking of speech) in a group of adults who 1) read a text aloud, 2) listened to a recording of their own speech (i.e., playback), and 3) listened to another speech recording. Reading aloud was here used as a particular form of speech production that shares various processes with natural speech. During reading aloud, the reader's brain tracked the slow temporal fluctuations of the speech output. Specifically, auditory cortices tracked phrases (<1 Hz) but to a lesser extent than during the two speech listening conditions. Also, the tracking of words (2-4 Hz) and syllables (4-8 Hz) occurred at parietal opercula during reading aloud and at auditory cortices during listening. Directionality analyses were then used to get insights into the monitoring systems involved in the processing of self-generated auditory information. Analyses revealed that the cortical tracking of speech at <1 Hz, 2-4 Hz and 4-8 Hz is dominated by speech-to-brain directional coupling during both reading aloud and listening, i.e., the cortical tracking of speech during reading aloud mainly entails auditory feedback processing. Nevertheless, brain-to-speech directional coupling at 4-8 Hz was enhanced during reading aloud compared with listening, likely reflecting the establishment of predictions about the auditory consequences of speech before production. These data bring novel insights into how auditory verbal information is tracked by the human brain during perception and self-generation of connected speech.


Phase Amplified Correlation for Improved Sub-pixel Motion Estimation.
Phase correlation (PC) is widely employed by several sub-pixel motion estimation techniques in an attempt to accurately and robustly detect the displacement between two images. To achieve sub-pixel accuracy, these techniques employ interpolation methods and function-fitting approaches on the cross-correlation function derived from the PC core. However, such motion estimation techniques still present a lower bound of accuracy that cannot be overcome. To allow room for further improvements, we propose in this paper the enhancement of the sub-pixel accuracy of motion estimation techniques by employing a completely different approach: the concept of motion magnification. To this end, we propose the novel phase amplified correlation (PAC) that integrates motion magnification between two compared images inside the phase correlation part of frequencybased motion estimation algorithms and thus directly substitutes the PC core. The experimentation on magnetic resonance (MR) images and real video sequences demonstrates the ability of the proposed PAC core to make subtle motions highly distinguishable and improve the sub-pixel accuracy of frequency-based motion estimation techniques.


Dislocations of the lunate with and without fracture of the scaphoid.
A review of 61 patients with dislocation of the lunate (some with and some without fracture of the scaphoid) showed that the majority had satisfactory results at an average follow-up of three and a half years. Most patients with a simple dislocation had a good or satisfactory result; radiological instability was noted in a quarter of the wrists but was not often associated with symptoms. Two-thirds of the patients with an associated fracture of the scaphoid had a good or satisfactory result. Immediate percutaneous wire fixation of the reduced scaphoid, whether it is fractured or not, is the best way of maintaining normal anatomical relationship while the ligaments and fracture heal; this may further improve the prognosis. In most cases extreme dorsiflexion of the wrist appeared to be the mechanism of injury.


Keeping up: the nurse executive's present and future role in information technology.
Information management is a required competency for nurse executives, both for current and future practice. This article describes the chief nursing executive's role in information technology, presents suggestions for maintaining information technology competency, and shares how one hospital devised a simple tool to make information more usable for the nursing leadership team.


The distribution of synaptotagmin II in RBL-2H3 and its regulation on exocytosis of lysosomes in RBL-2H3.
Synaptotagmin (Syt) constitutes a family of membrane-trafficking proteins, so far nearly 20 Syts have been discovered. Extensive work showed that synatotagmins were a potential Ca2+ sensor for regulated exocytosis. This study was to investigate the expression and location of synaptotagmin II (Syt2) in RBL-2H3 (RBL) and its role in regulating exocytosis of RBL. The expression of Syt2 in RBL was confirmed by Western blot. The recombinant expression vector pEGFP-N1-Syt2 was constructed and transfected into RBL by electroporation, the stable transfectant RBL-Syt2-S expressing fusion protein Syt2-EGFP were obtained and Syt2 was highly concentrated at plasma membrane with little detected in cytoplasm. To analyze the role of Syt2 during exocytosis of RBL, the release of cathepsin D was assayed by immunoblotting. Compared with control, the release of cathepsin D by RBL-Syt2-S was markedly decreased. The results indicated that Syt2 played a negative regulation in exocytosis of lysosomes in RBL.


Shell and small particles; evaluation of new column technology.
The performance of 5 cm long columns packed with shell particles was compared to totally porous sub-2 microm particles in gradient and isocratic elution separations of hormones (dienogest, finasteride, gestodene, levonorgestrel, estradiol, ethinylestradiol, noretistherone acetate, bicalutamide and tibolone). Peak capacities around 140-150 could be achieved in 25 min with the 5 cm long columns. The Ascentis Express column (packed with 2.7 microm shell particles) showed similar efficiency to sub-2 microm particles under gradient conditions. Applying isocratic separation, the column of 2.7 microm shell particles had a reduced plate height minimum of approximately h=1.6. It was much smaller than obtained with totally porous particles (h approximately = 2.8). The impedance time also proved more favorable with 2.7 microm shell particles than with totally porous particles. The influence of extra-column volume on column efficiency was investigated. The extra-column dispersion of the chromatographic system may cause a shift of the HETP curves.


[ Exsanguination, extreme hemodilution and autologous retransfusion in cardiopulmonary bypass].
In ten dogs and seven patients undergoing open heart surgery, 94% of circulatory volume was replaced by electrolitic solutions; extracted blood was stored temporarily at 5degreesC. Usage of blood was avoided for replacement of extracorporeal fluid circuit and blood lost during surgery. After cardiopulmonar bypass, storage blood was transfused. In both experimental and clinical conditions neither renal, electrolitic nor blood alterations were observed.


Predicting mortality with biomarkers: a population-based prospective cohort study for elderly Costa Ricans.
Little is known about adult health and mortality relationships outside high-income nations, partly because few datasets have contained biomarker data in representative populations. Our objective is to determine the prognostic value of biomarkers with respect to total and cardiovascular mortality in an elderly population of a middle-income country, as well as the extent to which they mediate the effects of age and sex on mortality. This is a prospective population-based study in a nationally representative sample of elderly Costa Ricans. Baseline interviews occurred mostly in 2005 and mortality follow-up went through December 2010. Sample size after excluding observations with missing values: 2,313 individuals and 564 deaths. prospective death rate ratios for 22 baseline biomarkers, which were estimated with hazard regression models. Biomarkers significantly predict future death above and beyond demographic and self-reported health conditions. The studied biomarkers account for almost half of the effect of age on mortality. However, the sex gap in mortality became several times wider after controlling for biomarkers. The most powerful predictors were simple physical tests: handgrip strength, pulmonary peak flow, and walking speed. Three blood tests also predicted prospective mortality: C-reactive protein (CRP), glycated hemoglobin (HbA1c), and dehydroepiandrosterone sulfate (DHEAS). Strikingly, high blood pressure (BP) and high total cholesterol showed little or no predictive power. Anthropometric measures also failed to show significant mortality effects. This study adds to the growing evidence that blood markers for CRP, HbA1c, and DHEAS, along with organ-specific functional reserve indicators (handgrip, walking speed, and pulmonary peak flow), are valuable tools for identifying vulnerable elderly. The results also highlight the need to better understand an anomaly noted previously in other settings: despite the continued medical focus on drugs for BP and cholesterol, high levels of BP and cholesterol have little predictive value of mortality in this elderly population.


Cancer incidence and mortality in Henan province, 2012.
Population-based cancer registration data in 2012 from all available cancer registries in Henan province were collected by Henan Office for Cancer Research and Control. The numbers of new cancer cases and cancer deaths in Henan province with compiled cancer incidence and mortality rates were estimated. In 2015, all registries' data in Henan province were qualified for the national cancer registry annual report in 2012. The pooled data were stratified by area (urban/rural), gender, age group (0, 1.4, 5.9, 10.14, …, 85+) and cancer type. New cancer cases and deaths were estimated using age-specific rates and corresponding population of Henan province in 2012. The Chinese census data in 2000 and Segi's population were applied for age-standardized rates. All the rates were expressed per 100,000 person-years. Qualified 19 cancer registries (4 urban and 15 rural registries) covered 16,082,688 populations of Henan province in 2012. The percentage of cases with morphologically verified (MV%) and death certificateonly cases (DCO%) were 69.84% and 2.30%, respectively, and the mortality to incidence rate ratio (M/I) was 0.64. It was estimated that there were 248,510 new cancer cases and 158,630 cancer deaths in Henan province in 2012. The incidence rate was 266.17/100,000 (288.61/100,000 in males and 241.86/100,000 in females), the age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 208.95/100,000 and 206.41/100,000 with the cumulative incidence rate (0.74 years old) of 24.30%. The crude incidence rate in urban areas was higher than that in rural areas. However, after adjusted by age, the cancer incidence rate in rural was higher than that in urban areas. The crude mortality of all cancers in Henan province was 169.90/100,000 (201.23/100,000 in males and 135.95/100,000 in females). The age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 131.20/100,000 and 130.80/100,000, respectively. Among the patients aged 0.74 years, the cumulative mortality rate was 15.03%. The crude cancer mortality rate in urban areas was higher than that of rural areas. However, the age-standardized rate in rural areas was higher than that of urban areas. Cancers of lung, stomach, esophagus, liver, female breast, colorectum, cervix, brain, uterus and ovary were the most common cancers, accounting for about 82.80% of all cancer new cases. Lung cancer, stomach cancer, esophageal cancer, liver cancer, colorectal cancer, female breast cancer, brain cancer, leukemia, pancreatic cancer and cervix cancer were the leading causes of cancer deaths, accounting for about 88.50% of all cancer deaths. The burden between urban and rural, males and females were different. Registration data of Henan province was qualified to provide basic information on population-based cancer incidence, mortality for cancer prevention and control. The upper digestive tract cancer burden in Henan province, especially for males in rural areas, was higher. The incidence rate of female breast cancer was higher in urban areas. Targeted prevention, early detection and treatment programs should be carried out by health department to control the cancer burden.


Involvement of tachykinins and NK1 receptor in the joint inflammation with collagen type II-specific monoclonal antibody-induced arthritis in mice.
Rheumatoid arthritis (RA) is a chronic multisystem disease characterized by persistent joint inflammation associated with severe pain. Because RA is an immune-mediated joint disease and because type II collagen is considered an autoantigen, rodent models of arthritis using collagen type II-specific monoclonal antibodies are valuable for studying the pathogenesis of autoimmune arthritis and for evaluating therapeutic strategies. The tachykinin family peptides, substance P (SP) and hemokinin-1 (HK-1), are expressed in the nervous systems and in many peripheral organs and immunocompetent cells and activate tachykinin NK1 receptors with similar affinities. NK1 receptors are involved in the inflammation and hyperalgesia associated with a variety of inflammatory diseases. In the present study, we examined the involvement of SP and HK-1 in the joint inflammation and hyperalgesia in a collagen antibody-induced arthritis (CAIA) model in mice. The messenger RNA expression levels of the TAC1 gene encoding SP and of the TAC4 gene encoding HK-1 were decreased in the dorsal root ganglia and spinal cord at the peak of the inflammatory symptoms in CAIA. Systemic injection of an NK1 receptor antagonist, WIN 51708, significantly inhibited the joint swelling, but not the mechanical allodynia, on day 7 in CAIA mice. The messenger RNA expression levels of TAC1 and TAC4 in the dorsal root ganglia and dorsal spinal cord were unaffected by treatment with WIN 51708. These findings suggest that tachykinins and NK1 receptors play a key role in joint inflammation, rather than in nociceptive sensitization, in CAIA.


One-pot strategy for on-site enzyme production, biomass hydrolysis, and ethanol production using the whole solid-state fermentation medium of mixed filamentous fungi.
The efficient use of renewable lignocellulosic feedstocks to obtain biofuels and other bioproducts is a key requirement for a sustainable biobased economy. This requires novel and effective strategies to reduce the cost contribution of the cellulolytic enzymatic cocktails needed to convert the carbohydrates into simple sugars, in order to make large-scale commercial processes economically competitive. Here, we propose the use of the whole solid-state fermentation (SSF) medium of mixed filamentous fungi as an integrated one-pot strategy for on-site enzyme production, biomass hydrolysis, and ethanol production. Ten different individual and mixed cultivations of commonly used industrial filamentous fungi (Aspergillus niger, Aspergillus oryzae, Trichoderma harzianum, and Trichoderma reesei) were performed under SSF and the whole media (without the extraction step) were used in the hydrolysis of pretreated sugarcane bagasse. The cocultivation of T. reesei with A. oryzae increased the amount of glucose released by around 50%, compared with individual cultivations. The release of glucose and reducing sugars achieved using the whole SSF medium was around 3-fold higher than obtained with the enzyme extract. The addition of soybean protein (0.5% w/w) during the hydrolysis reaction further significantly improved the saccharification performance by blocking the lignin and avoiding unproductive adsorption of enzymes. The results of the alcoholic fermentation validated the overall integrated process, with a volumetric ethanol productivity of 4.77 g/L.h, representing 83.5% of the theoretical yield. These findings demonstrate the feasibility of the proposed one-pot integrated strategy using the whole SSF medium of mixed filamentous fungi for on-site enzymes production, biomass hydrolysis, and ethanol production. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:671-680, 2018.


Geology and paleontology of the Upper Cretaceous Kem Kem Group of eastern Morocco.
The geological and paleoenvironmental setting and the vertebrate taxonomy of the fossiliferous, Cenomanian-age deltaic sediments in eastern Morocco, generally referred to as the "Kem Kem beds", are reviewed. These strata are recognized here as the Kem Kem Group, which is composed of the lower Gara Sbaa and upper Douira formations. Both formations have yielded a similar fossil vertebrate assemblage of predominantly isolated elements pertaining to cartilaginous and bony fishes, turtles, crocodyliforms, pterosaurs, and dinosaurs, as well as invertebrate, plant, and trace fossils. These fossils, now in collections around the world, are reviewed and tabulated. The Kem Kem vertebrate fauna is biased toward large-bodied carnivores including at least four large-bodied non-avian theropods (an abelisaurid, Spinosaurus, Carcharodontosaurus, and Deltadromeus), several large-bodied pterosaurs, and several large crocodyliforms. No comparable modern terrestrial ecosystem exists with similar bias toward large-bodied carnivores. The Kem Kem vertebrate assemblage, currently the best documented association just prior to the onset of the Cenomanian-Turonian marine transgression, captures the taxonomic diversity of a widespread northern African fauna better than any other contemporary assemblage from elsewhere in Africa.


Activation of NK cells is associated with HIV-1 disease progression.
The main predictor of HIV-1 disease progression is CD8(+) T cell activation, characterized by elevated expression of CD38 and HLA-DR. NK cells are also activated in viremic HIV-1-infected individuals. However, the relationship between NK cell activation and HIV-1 disease progression remains undefined. We characterized NK cell activation and its association with disease progression in treatment of naive HIV-1-infected individuals, who naturally maintained low/undetectable viremia (elite and viremic controllers), compared with progressors and AIDS subjects, and treated individuals. Our results show that CD38 expression on NK cells, predominantly in the cytotoxic CD56(dim)CD16(+) subset, is associated with HIV-1 disease progression (CD4(+) T cell count and pVL), T cell activation (percentage of CD38(+)HLA-DR(+) T cells), sCD14, inflammation, and innate immune activation. Moreover, NK cell activation is increased in HIV-1-infected subjects progressing to AIDS but not in elite and viremic controllers. ART partially reduces the proportion of activated NK cells. Furthermore, our results show that individuals, who naturally control viremia, maintain low levels of innate immune activation similar to those of uninfected controls.


Clonal identity between skin and synovial tissue in a case of mycosis fungoides with polyarthritis.
Polyarthritis in the presence of a cutaneous T-cell lymphoma is a rare phenomenon. We describe a case of mycosis fungoides with development of a symmetric erosive polyarthritis of the small hand joints and feet, diagnosed as rheumatoid arthritis. An identical monoclonal T-cell population in the skin and in the synovium was detected by T-cell receptor gene rearrangement analysis, illustrating articular dissemination of lymphoma cells. Differentiating mycosis fungoides-associated arthritis from rheumatoid arthritis may have important implications for treatment. Based on this case, the relevant literature, and the newest disease concepts, pathogenic mechanisms and therapeutic options of mycosis fungoides-associated arthritis are discussed.


Preoperative QTc Interval is Not Associated With Intraoperative Cardiac Events or Mortality in Liver Transplantation Patients.
The primary objective of this study was to determine whether liver transplantation recipients with preoperative prolonged corrected (QTc) intervals have a higher incidence of intraoperative cardiac events and/or postoperative mortality compared with their peers with normal QTc intervals. This was a retrospective cohort study. Single academic hospital in New York, NY. Patients undergoing liver transplantation between 2007 and 2016. None. Data relating to all liver transplantation recipients with preoperative electrocardiograms were queried from an institutional anesthesia data warehouse and electronic medical records. Primary outcomes were a composite outcome of intraoperative cardiac events and postoperative mortality. Patients with a prolonged QTc interval (>450 ms for men, >470 ms for women) did not demonstrate an association with intraoperative cardiac events, 30- or 90-day mortality, in-hospital mortality, or overall mortality compared with recipients in the normal QTc interval group. A prolonged QTc was found to be associated with increased anesthesia time, surgical time, length of hospital stay, and incidence of fresh frozen plasma and platelets transfusion. Prolonged QTc interval is not associated with an increased incidence of intraoperative cardiac events or mortality in liver transplantation recipients. The demonstrated correlation among QTc length and Model for End-stage Liver Disease score, blood component requirements, surgical and anesthetic times, and hospital length of stay likely represents the association between QTc length and severity of liver disease.


Practice guidelines, patient interests, and risky procedures.
A clinical scenario is described where an anaesthetist is concerned about the seemingly high risk/benefit ratio relating to laparoscopic versus standard inguinal hernia operations. Some options for further action by the anaesthetist are introduced. The remainder of the paper explores the question of who can legitimately assess the acceptability of risk/benefit ratios, and defends the use of practice guidelines at the expense of so called clinical freedom. It is argued that respect for persons is not breached by limiting the treatment options offered to patients to those therapies which have a 'reasonable' risk/benefit ratio. This 'reasonableness' is context dependent, and should be properly decided by those with expertise in the field.


Human-directed aggression and pica in a 1-year-old cat, which worsened following international relocation.
A 14-month-old female spayed Arabian Mau cat was presented for preparation for international air travel and relocation. It was also showing aggressive behaviours towards its owners and visitors to the home, with daily episodes of jumping at, scratching and biting the owners' hands and legs. In addition, the cat was chewing on and ingesting wool and fabric items. Diagnoses of aggression occurring as misplaced play/predatory behaviour, fear-based aggression towards visitors and pica were made, and recommendations were given for both the behavioural presentations as well as to prepare for the family's relocation to a new country and home. These recommendations included the use of long-acting psychotropic medications, which were declined at the time. After arrival in the new home, the cat's aggression and pica worsened, so the owners requested a follow-up appointment. At this point, the selective serotonin reuptake inhibitor (SSRI) fluoxetine was initiated and after 6 weeks of medication, the owners reported a significant improvement in all behavioural signs. There is limited published information on the development and/or worsening of behaviour problems after stressful or traumatic events, such as international relocation. Furthermore, the management of concurrent behavioural presentations, such as, in this case, human-directed aggression and pica, can be challenging. This case provides an example of how this may be achieved. Finally, this case shows how the use of long-acting psychotropic medication, such as the SSRI fluoxetine, can be important and effective in managing feline behaviour problems.


The predictive value of dorsal cingulate activity and fractional anisotropy on long-term PTSD symptom severity.
Posttraumatic stress disorder (PTSD) can be treated with trauma-focused therapy, although only about 50% of the patients recover on the short-term. In order to improve response rates it is important to identify who will and will not recover from trauma-focused therapy. Although previous studies reported dorsal anterior cingulate cortex (ACC) activity, as well as dorsal cingulum bundle white matter microstructure integrity as markers for the persistence of PTSD symptoms on the short-term, it remains unclear whether these markers also predict long-term PTSD symptom severity. PTSD patients (n = 57) were investigated with clinical interviews and an MRI protocol before the start of treatment. Clinical interviews were repeated after 6-8 months of treatment (short-term follow-up), and on average 4 years later (long-term follow-up). Twenty-eight PTSD patients returned for the long-term follow-up. Dorsal ACC activity in response to negative images, and fractional anisotropy (FA) of the dorsal cingulum were the neural markers investigated. In this long-term follow-up sample (n = 28), dorsal ACC activity and dorsal cingulum FA values significantly predicted CAPS scores on short- and long-term follow-up. The results remained significant after controlling for baseline CAPS score, early trauma, and comorbidity. This study confirms the importance of the cingulate cortex activation and white matter integrity not only for short-term treatment outcome, but also for PTSD long-term symptom severity. Future treatments should target ACC function in particular during treatment in order to improve response rates.


[A temporary reduction of emotional reactivity in postweaning, prejuvenile rats: examination by the Runway Test].
Developmental change of emotional reactivity in Wistar rats was investigated by two experiments using the Runway Test. Rats were tested at 20, 30, 40, 60, and 90 days of age for three successive days. First, a cross-sectional comparison of behavior in the Runway Test showed that 30-day-old rats were faster to enter the runway region, faster to reach the end section, and traversed more sections than other age groups. Rats at 60 and 90 days of age defecated more bolles and urinated more. Second, longitudinal comparisons showed that the ambulation of 30- and 40-day-old rats increased gradually over test days, suggesting lowered emotional reactivity. But 60- and 90-day-old rats showed asymptotic level of ambulation and no increase between days and less defecation. These results suggested that postweaning prejuvenile rats showed a temporary reduction of emotional reactivity in novel environments. Also, their emotional reactivity elevated gradually, and remained stable in each individual level.


Attenuated early inflammatory response in solid organ recipients with COVID-19.
Immunosuppression leaves transplanted patients at particular risk for severe acute respiratory syndrome 2 (SARS-CoV-2) infection. The specific features of coronavirus disease 2019 (COVID-19) in immunosuppressed patients are largely unknown and therapeutic experience is lacking. Seven transplanted patients (two liver, three kidneys, one double lung, one heart) admitted to the Ludwig-Maximilians-University Munich because of COVID-19 and tested positive for SARS-CoV-2 were included. The clinical course and the clinical findings were extracted from the medical record. The two liver transplant patients and the heart transplant patient had an uncomplicated course and were discharged after 14, 18, and 12 days, respectively. Two kidney transplant recipients were intubated within 48 hours. One kidney and the lung transplant recipients were required to intubate after 10 and 15 days, respectively. Immunosuppression was adapted in five patients, but continued in all patients. Compared to non-transplanted patients at the ICU (n = 19) the inflammatory response was attenuated in transplanted patients, which was proven by decreased IL-6 blood values. This analysis might provide evidence that continuous immunosuppression is safe and probably beneficial since there was no hyperinflammation evident. Although transplanted patients might be more susceptible to an infection with SARS-CoV-2, their clinical course seems to be similar to immunocompetent patients.


Structurally flexible pyrrolidinium- and morpholinium-based ionic liquid electrolytes.
Ion transport measures and details as well as physico-chemical and electrochemical properties are presented for a small set of structurally flexible pyrrolidinium (Pyrr) and morpholinium (Morph) cation-based ionic liquids (ILs), all with oligoether phosphate-based anions. All have high thermal stabilities, low glass transition temperatures, and wide electrochemical stability windows, but rather moderate ionic conductivities, where both the anions and the cations of the Pyrr-based ILs diffuse faster than those of the Morph-based ILs. Overall, the Pyrr-based ILs show significantly more promise as high-temperature supercapacitor electrolytes, rendering a specific capacitance of 164 F g-1 at 1 mV s-1, a power density of 609 W kg-1 and a specific energy density of 27 W h kg-1 at 90 °C in a symmetric graphite supercapacitor.


[Exogenous estrogen improved calcium homeostasis and skeletal mineralization in vitamin D receptor gene knockout female mice].
It is well known that estrogen can inhibit bone absorption, decrease bone turnover and preserve bone mass. Some studies indicated that the effect of estrogen on calcium and bone is relative to vitamin D system, while others also reported that this effect of estrogen is independent of vitamin D. The genomic effect of 1alpha, 25(OH)(2)D(3)is mediated by the nuclear vitamin D receptor (VDR) in a ligand-dependent manner. Hypocalcemia, hyperparathyroidism and osteomalacia are developed in VDR gene knockout mice. To determine whether the effect of estrogen on calcium and bone is dependent on VDR, this study examined the effect of exogenous estrogen on calcium and bone homeostasis in VDR gene knockout mice. Male and female wild type (WT) and VDR gene knockout heterozygous mice were mated each other and the genotyping of their offsprings were determined by PCR. At age of 21-day, WT and knockout mice were weaned and treated by one of three different regimens: (1) WT-vehicle group: the WT mice were injected with normal saline; (2) VDR KO-vehicle group: the VDR gene knockout mice were injected with normal saline; (3) VDR KO-E group: the VDR gene knockout mice were subcutaneously injected with estradiol, 0.2 mug per mouse, once daily for 1 month. The bone mineral density (BMD) of mice was measured using dual-energy X-ray absorptiometry. All mice were sacrificed at age of 50-day. Blood was taken by heart puncture under anesthesia and serum calcium was measured by autoanalyser.Tibiae were removed, fixed and embedded with the methylmethacrylate (MMA), and undecalcified sections were cut. These sections were stained for mineral with the von Kossa staining procedure and counterstained with toluidine blue. Static histomorphometric analyses were performed on those stained sections. The results showed that the serum calcium level was (2.10+/-0.37) mmol/L in the VDR KO-vehicle mice and rose to (2.80+/-0.41) mmol/L in the VDR KO-E mice although it was still lower than WT-vehicle mice [(3.10+/-0.48) mmol/L]. BMD and mineralized trabeculer volume were increased significantly in VDR KO-E group compared with that in VDR KO-vehicle group. These results suggest that exogenous estrogen can improve calcium absorption and skeletal mineralization in a VDR-independent manner.


Surface polarization enhances ionic transport and correlations in electrolyte solutions nanoconfined by conductors.
Layered materials that perform mixed electron and ion transport are promising for energy harvesting, water desalination, and bioinspired functionalities. These functionalities depend on the interaction between ionic and electronic charges on the surface of materials. Here we investigate ion transport by an external electric field in an electrolyte solution confined in slit-like channels formed by two surfaces separated by distances that fit only a few water layers. We study different electrolyte solutions containing monovalent, divalent, and trivalent cations, and we consider walls made of non-polarizable surfaces and conductors. We show that considering the surface polarization of the confining surfaces can result in a significant increase in ionic conduction. The ionic conductivity is increased because the conductors' screening of electrostatic interactions enhances ionic correlations, leading to faster collective transport within the slit. While important, the change in water's dielectric constant in confinement is not enough to explain the enhancement of ion transport in polarizable slit-like channels.


A Chimera Containing CD4+ and CD8+ T-Cell Epitopes of the Leishmania donovani Nucleoside Hydrolase (NH36) Optimizes Cross-Protection against Leishmania amazonesis Infection.
The Leishmania donovani nucleoside hydrolase (NH36) and NH A34480 of Leishmania amazonensis share 93% of sequence identity. In mice, the NH36 induced protection against visceral leishmaniasis is mediated by a CD4+ T cell response against its C-terminal domain (F3). Besides this CD4+ Th1 response, prevention and cure of L. amazonensis infection require also additional CD8+ and regulatory T-cell responses to the NH36 N-terminal (F1 domain). We investigated if mice vaccination with F1 and F3 domains cloned in tandem, in a recombinant chimera, with saponin, optimizes the vaccine efficacy against L. amazonensis infection above the levels promoted by the two admixed domains or by each domain independently. The chimera induced the highest IgA, IgG, and IgG2a anti-NH36 antibody, IDR, IFN-γ, and IL-10 responses, while TNF-α was more secreted by mice vaccinated with F3 or all F3-contaning vaccines. Additionally, the chimera and the F1 vaccine also induced the highest proportions of CD4+ and CD8+ T cells secreting IL-2, TNF-α, or IFN-γ alone, TNF-α in combination with IL-2 or IFN-γ, and of CD4+ multifunctional cells secreting IL-2, TNF-α, and IFN-γ. Correlating with the immunological results, the strongest reductions of skin lesions sizes were determined by the admixed domains (80%) and by the chimera (84%), which also promoted the most pronounced and significant reduction of the parasite load (99.8%). Thus, the epitope presentation in a recombinant chimera optimizes immunogenicity and efficacy above the levels induced by the independent or admixed F1 and F3 domains. The multiparameter analysis disclosed that the Th1-CD4+ T helper response induced by the chimera is mainly directed against its FRYPRPKHCHTQVA epitope. Additionally, the YPPEFKTKL epitope of F1 induced the second most important CD4+ T cell response, and, followed by the DVAGIVGVPVAAGCT, FMLQILDFYTKVYE, and ELLAITTVVGNQ sequences, also the most potent CD8+ T cell responses and IL-10 secretion. Remarkably, the YPPEFKTKL epitope shows high amino acid identity with a multipotent PADRE sequence and stimulates simultaneously the CD4+, CD8+ T cell, and a probable T regulatory response. With this approach, we advanced in the design of a NH36 polytope vaccine capable of inducing cross-protection to cutaneous leishmaniasis.


Transcription of clpP is enhanced by a unique tandem repeat sequence in Streptococcus mutans.
Streptococcus mutans, the primary causative agent of human dental caries, contains a single copy of the gene encoding ClpP, the chief intracellular protease responsible for tolerance to various environmental stresses. To better understand the role of ClpP in stress response, we investigated the regulation of clpP expression in S. mutans. Using semiquantitative reverse transcription-PCR analysis, we observed that, under nonstressed conditions, clpP expression is somewhat constant throughout the growth phases, although it gradually decreases as cells enter the late stationary phase. The half-life of the clpP transcript was found to be less than 1 minute. Sequence analysis of the clpP locus reveals the presence of a 50-bp tandem repeat sequence located immediately upstream of the clpP promoter (PclpP). PCR and DNA sequence analyses suggest that the number of tandem repeat units can vary from as few as two to as many as nine, depending on the particular S. mutans isolate. Further analysis, using a transcriptional reporter fusion consisting of PclpP fused to a promoterless gusA gene, indicates that the presence of the repeat sequence region within PclpP results in an approximately fivefold increase in expression from PclpP compared to the repeat-free transcriptional reporter fusion. CtsR, a transcriptional repressor that negatively regulates clpP expression, has no effect on this repeat-mediated induction of clpP transcription. Furthermore, the repeat sequence is not necessary for the induction of clpP under stress conditions. Database searches indicate that the region containing the tandem repeats is absent in the clpP loci in other bacteria, including other closely related Streptococcus spp., suggesting that the repeat sequences are specific for the induction of clpP expression in S. mutans. We speculate that a host-specific transcriptional activator might be involved in the upregulation of clpP expression in S. mutans.


NOX4 mediates hypoxia-induced proliferation of human pulmonary artery smooth muscle cells: the role of autocrine production of transforming growth factor-{beta}1 and insulin-like growth factor binding protein-3.
Persistent hypoxia can cause pulmonary arterial hypertension that may be associated with significant remodeling of the pulmonary arteries, including smooth muscle cell proliferation and hypertrophy. We previously demonstrated that the NADPH oxidase homolog NOX4 mediates human pulmonary artery smooth muscle cell (HPASMC) proliferation by transforming growth factor-beta1 (TGF-beta1). We now show that hypoxia increases HPASMC proliferation in vitro, accompanied by increased reactive oxygen species generation and NOX4 gene expression, and is inhibited by antioxidants, the flavoenzyme inhibitor diphenyleneiodonium (DPI), and NOX4 gene silencing. HPASMC proliferation and NOX4 expression are also observed when media from hypoxic HPASMC are added to HPASMC grown in normoxic conditions, suggesting autocrine stimulation. TGF-beta1 and insulin-like growth factor binding protein-3 (IGFBP-3) are both increased in the media of hypoxic HPASMC, and increased IGFBP-3 gene expression is noted in hypoxic HPASMC. Treatment with anti-TGF-beta1 antibody attenuates NOX4 and IGFBP-3 gene expression, accumulation of IGFBP-3 protein in media, and proliferation. Inhibition of IGFBP-3 expression with small interfering RNA (siRNA) decreases NOX4 gene expression and hypoxic proliferation. Conversely, NOX4 silencing does not decrease hypoxic IGFBP-3 gene expression or secreted protein. Smad inhibition does not but the phosphatidylinositol 3-kinase (PI3K) signaling pathway inhibitor LY-294002 does inhibit NOX4 and IGFBP-3 gene expression, IGFBP-3 secretion, and cellular proliferation resulting from hypoxia. Immunoblots from hypoxic HPASMC reveal increased TGF-beta1-mediated phosphorylation of the serine/threonine kinase (Akt), consistent with hypoxia-induced activation of PI3K/Akt signaling pathways to promote proliferation. We conclude that hypoxic HPASMC produce TGF-beta1 that acts in an autocrine fashion to induce IGFBP-3 through PI3K/Akt. IGFBP-3 increases NOX4 gene expression, resulting in HPASMC proliferation. These observations add to our understanding hypoxic pulmonary vascular remodeling.