Processes in acceptance and commitment therapy and the rehabilitation of chronic fatigue.
Acceptance and commitment therapy (ACT) has never been tested for patients with chronic fatigue. We aimed to test if a 3.5-week ACT rehabilitation program for patients with chronic fatigue improved quality of life (QoL), fatigue, and psychological flexibility. Further, to test if improvements in QoL and fatigue were associated with improvement in psychological flexibility, and if psychological flexibility explained variance above and beyond maladaptive cognitions typically targeted in CBT for fatigue. Patients (n = 140) who had been on sick leave > 8 weeks due to chronic fatigue received a 3.5-week non-controlled inpatient rehabilitation program based on ACT. A physician and a psychologist examined the patients, assessing medication use and SCID-I diagnoses. Patients completed questionnaires about somatic complaints, psychological complaints, and maladaptive cognitions before and after treatment. At post-treatment, patients reported improved QoL (p < 0.001; g = 1.07) and less fatigue (p < 0.001; g = 1.08), but not increased psychological flexibility (p = 0.6). Changes in psychological flexibility was associated with improved QoL, but not fatigue, in hierarchical regression analyses. When adjusting for other cognitions, changes in fear-avoidance cognitions and all-or-nothing thoughts, but not psychological flexibility, were associated with improved QoL and fatigue. The ACT-based treatment improved QoL and reduced fatigue for patients with chronic fatigue with large effect sizes. Improvement was associated with a reduction in fear-avoidance cognitions and all-or-nothing thoughts, but not psychological flexibility.


Hyperinsulinemia rather than insulin resistance itself induces blood pressure elevation in high fat diet-fed rats.
To investigate if insulin resistance per se or the accompanying hyperinsulinemia induced hypertension and its underlying mechanisms. Sprague-Dawley rats were randomized into normal diet-fed group (ND group) and high-fat diet-fed group (HFD group). Then, the HFD group was further randomly divided into the control group (HFD_C group), the PIO group (treated with pioglitazone), the STZ_DM group (to induce diabetes with streptozotocin) and the DM+Ins group (streptozotocin injection followed by insulin treatment). Insulin sensitivity, plasma insulin, endothelin-1, norepinephrine, aldosterone, angiotensinⅡ and 24-h urinary sodium excretion (USE) levels of the groups were measured and analyzed. A multiple stepwise regression analysis method was applied to exam our hypothesis. Compared to HFD_C group, the groups with lower plasma insulin, the PIO group and STZ_DM group, showed higher USE and lower blood pressure. The groups with higher plasma insulin (but same level of insulin resistance), the HFD_C group and DM+Ins group, showed lower USE and higher blood pressure. The 24-h urinary sodium excretion was the most important contributor to the significant changes of blood pressure with an R2 of 25.2% in this animal experiment. It is the compensatory hyperinsulinemia rather than insulin resistance per se that causes blood pressure elevation. The urinary sodium excretion is the key mediator among the multiple mechanisms. Therapies targeting hyperinsulinemia and restricting salt intake may favor a better control of hypertension associated with insulin resistance.


A new strategy to count and sort neutrophil-derived extracellular vesicles: Validation in infectious disorders.
Newly recognized polymorphonuclear neutrophil (PMNs) functions include the ability to release subcellular mediators such as neutrophil-derived extracellular vesicles (NDEVs) involved in immune and thrombo-inflammatory responses. Elevation of their plasmatic level has been reported in a variety of infectious and cardiovascular disorders, but the clinical use of this potential biomarker is hampered by methodological issues. Although flow cytometry (FCM) is currently used to detect NDEVs in the plasma of patients, an extensive characterization of NDEVs has never been done. Moreover, their detection remains challenging because of their small size and low antigen density. Therefore, the objective of the present study was first to establish a surface antigenic signature of NDEVs detectable by FCM and therefore to improve their detection in biological fluids by developing a strategy allowing to overcome their low fluorescent signal and reduce the background noise. By testing a large panel of 54 antibody specificities already reported to be positive on PMNs, we identified a profile of 15 membrane protein markers, including 4 (CD157, CD24, CD65 and CD66c) never described on NDEVs. Among them, CD15, CD66b and CD66c were identified as the most sensitive and specific markers to detect NDEVs by FCM. Using this antigenic signature, we developed a new strategy combining the three best antibodies in a cocktail and reducing the background noise by size exclusion chromatography (SEC). This strategy allowed a significant improvement in NDEVs enumeration in plasma from sepsis patients and made it feasible to efficiently sort NDEVs from COVID-19 patients. Altogether, this work opens the door to a more valuable measurement of NDEVs as a potential biomarker in clinical practice. A similar strategy could also be applied to improve detection by FCM of other rare subpopulations of EVs generated by tissues with limited access, such as vascular endothelium, cancer cells or placenta.


Evolutionary relationship and application of a superfamily of cyclic amidohydrolase enzymes.
Cyclic amidohydrolases belong to a superfamily of enzymes that catalyze the hydrolysis of cyclic C-N bonds. They are commonly found in nucleotide metabolism of purine and pyrimidine. These enzymes share similar catalytic mechanisms and show considerable structural homologies, suggesting that they might have evolved from a common ancestral protein. Homology searches based on common mechanistic properties and three-dimensional protein structures provide clues to the evolutionary relationships of these enzymes. Among the superfamily of enzymes, hydantoinase has been highlighted by its potential for biotechnological applications in the production of unnatural amino acids. The enzymatic process for the production of optically pure amino acids consists of three enzyme steps: hydantoin racemase, hydantoinase, and N-carbamoylase. For efficient industrial application, some critical catalytic properties such as thermostability, catalytic activity, enantioselectivity, and substrate specificity require further improvement. To this end, isolation of new enzymes with desirable properties from natural sources and the optimization of enzymatic processes were attempted. A combination of directed evolution techniques and rational design approaches has made brilliant progress in the redesign of industrially important catalytic enzymes; this approach is likely to be widely applied to the creation of designer enzymes with desirable catalytic properties.


Connection between organizational culture and climate and empowerment: The perspective of nurse managers.
Health-care organizations differ from other institutions due to their unique structure and management. Organizational culture and climate are the key constructs that compose the organizational social context, and might have an impact on employees, such as nurse managers, and the organization itself. The aim of this study was to analyze the connections between organizational culture and climate and work-related empowerment, and also to present culture and climate profiles at team and organization levels. The research was carried out in Lithuania among 193 nurse managers in seven hospitals using a questionnaire that measured organizational culture and climate (Organizational Social Context instrument), and work-related empowerment (Conditions for Work Effectiveness Questionnaire-II and Work Empowerment Questionnaire). The findings showed that nurse managers were both structurally and psychologically empowered when the organizational culture was proficient and resistant, and the climate was engaged and functional. These results suggest that nurse managers are more likely to be empowered when there is an appropriate organizational culture and climate in the workplace. Creating an empowering work environment might have a positive impact on individual and organizational outcomes.


Prediction model for 30-day morbidity after gynecological malignancy surgery.
The potential risk of postoperative morbidity is important for gynecologic cancer patients because it leads to delays in adjunctive therapy and additional costs. We aimed to develop a preoperative nomogram to predict 30-day morbidity after gynecological cancer surgery. Between 2005 and 2015, 533 consecutive patients with elective gynecological cancer surgery in our center were reviewed. Of those patients, 373 and 160 patients were assigned to the model development or validation cohort, respectively. To investigate independent predictors of 30-day morbidity, a multivariate Cox regression model with backward stepwise elimination was utilized. A nomogram based on this Cox model was developed and externally validated. Its performance was assessed using the concordance index and a calibration curve. Ninety-seven (18.2%) patients had at least one postoperative complication within 30 days after surgery. After bootstrap resampling, the final model indicated age, operating time, and serum albumin level as statistically significant predictors of postoperative morbidity. The bootstrap-corrected concordance index of the nomogram incorporating these three predictors was 0.656 (95% CI, 0.608-0.723). In the validation cohort, the nomogram showed fair discrimination [concordance index: 0.674 (95% CI = 0.619-0.732] and good calibration (P = 0.614; Hosmer-Lemeshow test). The 30-day morbidity after gynecologic cancer surgery could be predicted according to age, operation time, and serum albumin level. After further validation using an independent dataset, the constructed nomogram could be valuable for predicting operative risk in individual patients.


Richard Pfeiffer's typhoid vaccine and Almroth Wright's claim to priority.
Following the 1892 cholera pandemic, Richard Pfeiffer, Director of the science section of Robert Koch's Institute for Hygiene in Berlin, began laboratory-based studies on the pathogenesis of the disease using an animal model. These investigations resulted in his discovery of bacterial endotoxin; recognition of the bacteriolytic properties of both animal and human immune sera; and identification of the specific nature of protective immune responses. His research led naturally from cholera to typhoid fever and in November 1896 Pfeiffer published the results of experimental studies on a typhoid vaccine. In September 1896 Almroth Wright, a professor of pathology in the British Army Medical School, published a short note entitled "Typhoid Vaccination". It was appended to a review on the use of styptics to control defective blood coagulation: his previous research studies had a physiological basis that stemmed from earlier studies on tissue fibrinogen. In December 1895, Wright had been commissioned by the Army Medical Department to develop a typhoid vaccine and he later admitted that such work began only after he had spoken with Pfeiffer. In January 1897 Wright published a further paper in which he claimed precedence over Pfeiffer in the introduction of anti-typhoid vaccination. This self-entitlement has subsequently been accepted, primarily because the British Army approved typhoid vaccination in 1914 at the beginning of the First World War. That time has been used as their starting point by many of Wright's biographers, but without any attempt to confirm Wright's claim to priority. This paper concludes Richard Pfeiffer, not Almroth Wright, provided the first account of human typhoid vaccination. It also provides early examples of laboratory-based responses to pandemic and epidemic infectious diseases.


The Impact of Age on Urethroplasty Success.
To determine if age is an independent predictor of surgical success in patients undergoing urethroplasty. Urethroplasty performed by excision and primary anastomosis depends on vascular collateralization. Successful augmented urethroplasty depends on graft neovascularization. Older patients have more comorbid conditions including peripheral vascular disease associated with reduced penile blood flow. This is a retrospective review of urethroplasties from 11 institutions. Primary outcome was functional success at 1 year from surgery, defined as freedom from post-urethroplasty procedures. Secondary outcome was freedom from cystoscopic evidence of stricture recurrence at 3 months. Study outcomes were compared between 2 age cohorts (<60 years old and ≥60 years old). Multivariable logistic regression analysis evaluated the influence of patient factors on our primary and secondary outcomes, using age as a continuous variable. Of 322 urethroplasties, 258 were performed in patients <60 years and 64 in patients ≥60 years. Median follow-up was 1.8 years. The following were not significantly different between groups: stricture length or location, smoking status, number of previous urethrotomies or dilations, and urethroplasty type. The following were more common in patients ≥60 years: diabetes, hypertension, hyperlipidemia, coronary artery and peripheral vascular disease, chronic obstructive pulmonary disease, and cancer. There was no difference in need for repeat procedures or anatomic recurrence between age groups or with increasing age. Stricture length was the only statistically significant clinical factor. Urethroplasty success may be affected by comorbidities but not age. Age alone should not be used as an absolute exclusion criterion for men needing urethral reconstruction.


Pathophysiological changes of inflammatory syndrome in multiple sclerosis after instituting therapeutic plasmapheresis.
In autoimmune conditions affecting the central and peripheral CNS as well as in multiple sclerosis (MS), the inflammatory syndrome is present with the onset of this disease. The present paper aimed to highlight the inflammatory syndrome based on the leukergia test, the total blood viscosity test, blood filterability test as well as on other tests. The early instituting of the therapeutic plasmapheresis beneficially modified the clinical status, the biological and pathophysiological behavior of the patient's illness. Objective of the paper: The aim was to highlight the importance, advantages, and pathophysiological changes after therapeutic plasmapheresis in five cases, in patients hospitalized with the diagnosis of multiple sclerosis. Material and method: In order to emphasize the inflammatory syndrome, the determination of leukergia assay, the total blood viscosity test and the blood filterability test were added to regular examinations, conducted on the batch of patients included in the study. Results and discussions: As a result of using therapeutic plasmapheresis, the inflammatory parameters in patients with multiple sclerosis improved beneficially as it was proven by the values of inflammatory tests before and after plasmapheresis. Conclusions: In the treatment of multiple sclerosis, plasmapheresis proved to be a medical method that significantly reduced autoimmune inflammatory "installed" syndrome.


[Isolation, purification and physico-chemical properties of immunoactive constituents from the fruit of Lycium barbarum L].
Three glycoconjugates, LbGp3, LbGp4 and LbGp5, were isolated from the fruit of Lycium barbarum L. Molecular weights of LbGp3, LbGp4 and LbGp5 were 9.25 x 10(4), 21.48 x 10(4) and 2.37 x 10(4), respectively. Carbohydrate contents of LbGp3, LbGP4 and LbGp5 were 93.6%, 85.6%, 8.6%, respectively. LbGp3 was composed of Ara and Gal in a molar ratio of 1:1. LbGp4 was composed of Ara, Gal, Rha and Glc in a molar ratio of 1.5:2.5:0.43:0.23. LbGp5 was composed of Rha, Ara, Xyl, Gal, Man and Glc in a molar ratio of 0.33:0.52:0.42:0.94:0.85:1. Elemental analysis of N contents: LbGp3 0.83%, LbGp4 1.72%, LbGp5 9.58%. The linkage between the glycan and protein may be of O-linkage in LbGp4.


Lack of compliance of European Public Assessment Reports to guidelines for paediatric drug development before the introduction of paediatric investigation plans.
According to the International Conference on Harmonisation (ICH) and Food and Drug Administration (FDA) guidelines for paediatric clinical trials, bridging procedures can be used if disease progression, exposure-response relationships, and clinical endpoints are similar in adults and children. In these circumstances, confirmatory efficacy trials are not necessary; the evaluation of pharmacokinetics and safety ought to be sufficient for drug approval. The aim of this study was to assess whether the clinical trials and strategy for market approval authorisation (MAAs) in paediatric indications reflect the guidelines for bridging of adult data. A total of 95 European Public Assessment Reports (EPARs) published between 1995 and 2007 were reviewed. From every report, data extraction was performed according to the phase of development, scope of analysis, number of dose levels, dosage form, and demographics of the subjects enrolled in the trial. Data analysis consisted of an initial grouping of the studies by the degree of compliance to bridging guidelines. Our analysis reveals that only 66% of the trials (n = 174) can be classified as needed, while 22% of the trials (n = 59) could have been designed and performed differently from the approved protocol (partially required). Moreover, 12% (n = 30) of the studies were deemed completely unnecessary. A potential limitation in our study was that the dates of start and completion of the clinical studies were not available. Therefore, some EPARs have been included that may reflect common practice in the period that precedes the introduction of the ICH E11 guidelines. Yet, this should not obscure the points identified with regard to the lack of compliance to guidelines before the introduction of the paediatric legislation and the requirements for a paediatric investigation plan. Paediatric trials are desirable and necessary to address important unmet medical needs. However, the types of studies supporting regulatory approval do not always reflect the recommendations available in paediatric guidelines, which allow for extrapolation and bridging approaches. This situation may be explained by the lack of awareness about the prerequisites for the use of bridging concepts and of a clear process for evaluating different strategies in paediatric development.


The effect of various forms of milk on gastric-acid secretion. Studies in patients with duodenal ulcer and normal subjects.
Milk is commonly recommended as therapy for patients with peptic ulcer. The purpose of this study was to examine the effect of various forms of milk and 0.15 M NaCl (control) on gastric-acid secretion in five patients with duodenal ulcer during a period of remission and in five normal subjects. A significant (P less than 0.05) increase in acid secretion in both groups was produced by 240 ml of whole, low-fat, and nonfat milk. The acid secretory responses to milk were equivalent to approximately 20% to 35% of maximal betazole - or pentagastrin-stimulated acid output. Gastric-acid secretion produced a significant (P less than 0.05) increase in acid secretion in the patients with duodenal ulcer but not in the normal subjects. Because milk contains both protein and calcium, and each are stimulants of gastric-acid secretion, there is reason to question its frequent ingestion by patients with peptic ulcer.


[Pharyngo-colonic anastomosis for esophageal reconstruction in the treatment of diffuse corrosive esophageal stricture].
To observe the experience and the outcome of pharyngo-colonic anastomosis for esophageal reconstruction in diffuse corrosive esophageal stricture involving hypopharynx. This retrospective report reviews the experience and results of 14 patients who underwent esophageal reconstruction by pharyngo-colonic anastomosis without resection of intra thoracic stricture esophagus. The left half colonic segment was pulled up to the neck through the substernal space in all patients. There was no operative or hospital death. Postoperative complications include cervical anastomotic fistula in four patients, rupture of the abdominal incision in 1. The length of follow-up ranged from half year to 10 years with an average of 4 years. Anastomotic stenosis occurred in 2 patients. One case improved after dilatation and the other one healed by plastic operation. One patient began to vomit after diet in seven months later with barium swallowing the abdominal colon graft was redundant and this patient was cured with side by side between the colon and the stomach. The successful reconstruction for hypo-pharyngo-esophageal stricture requires a correct and larger hypopharyngeal opening and a good anastomotic technique. From our experience this procedure is shown to be safe and effective.


Breastfeeding is related to atypical autonomic and behavior regulation in infants with a history of excessive crying.
The study investigated autonomic regulation during feeding in six-month old infants with a history of excessive crying (EC) and social-behavioral development at 12 and 24 months. When contrasted with non-EC infants (NEC), EC infants had atypical autonomic responses observed as dampened reductions in respiratory sinus arrhythmia (RSA) and decreases in heart period (HP) during feeding. EC infants demonstrated atypical autonomic regulation only if they were bottle-fed, while breastfed EC infants had patterns of autonomic regulation similar to NEC infants. Behavioral data suggest that while a history of EC was related to social-emotional behaviors at 12 and 24 months, breastfeeding may buffer the behavioral effects of EC on sociability at 24 months.


Synthesis and Bioevaluation of 2-Styrylquinoxaline Derivatives as Tau-PET Tracers.
This study focused on designing and evaluating Tau-PET tracers for noninvasive positron emission computed tomography (PET) imaging of neurofibrillary tangles (NFTs), a hallmark pathology of Alzheimer's disease (AD). The tracers were synthesized with a 2-styrylquinoxaline scaffold and varying lengths of FPEG chains. The compound [18F]15, which had two ethoxy units, showed high affinity for recombinant K18-Tau aggregates (Ki = 41.48 nM) and the highest selectivity versus Aβ1-42 aggregates (8.83-fold). In vitro autoradiography and fluorescent staining profiles further validated the binding of [18F]15 or 15 toward NFTs in brain sections from AD patients and Tau-transgenic mice. In normal ICR mice, [18F]15 exhibited an ideal initial brain uptake (11.21% ID/g at 2 min) and moderate washout ratio (2.29), and micro-PET studies in rats confirmed its ability to penetrate the blood-brain barrier with the peak SUV value of 1.94 in the cortex. These results suggest that [18F]15 has the potential to be developed into a useful Tau-PET tracer for early AD diagnosis and evaluation of anti-Tau therapeutics.


Pregnancy during lamivudine therapy in chronic hepatitis B--case report.
In case of a pregnancy in a patient infected with hepatitis B virus there is a risk of intrauterine fetus infection, which rises significantly with the serological profile of positive hepatitis B surface antigen, hepatitis Be antigen and in the presence of HBV DNA in serum. Therefore, in clinical practice the monitoring of antiviral therapy in chronic hepatitis B in women of reproductive age is becoming especially important. The safety of lamivudine use in pregnant women infected with hepatitis B virus has not yet been proven. In this case, the patient became pregnant during the treatment with lamivudine and when hepatitis B virus replication markers were present in the serum (hepatitis B surface antigen, hepatitis Be antigen, hepatitis B virus DNA). Treatment with lamivudine lasted through the first 6 weeks of pregnancy, which was complicated by a possibility of intrauterine hepatitis B virus infection, did not cause any fetus injury.


Significance of RBP4 in patients with gestational diabetes mellitus: a case-control study of Han Chinese women.
The role of retinol binding protein 4 (RBP4) in insulin resistance was recently identified. Our study investigated the correlation between RBP4 levels with lipid and glucose metabolism in a case-control study of women with gestational diabetes mellitus (GDM). Between May 2008 and May 2010, 70 pregnant women (24-28 weeks gestation) were recruited, including 35 women with GDM and 35 healthy controls. Blood samples were collected prior to and after oral glucose tolerance tests (OGTT) to detect serum RBP4, insulin, glycated hemoglobin, triglyceride (TG) and total cholesterol (TC) levels; the insulin resistance index (HOMA-IR) was calculated. Serum RBP4 levels in the GDM group were significantly higher than the control group (22.9 ± 3.09 µg/ml versus 17.9 ± 3.91 µg/ml; p < 0.01). Insulin, TC and TG levels in the GDM group and the control group were all significantly higher than the control group (p < 0.05). Serum RBP4 levels in the GDM group were correlated with HOMA-IR, TG and blood glucose levels at 1 h and 2 h after glucose was administered (r = 0.49, 0.49, 0.52,0.52, respectively; p < 0.01). In conclusion, serum RBP4 levels are elevated in GDM cases than controls. In addition, RBP4 correlates with abnormalities of insulin resistance, glucose and lipid metabolism.


The mothers' experiences in the pediatrics hemodialysis unit.
The need for hemodialysis exerts a deep impact on the lives of children and adolescents with end-stage kidney chronic failure and their mothers, who predominantly assume the care related to treatment. The hemodialysis requires that the mother accompanies the child during sessions at least three times a week and, since it is not a healing practice, they also experience the waiting for a kidney transplant, attributing different meanings to this experience. To understand what it means for the mothers to accompany the child in a Pediatric Hemodialysis Unit and to construct a theoretical model representing this experience. The Symbolic Interactionism was adopted as a theoretical model and the Grounded Theory as a methodological framework. Data were collected through interviews with 11 mothers. The comparative analysis of the data enabled the identification of two phenomena that compose the experience: "Seeing the child´s life being sucked by the hemodialysis machine" expresses the experiences of the mothers that generates new demands to comprehend the new health conditions of their children and "Giving new meaning to the dependence of the hemodialysis machine" that represents the strategies employed to endure the experience. The relationship of these phenomena allowed the identification of the main category: "Having the mother's life imprisoned by the hemodialysis machine", from which we propose a new theoretical model. The results of the study allow us to provide a theoretical ground for planning an assistance that meets the real needs of the mothers, identifying aspects that require intervention.


Prevalence of Brucella melitensis and Brucella abortus Fluoroquinolones Resistant Isolates: A Systematic Review and Meta-Analysis.
Background: Brucellosis impact both animals and humans worldwide. However, using antibiotics for brucellosis remains controversial despite decades of research. Relapse can complicate treatment in this area. Since the mid-1980s, microbiologists, and physicians have studied fluoroquinolones' use for treating human brucellosis. The principal advantages of fluoroquinolones are their intracellular antimicrobial activity, low nephrotoxicity, good pharmacokinetics, and the lack of drug-level monitoring. Fluoroquinolones inhibit disease recurrence. In vitro and clinical data were used to study the prevalence of Brucella melitensis and Brucella abortus fluoroquinolone-resistant isolates. Methods: The PubMed, Scopus, Embase, and Web of Science databases were carefully searched until August 6, 2022, for relevant papers. The number of resistant isolates and sample size were used to estimate the proportion of resistant isolates, fitting a model with random effects, and DerSimonian-Laird estimated heterogeneity. Furthermore, meta-regression and subgroup analyses were used to assess the moderators to identify the sources of heterogeneity. Meta-analysis was performed using R software. Results: Forty-seven studies evaluated fluoroquinolone resistance in Brucella spp. Isolates. Fluoroquinolones have shown high in vitro efficacy against Brucella spp. The resistance rates to ofloxacin, sparfloxacin, fleroxacin, pefloxacin, and lomefloxacin were 2%, 1.6%, and 4.6%, respectively. Conclusion: Clinical in vitro tests demonstrated that fluoroquinolones can eradicate Brucella spp. Owing to first-line medication resistance, recurrence, and toxicity, it is essential to standardize the Brucella antimicrobial susceptibility test method for a more precise screening of resistance status. Fluoroquinolones are less resistant to fluoroquinolone-based treatments in modern clinical practice as alternatives to standard therapy for patients with brucellosis relapse after treatment with another regimen and in patients who have developed toxicity from older agents.


Is low-intensity anticoagulant therapy possible with an open pivot valve?: analysis of its development.
In 1976, the authors became the codevelopers of the first successful bileaflet heart valve which has become the standard in valvular surgery. However, there still remains a significant rate of thromboembolism and thrombosis which can be attributed to the inherent design of cavities in the pivot area. These cavities contribute to stagnant areas that lead to thrombus formation. The literature indicates that this rate is approximately 2% to 2.5% per patient year. To maintain these thromboembolism rates, certain levels of warfarin have had to be used leading to a significant rate of bleeding complications. We present the theory and development of the new generation of heart valves without cavities and with an open semisphere pivot area. Results of 912 years of clinical studies of almost 50,000 valves, as well as additional features that have been incorporated to improve hemodynamics and quality of life for the patient, are discussed. The clinical results of the European Community Certification and U.S. Food and Drug Administration premarket application (PMA) studies also are given. The differences in the pivot area suggest that a reduction in thromboembolism is possible at anticoagulant levels as low as 1.5 international normalization ratio (INR) resulting in virtually no bleeding complications. Midterm clinical results are encouraging, and studies are being conducted presently to eliminate totally anticoagulants in certain patients.


Experimental reactivation of equine herpesvirus-3 following corticosteroid treatment.
State of latency, well known for several herpesviruses, has been proposed for equine herpesvirus-3 (EHV-3) and supported by epidemiological observations. No detailed assessment about reactivation, patterns of excretion and reexcretion has been formally reported. An experimental reactivation study by corticosteroid treatment in previously naturally infected horses was therefore carried out. Two polo mares with clinical and virologically confirmed history of equine coital exanthema were injected with dexamethasone and prednisolone on 3 successive days. Clinical signs, body temperature and clinical samples for virological and serological studies were obtained daily. Mares did not show any systemic clinical signs or hyperthermia. EHV-3 shedding, seroconversion and the presence of a small lesion were observed in one of the mares under study 2 weeks after corticosteroid treatment. The results demonstrate that this virus exhibits a latency-reactivation behaviour similar to that of other alpha herpesviruses. Reactivation of latency may have an important bearing on the appearance of clinical signs in mares and/or stallions during the breeding season without the actual evidence of transfer from mare to stallion or vice versa.


[Pure primary prostate transitional cell carcinoma. A review of our series].
Primary prostate transitional cell carcinoma is a very uncommon tumor, that represents about 1% of all prostate tumours. In our institution, only six patients have been diagnosed with pure transitional cell prostate carcinoma until 2002. Bladder origin of the neplasic was ruled out in all cases. We report a study about the progression and survival of prostate transitional cell carcinoma. These prostatic tumours carry a poor prognostic (median survival is 4.6 months) with a strong tendency to metastatic spread. Therefore, we suggest a radical prostatectomy (without cystectomy) when it rules out bladder origin tumour.


Immunodeficiency and autoimmunity coming together: a nearly missed diagnosis.
The coexistence of human immunodeficiency virus (HIV) and systemic lupus erythematosus (SLE) appears to be unusual and the prevalence of patients who carry the dual diagnosis is currently unknown. We hereby present a case of a C4 deficient HIV-1 positive Caucasian female under highly active antiretroviral therapy for the past eight years, admitted to hospital with an aggressive and potentially fatal clinical presentation of SLE. There was a favorable outcome despite a significant diagnostic delay. Despite its rarity, the case highlights that this association is remarkable and may be overlooked by clinicians familiar with either condition.


Sensitivity of different ADL measures to apraxia and motor impairments.
To determine whether specifically designed activities of daily living (ADL) observations can measure disability due to apraxia with more sensitivity than the Barthel ADL Index, a conventional functional scale. Cross-sectional study. Rehabilitation centres and nursing homes. One hundred and six left hemisphere stroke patients with apraxia, hospitalized in rehabilitation centres and nursing homes. ADL observations, Barthel ADL Index, an apraxia test, Motricity Index, Functional Motor Test. Multivariate analyses showed that the specific ADL observations were associated with severity of apraxia (and not with motor impairments). The Barthel ADL Index was associated with motor impairments (and not with severity of apraxia). The assessment of disability in stroke patients with apraxia cannot rely only on the Barthel ADL Index. In addition, the specific ADL observation procedure is needed to measure disability due to apraxia.


Definition of the immune evasion-replication interface of rabies virus P protein.
Rabies virus phosphoprotein (P protein) is a multifunctional protein that plays key roles in replication as the polymerase cofactor that binds to the complex of viral genomic RNA and the nucleoprotein (N protein), and in evading the innate immune response by binding to STAT transcription factors. These interactions are mediated by the C-terminal domain of P (PCTD). The colocation of these binding sites in the small globular PCTD raises the question of how these interactions underlying replication and immune evasion, central to viral infection, are coordinated and, potentially, coregulated. While direct data on the binding interface of the PCTD for STAT1 is available, the lack of direct structural data on the sites that bind N protein limits our understanding of this interaction hub. The PCTD was proposed to bind via two sites to a flexible loop of N protein (Npep) that is not visible in crystal structures, but no direct analysis of this interaction has been reported. Here we use Nuclear Magnetic Resonance, and molecular modelling to show N protein residues, Leu381, Asp383, Asp384 and phosphor-Ser389, are likely to bind to a 'positive patch' of the PCTD formed by Lys211, Lys214 and Arg260. Furthermore, in contrast to previous predictions we identify a single site of interaction on the PCTD by this Npep. Intriguingly, this site is proximal to the defined STAT1 binding site that includes Ile201 to Phe209. However, cell-based assays indicate that STAT1 and N protein do not compete for P protein. Thus, it appears that interactions critical to replication and immune evasion can occur simultaneously with the same molecules of P protein so that the binding of P protein to activated STAT1 can potentially occur without interrupting interactions involved in replication. These data suggest that replication complexes might be directly involved in STAT1 antagonism.


Lipopolysaccharides and hydrogen peroxide induce contrasting pathological conditions in dental pulpal cells.
To determine the effects of lipopolysaccharides (LPS), hydrogen peroxide (H2 O2 ), and both combined on cell proliferation/differentiation, inflammation, mitochondrial dynamics as indicated by mitochondrial fission/fusion, antioxidants as indicated by superoxide dismutase 2 (SOD2), and apoptosis of human dental pulpal cells (HDPCs). Pulpal tissues from eight healthy subjects (n = 8) were collected from Faculty of Dentistry, Chiang Mai University. Isolated HDPCs from healthy donors were divided into four experimental groups: vehicle, 20 μg/ml LPS, 400 μM H2 O2 , and the two combined. All experimental groups were investigated to assess cell proliferation, mineralization, differentiation, inflammation, mitochondrial dynamics, antioxidants, and apoptosis. H2 O2 and combined agents decreased cell proliferation of HDPCs equally. LPS, H2 O2, and both combined decreased mineralization and differentiation with an increase in tumour necrosis factor-alpha (TNF-α) levels. Surprisingly, LPS and combined agents increased SOD2 expression and caused an imbalance in mitochondrial dynamics. A significant increase in apoptosis was observed in the case of H2 O2 and combined agents. These findings suggest that LPS induced inflammation, imbalanced mitochondrial dynamics, and reduced cell differentiation without altering apoptosis and cell proliferation. However, H2 O2 decreased cell proliferation, and differentiation, and increased inflammation, and apoptosis without interfering with mitochondrial dynamics. Based on our findings, combining LPS and H2 O2 could be potentially used as the inducers in in vitro study to mimic the clinical pulpitis.


Tuberculosis due to drug-resistant Mycobacterium bovis in pregnancy.
We describe the management practices adopted in a case of pulmonary and extra-pulmonary tuberculosis caused by an isoniazid/pyrazinamide resistant strain of Mycobacterium bovis in a 26-week pregnant woman. She was initially treated with rifampin, isoniazid and ethambutol, pre-term delivery was induced and streptomycin was then added to the regimen. Screening of the new-born revealed no signs of either disease or infection. Isoniazid prophylaxis was not administered and the new-born was vaccinated and isolated from the mother for two months; however she continued to be fed with her mother's milk for the whole period.


Development and initial validation of an instrument to measure perceived coercion to enter treatment for substance abuse.
The present study involved 3 phases that led to the development and initial validation of the Perceived Coercion Questionnaire (PCQ), a scale that researchers use to measure perceptions of coercion of drug and alcohol users to enter drug and alcohol treatment. In Phase 1, the authors used focus groups to generate 48 pilot items. In Phase 2, the items were administered to a sample of 158 drug and alcohol users who were in residential treatment within a therapeutic community setting. Item and exploratory factor analyses reduced the number of items to 32, which represented 6 homogeneous and internally reliable subscales. In Phase 3, the PCQ was administered to a second sample of 362 drug and alcohol users. Confirmatory factor analysis led to a final scale of 30 items across 6 subscales that demonstrated sound consistency and validity. Implications for research and practice are highlighted.


Examining relationships between receiving mental health services in the Pennsylvania prison system and time served.
This study examined a cohort of 7,046 men who were released from the Pennsylvania State prison system between 1999 and 2002 to Philadelphia County to assess the relationships between receipt of mental health services in prison and prison exit. Administrative data on prison stays for 7,046 men released from Pennsylvania prisons to Philadelphia locations were analyzed. Of the 7,046 men, 8.7% received ongoing or intensive mental health services and 25.9% received mental health services while incarcerated. Multivariate analyses indicate that use of mental health services was positively associated with increased odds of serving the full prison sentence (as opposed to receiving parole), although the relationship between mental health services received and length of prison episode was inconclusive. Dynamics related to prison release warrant further attention in efforts to reduce the prevalence of mental illness in prisons and to facilitate community reentry for persons so diagnosed.


[Ogilvie's syndrome and non-mechanical obstructions].
Ogilvie's syndrome and chronic intestinal pseudo-obstructions are two aspects of non-mechanical obstruction. The syndrome consists of acute colonic obstruction due to multiple causes and is characterized by passive dilatation of the colon without downstream obstacle. Treatment is primarily medical, except in cases with complications such as perforation by symptomatic treatment and, sometimes, by decompression colonoscopy. The most severe complication is perforation of the colon which may require colonic excision. Chronic intestinal pseudo-obstruction is characterized by chronic disorders mostly due to abnormalities of nervous plexuses and smooth muscle of the small and large bowels. It occurs in children and surgical abstention may lead to repeated but unfortunately ineffective operations. The only treatment recognized is digestive tract bypass combined with total parenteral feeding.


Identification of host factors potentially involved in RTM-mediated resistance during potyvirus long distance movement.
The long distance movement of potyviruses is a poorly understood step of the viral cycle. Only factors inhibiting this process, referred to as "Restricted TEV Movement" (RTM), have been identified in Arabidopsis thaliana. On the virus side, the potyvirus coat protein (CP) displays determinants required for long-distance movement and for RTM-based resistance breaking. However, the potyvirus CP was previously shown not to interact with the RTM proteins. We undertook the identification of Arabidopsis factors which directly interact with either the RTM proteins or the CP of lettuce mosaic virus (LMV). An Arabidopsis cDNA library generated from companion cells was screened with LMV CP and RTM proteins using the yeast two-hybrid system. Fourteen interacting proteins were identified. Two of them were shown to interact with CP and the RTM proteins suggesting that a multiprotein complex could be formed between the RTM proteins and virions or viral ribonucleoprotein complexes. Co-localization experiments in Nicotiana benthamiana showed that most of the viral and cellular protein pairs co-localized at the periphery of chloroplasts which suggests a putative role for plastids in this process.


Efficacy of Drug-Eluting Beads Transarterial Chemoembolization Plus Camrelizumab Compared With Conventional Transarterial Chemoembolization Plus Camrelizumab for Unresectable Hepatocellular Carcinoma.
The purpose of this study was to compare the efficacy and safety of drug-eluting beads transarterial chemoembolization plus camrelizumab (D-TACE-C) with conventional transarterial chemoembolization plus camrelizumab (C-TACE-C) in the treatment of patients with unresectable hepatocellular carcinoma (HCC). This was a retrospective study that evaluated the consecutive medical records of patients with unresectable HCC who had undergone D-TACE-C or C-TACE-C from April 2020 to August 2021. Efficacy of treatment was evaluated using tumor response, progression-free survival (PFS) and survival rates. The adverse events were recorded. A total of 54 patients were included in this study, including 27 patients who had received D-TACE-C treatment, and 27 patients who had received C-TACE-C treatment. The median PFS and DCR in the D-TACE-C group were significantly longer than those for the C-TACE-C group (PFS: 10 vs. 3 months, P=.017; DCR: 70.4% vs. 40.7%, P = .028). Cox regression analysis showed that D-TACE-C was the only protective factor for PFS. The 6-month and 12-month survival rates in D-TACE-C group and C-TACE-C group were 85.2% versus 79.4% (P = .646) and 65.2% versus 65.1% (P = .903), respectively. Reactive cutaneous capillary endothelial proliferation was the most common adverse event associated with the treatment. There was no significant difference in the adverse events related to TACE and camrelizumab between the two groups. No treatment-related deaths occurred in this study. D-TACE-C is a safe and well-tolerated treatment, and may produce better PFS and tumor response in patients with unresectable HCC than C-TACE-C.


Linné's floral clock is slow without pollinators--flower closure and plant-pollinator interaction webs.
Temporal patterns of flower opening and closure within a day are known as Linné's floral clock. Time of flower closure has been explained mainly by light in the traditional botanical literature. We show with a set of experiments that Asteraceae flower heads can close within three hours after pollination, whereas un-pollinated flower heads stay open until the late afternoon. This suggests that closing time strongly depends on pollinators. Using plant-pollinator interaction webs we further demonstrate that the daily pattern of flower opening and the rapid response to pollination can impose strong temporal dynamics on interspecific interactions within a single day. We observed pollinator species turnover and changes in facilitation vs. competition among plants. Our results show for the first time that pollination induces rapid flower closure on the community level. This causes imprecision in Linné's floral clock with far-reaching consequences for plant-pollinator interactions.


The synthesis and properties of oligoribonucleotide-spermine conjugates.
Polyamines stabilise nucleic acids against chemical and enzymatic degradation, facilitate the formation of secondary and tertiary structures and enhance cellular uptake. Therefore methods for the syntheses of polyamine-nucleic acid conjugates are of interest. A route for the syntheses of RNA-spermine conjugates has been developed. The polyamine was introduced to the C-5 position of uridine via an ethyl tether and the molecule elaborated into a synthon suitable for oligoribonucleotide assembly. The resultant oligomers were components of the hairpin ribozyme. Characterisation of the spermine-conjugated catalytic RNA revealed that attachment of the polyamine was well tolerated in three of four positions, namely U41, U37 and U34, suggesting that conjugation to C-5 brings about minimal structural perturbation.


Safety analysis of new medications in clinical trials: a simulation study to assess the differences between cause-specific and subdistribution frameworks in the presence of competing events.
Safety is an essential part of the evaluation of new medications and competing risks that occur in most clinical trials are a well identified challenge in the analysis of adverse events. Two statistical frameworks exist to consider competing risks: the cause-specific and the subdistribution framework. To date, the application of the cause-specific framework is the standard practice in safety analyses. Here we analyze how the safety analysis results of new medications would be affected if instead of the cause-specific the subdistribution framework was chosen. We conducted a simulation study with 600 participants, equally allocated to verum and control groups and a 30 months follow-up period. Simulated trials were analyzed for safety in a competing risk (death) setting using both the cause-specific and subdistribution frameworks. Results show that comparing safety profiles in a subdistribution setting is always more pessimistic than in a cause-specific setting. For the group with the longest survival and a safety advantage in a cause-specific setting, the advantage either disappeared or a disadvantage was found in the subdistribution analysis setting. These observations are not contradictory but show different perspectives. To evaluate the safety of a new medication over its comparator, one needs to understand the origin of both the risks and the benefits associated with each therapy. These requirements are best met with a cause-specific framework. The subdistribution framework seems better suited for clinical prediction, and therefore more relevant for providers or payers, for example.


Influence of bariatric surgery on the expression of nesfatin-1 in rats with type 2 diabetes mellitus.
Bariatric surgery has been reported to be very effective in the remission of type 2 diabetes mellitus (T2DM). However, the mechanism is still under debate. Nesfatin-1, a recently discovered anorexigenic neuropeptide, was reported to be very important in glucose metabolism and regulating food intake. In this study, the effects of bariatric surgery on the expression and regulation of nesfatin-1 were discussed. T2DM was induced in SD rats by a diet high in sugar and fat plus a low dose of streptozotocin (STZ) (25 mg/kg) injection. Bariatric surgeries, including Roux-En-Y Gastric Bypass (RYGB) and sleeve gastrectomy (SG), were performed on these rats. Two months after the surgery, the plasma nesfatin-1 level and the expression of nesfatin-1 in different organs of the rats were tested. Next, in vivo administration of nesfatin-1 after surgery was performed to investigate the role of nesfatin-1 in bariatric surgery. Both RYGB and SG could reduce the weight of the rats. However, only RYGB had significant effects on the blood glucose level. Neither surgeries seemed to affect the blood concentration of insulin. However, RYGB significantly improved insulin sensitivity. Expression of nesfatin-1 in the plasma and relative organs decreased in T2DM rats and rose again after RYGB; however, this pattern did not occur in SG. Injection of nesfatin-1 after SG significantly improved insulin resistance and reduced blood glucose levels. Nesfatin-1 may improve insulin sensitivity in T2DM rats and thus plays a very important role in the remission of T2DM after RYGB. This neuropeptide could be a new target for directing future improvements in the bariatric surgical process.


Influence of attention manipulation on emotion and autonomic responses.
Psychopathologies such as depression and anxiety have been associated with self-consciousness, a trait focusing on the self in terms of emotions and social images. A technique designed to shift attention away from the self tends to reduce anxiety, so the present purpose was to assess the effect of self body-state information on an individual's emotional and autonomic activity. 24 undergraduate and graduate students (10 men and 14 women), ages 19 to 27 years (M = 22.1, SD = 2.5), were recruited as subjects. Focusing on body-state during an anxiety-inducing situation led to an increase of low to high frequency ratio of heart-rate variability which reflected cardiac sympathovagal balance. That is, attending to one's own bodily states enhanced relative sympathetic activity compared to parasympathetic activity, which can be interpreted as one of the physiological emotional responses elicited by anxiety.


Synthesis of a NbO Type Homochiral Cu(II) Metal-Organic Framework: Ferroelectric Behavior and Heterogeneous Catalysis of Three-Component Coupling and Pechmann Reactions.
A chiral tetracarboxylic acid ligand, H4L, incorporating the (S)-(+)-2-methylpiperazine moiety in its middle, solvothermally forms a homochiral Cu(II) framework, {[Cu2(L)(H2O)2]·(4DMF)(4H2O)}n (LCu). It forms a non-interpenetrated structure consisting of [Cu2(COO)4] paddle-wheel secondary bonding units (SBUs) with NbO topology. Interestingly, the framework LCu exhibits excellent ferroelectric properties. It shows a remnant polarization (Pr) of ∼3.5 μC cm-2 and a coercive field (Ec) of ∼12 kV cm-1 with a distinct electric hysteresis loop. Dielectric studies of LCu reveal almost frequency-independent behavior with a dielectric constant (εr) of ∼42 and a low dielectric loss (tan δ) of ∼0.04 up to 106 Hz, for potential use in high-frequency applications. In addition, activated framework LCu' having uncoordinated metal sites acts as an efficient heterogeneous catalyst in the three-component coupling of amines, aldehydes, and alkynes, as well as in Pechmann reactions of phenols with β-ketoesters.


Generalized synchronization in directionally coupled systems with identical individual dynamics.
A simple chaotic flow is presented, which when driven by an identical copy of itself, for certain initial conditions, is able to display generalized synchronization instead of identical synchronization. Being that the drive and the response are observed in exactly the same coordinate system, generalized synchronization is demonstrated by means of the auxiliary system approach and by the conditional Lyapunov spectrum. This is interpreted in terms of changes in the structure of the system stationary points, caused by the coupling, which modify its global behavior.


The efficacy of low-dose intranasal scopolamine for motion sickness.
Scopolamine is an effective motion sickness prophylactic, but oral and transdermal formulations are slowly absorbed. To enhance absorption and potentially efficacy, an intranasal formulation of scopolamine (INSCOP) was tested. There were 16 motion sickness susceptible subjects with an average age of 23.5 +/- 3.0 yr and an average score of 11.3 +/- 4.7 on the Modified Motion Sickness Susceptibility Questionnaire-Short Form who volunteered to participate in the study. Each subject was given 0.4 mg of INSCOP and a placebo in a randomized, double-blind crossover design and, at 40 min post-dose, experienced Coriolis cross-coupling in a staircase progression until moderate nausea. Efficacy data and cognitive, physiological, and alertness assessments were collected during baseline control and throughout experimental testing. Intranasal scopolamine significantly increased the mean number of head movements tolerated [INSCOP 275.9 +/- 120.5, Placebo 230.7 +/- 76.4; t (15) = 2.21]. Estimation of medication absorption via plasma concentration indicated the drug was absorbed relatively rapidly to measurable levels by 15 min post-administration. Diastolic blood pressures and heart rate were significantly lower after administration of INSCOP compared to placebo. No significant cognitive or medication side effects were reported. Subjects reported no significant decrease in alertness as indicated by the Karolinska Sleepiness Scale. Results of the current study strongly suggest that intranasal scopolamine is efficacious for the treatment of motion sickness in susceptible individuals with no significant cognitive or sedative effects. Intranasal delivery offers a promising alternative for use in dynamic operational environments without cognitive detriment or increased side effects.


Essential oils have different effects on human pathogenic and commensal bacteria in mixed faecal fermentations compared with pure cultures.
A static batch culture system inoculated with human faeces was used to determine the influence of essential oil compounds (EOCs) on mixed faecal microbiota. Bacteria were quantified using quantitative PCR of 16S rRNA genes. Incubation for 24 h of diluted faeces from six individuals caused enrichment of Bifidobacterium spp., but proportions of other major groups were unaffected. Thymol and geraniol at 500 p.p.m. suppressed total bacteria, resulting in minimal fermentation. Thymol at 100 p.p.m. had no effect, nor did eugenol or nerolidol at 100 or 500 p.p.m. except for a slight suppression of Eubacterium hallii. Methyl isoeugenol at 100 or 500 p.p.m. suppressed the growth of total bacteria, accompanied by a large fall in the molar proportion of propionate formed. The relative abundance of Faecalibacterium prausnitzii was unaffected except with thymol at 500 p.p.m. The ability of EOCs to control numbers of the pathogen Clostridium difficile was investigated in a separate experiment, in which the faecal suspensions were amended by the addition of pure culture of C. difficile. Numbers of C. difficile were suppressed by thymol and methyl isoeugenol at 500 p.p.m. and to a lesser extent at 100 p.p.m. Eugenol and geraniol gave rather similar suppression of C. difficile numbers at both 100 and 500 p.p.m. Nerolidol had no significant effect. It was concluded from these and previous pure-culture experiments that thymol and geraniol at around 100 p.p.m. could be effective in suppressing pathogens in the small intestine, with no concern for beneficial commensal colonic bacteria in the distal gut.


Markers of atresia in ovarian follicular components from rhesus monkeys treated with estradiol-17 beta.
A new model for the investigation of atresia in rhesus monkeys is presented. This model is based upon the reliable induction of an atresia-like process in the dominant preovulatory follicle (DF) by estradiol-17 beta administered subcutaneously via Silastic capsules for 24 h. Data obtained from follicular contents aspirated from treated animals demonstrated alterations in the putative markers of atresia similar to those described in other models of atresia. Although follicle size and appearance and volume of follicular fluid (FF) were unaltered in treated animals, FF was much more viscous than that aspirated from follicles in untreated animals; this was apparently due to a greater quantity of intercellular matrix that was sensitive to digestion by hyaluronidase. In treated animals, FF concentrations of estrogen (E) and progesterone (P) were depressed 3- and 6.6-fold, respectively. Viability of granulosa cells (GC) from these animals was reduced by 40%, as was their ability to release basal amounts of E and P in vitro. Accumulation of P by GC from treated animals approximated unstimulated control levels when human follicle-stimulating hormone (hFSH) was included in the culture. Therefore, FSH may have a limited capability to "rescue" GC from atresia induced by estradiol. The percentage of cells that bound 125I-hFSH maximally, as measured by autoradiography following 72 h in culture, was not altered by treatment. Oocytes from animals treated with estradiol showed signs of degeneration at aspiration, and deteriorated further in culture. This model is unique in that atresia can be induced in the single DF of a primate species, and thus avoids the disadvantages inherent to studying atresia of heterogeneous follicles in polytocous species.(ABSTRACT TRUNCATED AT 250 WORDS)


Effective temperature of active fluids and sheared soft glassy materials.
The dynamics within active fluids, driven by internal activity of the self-propelled particles, is a subject of intense study in non-equilibrium physics. These systems have been explored using simulations, where the motion of a passive tracer particle is followed. Similar studies have been carried out for a soft glassy material that is driven by shearing its boundaries. In both types of systems the non-equilibrium motion have been quantified by defining a set of "effective temperatures", using both the tracer particle kinetic energy and the fluctuation-dissipation relation. We demonstrate that these effective temperatures extracted from the many-body simulations fit analytical expressions that are obtained for a single active particle inside a visco-elastic fluid. This result provides testable predictions and suggests a unified description for the dynamics inside active systems.


Birch's Law: Why Is It So Good?
Birch's law arises in the physics of solids as a linear approximation, in a certain range of density, of a power law. For a change of chemical composition within the same crystal structure, the velocity-density relation is constant with a slope of nearly -0.5 in the first-order approximation.


Comparison of three screening methods to select mixed-microbial inoculum for mixed-acid fermentations.
Using a mixed culture of microorganisms, the carboxylate platform converts biomass into hydrocarbons and chemicals. To develop a method that identifies the highest performing inoculum for carboxylate fermentations, five bacterial communities were screened and ranked by three fermentation performance tests: (1) 30-day batch screen, (2) 28-day continuum particle distribution model (CPDM), and (3) 5-month continuous countercurrent fermentation trains. To screen numerous inocula sources, these tests were used sequentially in an aseptic environment. For the batch-fermentation screen, Inoculum 1 achieved the highest conversion. For the CPDM evaluation, the operating map for Inoculum 1 had the highest performance. For the continuous countercurrent fermentation, the train resulting from Inoculum 1 was among the best performers. This study suggests that the three screens are a useful and predictive method for choosing optimal inocula sources. The bacterial community with optimal performance in these three screens could be considered for use in commercial-scale fermentations.


Metabolic Pathways Regulated by Chitosan Contributing to Drought Resistance in White Clover.
Increased endogenous chitosan (CTS) could be associated with improved drought resistance in white clover (Trifolium repens). Plants were pretreated with or without 1 mg/mL CTS and then were subjected to optimal or water-limited condition in controlled growth chambers for 6 days. Phenotypic and physiological results indicated that exogenous CTS significantly improved drought resistance of white clover. Metabolome results showed that exogenous CTS induced a significant increase in endogenous CTS content during dehydration accompanied by the maintenance of greater accumulation of sugars, sugar alcohols, amino acids, organic acids, and other metabolites (ascorbate, glutathione, flavonoids, putrescine, and spermidine). These compounds are associated with osmotic adjustment, antioxidant defense, stress signaling, and energy metabolism under stress condition. Similarly, transcriptome revealed that many genes in relation to amino acid and carbohydrate metabolism, energy production and conversion, and ascorbate-glutathione and flavonoid metabolism were significantly up-regulated by CTS in response to dehydration stress. CTS-induced drought resistance was associated with the accumulation of stress protective metabolites, the enhancement of ascorbate-glutathione and tricarboxylic acid cycle, and increases in the γ-aminobutyric acid shunt, polyamine synthesis, and flavonoids metabolism contributing to improved osmotic adjustment, antioxidant capacity, stress signaling, and energy production for stress defense, thereby maintaining metabolic homeostasis under dehydration stress.


Family history and colorectal cancer screening: a survey of physician knowledge and practice patterns.
Risk stratification is essential to effective implementation of colorectal cancer (CRC) screening strategies. The objectives of this study were to assess and compare the current knowledge and practice patterns of gastroenterologists and primary care physicians regarding familial risk of CRC. We conducted a survey of regional gastroenterologists and a sample of university- and community-based primary care physicians. The survey instrument assessed physician knowledge of screening recommendations and current practices for individuals with family histories of CRC, adenomatous polyps (APs), familial adenomatous polyposis (FAP), and hereditary nonpolyposis cancer (HNPCC). The instrument also elicited data about familial risk assessment, documentation, and notification of at-risk family members. Thirty-five gastroenterologists (65%) and 58 primary care physicians (92%) completed the survey. Most gastroenterologists and primary care physicians (85% vs 72%) chose age 40 as the appropriate age to begin screening for a family history of CRC, but relatively few (37% vs 36%) recommended screening at age 40 for a family history of APs. Gastroenterologists were significantly more likely to recommend screening for FAP at puberty (80% vs 27%, p < 0.001) and for HNPCC at age 25 (73% vs 50%, p = 0.04). Colonoscopy was the preferred screening strategy by both groups for family histories of CRC (97%), HNPCC (97%), and APs (77%); primary care physicians also preferred colonoscopy for family histories of CRC (72%) and HNPCC (76%) but flexible sigmoidoscopy plus fecal occult blood testing for a family history of APs (38%). Gastroenterologists were more likely to recommend genetic testing for persons at risk of FAP (91% vs 71%, p = 0.03) and HNPCC (72% vs 57%, p = 0.18), routinely inquire about a family history of CRC or APs (93% vs 63%, p < 0.001), and recommend notification of at-risk first-degree relatives with family histories of CRC (94% vs 55%, p < 0.001) or AP (53% v.s 6%, p < 0.001). Although gastroenterologists are more likely than primary care physicians to elicit a family history of colorectal neoplasia and implement appropriate screening strategies, overall compliance with recommended guidelines and notification of at-risk relatives are suboptimal. Novel approaches for improving awareness of the available screening guidelines are needed.


Postdiagnosis body fatness, weight change and breast cancer prognosis: Global Cancer Update Program (CUP global) systematic literature review and meta-analysis.
Previous evidence on postdiagnosis body fatness and mortality after breast cancer was graded as limited-suggestive. To evaluate the evidence on body mass index (BMI), waist circumference, waist-hip-ratio and weight change in relation to breast cancer prognosis, an updated systematic review was conducted. PubMed and Embase were searched for relevant studies published up to 31 October, 2021. Random-effects meta-analyses were conducted to estimate summary relative risks (RRs). The evidence was judged by an independent Expert Panel using pre-defined grading criteria. One randomized controlled trial and 225 observational studies were reviewed (220 publications). There was strong evidence (likelihood of causality: probable) that higher postdiagnosis BMI was associated with increased all-cause mortality (64 studies, 32 507 deaths), breast cancer-specific mortality (39 studies, 14 106 deaths) and second primary breast cancer (11 studies, 5248 events). The respective summary RRs and 95% confidence intervals per 5 kg/m2 BMI were 1.07 (1.05-1.10), 1.10 (1.06-1.14) and 1.14 (1.04-1.26), with high between-study heterogeneity (I2 = 56%, 60%, 66%), but generally consistent positive associations. Positive associations were also observed for waist circumference, waist-hip-ratio and all-cause and breast cancer-specific mortality. There was limited-suggestive evidence that postdiagnosis BMI was associated with higher risk of recurrence, nonbreast cancer deaths and cardiovascular deaths. The evidence for postdiagnosis (unexplained) weight or BMI change and all outcomes was graded as limited-no conclusion. The RCT showed potential beneficial effect of intentional weight loss on disease-free-survival, but more intervention trials and well-designed observational studies in diverse populations are needed to elucidate the impact of body composition and their changes on breast cancer outcomes.


The ecosystem impacts of dominant species exclusion in a prairie restoration.
Dominant species often have disproportionately high abundance in restored communities compared to native remnants, which potentially could reduce the conservation value of restorations. Research is needed to determine how the abundance of dominant species in restoration plantings affects community assembly, species diversity, and ecosystem function. Most studies of dominant species in grasslands were modeled after experiments on keystone species, using the short-term experimental removal of dominants to test their functional role in ecosystems. However, the removal of established dominants constitutes a major disturbance that may influence the interpretation of their long-term functional impact. To address this, we experimentally assembled high-diversity tallgrass prairie communities that included or excluded the predicted dominant species (Andropogon gerardii and Sorghastrum nutans) from the seed mix at the time of planting, but without further manipulation of community composition. From 2013 to 2019, we measured several ecosystem functions and community dynamics in the presence or absence of dominants. Communities that included the dominant species had lower species richness, greater aboveground biomass, and reduced light availability at the soil surface. Dominant species presence also increased soil nutrient availability and rates of litter decomposition, although dominant grass litter decomposed more slowly than litter from other common species in both treatments. In the absence of the dominant grasses, communities were instead dominated by a common unplanted forb, Solidago altissima, and there was partial compensation in ecosystem functioning in these forb-dominated communities. The effects of dominant species exclusion may only be apparent in long-term studies of experimentally assembled communities that avoid the legacy effects associated with removal experiments. Furthermore, our results suggest that prairie restorations that limit or exclude the dominant grasses in seed mixes may achieve higher species diversity, increasing the conservation value of these systems.


Molecular characterisation of oestrogen receptor ERα and the effects of bisphenol A on its expression during sexual development in the Chinese giant salamander (Andrias davidianus).
The aim of this study was to characterise the molecular structure of the oestrogen receptor ERα and to evaluate the effect of bisphenol A (BPA) on ERα expression during sexual development of the Chinese giant salamander (Andrias davidianus). The ERα cDNA of A. davidianus includes an open reading frame of 1755bp (encoding 584 amino acids), a 219-bp 5' untranslated region (UTR) and a 611-bp 3'UTR. A polyadenylation signal was not found in the 3'UTR. Amino acid sequence analysis showed high homology between ERα of A. davidianus and that of other amphibians, such as Andrias japonicas (99.66% identity) and Rana rugose (81.06% identity). In 3-year-old A. davidianus, highest ERα expression was observed in the liver and gonads. During different developmental stages in A. davidianus (from 1 to 3 years of age), ERα expression in the testes increased gradually. ERα was localised in the epithelial cells of seminiferous lobules and in interstitial cells. ERα-positive cells were more abundant in the interstitial tissue during testicular development. ERα was located in the nucleus of oocytes during ovary development. We found that the sex of 6-month-old A. davidianus larvae could not be distinguished anatomically. The sex ratio did not change after larvae were treated with 10μM BPA for 1 month. However, BPA treatment reduced bodyweight and ERα expression in the gonads in male larvae.


Temperament Types at Age 3 and Smartphone Overdependence at Age 10.
Few studies have addressed the longitudinal links between early temperament types and later problematic smartphone use. This study aims to identify children's early temperament types at age 3 and to examine the link between the temperament types and smartphone overdependence at age 10. This study utilized a population-based data set presented by the Panel Study on Korean Children. Based on emotionality, activity, and sociability levels at age 3, children were clustered into similar temperament types. Links between the early temperament types and the risks of smartphone overdependence at age 10 were identified through analyses of covariances and binary logistic regressions. Three early temperament types were identified among Korean children: reactive (28.1%), sociable (37.2%), and cautious (34.8%). Children's smartphone dependence at age 10 differed according to the temperament types identified at age 3. Compared to children with the sociable temperament type, children with the reactive type or the cautious type had an increased risk of smartphone overdependence. The link between temperament types at age 3 and smartphone overdependence at age 10 was meaningful. The cautious children were the most vulnerable group to the risk of smartphone overdependence. Temperament type identification in early years may be a useful measure for screening groups of children who are at risk for problematic smartphone use and need proactive interventions.


Improvement project to reduce surgical site infections: a retrospective cohort study.
Surgical site infections are one of the main problems related to health care. In Brazil, they are responsible for 14 to 16% of infections related to health care. This study sought to analyze the effect of implementing a package of measures to reduce surgical site infections (SSI) in heart surgeries, kidney transplants and herniorrhaphies and to evaluate adherence to the safe surgery checklist in a university hospital. this is a retrospective cohort study with data collection in a time series for the period from 2018 to 2020. we analyzed 222 medical records referring to the surgeries under study performed in the year 2020, in which data were collected from the patients and the care package prevention measures. SSI data and adherence to the safe surgery checklist were analyzed in the years 2018, 2019 and 2020, totaling 268, 300 and 222 procedures analyzed, respectively. the study showed a significant reduction in the SSI rate with greater adherence to the protocol, which was not maintained and was influenced by the COVID-19 pandemic. Thus, the sustainability of this action represents a challenge to be overcome, in order to establish a safer environment for the patient and a better quality of service.


Functional maturation of tactile sensory fibers in the kitten.
The maturation of tactile coding capacities was investigated in sensory fibers supplying the forelimb footpads in anesthetized kittens. Fibers were isolated by microdissection from the median or ulnar nerves of neonatal kittens (1st to 5th postnatal day) and kittens in the age categories 10-15, 25-30, 55-63, and 83-90 days. The use of quantitative, reproducible tactile stimuli, in particular, cutaneous vibration, and objective analytical procedures enabled response parameters to be quantified and compared at different ages with those of adult fibers. While three classes of myelinated tactile sensory fibers are associated with the footpads in adult cats, one of them slowly adapting (SA) and two, the rapidly adapting (RA) and pacinian corpuscle (PC) classes, showing pure dynamic sensitivity, this breakdown into three classes is not apparent until 10-15 days after birth. In all age groups, the SA fibers displayed responses that were graded depending on the magnitude of the skin indentation. However, in younger kittens (less than 25-30 days) plateau levels of response were sometimes attained over a narrow range (0.5 mm) of indentation. From 10-15 days, when RA fibers are identifiable, their sensitivity, as measured by absolute and 1:1 thresholds to cutaneous vibration, was independent of age at low vibration frequencies, less than or equal to 80 Hz. However, at high frequencies, e.g., 200 Hz, their thresholds appeared to decrease during the 1st postnatal month with a resulting expansion in their bandwidth of vibratory sensitivity. At their best frequency, around 30 Hz, RA fibers appear mature by 10-15 days in their capacity for encoding vibratory frequency information. The PC class of tactile afferents displayed the most striking functional changes with age. Their vibratory bandwidths, at 50-micron amplitude, expand from an upper limit of about 200-300 Hz in the neonate to mature values of about 800-1,000 Hz over a 2-mo postnatal period.(ABSTRACT TRUNCATED AT 400 WORDS)


Atypical lymphocyte in dengue hemorrhagic fever: its value in diagnosis.
Simple peripheral and buffy coat smear were studied in 40 serological confirmed dengue hemorrhagic fever patients, and in other patients with viral and bacterial infections. Atypical lymphocytosis was found in majority of dengue hemorrhagic fever both associated with secondary and also in dengue fever with primary infection as compared to other infections. The time course relationship of atypical lymphocytosis, platelet and hematocrit level were discussed, concerning their value as diagnostic and prognostic criteria in dengue hemorrhagic fever.


Clinical characteristics, treatment patterns, disease burden, and persistence/adherence in patients with asthma initiating inhaled triple therapy: real-world evidence from Japan.
Objectives: To help optimize triple therapy use, treatment patterns and disease burden were investigated in patients in Japan with persistent asthma who initiated multi-inhaler triple therapy (inhaled corticosteroid/long-acting β2-agonist/long-acting muscarinic antagonist; ICS/LABA/LAMA).Methods: This retrospective, observational cohort study using health insurance claims data included adults with persistent asthma who initiated triple therapy in 2016. Patients who were prescribed ICS/LABA in 2016 were included as an ICS/LABA-matched cohort. Patients were stratified into those with asthma only and those with asthma and chronic obstructive pulmonary disease (COPD) codes (asthma-COPD overlap [ACO]). Patient data from 1-year prior to 1 year post index date were analyzed.Results: For patients with asthma only in the triple therapy and ICS/LABA cohorts, baseline demographics were similar. A higher proportion of the triple-therapy cohort than the ICS/LABA cohort was receiving high-dose ICS at index (68.2% and 27.6%, respectively), and had experienced an exacerbation in the last year (64.0% and 29.4%, respectively). The proportion of patients with asthma only who developed any exacerbation was lower in the year following initiation of triple therapy compared with the year prior to initiation of triple therapy (45.8% vs 64.0%, respectively). For asthma only patients receiving triple therapy, the mean (standard deviation) proportion of days covered and medication possession ratio was 0.51 (0.36) and 0.86 (0.16), respectively. Similar trends were seen in patients with ACO in the triple-therapy and ICS/LABA cohorts.Conclusion: Evidence from this study may serve as a reference for the use of inhaled triple therapy for asthma.


Weight Loss Interventions for Adolescents With Intellectual Disabilities: An RCT.
In this randomized trial, we compared the effectiveness of 2 diets (enhanced stop light diet [eSLD] versus conventional meal plan diet [CD]) and 2 delivery strategies (face-to-face [FTF] versus remote delivery [RD]) on weight loss across 6 months in adolescents with intellectual and developmental disabilities who were overweight or obese. Participants were randomly assigned to 1 of 3 arms (FTF/CD, RD/CD, or RD/eSLD) and asked to attend one-on-one sessions with a health educator every 2 weeks to aid in maintaining compliance with recommendations for a reduced-energy diet and increased physical activity. The CD followed the US dietary guidelines. The eSLD used the stop light guide and was enhanced with portion-controlled meals. The FTF arm was delivered during in-person home visits. The RD arms were delivered by using video conferencing. A total of 110 adolescents with intellectual and developmental disabilities (aged ∼16 years, 53% female, BMI 33) were randomly assigned to the FTF/CD (n = 36), RD/CD (n = 39), or RD/eSLD (n = 35) group. Body weight at 6 months was obtained from 97%, 100%, and 86% of participants in the FTF/CD, RD/CD, and RD/eSLD arms, respectively. The eSLD elicited significantly greater weight loss than the CD: RD/eSLD (-5.0 ± 5.9 kg; -6.4%) versus RD/CD (-1.8 ± 4.0 kg; -2.4%) (P = .01). However, weight loss did not differ by delivery strategy: FTF/CD (-0.3 ± 5.0 kg; -0.2%) versus RD/CD (-1.8 ± 4.0 kg; -2.4%) (P = .20). The eSLD elicited significantly greater 6-month weight loss compared with a CD when both interventions were delivered remotely. Minimal 6-month weight loss, which did not differ significantly between FTF delivery and RD, was observed with a CD.


[Turpentine baths in rehabilitation of patients with chronic obstructive pulmonary disease].
We have investigated effects of turpentine baths with white emultion, yellow solution and mixed on the course of inflammation, immunocompetent system, external respiration function, pulmonary cardiohemodynamics, physical performance in patients with chronic obstructive pulmonary disease. We developed differential indications for each bath variant depending on the features of a clinical picture of the disease, comorbid pathology and revealed contraindications to their administration.


[Glutamatergic neurotransmission, depression and antidepressants].
Depression is a psychiatric disorder that affects 20% of the population. Despite the efforts aimed to identify the mechanisms underlying its behavioral and affective symptoms, no consensus has been reached. In the last years two new theories, the glutamatergic and the genomic ones, have been proposed. Upon the first, the exposition to stressful stimuli increases hippocampal glutamatergic neurotransmission and triggers excitotoxic changes. The second one postulates that depression is closely correlated with neuronal atrophy due to a decrease in BDNF. The aim of this work is to review recent findings about the glutamatergic neurotransmission and its implication in animal models of depression, depressed patients and in both conditions after the antidepressant treatment. We also tried to identify possible links between these observations and the genomic theory.


Frequency of the allelic variant c.1150T > C in exon 10 of the fibroblast growth factor receptor 3 (FGFR3) gene is not increased in patients with pathogenic mutations and related chondrodysplasia phenotypes.
Mutations in the FGFR3 gene cause the phenotypic spectrum of FGFR3 chondrodysplasias ranging from lethal forms to the milder phenotype seen in hypochondroplasia (Hch). The p.N540K mutation in the FGFR3 gene occurs in ∼70% of individuals with Hch, and nearly 30% of individuals with the Hch phenotype have no mutations in the FGFR3, which suggests genetic heterogeneity. The identification of a severe case of Hch associated with the typical mutation c.1620C > A and the occurrence of a c.1150T > C change that resulted in a p.F384L in exon 10, together with the suspicion that this second change could be a modulator of the phenotype, prompted us to investigate this hypothesis in a cohort of patients. An analysis of 48 patients with FGFR3 chondrodysplasia phenotypes and 330 healthy (control) individuals revealed no significant difference in the frequency of the C allele at the c.1150 position (p = 0.34). One patient carrying the combination `pathogenic mutation plus the allelic variant c.1150T > C' had a typical achondroplasia (Ach) phenotype. In addition, three other patients with atypical phenotypes showed no association with the allelic variant. Together, these results do not support the hypothesis of a modulatory role for the c.1150T > C change in the FGFR3 gene.


Evidence for GAP-43 within descending spinal axons in the North American opossum, Didelphis virginiana.
We have shown previously that GAP-43, a growth associated protein characteristically present in growing and regenerating axons, is relatively abundant in the spinal cord of adult opossums. In the present study, we combined the orthograde transport of the fluorescent marker Fluoro-Ruby with immunofluorescence for GAP-43 to determine if any of it is present within descending spinal axons. When Fluoro-Ruby was injected into the red nucleus and midbrain tegmentum, the medial pontine or medullary reticular formation, the medullary raphe or the lateral vestibular nucleus, axons were labeled in the expected areas of the spinal cord, but in most cases none showed evidence for GAP-43. In two of the four cases with rubral injections, however, a few labeled axons within the rubrospinal tract showed GAP-43 immunofluorescence, and in one case with an injection of the gigantocellular reticular nucleus and adjacent raphe, labeled axons within lamina IX immunostained for the protein. Since serotoninergic neurons are present within the gigantocellular reticular nucleus and adjacent raphe, and axons of the same phenotype are abundant within lamina IX, we asked whether serotoninergic axons contain GAP-43. When sections of the spinal cord were immunostained for both serotonin and GAP-43, many axons within lamina IX showed evidence for both substances. Such axons appeared to contact presumptive motoneurons. In cases with Fluoro-Ruby injections of the forelimb motor cortex, labeled axons were present within the pyramidal tract, and some of them showed evidence for GAP-43.


Immunohistochemical localization of estrogen receptors ERalpha and ERbeta in the spiny mouse (Acomys cahirinus) ovary during postnatal development.
This study was designed to determine the expression pattern of estrogen receptor (ER) subtypes in the Acomys cahirinus ovarian cells during its postnatal development. Immunohistochemical studies revealed the presence of ERalpha and ERbeta in germinal epithelium cells and interstitial tissue. Both these ER subtypes were also seen in granulosa cells and oocytes of growing follicles, however, the level of ERbeta expression was higher in comparison with ERalpha. In contrast to ERbeta, ERalpha protein was also present in theca cells. The expression of ERs increased with animals' age, but it decreased during follicular maturation. Moreover, the immunolocalization of ER subtypes in luteal cells showed that not ERbeta, but ERalpha expression is up-regulated throughout corpus luteum development. These immunohistochemical studies demonstrate, for the first time, that ERalpha is also expressed in the mouse granulosa cells and it may be a mediator of estrogen action in granulosa cells proliferation and differentiation.


Efficacy of CO2 laser surgery in treating squamous intraepithelial lesions. An analysis of clinical and virologic results.
This paper reports the clinical and virologic results of CO2 laser treatment for squamous intraepithelial lesions in 154 patients. On the basis of cervical canal involvement, vaporization or conization was performed. Failure rates following the first and second treatments were 4.5% and 0%, respectively. However, human papillomavirus persistence in several women with completely normal follow-up suggests that one of the possible mechanisms of failure could be reexposure of the healing area to a viral reservoir within the "normal" epithelium.


Optimizing buffering chemistry to maintain near neutral pH of broiler feed during pre-enrichment for Salmonella.
Salmonella is a human pathogen that can accompany live broilers to the slaughter plant, contaminating fully processed carcasses. Feed is one potential source of Salmonella to growing broilers. Monitoring feed for the presence of Salmonella is part of good agricultural practice. The first step in culturing feed for Salmonella (which may be at low numbers and sub-lethally stressed) is to add it to a pre-enrichment broth which is incubated for 24 h. During the course of pre-enrichment, extraneous bacteria metabolize carbohydrates in some feed and excrete acidic byproducts, causing the pH to drop dramatically. An acidic pre-enrichment pH can injure or kill Salmonella resulting in a failure to detect, even if it is present and available to infect chickens. The objective of this study was to test an array of buffering chemistries to prevent formation of an injurious acidic environment during pre-enrichment of feed in peptone water. Five grams of feed were added to 45 mL of peptone water buffered with carbonate, Tris pH 8, and phosphate buffering ingredients individually and in combination. Feed was subjected to a pre-enrichment at 35°C for 24 h; pH was measured at 0, 18, and 24 h. Standard phosphate buffering ingredients at concentrations up to 4 times the normal formulation were unable to fully prevent acidic conditions. Likewise, carbonate and Tris pH 8 were not fully effective. The combination of phosphate, carbonate, and Tris pH 8 was the most effective buffer tested. It is recommended that a highly buffered pre-enrichment broth be used to examine feed for the presence of Salmonella.


Two kinetically distinct tRNAile isoacceptors in Escherichia coli C6.
The isoleucine acceptance of tRNA from Escherichia coli C6 was previously shown to be influenced by the synthetase level (Marashi, F. and Harris, C.L. 1977. Biochim. Biophys. Acta 477, 84-88). We show here that the increased acceptance observed at higher enzyme levels is accompanied by an increase in the aminoacylation of one tRNAile species. Hence, tRNAile, a minor species at low enzyme levels, is a major isoacceptor after full aminoacylation. The two major isoleucine species have been purified using a combination of BD-cellulose, DEAE-Sephadex A-50 and methylated albumin kieselguhr chromatography. tRNAile (1511 pmoles ile/A260 of tRNA) was found to be slowly acylated, with 2a Vmax one-seventh that observed with tRNAil3le (1475 pmoles ile/A260). Two-dimensional TLC analysis of RNase T2 digests revealed differences in nucleotide content between the purified tRNAs. These results are discussed in terms of the presence of slow and fast tRNAile species in E. coli.


Tinnitus in children with hearing loss.
The results are reported of a survey of tinnitus in deaf children in secondary-school age. Of 158 children in five units for the partially hearing and two schools for the deaf. 78 were found to have tinnitus. The tinnitus was constant in two children and intermittent in the remaining 76. The frequency with which the tinnitus occurred, and its duration and loudness, are reported. Some children claimed that tinnitus reduced their hearing ability and speech discrimination. It some, tinnitus was associated with headache or vertigo. When it was unilateral, tinnitus was more commonly on the side of the better-hearing ear. A group of children was defined in whom the tinnitus had features that made it a particularly troublesome symptom.


MicroRNA-26a regulates RANKL-induced osteoclast formation.
Osteoclasts are unique cells responsible for the resorption of bone matrix. MicroRNAs (miRNAs) are involved in the regulation of a wide range of physiological processes. Here, we examined the role of miR-26a in RANKL-induced osteoclastogenesis. The expression of miR-26a was up-regulated by RANKL at the late stage of osteoclastogenesis. Ectopic expression of an miR-26a mimic in osteoclast precursor cells attenuated osteoclast formation, actin-ring formation, and bone resorption by suppressing the expression of connective tissue growth factor/CCN family 2 (CTGF/CCN2), which can promote osteoclast formation via up-regulation of dendritic cell-specific transmembrane protein (DC-STAMP). On the other hand, overexpression of miR-26a inhibitor enhanced RANKL-induced osteoclast formation and function as well as CTGF expression. In addition, the inhibitory effect of miR-26a on osteoclast formation and function was prevented by treatment with recombinant CTGF. Collectively, our results suggest that miR-26a modulates osteoclast formation and function through the regulation of CTGF.


Rhythmic and light-inducible appearance of clock-associated pseudo-response regulator protein PRR9 through programmed degradation in the dark in Arabidopsis thaliana.
In Arabidopsis thaliana, it is currently believed that the members of a small family of PSEUDO-RESPONSE REGULATOR (PRR) proteins, including TOC1 (TIMING OF CAB EXPRESSION 1), coordinately play roles close to the circadian clock. Among these PRR members, the PRR9 gene is unique in that not only does its transcription oscillate diurnally, but it is also rapidly induced by light in a manner dependent on phytochromes. These events at the level of transcription must be crucial for the clock-associated functions of PRR9. Nonetheless, little is known about the expression of the PRR9 protein product itself in plant cells. Here, we show that PRR9 polypeptides themselves oscillate diurnally, and that they accumulate rapidly in response to light. Our work further suggests that the presence of PRR9 polypeptides is controlled through proteasome-mediated programmed degradation in the dark.


Critical Review of Outcomes from Radical Cystectomy: Can Complications from Radical Cystectomy Be Reduced by Surgical Volume and Robotic Surgery?
Radical cystectomy (RC) is a highly complex procedure with multiple risks for perioperative complications. We reviewed the literature to report perioperative outcomes and the incidence of complications in contemporary RC series. We focused on the potential impact of surgical approach and surgeon volume on these outcomes. A systematic literature search was performed in December 2015 using the Medline, Embase, and Web of Science databases for articles published in English between 2005 and 2015. The search strategy included the terms complications, cystectomy, robotic assisted radical cystectomy, and surgical volume, alone or in combination. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. Our searches retrieved 49 papers. Open RC (ORC) and robot-assisted RC (RARC) are morbid procedures with consistent risk of perioperative complications (mean weighted incidence: 48.7%; range: 27.0-72.5%). Higher hospital and surgeon volumes were associated with reduced risks of perioperative complications. Prior robotic expertise in radical prostatectomy showed a beneficial protective risk on development of complications after RARC. Surgical volume appears to be a good predictor of safety in ORC and RARC. RARC is associated with reduced estimated blood loss and lower perioperative transfusion rates compared with ORC. Further evidence is needed to support the reproducibility of intracorporeal diversion during RARC, beyond large tertiary referral centers. Several strategies have been demonstrated to be effective for reducing the risk of incurring perioperative complications and should be pursued by physicians. Despite improvements in quality of care, RC remains a challenging procedure with high morbidity, regardless of surgical approach. RARC is a safe procedure with potential advantages in terms of reduced blood loss and transfusion rates. Surgical volume appears to be related to the improvement of perioperative outcomes and complications. Radical cystectomy is a challenging and morbid procedure. The robotic approach has gained popularity and proved to be safe and effective in tertiary referral centers, although further studies are needed to confirm its wide reproducibility. Centers with higher surgical volume have lower incidence of perioperative complications.


Estradiol and reproduction in the South American toad Rhinella arenarum (Amphibian, Anura).
Rhinella arenarum is a South American toad with wide geographic distribution. Testes of this toad produce high amount of androgens during the non reproductive season and shift steroid synthesis from androgens to 5α-pregnanedione during the breeding. In addition, plasma estradiol (E2) in males of this species shows seasonal variations but, since testes of R. arenarum do not express aromatase, the source of plasma E2 remained unknown for several years. However, the Bidder's organ (BO), a structure located at one pole of each testis, is proposed to be the main source of E2 in male's toads since it expresses several steroidogenic enzymes and is able to produce E2 from endogenous substrates throughout the year. In addition, there were significant correlations between plasma E2 and total activity of BO aromatase, and between plasma E2 and the amount of hormone produced by the BO in vitro. In the toad, apoptosis induced by in vitro treatment with E2 was mostly detected in spermatocytes during the breeding and in spermatids during the post-reproductive season, suggesting that this steroid has an important role in controlling spermatogenesis. However, in vitro treatment with E2 had no effect on proliferation. This evidence suggests that the mechanism of action of E2 on amphibian spermatogenesis is complex and more studies are necessary to fully understand the role of estrogens regulating the balance between cellular proliferation and apoptosis. In addition, in R. arenarum in vitro studies suggested that E2 has no effect on CypP450c17 protein levels or enzymatic activity, while it reduces 3β-hydroxysteroid dehydrogenase/isomerase (3β-HSD/I) activity during the post reproductive season. As well, E2 regulates FSHβ mRNA expression all over the year suggesting a down regulation process carried out by this steroid. The effect on LHβ mRNA is dual, since during the reproductive season estradiol increases the expression of LHβ mRNA while in the non-reproductive season it has no effect. In conclusion, the effect of E2 on gonadotropins and testicular function is complex, not clearly understood and probably varies depending on the species. The aim of the current article is to review evidence on reproductive endocrinology and on the role of estradiol regulating reproduction in amphibians, with emphasis on the South American species Rhinella arenarum.