Association Between Buprenorphine Dose and the Urine "Norbuprenorphine" to "Creatinine" Ratio: Revised.
Utilizing a 1-year chart review as the data, Furo et al. conducted a research study on an association between buprenorphine dose and the urine "norbuprenorphine" to "creatinine" ratio and found significant differences in the ratio among 8-, 12-, and 16-mg/day groups with an analysis of variance (ANOVA) test. This study expands the data for a 2-year chart review and is intended to delineate an association between buprenorphine dose and the urine "norbuprenorphine" to "creatinine" ratio with a higher statistical power. This study performed a 2-year chart review of data for the patients living in a halfway house setting, where their drug administration was closely monitored. The patients were on buprenorphine prescribed at an outpatient clinic for opioid use disorder (OUD), and their buprenorphine prescription and dispensing information were confirmed by the New York Prescription Drug Monitoring Program (PDMP). Urine test results in the electronic health record (EHR) were reviewed, focusing on the "buprenorphine," "norbuprenorphine," and "creatinine" levels. The Kruskal-Wallis H and Mann-Whitney U tests were performed to examine an association between buprenorphine dose and the "norbuprenorphine" to "creatinine" ratio. This study included 371 urine samples from 61 consecutive patients and analyzed the data in a manner similar to that described in the study by Furo et al. This study had similar findings with the following exceptions: (1) a mean buprenorphine dose of 11.0 ± 3.8 mg/day with a range of 2 to 20 mg/day; (2) exclusion of 6 urine samples with "creatinine" level <20 mg/dL; (3) minimum "norbuprenorphine" to "creatinine" ratios in the 8-, 12-, and 16-mg/day groups of 0.44 × 10-4 (n = 68), 0.1 × 10-4 (n = 133), and 1.37 × 10-4 (n = 82), respectively; however, after removing the 2 lowest outliers, the minimum "norbuprenorphine" to "creatinine" ratio in the 12-mg/day group was 1.6 × 10-4, similar to the findings in the previous study; and (4) a significant association between buprenorphine dose and the urine "norbuprenorphine" to "creatinine" ratios from the Kruskal-Wallis test (P < .01). In addition, the median "norbuprenorphine" to "creatinine" ratio had a strong association with buprenorphine dose, and this association could be formulated as: [y = 2.266 ln(x) + 0.8211]. In other words, the median ratios in 8-, 12-, and 16-mg/day groups were 5.53 × 10-4, 6.45 × 10-4, and 7.10 × 10-4, respectively. Therefore, any of the following features should alert providers to further investigate patient treatment compliance: (1) inappropriate substance(s) in urine sample; (2) "creatinine" level <20 mg/dL; (3) "buprenorphine" to "norbuprenorphine" ratio >50:1; (4) buprenorphine dose >24 mg/day; or (5) "norbuprenorphine" to "creatinine" ratios <0.5 × 10-4 in patients who are on 8 mg/day or <1.5 × 10-4 in patients who are on 12 mg/day or more. The results of the present study confirmed those of the previous study regarding an association between buprenorphine dose and the "norbuprenorphine" to "creatinine" ratio, using an expanded data set. Additionally, this study delineated a clearer relationship, focusing on the median "norbuprenorphine" to "creatinine" ratios in different buprenorphine dose groups. These results could help providers interpret urine test results more accurately and apply them to outpatient opioid treatment programs for optimal treatment outcomes.


A multipurpose rubber adaptor.
A multipurpose rubber right-angle adaptor has been described. Thic can connect the patient to both masks and endotracheal tubes in several anaesthetic systems.


Warburg revisited: regulation of mitochondrial metabolism by voltage-dependent anion channels in cancer cells.
The bioenergetics of cancer cells is characterized by a high rate of aerobic glycolysis and suppression of mitochondrial metabolism (Warburg phenomenon). Mitochondrial metabolism requires inward and outward flux of hydrophilic metabolites, including ATP, ADP and respiratory substrates, through voltage-dependent anion channels (VDACs) in the mitochondrial outer membrane. Although VDACs were once considered to be constitutively open, closure of the VDAC is emerging as an adjustable limiter (governator) of mitochondrial metabolism. Studies of VDACs reconstituted into planar lipid bilayers show that tubulin at nanomolar concentrations decreases VDAC conductance. In tumor cell lines, microtubule-destabilizing agents increase cytoplasmic free tubulin and decrease mitochondrial membrane potential (ΔΨ(m)), whereas microtubule stabilization increases ΔΨ(m). Tubulin-dependent suppression of ΔΨ(m) is further potentiated by protein kinase A activation and glycogen synthase kinase-3β inhibition. Knockdown of different VDAC isoforms, especially of the least abundant isoform, VDAC3, also decreases ΔΨ(m), cellular ATP, and NADH/NAD+, suggesting that VDAC1 and VDAC2 are most inhibited by free tubulin. The brake on mitochondrial metabolism imposed by the VDAC governator probably is released when spindles form and free tubulin decreases as cells enter mitosis, which better provides for the high ATP demands of chromosome separation and cytokinesis. In conclusion, tubulin-dependent closure of VDACs represents a new mechanism contributing to the suppression of mitochondrial metabolism in the Warburg phenomenon.


Eating patterns-- a prognosis for China.
China has shifted its dietary patterns because of economic change. As people have more money to spend they buy more processed food which tends to be energy-dense and nutrient-poor. There are substantial differences in dietary patterns between urban and rural populations. Rural residents tend to maintain the basic traditional diet. while urban and richer rural residents tend to consume more high-fat food and processed sugar-based foods. If no action is taken to intervene or guide people's food consumption behavior: consumption of cereals, sugar and vegetables will decline; poultry consumption will increase; and the demand for beef, mutton, eggs and milk will increase. An analysis of food consumption in Shanghai during 1950-1982 revealed the mortality rate of heart disease, cerebrovascular disease and cancer were positively correlated with meat, egg and sugar consumption and negatively correlated with cereal consumption. The projections for chronic disease based on demographic change, risk factor and disease estimations indicate that by the year 2030 in China, there will be annually 800,000 deaths by coronary heart disease, 3 million from strokes and 1.7 million due to lung cancer. These figures call for the government and public to take timely actions to avoid over-consumption of animal foods. Although disease pattern change is related to a series of factors, the role nutrition plays in health promotion and disease prevention should not be underestimated.


Measurement of motor unit action potentials: procedural considerations.
Many factors influence the observed magnitude and shape of motor unit action potentials (MUAP). Several of these are related to procedures used during the electromyographic examination. An examiner must be aware of the procedural factors which may alter his observations. These include the following: strength of contraction; placement of the ground and reference electrodes; site, depth and pattern of electrode penetration; distance of active electrode penetration; distance of active electrode discharging unit; and separation of observation sites. The number of different MUAP observed and the number of observations of each MUAP become important when formulating a statistical report. The acceptable level of variation between serial samples of the same motor unit may determine the number of different units available for analysis. The selection of the point where the MUAP begins, ends and deflects maximally can influence the recorded observations.


Is there a functional linkage between neurotransmitter uptake mechanisms and presynaptic receptors?
The possibility of interaction between neurotransmitter uptake mechanisms and presynaptic receptors regulating transmitter release was investigated using rat brain synaptosomes in superfusion. Various conditions were considered including: absence of substrate for the uptake with uptake potentially operative; absence of substrate and presence of uptake inhibitors; and uptake activated by added substrate, with or without uptake inhibitors. The release of [3H]-5-hydroxytryptamine ([3H]-5-HT) evoked by 15 mM KCl from cerebral cortex synaptosomes was inhibited by lysergic acid diethylamide. The 5-HT uptake inhibitors citalopram and chlorimipramine did not affect the inhibitory action of lysergic acid diethylamide. Clonidine decreased both the K+-evoked release of [3H]norepinephrine and that of [3H]-5-HT in cortical synaptosomes through the activation of presynaptic alpha-2 adrenoceptors. In superfusion conditions, the action of clonidine on [3H]norepinephrine release was not antagonized by the norepinephrine uptake inhibitors desipramine or cocaine; similarly, the inhibition of [3H]-5-HT release was unaffected when 5-HT uptake was blocked. The K+-evoked release of [3H]dopamine from striatal nerve terminals was potentiated by acetylcholine (ACh) through the activation of muscarinic presynaptic receptors. The action of ACh was not modified by the presence of nomifensine, a dopamine uptake inhibitor. Finally, in superfused cortical synaptosomes, the block of the high-affinity uptake of choline by hemicholinium-3 had no effect on the muscarinic autoreceptor-mediated inhibition of [3H]ACh release by ACh. Altogether the present results do not support the previously proposed idea that in nerve terminals a functional coupling may exist between uptake mechanisms and presynaptic receptors.


Interleukin-1beta and its type 1 receptor are expressed in developing neural circuits in the frog, Xenopus laevis.
The cytokine interleukin-1 beta (IL-1beta) is an evolutionarily conserved molecule that was originally identified in the immune system. In addition to regulating peripheral immune responses, IL-1beta plays an important role in mediating neural-immune interactions and regulating glial activities during healing and repair in the damaged nervous system. Active IL-1beta is produced by interleukin-converting enzyme (ICE), a caspase thought to be involved in the induction of apoptosis. We report that, in the developing frog, Xenopus laevis, IL-1beta and the IL-1 type 1 receptor proteins are coexpressed in specific neurons that comprise early sensory-motor circuits. IL-1beta and IL-1 type 1 receptor proteins are colocalized in specific midbrain and hindbrain reticular cells, including Mauthner's neuron; specific cells in the trigeminal (fifth), lateral line (seventh), and vestibular (eighth) cranial ganglia; oculomotor neurons; and the primordial Purkinje cells of the lateral cerebellar auricle. In the spinal cord, Rohon-Beard sensory neurons, dorsal root ganglion cells, and primary motoneurons are immunopositive. Anteriorly, the olfactory pits, olfactory nerves, and olfactory bulbs are labeled, as are retinal cells, especially photoreceptor inner segments. With regard to the function of IL-1beta during neural development, IL-1beta and its type 1 receptor are present throughout the course of neural development in identifiable, long-lived neurons, such as Mauthner's neuron. These and other data suggest that IL-1beta and its type 1 receptor may be involved in the maintenance of cell survival rather than induction of neuronal death.


The effect of dietary factors on nitrosoproline levels in human urine.
The effect of dietary components on the levels of nitrosoproline ( NPRO ) excreted over a 24 h period in the urine was examined in volunteers ingesting known amounts of various food products. The ingestion of nitrite-preserved meats (85-170 g per meal), including canned, rolled or Yunnan ham, cured pork, luncheon meat, and various Chinese and European-style sausages, led to urinary NPRO excretion levels ranging from 2.5 to 78.5 micrograms/24 h, whereas the consumption of non-preserved meat and fish products, including chicken, herring, salmon, shrimp, ground beef (hamburger), pork chops and beef liver, led to relatively low NPRO excretion levels, ranging from 0.0 to 0.8 micrograms/24 h. The urinary NPRO levels of 22 vegetarians and 14 lacto-vegetarians averaged 0.8 and 1.4 micrograms/24 h, respectively. A change from a nitrite-preserved meat diet to a vegetarian diet was accompanied by an approximately six-fold reduction in urinary NPRO levels; however, these remained above control levels for at least 3 days following the dietary change. The relatively high NPRO levels following the ingestion of nitrite-preserved meats could not be reduced by nitrite-trapping chemicals, including ascorbic acid, ferulic acid, caffeic acid, or phenolic-containing mixtures such as coffee and tea, which were effective in suppressing endogenous NPRO formation following the intake of nitrate and proline. The high urinary NPRO levels after ingestion of preserved meat products appear to be due to the consumption of preformed NPRO . An understanding of the relative contribution of preformed and endogenously formed nitrosamines appears to be essential when designing dietary intervention programmes.


Haemodynamic and EEG changes during rapid-sequence induction of anaesthesia.
The relationship between the changes in haemodynamic function and the electroencephalogram (EEG) during rapid-sequence induction of anaesthesia was studied in 15 ASA I patients. Anaesthesia was induced with a bolus thiamylal (5 mg.kg-1 iv) followed by succinylcholine (1 mg.kg-1). Tracheal intubation was attempted one minute after the injection of succinylcholine. The EEG was monitored by a computerized aperiodic analysis device, the Lifescan (Neurometrics, San Diego, CA) using the activity edge (AE) to detect brain electrical activity. After induction of anaesthesia, systolic blood pressure (sBP) decreased by 11% from the baseline value, and the AE decreased from 13.0 Hz to 3.4 Hz. Following tracheal intubation, the sBP increased from the post-induction values by 44% (P < 0.05), and the AE increased to 13.1 Hz (P < 0.05) simultaneously. In conclusion, rapid-sequence induction using thiamylal (5 mg.kg-1) caused depression in brain activity as assessed by AE, while laryngoscopy and tracheal intubation caused an increase in activity. This indicates that this dose of thiamylal for rapid-sequence induction may not be sufficient to sustain an adequate anaesthetic level and blunt the haemodynamic responses to intubation.


Coexistence of stationary and traveling waves in reaction-diffusion-advection systems.
The flow- and diffusion-distributed structures (FDS) and the differential-flow instability (DIFI) are mechanisms that give rise to static and traveling waves in reactive flows with general, species-dependent transport terms. Here we consider a general framework which supports the simultaneous existence of FDS and DIFI patterns. We study the necessary conditions for each instability in general and compare them in order to derive their connection. The interaction between FDS and DIFI patterns gives rise to interesting wave behavior including stationary, upstream, and downstream traveling waves as well as an interesting regime where stationary and traveling waves coexist.


[The skin vasomotor dysfunction of the juvenile muscular atrophy of the distal upper limb--investigation by the ice water immersion test].
We investigated the skin vasomotor function of the juvenile muscular atrophy of the distal upper limb (JMA) by the ice water immersion test. The skin temperature of the bilateral second fingers during ice water immersion were measured in 17 patients with JMA and 25 normal controls. The insufficient fall of the skin temperature during ice water immersion was observed in 5 patients (3 patients in atrophic side, 2 patients in non-atrophic side). The insufficient recovery of the skin temperature was observed in 6 patients (3 patients in atrophic side, 3 patients in non-atrophic side). The both of the insufficient fall and recovery of the skin temperature was observed in one patient (both sides). The insufficient fall of the skin temperature indicates the hypofunction of skin vasomotor activity, and the insufficient recovery of the skin temperature indicates the hyperfunction of skin vasomotor activity because JMA has no disturbance of the peripheral sensory nerve fibers. We conclude that the responsible lesion of these abnormalities may be in the descending sympathetic tract in the cervical spinal cord.


[Surgery for abdominal aortic aneurysm. What is an acceptable complications rate?].
At the annual meeting of the Vascular Section of the Scandinavian Surgical Society in 1993 it was decided to discuss standards for quality in vascular surgery. This article is discussing operations for abdominal aortic aneurysms with special reference to early mortality and complications like graft infection and aortoenteric fistula. The discussion is based on national vascular registers and investigations on vascular surgical activity in the Scandinavian countries. In addition, a survey of the literature is given. Although these data should be regarded as a guide-line only, we feel that one should try to keep the 30 day mortality following elective resection for asymptomatic abdominal aortic aneurysm below 5-7 per cent. A mortality less than 50-60 per cent following operation for ruptured aneurysm may be regarded as reasonable. Patient-selection regarding age, concomitant disease etc. could significantly influence these results, and should be taken into consideration when comparison between different series is made. Graft infection is a serious complication and if the frequency is higher than 2 per cent, or there is an accumulation of graft infections in a vascular centre, the hospital routines should be reviewed carefully. The occurrence of infection is higher following operations for ruptured aneurysms than following elective operations. Early operations for haemorrhage and early occlusion should be below 5-6 per cent. Some authors have shown a correlation between the volume of operation, postoperative mortality and the frequency of complications. We therefore think that it might be reasonable to suggest that at least patients who have concomitant diseases like serious coronary heart disease or renal insufficiency should be operated on in vascular centres.(ABSTRACT TRUNCATED AT 250 WORDS)


Primary prevention of deep venous thrombosis and pulmonary embolism in acute spinal cord injured patients.
Prospective clinical trial. To evaluate the efficacy of a specific protocol for prevention of thrombo-embolic disease occurring during the acute stage of spinal cord lesions, based on the simultaneous use of pharmacological plus mechanical procedures. Regional Spinal Unit of Florence, Italy. Deep venous thrombosis (DVT) is a dangerous pathology whose first clinical sign can be represented by unexpected pulmonary embolism (PE). Its incidence in acute spinal cord injured (SCI) patients is reported to range between 9% and 90%. Its prevention represents one of the major challenges for the clinicians involved in the care of such patients. Two hundred and seventy-five SCI patients consecutively admitted to our Centre were investigated by colour doppler ultrasonography of lower limbs and pelvis on admission, after 30-45 days and whenever clinically requested. Subcutaneous Nadroparine, a low molecular weight heparin (LMWH), plus early mobilisation, permanently dressed gradient elastic stockings (PGES), and external sequential pneumatic compression (ESPC) of the lower limbs, applied during the first 30 days after injury, were given to all of them. Colour doppler ultrasonography (CDUS) complete investigations of the lower limbs and pelvis were performed on admission, after 30-45 days and whenever clinically requested. The patients were divided into two groups according to their time interval from injury to the admission to our Centre. The incidence of detected DVT was 2% in those patients (99) admitted early to our centre (within 72 h from the trauma), who immediately received our prophylactic protocol. No PE was reported. The other group of patients (176), all admitted between 8 and 28 days (mean 12 days) developed DVT in 26% of cases. None of these patients received ESPC before being admitted to our Centre. No patient had been admitted between 3 and 8 days interval time post injury. Early application of pharmacological plus mechanical treatment for DVT prevention produces a marked reduction in such complications. It also reduces the risks of morbidity and mortality in our patients, and, not least, reduces the hospitalization costs during the early period of rehabilitation.


Simultaneous Papillary Carcinoma in Thyroglossal Duct Cyst and Thyroid.
Thyroglossal duct cyst (TDC) is a cystic expansion of a remnant of the thyroglossal duct tract. Carcinomas in the TDC are extremely rare and are usually an incidental finding after the Sistrunk procedure. In this report, an unusual case of a 36-year-old woman with concurrent papillary thyroid carcinoma arising in the TDC and on the thyroid gland is presented, followed by a discussion of the controversies surrounding the possible origins of a papillary carcinoma in the TDC, as well as the current management options.


Screening and early treatment of primary liver cancer--with special reference to the east part of China.
The discovery of tumor marker alpha-foetoprotein (AFP) in hepatocellular carcinoma (HCC) and its application in screening has greatly contributed to early diagnosis. Of the more than five million natural population screened in our country since 1971, over one thousand cases of HCC have been detected. The percentage of subclinical cancer has been increased to 60.7% since passive reverse hemagglutination test was employed as initial screening in 1974. Diagnosis of subclinical HCC by AFP depends upon its absolute value, its serial change and interrelationship between serial change of AFP and SGPT. Subclinical HCC only amounted to 0.4-0.9% in clinical cases, but it went up to 44.7-71.2% in mass survey patients. Small HCC also rarely occurred in literature, however, the number of cases of small HCC resected has exceeded one hundred in our country, it amounting to 56.8-72.7% of the resected cases in mass survey patients. Results of a comparative study of mass survey and clinical patients demonstrated that 1-year, 2-year and 3-year survival being 14.8%, 7.4% and 5.5% and in clinical patients; 45.2%, 16.4% and 4.1% in mass survey patients who received conservative treatment; and 79.1%, 67.8% and 61.6% who received surgical resection. Unsolved problems and future prospects were also discussed.


Exploring the discourse between genetic counselors and Orthodox Jewish community members related to reproductive genetic technology.
Genetic technology is complex, relatively new and involves sensitive issues pertaining to personhood and reproduction. While ethno cultural barriers to genetic care are well documented, little attention has been devoted to understanding religious beliefs pertaining to genetic services. This study evaluated the discourse between genetic counselors and Orthodox Jewish community members' perceptions of reproductive genetic technology. A cross section of the Orthodox Jewish community was sampled through purposeful and snowball recruitment for in-depth interviews with key informants. Genetic counselors felt apprehensive about serving the Orthodox Jewish population and were unaware of social norms, religious and cultural practices unique to this population. Similarly, Orthodox Jewish consumers exhibited major misgivings about genetic testing. Importantly, stereotypic expectations by both counselors and consumers exacerbated existing communication difficulties. Cultural differences and poor communication between genetic counselors and Orthodox Jewish community members impeded the ability of the Orthodox Jewish community to utilize genetic services. This work illuminates complex issues pertaining to medical encounters between providers and patients with ideological, social and cultural differences. In particular, issues of access to care and transcultural competence in serving religious minority groups, such as Orthodox Jews are presented. On the whole, this group is largely unrecognized in the minority health literature in spite of barriers and challenges that they face. Findings of this study may have application to other cloistered and highly observant religious groups when dealing with reproductive technology and other populations with diverse values, beliefs and behaviors pertaining to reproductive health.


Tracing human mobility in central Europe during the Upper Paleolithic using sub-seasonally resolved Sr isotope records in ornaments.
Mobility of people and goods during the Upper Paleolithic has proven difficult to reconstruct given the relative rareness of remains. Nevertheless, archaeological contexts like the Late Pleistocene horizon of Borsuka Cave (Southern Poland) represent a unique opportunity to explore patterns of objects' transportation across Central Europe. We investigated the origin of four ornaments made of European elk (Alces alces L.) incisors recovered at Borsuka Cave - the oldest known burial site in Poland, possibly a child grave. Laser-ablation plasma source mass spectrometric analyses of trace elements and Sr isotopic compositions revealed that one elk was roaming within a geologically uniform area while the others changed their pastures during their lifetimes. The non-local origin of the elk teeth is inferred from their exotic Sr isotopic compositions and the lack of evidence for the presence of elk in this territory during the Pleistocene. Instead, the elks' Sr isotopic composition show good agreement with sites near the Austria-Slovakia border region and northern Hungary, ~250 km away from the study site. We argue that the artefacts were most likely brought to Borsuka Cave by humans or by a network of exchange, so far never reported in the time range 32.5-28.8 ka cal BP for Southern Poland.


Difficult temperament and negative parenting in early childhood: a genetically informed cross-lagged analysis.
A genetically informed longitudinal cross-lagged model was applied to twin data to explore etiological links between difficult temperament and negative parenting in early childhood. The sample comprised 313 monozygotic (MZ) and dizygotic (DZ) twin pairs. Difficult temperament and negative parenting were assessed at ages 2 and 3 using parent ratings. Both constructs were interrelated within and across age (rs .34-.47) and showed substantial stability (rs .65-.68). Difficult temperament and negative parenting were influenced by genetic and environmental factors at ages 2 and 3. The genetic and nonshared environmental correlations (rs .21-.76) at both ages suggest overlap at the level of etiology between the phenotypes. Significant bidirectional associations between difficult temperament and negative parenting were found. The cross-lagged association from difficult temperament at age 2 to negative parenting at age 3 and from negative parenting at age 2 and difficult temperament at age 3 were due to genetic, shared environmental, and nonshared environmental factors. Substantial novel genetic and nonshared environmental influences emerged at age 3 and suggest change in the etiology of these constructs over time.


Pharmacokinetics and serum concentration--effect relationship of intravenous deslanoside.
The antibodies of two commercially available digoxin-radioimmunoassay kits showed complete equimolar cross-reactivity with deslanoside and were used to determine serum levels of the latter glycoside. The serum concentrations of deslanoside were measured after a single intravenous dose of 1.2 mg in four patients recuperating after acute myocardial infarction. A phase of log-linear elimination (pseudoequilibrium) was reached after 4--8 h, and the biological half-life was 38-77 h (median 51 h). In a second study, the serum concentration was determined daily in 15 patients given multiple intravenous doses of the drug for atrial fibrillation and/or congestive heart failure. Symptoms or signs of digitalis toxicity occurred in six patients given a loading dose of deslanoside followed by daily maintenance doses of 0.4--0.6 mg. One of the patients tolerated a steady-state serum concentration of 3.9 micrograms/L (4.1 nmol/L) without toxicity symptoms. The findings in the remaining 14 patients suggest that the upper limit of the "therapeutic" concentration range is approximately 2.5 micrograms/L (2.7 nmol/L). A significant positive correlation (p less than 0.001) was found between the serum concentration of the drug and serum creatinine. Reduction of the maintenance dose of deslanoside is recommended in patients with impaired renal function.


The transiting dust clumps in the evolved disc of the Sun-like UXor RZ Psc.
RZ Psc is a young Sun-like star, long associated with the UXor class of variable stars, which is partially or wholly dimmed by dust clumps several times each year. The system has a bright and variable infrared excess, which has been interpreted as evidence that the dimming events are the passage of asteroidal fragments in front of the host star. Here, we present a decade of optical photometry of RZ Psc and take a critical look at the asteroid belt interpretation. We show that the distribution of light curve gradients is non-uniform for deep events, which we interpret as possible evidence for an asteroidal fragment-like clump structure. However, the clumps are very likely seen above a high optical depth midplane, so the disc's bulk clumpiness is not revealed. While circumstantial evidence suggests an asteroid belt is more plausible than a gas-rich transition disc, the evolutionary status remains uncertain. We suggest that the rarity of Sun-like stars showing disc-related variability may arise because (i) any accretion streams are transparent and/or (ii) turbulence above the inner rim is normally shadowed by a flared outer disc.


Chronotype, class times, and academic achievement of university students.
Numerous studies over the years have documented an effect of human chronotypes on physiological and psychological processes. Studies evaluating the impact of an individual's chronotype on his/her academic achievement have indicated that morning chronotypes have an academic advantage over evening chronotypes. However, these studies did not account for the time of day in which the participants were being evaluated. The goal of the present study was to examine whether morning chronotypes do have an academic advantage over evening chronotypes when the time of day of classes and exams is taken into consideration. We obtained morningness-eveningness scores and course grades from 207 university students who took classes (and exams) at different times of the day. We confirmed that morning chronotypes attain better grades than evening chronotypes, although the association is weak (r2 = 0.02). The difference persisted even after the time of day of classes and exams was taken into consideration. This is probably due to the fact that evening chronotypes are generally more sleep deprived than morning chronotypes as a result of the early schedule of most schools, which can impair their performance both early and late in the day.


A retrospective study of diseases in Ambystoma mexicanum: a report of 97 cases.
Ambystoma mexicanum kept as pets are affected by a variety of diseases. However, no reports regarding the incidence of specific diseases are available. This study aimed to identify the diseases that occur frequently in this species by surveying the incidence of conditions in pet A. mexicanum specimens brought to a veterinary hospital. The sample comprised 97 pet A. mexicanum individuals brought to the authors' hospital during the 82-month period, i.e., from January 2008 to October 2014. In total, 116 diseases were identified. The most common disease was hydrocoelom (32 cases; 27.5% of all cases). Elucidating the pathogenesis of hydrocoelom, which has a high prevalence rate, is vital to maintaining the long-term health of A. mexicanum pets.


High Level of Endotoxemia Following Out-of-Hospital Cardiac Arrest Is Associated With Severity and Duration of Postcardiac Arrest Shock.
To investigate the contribution of endotoxemia to the severity of postcardiac arrest shock. A prospective monocentric study. A tertiary hospital in Paris, France. Patients admitted in our ICU after a successfully resuscitated out-of-hospital cardiac arrest. None. Endotoxin measurement was performed in the 12 hours following return of spontaneous circulation using the endotoxin activity assay. Endotoxin level was classified as low (< 0.4 endotoxin activity), intermediate (0.4 to < 0.6 endotoxin activity), or high (≥ 0.6 endotoxin activity) according to manufacture guidelines. Severity of shock was assessed by the vasopressor-free days and by the mean daily dose of vasopressor to insure a mean arterial pressure of 65-75 mm Hg. Among 92 patients included in the study, 60 presented a postcardiac arrest shock. Endotoxemia level was higher in patients with postcardiac arrest shock. Among these patients, by multivariate linear regression, high endotoxin class (adjusted estimate -2.0; 95% CI, -3.90 to -0.11), public place of cardiac arrest (adjusted estimate, 1.47; 95% CI, 0.007 to 2.93), and time to return of spontaneous circulation (adjusted estimate -0.08; 95% CI, -0.13 to -0.03) were independently associated with the number of vasopressor-free days. Furthermore, high endotoxin class (adjusted estimate, 97.95; 95% CI, 20.5 to 175.4) and a nonshockable rhythm (adjusted estimate, 59.9; 95% CI, 6.2 to 113.7) were the sole factors independently associated with the mean daily dose of vasopressors. In patients successfully resuscitated from cardiac arrest with a postcardiac arrest shock, high level of endotoxemia is independently associated with duration of postcardiac arrest shock and the amount of vasopressive drugs. Whether treatment targeting endotoxemia could be beneficial in the management of postcardiac arrest shock needs to be studied in further randomized controlled studies.


Moving and handling: reducing risk through assessment.
Manual handling injuries can occur almost anywhere in a healthcare environment, and most staff perform a variety of moving and handling tasks every day. Heavy lifting, awkward posture, and previous or existing injury can increase the risk of musculoskeletal disorders. A healthcare professional's involvement in moving and handling is more widespread than it might appear, and their actions and understanding of techniques, legislation and guidelines have a direct effect on patient care. Every situation that involves the handling, or partial handling, of a person presents varying levels of risk to the patient and the carer. Maintaining a good level of patient mobility and independence is an essential part of care delivery and can reduce the risk of long-term physical and psychological effects. Delivery of care should focus on the individual's capacity, not their incapacity, to ensure that they are treated with dignity and respect.


The dual RAF/MEK inhibitor CH5126766/RO5126766 may be a potential therapy for RAS-mutated tumor cells.
Although melanoma is the most aggressive skin cancer, recent advances in BRAF and/or MEK inhibitors against BRAF-mutated melanoma have improved survival rates. Despite these advances, a treatment strategy targeting NRAS-mutated melanoma has not yet been elucidated. We discovered CH5126766/RO5126766 as a potent and selective dual RAF/MEK inhibitor currently under early clinical trials. We examined the activity of CH5126766/RO5126766 in a panel of malignant tumor cell lines including melanoma with a BRAF or NRAS mutation. Eight cell lines including melanoma were assessed for their sensitivity to the BRAF, MEK, or RAF/MEK inhibitor using in vitro growth assays. CH5126766/RO5126766 induced G1 cell cycle arrest in two melanoma cell lines with the BRAF V600E or NRAS mutation. In these cells, the G1 cell cycle arrest was accompanied by up-regulation of the cyclin-dependent kinase inhibitor p27 and down-regulation of cyclinD1. CH5126766/RO5126766 was more effective at reducing colony formation than a MEK inhibitor in NRAS- or KRAS-mutated cells. In the RAS-mutated cells, CH5126766/RO5126766 suppressed the MEK reactivation caused by a MEK inhibitor. In addition, CH5126766/RO5126766 suppressed the tumor growth in SK-MEL-2 xenograft model. The present study indicates that CH5126766/RO5126766 is an attractive RAF/MEK inhibitor in RAS-mutated malignant tumor cells including melanoma.


In vitro lactate metabolism by ruminal ingesta.
Ruminal ingesta (300 ml) obtained from a fistulated cow fed alfalfa hay (H), 3.6 kg of grain mixture with corn silage fed ad libitum (S), 2.5:1 grain-alfalfa hay mixture (G), or a 2.5:1 grain-alfalfa hay mixture providing 545 g of sodium and calcium lactate daily (L) were incubated for 8 hr with nonpolymerized sodium lactate or 17% polymerized lactic acid neutralized to pH 6.7. Polymerization had no effect on the rate of lactate utilization. The initial rates of lactate metabolism for the H, G, S, and L ingesta were 0.72, 0.95, 1.8, and 3.4 meq per 100 ml of rumen fluid per hr, respectively. Lactate-2-(14)C was incubated for 4 hr with each type of ruminal ingesta. Of the label recovered in the volatile fatty acids (VFA), 74.1, 61.2, 49.3, and 38.9% was recovered in acetate, and 9.4, 19.8, 23.3, and 51.9% was recovered in propionate with H, G, S, and L ingesta, respectively. The balance of label was distributed between butyrate and valerate. The titratable VFA did not follow this pattern of production. With the hay ingesta, lactate metabolism resulted in a net loss of acetate and a large increase in butyrate. Little propionate was produced. The G, S, and L ingesta metabolized lactate to yield progressively more propionate and less butyrate. Evidence was gathered to suggest that acetate was the primary end product of lactate metabolism but that oxidation of lactate to pyruvate dictated the synthesis of butyrate from acetate to maintain an oxidation-reduction balance. It was noted that acetate and butyrate production from lactate was pH-dependent, with acetate production maximal at pH 7.4 and butyrate at 6.2. Propionate production was largely unaffected within this pH range.


Acoustic evidence for right-edge prominence in Nafsan.
Oceanic languages are often described as preferring primary stress on penultimate syllables, but detailed surveys show that many different types of prominence patterns have been reported across and within Oceanic language families. In some cases, these interact with segmental and phonotactic factors, such as syllable weight. The range of Oceanic prominence patterns is exemplified across Vanuatu, a linguistically diverse archipelago with over 130 languages. However, both impressionistic and instrumentally-based descriptions of prosodic patterns and their correlates are limited for languages of this region. This paper investigates prominence in Nafsan, an Oceanic language of Vanuatu for which previous observations of prominence differ. Acoustic and durational results for disyllabic and trisyllabic Nafsan words show a clear pattern of higher fundamental frequency values in final syllables, regardless of vowel length, pointing towards a preference for prominence at the right edge of words. Short vowels also show centralisation in penultimate syllables, providing supporting evidence for right-edge prominence and informing the understanding of vowel deletion processes in Nafsan.


Devic's syndrome and mixed connective tissue disease: an unusual association.
Devic's disease or neuromyelitis optica (NMO) is an autoimmune, inflammatory and demyelinating pathology of the central nervous system that affects the optic nerve and the spinal cord. Diagnosis confirmed by imaging, magnetic resonance (MR) and the presence of the anti-aquaporin 4 antibody (anti-AQP4). We describe two cases of patients with mixed connective tissue disease (MCTD) and Devic's disease, who had anti-AQP4 positive and areas with neuroaxis MR abnormalities, showing this rare association.


Malaria: diagnosis, treatment and management of a critically ill patient.
Malaria is a significant cause of mortality in many countries and remains the most prevalent parasitic tropical infection. The World Health Organization estimates that 50% of the world's population is at risk of malaria, with most deaths occurring in sub-Saharan Africa. This case study explores the management of a malaria patient admitted to a critical care unit in Zambia, a lower-middle-income country in sub-Saharan Africa. While malaria is prevalent in Zambia and other countries, in the UK all malaria is imported and less frequently seen by health professionals. This case study will raise the profile of malaria, including its recognition, diagnosis and treatment. This information will assist nurses in both low- and high-income countries to translate theory into practice and improve nurses' understanding of a condition rarely seen in UK critical care practice.


Oral rehabilitation of a patient with amelogenesis imperfecta using removable overlay denture: a clinical report.
The aim of this study was oral rehabilitation of 17-year old patient with amelogenesis imperfecta using removable overlay denture in order to satisfy her esthetic and functional expectations and enhance her self-image. Amelogenesis imperfecta (AI) is a group of genetic disorders that primarily affect the quality and quantity of amelogenesis in both primary and permanent dentitions. The main clinical characteristics are severe attrition, tooth sensitivity and unesthetic appearance. This clinical report illustrates the oral rehabilitation of a 17-year-old girl with hypoplastic-hypomature type of AI with cobalt-chromium (Co-Cr) overlay removable partial denture (ORPD) that is one of the most economical and biocompatible replacements for noble metal and nickel-chromium (Ni-Cr) alloy. The presented case report suggests that Co-Cr ORPD can be a good temporary or even permanent treatment option for AI patients with limited budget, low esthetic concerns or medical limitations. There are major advantages in cast metal ORPDs; they are simpler, less traumatic and less expensive than fixed prosthetic options. This case report supports their use in patients with amelogenesis imperfecta.


Nasal cytology.
Nasal cytology represents a useful, inexpensive and easy-to-apply diagnostic method to better detail the phenotypic characteristics of rhinitis. In fact, it allows to detect and quantify the cell population within the nasal mucosa at a given time. The technique involves sampling, processing and microscope reading. Sampling requires the collection of cells from the surface of nasal mucosa that is usually done by a sterile disposable curette. Samples should be collected from the middle portion of the inferior turbinate where the ratio ciliate/mucinous cells is expected to be well balanced. This totally painless procedure is performed under anterior rhinoscopy, with an appropriate light source. The sample staining is executed using the common May-Grünwald-Giemsa (MGG). The stained sample is read at optical microscopy with a 1000x objective and with oil detecting the presence of inflammatory elements (eosinophils, mast cells, neutrophils and lymphocytes) in nasal mucosa, as in the case of allergic and non-allergic rhinitis. Nasal cytology is easy to perform, non-invasive, inexpensive and repeatable in the same subject, also at short time intervals. For these reasons it represents an affordable diagnostic technique that can be applied in all age ranges, to better differentiate pathological conditions and also to evaluate the effects of various stimuli (allergens, infectious, irritants) or the effect of treatments.


Carbohydrate intake modifies associations between ANGPTL4[E40K] genotype and HDL-cholesterol concentrations in White men from the Atherosclerosis Risk in Communities (ARIC) study.
Common allelic variation in the angiopoietin-like 4 gene (ANGPTL4[E40K]) has been associated with low triglyceride (TG) and high HDL-C. We examined whether dietary macronutrient intake modified associations between ANGPTL4[E40K] variation and TG and HDL-C in White men and women from the Atherosclerosis Risk in Communities study. Diet was assessed by food frequency questionnaire. Intake of fat (total fat [TF], saturated fat [SF], monounsaturated fat [MUFA], polyunsaturated fat [PUFA], and n-3 PUFA) and carbohydrate were expressed as percentage of total energy intake. ANGPTL4 A allele carriers (n=148 in men, 200 in women) were compared to non-carriers (n=3667 in men, 4496 in women). Interactions were tested separately in men and women, adjusting for study center, age, smoking, physical activity, BMI, and alcohol intake. ANGPTL4 A allele carriers had significantly greater HDL-C and lower TG than non-carriers (p<or=0.001). In all participants, carbohydrate intake was inversely associated with HDL-C and positively associated with TG, whereas TF, SF, and MUFA showed opposite associations with TG and HDL-C (p<0.001). These relations were uniform between sex-specific genotype groups, with one exception. In men, but not women, the inverse association between carbohydrate and HDL-C was stronger in A allele carriers (beta+/-S.E. -1.80+/-0.54) than non-carriers (beta+/-S.E. -0.54+/-0.11, p(interaction)=0.04 in men and 0.69 in women; p 3-way interaction=0.14). These data suggest that ANGPTL4 variation and relative contributions of dietary fat and carbohydrate influence TG and HDL-C concentrations. In men, ANGPTL4 variation and dietary carbohydrate may interactively influence HDL-C.


Clavaspirin, an antibacterial and haemolytic peptide from Styela clava.
We cloned the precursor of a novel peptide from a cDNA library prepared from pharyngeal tissues of the tunicate, Styela clava. Its sequence predicted a histidine-rich, amidated 23-residue peptide (FLRF(IG)SVIHGIGHLVHHIGVAL-NH2) that we named clavaspirin. A synthetic clavaspirin was prepared and it was found that it killed Gram-positive and Gram-negative bacteria, permeabilized the outer and inner membranes of Escherichia coli, lysed phosphatidylglycerol (POPG) liposomes, and was potently haemolytic towards human and bovine erythrocytes. Each of these activities was performed more effectively at an acidic pH. Circular dichroism measurements of synthetic clavaspirin revealed a largely alpha-helical structure and polarized and residue-specific FTIR spectrometry showed that its association with phospholipid membranes was influenced by pH. Peptides such as clavaspirin may equip tunicate haemocytes to mediate cytotoxicity and participate in antimicrobial defence.


Dyadic adjustment in chronic illness: does relationship talk matter?
Relationship talk involves talking about the nature and state of one's relationship. To determine the effectiveness of talking about the relationship when one spouse has a chronic illness, the study involved completion of a confidential questionnaire by 182 married couples. Ninety of these were couples in which both partners were healthy, and 92 were couples in which one spouse had a chronic illness. Results of multilevel modeling analyses showed that the association between relationship talk and dyadic adjustment was stronger for women than for men and for couples with an ill spouse than for couples where both spouses were healthy. These findings highlight the importance of taking a relationship perspective and suggest that relationship talk is a potentially useful tool couples can use in their repertoire of relationship-enhancing behaviors during chronic illness.


Cyclic AMP blocks cell growth through Raf-1-dependent and Raf-1-independent mechanisms.
It is widely accepted that cyclic AMP (cAMP) can block cell growth by phosphorylating Raf-1 on serine 43 and inhibiting signaling to extracellular signal-regulated protein kinase. We show that the suppression of Raf-1 by cAMP is considerably more complex than previously reported. When cellular cAMP is elevated, Raf-1 is phosphorylated on three residues (S43, S233, and S259), which work independently to block Raf-1. Both Ras-dependent and Ras-independent processes are disrupted. However, when cAMP-insensitive versions of Raf-1 are expressed in NIH 3T3 cells, their growth is still strongly suppressed when cAMP is elevated. Thus, although Raf-1 appears to be an important cAMP target, other pathways are also targeted by cAMP, providing alternative mechanisms that lead to suppression of cell growth.


Stoichiometry and food-chain dynamics.
Traditional models of chemostat systems looking at interactions between predator, prey and nutrients have used only a single currency, such as energy or nitrogen. In reality, growth of autotrophs and heterotrophs may be limited by various elements, e.g. carbon, nitrogen, phosphorous or iron. In this study we develop a dynamic energy budget model chemostat which has both carbon and nitrogen as currencies, and examine how the dual availability of these elements affects the growth of phytoplankton, trophic transfer to zooplankton, and the resulting stability of the chemostat ecosystem. Both species have two reserve pools to obtain a larger metabolic flexibility with respect to changing external environments. Mineral nitrogen and carbon form the base of the food chain, and they are supplied at a constant rate. In addition, the biota in the chemostat recycle nutrients by means of respiration and excretion, and organic detritus is recycled at a fixed rate. We use numerical bifurcation analysis to assess the model's dynamic behavior. In the model, phytoplankton is nitrogen limited, and nitrogen enrichment can lead to oscillations and multiple stable states. Moreover, we found that recycling has a destabilizing effect on the food chain due to the increased repletion of mineral nutrients. We found that both carbon and nitrogen enrichment stimulate zooplankton growth. Therefore, we conclude that the concept of single-element limitation may not be applicable in an ecosystem context.


Pex14 is the sole component of the peroxisomal translocon that is required for pexophagy.
Pex14 was initially identified as a peroxisomal membrane protein that is involved in docking of the soluble receptor proteins Pex5 and Pex7, which are required for import of PTS1- or PTS2-containing peroxisomal matrix proteins. However, Hansenula polymorpha Pex14 is also required for selective degradation of peroxisomes (pexophagy). Previously we showed that Pex1, Pex4, Pex6 and Pex8 are not required for this process. Here we show that also in the absence of various other peroxins, namely Pex2, Pex10, Pex12, Pex13 and Pex17, pexophagy can normally occur. These peroxins are, like Pex14, components of the peroxisomal translocon. Our data confirm that Pex14 is the sole peroxin that has a unique dual function in two apparent opposite processes, namely peroxisome formation and selective degradation.


An image-based high-content screening for compounds targeting Toxoplasma gondii repurposed inhibitors effective against the malaria parasite Plasmodium falciparum.
Apicomplexa phylum includes numerous obligate intracellular protozoan parasites that are life threatening for humans and animals. In this context, Plasmodium falciparum and Toxoplasma gondii are of particular interest, as they are responsible for malaria and toxoplasmosis, respectively, for which efficient vaccines are presently lacking and therapies need to be improved. Apicomplexan parasites have a highly polarized morphology, with their apical end containing specific secretory organelles named rhoptries and micronemes, which depend on the unique receptor and transporter sortilin TgSORT for their biogenesis. In the present study, we took advantage of the subcellular polarity of the parasite to engineer a clonal transgenic Toxoplasma line that expresses simultaneously the green fluorescent protein TgSORT-GFP in the post-Golgi-endosome-like compartment and the red fluorescent protein rhoptry ROP1-mCherry near the apical end. We utilized this fluorescent transgenic T. gondii to develop a miniaturized image-based phenotype assay coupled to an automated image analysis. By applying this methodology to 1,120 compounds, we identified 12 that are capable of disrupting the T. gondii morphology and inhibiting intracellular replication. Analysis of the selected compounds confirmed that all 12 are kinase inhibitors and intramembrane pumps, with some exhibiting potent activity against Plasmodium falciparum. Our findings highlight the advantage of comparative and targeted phenotypic analysis involving two related parasite species as a means of identifying molecules with a conserved mode of action.


Entropic folding pathway of human epidermal growth factor explored by disulfide scrambling and amplified collective motion simulations.
Epidermal growth factor (EGF) regulates cell proliferation and differentiation by binding to the EGF receptor (EGFR) extra-cellular domains. Human EGF is a small, single-chain protein comprising three distinct loops (A, B, and C), which are connected by three disulfide bridges (Cys6-Cys20, Cys14-Cys31, and Cys33-Cys42). These disulfide bridges are essential for structural stability and biological activity. EGF was extensively studied by disulfide scrambling, an experimental technique for the conformational entrapment of intermediate states, which allows us to study the folding pathway of proteins containing disulfide bonds. The experimental results showed that there is a major 2-disulfide intermediate (denoted EGF-II) and that the native disulfide bonding pattern is less prevalent in one of the mutants. In this article, we investigated for the first time the solution conformations of wild-type EGF, EGF-II, and the mutant S9C through extensive molecular dynamics (MD) simulations in water using both the standard MD technique and a recently developed amplified-collective-motion (ACM) sampling method. Compared to standard MD simulations, we achieved a much more enhanced sampling by the ACM simulations, and the structures were sufficiently relaxed to estimate configurational entropies. The simulation results suggest a predominantly entropic folding pathway governed by the disorder of three functional loop regions. Although EGF-II exhibits two native disulfide bonds (Cys14-Cys31 and Cys33- Cys42), its large configurational entropy inhibits a direct transition to the native structure in the folding process. When Ser9 is mutated into Cys, a non-native disulfide bridge Cys9- Cys20 is slightly more favorable than the native Cys6-Cys20 because a less constrained N-terminus affords larger entropy. Isomers that are functionally less active also exhibit a more localized dynamics of the functional loop regions, which may suggest a possible mechanism for the modulation of EGF activity.


Cystatin C: a new marker of biocompatibility or a good marker for the redistribution of LMW proteins during hemodialysis?
The mechanism(s) behind the larger relative increase of Plasma beta 2 microglobulin (P-beta 2m) than that of Plasma albumin (P-alb) during Cuprophan hemodialysis is disputed. To elucidate this phenomenon P-alb, P-beta 2m (MW 11,800) and Plasma cystatin (P-cC; MW 13,000) an inhibitor of cystein proteinases, were determined before and after a Cuprophan or polysulphone hemodialysis (4-7 hr, QB 200 ml/min) in 30 stable regular dialysis treatment (RDT) patients. Body weight (BW) decreased by 2.5 +/- 1.4% (mean +/- SD). P-alb, P-beta 2m and P-cC increased by 11.4 +/- 14.8%, 15.4 +/- 11.5%, and 22.1 +/- 14.3%, respectively, during Cuprophan dialysis. The relative increase of P-cC was larger than that of P-beta 2m (P less than 0.05) and that of P-alb (P less than 0.02). During polysulphone dialysis BW decreased by 4.1 +/- 1.8%. P-alb, P-beta 2m, and P-cC increased almost equally by 28.1 +/- 18, 26.5 +/- 19.2, and 26.8 +/- 14.4%, respectively. These results are hard to interpret. Is the increase in P-cC a new marker of biocompatibility or does it reflect the true shift of low molecular weight (LMW) proteins between the interstitial and the plasma volume during hemodialysis better than P-beta 2m? In vitro studies indicate that small amounts of both Serum beta 2m (S-beta 2m) and Serum cystatin C (S-cC) are adsorbed to or sieved through the Cuprophan membrane, findings which render the kinetics of LMW proteins during hemodialysis still more complex.


Acute lipoprivation suppresses pulsatile luteinizing hormone secretion without affecting food intake in female rats.
The present study examined the effect of acute lipoprivation on pulsatile luteinizing hormone (LH) secretion in both normal-fat diet, ad libitum-fed and fasted female rats. To produce an acute lipoprivic condition, mercaptoacetate (MA), an inhibitor of fatty acid oxidation, was administered intraperitoneally to ad libitum-fed or 24-h fasted ovariectomized (OVX) rats with or without an estradiol (E2) implant, that produces a negative feedback effect on LH pulses. The steroid treatment was performed to determine the effect of estrogen on lipoprivic changes in LH release, because estrogen enhances fasting- or glucoprivation-induced suppression of LH pulses. Pulsatile LH secretion was suppressed by MA administration in a dose-dependent manner in the ad libitum-fed OVX and OVX+E2 rats. LH pulses were more severely suppressed in the 24-h-fasted OVX and OVX+E2 rats compared to the ad libitum-fed rats. Estrogen slightly enhanced lipoprivic suppression but the effect was not significant. In the present study, increased plasma glucose and free-fatty acid concentrations may indicate a blockade of fatty acid metabolism by the MA treatment, but food intake was not affected by any of the MA doses. Acute vagotomy did not block lipoprivic suppression of LH pulses. Thus, the present study indicates that lipid metabolism is important for maintenance of normal reproductive function even in rats fed a normal-fat diet and lipoprivation may be more critical in fasted animals that probably rely more heavily on fatty acid oxidation to maintain appropriate metabolic fuel levels. In addition, failure of blockade of lipoprivic LH inhibition by vagotomy suggests that lipoprivic information resulting in LH suppression is not transmitted to the brain via the vagus nerve.


Obstructive sleep apnea in the morbidly obese. An indication for gastric bypass.
Two morbidly obese patients were described as having severe obstructive sleep apnea syndrome with several apneic periods occurring during sleep that produced substantial oxygen desaturation and, in one patient, cardiac arrhythmias. These patients, by dieting, had noted specific "trigger" weights at which they would manifest symptoms of lethargy, hypersomnolence, and snoring. Both were treated with tracheostomy, and after several days without apnea their cardiac and respiratory status stabilized and they underwent loop gastric bypass. Successful weight loss ensued and repeated sleep studies disclosed no further apneic periods (with the tracheostomies occluded), and so their tracheostomies were removed. We consider sleep apnea syndrome to be an indication for bariatric surgery.


Radiation recall gastritis secondary to combination of gemcitabine and erlotinib in pancreatic cancer and response to PPI - a case report.
Radiation recall gastritis is rare but can be induced after concurrent chemoradiation for pancreatic cancer. We report a patient with pancreatic cancer who developed radiation-recall gastritis related to a combination of gemcitabine and erlotinib. A 54-year-old female with unresectable pancreatic cancer received gemcitabine in combination with radiation therapy followed by chemotherapy with gemcitabine and erlotinib. After completing 2 cycles of chemotherapy, the patient had epigastric pain, nausea, and vomiting. Abdominal computed tomography (CT) scan revealed diffuse wall thickening of the stomach, and esophagogastroduodenoscopy (EGD) showed multiple gastric ulcers. The patient was treated with proton pump inhibitors (PPI) and was continued on maintenance chemotherapy. Two months later, the patient presented with the similar symptoms and persistent gastric ulcers were observed during subsequent EGD. Nevertheless, the patient's symptom had resolved with PPI therapy. Thus, the patient underwent maintenance chemotherapy with gemcitabine and erlotinib for additional 4 cycles. Eventually, follow-up abdominal CT Scan and EGD at 6 months demonstrated resolution of the gastric ulcers. Physicians should be aware of the possibility of radiation recall gastritis associated with a combination of gemcitabine and erlotinib. Administration of PPIs may mitigate the adverse effects of gemcitabine and erlotinib in the presence of radiation recall gastritis; however further studies are warranted.


Management strategies for promoting successful breastfeeding.
Clinicians can promote a successful breastfeeding experience by providing support, anticipatory guidance and practical information. This article presents the components of early follow-up and guidelines for assessment. Management strategies for common problems are discussed, such as nipple soreness, cracked nipples, plugged ducts and mastitis, insufficient infant weight gain, perceived inadequacy of milk supply, breast-milk jaundice, sexual adjustment and failure at breastfeeding. Breastfeeding guidelines for employed mothers and adoptive mothers are indicated.


Evaluation of a Case Management to Support Families With Children Diagnosed With Spinal Muscular Atrophy-Protocol of a Controlled Mixed-Methods Study.
Background: Spinal muscular atrophy (SMA) is a rare neuromuscular disease characterized by degeneration of the anterior horn cells in the spinal cord, resulting in muscle atrophy, and proximal muscle weakness. SMA presents with a wide range of symptoms requiring multiple clinical specialists and therapists. Integrating care between disciplines can be challenging due to the dynamic course of the disease, and great distances between specialist centers and local providers. Insufficient care integration can lead to suboptimal quality of care and more difficulties for patients and families. This study aims to improve care integration through a Case Management intervention, and taking a mixed-methods approach, to evaluate its impact. Methods: An exploratory, controlled, two-armed study with baseline, post- and follow-up measurement and process evaluation is conducted to evaluate our intervention compared to usual care. Through a multi-perspective state analysis, we investigate the experiences of caregivers and healthcare providers concerning the actual healthcare quality of patients with SMA I and II. Semi-structured interviews and care diaries are used. We apply that data to conceive a tailored Case Management intervention supplemented by a digital platform. The intervention's effect is examined in comparison to a control group taking a mixed-methods approach. As primary endpoints, we investigate the caregivers' health-related quality of life and the quality of care integration. Secondary endpoints are the use of healthcare services (patients and caregivers) and costs. We assess the process quality from the perspectives of caregivers and healthcare providers through semi-structured interviews. Discussion: This is an exploratory, controlled study to assess the impact of a tailored Case Management intervention to improve the care of patients with SMA I and II. After the evaluation, results on feasibility, expected effect sizes, and process quality will be available. On this basis, future randomized controlled trials can be planned. If demonstrated beneficial, the experience gained within this study may also be valuable for care strategies in other regions and other (non-pediatric) patient groups with rare diseases and/or chronic, complex conditions. Clinical Trial registration:https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00018778, identifier: DRKS00018778.


Metabolic Signaling to Chromatin.
There is a dynamic interplay between metabolic processes and gene regulation via the remodeling of chromatin. Most chromatin-modifying enzymes use cofactors, which are products of metabolic processes. This article explores the biosynthetic pathways of the cofactors nicotinamide adenine dinucleotide (NAD), acetyl coenzyme A (acetyl-CoA), S-adenosyl methionine (SAM), α-ketoglutarate, and flavin adenine dinucleotide (FAD), and their role in metabolically regulating chromatin processes. A more detailed look at the interaction between chromatin and the metabolic processes of circadian rhythms and aging is described as a paradigm for this emerging interdisciplinary field.


The management of metatarsus adductus et supinatus.
Forty-three patients with 69 feet affected by isolated metatarsus adductus et supinatus were reviewed. Of these, 20 patients (with 31 involved feet) had been treated expectantly and spontaneous resolution had occurred with time. The remaining 23 patients (with 38 feet) had required anteromedial release; the operative technique is described. Excellent results were uniformly achieved in both groups, with neither recurrence nor complications in the operatively treated feet. There was a consistent correlation between good clinical results and a naviculo -metatarsal angle of less than 100 degrees. The timing of soft-tissue release did not influence the final outcome.


Strength Development and Strain Localization Behavior of Cemented Paste Backfills Using Portland Cement and Fly Ash.
This study examines the combined performance of Portland cement (PC), the binder, and fly ash (FA), the additive, towards improving the mechanical performance of the South Australian copper-gold underground mine cemented paste backfill (CPB) system. A series of unconfined compressive strength (UCS) tests were carried out on various mix designs to evaluate the effects of binder and/or additive contents, as well as curing time, on the CPB's strength, stiffness and toughness. Moreover, the failure patterns of the tested samples were investigated by means of the three-dimensional digital image correlation (DIC) technique. Making use of several virtual extensometers, the state of axial and lateral strain localization was also investigated in the pre- and post-peak regimes. The greater the PC content and/or the longer the curing period, the higher the developed strength, stiffness and toughness. The use of FA alongside PC led to further strength and stiffness improvements by way of inducing secondary pozzolanic reactions. Common strength criteria for CPBs were considered to assess the applicability of the tested mix designs; with regards to stope stability, 4% PC + 3% FA was found to satisfy the minimum 700 kPa threshold, and thus was deemed as the optimum choice. As opposed to external measurement devices, the DIC technique was found to provide strain measurements free from bedding errors. The developed field of axial and lateral strains indicated that strain localization initiates in the pre-peak regime at around 80% of the UCS. The greater the PC (or PC + FA) content, and more importantly the longer the curing period, the closer the axial stress level required to initiate localization to the UCS, thus emulating the failure mechanism of quasi-brittle materials such as rock and concrete. Finally, with an increase in curing time, the difference between strain values at the localized and non-localized zones became less significant in the pre-peak regime and more pronounced in the post-peak regime.


Fungal and yeast infections of the central nervous system. A clinical review.
In the past 20 years, there has been a marked increase in the number of reported cases of meningitis and brain abscess due to fungi and yeasts. This increase is due in part to better diagnostic techniques and greater awareness of the possibility of fungal invasion of the nervous system; but the increase can also be attributed to a growing pool of severely compromised hosts, many of whom are undergoing treatment with adrenal glucocorticoids or immunosuppressive agents. The diagnosis and treatment of aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, cryptococcosis, infections caused by dematiaceous fungi, histoplasmosis, paracoccidioidomycosis, petriellidosis, and sporotrichosis, as well as relatively rare infections of the central nervous system caused by other fungi, are discussed. The efficacy of amphotericin B and 5-fluorocytosine in the treatment of CNS fungal and yeast infections is also evaluated.


Enhanced production of 1,2-propanediol by tpi1 deletion in Saccharomyces cerevisiae.
Saccharomyces cerevisiae was metabolically engineered to improve 1,2-propanediol production. Deletion of the tpi1 (triosephosphate isomerase) gene in S. cerevisiae increased the carbon flux to DHAP (dihydroxylacetone phosphate) in glycolysis, resulting in increased glycerol production. Then, the mgs and gldA genes, the products of which convert DHAP to 1,2-propanediol, were introduced to the tpi1-deficient strain using a multicopy plasmid. As expected, the intracellular level of methylglyoxal was increased by introduction of the mgs gene in S. cerevisiae and that of 1,2-propanediol by introduction of both the mgs and gldA genes. As a result, 1.11 g/l of 1,2-propanediol was achieved in flask culture.


Utilization of exogenous pyrimidines as a source of nitrogen by cells of the yeast Rhodotorula glutinis.
Uptake and intracellular transformation of pyrimidines supplying cells of the yeast Rhodotorula glutinis with nitrogen have been studied. The amine nitrogen of cytosine was found to be the easiest to utilize. The presence in the medium of inorganic ammonia along with cytosine had a slight effect on cytosine deaminase (EC 22.214.171.124) activity. The uracil produced entered into the nutrient medium with no fission break of the pyridmidine ring. In the absence of any other source of nitrogen, the cells of the yeast R. glutinis utilized nitrogen of the pyrimidine ring of oxypyrimidines. Catabolism of uracil followed the reductive pattern, with release of carbon dioxide; this was accompanied by synthesis of the key enzyme of pyrimidine catabolism, dihydrouracil dehydrogenase (EC 188.8.131.52), whose activity rose 10-fold. With thymidne as the sole source of nitrogen, the lag-phase growth of the yeast cells was maximum. Catabolism of the pyrimidine ring of thymine was possibly preceded by its transformation into uracil. With no source of nitrogen easily utilized, the uridine 5'-monophosphate content in the generally acid-soluble pool rose. Our discussion of the regulation of catabolism of exogenous pyrimidine bases by the yeast R. glutinis takes into account the fact that transformations of pyrimidine bases are determined by how easily the cells can use a particular base as a source of nitrogen.


Pityriasis Rosea: Diagnosis and Treatment.
Pityriasis rosea is a common self-limiting rash that usually starts with a herald patch on the trunk and progresses along the Langer lines to a generalized rash over the trunk and limbs. The diagnosis is based on clinical and physical examination findings. The herald patch is an erythematous lesion with an elevated border and depressed center. The generalized rash usually presents two weeks after the herald patch. Patients can develop general malaise, fatigue, nausea, headaches, joint pain, enlarged lymph nodes, fever, and sore throat before or during the course of the rash. The differential diagnosis includes secondary syphilis, seborrheic dermatitis, nummular eczema, pityriasis lichenoides chronica, tinea corporis, viral exanthems, lichen planus, and pityriasis rosea-like eruption associated with certain medications. Treatment is aimed at controlling symptoms and consists of corticosteroids or antihistamines. In some cases, acyclovir can be used to treat symptoms and reduce the length of disease. Ultraviolet phototherapy can also be considered for severe cases. Pityriasis rosea during pregnancy has been linked to spontaneous abortions.


The optimal exercise parameters of Tai Chi on the effect of glucose and lipid metabolism in patients with type 2 diabetes mellitus: A meta-analysis.
To explore the optimal exercise parameters of Tai Chi for improving glucose and lipid metabolism in type 2 diabetes mellitus (T2DM) patients. This meta-analysis was conducted in accordance with the reporting guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Six databases were retrieved, with retrieval dates ranging from the establishment of the databases to December 2022. Data extraction and study quality assessment were independently performed by two researchers according to the Physical Therapy Evidence Database (PEDro) scale. The effects of different Tai Chi exercise parameters on glucose and lipid metabolism in T2DM patients were analyzed by subgroup analyses and meta-regressions. A total of sixteen randomized controlled trials were included in the meta-analysis. The results indicated that Tai Chi had a significant and moderate impact on fasting blood glucose in T2DM patients, as well as a significant and large impact on glycosylated hemoglobin. Tai Chi had a significant and moderate impact on triglyceride, and a small, non-significant improvement on total cholesterol. The intervention frequency and duration of a single session were identified as predictors of the impact of Tai Chi on triglyceride. The optimal exercise parameters identified were the 24-style simplified Tai Chi, with a recommended exercise duration of 45-60 min per session, performed 5-7 times per week, and continued for at least 4-7 weeks. Tai Chi can significantly improve the glucose and lipid metabolism in T2DM patients, and the 24-style simplified Tai Chi with high exercise frequency and short duration may be the optimal exercise parameter for enhancing glucose and lipid metabolism. Registration number: CRD42023395282.


Sensing of sulfur dioxide by base metal thiolates: structures and properties of molecular NiN2S2/SO2 adducts.
The cis-dithiolate N2S2Ni complex bismercaptoethanediazacycloheptanenickel(II), (bme-dach)Ni or Ni-1', takes up two equivalents of sulfur dioxide in which thiolate-sulfur to SO2-sulfur interactions are well-defined by X-ray crystallography. Ni-1' x 2SO2, C9H18N2NiO4S4, yields monoclinic crystals belonging to the P2(1)/c space group: a = 10.308(4) angstroms, b = 13.334(5) angstroms, c = 10.842(4) angstroms, alpha = 90 degrees, beta = 91.963(6) degrees, gamma = 90 degrees, and Z = 4. Further characterization by nu(SO) IR spectroscopy, thermal gravimetric analysis, electronic spectroscopy, and visual color changes upon reversible SO2 adduct formation establish Ni-1' and the analogous bismercaptoethanediazacyclooctane derivative, (bme-daco)Ni, Ni-1, to be viable candidates for technical development as chemical sensors of this noxious gas. Visual SO2 detection limits of Ni-1 and Ni-1' are established at 25 and 100 ppm, respectively. Both the Ni-1' x 2SO2 adduct and the Ni-1' reactant are air stable. In addition, the stability of Ni-1' x SO2 to vacuum and removal of SO2 by heating make Ni-1' a possible storage/controlled release complex for SO2 gas.


p38 MAPK inhibition decreases TNF-alpha production and enhances postischemic human myocardial function.
TNF-alpha is a proinflammatory cytokine implicated in myocardial dysfunction following ischemia/reperfusion (I/R). I/R results in myocardial production of TNF-alpha and TNF-alpha suppresses myocardial contractility. p38 mitogen-activated protein kinase (MAPK) is a redox-sensitive protein kinase involved in intracellular signaling leading to TNF-alpha production. It remains unknown if the human heart produces TNF-alpha after I/R and, if so, whether p38 MAPK is involved. p38 MAPK inhibition enhances human myocardial post-I/R contractile function by inhibition of myocardial TNF-alpha production. Human atrial trabeculae were suspended in organ baths, field simulated at 1 Hz, and force development was recorded. Following a 90-min equilibration, trabeculae were exposed to a p38 MAPK inhibitor (SB 203580, 1 microM) or vehicle (each n = 6) prior to simulated ischemia (45 min hypoxia, substrate-free, rapid pacing at 3 Hz) followed by 120 min reoxygenation. Myocardial TNF-alpha levels were measured by ELISA at end reoxygenation. I/R increased human myocardial TNF-alpha levels from 26.9 +/- 9.3 to 83.9 +/- 19.2 pg/g wet tissue (P < 0.05 perfusion vs I/R; ANOVA Bonferroni/Dunn), while p38 MAPK inhibition decreased post-I/R myocardial TNF-alpha levels to 32.3 +/- 8.0 pg/g wet tissue (P > 0.05 p38 MAPK inhibition vs I/R). p38 MAPK inhibition improved postischemic force development from 18.5 +/- 2.1 to 37.0 +/- 2.0% baseline developed force (%BDF; P < 0.05 I/R vs p38 MAPK inhibition). (1) The human heart produces TNF-alpha after I/R, (2) p38 MAPK mediates myocardial I/R-induced TNF-alpha production, (3) p38 MAPK inhibition limits functional impairment after I/R, and (4) inhibition of ischemia-induced TNF-alpha production may represent a potent therapeutic strategy for improving myocardial function after angioplasty, coronary bypass, or heart transplantation.


Thyroid Function Characteristics and Determinants: The Rotterdam Study.
Information on determinants and change of thyroid function over time is sparse and conflicting but crucial for clinical interpretation and research. Therefore, our aim was to systematically investigate determinants of thyroid-stimulating hormone (TSH), free thyroxine (FT4) (as markers of thyroid function), their mutual relation (as marker of thyroid function set point) and changes in thyroid function over time. We included 9402 participants from the Rotterdam Study not taking thyroid medication and with available thyroid function measurements. Repeated measurements (6.5-year interval) were available for 1225 participants. The association of selected determinants with TSH, FT4, and their mutual relation (reflecting thyroid function set point) was estimated using linear regression models using restricted cubic splines with three knots. The factors investigated were age, sex, body mass index (BMI), tobacco smoking, alcohol use, thyroperoxidase antibodies (TPOAb), and common genetic factors. Most influential determinants of TSH were age, smoking, genetic determinants, and TPOAb levels (p < 0.001). For FT4, most influential determinants were age, BMI, sex, genetic determinants and TPOAb levels (p < 0.001). Older age, female sex, and increased TPOAb levels were associated with a stronger relation between TSH and FT4. TSH levels did not change over time, irrespective of age. FT4 levels increased over time, most prominently in those older than 65 years of age (mean increase of 4.5 pmol/L). The main factors that influence the relationship between thyroid hormone and molar concentrations of TSH in our population-based cohort study are age, smoking, BMI, TPOAb levels, and common genetic variants. The set point that determines TSH secretion as it relates to negative thyroid hormone feedback is modified by age, sex and TPOAb positivity. FT4 levels increase over time, with a more pronounced increase in the elderly, while TSH values seem stable over time. Our results question the current notion of an increase of TSH with increasing age.


Mechanical, biochemical, and dietary determinants of the functional model of bone development of the radius in children and adolescents.
This study examined the degree to which various mechanical, biochemical, and dietary factors are related to nonweight bearing bone properties in 172 healthy peri-pubertal children (age, 11.7 ± 2.0 years). Dominant radial speed of sound (rSOS) was measured by transaxial quantitative ultrasound at distal radius. Potential modulating factors included somatic maturity offset (years from age of peak height velocity), grip strength, forearm lean cross-sectional area (CSA), physical activity, nutritional intake, and amino-terminal cross-linking propeptide (NTx), reflecting bone resorption. In a hierarchical regression, grip strength adjusted for CSA was the second most important predictor of rSOS after the maturity offset (β = 0.22 and β = 0.33, respectively; R2 = 0.16). When relative grip strength was added to the model the contribution of sex was no longer significant. Calcium intake was a significant predictor of rSOS only after NTx was accounted for in the model (β = 0.17, R2 = 0.21). This may suggest that calcium's effects on the muscle-bone unit may be modulated through bone resorption. In the final model, relative grip strength together with maturity offset, dietary calcium, and NTx explained up to 21% of the variance in rSOS in this cohort of children. Therefore, during the peri-pubertal stage, size-adjusted forearm muscle strength is related to radial bone strength after controlling for maturity, with calcium intake having a potential indirect association through NTx.


Dendritic cell vaccination with xenogenic polypeptide hormone induces tumor rejection in neuroendocrine cancer.
No relevant breakthrough has yet been achieved in the identification of tumor antigens in many neuroendocrine cancer types that exist, such as malignant gastrinoma, insulinoma, or medullary thyroid carcinoma. The aim of this study was to proof the concept of dendritic cell immunization with a tumor cell-specific polypeptide hormone as a target molecule in a transgenic mouse model for medullary thyroid carcinoma (Ret/Cal mice). Ret/Cal mice were repeatedly immunized for up to 6 months with amino acid-modified (xenogenic) calcitonin-pulsed dendritic cells. Xenogenic calcitonin was chosen for immunization due to its higher immunogenicity as compared with murine calcitonin. Lymph nodes from control protein-immunized mice did not show any macroscopic abnormalities, whereas tumor peptide-treated mice revealed in general profoundly enlarged lymph nodes. In tetramer analysis of paratumorous lymph nodes, 1.9% to 3.1% of all infiltrating CD8(+) T cells were specific for one of three tumor epitopes tested. Analysis of the activated IFN-gamma-secreting component in splenic cells revealed an average of 2.8% tumor epitope-specific CD8(+) cells. Immunohistochemistry revealed strong CD8(+) tumor infiltration in calcitonin-vaccinated mice. In addition, these cells also showed strong in vitro lysis capacity at up to 63.3%. Most importantly, calcitonin-immunized mice revealed largely diminished tumor outgrowth (-74.3%) compared with control mice (P < 0.0001). Likewise, serum calcitonin levels in calcitonin-vaccinated Ret/Cal mice were lower than in the control group. These results have a major effect, as they are the first to establish a role for xenogenic polypeptide hormones as target molecules for immunotherapy in endocrine malignancies.


The effect of contour closure on shape recognition.
Recent research on the Gestalt principle of closure has focused on how the presence of closure affects the ability to detect contours hidden in cluttered visual arrays. Some of the earliest research on closure, however, dealt with encoding and recognizing closed and open shapes, rather than detection. This research re-addresses the relation between closure and shape memory, focusing on how contour closure affects the ability to learn to recognize novel contour shapes. Of particular interest is whether closed contour shapes are easier to learn to recognize and, if so, whether this benefit is due to better encoding of closed contour shapes or easier comparison of closed contour shapes to already learned shapes. The results show that closed contours are indeed easier to recognize and, further, that this advantage appears to be related to better encoding.


Outward bulging of the right parietal bone in connection with fibrous dysplasia in an infant: a case report.
Fibrous dysplasia (FD) is a developmental disease of bone in which there is replacement of normal spongiosa and filling of the medullary cavity of affected bones by an abnormal fibrous tissue that contains trabeculae of poorly calcified primitive bone formed by osseous metaplasia. Fibrous dysplasia is a common benign bone disease existing in monostotic and polyostotic forms. It is sometimes associated with aneurysmal bone cysts, and it is a component of McCune-Albright and Mazabraud syndromes. We describe here a 4-months old Austrian infant who presented with a hard bulging painless mass of (5 x 3 cm) of the right parietal bone. Radiographs showed a large irregular osteolytic lesion. T1-weighted MR image showed significant expansile lesion associated with a dense zone of calcification in the diploic space. To the best of our knowledge this is the first clinical report of an infant with early presentation of monostotic fibrous dysplasia of the right parietal bone. Fibrous dysplasia of the skull is a painless progressively expanding destructive bone swellings produce cosmetic deformities. The clinical course may be unpredictable, with sudden appearance of symptoms, some of which can be important and irreversible. In our present patient, the possibility that an early surgical correction might positively interfere with the natural history of the lesion has to be evaluated by taking into account the obvious difficulties that will be encountered in reconstructing the skull after a wide excision of the pathologic bone.


Anticoagulation Alone for Aortic Segment Treatment in Symptomatic Primary Aortic Mural Thrombus Patients.
Primary aortic mural thrombus (AMT) is a rare entity. Asymptomatic AMT may be found in imaging studies for other disease studies. Symptomatic AMT as embolic events may localize in the arterial branches of the aorta; limb ischemia is the most usual clinical presentation, though. However, when proximal aorta is compromised, visceral branches occlusion and ischemia may determine morbidity and mortality in these patients. We performed a retrospective study with collection of data from January 2011 to September 2016. Medical records of patients were reviewed for: demographic data, cardiovascular risk factors or any known prothrombotic predisposing condition, clinical presentation, vessel of embolism, localization of aortic thrombus, treatment of AMT and symptoms, follow-up, and computed tomography scan imaging findings. A total of 8 patients were included in the study. Mean age was 54.7 ± 11.5 years, with male/female ratio 3:1. Four (50%) patients had AMT at the arch or descending aorta, 3 (37.5%) patients in the infrarenal sector, and the remaining in the visceral aorta. All but one patient received anticoagulation alone for the aortic thrombus. Patient with femoral thromboembolectomy died in the early postoperative time due to severe massive embolism. Median follow-up was 23 months (range, 1-50). Five out of seven patients showed complete aortic thrombus resolution in imaging follow up. None of the patients presented recurrence of embolic events. An anticoagulation first-approach treatment may be reasonable if mild organ damage is encountered. This strategy may be continued if no recurrences in embolic events are encountered, as high percentage of thrombus resolution is expected. Open or endovascular may be saved for life-threatening visceral or arch branches damage.


Operating characteristics of residential care communities, by community bed size: United States, 2012.
In 2012, the majority of residential care communities had 4–25 beds, yet 71% of residents lived in communities with more than 50 beds. A lower percentage of communities with 4–25 beds were chain-affiliated, nonprofit, and in operation 10 years or more, compared with communities with 26–50 and more than 50 beds. Dementia-exclusive care or dementia care units were more common as community size increased. A higher percentage of communities with more than 50 beds screened for cognitive impairment and offered dementia-specific programming compared with communities with 4–25 and 26–50 beds. A higher percentage of communities with more than 50 beds screened for depression compared with communities with 4–25 beds. Compared with communities with 4–25 beds, a higher percentage of communities with 26–50 beds and more than 50 beds provided therapeutic, hospice, mental health, and dental services; but a lower percentage of communities with more than 50 beds provided skilled nursing services than did smaller communities. This report presents national estimates of residential care communities, using data from the first wave of NSLTCP. This brief profile of residential care communities provides useful information to policymakers, providers, researchers, and consumer advocates as they plan to meet the needs of an aging population. The findings also highlight the diversity of residential care communities across different sizes. Corresponding state estimates and their standard errors for the national figures in this data brief can be found on the NSLTCP website at http://www.cdc.gov/nchs/nsltcp/ nsltcp_products.htm. These national and state estimates establish a baseline for monitoring trends among residents living in residential care.


Syrinx resolution is correlated with the upward shifting of cerebellar tonsil following posterior fossa decompression in pediatric patients with Chiari malformation type I.
Chiari malformation type I (CMI) is characterized by deformed hindbrain. This study aimed to quantitatively evaluate the alterations in position of hindbrain after Posterior fossa decompression (PFD), and to identify the factors associated with syrinx resolution in pediatric patients with CMI. Eighty-seven patients, aged from 5 to 18 years, who underwent PFD for CMI between September 2006 and September 2012 were retrospectively reviewed. On mid-sagittal MR images, the position of medulla oblongata and cerebellum was quantitatively evaluated preoperatively and at follow-up. The maximal syrinx/cord (S/C) ratio and syrinx length were also measured. Significant improvement of syrinx was defined as a more than 20 % decrease in maximal S/C ratio or length on follow-up MRI. Neurological deficits were found in 51 of the 87 patients preoperatively and 37 (72.4 %) of them obtained improvement of their symptoms at the last visit. Overall, upward shifting of the tip of cerebellar tonsil was observed in 66 (75.9 %) patients at the last follow-up. Moreover, the mean longitudinal distance of the tip of cerebella tonsil changed from 16.47 ± 5.00 to 13.89 ± 4.38 mm (P < 0.001) at final follow-up. Significant syrinx resolution was noticed in 79 (90.8 %) cases. Pointed cerebellar tonsils were found in 85 (97.7 %) of our patients preoperatively and 78 (91.8 %) of them acquired round cerebellar tonsils after PFD. The improvement of maximal S/C ratio was significantly correlated with upward shifting of the tip of cerebellar tonsil (P = 0.023). Following PFD for CMI, position and morphology of the cerebellar tonsil could revert to normal in most of the pediatric patients, and the upward shifting of the tip of cerebellar tonsil is significantly correlated with syrinx improvement. From this study, PFD without shunting may be effective for syrinx secondary to CMI in pediatric population.


Intranasal NAP (davunetide) decreases tau hyperphosphorylation and moderately improves behavioral deficits in mice overexpressing α-synuclein.
Genome-wide association studies have identified strong associations between the risk of developing Parkinson's disease (PD) and polymorphisms in the genes encoding α-synuclein and the microtubule-associated protein tau. However, the contribution of tau and its phosphorylated form (p-tau) to α-synuclein-induced pathology and neuronal dysfunction remains controversial. We have assessed the effects of NAP (davunetide), an eight-amino acid peptide that decreases tau hyperphosphorylation, in mice overexpressing wild-type human α-synuclein (Thy1-aSyn mice), a model that recapitulates aspects of PD. We found that the p-tau/tau level increased in a subcortical tissue block that includes the striatum and brain stem, and in the cerebellum of the Thy1-aSyn mice compared to nontransgenic controls. Intermittent intranasal NAP administration at 2 μg/mouse per day, 5 days a week, for 24 weeks, starting at 4 weeks of age, significantly decreased the ratio of p-tau/tau levels in the subcortical region while a higher dose of 15 μg/mouse per day induced a decrease in p-tau/tau levels in the cerebellum. Both NAP doses reduced hyperactivity, improved habituation to a novel environment, and reduced olfactory deficits in the Thy1-aSyn mice, but neither dose improved the severe deficits of motor coordination observed on the challenging beam and pole, contrasting with previous data obtained with continuous daily administration of the drug. The data reveal novel effects of NAP on brain p-tau/tau and behavioral outcomes in this model of synucleinopathy and suggest that sustained exposure to NAP may be necessary for maximal benefits.


Uncomplicated jejunal diverticulosis with pneumoperitoneum.
Small bowel diverticulosis is a rare finding within all bowel diverticuloses and jejunal diverticulosis is even rarer. Their relative clinical rarity and varied presentation may make diagnosis both delayed and difficult. We experienced a case of jejunal diverticulosis, which was diagnosed intraoperatively. A 55-year-old woman was admitted to Emergency Department with pneumoperitoneum on plain chest and abdominal film from a local clinic. She was hemodynamically stable with minimal tenderness on the left upper quadrant of the abdomen but no rebound tenderness. At surgery, small bowel torsion and jejunal diverticulosis were confirmed. Over 30 variable sized small bowel diverticula were noted on the mesenteric side of the proximal jejunum. The affected segment of the jejunum was about 180 cm. On exploration, we could not find any perforation site. No postoperative complications were observed, and the patient made a full recovery. Jejunal diverticulosis is rare, but it should not be regarded as insignificant.


Preclinical Alzheimer Disease Drug Development: Early Considerations Based on Phase 3 Clinical Trials.
The number of people in the United States living with Alzheimer disease (AD) is growing, resulting in significant clinical and economic impact. Substantial research investment has led to drug development in stages of AD before symptomatic dementia, such as preclinical AD. Although there are no treatments approved for preclinical AD, there are currently 6 phase 3 clinical trials for preclinical AD treatments. In this article, we review these clinical trials and highlight considerations for future coverage decisions. In line with the definition of preclinical AD, enrollment in these trials focuses on cognitively unimpaired patients that are at high risk of AD because of family history and then genetic testing or brain imaging. Enrollment in most of these trials also allows for younger patients, including those aged under 65 years. Primary clinical trial endpoints focus on cognition often 4 or more years after treatment. Secondary endpoints include other measures of cognition and function, as well as biomarkers. Review of these trials brings to light a few potential considerations when covering these new medications in the future. First, novel and potentially costly approaches involving genetic testing and/or positron emission tomography imaging may be needed to identify appropriate patients and should be developed efficiently. Second, the long duration of these clinical trials suggest that there may be a need for alternative payment approaches in the United States that encourage early payers to pay for a medication for which the long-term benefits may not be realized until after the beneficiary is no longer with the health plan. Third, the value of AD treatments may differ across populations, creating a potential role for indication-based or population-based contracting. Finally, considering the potentially high budgetary impact and little real-world evidence for a new drug class, payers and manufacturers may want to consider outcomes-based payment approaches and coverage with evidence development to mitigate uncertainty about the value of the treatment demonstrated in well-defined populations in clinical trials versus more heterogeneous real-world settings. DISCLOSURES: This work was funded through a generous gift from the Global CEO Initiative on Alzheimer Disease. Hung reports grants from Agency for Healthcare Research and Quality and Pharmaceutical Research and Manufacturers of America outside the submitted work and past employment at CVS Health and BlueCross BlueShield Association. McClellan is an independent board member on the boards of Johnson & Johnson, Cigna, Alignment Healthcare, and Seer; co-chairs the Accountable Care Learning Collaborative and the Guiding Committee for the Health Care Payment Learning and Action Network; and receives fees for serving as an advisor for Cota and MITRE. Hamilton Lopez and Schneider have nothing to disclose. Part of this work was presented at the 2019 AMCP Nexus Meeting, October 29-November 1, 2019, in National Harbor, MD.


Use of Ultrasound Guidance During Cannulation of Arteriovenous Fistulas.
Individuals who require renal replacement therapy overwhelmingly choose outpatient hemodialysis. Appropriate cannulation techniques are an essential element in access preservation and in the prevention of access-related complications. Missed cannulations can result in damage of arteriovenous fistulas (AVFs) and arteriovenous grafts (AVGs). Ultrasound-guided cannulation is an effective technique for the placement of peripheral intravenous (IV) catheters and central venous catheters (CVCs) for hemodialysis. The purposes of this project were to determine if ultrasound-guided cannulation of AVFs decreased the number of missed cannulations, to determine staff and patient perceptions regarding cannulation, and to implement a quality incentive program (QIP) to implement an evidence-based ultrasound-guided policy and procedure, training program, and competency evaluation at a hospital-based dialysis facility.