Hereditary Renal Diseases.
Hereditary kidney disease comprises approximately 10% of adults and nearly all children who require renal replacement therapy. Technologic advances have improved our ability to perform genetic diagnosis and enhanced our understanding of renal and syndromic diseases. In this article, we review the genetics of renal diseases, including common monogenic diseases such as polycystic kidney disease, Alport syndrome, and Fabry disease, as well as complex disorders such as congenital anomalies of the kidney and urinary tract. We provide the nephrologist with a general strategy to approach hereditary disorders, which includes a discussion of commonly used genetic tests, a guide to genetic counseling, and reproductive options such as prenatal diagnosis or pre-implantation genetic diagnosis for at-risk couples. Finally, we review pregnancy outcomes in certain renal diseases.


Applicability of textual clinical practice guidelines: impact of physician interpretation.
1) Determine whether textual Clinical Practice Guidelines (CPGs) are interpreted accurately and unequivocally by targeted physicians. 2) Specify audience and perception of the CPGs. Comparative analysis of answers given by a panel of general practitioners to a series of questions and clinical case studies related to three textual CPGs produced and published by the French National Agency for Accreditation and Evaluation in Health (ANAES). 68 to 96% of physicians are aware of the existence of the CPGs studied. Less than 50% state having read them. On average, 38% of physician interpretations of CPGs are incorrect (i.e., not in agreement with expert interpretation). Furthermore, there is disagreement among physicians responses. This study credits the argument of disparities in practice which derive from inaccurate and discordant CPGs' interpretations. The results should prompt those responsible for producing such decision-making support to design documents that are better structured, less ambiguous, and more precise. In a model which facilitates their computerisation the expression of CPGs provides a solution that should be included upstream in the publication process.


Parental spirituality in life-threatening pediatric cancer.
This study addressed parental spirituality in the context of pediatric cancer with a poor prognosis. Drawing upon previous research implementing a longitudinal grounded theory design examining parental hope, 35 parents were interviewed regarding their experiences with an emergent description of the role of spirituality in parents' daily lives. Spirituality included religious beliefs and practices, notions of a higher force or cosmos, relationship with a divine being, as well as elements emerging from meaning-making and relationships. Parental expectations of spirituality remained relatively constant across data collection time points (3-9 months postdiagnosis), although limited variation occurred relative to shifting circumstance (e.g., deterioration of the child's condition). Spirituality appeared to offer: greater acceptance of parents' inability to protect their child from harm related to her/his life-threatening illness, guidance and emotion decompression, and support from one's faith community. Recommendations for integrating spiritual assessment in clinical care practice are offered.


What are the participants' perspective and the system-based impact of a standardized, inter-professional morbidity/mortality-conferences in a children's hospital?
Morbidity and mortality conferences (MMC) are well established but little data exists on inter-professional aspects, system-based outcomes and characteristics in pediatric departments. Our study aim was to analyze the system-based impact and to assess participant's perspectives on standardized, inter-professional MMCs in a children's hospital. In a prospective observational analysis the inter-professional MMCs held at a tertiary teaching children's hospital in Switzerland were analyzed for (I) resulting clinical consequences and (II) participants perception on format, usefulness and no-blame atmosphere. Eighteen MMC, discussing 29 cases were analyzed. Twenty-seven clinical errors/problems were identified and 17 clinical recommendations were developed: ten new or changed clinical guidelines, two new therapeutic alternatives, three new teaching activities, and two guidelines on specific diagnostics. Altogether, the 466 participants evaluated the conferences favorably. Little differences were seen in the evaluations of physicians of different disciplines or seniority but non-physicians scored all questions lower than physicians. Overall, three quarters of the participants felt that there was a no-blame culture during the conferences but results varied depending on the cases discussed. An inter-professional MMC can have relevant impact on clinical practice and affect system-based changes. Inter-professional conferences are profitable for all participants but evaluated differently according to profession. A standardized format and the presence of a moderator are helpful, but not a guarantee for a no-blame culture. Highly emotional cases are a risk factor to relapse to "blame and shame". A time gap between the event and the MMC may have a beneficial effect. Inter-professional communication; inter-professional health care; learning from failure; morbidity and mortality conference (MMC); patient safety; psychological safety.


Risk Factors for Depression in Long-term Care: A Prospective Observational Cohort Study.
Objectives: Depression among older adults in long-term care remains a problem, despite the uptake of antidepressants and the development of intervention programs. A better understanding of the risk factors for depression is much needed. Guided by a systematic assessment of the evidence, this prospective observational cohort study sought to clarify existing evidence, identify modifiable risk factors and explore novel variables. Methods: Adults aged ≥65 (T1 n=147, T2 n= 81) were recruited from 15 long-term-care facilities in Melbourne, Australia. Cognitive impairment, functional impairment, pain, sleep disturbance, social support, and person-environment fit were investigated as risk factors. Outcomes were depressive symptoms and indicated Major Depressive Episode. Results: Generalized Estimating Equations (GEE) identified that changes in pain (b= 0.06, p<.05), sleep disturbance (b= 0.02, p< .001), social support (b= -0.02, p< .001) and person-environment fit (b= -0.02, p= <.01) were significantly associated with changes in depression score. Conclusions: Pain, sleep disturbance, social support, and person-environment fit are modifiable risk factors, making them strongly positioned to strategically inform prevention and intervention strategies. Clinical Implications: Individuals with clinically significant symptoms on these risk factors for depression should be selected for interventions that target these risk factors. For depressed individuals, psychotherapy should prioritize the potential role of these risk factors. Finally, these risk factors should be used as screening and monitoring variables: clinically significant changes in symptoms warrant investigation.


Risk of cerebrovascular accident in patients with primary biliary cirrhosis: a systematic review and meta-analysis.
Dyslipidemia is common among patients with primary biliary cirrhosis (PBC) and might increase the risk of cerebrovascular accident (CVA). However, data from epidemiologic studies remain inconclusive. This study aims to further investigate this association. We carried out a systematic review and meta-analysis of observational studies that compared the risk of CVA in patients with PBC versus controls. Pooled risk ratios and 95% confidence intervals were combined using a random-effect, generic inverse variance method of DerSimonian and Laird. Four studies with 2309 patients with PBC were identified and included in our data analysis. The pooled risk ratio of CVA in patients with PBC was 1.11 (95% confidence interval, 0.81-1.51). The statistical heterogeneity was insignificant, with an I of 14%. A significantly increased risk of CVA among patients with PBC was not observed in this study.


Comprehensive bio-imaging using myocardial perfusion reserve index during cardiac magnetic resonance imaging and high-sensitive troponin T for the prediction of outcomes in heart transplant recipients.
We sought to determine the ability of quantitative myocardial perfusion reserve index (MPRI) by cardiac magnetic resonance (CMR) and high-sensitive troponin T (hsTnT) for the prediction of cardiac allograft vasculopathy (CAV) and cardiac outcomes in heart transplant (HT) recipients. In 108 consecutive HT recipients (organ age 4.1±4.7 years, 25 [23%] with diabetes mellitus) who underwent cardiac catheterization, CAV grade by International Society for Heart & Lung Transplantation (ISHLT) criteria, MPRI, late gadolinium enhancement (LGE) and hsTnT values were obtained. Outcome data including cardiac death and urgent revascularization ("hard cardiac events") and revascularization procedures were prospectively collected. During a follow-up duration of 4.2±1.4 years, seven patients experienced hard cardiac events and 11 patients underwent elective revascularization procedures. By multivariable analysis, hsTnT and MPRI both independently predicted cardiac events, surpassing the value of LGE and CAV by ISHLT criteria. Furthermore, hsTnT and MPRI provided complementary value. Thus, patients with high hsTnT and low MPRI showed the highest rates of cardiac events (annual event rate=14.5%), while those with low hsTnT and high MPRI exhibited excellent outcomes (annual event rate=0%). In conclusion, comprehensive "bio-imaging" using hsTnT, as a marker of myocardial microinjury, and CMR, as a marker of microvascular integrity and myocardial damage by LGE, may aid personalized risk-stratification in HT recipients.


Outcomes of Medical and Surgical Management in Aqueous Misdirection Syndrome.
To report the outcomes of medical and surgical management in patients diagnosed with aqueous misdirection syndrome (AMS). A retrospective chart review of all cases diagnosed with AMS at a single tertiary care eye center during the period from 2014 to 2021. Outcome measures were anatomical success (deepening of the anterior chamber (AC)), functional success (improvement in visual acuity), and treatment success (control of intraocular pressure (IOP)). A total of 26 eyes with AMS from 24 patients were included. The patients were followed for a mean duration of 24 ± 18 months. Although some patients initially responded to medical and laser therapy, all but one (3.8%) eventually required surgery during the first 3 months after presentation. The mean duration from presentation until surgery was 45.9 ± 45.8 days (range: 2-119 days). The majority of cases (69.2%) were managed by pars plana vitrectomy. At the last follow-up visit, anatomical success was achieved in 20 (76%) eyes, 15 (57%) eyes had a final visual acuity that was either similar to or better than baseline, and successful control of IOP was achieved in 17 (65%) eyes. Univariate analysis revealed that a history of trabeculectomy as a cause of AMS was a risk factor for treatment failure (OR, 7.8; 95% CI, 1.16-52.35; P, 0.02). Our findings indicate that medical and laser management of AMS provide temporary control, and almost all patients eventually require surgery within the first 3 months. A history of trabeculectomy was found to be a risk factor for treatment failure.


Dynamical and bursty interactions in social networks.
We present a modeling framework for dynamical and bursty contact networks made of agents in social interaction. We consider agents' behavior at short time scales in which the contact network is formed by disconnected cliques of different sizes. At each time a random agent can make a transition from being isolated to being part of a group or vice versa. Different distributions of contact times and intercontact times between individuals are obtained by considering transition probabilities with memory effects, i.e., the transition probabilities for each agent depend both on its state (isolated or interacting) and on the time elapsed since the last change in state. The model lends itself to analytical and numerical investigations. The modeling framework can be easily extended and paves the way for systematic investigations of dynamical processes occurring on rapidly evolving dynamical networks, such as the propagation of an information or spreading of diseases.


[Auto-immune hypoglycemic syndrome induced by pyritinol].
The auto-immune hypoglycemic syndrome is characterized by the association of hypoglycemia (clinical and/or biological) and anti-insulin antibodies in patients who have never received exogenous insulin. Initially this syndrome was most often described in Japanese patients some of whom were treated with drugs containing a sulfydril group. We now recall the case of a female caucasian patient treated with Pyritinol for rhumatoid polyarthritis and who presented severe spontaneous hypoglycemia linked with the presence of anti-insulin antibodies in her serum. The level of her antibodies decreased abruptly on suspension of the drug. The recent and more developed characterization techniques of the different forms of circulating insulin and of their antibodies may help to differenciate an auto-immune hypoglycemia from hypoglycemia due to the secret auto-administration of bovine and porcine insuline, and permit us to suggest that an abnormality in the structure of the molecule of insulin might be a cause of this syndrome. However, the exact mechanism of hypoglycemia linked with the presence of anti-insulin auto-antibodies is not yet clear as is the predisposition of a drug with a sulfydril group to induce such an auto-immune phenomenon.


Topical antibiotic ointments for staphylococcal nasal carriers: survey of current practices and comparison of bacitracin and vancomycin ointments.
One measure used in the management of staphylococcal disease outbreaks in newborn nurseries is to obtain nasal cultures from nursery personnel and then treat nasal carriers with topical antibiotic ointments. Because recent infection control guide-surveyed current practices in larger hospitals in the U.S.A. Seventy-one percent of respondents indicated that they would obtain nasal cultures from personnel during a staphylococcal disease outbreak, and 40% indicated that they would prescribe topical antibiotic ointments for personnel with positive nasal cultures before the results of bacteriophage typing became known. Because little has been written about the efficacy of topical intranasal antibiotics within the past decade, we compared bacitracin ointment with a vancomycin ointment for treatment of the staphylococcal nasal carrier state. Both ointments reduced nasal carriage in the majority of instances. However, similar reduction was also observed in an untreated control group. The need for different approaches to the problem of nasal carriers is discussed.


Inflection Point of the Localized Surface Plasmon Resonance Peak: A General Method to Improve the Sensitivity.
The shift of the localized surface plasmon resonance (LSPR) spectrum is widely used in bio- and chemical sensing. Traditionally, the shift is monitored at the peak maximum of the extinction spectrum. We demonstrate that the inflection point at the long wavelength side of the peak maximum shows better refractive index sensitivity than the peak maximum. A consistent improvement in bulk refractive index sensitivity of 18-55% is observed for six different nanoparticles such as spherical particles of different sizes, nanostar and nanorods with different aspect ratios. Local refractive index changes induced by molecular adsorption confirm the superior performance of the method. We contribute this improvement in sensitivity to the change in shape of the LSPR peak in response to an increase of the local refractive index. We further illustrate the advantage of using the inflection point method for analyzing DNA adsorption on U-shaped metamaterials, and for using 17 nm spherical gold nanoparticles for detection of matrix metalloprotease 7 (MMP-7), a biomarker that is heavily up-regulated during certain cancers. With the inflection point, the limit of detection (LOD) for MMP-7 is improved to 0.094 μg/mL from 0.22 μg/mL. This improvement may facilitate early diagnosis of salivary and colorectal cancers. We also envision that this generic method can be employed to track minute optical responses in other analytical areas.


Determination of three optical properties from subdiffusive spatially resolved reflectance calculations.
We report a theoretical study on the determination of three optical properties from spatially resolved reflectance calculations. In particular, the reduced scattering coefficient μs′, the absorption coefficient μa, and the recently defined phase function parameter σ are identified. The solution of the inverse problem is based on the principal component analysis of a large set of reflectance profiles that were calculated using an analytical solution of the radiative transfer equation. Different phase function types were studied to test the method in the range of 0.63 mm−1≤μs′≤4.2 mm−1 and 0.002 mm−1≤μa≤0.1 mm−1. For curves impaired with noise, we were able to reconstruct μs′ and μa with relative median errors of 2.5% and 12%, respectively, and σ with an absolute median error of 0.04.


Extra-anatomical Obturator Bypass Due to Groin Infection.
A rather common side effect of using prosthetic grafts is infection of the groin area. Infections in the groin may be avoided by performing arterial bypass tenneling via the obturator foramen during lower extremity revascularization. This study aimed to evaluate the safety and efficacy of extra-anatomical bypass obturator in patients with groin infection. This cohort included a convenient sample of 100 patients with groin infections who planned to do an extra-anatomical obturator bypass. All patients were subjected to history taking and clinical assessment. Ultrasonography with duplex screening is a good initial technique to assess groin masses. Combination of computed tomography (CT) or magnetic resonance imaging (MRI) with indium-labeled leucocyte scintigraphy can also play a role in the diagnosis. Inflow from the already-existing graft limb was used in 54% of obturator canal bypass (OCB) procedures, with 32 limbs coming from the main iliac (27.3%) and 6 limbs from the infrarenal aorta (5.1%). The distal superficial femoral artery was used in 21 limbs (17.9%), while the above-knee popliteal artery was selected as the outflow artery in 82% of cases. Primary aided patency was 68% at 24 months, according to Kaplan-Meier analysis, whereas primary patency was 63% at that time. At 24 months, the secondary patency of the OCB was 83%. In case of groin infections, an excellent option to restore flow is an obturator bypass graft. This graft is strong, reliable, and safe. As a result of its high patency rate, it may be the first choice in certain circumstances.


Ethanol extraction by supported liquid membrane during fermentation.
A supported liquid membrane system was developed for the extraction of ethanol during semicontinuous fermentation of Saccharomyces bayanus. it consisted of a porous Teflon sheet as support, soaked with isotridecanol. This assembly permitted combining biocompatibility, permeation efficiency, and stability. The removal of ethanol from the cultures led to decreased inhibition and, thus, to a gain in conversion of 452 g/L glucose versus 293 g/L glucose without extraction. At the same time, the ethanol volumetric productivity was enhanced 2.5 times, due to an improvement of yeast viability, while the substrate conversion yield was maintained above 95% of its theoretical value. Besides these improvements in fermentation performances, the process resulted in ethanol purification, since the separation was selective towards microbial cells and carbon substrate, and likely selective to mineral ions present in the fermentation broth. For pervaporation, a concentration of ethanol four times greater was obtained in the collected permeate.


Plasmid-associated genes in the model micro-symbiont Sinorhizobium meliloti 1021 affect the growth and development of young rice seedlings.
Sinorhizobium meliloti strain 1021 and its closely related strain Rm2011 inhibit rice seedling (Oryza sativa L. cv. Pelde) growth and development under certain rice-growing conditions. Experiments showed that inoculation of seedlings with approximately less than 10 cells of 1021 was sufficient to cause this inhibition. By using a series of plasmid-cured and plasmid-deleted derivatives of Rm2011, it was found that interactions between genes encoded on pSymA, and possibly pSymB, of Rm2011, affected rice growth and development by affecting both/either the plant and/or the bacteria. Further studies found that genes potentially related to indole-3-acetic acid (IAA) synthesis and nitrate metabolism, encoded on pSymA, were involved in rice growth inhibition in Sm1021- and Sm2011-treated rice seedlings. We conclude that the rice growth inhibition by S. meliloti Sm1021 is pSymA-associated and is induced by environmental nitrate.


[Comparison between torasemide and furosemide in the treatment of ascites in cirrhotic patients].
Twenty patients with cirrhosis and ascites were randomly divided in two groups to receive 20 mg/die of the new-loop-diuretic torasemide (T), and 50 mg/die of furosemide (F). All patients also received 200 mg/die of potassium canrenoate. Natriuretic and diuretic effects and consequent loss of weight were significantly better in the torasemide-group (T-group). Otherwise, loss of potassium and sodium/potassium ratio in urine were not significantly higher for T-group. Ammonium lowered with T and remained unchanged with F, but the difference was not statistically significant. No change was observed in blood-pressure, pulse-frequency, electrolyte plasmatic levels, azotemia, creatininemia and serum albumin. A significant increase of diuresis was obtained from the fourth day of treatment onwards by replacing F with T in the F-group. The T-group maintained T for eight days just to evaluate its efficacy and tolerability in the middle term: diuresis kept efficient and no side-effects occurred. This trial showed that T was a good and handy drug for cirrhosis with ascites whether as an alternative to F, or as a sequential treatment.


New developments in nitrosovasodilator therapy.
Under basal conditions, nitric oxide (NO) modulates vascular tone, serves as an antithrombotic agent, and inhibits vascular smooth muscle cell proliferation. NO deficiency has been implicated in the pathophysiology of several vascular disorders, including hypertension, atherosclerosis, and restenosis, and provides a plausible biologic basis for the use of NO replacement therapy in these conditions. Treatment with conventional nitrate preparations is limited by a short therapeutic half-life, systemic absorption with potentially adverse hemodynamic effects, and drug tolerance. To overcome these limitations, novel delivery systems and novel NO donors have been developed that offer selective effects, a prolonged half-life, and a reduced incidence of tolerance.


[A phase I study of carboplatin].
A phase I study of carboplatin was conducted using a single dose schedule. Escalating doses of 200, 300, 400 and 500mg/m2 were administered without hydration up to a total of 21 cycles in 18 patients with various solid tumors. A dose-limiting factor was thrombocytopenia, and leukopenia was also dose-related. A major clinical toxicity was gastrointestinal toxicity, while nephrotoxicity was extremely mild. The optimal dose for phase II trials was judged to be 300mg/m2 q 4w in poor-risk patients and 400mg/m2 q 4w in good-risk patients, respectively. Pharmacokinetics were studied in 11 patients.


Fetal goitrous hypothyroidism followed by neonatal transient hyperthyroidism. A case report.
We report a case of fetal goitrous hypothyroidism followed by neonatal transient hyperthyroidism. A fetal goiter (26 x 38 mm) was detected by ultrasound and magnetic resonance imaging at 29 weeks of gestation. Hypothyroidism was confirmed by cordocentesis, which revealed an elevated TSH (255 microIU/ml) and a low free T4 (0.4 ng/dl). The fetal goiter decreased in size after treatment with four 240-microgram intra-amniotic administrations of levothyroxine. A 2,829-gram male neonate was delivered vaginally at 37 weeks of gestation, showing an euthyroid status at birth. On day 3, free T3 was 6.9 pg/ml and free T4 was 6.4 ng/dl, indicating hyperthyroidism. This persisted for 4 months. His thyroid functions reverted to normal at 4 months of age and have been within normal range since. Undetermined factors might be involved in the development of thyroid dysfunction in the perinatal period.


[Conducting clinical studies during the epidemics of communicable diseases: perspectives of methodology and health economics].
In the setting of epidemics of communicable diseases, early initiation of epidemiological and clinical data collection and analysis and conducting relevant researches are essential to the success of epidemic containment. The coronavirus disease 2019 (COVID-19), starting initially as an epidemic in China in late 2019 and now becoming a pandemic globally, poses grave challenges to the global health care systems while also provides an opportunity for studying infectious diseases in the perspective of methodology. The authors propose the evaluation methods for case reports, randomized controlled trials (RCTs), real-world evidence studies and health economics researches during an epidemic. Case reports, which are of important value for health care workers during outbreaks of infectious diseases, should be written in standard format and style and published following a strict peer review process. RCTs provides the gold standard for evaluating the effectiveness of a given treatment for the patients from the outbreaks. We review the potential challenges faced in conducting RCTs during the outbreaks. The real-world data collected from the cases in designated hospitals allow the verification of the safety and effectiveness of the intervention measures. The data from health economics research also provide important support for optimizing communicable disease prevention and control strategies. Herein we summarize the health economics research methods, study design, and technical points during the outbreaks. We recommend that clinical research and health economics research be incorporated into the prevention and control plan and measures be taken to ensure both the standards and feasibility of these studies to improve the response capacity against outbreaks of communicable diseases.


Prediction of graft survival of living-donor kidney transplantation: nomograms or artificial neural networks?
An artificial neural networks (ANNs) model was developed to predict 5-year graft survival of living-donor kidney transplants. Predictions from the validated ANNs were compared with Cox regression-based nomogram. Out of 1900 patients with living-donor kidney transplant; 1581 patients were used for training of the ANNs (training group), the remainder 319 patients were used for its validation (testing group). Many variables were correlated with the graft survival by univariate analysis. Significant ones were used for ANNs construction of a predictive model. The same variables were subjected to a multivariate statistics using Cox regression model; their result was the basis of a nomogram construction. The ANNs predictive model and the nomogram were used to predict the graft survival of the testing group. The predicted probability(s) was compared with the actual survival estimates. The ANNs sensitivity was 88.43% (95% confidence interval [CI] 86.4-90.3), specificity was 73.26% (95% CI 70-76.3), and predictive accuracy was 88% (95% CI 87-90) in the testing group, whereas nomogram sensitivity was 61.84% (95% CI 50-72.8) with 74.9% (95% CI 69-80.2) specificity and predictive accuracy was 72% (95% CI 67-77). The positive predictive value of graft survival was 82.1% and 43.5% for the ANNs and Cox regression-based nomogram, respectively, and the negative predictive value was 82% and 86.3% for the ANNs and Cox regression-based nomogram, respectively. Predictions by both models fitted well with the observed findings. These results suggest that ANNs was more accurate and sensitive than Cox regression-based nomogram in predicting 5-year graft survival.


Quantitative nuclear proteomics identifies that miR-137-mediated EZH2 reduction regulates resveratrol-induced apoptosis of neuroblastoma cells.
Neuroblastoma is the most common pediatric extracranial solid tumor with a broad spectrum of clinical behavior and poor prognosis. Despite intensive multimodal therapy, ongoing clinical trials, and basic science investigations, neuroblastoma remains a complex medical challenge with a long-term survival rate less than 40%. In our study, we found that resveratrol (3, 5, 4'-trihydroxystilbene, RSV), a naturally occurring phytoalexin, possesses an anticancer activity through blocking cell growth and inducing apoptosis in neuroblastoma cell line Neuro-2a (N-2a) cells. Using stable isotope labeling with amino acids in cell culture (SILAC) and quantitative proteomic analysis, we found that 395 proteins were up-regulated and 302 proteins were down-regulated in the nucleus of N-2a cells treated with RSV. Among these, the polycomb protein histone methyltransferase EZH2 was reduced significantly, which is aberrantly overexpressed in neuroblastoma and crucial to maintain the malignant phenotype of neuroblastoma by epigenetic repression of multiple tumor suppressor genes. EZH2 reduction further led to decreased H3K27me3 level and reactivation of neuroblastoma tumor suppressor genes CLU and NGFR. Disruption EZH2 expression by RNA interference-mediated knockdown or pharmacologic inhibition with DZNep triggered cellular apoptosis in N-2a cells. We found that the up-regulation of miR-137 level was responsible for reduced EZH2 level in tumor suppression induced by RSV. Inhibition of miR-137 expression rescued the cellular apoptosis phenotypes, EZH2 reduction, and CLU and NGFR reactivation, associated with RSV treatment. Taken together, our findings present for the first time, an epigenetic mechanism involving miR-137-mediated EZH2 repression in RSV-induced apoptosis and tumor suppression of neuroblastoma, which would provide a key potential therapeutic target in neuroblastoma treatment.


Increased affective ultrasonic communication during fear learning in adult male rats exposed to maternal immune activation.
Maternal exposure to infection during pregnancy greatly increases the risk of psychopathology in the offspring. In support of clinical findings, rodent models of maternal immune activation (MIA) show that prenatal exposure to pathogens can induce phenotypic changes in the offspring associated with schizophrenia, autism, depression and anxiety. In the current study, we investigated the effects of MIA via polyinosinic:polycytidylic acid (poly I:C) on emotional behavior and communication in rats. Pregnant rats were administered poly I:C or saline on gestation day 15 and male offspring were tested in an auditory fear conditioning paradigm in early adulthood. We found that prenatal poly I:C exposure significantly altered affective signaling, namely, the production of aversive 22-kHz ultrasonic vocalizations (USVs), in terms of call number, structure and temporal patterning. MIA led to an increase in aversive 22-kHz USVs to 300% of saline controls. Offspring exposed to MIA not only emitted more 22-kHz USVs, but also emitted calls that were shorter in duration and occurred in bouts containing more calls. The production of appetitive 50-kHz USVs and audible calls was not affected. Intriguingly, alterations in aversive 22-kHz USV emission were observed despite no obvious changes in overt defensive behavior, which highlights the importance of assessing USVs as an additional measure of fear. Aversive 22-kHz USVs are a prominent part of the rat's defensive behavioral repertoire and serve important communicative functions, most notably as alarm calls. The observed changes in aversive 22-kHz USVs show that MIA has long-term effects on emotional behavior and communication in exposed rat offspring.


Uncontrolled hypertension and hyperreninemia after hemorrhage in a patient with end-stage renal disease and acquired renal cysts.
Acquired cystic kidney disease occurs in over 74% of patients with ESRD on hemodialysis for more than 4 yr. A variety of complications have been associated with these cysts including bleeding, lithiasis, infection, obstruction, and malignant transformation. An ESRD patient who developed accelerating hypertension secondary to an acute perinephric hematoma due to a bleeding-acquired renal cyst is described. The hypertension, which was refractory to aggressive drug therapy, was controlled only after the involved kidney was removed, after the demonstration of an elevated ipsilateral renal vein renin level. This is the first case reported in which worsening hypertension, apparently due to the "Page Kidney," developed as a complication of perinephric bleeding in an ESRD patient with acquired cystic kidney disease.


Analysis of baseline, average, and longitudinally measured blood pressure data using linear mixed models.
This article compares baseline, average, and longitudinal data analysis methods for identifying genetic variants in genome-wide association study using the Genetic Analysis Workshop 18 data. We apply methods that include (a) linear mixed models with baseline measures, (b) random intercept linear mixed models with mean measures outcome, and (c) random intercept linear mixed models with longitudinal measurements. In the linear mixed models, covariates are included as fixed effects, whereas relatedness among individuals is incorporated as the variance-covariance structure of the random effect for the individuals. The overall strategy of applying linear mixed models decorrelate the data is based on Aulchenko et al.'s GRAMMAR. By analyzing systolic and diastolic blood pressure, which are used separately as outcomes, we compare the 3 methods in identifying a known genetic variant that is associated with blood pressure from chromosome 3 and simulated phenotype data. We also analyze the real phenotype data to illustrate the methods. We conclude that the linear mixed model with longitudinal measurements of diastolic blood pressure is the most accurate at identifying the known single-nucleotide polymorphism among the methods, but linear mixed models with baseline measures perform best with systolic blood pressure as the outcome.


LC-MS/MS identification of doublecortin as abundant beta cell-selective protein discharged by damaged beta cells in vitro.
There is a clinical need for plasma tests that can directly detect injury to pancreatic beta cells in type 1 diabetes. Such tests require biomarkers that are abundantly and selectively released into plasma by damaged beta cells. We combined LC-MS/MS proteomics and tissue-comparative transcriptomics of FACS-purified beta cells for bottom-up identification of candidate markers. Less than 10% of 467 proteins detected in beta cells showed endocrine-enriched expression. One surprising candidate was the neuronal migration marker doublecortin: in situ analysis revealed uniform doublecortin expression in the cytoplasm of all beta cells. Western blotting and real-time PCR confirmed its strong beta cell-selectivity outside the brain and its high molar abundance, indicating promising biomarker properties in comparison to GAD65, a more established marker of beta cell injury. DCX potential was validated in vitro: chemically-induced necrosis of rat and human beta cells led to a discharge of intracellular doublecortin into the extracellular space, proportionate to the amount of injured cells, and similar to GAD65. In vivo, recombinant DCX showed favorable pharmacokinetic properties, with a half-life in plasma of around 3h. Combined, our findings provide first proof-of-principle for doublecortin as biomarker for beta cell injury in vitro, advocating its further validation as biomarker in vivo.


Workshop on late effects of irradiation to the head and neck in infancy and childhood.
A summary statement for the Workshop on Late Effects of Irradiation to the Head and Neck in Infancy and Childhood is presented. The Workshop, conducted by the National Cancer Institute with the cooperation of several other organizations, was convened to determine the present status of knowledge about thyroid disease related to irradiation of the head and neck and to develop guidelines with respect to detection, diagnosis, treatment, and followup. It was decided that surgical exploration should be considered for all palpable thyroid nodules, particularly those that are firm and clearly demarcated and appear as a "cold" area on the scan. Persons at risk because of prior irradiation to the head or neck should have regular reexaminations every one to two years.


New frontiers in the treatment of overactive bladder and incontinence.
In this article the author tries to forecast how urologists will treat the overactive bladder (OAB) in the next decade. He reviews drugs currently under development and also logical and exciting pharmacological targets that would be suitable targets for treating OAB in the future. The author also discusses intravesical therapy and alternative drug delivery methods, such as intravesical capsaicin and botulinum toxin. There are many advantages to advanced drug delivery systems, including the achievement of long-term therapeutic efficacy, decreased incidence and severity of side effects, and improved patient compliance. Special emphasis is placed on approaches to modulating bladder afferent nerve function to prevent OAB. Speculation on future techniques such as gene therapy can also be considered for treating OAB, because they may make it possible to access all of the genitourinary organs via minimally invasive techniques. Traditional anticholinergic therapies are limited in their effectiveness. There is great hope for future research and therapy for OAB and urinary incontinence.


Using sodium acetate for the synthesis of [Au(NHC)X] complexes.
The role of sodium acetate in the synthesis of [Au(NHC)Cl] complexes was examined. The use of this base was also investigated for the activation of C-H and S-H bonds by experimental and computational methods. The synthetic use of NaOAc to assemble these complexes is applicable to a wide range of NHCs and proceeds under air, under mild conditions and using technical grade green solvents.


Mycotoxins in milk for human nutrition: cow, sheep and human breast milk.
Mycotoxins are produced pre harvest by some molds and secreted into various food items of plant origin, such cereals, vegetables, spices, coffee and nuts. If the food items are not stored under adequate conditions, a post harvest contamination may also occur. Animals and humans take them up by food items and some of them are stored and accumulated in different tissues and organs, so that food of animal origin may be contaminated, too. Especially aflatoxin and ochratoxin are secreted into milk by consumers of contaminated food. Since milk represents the major food source of newborns and infants, they are notably exposed to these mycotoxins. This health risk for these individuals may be of particular importance, because their ability to metabolize these fungal toxic agents is not yet fully developed at this stage.


Oxygenation of 1-docosahexaenoyl lysophosphatidylcholine by lipoxygenases; conjugated hydroperoxydiene and dihydroxytriene derivatives.
Oxygenation of 1-docosahexaenoyl lysophosphatidylcholine (docosahexaenoyl-lysoPC) by soybean lipoxygenase-1 (LOX-1) or porcine leukocyte LOX was examined. The oxidized products were identified to be hydroperoxydocosahexaenoyl-lysoPC by UV and LC/MS spectrometric analyses. In SP-HPLC and chiral phase-HPLC analyses, the products from the oxygenation of docosahexaenoyl-lysoPC by soybean LOX-1 and porcine leukocyte LOX were found to contain hydroperoxide group mainly at C-17 and C-14, respectively with the S form as a major enantiomer. Next, the sequential exposure of docosahexaenoyl-lysoPC to soybean LOX-1 and porcine leukocyte LOX led to the formation of conjugated triene derivatives possessing a maximal absorption at 271 nm with shoulders at 262 and 281 nm. Based on MS-MS analysis, the conjugated triene derivatives were identified to be 10,17- or 16,17-dihydroxydocosahexaenoyl-lysoPC analogues, suggesting that the diols were produced mainly from hydrolysis of 16,17(S)-epoxide intermediate. In kinetic studies, docosahexaenoyl-lysoPC was more favorable than docosahexaenoic acid as substrate for soybean LOX-1 or leukocyte LOX. Taken together, it is proposed that docosahexaenoyl-lysoPC can be oxygenated as substrates for some lipoxygenases to form conjugated diene and/or triene derivatives.


Spontaneous formation of super water-repellent fractal surfaces in mixed wax systems.
Alkylketene dimers (AKDs) and triglyceride waxes form fractal surfaces spontaneously and show super water-repellent property. Spontaneous formation of fractal structures on their surfaces takes place when the meta-stable crystalline phase of the waxes transforms to the thermodynamically stable form of crystal. The triglyceride waxes form the meta-stable alpha-phase in whole specimen when solidified from their melt. In the case of AKD, on the other hand, only a small portion of the specimen solidifies in the meta-stable form of crystal. The surface of the AKD, however, becomes fractal in the whole part. We have, thus, examined the fractal structure formation in the mixed wax systems in which one wax forms fractal surfaces and the other one does not. In the stearic acid/tristearin mixed system as a typical one, the super water-repellent fractal surfaces form in the higher composition region of tristearin than that of the eutectic point in their mixture.


Efficacy of Rapid Rehabilitation Nursing in Postoperative Care in China: A Meta-Analysis.
Rapid rehabilitation nursing (RRN) has been increasingly adopted in China to improve patient outcomes following surgery. This systematic review and meta-analysis aimed to assess the impact of RRN on hospital stays, postoperative complications, postoperative pain, patients' quality of life (QOL), and patient satisfaction with nursing care compared to traditional nursing care. A systematic search of relevant databases, including PubMed, EMBASE, and Cochrane Library, was conducted to identify eligible studies. The standardized mean difference and 95% confidence intervals were calculated for continuous outcomes (hospital stays, postoperative pain, and QOL). Risk ratios (RRs) and 95% confidence intervals were used for dichotomous outcomes (postoperative complications, patient satisfaction with nursing care). Heterogeneity was assessed using the I2 statistic. Fixed-effects and random-effects models were calculated for each outcome measure. A total of 10 studies including 1,565 patients were included in the meta-analysis. Rapid rehabilitation nursing significantly reduced hospital stays and postoperative complications compared to traditional nursing care. Patients receiving RRN experienced lower postoperative pain scores and improved QOL, although the latter result was not statistically significant. Patient satisfaction with nursing care was significantly higher in the RRN group compared to traditional nursing care. Rapid rehabilitation nursing appears to be an effective approach for shortening hospital stays, reducing postoperative complications and postoperative pain, and increasing patient satisfaction with nursing care compared to traditional nursing care. The findings support the integration of RRN into clinical practice to enhance patient outcomes and patients' satisfaction with nursing care. Future research should focus on further investigating the impact of RRN on patients' QOL using larger, well-designed studies.


Simulated driving performance among daily and occasional cannabis users.
Daily cannabis users develop tolerance to some drug effects, but the extent to which this diminishes driving impairment is uncertain. This study compared the impact of acute cannabis use on driving performance in occasional and daily cannabis users using a driving simulator. We used a within-subjects design to observe driving performance in adults age 25 to 45 years with different cannabis use histories. Eighty-five participants (43 males, 42 females) were included in the final analysis: 24 occasional users (1 to 2 times per week), 31 daily users and 30 non-users. A car-based driving simulator (MiniSim™, National Advanced Driving Simulator) was used to obtain two measures of driving performance, standard deviation of lateral placement (SDLP) and speed relative to posted speed limit, in simulated urban driving scenarios at baseline and 30 min after a 15 min ad libitum cannabis smoking period. Participants smoked self-supplied cannabis flower product (15% to 30% tetrahydrocannabinol (THC). Blood samples were collected before and after smoking (30 min after the start of smoking). Non-users performed the same driving scenarios before and after an equivalent rest interval. Changes in driving performance were analyzed by repeated measures general linear models. Mean whole blood THC cannabinoids concentrations post smoking were use THC = 6.4 ± 5.6 ng/ml, THC-COOH = 10.9 ± 8.79 ng/mL for occasional users and THC = 36.4 ± 37.4 ng/mL, THC-COOH = 98.1 ± 90.6 ng/mL for daily users. On a scale of 0 to 100, the mean post-use score of subjective high was similar in occasional users and daily users (52.4 and 47.2, respectively). In covariate-adjusted analysis, occasional users had a significant increase in SDLP in the straight road segment from pre to post compared to non-users; non-users decreased by a mean of 1.1 cm (25.5 cm to 24.4 cm) while occasional users increased by a mean of 1.9 cm (21.7 cm to 23.6 cm; p = 0.02). Daily users also increased adjusted SDLP in straight road segments from baseline to post-use (23.2 cm to 25.0 cm), but the change relative to non-users was not statistically significant (p = 0.08). The standardized mean difference in unadjusted SDLP from baseline to post-use in the straight road segments comparing occasional users to non-users was 0.64 (95% CI 0.09 - 1.19), a statistically significant moderate increase. When occasional users were contrasted with daily users, the baseline to post changes in SDLP were not statistically significant. Daily users exhibited a mean decrease in baseline to post-use adjusted speed in straight road segments of 1.16 mph; a significant change compared to slight speed increases in the non-users and occasional users (p = 0.02 and p = 0.01, respectively). We observed a decrement in driving performance assessed by SDLP after acute cannabis smoking that was statistically significant only in the occasional users in comparison to the nonusers. Direct contrasts between the occasional users and daily users in SDLP were not statistically significant. Daily users drove slower after cannabis use as compared to the occasional use group and non-users. The study results do not conclusively establish that occasional users exhibit more driving impairment than daily users when both smoke cannabis ad libitum.


Utility of spine surgery: a comparison of common elective orthopaedic surgical procedures.
A 1-year prospective observational cohort study. To compare the utility before and 1 year after elective spine surgery with some other common orthopaedic surgical procedures. By using global measures like EQ-5D and SF-36 for the determination of the utility, the changes in quality of life, quality of life (QoL) after an intervention different diagnoses, and treatments can be compared. Total hip replacement (THR) has become almost golden standard in this respect. Seven hundred seventy-seven subjects with different common orthopaedic diagnoses scheduled for elective surgery were just before surgery and 1 year after surgery answering both EQ-5D and SF-36. Four groups with different spine diagnoses and procedures were formed and compared with 8 other diagnoses and treatment groups. Before surgery, subjects with spine diagnoses reported the lowest QoL of all diagnoses compared. Surgery for spinal stenosis, spondylolisthesis, and instability meant the largest improvement of all surgical interventions. Surgery for NHP gave a moderately good improvement, whereas surgery for CLBP only marginally improved those operated. Particularly THR but also TKR more or less completely normalized QoL but made it from a relatively high preoperative level. The greatest improvements after spine surgery, other surgical procedures, and different diagnoses were in the pain/discomfort domain. Spinal surgery in spinal stenosis, spondylolisthesis, and instability had in comparison to other types of elective orthopaedic surgery an outstanding better ability to improve the operated subject's health-related quality of life than other types of elective orthopaedic surgery. The utility of HNP surgery was somewhat lower and was rather marginal for those operated for nonspecific CLBP.


Gender inequality among medical, pharmaceutical and dental practitioners in French hospitals: Where have we been and where are we now?
Women are under-represented in senior academic and hospital positions in many countries. The authors aim to assess the place and the evolution of all appointed female and male health practitioners' working in French public Hospitals. Data of this observational study were collected from the National Management Centre (Centre National de Gestion) from 2015 up to January 1, 2020. First, the authors described demographic characteristics and specialties of all appointed medicine, pharmacy, and dentistry doctors' working as Hospital Practitioners, Associate Professors, and Full Professors in French General and University-affiliated Hospitals in 2020. Then, they retrospectively reported the annual incidence of new entrance according to gender and professional status from 1999 to 2019 thanks to the appointment date of all practitioners in activity between 2015 and 2020. In 2020, 51 401 appointed practitioners (49.7% of female) were in activity in French public hospitals with a large majority being medical doctors (92.4%) compared to pharmacists (6%) and dentists (1.6%). Women represented 52.5% of the Hospital Practitioners, 48.6% of the Associate Professors, and 22.0% of the Full Professors (p < 0.001). There were disparities between the rates of female Full Professors in medicine (20.6%), pharmacy (36.1%), and dentistry (44.3%, p < 0.001). Women were appointed Hospital Practitioners and Associate Professors earlier than men (respectively 37.1 versus 38.8 years, p < 0.001 and 36.1 versus 36.5 years, p = 0.04), and at a later age among Full Professors (43.7 versus 41.9 years, p < 0.001). Compared to men, the annual proportion of appointed women varied significantly between 1999 and 2019 from 47.6% to 60.4% for Hospital Practitioners, from 50.0% to 44.6% for Associate Professors, and from 11.2% to 33.3% for Full Professors (p < 0.001 for trend). Although more and more women occupy positions in French hospitals, there is still a gender gap regarding access to Full Professor status in medicine and pharmacy, but not in dentistry. The disparity in numbers makes comparison difficult. Despite a trend towards gender equality during the last twenty years, it has not yet been achieved regarding access to the highest positions.


Ultra-stable 1064-nm neodymium-doped yttrium aluminum garnet lasers with 2.5 × 10-16 frequency instability.
Cavity-stabilized ultra-stable optical oscillators are one of the core ingredients in the ground-based or spaceborne precision measurements such as optical frequency metrology, test of special relativity, and gravitational wave observation. We report in detail the development of two ultra-stable systems based on 1064-nm neodymium-doped yttrium aluminum garnet lasers and 20-cm optical cavities. The optical cavities adopt ultra-low-loss silica mirrors with compensating rings. An electro-optic crystal with a wedged angle is used to reduce the residual amplitude modulation. Using two-stage thermal control, long-term stabilities of 100 µK are achieved for the outer wall of the vacuum chamber housing the optical cavity. Two additional thermal shields increased the time constant of the optical cavities to 70 h. By operating the optical cavity at the temperature of zero coefficient of thermal expansion, the frequency stability reaches 2.5 × 10-16 at 10 s averaging time and remains below 5 × 10-16 with an extended time of 1000 s after removing the first- and second-order drifts. The dependence of the laser linewidth on the measurement time is tested against a simplified theoretical model.


The Direct Cost of Managing a Rare Disease: Assessing Medical and Pharmacy Costs Associated with Duchenne Muscular Dystrophy in the United States.
A Duchenne muscular dystrophy (DMD) cohort was identified using a claims-based algorithm to estimate health care utilization and costs for commercially insured DMD patients in the United States. Previous analyses have used broad diagnosis codes that include a range of muscular dystrophy types as a proxy to estimate the burden of DMD. To estimate DMD-associated resource utilization and costs in a sample of patients identified via a claims-based algorithm using diagnosis codes, pharmacy prescriptions, and procedure codes unique to DMD management based on DMD clinical milestones. DMD patients were selected from a commercially insured claims database (2000-2009). Patients with claims suggestive of a non-DMD diagnosis or who were aged 30 years or older were excluded. Each DMD patient was matched by age, gender, and region to controls without DMD in a 1:10 ratio (DMD patients n = 75; controls n = 750). All-cause health care resource utilization, including emergency department, inpatient, outpatient, and physician office visits, and all-cause health care costs were examined over a minimum 1-year period. Costs were computed as total health-plan and patient-paid amounts of adjudicated medical claims (in annualized U.S. dollars). The average age of the DMD cohort was 13 years. Patients in the DMD cohort had a 10-fold increase in health care costs compared with controls ($23,005 vs. $2,277, P < 0.001). Health care costs were significantly higher for the DMD cohort across age strata and, in particular, for DMD patients aged 14-29 years ($40,132 vs. $2,746, P < 0.001). In the United States, resource use and medical costs of DMD are substantial and increase with age. Funding for this study (GHO-10-4441) was provided by GlaxoSmithKline (GSK). Optum was contracted by GSK to conduct the study. Thayer was an employee of Optum Health Economics and Outcomes Research at the time of this study and was not compensated for her participation as an author of this manuscript. Bell is an employee and shareholder of GSK. McDonald has been a consultant for GSK, Sarepta, PTC Therapeutics, Biomarin, and Catabasis on clinical trials regarding Duchenne muscular dystrophy clinical trial design, endpoint selection, and data analysis; Mitobridge for drug development; and Eli Lilly as part of a steering committee for clinical trials. Study concept and design were contributed primarily by Bell, along with Thayer and McDonald. Thayer collected the data, and data interpretation was performed by Thayer and Bell, along with McDonald. The manuscript was written by Thayer and Bell, along with McDonald, and revised by all the authors.


[Renal cell carcinoma with venous invasion: therapy--prognosis].
Between 1966 and 1988 a total of 406 patients with renal cell carcinoma (RCC) was treated at our department. Among these 51 patients were found to have gross renal vein involvement, in 21 cases with extension into V. cava. In one case the tumor-thrombus has been reaching the level of the hepatic veins, in two cases the right atrium. MR and sonography, especially echocardiography, seems to be the best choice of diagnostics. Because of the advanced stage of disease only 21 patients were selected for operative treatment, in two cases under extracorporal circulation. Prognosis seems to be very poor, 11 patients (more than 50%) died within 2 years after diagnosis. But still the high risk and the great expense of tumor nephrectomy and thrombectomy in such cases, even with substitution of extracorporal circulation, seems to be justified by the actuarial 5-year survival rate of 20%.


Sprayable microencapsulated sex pheromone formulation for mating disruption of oriental fruit moth (Lepidoptera: Tortricidae) in Australian peach and pear orchards.
Areawide mating disruption treatments have been effective in controlling infestation of oriental fruit moth, Grapholita molesta (Busck) (Lepidoptera: Tortricidae), in Australian pome and stone fruit orchards. Although successful, the areawide mating disruption program has been an expensive approach by using hand-applied Isomate dispensers. Sprayable microencapsulated (MEC) pheromone formulations that can be applied with standard spray equipment could substantially reduce the cost of application. Field trials conducted during two consecutive seasons (2002-2004) demonstrated that monthly applications of MEC-OFM phase V (3M Canada, London, Ontario, Canada) at a rate of 125 ml/ha (37.1 g [AI]/ha) in replicated 2-ha blocks of both peaches and pears reduced oriental fruit moth shoot tip and fruit damage as effectively as a single application of Isomate OFM Rosso hand-applied dispensers (500 dispensers per ha) and as or more effectively than standard broad-spectrum insecticide sprays. Fruit protection was achieved despite high oriental fruit moth population densities in both crops as measured by moth catches in terpinyl acetate food and pheromone traps. Similar numbers of oriental fruit moths were captured among all treatments in food traps but captures of males in pheromone traps were disrupted (96-99%) in pheromone-treated blocks relative to controls. The results of this study suggest that microencapsulated formulations of pheromone could be effectively used in areawide mating disruption programs for oriental fruit moth in Australia as a cost-saving alternative to reservoir-style dispensers requiring labor-intensive hand application.


The processing of animacy in noun-classifier combinations in reading Korean: An ERP study.
A key issue in the area of language processing is the mechanism underlying the processing of animacy information during sentence comprehension. In this ERP study, we investigated the temporal dynamics of animacy processing in Korean noun-classifier combinations that do not involve verb-noun thematic processing. We manipulated semantic and animacy relationships between nouns and their following classifiers, and there were three conditions in our experiment: (a) correct, (b) semantic mismatch, or (c) animacy mismatch. The results showed that both noun-classifier mismatch conditions evoked a biphasic N400-P600 effect, but there was no P600 difference between the two mismatch conditions. However, further analyses indicated that the animacy mismatch condition evoked a less negative-going waveform than the semantic mismatch condition in the 400-500 ms time window. Our findings suggest that the brain processes animacy information differently from other semantic features in noun-classifier combinations in Korean, and additional animacy mismatch blocked further fine-grained semantic processing. The ERP evidence also suggests that the role of animacy in sentence comprehension varies according to language type and sentence structure. Whether animacy participates in the construction of verb-noun thematic relationships in sentences may be an important factor that influences the neural patterns of animacy processing in language comprehension.


[Positron emission tomography in head and neck squamous cell carcinomas].
18F-Fluorodeoxyglucose positron emission tomography (PET) is an imaging modality which is becoming increasingly esential in oncology, especially in the management of head and neck squamous cell carcinomas (SCC). The most common uses of the PET are listed in this thematic study: initial staging, cervical lymph node metastases from an unknown primary tumor and post-therapeutic follow-up. The advantages and drawbacks of this imaging tool are exposed here according to both our experience and data from the literature. Decision schemes are suggested for each use so as to optimize the use of this imaging modality in the management of these SCC. Other fields of application for the PET are mentioned, such as the in-progress evaluation of response to chemotherapy, the interest of this imaging tool in radiotherapy as well as current biochemical developments concerning new tracers.


Electrostatic precursors to granular slip events.
It has been known for over a century that electrical signals are produced by material failure, for example during crack formation of crystals and glasses, or stick-slip motion of liquid mercury on glass. We describe here new experiments revealing that slip events in cohesive powders also produce electrical signals, and remarkably these signals can appear significantly in advance of slip events. We have confirmed this effect in two different experimental systems and using two common powdered materials, and in a third experiment we have demonstrated that similar voltage signals are produced by crack-like defects in several powdered materials.


Effect of Na+ and K+ on Cl- distribution in guinea-pig vas deferens smooth muscle: evidence for Na+, K+, Cl- co-transport.
1. Smooth muscle cells of the guinea-pig vas deferens after Cl- depletion actively reaccumulate ions to a level many times higher than that predicted by a passive distribution, even when anion exchange (largely responsible for Cl- movements in this preparation) is inhibited by DIDS (4,4'-diisothiocyanostilbene-2,2'-disulphonic acid). The cells therefore must possess a second mechanism for Cl- accumulation. We have now investigated the ionic requirement of this mechanism using a combination of ion analysis, 36Cl fluxes and direct measurement of the intracellular Cl- activity (aiCl). 2. In the steady state, the Cl- content of tissues was 12-16% less in Na(+)-free solution than in normal Krebs solution. 3. Loss of 36Cl into Cl(-)-free solution was slowed by the absence of Na+ and accelerated on its readdition. Uptake of 36Cl by Cl(-)-depleted tissues was also reduced in the absence of extracellular Na+, particularly at longer time intervals as uptake reached completion. These effects occurred in the presence and absence of CO2-HCO3- and in the presence of DIDS. 4. The initial rate of rise of aiCl on readdition of Cl- to Cl(-)-depleted cells was not significantly affected by the absence of Na+ in the presence of a functional anion exchange, but aiCl stabilized at a lower value than in normal solution. Readdition of Na+ stimulated a rise in aiCl to the control level. Removal and readdition of K+ under these conditions had negligible effects. 5. When anion exchange was inhibited by the presence of DIDS, removal and readdition of Na+ caused, respectively, a marked inhibition and stimulation of the rise in aiCl during Cl- reaccumulation. Under these conditions removal and readdition of K+ had similar effects. 6. The results suggest that Na+, K+, Cl- co-transport is involved in transmembrane movements of Cl- at least when the anion exchange mechanism is blocked. 7. The possibility that the marked effects of changes in external Na+ on transmembrane Cl- movements in the presence of a functional anion exchange mechanism are caused by secondary effects due to changes in intracellular pH as well as to suppression of Na+, K+, Cl- co-transport is discussed.


Spontaneous subarachnoid hemorrhage due to ruptured cavernous internal carotid artery aneurysm after medical prolactinoma treatment.
Aneurysms of the cavernous segment of the internal carotid artery (ICA) are believed to have a low risk of subarachnoid haemorrhage (SAH), given the confines of the dural rings and the anterior clinoid process. The risk may be greater when the bony and dural protection has been eroded. We report a case of spontaneous SAH from rupture of a cavernous ICA aneurysm in a patient whose large prolactinoma had markedly decreased in size as the result of cabergoline treatment. After passing a balloon test occlusion, the patient underwent successful endovascular vessel deconstruction. This case suggests that an eroding skull base lesion may distort normal anterior cranial base anatomy and allow communication between the cavernous ICA and subarachnoid space. The potential for SAH due to cavernous ICA aneurysm rupture should be recognised in patients with previous pituitary or other skull base lesions adjacent to the cavernous sinus.


Novel methods to optimize the effects of transcranial direct current stimulation: a systematic review of transcranial direct current stimulation patents.
Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that has been extensively studied. While there have been initial positive results in some clinical trials, there is still variability in tDCS results. The aim of this article is to review and discuss patents assessing novel methods to optimize the use of tDCS. A systematic review was performed using Google patents database with tDCS as the main technique, with patents filling date between 2010 and 2015. Twenty-two patents met our inclusion criteria. These patents attempt to address current tDCS limitations. Only a few of them have been investigated in clinical trials (i.e., high-definition tDCS), and indeed most of them have not been tested before in human trials. Further clinical testing is required to assess which patents are more likely to optimize the effects of tDCS. We discuss the potential optimization of tDCS based on these patents and the current experience with standard tDCS.


Predictive value of serum alkaline DNase activity variations in treatment of head and neck cancer.
The aim of this study was to evaluate the variation in serum alkaline DNase activity (SADA) as a means of therapeutic monitoring in patients with head and neck cancer. Blood samples from 40 patients were collected before, during, and some weeks up to months after therapy. A decrease in SADA during treatment was usually associated with a primary clinical response, while no decrease indicated non-response to therapy. In patients with complete tumor regression the initial decrease of SADA was usually followed by an increase exceeding the initial level. A similar increase was not observed in patients with tumor progression.


[Which medical errors do general practitioners make? Data from the Expert Arbitration and Advisory Board of the Baden-Württemberg State Medical Association].
In Germany, medical error reporting systems are well established. They collect information reported principally by physicians. Systematic data collection concerning medical errors is also performed by expert arbitration and advisory boards of the German State Medical Associations. Data base MERS (Medical Error Reporting System); cases from the Expert Arbitration and Advisory Board of the State Baden-Württemberg from the years 2004-2011 (8,042 cases) were evaluated as follows: extraction of the cases from general practitioners (n=307, 4%); categorisation of the type of error and degree of severity; classification according to ICD-10 (International Classification of Diseases); overview of confirmed cases including commentaries of the above board; logistic regression analysis of factors potentially associated with confirmed cases. In 26% (n=80) the board confirmed medical errors. 55% of the errors were assigned to the category "diagnosis" (n=44), 21% to "general therapy" (n=17), 8% to "operative therapy" ("minor surgical operations") (n=6) and 10% to "injections" (n=8). 29% of cases (n=23) were associated with permanent damage or death. The majority of cases could be assigned to ICD-10 categories "I" (cardiovascular system, n=20) and "S-T" or "V-Y" (consequences of external causes or external causes of morbidity and mortality, n=34). No significant associations were found by logistic regression analysis. The rate of confirmed cases corresponds with the rate of all medical disciplines. The presented overview is illustrative and may be of help to avoid errors by using it for continuing medical education.


Recognition of RNA polymerase II carboxy-terminal domain by 3'-RNA-processing factors.
During transcription, RNA polymerase (Pol) II synthesizes eukaryotic messenger RNA. Transcription is coupled to RNA processing by the carboxy-terminal domain (CTD) of Pol II, which consists of up to 52 repeats of the sequence Tyr 1-Ser 2-Pro 3-Thr 4-Ser 5-Pro 6-Ser 7 (refs 1, 2). After phosphorylation, the CTD binds tightly to a conserved CTD-interacting domain (CID) present in the proteins Pcf11 and Nrd1, which are essential and evolutionarily conserved factors for polyadenylation-dependent and -independent 3'-RNA processing, respectively. Here we describe the structure of a Ser 2-phosphorylated CTD peptide bound to the CID domain of Pcf11. The CTD motif Ser 2-Pro 3-Thr 4-Ser 5 forms a beta-turn that binds to a conserved groove in the CID domain. The Ser 2 phosphate group does not make direct contact with the CID domain, but may be recognized indirectly because it stabilizes the beta-turn with an additional hydrogen bond. Iteration of the peptide structure results in a compact beta-spiral model of the CTD. The model suggests that, during the mRNA transcription-processing cycle, compact spiral regions in the CTD are unravelled and regenerated in a phosphorylation-dependent manner.


A model for pregnancy rates after IVF-ET in patients with infertility and endometriosis.
The objective of the present study was to examine the clinical factors influencing the pregnancy rate of infertile patients with endometriosis and establish a predictive model. This study included 158 patients (158 cycles) with infertility and endometriosis who underwent laparoscopic surgery, and in vitro fertilization and embryo transfer (IVF-ET) were evaluated retrospectively between January 2019 and December 2020. The clinical factors in the pregnant and non-pregnant group were analyzed by univariate analysis. Statistically significant variables were subsequently used for multivariate logistic regression to establish the prediction model. Multivariate logistic regression analyses showed that GnRH-a treatment after operation (OR, 6.562; 95% CI: 2.782-15.477; p<0.01), ASRM stage (OR, 0.218; 95% CI: 0.093-0.509; p<0.05), the number of high-quality transferred embryos (OR, 3.155; 95% CI: 1.647-6.047; p<0.05) were independently associated with successful pregnancy. The area under the curve (AUC) of the prediction model was 0.774 (95% CI: 0.700-0.847). According to Hosmer-Lemeshow, the model was well fitted (p>0.05). We applied the bootstrapping method to internal validation, and the result showed that the pregnancy rate predicted by the model and the real data were consistent. The models for predicting pregnancy rates after IVF-ET in infertility and endometriosis patients showed high accuracy. The effective methods to increase the number of high-quality embryos need further study.


Two or three screws for fixation of femoral neck fractures?
This study compares the stability of 3 cannulated cancellous lag screws with that of 2 cannulated cancellous lag screws for fixation of subcapital femoral neck fractures. Using 10 matched pairs of human cadaveric femurs, subcapital femoral neck osteotomies were created, reduced, and then randomized to 1 of the 2 fixation methods. The constructs were tested with anterior loading to 500 N, incremental axial loading from 100 N to 1000 N, and cyclic loading at 1000 N. The specimens stabilized using 3 screws showed greater resistance to anterior loading, less inferior femoral head displacement, and less superior gapping at the osteotomy site. Although 2 screws may be an acceptable fixation method for this fracture type, the addition of a third screw provides supplemental stability and appears justified.


Another look at co-treatment with growth hormone and human menopausal gonadotrophins in poor ovarian responders.
The objective of this study was to evaluate whether a combined human growth hormone (HGH) and human menopausal gonadotrophin (HMG) treatment can improve ovulation induction in poor ovarian responders. Ten patients aged 28-43 years and requiring > 25 ampoules of HMG for ovulation were admitted to the study. Pituitary growth hormone reserve was evaluated by clonidine stimulation and insulin tolerance tests before commencement of treatment. The patients underwent one treatment cycle with D-tryptophan-6-luteinizing hormone-releasing hormone (D-Trp6-LHRH) and HMG and another cycle with D-Trp6-LHRH, HMG and HGH. Serum HGH, insulin-like growth factor (IGF)-I and oestradiol were measured throughout the two treatment cycles and follicular maturation was assessed by ultrasonographic studies. All patients tested showed no elevation of their serum HGH concentration during a clonidine test, but showed an adequate response during insulin tolerance tests. No significant difference was found in the number of HMG ampoules, duration of treatment, number of leading follicles, and serum oestradiol concentration between the two treatment cycles. Co-treatment with HGH and HMG did not improve ovarian performance in poor ovarian responders. No correlation was found between the results of HGH pituitary function tests and the ovarian response to gonadotrophins.


Workplace interventions associated with influenza vaccination coverage among health care personnel in ambulatory care settings during the 2013-2014 and 2014-2015 influenza seasons.
Vaccination of health care personnel (HCP) can reduce influenza-related morbidity and mortality among HCP and their patients. This study investigated workplace policies associated with influenza vaccination among HCP who work in ambulatory care settings without influenza vaccination requirements. Data were obtained from online surveys conducted during April 2014 and April 2015 among nonprobability samples of HCP recruited from 2 preexisting national opt-in Internet panels. Respondents were asked about their vaccination status and workplace policies and interventions related to vaccination. Logistic regression models were used to assess the independent associations between each workplace intervention and influenza vaccination while controlling for occupation, age, and race or ethnicity. Among HCP working in ambulatory care settings without a vaccination requirement (n = 866), 65.7% reported receiving influenza vaccination for the previous influenza season. Increased vaccination coverage was independently associated with free onsite vaccination for 1 day (prevalence ratio [PR], 1.38; 95% confidence interval [CI], 1.07-1.78 or >1 day PR, 1.58; 95% CI, 1.29-1.94) and employers sending personal vaccination reminders (PR, 1.20; 95% CI, 0.99-1.46). Age ≥65 years (PR, 1.30; 95% CI, 1.07-1.56) and working as a clinical professional (PR, 1.26; 95% CI, 1.06-1.50) or clinical nonprofessional (PR, 1.28; 95% CI, 1.03-1.60) were also associated with higher coverage. Vaccination coverage increased with increasing numbers of workplace interventions. Implementing workplace vaccination interventions in ambulatory care settings, including free onsite influenza vaccination that is actively promoted, could help increase influenza vaccination among HCP.


The effect of hearing aid signal-processing schemes on acceptable noise levels: perception and prediction.
The acceptable noise level (ANL) test determines the maximum noise level that an individual is willing to accept while listening to speech. The first objective of the present study was to systematically investigate the effect of wide dynamic range compression processing (WDRC), and its combined effect with digital noise reduction (DNR) and directional processing (DIR), on ANL. Because ANL represents the lowest signal-to-noise ratio (SNR) that a listener is willing to accept, the second objective was to examine whether the hearing aid output SNR could predict aided ANL across different combinations of hearing aid signal-processing schemes. Twenty-five adults with sensorineural hearing loss participated in the study. ANL was measured monaurally in two unaided and seven aided conditions, in which the status of the hearing aid processing schemes (enabled or disabled) and the location of noise (front or rear) were manipulated. The hearing aid output SNR was measured for each listener in each condition using a phase-inversion technique. The aided ANL was predicted by unaided ANL and hearing aid output SNR, under the assumption that the lowest acceptable SNR at the listener's eardrum is a constant across different ANL test conditions. Study results revealed that, on average, WDRC increased (worsened) ANL by 1.5 dB, while DNR and DIR decreased (improved) ANL by 1.1 and 2.8 dB, respectively. Because the effects of WDRC and DNR on ANL were opposite in direction but similar in magnitude, the ANL of linear/DNR-off was not significantly different from that of WDRC/DNR-on. The results further indicated that the pattern of ANL change across different aided conditions was consistent with the pattern of hearing aid output SNR change created by processing schemes. Compared with linear processing, WDRC creates a noisier sound image and makes listeners less willing to accept noise. However, this negative effect on noise acceptance can be offset by DNR, regardless of microphone mode. The hearing aid output SNR derived using the phase-inversion technique can predict aided ANL across different combinations of signal-processing schemes. These results suggest a close relationship between aided ANL, signal-processing scheme, and hearing aid output SNR.


Student nurse attitudes towards homeless clients: a challenge for education and practice.
The purpose of this research was to describe attitudes of nursing students (and paramedic officers) towards marginalized clients. Convenience quota sampling in a major health faculty was employed. Students participated on a voluntary basis. A 58-item Likert scale, developed by the authors, assessed the student nurses' attitudes. In general, attitudes towards homeless clients were neutral; detailed analyses, however, revealed that student nurses would decline to care for homeless clients in various situations. Personal experience with homeless patients and positive attitudes of nurses significantly contributed to increased quality of care and equality of treatment for homeless clients. Certain student nurse behaviors warrant immediate attention to prevent marginalized patients from being exposed to unfair, inaccessible and biased nursing care. Based on our results, we recommend that further research attention be paid to the role of ethics education and faculty behaviors, as faculty members serve as role models for professionalization.


Healthcare utilization by children with asthma displaced by Hurricane Katrina.
To assess the performance of TexKat, the largest Hurricane Katrina Medicaid Emergency Waiver, in providing care to asthmatic children. Medicaid enrollment and encounter data for 2004 and 2006 from Louisiana and Texas were analyzed in a pre-post comparison. Changes in utilization by children in the waiver were compared to changes in utilization by children in Medicaid in three control groups: children in Louisiana counties that were designated as a disaster assistance area but who were not displaced; children in Louisiana counties that were not designated as a disaster assistance area, and children in Texas. The analysis included prescriptions for controller and quick-relief medications as well as encounters in inpatient, emergency, outpatient, and office settings. The sample proportion of TexKat enrollees who had a prescription filled for controller medications fell from 0.37 to 0.28 between 2004 and 2006. By contrast, the sample proportions for the three control groups were relatively unchanged or increased. The inferential analysis indicated that the 2004-2006 change in proportions for the TexKat group differed from the changes for each of the three control groups (p-value < 0.001). For office and emergency department visits, the 2004-2006 decreases in both the proportion of subjects with a visit and the average number of visits for the TexKat group were greater than the changes for the control groups (p-value < 0.001). While TexKat appears to have largely been successful in preventing extreme utilization disruptions, the analysis suggests that children in the program may have received inadequate care.


MRI-Based Quantitative Osteoporosis Imaging at the Spine and Femur.
Osteoporosis is a systemic skeletal disease with a high prevalence worldwide, characterized by low bone mass and microarchitectural deterioration, predisposing an individual to fragility fractures. Dual-energy X-ray absorptiometry (DXA) has been the clinical reference standard for diagnosing osteoporosis and for assessing fracture risk for decades. However, other imaging modalities are of increasing importance to investigate the etiology, treatment, and fracture risk. The purpose of this work is to review the available literature on quantitative magnetic resonance imaging (MRI) methods and related findings in osteoporosis at the spine and proximal femur as the clinically most important fracture sites. Trabecular bone microstructure analysis at the proximal femur based on high-resolution MRI allows for a better prediction of osteoporotic fracture risk than DXA-based bone mineral density (BMD) alone. In the 1990s, T2 * mapping was shown to correlate with the density and orientation of the trabecular bone. Recently, quantitative susceptibility mapping (QSM), which overcomes some of the limitations of T2 * mapping, has been applied for trabecular bone quantifications at the spine, whereas ultrashort echo time (UTE) imaging provides valuable surrogate markers of cortical bone quantity and quality. Magnetic resonance spectroscopy (MRS) and chemical shift encoding-based water-fat MRI (CSE-MRI) enable the quantitative assessment of the nonmineralized bone compartment through extraction of the bone marrow fat fraction (BMFF). Furthermore, CSE-MRI allows for the differentiation of osteoporotic vs. pathologic fractures, which is of high clinical relevance. Lastly, advanced postprocessing and image analysis tools, particularly considering statistical parametric mapping and region-specific BMFF distributions, have high potential to further improve MRI-based fracture risk assessments at the spine and hip. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY STAGE: 2.


How did Latinxs near the U.S.-Mexico border fare during the COVID-19 pandemic? A snapshot of anxiety, depression, and posttraumatic stress symptoms.
The current study documented levels of anxiety, depression, posttraumatic stress, and COVID-19 fears and impacts among Latinxs living near the U.S.-Mexico border during the COVID-19 pandemic. Participants of this cross-sectional study were 305 Latinx adults living in the Rio Grande Valley (RGV) who completed an online survey between June and November 2020. About half of participants scored above the cut-off for anxiety (50.2%; GAD-7 scores ≥10) and depression (48.8%; PHQ-9 scores ≥10), and more than a quarter of participants showed clinical levels of posttraumatic stress (27.3%; PCL-5 scores ≥31). Latinxs reported on average 22 types of negative pandemic life impacts on the Epidemic-Pandemic Impacts Inventory. Endorsement of mental health symptoms, severity of COVID-19 fears, and COVID-related life impacts varied based on several demographic characteristics including gender, marital status, educational attainment, employment, income, insurance coverage, vulnerability to COVID-19, and essential worker status. Overall, the cross-sectional results of this study revealed that RGV Latinx residents experienced high levels of psychological distress during the pandemic. Results suggest that Latinx women were most affected by the psychological consequences of the pandemic. More research is needed with communities living near the U.S.-Mexico border as they may be particularly vulnerable to mental health problems during the pandemic.


Impact of alcohol consumption among patients in hepatitis C virus treatment.
Recent studies have questioned the recommendation of abstinence from alcohol for at least 6 months for alcoholic patients to be treated for hepatitis C. The present study aimed to assess the impact of alcohol consumption among patients undergoing hepatitis C treatment. In this cross-sectional study, 121 patients [78 (64.5%) men; 28-70 years] were evaluated. They were divided as follows: patients who consumed <12 g of ethanol/day throughout life (Group 1), 12-59 g/day (Group 2) and ≥60 g/day (Group 3). Patients were treated with pegyla-ted-interferon plus ribavirin. These three groups could not be distinguished in terms of the severity of liver fibrosis and frequency of HCV genotype-1 infection. In Group 3, treatment discontinuation (32.4%) was higher than in the Group 1 (9.4%) or Group 2 (0%), it was higher among patients who drank during treatment (66.7% vs 21.4%) and among those who had not been abstinent for at least 6 months (72.7% vs 15.4%). Moderate alcohol drinkers showed good adherence and did not discontinue the treatment. The frequencies of sustained viral response among patients in Group 3 (44.4%) were similar to those in Group 1 (61%) and Group 2 (68.4%). Heavy drinkers more often discontinued treatment for hepatitis C, but those that received this treatment had acceptable sustained viral response rates. These results suggest that heavy drinkers should not be systematically excluded from the treatment, but they should be monitored to avoid drinking and abandoning treatment, mainly those who have not been abstinent for at least 6 months.


Dynamics of microvascular oxygen pressure during rest-contraction transition in skeletal muscle of diabetic rats.
Type I diabetes reduces dramatically the capacity of skeletal muscle to receive oxygen (QO(2)). In control (C; n = 6) and streptozotocin-induced diabetic (D: n = 6, plasma glucose = 25.3 +/- 3.9 mmol/l and C: 8.3 +/- 0.5 mmol/l) rats, phosphorescence quenching was used to test the hypothesis that, in D rats, the decline in microvascular PO(2) [Pm(O(2)), which reflects the dynamic balance between O(2) utilization (VO(2)) and QO(2)] of the spinotrapezius muscle after the onset of electrical stimulation (1 Hz) would be faster compared with that of C rats. Pm(O(2)) data were fit with a one or two exponential process (contingent on the presence of an undershoot) with independent time delays using least-squares regression analysis. In D rats, Pm(O(2)) at rest was lower (C: 31.2 +/- 3.2 mmHg; D: 24.3 +/- 1.3 mmHg, P < 0.05) and at the onset of contractions decreased after a shorter delay (C: 13.5 +/- 1.8 s; D: 7.6 +/- 2.1 s, P < 0.05) and with a reduced mean response time (C: 31.4 +/- 3.3 s; D: 23.9 +/- 3.1 s, P < 0.05). Pm(O(2)) exhibited a marked undershoot of the end-stimulation response in D muscles (D: 3.3 +/- 1.1 mmHg, P < 0.05), which was absent in C muscles. These results indicate an altered VO(2)-to-QO(2) matching across the rest-exercise transition in muscles of D rats.


Revisiting cognitive rehearsal as an intervention against incivility and lateral violence in nursing: 10 years later.
Ten years ago, Griffin wrote an article on the use of cognitive rehearsal as a shield for lateral violence. Since then, cognitive rehearsal has been used successfully in several studies as an evidence-based strategy to address uncivil and bullying behaviors in nursing. In the original study, 26 newly licensed nurses learned about lateral violence and used cognitive rehearsal techniques as an intervention for nurse-to-nurse incivility. The newly licensed nurses described using the rehearsed strategies as difficult, yet successful in reducing or eliminating incivility and lateral violence. This article updates the literature on cognitive rehearsal and reviews the use of cognitive rehearsal as an evidence-based strategy to address incivility and bullvina behaviors in nursing.


Heterogeneity in spatial P-distribution and foraging capability by Zea mays: effects of patch size and barriers to restrict root proliferation within a patch.
Localized proliferation of roots in nutrient-enriched patches seems to be an adaptive response in many plants, but its function is still debatable. To understand the efficiency and limitation of foraging behaviour, the impact of patch size and the presence or absence of a barrier to root proliferation within phosphorus (P)-enriched patches was examined. In pots filled with P-poor soil, six treatments of heterogeneous P supply were prepared: three patch sizes with or without a root barrier between patches. In addition, a homogeneous P supply treatment was also prepared. Irrespective of these treatments, each pot received the same total amount of P. Maize (Zea mays) was grown in each pot for 45 d in a greenhouse. P content and biomass were greatest in plants grown in the largest patch due to successful root proliferation, and were higher in the presence of a root barrier. Interestingly, plants preferentially developed adventitious nodal roots projecting from the stem into the P-enriched soil, particularly in the largest patch with a root barrier. Removal of the barrier reduced the P-uptake capacity per unit root surface area or volume in P-enriched patches, revealing that the P-uptake capacity per root can be suppressed even in P-rich soil if other portions on the root axis encounter P-poor conditions. The results suggest that the efficiency of root morphological plasticity is largely determined by the size of the P-enriched patch. Furthermore, the results imply a novel aspect of P-uptake physiology that roots in heterogeneous P cannot demonstrate their potential capacity, as would be observed in roots encountering P continuously; this effect is probably mediated by an internal root factor.


Contrasting effects of captopril and nifedipine in normotensive patients with incipient diabetic nephropathy.
Microalbuminuria is a reliable predictor of the eventual development of overt diabetic nephropathy and blood pressure is known to accelerate the course of this nephropathy. In the present studies, the effect of a 6-week treatment by placebo (n = 7), nifedipine (n = 7) and captopril (n = 8) on renal function and urinary excretion of albumin (UAE) was investigated in normotensive, insulin-dependent, diabetic patients with incipient nephropathy (UAE greater than 15 micrograms/min). No change in arterial pressure, renal function or UAE was observed in the placebo group. In response to captopril and nifedipine, mean arterial pressure decreased slightly and similarly in both groups. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) increased to a similar extent in the nifedipine group, thus resulting in no change in filtration fraction (FF). In response to captopril, GFR was unchanged whilst ERPF increased; as a consequence FF decreased. Opposite changes in UAE were observed in response to the two treatments; UAE decreased by 40% in the captopril group and by 40% in nifedipine-treated patients. These results indicate that intrarenal changes may be crucial with respect to the effect of therapy on UAE. It is suggested that only agents which reduce FF and probably intraglomerular capillary pressure, such as converting enzyme inhibitors, alter UAE and may possibly interfere with the course of incipient diabetic nephropathy in normotensive patients.


Shared cell adhesion molecule (CAM) homology domains point to CAMs signalling via FGF receptors.
A number of cell adhesion molecules (CAMs) promote neurite outgrowth following transfection and expression in a variety of monolayer cells. We have shown that N-cadherin, L1 and some isoforms of NCAM can stimulate neurite outgrowth from PC12 cells and primary neurons following transfection and expression at physiologically relevant levels in NIH-3T3 cells. A number of observations suggest that these CAMs stimulate neurite outgrowth by activating a convergent second messenger pathway in neurons rather than by modulating adhesion per se, and that an early or initial step in the pathway involves activation of a tyrosine kinase. The observation that the fibroblast growth factor receptor (FGFR) contains an evolutionarily conserved sequence with homology to the above CAMs (the CAM homology domain-CHD) points to the possibility that CAMs might interact with, and signal via, FGFR tyrosine kinases. This hypothesis has been substantiated by a number of independent experimental tests. We present a speculative model in which the evolutionary conservation of a pair of complementary binding motifs can account for a direct binding interaction between FGFR and the above three CAMs.


Tooth-supported stud-retained prostheses: three case reports.
The use of teeth as overdenture abutments is a common form of treatment. However, most roots are used only fur support. Simple stud precision attachments will also aid the retention of the prosthesis. This article presents three different cases where studs have been used to help retain removable prostheses.


Outcomes of a community-based lifestyle programme for adults with diabetes or pre-diabetes.
INTRODUCTION Diabetes, a long-term condition increasing in prevalence, requires ongoing healthcare management. Exercise alongside lifestyle education and support is effective for diabetes management. AIM To investigate clinical outcomes and acceptability of a community-based lifestyle programme for adults with diabetes/prediabetes at programme completion and 3-month follow-up. METHODS The 12-week community programme included twice-weekly sessions of self-management education and exercise, supervised by a physiotherapist, physiotherapy students and a nurse. Clinical outcomes assessed were cardiorespiratory fitness, waist circumference, exercise behaviour and self-efficacy. A standardised evaluation form was used to assess programme acceptability. RESULTS Clinically significant improvements were found from baseline (n = 36) to programme completion (n = 25) and 3-months follow-up (n = 20) for the six minute walk test (87 m (95%CI 65-109; p ≤ 0.01), 60 m (95%CI 21-100; p ≤ 0.01)), waist circumference (-3 cm (95%CI -6 to -1), -3 cm (95%CI -6 to 1)), exercise behaviour (aerobic exercise 53 min/week (95%CI 26 to 81; p ≤ 0.01), 71 min/week (95%CI 25 to 118; p ≤ 0.01)) and self-efficacy (0.7 (95%CI -0.2 to 1.6), 0.8 (95%CI 0.04 to 1.5)). Good programme acceptability was demonstrated by themes suggesting a culturally supportive, motivating, friendly, informative atmosphere within the programme. The attrition rate was 30% but there were no adverse medical events related to the programme. DISCUSSION The programme was safe and culturally acceptable and outcomes demonstrated clinical benefit to participants. The attrition rate was largely due to medical reasons unrelated to the programme. This model of a community-based lifestyle programme has the potential to be reproduced in other regions and in adults with similar long-term conditions. KEYWORDS Diabetes Mellitus Type II; Prediabetic state; Co-morbidity; Exercise; Self-management.


Metabolic and toxicological considerations for the latest drugs used to treat irritable bowel syndrome.
The high prevalence of irritable bowel syndrome (IBS), a chronic gastrointestinal (GI) disorder, its lack of satisfactory effective drugs and its complicated pathophysiology lead to the demand of new therapeutic agents. During a new drug development process, the pharmacokinetic profiling is of a great considerable importance comparable to drug's efficacy. This involves the drug's absorption, distribution, metabolism and excretion, all of which are crucial to its usefulness. In addition, the toxicological profile and possible adverse reactions of the drug should be identified. Also its interactions should be identified at different phases of trials. Several pharmacokinetic studies are carried out to achieve drugs with the best absorption and bioavailability and the least adverse effects and lowest toxicity. To make an update on new clinically introduced drugs for IBS and their dynamics and kinetics data, the present systematic review was accomplished. All relevant bibliographic databases were searched from the year 2003 up to May 2012 to identify all clinical trials that evaluated the potential efficacy of a novel agent in IBS. Some evaluated drugs, such as ramosetron (5-HT3 antagonist) and pexacerfont (CRF1 receptor antagonist), have shown some benefits in diarrhea-predominant IBS (D-IBS), while, prucalopride and mosapride (5-HT4 agonist) with prokinetic effect were found useful in constipation-predominant IBS (C-IBS). Besides, dexloxiglumide, lubiprostone and linaclotide have shown beneficial effects in C-IBS patients. Melatonin regulates GI tract motility and, asimadoline, gabapentin and pregabalin show reduction of pain threshold and visceral hypersensitivity. Glucagon-like peptide analog, calcium-channel blockers and neurokinin receptor antagonists have shown benefits in pain attacks. More time is required to indicate both efficacy and safety in long-term treatment due to multifactorial pathophysiology, variations in individual responses and insufficient assessment methods, which limit the right decision-making process about the efficacy and tolerability of these new drugs.