Effect of supplemental zinc on the growth and serum zinc concentrations of prepubertal children: a meta-analysis of randomized controlled trials.
Multiple studies have been carried out to assess the effect of zinc supplementation on children's growth. The results of these studies are inconsistent, and the factors responsible for these varied outcomes are unknown. Meta-analyses of randomized controlled intervention trials were therefore completed to assess the effect of zinc supplementation on the physical growth and serum zinc concentrations of prepubertal children. A total of 33 acceptable studies with appropriate data were identified by MEDLINE (National Library of Medicine, Bethesda, MD) searches and other methods. Weighted mean effect sizes (expressed in SD units) were calculated for changes in height, weight, weight-for-height, and serum zinc concentration by using random-effects models; factors associated with effect sizes were explored by meta-regression techniques. Zinc supplementation produced highly significant, positive responses in height and weight increments, with effect sizes of 0.350 (95% CI: 0.189, 0.511) and 0.309 (0.178, 0.439), respectively. There was no significant effect of zinc on weight-for-height indexes [weighted mean effect size: -0.018 (-0.132, 0.097)]. Zinc supplementation caused a large increase in the children's serum zinc concentrations, with an effect size of 0.820 (0.499, 1.14). Growth responses were greater in children with low initial weight-for-age z scores and in those aged >6 mo with low initial height-for-age z scores. Interventions to improve children's zinc nutriture should be considered in populations at risk of zinc deficiency, especially where there are elevated rates of underweight or stunting. The population mean serum zinc concentration is a useful indicator of the successful delivery and absorption of zinc supplements in children.


Vinylphosphonium and 2-aminovinylphosphonium salts - preparation and applications in organic synthesis.
The main synthetic routes towards vinylphosphonium salts and their wide applications in organic synthesis are discussed in this review. Particular attention is paid to the use of these compounds as building blocks for the synthesis of carbo- and heterocyclic systems after their prior transformation into the corresponding phosphorus ylides, followed by the intramolecular Wittig reaction with various types of nucleophiles containing a carbonyl function in their structures.


Pelvic Bone Hydatidosis: A Dangerous Crippling Disease.
Hydatid disease is one of the most complicated and devastating conditions caused by Echinococcus granulosus. This globally distributed disease continues to be an important public health concern in many low- and middle-income countries. The liver and the lungs are the most frequently involved sites, but virtually any organ system can be affected. Osseous hydatidosis is relatively less common, but it is extremely debilitating and difficult to manage due to frequent recurrences. Patients often demonstrate a delayed clinical presentation as bone involvement is predominantly a silent and slowly progressive disease with a long latent period. Radiological investigations play an important role in the diagnosis. Although standard therapeutic guidelines are not available, the treatment of choice is a combination of chemotherapy and surgery. Clinicians should perform a lifelong follow-up for early detection of potential recurrence and sequels. This paper aims to highlight hydatid disease of the pelvic bone as an important differential diagnosis of tubercular hip arthritis, especially in areas with high echinococcosis prevalence.


Health insurance in China and India: segmented roles for public and private financing.
Surveys suggest that over the past five to ten years, the amount of health insurance premiums collected has grown at an average rate of 34 percent in India and 43 percent in China. A variety of public and private insurance schemes play important roles in enabling health care provision for unique populations in these two countries. This paper provides an overview of the trends in health insurance as a financing mechanism for health care in China and India. It suggests a broad policy approach to aligning and mobilizing forces that would allow segmented expansion of public and private health insurance.


The biochemistry and pharmacology of mesoamygdaloid dopamine neurons.
Populations of DA neurons innervating the component nuclei of the amygdaloid complex differ in their inferred density of innervation, estimated rate of impulse activity, and adaptive response to the prolonged administration of antipsychotic drugs. Mesoamygdaloid DA neurons have in common the absence of tonically inhibitory, nerve terminal autoreceptors regulating DA synthesis, the nonassociation with a DA-stimulated adenylate cyclase, and the regulation of DA synthesis by receptor-mediated neuronal feedback mechanisms and end-product inhibition. The output of the amygdaloid complex appears to be organized into distinct functions subserved by component nuclei. The present findings suggest a differing role for DA afferents in modulating the functional output of discrete nuclei. The significance of this focal influence will be speculative pending a more complete understanding of the physiology of DA neurotransmission in the amygdaloid complex. Populations of DA neurons innervating discrete amygdaloid nuclei exhibit a composite of mechanisms of regulation and signal transduction and pharmacology that differ from that of other mesotelencephalic DA systems. These comparisons highlight the fact that the nucleus accumbens and olfactory tubercle do not represent or reflect DA neurotransmission in the limbic system. The study of the physiology, pharmacology, and pathology of mesolimbic DA neurons can and should extend beyond the nucleus accumbens and olfactory tubercle to the amygdala and other brain structures central to the organization of the limbic system. It is our opinion that the term "mesolimbic" DA system has purely anatomical connotations and that a more specific terminology (e.g., meso-central amygdaloid nuclear) would express the functional organization of this system more accurately.


Educational Quality of YouTube Cholesteatoma Surgery Videos: Areas for Improvement.
Otolaryngology surgical education continues to evolve where trainees increasingly use videos to learn technical skills. Trainees commonly use YouTube, but no study to date has evaluated the educational quality (EQ) of otologic surgical videos on YouTube. We aim to assess the EQ of cholesteatoma surgical videos. Cholesteatoma surgical videos were queried using YouTube search terms, assessed using LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS), a validated assessment tool for publication, and categorized into low (0-6), medium (7-12), and high (13-18) EQ groups. In total, 74 videos were identified (mean LAP-VEGaS score = 9.6 ± 4.0) and 44.6% had medium EQ. Videos commonly lacked graphic aids to highlight anatomy (71.6%) and postprocedural outcomes (68.9%). LAP-VEGaS scores were greater in videos originating from US surgeons compared to non-US surgeons (12.4 ± 3.4 vs 8.0 ± 3.5; P < .001). Our study highlights that otolaryngology trainees may experience difficulty finding high-EQ cholesteatoma surgery videos on YouTube. Areas for improved EQ content are discussed. Level of evidence: IV.


Stereological Study of Changes of GABA-Immunoreactive Neurons in Spinal Dorsal Horn of SNI Rats.
To observe the changes in the mechanical withdrawal threshold (MWT) and the proportion of GABA-immunoreactive neurons in spinal dorsal horn (SDH) of the spared nerve injury (SNI) rat model. Thirty-six healthy male SD rats were randomly divided into a sham-operated group (group D, n = 18) and an SNI group (group S, n = 18). The left sciatic nerve trunk and three branches were exposed, two of which, known as tibial and the peroneal nerve, were ligated and cut off. The sural nerve was preserved to build the SNI model in group S. The left sciatic nerve trunk and three branches were only exposed in group D. MWT tests were performed on the medial and lateral sides of the rats' left hindpaw 1 day before surgery and at 7th, 14th, and 28th day after surgery. In group S, compared with the baseline measured 1 day before surgery, MWT on the medial and lateral sides of the rats' left hindpaw decreased significantly on the 7th, 14th, and 28th days after surgery (P < 0.05), while in group D, there was no statistically significant difference (P > 0.05). Compared with right SDH, there were not statistically significant reductions in the proportions of GABAergic neurons of left SDH on 7th and 28th day after SNI (P > 0.05); however, the proportion of GABAergic neurons in left SDH significantly decreased, compared with that in right side on 14th day after SNI (P < 0.05). On the same way, the proportions of GABAergic neurons on 7th, 14th, and 28th day after surgery were not statistically different (P > 0.05) in group D. The SNI model could reduce the proportion of GABA-immunoreactive neurons in the rat's spinal dorsal horn on the nerve-injured side, and this change was lasting, which might be related to the transformation of the GABA-immunoreactive neurons.


Peer relations across contexts: individual-network homophily and network inclusion in and after school.
Peer relations across 2 contexts (in school and after school) were examined for 577 participants, approximately 12 years old, from 3 middle schools in Milan, Italy. The primary research questions were: Do peer networks from different contexts uniquely contribute to explaining variance in individual behavior? Do measures of peer preference and peer network inclusion across contexts uniquely contribute to explaining individual depressive symptoms? Structural equation models showed that both the in-school and the after-school peer networks uniquely contributed to explaining variance in 2 types of individual problem behavior (in-school problem behavior, after-school delinquency), and that similarity with the 2 peer networks varied according to behaviors specific to each context and across gender. Finally, both in-school and after-school peer network inclusion contributed to explaining variance in depressive symptoms, after controlling for classroom peer preference.


Classification of Skeletal Phenotypes of Adult Patients With Cleft Skeletal Class III Malocclusion Using Principal Component Analysis and Cluster Analysis.
The purpose of this study was to classify the skeletal phenotypes of adult patients with skeletal class III (C-III) malocclusion and unilateral or bilateral cleft lip and palate using principal component analysis and cluster analysis. The samples consisted of 81 adult C-III patients with cleft lip and palate (CLP) who underwent orthognathic surgery (OGS) or distraction osteogenesis (59 males and 22 females; 50 unilateral cleft lip and palate and 31 bilateral cleft lip and palate; mean age when lateral cephalograms were taken, 22.2±4.6 y). Thirteen angular and one ratio cephalometric variables were measured. Using 4 representative variables obtained from principal component analysis (SNA, SNB, Gonial angle, and Bjork sum), K-means cluster analysis was performed to classify the phenotypes. Then, statistical analysis was conducted to characterize the differences in the variables among the clusters. Five clusters were obtained from 3 groups: severely retrusive maxilla and moderately retrusive mandible group: cluster-1 (23.5%, severely hyperdivergent pattern), cluster-4 (27.2%, moderately hyperdivergent pattern), and cluster-5 (11.1%, normodivergent pattern); moderately retrusive maxilla and normal mandible group: cluster-2 (30.9%, normodivergent pattern); normal maxilla and moderately protrusive mandible group: cluster-3 (7.4%, normodivergent pattern). Although skeletal phenotypes were diverse, distribution of sex and cleft type did not differ among 5 clusters ( P >0.05). Sixty-two percent of cleft patients showed a severely retrusive maxilla and moderately retrusive mandible (cluster-1, cluster-4, and cluster-5), which indicated that these are the main cause of skeletal C-III malocclusion in CLP patients who were treated with OGS. Therefore, it is necessary to consider presurgical orthodontic treatment and surgical planning based on the skeletal phenotypes of CLP patients.


A graph-searching method for MLC leaf sequencing under constraints.
A new leaf-sequencing algorithm for step-and-shoot IMRT that is based on a graph-searching technique is described. An iterative process guided by a quantitative measure for the complexity of the initial or residual intensity pattern is used to identify the field segments shaped by a multileaf collimator (MLC). Given a user selected number of intensity levels, the algorithm searches deliverable segment candidates considering all intensity levels and two collimator positions separated by 90 degrees. The candidates for each intensity level are obtained as the least number of segments to cover the areas with equal or higher intensity. The shape of a deliverable segment is adjusted by leaving out certain beam elements for later delivery if this results in a simpler residual intensity pattern and the segment is still deliverable. For a MLC design that does not allow leaf interdigitation, it is initially assumed that a single segment cannot cover two disjoined areas. Among all candidates the segment with the greatest reduction of the complexity of the residual intensity distribution is chosen for the current step of iteration. The iterative process generates a set of deliverable segments of simply connected areas. These segments are combined later under specific MLC constraints. Different orders of segment combination are considered for minimizing the beam-on time. The final segments are sequenced to minimize the leaf travel. This algorithm has been tested using randomly generated intensity distributions and clinical cases for the Varian, Siemens, and Elekta MLC systems. The results show that as the number of intensity levels is increased, the numbers of segments and MUs increase only modestly. Using two collimator angles results in decreases in the required number of segments and the number of monitor units that can be as much as 20%.


In-vitro study of gonadotrophin signaling pathways in human granulosa cells in relation to progesterone receptor expression.
In humans, data on gonadotrophin-activated (LH, HCG and FSH) progesterone receptor expression and signalling pathways involved in matrix metalloproteinases (MMPs) expression presumably linked to the follicle rupture, are limited. Our hypothesis is LH, HCG and FSH increase progesterone receptor expression in granulosa cells through different signalling pathways, leading to an increased expression of ADAMTS-1 and MMP3/10, which may mediate follicular rupture through the transcription factor, HIF1A. Human granulosa cells were isolated from follicular aspirates obtained from 22 healthy women participating in our IVF programme for male-factor infertility. Progesterone receptor and HIF1A expression was assessed by immunofluorescence, and PKA-PKC-PI3K- ERK1/2, ADAMTS-1 and MMP3/10 expression by Western blot in pre-ovulatory and in cultured granulosa cells. Results show that HCG, LH and FSH regulate progesterone receptor expression and activate PKA, PKC, PI3K and ERK1/2 signalling pathways in granulosa cells but progesterone receptor expression is only mediated by PKA, PKC and ERK pathways. HCG, FSH and LH regulated MMPs expression through progesterone receptors. Moreover, HCG-progesterone-receptor-dependent HIF1A expression stimulated MMP3/10 expression but not that of ADAMTS-1. These results suggest differential downstream progesterone receptor signalling, as progesterone receptor regulates MMP3/10 expression via HIF1A, which is not involved in ADAMTS-1 expression.


Shallow aquifer response to climate change scenarios in a small catchment in the Guarani Aquifer outcrop zone.
Water availability restrictions are already a reality in several countries. This issue is likely to worsen due to climate change, predicted for the upcoming decades. This study aims to estimate the impacts of climate change on groundwater system in the Guarani Aquifer outcrop zone. Global Climate Models (GCM) outputs were used as inputs to a water balance model, which produced recharge estimates for the groundwater model. Recharge was estimated across different land use types considering a control period from 2004 to 2014, and a future period from 2081 to 2099. Major changes in monthly rainfall means are expected to take place in dry seasons. Most of the analysed scenarios predict increase of more than 2 ºC in monthly mean temperatures. Comparing the control and future runs, our results showed a mean recharge change among scenarios that ranged from ~-80 to ~+60%, depending on the land use type. As a result of such decrease in recharge rates, the response given by the groundwater model indicates a lowering of the water table under most scenarios.


Tibia Bone Microvascular Flow Dynamics as Compared to Anterior Tibial Artery Flow During Body Tilt.
We compared microvascular and macrovascular blood flows of the tibia and anterior tibial artery during graded whole-body tilt. We hypothesized equal responses for bone microvascular and macrovascular blood flows during varying angles of tilt. There were 18 volunteers who were randomly positioned in the following postures: supine, 15° head-up tilt, 6° head-up tilt, 6° head-down tilt, and 15° head-down tilt using an inversion table with reference to seated posture (baseline control). Ultrasonography quantified anterior tibial arterial diameter and peak systolic velocity, enabling calculation of macrovascular blood flow to the tibia. Tibial bone microvascular blood flow was measured noninvasively using photoplethysmography in the same leg. Transitioning from a seated position to a supine position, macrovascular blood flow did not change significantly (1.81 ± 1.18 to 2.80 ± 1.74cm 3 · s-1). However, bone microvascular flow increased significantly (0.36 ± 0.23 to 1.11 ± 0.79 V) from the seated to the supine position. Transitioning from a seated posture to 15° head-down tilt, both arterial macrovascular and bone microvascular flows increased significantly (1.81 ± 1.18 to 3.32 ± 2.08 cm3 · s-1 and 0.36 ± 0.23 V to 2.99 ± 2.71 V, respectively). The normalized flow for microvascular blood flow as a function of body tilt was significantly greater than that for macrovascular blood flow at 6° and 15° head-down tilt. These data do not support our hypothesis that bone microvascular flow and arterial macrovascular flow share equal responses to altered body tilt. Therefore, for a given decrease in local blood pressure in the leg with head-down body tilt, the magnitude of increase in blood flow is greater in the microcirculation as compared to the feeding artery.Becker RL, Siamwala JH, Macias BR, Hargens AR. Tibia bone microvascular flow dynamics as compared to anterior tibial artery flow during body tilt. Aerosp Med Hum Perform. 2018; 89(4):357-364.


Recommendations to enhance constructivist-based learning in Interprofessional Education using video-based self-assessment.
Interprofessional collaboration is crucial to the optimization of patient care. This paper aims to provide recommendations for implementing an innovative constructivist educational concept with the core element of video-based self-assessment. A course for students in medicine, physiotherapy, and nursing was developed through interprofessional, cross-institutional collaboration. The course consisted of drawing on prior knowledge about the work done by each professional group in regard to a specific clinical scenario and an interprofessional treatment situation, filming a role play of this treatment situation, and a structured self-assessment of the role play. We evaluated the preparation and implementation of the three courses conducted thus far. Concrete recommendations for implementation were made based on evaluation sheets (students), open discussions (tutors, instructors, institutions) and recorded meeting minutes (project managers, project participants). Basic recommendations for implementation include: selecting appropriate criteria for self-assessment and a simulated situation that offers members of each professional group an equal opportunity to act in the role play. In terms of administrative implementation we recommend early coordination among the professions and educational institutions regarding the target groups, scheduling and attendance policy to ensure participant recruitment across all professions. Procedural planning should include developing teaching materials, such as the case vignette and treatment scenario, and providing technical equipment that can be operated intuitively in order to ensure efficient recording. These recommendations serve as an aid for implementing an innovative constructivist educational concept with video-based self-assessment at its core.


Family physicians beliefs and attitudes regarding adult pneumococcal and influenza immunization in Lebanon.
Influenza and pneumococcal diseases are responsible for more deaths than all other vaccine-preventable diseases combined. Despite all efforts, the vaccination rate is below target. To assess knowledge and beliefs of family physicians in Lebanon regarding influenza and pneumococcal vaccines, to identify adult immunization barriers, to assess physicians' use of evidence-based strategies to improve adult immunization and identify barriers to implementation of such strategies. All 52 Lebanese family physicians attending the annual family medicine conference in Beirut in November 2009 were asked to fill a self-administered questionnaire that included items inquiring about knowledge, beliefs, attitudes, barriers to these vaccines and their opinions regarding strategies to improve immunization rate. Response rate was 82.7%. Accurate knowledge of influenza and pneumococcal vaccination guidelines was 58.1% and 53.5%, respectively. Thirty-eight physicians (88.4%) believe that influenza and pneumococcal vaccines are important, while 36 (83.7%) recommend influenza vaccine and 33 (76.7%) pneumococcal vaccine. Barriers for recommending vaccines were reported by 14 participants (32.5%). Concerning the influenza vaccine, the most commonly reported barriers were patient's refusal and non-availability of the vaccine, followed by physicians' concerns about efficacy and safety. As for the pneumococcal vaccine, the most frequently reported barriers were patient's refusal, cost and physicians concerns about efficacy. Insufficient time and unknown immunization status were reported to be barriers of lesser importance. Twenty-six physicians (61%) reported physicians' reminders as the most important intervention to promote adult immunization, followed by patient education (48%). Lack of time and availability of electronic medical record were cited as important strategies to increase adult immunization rate. Education and intervention efforts are needed to overcome barriers faced by practitioners and to define the most effective strategies to overcoming these barriers.


Interaction of solitons with extended nonlinear defects.
The interaction of nonlinear Schrödinger solitons with extended inhomogeneities with modified nonlinear coefficients is investigated numerically. Decreased nonlinear coefficients act as nonlinear potential steps and yield transmission or reflection of the incoming soliton. For increased nonlinear coefficients (nonlinear potential wells) and a given range of initial velocities and nonlinearity mismatch, the scattering pattern exhibits periodically repeating regions of trapping and transmission as a function of the length of the inhomogeneity. It is shown that the escape of the soliton is due to a resonance between the period of the shape oscillations of the soliton inside the inhomogeneity and the length of the latter. The combined effect of overlapping linear and nonlinear potentials is also investigated.


Simple and Reliable Lift-Off Patterning Approach for Graphene and Graphene-Ag Nanowire Hybrid Films.
We present a simple, ultrasonic vibration-assisted lift-off-based patterning approach for graphene and graphene-Ag nanowire (NW) hybrid films. A 20 μm width pattern with uniform and smooth pattern edges was neatly defined on various rigid and flexible substrates. The patterned graphene-Ag NW electrodes showed a low sheet resistance of 19 Ω/sq with a high transmittance of 93% at 550 nm, a robust stability against oxidation, and a high reliability under a bending test. The electrodes also exhibited markedly higher performance than that of commercial fluorine-doped tin oxide electrodes for dye-sensitized solar cells. Given its low-cost, high throughput, and nondamaging effect, this simple and reliable patterning approach stimulates the practical applications of graphene-based flexible transparent electrodes in soft electronic and optoelectronic devices.


Preclinical to clinical translation of CNS transporter occupancy of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor.
Monoamine reuptake inhibitors exhibit unique clinical profiles that reflect distinct engagement of the central nervous system (CNS) transporters. We used a translational strategy, including rodent pharmacokinetic/pharmacodynamic modeling and positron emission tomography (PET) imaging in humans, to establish the transporter profile of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor. TD-9855 was a potent inhibitor of norepinephrine (NE) and serotonin 5-HT uptake in vitro with an inhibitory selectivity of 4- to 10-fold for NE at human and rat transporters. TD-9855 engaged norepinephrine transporters (NET) and serotonin transporters (SERT) in rat spinal cord, with a plasma EC50 of 11.7 ng/mL and 50.8 ng/mL, respectively, consistent with modest selectivity for NET in vivo. Accounting for species differences in protein binding, the projected human NET and SERT plasma EC50 values were 5.5 ng/mL and 23.9 ng/mL, respectively. A single-dose, open-label PET study (4-20mg TD-9855, oral) was conducted in eight healthy males using the radiotracers [(11)C]-3-amino-4- [2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile for SERT and [(11)C]-(S,S)-methylreboxetine for NET. The long pharmacokinetic half-life (30-40 h) of TD-9855 allowed for sequential assessment of SERT and NET occupancy in the same subject. The plasma EC50 for NET was estimated to be 1.21 ng/mL, and at doses of greater than 4 mg the projected steady-state NET occupancy is high (>75%). After a single oral dose of 20mg, SERT occupancy was 25 (±8)% at a plasma level of 6.35 ng/mL. These data establish the CNS penetration and transporter profile of TD-9855 and inform the selection of potential doses for future clinical evaluation.


Individual differences in skill acquisition and transfer assessed by dual task training performance and brain activity.
Assessment of expertise development during training program primarily consists of evaluating interactions between task characteristics, performance, and mental load. Such a traditional assessment framework may lack consideration of individual characteristics when evaluating training on complex tasks, such as driving and piloting, where operators are typically required to execute multiple tasks simultaneously. Studies have already identified individual characteristics arising from intrinsic, context, strategy, personality, and preference as common predictors of performance and mental load. Therefore, this study aims to investigate the effect of individual difference in skill acquisition and transfer using an ecologically valid dual task, behavioral, and brain activity measures. Specifically, we implemented a search and surveillance task (scanning and identifying targets) using a high-fidelity training simulator for the unmanned aircraft sensor operator, acquired behavioral measures (scan, not scan, over scan, and adaptive target find scores) using simulator-based analysis module, and measured brain activity changes (oxyhemoglobin and deoxyhemoglobin) from the prefrontal cortex (PFC) using a portable functional near-infrared spectroscopy (fNIRS) sensor array. The experimental protocol recruited 13 novice participants and had them undergo three easy and two hard sessions to investigate skill acquisition and transfer, respectively. Our results from skill acquisition sessions indicated that performance on both tasks did not change when individual differences were not accounted for. However inclusion of individual differences indicated that some individuals improved only their scan performance (Attention-focused group), while others improved only their target find performance (Accuracy-focused group). Brain activity changes during skill acquisition sessions showed that mental load decreased in the right anterior medial PFC (RAMPFC) in both groups regardless of individual differences. However, mental load increased in the left anterior medial PFC (LAMPFC) of Attention-focused group and decreased in the Accuracy-focused group only when individual differences were included. Transfer results showed no changes in performance regardless of grouping based on individual differences; however, mental load increased in RAMPFC of Attention-focused group and left dorsolateral PFC (LDLPFC) of Accuracy-focused group. Efficiency and involvement results suggest that the Attention-focused group prioritized the scan task, while the Accuracy-focused group prioritized the target find task. In conclusion, training on multitasks results in individual differences. These differences may potentially be due to individual preference. Future studies should incorporate individual differences while assessing skill acquisition and transfer during multitask training.


The Safety and Feasibility of the Single-Port Laparoscopic Repair of Intraperitoneal Bladder Rupture.
To evaluate the efficacy and safety of laparoendoscopic single-site surgery (LESS) in the repair of intraperitoneal bladder rupture. All consecutive patients who underwent LESS for intraperitoneal bladder rupture in three hospitals in Korea were included prospectively in this study. LESS was performed using a homemade single-port device composed of an Alexis wound retractor and a surgical glove. Of the 22 patients, 18 were male. The mean age was 40.50 ± 11.83 years. The mean body mass index was 24.19 ± 2.61 kg/m2. The cause of rupture was trauma (n = 21) or iatrogenic injury (n = 1). The mean bladder rupture diameter was 3.41 ± 1.01 cm. LESS bladder rupture repair was completed effectively in all patients. The mean operative time was 89.05 ± 11.29 minutes. The mean length of hospital stay was 2.91 ± 0.53 days. Postoperatively, none of the patients required patient-controlled analgesia, and none developed major complications. The urethral Foley catheter was removed 7.68 ± 2.08 days after surgery. LESS repair of intraperitoneal bladder rupture, which involves a homemade single-port device, was a feasible and safe alternative to conventional laparoscopy in this case series.


Diabetic glomerulopathy: unusual patterns and dual disease.
Diabetic glomerulopathy is a well-recognized consequence of both type I and type II diabetes. Occasionally, pathologic diagnosis may be challenging for the pathologist. These circumstances include atypical light microscopy or diabetic change with a second superimposed glomerulopathy (dual disease). We have compiled a selection of 12 renal biopsies from diabetic patients that show either an unusual pattern of nephropathy or "dual disease," as well as 2 cases in which the patient had no history of diabetes but had renal biopsies exhibiting changes consistent with diabetic nephropathy. The salient diagnostic features are discussed. To accurately assess these biopsies, immunofluorescence and electron microscopy become essential, and a broadened differential diagnosis must be considered.


Case 212: chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids.
History A previously healthy 23-year-old white man presented to the emergency department of our hospital with a 2-month history of dysarthria, progressively worsening vertigo, and difficulty walking. A diagnosis of retinitis pigementosa was made in this patient's childhood. He did not have any history of congenital syphilis. He did not have a history of nausea or vomiting, fever, weight loss, headache, photophobia, seizure, extremity weakness, or sensory disturbance. Physical examination revealed dysarthria, dysmetria, and ataxia. Kernig and Brudzinski signs were absent, and pathergy test results were negative. Laboratory evaluation revealed normal complete and differential blood counts and normal serum chemistry, including a normal serum angiotensin-converting enzyme level. Analysis of his serum was negative for antinuclear antibody (or ANA), cytoplasmic antineutrophil cvtoplasmic antibody (or cANCA), Sjögren syndrome antigens A and B (SS-A and SS-B, respectively), antitissue transglutaminase and antiendomysial antibodies, and paraneoplastic profile. Serum analysis was also negative for human immunodeficiency virus type 1 and type 2 RNA, Venereal Disease Research Laboratory (VDRL) test, rapid plasma regain (RPR), and fluorescent treponemal antibody absorption. Cerebrospinal fluid (CSF) analysis revealed clear fluid, a normal glucose level (64 mg/dL [3.6 mmol/L]; normal range, 40-70 mg/dL [2.2-3.9 mmol/L]), an elevated protein level (97 mg/dL; normal range, 12-60 mg/dL), and an elevated white blood cell count (7/mm(3) [0.007 ×10(9)/L] in tube 1 and 17/mm(3) [0.017 × 10(9)/L] in tube 2) with 84% lymphocytes. CSF immunoglobulin G level was elevated (30.1 mg/dL; normal, <5.9 mg/dL); however, there were no oligoclonal bands. Gram staining, acid-fast staining, and lactic acid, cryptococcal antigen, histoplasma antigen, herpes simplex virus polymerase chain reaction, VDRL, and RPR test results for CSF were negative. CSF did not grow any bacteria, fungus, or acid-fast bacillus at culture. CSF flow cytometry did not reveal a monoclonal lymphoid population. Initial imaging included brain magnetic resonance (MR) imaging. Computed tomography (CT) images of the chest, abdomen, and pelvis were normal (not shown). The patient's clinical symptoms and imaging findings responded to treatment with a high dose of oral steroids. However, the patient's symptoms exhibited clinical and radiologic progression after several attempts to taper the steroid dose.


Heat-balling wasps by honeybees.
Defensiveness of honeybee colonies of Apis cerana and Apis mellifera (actively balling the wasps but reduction of foraging) against predatory wasps, Vespa velutina, and false wasps was assessed. There were significantly more worker bees in balls of the former than latter. Core temperatures in a ball around a live wasp of A. cerana were significantly higher than those of A. mellifera, and also significantly more when exposed to false wasps. Core temperatures of bee balls exposed to false wasps were significantly lower than those exposed to V. velutina for both A. cerana and for A. mellifera. The lethal thermal limits for V. velutina, A. cerana and A. mellifera were significantly different, so that both species of honeybees have a thermal safety factor in heat-killing such wasp predators. During wasps attacks at the hives measured at 3, 6 and 12 min, the numbers of Apis cerana cerana and Apis cerana indica bees continuing to forage were significantly reduced with increased wasp attack time. Tropical lowland A. c. indica reduced foraging rates significantly more than the highland A. c. cerana bees; but, there was no significant effect on foraging by A. mellifera. The latency to recovery of honeybee foraging was significantly greater the longer the duration of wasp attacks. The results show remarkable thermal fine-tuning in a co-evolving predator-prey relationship.


Sustained transgene expression in rat kidney with naked plasmid DNA and PCR-amplified DNA fragments.
Recently, we developed a kidney-targeted gene transfer technique, in which naked DNA was injected into the renal vein while the renal vein and artery were clamped. Kidney-targeted DNA transfer with only the renal vein clamped is an important modification that may permit less invasive catheter-based gene transfer in future clinical applications. The preparation of PCR-amplified DNA fragments is less time-consuming than that of naked plasmid DNA. We examined rat erythropoietin (Epo) plasmid, pCAGGS-Epo, or PCR-amplified DNA fragment, fCAGGS-Epo, transfer into the rat kidney with only the renal vein clamped. The Epo level peaked at week 3 and then was sustained for 24 weeks, which resulted in significant erythropoiesis. This modified technique, allowing long-term expression of both PCR-amplified DNA fragments and naked plasmid DNA, could potentially be used for catheter-based gene transfer in humans, and could help determine the physiological functions of putative genes.


Obstructive Sleep Apnea-a Perioperative Risk Factor.
Obstructive sleep apnea (OSA) is a common disorder of breathing but is probably underappreciated as a perioperative risk factor. This review is based on pertinent articles, published up to 15 August 2015, that were retrieved by a selective search in PubMed based on the terms "sleep apnea AND anesthesia" OR "sleep apnea AND pathophysiology." The guidelines of multiple specialty societies were considered as well. OSA is characterized by phases of upper airway obstruction accompanied by apnea/hypoventilation, with hypoxemia, hypercapnia, and recurrent overactivation of the sympathetic nervous system. It has been reported that 22% to 82% of all adults who are about to undergo surgery have OSA. The causes of OSA are multifactorial and include, among others, an anatomical predisposition and /or a reduced inspiratory activation of the bronchodilator muscles, particularly when the patient is sleeping or has taken a sedative drug, anesthetic agent, or muscle relaxant. OSA is associated with arterial hypertension, coronary heart disease, and congestive heart failure. It can be assessed before the planned intervention with polysomnography and structured questionnaires (STOP/STOP-BANG), with sensitivities of 62% and 88%. The utility of miniaturized screening devices is debated. Patients with OSA are at risk for perioperative problems including difficult or ineffective mask ventilation and/or intubation, postoperative airway obstruction, and complications arising from other comorbid conditions. They should be appropriately monitored postoperatively depending on the type of intervention they have undergone, and depending on individually varying, patient-related factors; postoperative management in an intensive care unit may be indicated, although no validated data on this topic are yet available. OSA patients need care by specialists from multiple disciplines, including anesthesiologists with experience in recognizing OSA, securing the airway of OSA patients, and managing them postoperatively. No randomized trials have yet compared the modalities of general anesthesia for OSA patients with respect to postoperative complications or phases of apnea or hypopnea.


Comparison of novel methods in two-way enriched clinical trial design.
Two-way enriched design (TED) is a novel approach addressing placebo response in clinical trials. It is a two-stage, randomized, placebo-controlled trial design with enrichment in placebo non-responders and treatment responders at the second stage. All data from the first stage and data from placebo non-responders and treatment responders in the second stage are used for the final analysis of the treatment effect. The existing methods for the analysis of TED data include score tests with one, two, and three degrees of freedom. All these methods are only applicable to binary outcomes. However, there is an interest in continuous outcomes in clinical trials in psychiatry. In this manuscript, we apply some novel methods, including a repeated measures model, a weighted repeated measures model with weights from propensity score, and weights from K-means clustering, to analyze TED data for both binary outcomes and continuous outcomes. The simulation study indicates that the repeated measures model performs consistently well in preserving the type I error and achieving the minimum mean standard error as well as a higher power. The performance of the weighted repeated measures model with weights from K-means clustering improves with increasing sample size. Investigators can choose from these analytic approaches under different scenarios.


The application of chaotic oscillator in detecting weak resonant signal of MEMS resonator.
In this paper, a detection model of a chaotic oscillator is applied in the weak signal detection of an electrothermal excitation MEMS resonator, and the maximum Lyapunov exponent is used to obtain the threshold value and monitor the motion transition of a detection system. The phase drift caused by the electrothermal excitation is studied theoretically and experimentally, and according to the results of above study, the phase of a reference current signal is set to eliminate the phase when the resonator is in a resonant state. Then a new detection algorithm is proposed to detect the resonant signal. The simulation experiment on a weak signal under different magnifications and different levels of noises is conducted, after the impact of the quality factor Q of a resonator on detection results is analyzed. Finally, experiments on the output signal of a detected sensor sample are carried out by a proposed algorithm. Simulation and experiment results show that the detection model can effectively detect the weak signal and accurately obtain the resonant frequency, and it is immune to the noises.


Long-term Efficacy of Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia: Results of the Polish Adult Leukemia Study Group Observational Study.
To study the long-term clinical efficacy and tolerability of ibrutinib monotherapy in real-world relapsed and refractory chronic lymphocytic leukemia (RR-CLL) patients outside clinical trials. Clinical data of 171 RR-CLL patients treated with ibrutinib were collected within the observational study of the Polish Adult Leukemia Study Group. Median patient age was 64 years. Patients were pretreated with 3 (1-10) median lines of therapy, while 42 (24.6%) had 17p deletion. The median observation time was 40 months (range=1-59 months), while median ibrutinib monotherapy reached 37.5 months (range=0.4-59.2 months). Response was noted in 132 (77.2%) patients. The estimated 5-year progression-free survival (PFS) and overall survival (OS) rates were 61.1% (95%CI=49.3-70.9%) and 56.8% (95%CI=45.6-66.6%), respectively. At the time of analysis 97 (56.7%) remained under ibrutinib monotherapy. Ibrutinib is clinically effective and tolerable as a monotherapy in real-world RR-CLL patients.


Intraorbital tuberculosis: a case report.
A 75-year-old woman presented at the eye clinic of the University of llorin Teaching Hospital with swelling of the left eyelids and protrusion of the left eyeball. The swelling was painless. Physical examination revealed no systemic abnormality. An incisional biopsy of the lid swelling revealed tuberculous orbital involvement. She responded well to anti-tuberculosis therapy, with regression of the lid swelling and proptosis. The importance of including intraorbital tuberculosis as a differential of orbital swelling in the environment is emphasised.


Covariate-constrained randomization with cluster selection and substitution.
An ongoing cluster-randomized trial for the prevention of arboviral diseases utilizes covariate-constrained randomization to balance two treatment arms across four specified covariates and geographic sector. Each cluster is within a census tract of the city of Mérida, Mexico, and there were 133 eligible tracts from which to select 50. As some selected clusters may have been subsequently found unsuitable in the field, we desired a strategy to substitute new clusters while maintaining covariate balance. We developed an algorithm that successfully identified a subset of clusters that maximized the average minimum pairwise distance between clusters in order to reduce contamination and balanced the specified covariates both before and after substitutions were made. Simulations were performed to explore some limitations of this algorithm. The number of selected clusters and eligible clusters were varied along with the method of selecting the final allocation pattern. The algorithm is presented here as a series of optional steps that can be added to the standard covariate-constrained randomization process in order to achieve spatial dispersion, cluster subsampling, and cluster substitution. Simulation results indicate that these extensions can be used without loss of statistical validity, given a sufficient number of clusters included in the trial.


Enhancement of Refractive Index Sensitivity Using Small Footprint S-Shaped Double-Spiral Resonators for Biosensing.
We demonstrate an S-shaped double-spiral microresonator (DSR) for detecting small volumes of analytes, such as liquids or gases, penetrating a microfluidic channel. Optical-ring resonators have been applied as label-free and high-sensitivity biosensors by using an evanescent field for sensing the refractive index of analytes. Enlarging the ring resonator size is a solution for amplifying the interactions between the evanescent field and biomolecules to obtain a higher refractive index sensitivity of the attached analytes. However, it requires a large platform of a hundred square millimeters, and 99% of the cavity area would not involve evanescent field sensing. In this report, we demonstrate the novel design of a Si-based S-shaped double-spiral resonator on a silicon-on-insulator substrate for which the cavity size was 41.6 µm × 88.4 µm. The proposed resonator footprint was reduced by 680 times compared to a microring resonator with the same cavity area. The fabricated resonator exposed more sensitive optical characteristics for refractive index biosensing thanks to the enhanced contact interface by a long cavity length of DSR structures. High quality factors of 1.8 × 104 were demonstrated for 1.2 mm length DSR structures, which were more than two times higher than the quality factors of microring resonators. A bulk sensitivity of 1410 nm/RIU was calculated for detecting 1 µL IPA solutions inside a 200 µm wide microchannel by using the DSR cavity, which had more than a 10-fold higher sensitivity than the sensitivity of the microring resonators. A DSR device was also used for the detection of 100 ppm acetone gas inside a closed bottle.


Very Short-Term Surface Solar Irradiance Forecasting Based On FengYun-4 Geostationary Satellite.
An algorithm to forecast very short-term (30-180 min) surface solar irradiance using visible and near infrared channels (AGRI) onboard the FengYun-4A (FY-4A) geostationary satellite was constructed and evaluated in this study. The forecasting products include global horizontal irradiance (GHI) and direct normal irradiance (DNI). The forecast results were validated using data from Chengde Meteorological Observatory for four typical months (October 2018, and January, April, and July 2019), representing the four seasons. Particle Image Velocimetry (PIV) was employed to calculate the cloud motion vector (CMV) field from the satellite images. The forecast results were compared with the smart persistence (SP) model. A seasonal study showed that July and April forecasting is more difficult than during October and January. For GHI forecasting, the algorithm outperformed the SP model for all forecasting horizons and all seasons, with the best result being produced in October; the skill score was greater than 20%. For DNI, the algorithm outperformed the SP model in July and October, with skill scores of about 12% and 11%, respectively. Annual performances were evaluated; the results show that the normalized root mean square error (nRMSE) value of GHI for 30-180 min horizon ranged from 26.78% to 36.84%, the skill score reached a maximum of 20.44% at the 30-min horizon, and the skill scores were all above 0 for all time horizons. For DNI, the maximum skill score was 6.62% at the 180-min horizon. Overall, compared with the SP model, the proposed algorithm is more accurate and reliable for GHI forecasting and slightly better for DNI forecasting.


[Malaria chemoprophylaxis].
Malaria is a serious infection, and prevention traditionally relies on chemoprophylaxis during and after exposure. The risk of side effects from chemoprophylaxis needs to be balanced against the risk of infection, and there has been conducted only one prospective, double-blind study comparing the suspected side effects of mefloquine (Lariam), atovaquone/proguanil (Malarone), doxycycline and chloroquine/proguanil. Therefore the current recommendations are based on descriptive studies and case reports. There is a lack of data on the risk of infection in travellers, and the national statistics on the number of imported cases are not very useful as long as the total number of travellers at risk is not known. The risk to travellers is therefore estimated from data on malaria in the indigenous population, while the risk for travellers is expected to be lower. Atovaquone/proguanil has been registered in Europe for travels of up to four weeks, but in the United States there is no upper limit for the duration of use. It is not possible to prescribe efficient prophylaxis to pregnant women in the first trimester or infants below 11 kilograms of body weight travelling to tropical Africa.


Post-natal development of ganglia in the lower lumbar sympathetic chain of the rat.
The initial stages in the development of functional synapses have been examined in ganglia of the lower lumbar sympathetic chain of the rat using intracellular recording techniques. In animals of age up to 7 days post-natal, many impaled cells were inexcitable and possessed no synaptic input. The proportion of excitable cells impaled increased with the age of the animal. Two types of action potential could be identified. Initially the synaptic input consisted of one or a few subthreshold synaptic potentials. The number of preganglionic inputs to each cell increased over the first 1-2 weeks after birth. The quantal content of each input was initially very low. At least some inputs showed an increase in quantal content during development; eventually one or occasionally two inputs became suprathreshold. Voltage-clamp studies indicated that the time course of excitatory synaptic currents did not change during development. The amplitudes of miniature excitatory synaptic currents in animals aged less than 10 days were some three to five times the size of those recorded from mature animals.


Immunogenetics of rheumatoid arthritis and primary Sjögren's syndrome: DNA polymorphism of HLA class II genes.
We investigated the DNA restriction fragment length polymorphism (RFLP) of the Major Histocompatability Complex (MHC) class II genes: HLA-DRB, -DQA, -DQB, DPA, and -DFB in 24 patients with rheumatoid arthritis (RA), in 19 patients with primary Sjögren's syndrome (primary SS), and healthy Danes. The frequencies of DNA fragments associated with the following HLA class II genes were increased in RA when compared to normal controls: DRB1*04 (DR4) (relative risk, RR = 7.4, P less than 10(-3), DRB4*0101 (DRw53) (RR = 9.6, P less than 10(-3), DQA1*0301 (RR = 9.6, P less than 10(-3), DQB1*0301 (DQw7) (RR = 2.8, P less than 0.05, 'corrected' P greater than 0.05), and DQB1*0302 (DQw8) (RR = 4.5, P less than 10(-2). Negative associations were found between RA and DRB1*1501 (DR2/DRw15) (RR = 0.2, P less than 10(-2) and DQB1*0602 (DQw6) (RR = 0.2, P less than 10(-2), 'corrected' P greater than 0.05). The frequencies in RA of other HLA class II associated DNA fragments including DPA and DPB and the antigens DPw1-w6 defined by primed lymphocyte stimulation, did not differ significantly from those in controls. In primary SS, the frequency of HLA-B8 was significantly increased (RR = 9.0, P less than 10(-3). Positive associations were found between primary SS and DNA fragments associated with DRB1*03/13 (RR = 6.8, P less than 10(-3), DRB3*0101 (DRw52) (RR = 5.7, P less than 10(-2), DQA1*0501 (RR = 6.8, P less than 10(-3), DQB1*0201 (DQw2) (RR = 11.6, P less than 10(-5), and DQB1*0602 (DQw6) (RR = 2.7, P less than 0.05, 'corrected' P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Oxotechnetium(V) complexes with a novel class of tridentate thiosemicarbazide ligands.
A novel tridentate thiosemicarbazide-type ligand class with an SNS donor set, H(2)L(1), was prepared by reactions of N-[N',N'-dialkylamino(thiocarbonyl)]benzimidoyl chlorides with thiosemicarbazides. H(2)L(1) ligands readily react with (NBu(4))[TcOCl(4)] in MeOH under the formation of red oxotechnetium(V) complexes of composition [TcOCl(L(1))]. The monomeric, five-coordinate compounds are air-stable and bind (L(1))(2-) tridentate in the equatorial coordination sphere. The compounds represent the first examples of oxotechnetium(V) complexes with NS chelate-bonded thiosemicarbazones.


Non-empirical calculations of NMR indirect carbon-carbon coupling constants. Part 8--monocycloalkanes.
Carbon-carbon and carbon-hydrogen spin-spin coupling constants were calculated in the series of the first six monocycloalkanes using SOPPA and SOPPA(CCSD) methods, and very good agreement with the available experimental data was achieved, with the latter method showing slightly better results in most cases, at least in those involving calculations of J(C,C). Benchmark calculations of all possible 21 coupling constants J(C,C), J(C,H) and J(H,H) in chair cyclohexane revealed the importance of using the appropriate level of theory and adequate quality of the basis sets. Many unknown couplings in this series were predicted with high confidence and several interesting structural trends (hybridization effects, multipath coupling transmission mechanisms, hyperconjugative interactions) were elucidated and are discussed based on the present calculations of spin-spin couplings.


A Survey of Coccidia and Nematodes in Pastured Poultry in the State of Georgia.
The aim of this study was to evaluate and quantify the parasitological challenge in pastured poultry production in the state of Georgia. Over the course of 1 yr, fecal samples from six turkey flocks, 10 broiler flocks, and 13 layer flocks were collected on a pastured farm in 2-wk intervals to determine counts of Eimeria oocysts and nematode eggs. Average coccidia counts were 10,198 oocysts per gram of feces (OPG) in broiler flocks, 1470 OPG in layer flocks, and 695 OPG in turkey flocks. The means in broiler and turkey flocks were higher at their first week on pasture. Counts in broilers and layers were significantly higher in spring than in winter and summer. Coccidia counts in broilers were lower than published numbers in conventionally reared poultry, indicating the rotation system of the pastures might effectively reduce the infection pressure. Next-generation sequencing of PCR products showed the presence of most described Eimeria spp. in broilers, layers, and turkeys. In addition, operational taxonomic units (OTUs) x, y, and z were found. The frequency of species was similar for broilers and layers, with the exception that Eimeria praecox and OTU z were more common in layers. In layer flocks, the average count of roundworm eggs per gram of feces (EPG) was 509 EPG with 80% of the samples being positive. The mean counts had no clear pattern related to age. There was an increase of EPG with the increase of temperatures during spring and summer with the peak at midfall. Worm eggs from laying hens were identified as Ascaridia galli. The seasonal differences suggest that higher temperatures might result in an increase of egg survival and sporulation in the environment.


A capsaicin (8%) patch in the treatment of severe persistent inguinal postherniorrhaphy pain: a randomized, double-blind, placebo-controlled trial.
Persistent pain after inguinal herniorrhaphy is a disabling condition with a lack of evidence-based pharmacological treatment options. This randomized placebo-controlled trial investigated the efficacy of a capsaicin 8% cutaneous patch in the treatment of severe persistent inguinal postherniorrhaphy pain. Forty-six patients with persistent inguinal postherniorrhaphy pain were randomized to receive either a capsaicin 8% patch or a placebo patch. Pain intensity (Numerical Rating Scale [NRS 0-10]) was evaluated under standardized conditions (at rest, during movement, and during pressure) at baseline and at 1, 2 and 3 months after patch application. Skin punch biopsies for intraepidermal nerve fiber density (IENFD) measurements were taken at baseline and 1 month after patch application. Quantitative sensory testing was performed at baseline and at 1, 2, and 3 months after patch application. The primary outcome was comparisons of summed pain intensity differences (SPIDs) between capsaicin and placebo treatments at 1, 2 and 3 months after patch application (significance level P < 0.01). The maximum difference in SPID, between capsaicin and placebo treatments, was observed at 1 month after patch application, but the pain reduction was not significant (NRS, mean difference [95% CI]: 5.0 [0.09 to 9.9]; P = 0.046). No differences in SPID between treatments were observed at 2 and 3 months after patch application. Changes in IENFD on the pain side, from baseline to 1 month after patch application, did not differ between capsaicin and placebo treatment: 1.9 [-0.1 to 3.9] and 0.6 [-1.2 to 2.5] fibers/mm, respectively (P = 0.32). No significant changes in sensory function, sleep quality or psychological factors were associated with capsaicin patch treatment. The study did not demonstrate significant differences in pain relief between capsaicin and placebo treatment, although a trend toward pain improvement in capsaicin treated patients was observed 1 month after patch application. Clinicaltrialsregister.eu 2012-001540-22 ClinicalTrials.gov NCT01699854.


[Therapy realization and complications in the BFM-83 therapy study of acute myelogenous leukemia].
Data on the realization of therapy are available for 159 out of 173 (92%) protocol patients included in the study AML-BFM-83. The induction therapy could be carried out according to protocol in almost 80% of patients, with a dose compliance (= actual dose/prescribed dose) of greater than or equal to 80% for all substances. During the second therapy phase (consolidation) considerable deviations from the recommended therapy occurred in all nonresponders and in 34% of the patients who had achieved remission. The maintenance therapy had to be reduced in one third of the patients, mainly due to thrombopenias. Lethal complications caused by therapy-induced toxicity, occurred in 7 out of 173 cases (4%), and followed severe infections (mycoses), or other complications such as cardiotoxicity. The proportion of severe complications decreased from the induction through the first to the second consolidation phase. They were rare during maintenance therapy, but markedly more frequent in nonresponders and in children with early relapse (within 12 months). In view of the small differences in dose compliance, it is difficult to determine the prognostic significance of the realization to therapy. With the application of the COX regression and special life table analyses the dose compliance decreases in significance after including the known initial prognostic factors.(ABSTRACT TRUNCATED AT 250 WORDS)


Early and prolonged ECG alterations resembling a myocardial injury after severe amitriptyline poisoning.
Evidence of cardiovascular toxicity is present in the majority of tricyclic antidepressant overdoses. We report the case of a 63-year-old woman admitted to our department with a severe amitriptyline poisoning. The ECG at admission showed a pattern mimicking an acute anteroseptal subepicardial infarction. This pattern persisted for 11 days. Myocardial enzymes and echocardiographic findings never confirmed an ischemic event. At discharge, the ECG returned normal without cardiac or neurologic sequelae. Our experience suggest that after severe tricyclic antidepressant ingestion, ECG alterations resembling myocardial injury may occur early and last for a longer period than previously reported.


Dermatological conditions of the vulva.
Management of vulval conditions in the elderly will present no special problems if the following points are borne in mind: 1. The patient's condition will often be multifactorial; the components should be unravelled and the patient followed until the picture is clear. 2. Point 1 is particularly important because infections and neoplasia can easily go unrecognized. 3. Biopsy will often be needed. 4. Management of chronic dermatological conditions (especially where systemic treatment is indicated) is usually best carried out by the dermatologist. 5. It is vital to consider the area as one would any other as regards diagnosis of cutaneous and mucosal lesions. With this approach the vast majority of lesions can be accurately named and reasonable treatment given. To this end the naked-eye morphology, and the histopathological evidence which will sometimes be a necessary supplement, must be accurately described and understood. 6. The study of vulval conditions is interdisciplinary. 7. Much old and contentious terminology is now obsolete. The new classification is simple and should be universally applied by gynaecologists, dermatologists and pathologists so that other involved clinicians are helped rather than confused.


Limited energy migration and circumscribed multiphonon relaxation produced non-concentration quenching in a novel dazzling red-emitting phosphor.
White LED applications are still constrained by extremely efficient narrow band red emitting phosphors. Meanwhile, the concentration quenching induced by energy migration is the main reason that limits the emission intensity of a red emitting phosphor. Therefore, developing a novel red emitting material with energy migration limitations seems necessary. Here, we proposed and realized the non-concentration quenching doping of Eu3+ ions in a Sr9Y2-2xW4O24:xEu3+ (0 ≤ x ≤ 1.0) phosphor for the first time by means of host preferential selection. By clearly investigating the crystal structure and luminescence kinetics, the long-distance between the nearby Eu3+ ions and the low phonon energy are the main reasons that suppress the energy migration and the cross-relaxation among Eu3+ ions. These advantages result in a high internal (90.47%) and external quantum efficiency (42.1%) of Sr9Eu2W4O24. With the help of the Judd-Ofelt theory and the large value of oscillator strength Ω2, Eu3+ ions are verified to occupy the non-symmetric lattice site with high color purity (94.4%). In addition, only 5.2% emission intensity loss at 140 °C can guarantee its application in LED devices. Moreover, the SYWO:Eu3+ phosphor has high thermal tolerance, high color stability, excellent moisture resistance and superior physical/chemical stability, and thus has broad practical spectral application prospects. The prepared WLED shows superior performance, and the calculated NTSC values are as high as 101.8% and 104.7%, respectively. For comparison, the optical performances of the Sr9Y2W4O24:Eu3+ phosphor outperform those of the standard commercial red phosphors, Y2O3:Eu3+ and Y2O2S:Eu3+, and almost match that of K2MnF6. These results may pave the way for fresh approaches to the study of high-performance Eu3+-activated phosphors.


Comparison of the in vivo and in vitro antibacterial properties of providone iodine and chlorhexidine gluconate mouthrinses.
Clinical and laboratory studies were carried out to compare the antibacterial properties of two antiseptic mouthwashes, namely 1% povidone iodine and 0.2% chlorhexidine gluconate. In a group of 10 subjects after a single rinse with povidone iodine, an immediate mean fall in total salivary aerobes and anaerobes occurred, followed by a return to normal levels by 1-hour postrinsing. With chlorhexidine gluconate a similar but greater reduction in salivary bacterial counts was observed, which was still present up to the 7-h postrinsing period. Saliva samples obtained from the subjects 2 min after rinsing with providone iodine produced little or no inhibition to the growth of a test organism in vitro, whereas following chlorhexidine gluconate, antibacterial activity was present in the saliva specimens up to the 3-h sampling time. Using culture media containing comparable levels of soluble protein to saliva, the minimum inhibitory concentrations of povidone iodine against several standard test organisms were much higher than those of chlorhexidine gluconate. The results suggest that povidone iodine, as a mouthwash, exerts only an immediate antibacterial effect and unlike chlorhexidine, is not retained at antibacterial levels within the oral cavity after expectoration. This lack of prolonged action of povidone iodine in the oral cavity would appear to be relevant to its reported lack of antiplaque activity.


Characterization of pancreatic cancer with ultra-low tumor mutational burden.
In pancreatic cancer (PC), Tumor mutation burden (TMB) has been reported to be lower than in other cancers, with its clinical significance remaining unclear. We analyzed the dataset of whole-exome sequencing and gene expression profiling of 93 resected PC cases. The median TMB was 0.24. The TMB was classified as High (≥ 5.0), Low (< 5.0, ≥ 1.0), or Ultra-low (< 1.0). Nineteen samples (20%) were classified as TMB-low, and 74 (80%) were classified as TMB-ultra-low; no samples were TMB-high. TMB-ultra-low PC had significantly fewer borderline resectable lesions (P = 0.028) and fewer adenosquamous carcinomas (P = 0.003) than TBM-low PC. Furthermore, the TMB-ultra-low PC showed significantly lower detection rates of driver mutations and copy number variations. Microsatellite instability was not significantly correlated with the TMB status. The TMB-ultra-low PC had a significantly better prognosis than TBM-low PC (P = 0.023). A multivariate analysis identified TMB-ultra-low PC as an independent favorable prognostic factor (hazard ratio, 2.11; P = 0.019). A gene expression analysis showed that TMB-ultra-low PC was associated with reduced TP53 inactivation (P = 0.003) and reduced chromosomal instability (P = 0.001) compared to TBM-low PC. TMB-ultra-low PC had specific gene expression signatures and a better prognosis than TMB-low PC.


Demographic and lifestyle risk factors for gastroesophageal reflux disease and Barrett's esophagus in Australia.
We examined demographic and lifestyle risk factors for incidence of gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE) in an Australian cohort of 20,975 participants aged 40-63 at recruitment (1990-1994). Information on GERD and BE was collected between 2007 and 2010. GERD symptoms were defined as self-reported heartburn or acid regurgitation. BE was defined as endoscopically confirmed columnar-lined esophagus. Risk factors for developing GERD symptoms, BE diagnosis, age at symptom onset, and age at BE diagnosis were quantified using regression. During a mean follow-up of 15.8 years, risk of GERD symptoms was 7.5% (n = 1,318) for daily, 7.5% (n = 1,333) for 2-6 days/week, and 4.3% (n = 751) for 1 day/week. There were 210 (1.0%) endoscopically diagnosed BE cases, of whom 141 had histologically confirmed esophageal intestinal metaplasia. Female sex, younger age, lower socioeconomic position (SEP) and educational attainment, and former smoking were associated with higher GERD risk. Male sex and smoking were associated with earlier GERD symptom onset. Men, older participants, those with higher SEP, and former smokers were at higher BE risk. There was some evidence higher SEP was associated with earlier BE diagnosis. GERD and BE had different demographic risk factors but shared similar lifestyle factors. Earlier GERD symptom onset for men and smokers might have contributed to higher BE risk. The SEP patterns observed for GERD and BE suggest potential inequity in access to care. These findings would be important in the development of clinical risk prediction models for early detection of BE.


Xanthine oxidase inhibitory activity of extracts prepared from Polygonaceae species.
The xanthine oxidase (XO) inhibitory activity of aqueous and organic extracts of 27 selected species belonging in five genera (Fallopia, Oxyria, Persicaria, Polygonum and Rumex) of the family Polygonaceae occurring in the Carpathian Basin were tested in vitro. From different plant parts (aerial parts, leaves, flowers, fruits and roots), a total of 196 extracts were prepared by subsequent extraction with methanol and hot H2O and solvent-solvent partition of the MeOH extract yielding n-hexane, chloroform and 50% MeOH subextracts. It was found that the chloroform subextracts and/or the remaining 50% MeOH extracts of Fallopia species (F. bohemica, F. japonica and F. sachalinensis), Rumex species (R. acetosa, R. acetosella, R. alpinus, R. conglomeratus, R. crispus, R. hydrolapathus, R. pulcher, R. stenophyllus, R. thyrsiflorus, R. obtusifolius subsp. subalpinus, R. patientia) and Polygonum bistorta, Polygonum hydropiper, Polygonum lapathifolium and Polygonum viviparum demonstrated the highest XO inhibitory activity (>85% inhibition) at 400 µg/mL. The IC50 values of the active extracts were also determined. On the basis of the results, these plants, and especially P. hydropiper and R. acetosella, are considered worthy of activity-guided phytochemical investigations.


Microsatellite instability as a predictor of survival in head and neck cancer -- is there a link with colon cancer?
A reliable genetic marker to predict outcome for head and neck cancer is needed. In colon cancer, microsatellite instability (MSI) predicts response to therapy and improved prognosis. Colon cancer patients with MSI have a 60% improvement in survival as compared to patients without MSI. To assess whether MSI is a predictor of improved prognosis in head and neck cancer we used our tumor registry to find 8 patients treated between 1995 and 1998 with head and neck squamous cell carcinoma and either a history of colon cancer or a parent who had colon cancer. As a control, 15 T(2) or T(3) oral cavity cancers were used. The tumor specimens were obtained and laser capture microdissected for analysis using the following microsatellite markers: BAT25, BAT26, BAT40, D1S2883, D2S123, D3S1611, D5S346, D7S501 and D8S25. All 8 patients with head and neck cancer and a colon cancer history exhibited MSI or loss of heterozygosity (LOH) at 1 or more of the markers tested. Three patients had 2 abnormal markers, 1 patient had 3 abnormal markers and 1 had 7 abnormal markers. Only 1 of the patients with a colon cancer history, all of whom had MSI, developed recurrent head and neck cancer. Of the 15 control patients, 5 had MSI or LOH and 1 had MSI or LOH at 2 markers. Three of the 5 patients with MSI or LOH had a recurrence; hence MSI and LOH at these markers were uncommon, and there was no relation between MSI and outcome in patients without a history of colon cancer. These results support a possible alternative mode of carcinogenesis in patients with head and neck cancer and a history of colon cancer and, most significantly, that these cancers are a subgroup of head and neck cancer that may have a better prognosis.


Wide 3-dimensional macular ganglion cell complex imaging with spectral-domain optical coherence tomography in glaucoma.
To determine whether measurement of ganglion cell complex (GCC) thickness over a wide area (8-mm diameter) can improve the glaucoma-discriminating ability of spectral-domain optical coherence tomography (SD-OCT) compared to that in the standard macular area (6-mm diameter). Ninety-three subjects were enrolled, including 46 healthy eyes of 46 volunteers and 47 eyes of 47 glaucoma patients (23 eyes with preperimetric glaucoma [PPG] and 24 eyes with early glaucoma [EG]). All patients underwent SD-OCT raster scanning over a 9 mm × 9 mm square area centered on the fovea. Areas under the receiver operating characteristic curves (AROCs) were compared between wide sector (1-8-mm ring) and standard-size sector (1-6-mm ring) charts. AROCs for average GCC thickness in the wide chart were significantly greater than those of the standard chart in eyes with PPG (0.928 vs. 0.891; P = 0.038), EG (0.912 vs. 0.861; P = 0.003), and both (0.920 vs. 0.876; P = 0.004). Overall, the AROCs of regional GCC thicknesses were nearly comparable between the middle ring (4-6 mm) and outer ring (6-8 mm). Coefficients of variation were 0.68% and 0.97% in the standard and wide sector charts, respectively, in eyes with PPG, and 0.45% and 0.72% in the standard and wide sector charts, respectively, in eyes with EG. Addition of the GCC thickness outside the macula to the standard macular GCC thickness significantly increased the glaucoma-discriminating ability of SD-OCT.


Validation of a Spanish version of a 360° feedback tool for residents' performance: A pilot study.
The 360° feedback tool emerges as one of the most effective techniques for the assessment of humanistic qualities and communication skills of medical trainees, providing effective feedback. A valid Spanish version of this tool has not yet been published. The aim of this study was to evaluate the validity, reliability and feasibility rates of the Mini-peer Assessment Tool (Mini-PAT), a 360° feedback instrument, translated into Spanish applied on a cardiology residency program. : We translated the Mini-PAT questionnaire into Spanish. The validation sample included all residents in our cardiology program (n = 19). Each resident was evaluated by 8 raters chosen by themselves, through a 4-point Likert scale. Validity was evaluated with factor analysis and reliability by analyzing internal consistency using the Cronbach's alpha coefficient. Feasibility was defined by a minimum of 80% of the raters responding the questionnaire. The factor analysis clearly identified five item groupings, similar to the theoretical attributes predefined in the original questionnaire, providing evidence of the validity of the Spanish version. The Cronbach's alpha coefficient was 0.92, indicating high internal consistency of the items included. All the evaluators proposed completed the electronic form (152 surveys) demonstrating feasibility to implement. This study provides evidence of reliability and validity of the Spanish version of the 360° feedback tool Mini-PAT performed in a cardiology residency program to assess global performance and humanistic qualities.


Regulation of Circadian Clock Genes on Sleep Disorders in Traumatic Brain Injury Patients.
In patients with traumatic brain injury (TBI), whether sleep disorder is associated with disturbances in molecular rhythmicity is unclear. This study aimed to investigate the relationship between abnormal sleep and regulation by circadian rhythms in patients with TBI. We sampled buccal cells and human blood samples from patients with TBI diagnosed with sleep disorders and those with normal sleep and investigated differences in the expression levels of Clock, Per2, and Bmal1 between the 2 groups. The expression peaks of Clock, Per2, and Bmal1 were at 12:00. There was a statistically significant difference between the sleep disorder group and the normal sleep group in the level of Clock mRNA expression (P = 0.0003 in oral mucosa and P < 0.0001 in mononuclear cells). There was no significant between-group difference in Bmal1 mRNA expression level (P = 0.1187 in oral mucosa and P = 0.2094 in mononuclear cells). There were significant between-group differences in Per2 mRNA expression levels at 12:00 (P = 0.0102 in oral mucosa and P = 0.0006 in mononuclear cells) and 18:00 (P = 0.0004 in oral mucosa and P = 0.0015 in mononuclear cells) but no significant difference at 24:00 (P = 0.7838 in oral mucosa and P = 0.2808 in mononuclear cells). Abnormal expression levels of Per2, Clock, and Bmal1 were detected in patients with TBI-related sleep disorders. These novel findings demonstrate disturbances in the molecular clock in TBI patients and have important implications for our understanding of the aberrant rhythms reported in this disease.


Changes in cell number and lung morphology during early postpneumonectomy lung growth.
We studied early postpneumonectomy lung growth in adult rats with the aim of determining which lung cells and tissues were involved and what the magnitude of the changes was. Ultrastructural stereological-morphometric measurements were performed 7 days after left pneumonectomy; lung weight, DNA, and protein were also measured. Relative to sham controls, the number of type 2 epithelial cells per right lung increased 34% and the number of capillary endothelial cells increased 28%. The total type 1 epithelial cell volume and surface area both increased 26%, and the total volume and luminal surface area of the capillary endothelial cells increased 24 and 22%, respectively. The number of interstitial cells did not change significantly. The total number of lung cells in the alveolar region was increased 22%; this correlated with a 26% increase in right lung DNA content. We conclude that the main changes during early postpneumonectomy lung growth are increases in the number of type 2 epithelial cells and capillary endothelial cells and in the total capillary and alveolar epithelial surface area.


HLA-A, -B, -C expression in colon carcinoma mimics that of the normal colonic mucosa and is prognostically relevant.
Whether human leukocyte antigen (HLA)-A, -B, -C expression has any predictive value on the prognosis of human malignancies remains controversial. Herein, monoclonal antibodies with preferential reactivity for HLA-A, HLA-B, and HLA-C (HCA2, HC10, and L31) were used to stain an archival collection of 291 formalin-fixed/paraffin-embedded tissues, comprising neoplastic lesions from stages II and III colon carcinoma patients (n=165), and the uninvolved, morphologically normal mucosae from a subset (n=126) of these patients. Marked staining variability was detected not only in the tumors as in previous studies, but also in the normal paired mucosae. HLA-A, -B, -C expression was similar in approximately two thirds of the available 126 normal/neoplastic pairs, confirming in vivo our previous observation that most tumor cells mimic the HLA phenotypes of their normal counterparts. Both up and down-regulation occurred in the remaining third of the pairs, but did not coincide with high and low expression, respectively, conventionally evaluated on the tumor lesion only. Remarkably, a "paired" evaluation, but not high or low expression in the tumor, was predictive of the clinical outcome. Deviations from the expression in the normal paired mucosa (both increases and decreases) of HCA2-reactive class I molecules (possibly HLA-A), and down-regulation of L31-reactive class I molecules (possibly HLA-C), particularly in tumors from stage II patients, correlated with poor 5-year overall and disease-free survival, hazard risk ranging from 2 to 6, approximately. Thus, a paired immunohistochemical comparison reveals a novel immune evasion strategy that may impact on the prognosis of colon carcinoma.


Activation of 5-HT 1b/d receptor restores the cognitive function by reducing glutamate release, deposition of β-amyloid and TLR-4 pathway in the brain of scopolamine-induced dementia in rat.
This study evaluates the effect of 5-HT 1b/d agonist on cognitive function in scopolamine (SPN)-induced dementia in the rat. Dementia was induced by administration of SPN 2 mg/kg/day, intraperitoneally, for a duration of 21 days. The effect of zolmitriptan (ZMT) 30 mg/kg, intraperitoneally, was observed on cognitive function, and the parameters of oxidative stress like malondialdehyde (MDA) level, nitric oxide (NO), superoxide dismutase (SOD) and glutathione peroxidase (GPX) were estimated at the end. Histopathology study of brain tissue was performed for the determination of β-amyloid peptide, and qRT-PCR was used to determine the mRNA expression of Toll-like receptor 4 (TLR-4), IL-17 and β-amyloid. Data of the study suggested that treatment with ZMT alone and in combination with DMP (dextromethorphan) significantly (P < 0.01) decreases the escape latency in conditioned avoidance response (CAR) and transfer latency in elevated plus maze (EPM) as compared with negative control group. Moreover, the result of Morris water maze (MWM) shows an increase in retention time and a decrease in escape latency in ZMT alone and in combination with DMP-treated group of SPN-induced dementia than in the negative control group. There was a significant decrease in MDA and NO and increase in SOD and GPX in the brain tissues of ZMT and ZMT + DMP-treated group than negative control group. Histopathology study also suggested that the concentration of Aβ peptide decreases in the brain tissues in ZMT and ZMT + DMP-treated group than the negative control group. Moreover, ZMT treatment ameliorates the altered mRNA expression of TLR-4 and IL-17 in the brain tissue of SPN-induced dementia rat. In conclusion, ZMT restores the cognitive functions and impaired memory in SPN-induced dementia in the rat by decreasing oxidative stress and Aβ peptide in the brain tissue of rat.


Optimal temperature control for a structured model of plant cell culture.
This article calculates optimal open-loop temperature trajectories that maximize the average rate of product synthesis of a plant cell culture. It uses a previously published five-state mathematical model which describes the growth and product synthesis of a batch plant cell suspension culture of Catharanthus roseus under temperature control. The optimal open-loop temperatures maximize the final product concentration for predefined fermentation periods. A single switch in temperature is shown by computer simulation to be near optimal, with a 22% increase in final product yield over that obtained at the optimal constant temperature. Examination of the achieved final product yield as a function of fermentation period allows this period also to be chosen optimally. This time is reduced from 16 days in the constant temperature case to 12 days in the switched temperature case.


Postoperative rupture of an aortic aneurysmal dilation associated with a patent ductus arteriosus in a dog.
To describe an unusual case of fatal aortic aneurysm rupture after standard ligation of a left-to-right shunting patent ductus arteriosus (PDA) and review the literature concerning the causes of aneurysm and applicable medical physics of blood flow that may contribute to mural failure. Clinical case report. An 11-month-old female Brittany spaniel. A PDA was diagnosed in the dog after referral for a grade IV/IV cardiac murmur. Diagnostic tests performed included a minimum database, thoracic radiography, and echocardiography. Conventional surgical ligation of the PDA was performed. The postoperative recovery from anesthesia was uneventful. Approximately 5 hours after surgery, the dog vocalized once and collapsed. All resuscitative efforts failed. Necropsy showed a large, spiral rupture of the cranial and dorsal wall of the aorta that extended from the left subclavian artery to 2 cm distal to the PDA-aorta junction. No evidence of intramural, perianeurysmal hemorrhage or inflammation was noted. Histopathologic examination of the ruptured aneurysm showed that the wall lacked a defined tunica intima and endothelial cell layer. A distinct separation of the thinned tunica media parallel to the elastic fibers was noted. Dilatation of the aorta near the area of a PDA is one of the recognized abnormalities associated with the condition. Aneurysmal dilatation results from and contributes to abnormal blood flow dynamics and increased aortic wall tension, which promotes expansion. Although an unusual and previously unreported sequela, rupture of the aneurysm should be considered a possible complication when ligation of a PDA with a conspicuous aortic aneurysmal dilation is performed.


Skin-type hidradenoma of the breast parenchyma with t(11;19) translocation: hidradenoma of the breast.
Skin adnexal type tumors situated in the parenchyma of the breast are very rare. We report herein a case of solid-cystic hidradenoma of the breast. The tumor was situated in the parenchyma of the breast of a 55-year-old female and showed no connection to the overlying skin on ultrasound and radiology investigations, grossly and microscopically. Histologically, the tumor was identical to its cutaneous counterpart and was surrounded by breast tissue. The neoplasm was composed of solid and cystic areas. The cystic component, which predominated in the lesion, was filled with homogeneous eosinophilic material. The solid component consisted of several nodules with vague lobulated architecture protruding into the cystic spaces. The nodules were composed of cuboidal monomorphous cells that were continuous with larger polygonal cells and rare, large mucinous cells with basophilic granular cytoplasm. Several mammary ducts in close proximity to the tumor showed features of columnar cell hyperplasia. A 120-bp METC1/MAML2 fusion transcript was identified by RT-PCR and subsequent sequencing technique. This t(11;19) translocation has been reported in approximately 50% of hidradenomas of the skin.


Applications for Bacteriophage Therapy during Pregnancy and the Perinatal Period.
Pregnant women and their unborn children are a population that is particularly vulnerable to bacterial infection. Physiological changes that occur during pregnancy affect the way women respond to such infections and the options that clinicians have for treatment. Antibiotics are still considered the best option for active infections and a suitable prophylaxis for prevention of potential infections, such as vaginal/rectal Streptococcus agalactiae colonization prior to birth. The effect of such antibiotic use on the developing fetus, however, is still largely unknown. Recent research has suggested that the fetal gut microbiota plays a critical role in fetal immunologic programming. Hence, even minor alterations in this microbiota may have potentially significant downstream effects. An ideal antibacterial therapeutic for administration during pregnancy would be one that is highly specific for its target, leaving the surrounding microbiota intact. This review first provides a basic overview of the challenges a clinician faces when administering therapeutics to a pregnant patient and then goes on to explore common bacterial infections in pregnancy, use of antibiotics for treatment/prevention of such infections and the consequences of such treatment for the mother and infant. With this background established, the review then explores the potential for use of bacteriophage (phage) therapy as an alternative to antibiotics during the antenatal period. Many previous reviews have highlighted the revitalization of and potential for phage therapy for treatment of a range of bacterial infections, particularly in the context of the increasing threat of widespread antibiotic resistance. However, information on the potential for the use of phage therapeutics in pregnancy is lacking. This review aims to provide a thorough overview of studies of this nature and discuss the feasibility of bacteriophage use during pregnancy to treat and/or prevent bacterial infections.


Comparative pharmacokinetics and clinical experience with a new cephalosporin-derivative: cefazolin.
In a cross-over study in 12 normal individuals, the pharmacokinetic parameters of cefalotin, cefradine and cefazolin were determined after intravenous injection of 1,000 mg of each substance. The microbiological activities in urine and serum were determined using the agar diffusion test; the pharmacokinetic data were calculated by a computer system on the basis of a Fortran programme. Cefazolin has significantly higher serum concentrations than the other two cephalosporins, distinctly longer serum half-lives, higher protein binding, and smaller apparent volumina of distribution. In 36 inpatients with mainly chronical and acute infections of the urinary tract, we tested the antibacterial effectivity, the compatibility, and the application modalities of cefazolin. In 29 patients we had a satisfactory clinical result, in 25 cases we achieved the elimination of bacteria by the end of the therapy. The compatibility of cefazolin was good; apart from a minor, reversible, liver-specific increase in enzymes in 6 patients, no side effects could be detected.


Halogenated volatile anesthetics in the intensive care unit: current knowledge on an upcoming practice.
The aim of this narrative review was to highlight key points of volatile anesthetics administration in the intensive care unit (ICU), including AnaConDa® and Mirus® devices characteristics and the reported findings on clinical outcomes in critically ill patients. Intravenous sedation in the ICU is associated with issues, such as over- and under-sedation. Halogenated compounds, which can be safely administered by inserting a device in any ICU ventilation circuit, have interesting pharmacodynamic and pharmacokinetic profiles for patients with multi-organ failure. Moreover, analysis of the concentration of exhaled volatile compounds could help evaluation of sedation depth. A recent meta-analysis confirmed that rapid washout of the volatile anesthetics improved both extubation readiness and quality of awakening when compared to intravenous sedation. When administered for a long period, volatile anesthetics improved sedation stability with fewer dose adjustments. Pre- and post-conditioning properties of halogenated compounds are interesting and long-term exposition to this compound is investigated for a potential impact on mortality rate and ICU/hospital length of stay. For now, psychomotor side effects have been reported, mostly in infants, but there were no hepatic or renal injuries. Findings regarding hemodynamic stability are conflicting. Apart from sedation, volatile anesthetics were therapeutic in case reports of status asthmaticus and epilepticus and data are cumulating for benefits in cases of acute respiratory distress syndrome. According to current literature, they should be withheld in cerebral injury. To summarize, the use of volatile anesthetics for sedation is yet only approved by German guidelines, but could spread due to its potential benefits.


Fatty replacement of bone marrow after radiation therapy for Hodgkin disease: quantification with chemical shift imaging.
The authors studied the long-term fatty replacement of bone marrow in 23 patients who had received radiation therapy for Hodgkin disease, with T1-weighted magnetic resonance imaging and quantitative chemical shift imaging. T1-weighted images revealed a mostly homogeneous high-signal-intensity pattern, in contrast to the hypointense pattern of nonirradiated marrow. The degree of fatty replacement was objectively assessed with chemical shift imaging, comparing patients to age-matched healthy volunteers. The authors found an increase in relative fat signal of 37% in the thoracic spine and 34% in the lumbar spine. The relative fat signal of nonirradiated pelvic and femoral marrow was decreased by 8%, indicating marrow reconversion. No radiation dose dependence was found in the range from 25 to 50 Gy. No signs of marrow regeneration were observed 15-126 months after radiation therapy. With chemical shift imaging, the degree of long-term radiogenic fatty replacement of the bone marrow can be quantified, confirming the lack of regeneration after radiation therapy for Hodgkin disease.


Involvement of supraspinal and spinal segmental alpha-2-adrenergic mechanisms in the medetomidine-induced antinociception.
The effect of systemically administered medetomidine, a selective alpha-2-adrenoceptor agonist, was studied by electrophysiological recordings of the peripherally evoked responses of three different types of sensory neuronal populations in the rat: medial thalamic neurons exclusively responding to mechanical cutaneous stimuli at noxious intensities, spinothalamic tract neurons of the spinal cord responding exclusively or differentially to mechanical cutaneous stimuli at noxious intensities, and low-threshold mechanoreceptive spinal dorsal horn neurons with ascending projections. The neuronal effects were compared with the behavioral data obtained in mechanically and thermally induced nociceptive tail reflex tests in intact and spinal rats. A reversal of the antinociceptive effects was attempted by systemically (1.5 mg/kg, i.p.) or intrathecally (25 micrograms) administered atipamezole, a selective alpha-2-adrenoceptor antagonist. Systemically administered medetomidine produced an atipamezole-reversible, dose-dependent suppressive effect on the evoked responses of nociceptive medial thalamic and spinothalamic tract neurons. A lower dose of medetomidine was needed to suppress significantly (half-maximally) evoked responses of the nociceptive medial thalamic neurons (100 micrograms/kg) than those of the nociceptive spinothalamic tract neurons (300 micrograms/kg). The decrease of evoked responses of the nociceptive spinothalamic tract neurons was accompanied by a decrease in spontaneous activity. The responses of the low-threshold mechanoreceptive projection neurons of the spinal cord were not influenced by medetomidine (30-300 micrograms/kg). The reflex studies with a (anesthetic) medetomidine dose of 300 micrograms/kg indicated that in intact and otherwise drug-free rats, medetomidine produced a significant prolongation of the nociceptive reflex response latency to a tail-pinch and heat; these antinociceptive effects of systemic medetomidine were reversed by systemically and intrathecally applied atipamezole. In spinal rats systemically applied medetomidine (300 micrograms/kg) also produced a significant prolongation of the tail-flick latency, which was reversed by systemically applied atipamezole. The results suggest that a high anesthetic dose of systemically applied medetomidine (300 micrograms/kg) can suppress nociceptive sensory neuronal and reflex responses due to spinal segmental mechanisms through an action on alpha-2-adrenoceptors. This spinal effect is selective to responses of nociceptive neurons, and at least partly postsynaptic as indicated by the concomitant decrease in spontaneous activity. At a lower, subanesthetic (but sedative) dose (100 micrograms/kg) the antinociceptive effect of systemically applied medetomidine can be explained by supraspinal alpha-2-adrenergic mechanisms.


Some problems with cost-benefit analysis in health care.
...Arnold's article is very ambitious. He suggests rules that could be followed in order to decide whether health care should be rationed. He notes that explicit assessments of costs and benefits using the same monetary unit are rarely used. The main reason, it seems to me, is that the method of cost-benefit analysis is relatively difficult to apply in the context of health care. Arnold does not address the difficulties that are related to his approach. Thus, my impression is that the interest of his provocative article lies more in its ability to foster a useful debate than in the methodology itself. In this brief commentary, I will merely list some of the theoretical problems that occurred to me while reading this article....


Electrochemical properties of suprastructures galvanically coupled to a titanium implant.
In recent years, dental implants have been widely used for the aesthetic and functional restoration of edentulous patients. Dental implants and restorative alloys are required with high corrosion resistance. Suprastructures and implants of different compositions in electrical contact may develop galvanic or coupled corrosion problems. In addition to galvanic corrosion, crevice and pitting corrosion may occur in the marginal gap between dental implant assemblies. In this study, gold, silver-palladium, cobalt-chromium, and nickel-chromium suprastructures were used to investigate their galvanic and crevice corrosion characteristics in combination with titanium (Ti) implants. Potentiodynamic and potentiostatic testing were performed in artificial saliva at 37 degrees C. Potentiodynamic testing was carried out at the potential scan rate of 1 mV/s in the range of -600-1600 mV (SCE). Potentiostatic testing was performed with an open-circuit potential and current densities at -250, 0, and 250 mV (SCE) in artificial saliva. After electrochemical testing, surface morphologies and cross-sections were examined using micrographs of the samples. Potentiodynamic test results indicated that suprastructure/Ti implant couples produced passive current densities in the range of 0.5-12 microA/cm(2); Ti abutment/Ti implant and gold/Ti implant couples exhibited relatively low passive current densities; Co-Cr/Ti implant couples the highest. Co-Cr and Ni-Cr/Ti implant couples showed breakdown potentials of 700 and 570 mV (SCE), respectively. The open-circuit potentials of silver, Ti abutment, gold, Ni-Cr, and Co-Cr/Ti implant couples were -93.2 +/- 93.9, -123.7 +/- 58.8, -140.0 +/- 80.6, -223.5 +/- 35.1, and -312.7 +/- 29.8 mV (SCE), respectively, and did not change with immersion time. The couples exhibited cathodic current densities at -250 mV (SCE); in particular, gold and silver alloys showed high cathodic current densities of -3.18 and -6.63 microA/cm(2), respectively. At 250 mV (SCE), Ti abutment/Ti implant couples exhibited a minimum current density of 9.48 x 10(-2) microA/cm(2), but gold, Ni-Cr, Co-Cr, and silver/Ti implant couples exhibited 0.313, 1.27, 5.60, and 8.06 microA/cm(2), respectively. All couples exhibited relatively low current densities at 0 mV (SCE). Photomicrographs after electrochemical testing showed crevice or pitting corrosion in the marginal gap and at the suprastructure surface. Although of the tested samples Co-Cr/Ti implant couples showed the possibility of galvanic corrosion, its degree was not significant. However, it should be borne in mind that galvanic corrosion can accelerate localized corrosion, such as crevice or pitting corrosion.