Overexpression of Lifeact-GFP Disrupts F-Actin Organization in Cardiomyocytes and Impairs Cardiac Function.
Lifeact-GFP is a frequently used molecular probe to study F-actin structure and dynamic assembly in living cells. In this study, we generated transgenic zebrafish models expressing Lifeact-GFP specifically in cardiac muscles to investigate the effect of Lifeact-GFP on heart development and its application to study cardiomyopathy. The data showed that transgenic zebrafish with low to moderate levels of Lifeact-GFP expression could be used as a good model to study contractile dynamics of actin filaments in cardiac muscles in vivo. Using this model, we demonstrated that loss of Smyd1b, a lysine methyltransferase, disrupted F-actin filament organization in cardiomyocytes of zebrafish embryos. Our studies, however, also demonstrated that strong Lifeact-GFP expression in cardiomyocytes was detrimental to actin filament organization in cardiomyocytes that led to pericardial edema and early embryonic lethality of zebrafish embryos. Collectively, these data suggest that although Lifeact-GFP is a good probe for visualizing F-actin dynamics, transgenic models need to be carefully evaluated to avoid artifacts induced by Lifeact-GFP overexpression.


Minimized Bolus-Type Wireless Sensor Node with a Built-In Three-Axis Acceleration Meter for Monitoring a Cow's Rumen Conditions.
Monitoring rumen conditions in cows is important because a dysfunctional rumen system may cause death. Sub-acute ruminal acidosis (SARA) is a typical disease in cows, and is characterized by repeated periods of low ruminal pH. SARA is regarded as a trigger for rumen atony, rumenitis, and abomasal displacement, which may cause death. In previous studies, rumen conditions were evaluated by wireless sensor nodes with pH measurement capability. The primary advantage of the pH sensor is its ability to continuously measure ruminal pH. However, these sensor nodes have short lifetimes since they are limited by the finite volume of the internal liquid of the reference electrode. Mimicking rumen atony, we attempt to evaluate the rumen condition using wireless sensor nodes with three-axis accelerometers. The theoretical life span of such sensor nodes depends mainly on the transmission frequency of acceleration data and the size of the battery, and the proposed sensor nodes are 30.0 mm in diameter and 70.0 mm in length and have a life span of over 600 days. Using the sensor nodes, we compare the rumen motility of the force transducer measurement with the three-axis accelerometer data. As a result, we can detect discriminative movement of rumen atony.


The human H2A and H2B histone gene complement.
Sequences and expression patterns of newly isolated human histone H2A and H2B genes and the respective proteins were compared with previously isolated human H2A and H2B genes and proteins. Altogether, 15 human H2A genes and 17 human H2B genes have been identified. 14 of these are organized as H2A/H2B gene pairs, while one H2A gene and three H2B genes are solitary genes. Two H2A genes and two H2B genes turned outto be pseudogenes. The 13 H2A genes code for at least 6 different amino acid sequences, and the 15 H2B genes encode 11 different H2B isoforms. Each H2A/H2B gene pair is controlled by a divergent promoter spanning 300 to 330 nucleotides between the coding regions of the two genes. The highly conserved divergent H2A/H2B promoters can be classified in two groups based on the patterns of consensus sequence elements. Group I promoters contain a TATA box for each gene, two Oct-1 factor binding sites, and three CCAAT boxes. Group II promoters contain the same elements as group I promoters and an additional CCAAT box, a binding motif for E2F and adjacent a highly conserved octanucleotide (CACAGCTT) that has not been described so far. Five of the 6 gene pairs and 4 solitary genes with group I promoters are localized in the large histone gene cluster at 6p21.3-6p22, and one gene pair is located at 1q21. All group II promoter associated genes are contained within the histone gene subcluster at D6S105, which is located at a distance of about 2 Mb from the major subcluster at 6p21.3-6p22 containing histone genes with group I promoters. Almost all group II H2A genes encode identical amino acid sequences, whereas group I H2A gene products vary at several positions. Using human cell lines, we have analyzed the expression patterns of functional human H2A/H2B gene pairs organized within the two histone gene clusters on the short arm of chromosome 6. The genes show varying expression patterns in different tumor cell lines.


Methotrexate for maintaining remission in paediatric Crohn's patients with prior failure or intolerance to thiopurines: a multicenter cohort study.
Methotrexate [MTX] is an immunomodulating drug that can be used to maintain remission in patients with Crohn's disease [CD], but data on efficacy and tolerability in children and teenagers are scarce. We evaluated the long-term efficacy and tolerability of MTX monotherapy after thiopurine therapy in paediatric CD patients. A multicenter cohort of paediatric MTX users who stopped thiopurines due to ineffectiveness or intolerance between 2002 and 2012 were included and followed for at least 12 months. Relapse-free use was defined as steroid and biologics-free clinical remission after the introduction of MTX, and included intentional discontinuation of successful therapy before the end of the observation period. A total of 113 patients with CD in remission were followed while on MTX monotherapy, of whom 75 [66%] had failed on thiopurines and 38 [34%] had stopped thiopurines due to side effects. Median age at the introduction of MTX was 14 years [range 7 to 17], and 93% used the subcutaneous route. Kaplan-Meier analysis showed that 52% of the study cohort were still in steroid- and biologics-free remission after 12 months of MTX monotherapy, with a difference that did not reach significance between thiopurine-intolerant and thiopurine-failing patients [p = 0.21, log-rank test]. The findings of this cohort study suggest that MTX is an effective immunomodulator to maintain remission after stopping thiopurines. MTX maintenance should be considered before stepping up to anti-tumor necrosis factor alpha therapy. MTX is probably somewhat more effective in patients who stopped thiopurines due to side effects than in those who failed on thiopurines.


Mild hydrothermal crystal growth, structure, and magnetic properties of ternary U(IV) containing fluorides: LiUF5, KU2F9, K7U6F31, RbUF5, RbU2F9, and RbU3F13.
Single crystals of several ternary alkali uranium fluorides, LiUF5, KU2F9, K7U6F31, RbUF5, RbU2F9, and RbU3F13, have been obtained in a mild hydrothermal process using UO2(CH3CO2)2(H2O)2 as the uranium source. Their crystal structures were determined by single crystal X-ray diffraction. The uranium in the starting reagent was successfully reduced from U(6+) to U(4+) in a dilute hydrofluoric acid environment, aided by the presence of a copper salt. All materials exhibit highly complex crystal structures that range from two-dimensional to three-dimensional. The U(4+) cations are found in high (UF8 and UF9) coordination environments. The magnetic susceptibility measurements yielded effective magnetic moments of 3.01-3.83 μB for the U(4+) cations. The temperature dependent magnetic susceptibility measurements confirmed that the U(4+) cation exhibits a nonmagnetic singlet ground state at low temperatures. No long-range magnetic order was observed for any of the above compositions down to 2 K. Optical and thermal behaviors of the fluorides were also investigated.


Translation of capped virus mRNA in encephalomyocarditis virus-infected cells.
The pattern of protein synthesis in HeLa cells simultaneously infected with encephalomyocarditis virus (EMCV) and Semliki Forest virus (SFV) has been analysed throughout the time course of the infection. The ratio of the picornavirus protein gamma versus the togavirus late protein C increased when the m.o.i. of EMCV was raised, and the ratio of C/gamma increased with higher multiplicities of SFV. Under some conditions, the co-infected cells simultaneously synthesized the picornavirus and togavirus proteins, and the cells exclusively translated the capped 26S mRNA from SFV at the end of the co-infection experiment. The influence of the time of addition of the second virus on the relative translation of the capped and uncapped mRNAs was also studied. When HeLa cells were co-infected with 5 p.f.u./cell of EMCV and 200 p.f.u./cell of SFV, only the synthesis of SFV proteins was apparent, whereas if SFV was added 1 to 3 h later during the course of EMCV infection the cells synthesized picornavirus and togavirus proteins. If the cells were superinfected with SFV 1 h after EMCV addition, host protein synthesis was drastically inhibited after 3 h of EMCV infection. By 5 h post-infection both kinds of virus proteins were synthesized and at 7 h post-infection the cells preferentially translated the capped 26S mRNA from SFV. If cells were first infected with SFV (10 p.f.u./cell) and co-infected or superinfected at 1 h with EMCV (50 p.f.u./cell), shut-off of host protein synthesis occurred 3 h after infection and the cells synthesized both kinds of virus proteins. However, 9 h after infection the cells synthesized SFV proteins only. When double-infected HeLa cells were placed in a hypotonic medium, they mainly synthesized the togavirus late proteins, whereas under hypertonic conditions, they translated the picornavirus RNA exclusively. These results suggest that the two kinds of mRNAs (SFV 26S mRNA and EMCV 35S mRNA) are present in the infected cells and that the relative translation of each of them depends on the external ionic conditions.


Health registers for congenital malformations and in vitro fertilization.
Registers of reproductive outcomes can be used to obtain information about the incidence of health problems related to pregnancy and to study associated risk factors and underlying causes. In Australia, a national data system for congenital malformations, based on multiple sources of notifications, has provided data to determine the incidence of major malformations over a 3-year period (1981-1983) and to study regional variations in incidence possibly due to environmental or other teratogens. A national register of pregnancies resulting from in vitro fertilization (IVF) has been established by obtaining reports from IVF units for pregnancies completed by the end of 1983. This register, developed in collaboration with the Fertility Society of Australia, has been used to describe the characteristics of infertile couples and the management of IVF pregnancies and to determine the incidence of pregnancy losses and major congenital malformations. Confidentiality issues were important in setting up both data systems.


[Subglottic tracheal stenosis in Wegener disease. Report of two cases].
Granulomatosis with polyangiitis (GPA) or Wegener's disease is characterized by a granulomatous vasculitis of the upper and lower airways and kidney. It involves the lower respiratory tract causing subglottic tracheal stenosis, which occurs in approximately 22% of patients. We report two females aged 40 and 52 years, admitted to the hospital with a subglottic tracheal stenosis. Their symptoms and management are reviewed. The first patient responded to rituximab. The second patient required a tracheostomy.


Intestinal obstruction as a complication of continuous ambulatory peritoneal dialysis: a case report.
Continuous ambulatory peritoneal dialysis (CAPD) has gained in popularity in recent years as a mode of renal replacement therapy. We report a 23 year old patient who was initiated on CAPD using curley Tenckhoff catheter in January 1992. In May 1993, the patient presented with features suggestive of intestinal obstruction. Plain x-ray of the abdomen showed that the CAPD catheter had migrated to the left hypochondrium. During surgery for catheter removal, it was found that the intraperitoneal cuff was adherent to the greater omentum forming a band over which the jejunal loop was kinked causing obstruction. Within 24 hours of removal of the catheter, the intestinal obstruction was relieved. The problem encountered in our patient is unique in illustrating the reversible mechanical intestinal obstruction relieved by catheter removal.


Bayesian Inference for Reliability of Systems and Networks Using the Survival Signature.
The concept of survival signature has recently been introduced as an alternative to the signature for reliability quantification of systems. While these two concepts are closely related for systems consisting of a single type of component, the survival signature is also suitable for systems with multiple types of component, which is not the case for the signature. This also enables the use of the survival signature for reliability of networks. In this article, we present the use of the survival signature for reliability quantification of systems and networks from a Bayesian perspective. We assume that data are available on tested components that are exchangeable with those in the actual system or network of interest. These data consist of failure times and possibly right-censoring times. We present both a nonparametric and parametric approach.


Paclitaxel-eluting balloon dilation of biliary anastomotic stricture after liver transplantation.
To investigate the safety and effectiveness of endoscopic therapy with a paclitaxel-eluting balloon (PEB) for biliary anastomotic stricture (AS) after liver transplantation (LT). This prospective pilot study enrolled 13 consecutive eligible patients treated for symptomatic AS after LT at the University Hospital of Münster between January 2011 and March 2014. The patients were treated by endoscopic therapy with a PEB and followed up every 8 wk by endoscopic retrograde cholangiopancreatography (ERCP). In cases of re-stenosis, further balloon dilation with a PEB was performed. Follow-up was continued until 24 mo after the last intervention. Initial technical feasibility, defined as successful balloon dilation with a PEB during the initial ERCP procedure, was achieved in 100% of cases. Long-term clinical success (LTCS), defined as no need for further endoscopic intervention for at least 24 mo, was achieved in 12 of the 13 patients (92.3%). The mean number of endoscopic interventions required to achieve LTCS was only 1.7 ± 1.1. Treatment failure, defined as the need for definitive alternative treatment, occurred in only one patient, who developed recurrent stenosis with increasing bile duct dilatation that required stent placement. Endoscopic therapy with a PEB is very effective for the treatment of AS after LT, and seems to significantly shorten the overall duration of endoscopic treatment by reducing the number of interventions needed to achieve LTCS.


Trophoblast cellular adhesion molecule expression regulated by different genes and their correlation with pregnancy-induced hypertension.
It was to study trophoblast cell (TC) adhesion molecules regulated by different genes in the placental tissue (PT) of patients with pregnancy-induced hypertension (PIH), and the correlation with the severity of PIH. 42 patients with PIH (13 cases in the mild PIH group, 11 cases in the moderate PIH group, and 18 cases in the severe PIH group) and 40 patients with normal pregnancy (NP group) were included. mRNA and protein levels in matrix metalloproteinase (MMP)-9, MMP-2, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 of all patients were determined by semi-quantitative polymerase chain reaction (PCR) and Western blotting (WB), respectively. Compared to the NP group, MMP-9 and MMP-2 mRNA levels as well as their proteins in PT significantly decreased in PIH groups (P<0.05). MMP-9 mRNA was greatly lower in the severe PIH group than mild PIH group (P<0.05). MMP-2 mRNA in moderate and severe PIH groups was much lower than NP and mild PIH groups, and that in the severe PIH group was considerably lower than the moderate PIH group (P<0.05). TIMP-1 mRNA and its protein highly increased in PT in PIH groups than NP group (P<0.05). TIMP-2 mRNA was remarkably higher in the severe PIH group than in the NP group (P<0.05). mRNA and proteins of MMP-9 and MMP-2 decreased in PT of PIH patients, while TIMP-1 mRNA and its protein increased, which were correlated with the severity of PIH. MMP-9, MMP-2, and TIMP-1 were involved in the pathogenesis of PIH by regulating the infiltration of TCs.


Results of a survey of Veterinary Orthopedic Society members on the preferred method for treating cranial cruciate ligament rupture in dogs weighing more than 15 kilograms (33 pounds).
OBJECTIVE To determine which method (lateral fabellotibial suture [LFS], tibial plateau leveling osteotomy [TPLO], tibial tuberosity advancement [TTA], or tightrope-like braided multifilament suture secured with metallic buttons [TR]) Veterinary Orthopedic Society (VOS) members preferred for treating cranial cruciate ligament rupture (CCLR) in dogs weighing > 15 kg (33 lb), identify factors associated with this preference, and assess concerns related to surgical implant material used. DESIGN Cross-sectional study. SAMPLE 187 VOS members. PROCEDURES All registered VOS members received an online survey from June to July 2016. Responses were compiled and evaluated for associations with method preferences and perceived complications. RESULTS Overall response rate was 38.4% (221/575). Respondents had graduated from veterinary school a mean of 23 years prior to survey completion, and collectively they performed approximately 30,000 CCLR surgeries annually. The most commonly preferred method was TPLO (147 [78.6%]), followed by TTA (26 [13.9%]), the LFS procedure (11 [5.9%]), and the TR procedure (3 [1.6%]). The preference for TPLO was independent of board certification or college of training (American, European, or other College of Veterinary Surgeons). Non-board-certified surgeons, including general practitioners, also favored TPLO. The most common perceptions were that titanium implants (used for TTA) were associated with the lowest incidence of major complications, whereas braided multifilament suture (used for the TR procedure) was associated with the highest incidence of major complications. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that TPLO was preferred for treating CCLR in dogs weighing > 15 kg and that the TR procedure was perceived as having the highest complication rate. With results of this survey in mind, use of the TR procedure should be considered cautiously when treating CCLR.


Deiodinase knockdown during early zebrafish development affects growth, development, energy metabolism, motility and phototransduction.
Thyroid hormone (TH) balance is essential for vertebrate development. Deiodinase type 1 (D1) and type 2 (D2) increase and deiodinase type 3 (D3) decreases local intracellular levels of T3, the most important active TH. The role of deiodinase-mediated TH effects in early vertebrate development is only partially understood. Therefore, we investigated the role of deiodinases during early development of zebrafish until 96 hours post fertilization at the level of the transcriptome (microarray), biochemistry, morphology and physiology using morpholino (MO) knockdown. Knockdown of D1+D2 (D1D2MO) and knockdown of D3 (D3MO) both resulted in transcriptional regulation of energy metabolism and (muscle) development in abdomen and tail, together with reduced growth, impaired swim bladder inflation, reduced protein content and reduced motility. The reduced growth and impaired swim bladder inflation in D1D2MO could be due to lower levels of T3 which is known to drive growth and development. The pronounced upregulation of a large number of transcripts coding for key proteins in ATP-producing pathways in D1D2MO could reflect a compensatory response to a decreased metabolic rate, also typically linked to hypothyroidism. Compared to D1D2MO, the effects were more pronounced or more frequent in D3MO, in which hyperthyroidism is expected. More specifically, increased heart rate, delayed hatching and increased carbohydrate content were observed only in D3MO. An increase of the metabolic rate, a decrease of the metabolic efficiency and a stimulation of gluconeogenesis using amino acids as substrates may have been involved in the observed reduced protein content, growth and motility in D3MO larvae. Furthermore, expression of transcripts involved in purine metabolism coupled to vision was decreased in both knockdown conditions, suggesting that both may impair vision. This study provides new insights, not only into the role of deiodinases, but also into the importance of a correct TH balance during vertebrate embryonic development.


DDX6 (Rck/p54) is required for efficient hepatitis C virus replication but not for internal ribosome entry site-directed translation.
DDX6 (Rck/p54) is an evolutionarily conserved member of the SF2 DEAD-box RNA helicase family that contributes to the regulation of translation and storage and the degradation of cellular mRNAs. It interacts with multiple proteins and is a component of the micro-RNA (miRNA)-induced silencing complex (miRISC). Since miRNA-122 (miR-122) is essential for efficient hepatitis C virus (HCV) replication, we investigated the requirement for DDX6 in HCV replication in cultured hepatoma cells. Small interfering RNA (siRNA)-mediated knockdown of DDX6 and rescue with an siRNA-resistant mutant demonstrated that DDX6 expression is indeed required for optimal HCV replication. However, DDX6 knockdown did not impair miR-122 biogenesis or alter HCV responsiveness to miR-122 supplementation. Overexpression of DDX6 fused to EYFP (EYFP-DDX6) enhanced replication, whereas a helicase-deficient mutant with a substitution in the conserved DEAD-box motif II (DQAD) had a dominant-negative effect, reducing HCV yields. Coimmunoprecipitation experiments revealed an intracellular complex containing DDX6, HCV core protein, and both viral and cellular RNAs, the formation of which was dependent upon the C-terminal domain of DDX6 but not DDX6 helicase activity. However, since DDX6 abundance influenced the replication of subgenomic HCV RNAs lacking core sequence, the relevance of this complex is uncertain. Importantly, DDX6 knockdown caused minimal reductions in cellular proliferation, generally stimulated cellular translation ([(35)S]Met incorporation), and did not impair translation directed by the HCV internal ribosome entry site. Thus, DDX6 helicase activity is essential for efficient HCV replication, reflecting essential roles for DDX6 in HCV genome amplification and/or maintenance of cellular homeostasis.


Eradication of yaws: historical efforts and achieving WHO's 2020 target.
Yaws, one of the 17 neglected tropical diseases (NTDs), is targeted for eradication by 2020 in resolution WHA66.12 of the World Health Assembly (2013) and the WHO roadmap on NTDs (2012). The disease frequently affects children who live in poor socioeconomic conditions. Between 1952 and 1964, WHO and the United Nations Children's Fund (UNICEF) led a global eradication campaign using injectable benzathine penicillin. Recent developments using a single dose of oral azithromycin have renewed optimism that eradication can be achieved through a comprehensive large-scale treatment strategy. We review historical efforts to eradicate yaws and argue that this goal is now technically feasible using new tools and with the favorable environment for control of NTDs. We also summarize the work of WHO's Department of Control of Neglected Tropical Diseases in leading the renewed eradication initiative and call on the international community to support efforts to achieve the 2020 eradication goal. The critical factor remains access to azithromycin. Excluding medicines, the financial cost of yaws eradication could be as little as US$ 100 million. The development of new tools has renewed interest in eradication of yaws; with modest support, the WHO eradication target of 2020 can be achieved.


Binding of Phage-Encoded FlaGrab to Motile Campylobacter jejuni Flagella Inhibits Growth, Downregulates Energy Metabolism, and Requires Specific Flagellar Glycans.
Many bacterial pathogens display glycosylated surface structures that contribute to virulence, and targeting these structures is a viable strategy for pathogen control. The foodborne pathogen Campylobacter jejuni expresses a vast diversity of flagellar glycans, and flagellar glycosylation is essential for its virulence. Little is known about why C. jejuni encodes such a diverse set of flagellar glycans, but it has been hypothesized that evolutionary pressure from bacteriophages (phages) may have contributed to this diversity. However, interactions between Campylobacter phages and host flagellar glycans have not been characterized in detail. Previously, we observed that Gp047 (now renamed FlaGrab), a conserved Campylobacter phage protein, binds to C. jejuni flagella displaying the nine-carbon monosaccharide 7-acetamidino-pseudaminic acid, and that this binding partially inhibits cell growth. However, the mechanism of this growth inhibition, as well as how C. jejuni might resist this activity, are not well-understood. Here we use RNA-Seq to show that FlaGrab exposure leads C. jejuni 11168 cells to downregulate expression of energy metabolism genes, and that FlaGrab-induced growth inhibition is dependent on motile flagella. Our results are consistent with a model whereby FlaGrab binding transmits a signal through flagella that leads to retarded cell growth. To evaluate mechanisms of FlaGrab resistance in C. jejuni, we characterized the flagellar glycans and flagellar glycosylation loci of two C. jejuni strains naturally resistant to FlaGrab binding. Our results point toward flagellar glycan diversity as the mechanism of resistance to FlaGrab. Overall, we have further characterized the interaction between this phage-encoded flagellar glycan-binding protein and C. jejuni, both in terms of mechanism of action and mechanism of resistance. Our results suggest that C. jejuni encodes as-yet unidentified mechanisms for generating flagellar glycan diversity, and point to phage proteins as exciting lenses through which to study bacterial surface glycans.


["A decision meaning a new foundation...": from the Kaiser Wilhelm Institute for Anthropology, Human Genetics and Eugenics to the Max Planck Institute for Molecular Genetics].
The Max Planck Institute for Molecular Genetics (MPIMG) in Berlin-Dahlem dates its establishment to 1964. Its homepage makes no mention of its predecessor institutes, the Kaiser Wilhelm Institute for Anthropology, Human Genetics and Eugenics (KWIA) and the subsequent MPI for Comparative Genetics and Hereditary Pathology (MPIVEE). This article traces the two critical phases of transition regarding the constellations of academic staff, institutional and epistemic ruptures and continuities specific to the era. Only one of the five department heads from the final war years, Hans Nachtsheim, remained a researcher within the Max Planck Society (MPG); he nevertheless continued to advocate the pre-war and wartime eugenic agenda in the life sciences and social policy. The generational change of 1959/60 became a massive struggle within the institute, in which microbial genetics (with Fritz Kaudewitz) was pitted against human genetics (with Friedrich Vogel) and managed to establish itself after a fresh change in personnel in 1964/65. For the Dahlem institute, this involved a far-reaching reorientation of its research, but for the genetically oriented life sciences in the Max Planck Society as a whole it only meant that molecular biology, which was already being pursued in the West German institutes, gained an additional facility. With this realignment of research traditions, the Society was able to draw a line under the Nazi past without having to address it head-on.


Health information technology to facilitate communication involving health care providers, caregivers, and pediatric patients: a scoping review.
Pediatric patients with health conditions requiring follow-up typically depend on a caregiver to mediate at least part of the necessary two-way communication with health care providers on their behalf. Health information technology (HIT) and its subset, information communication technology (ICT), are increasingly being applied to facilitate communication between health care provider and caregiver in these situations. Awareness of the extent and nature of published research involving HIT interventions used in this way is currently lacking. This scoping review was designed to map the health literature about HIT used to facilitate communication involving health care providers and caregivers (who are usually family members) of pediatric patients with health conditions requiring follow-up. Terms relating to care delivery, information technology, and pediatrics were combined to search MEDLINE, EMBASE, and CINAHL for the years 1996 to 2008. Eligible studies were selected after three rounds of duplicate screening in which all authors participated. Data regarding patient, caregiver, health care provider, HIT intervention, outcomes studied, and study design were extracted and maintained in a Microsoft Access database. Stage of research was categorized using the UK's Medical Research Council (MRC) framework for developing and evaluating complex interventions. Quantitative and qualitative descriptive summaries are presented. We included 104 eligible studies (112 articles) conducted in 17 different countries and representing 30 different health conditions. The most common conditions were asthma, type 1 diabetes, special needs, and psychiatric disorder. Most studies (88, 85%) included children 2 to 12 years of age, and 73 (71%) involved home care settings. Health care providers operated in hospital settings in 96 (92%) of the studies. Interventions featured 12 modes of communication (eg, Internet, intranets, telephone, video conferencing, email, short message service [SMS], and manual downloading of information) used to facilitate 15 categories of functions (eg, support, medication management, education, and monitoring). Numerous patient, caregiver, and health care relevant outcomes have been measured. Most outcomes concerned satisfaction, use, usability, feasibility, and resource use, although behavior changes and quality of life were also reported. Most studies (57 studies, 55%) were pilot phase, with a lesser proportion of development phase (24 studies, 23%) and evaluation phase (11 studies, 11%) studies. HIT interventions addressed several recurring themes in this review: establishing continuity of care, addressing time constraints, and bridging geographical barriers. HIT used in pediatric care involving caregivers has been implemented differently in a range of disease settings, with varying needs influencing the function, form and synchronicity of information transfer. Although some authors have followed a phased approach to development, evaluation and implementation, a greater emphasis on methodological standards such as the MRC guidance for complex interventions would produce more fruitful programs of development and more useful evaluations in the future. This review will be especially helpful to those deciding on areas where further development or research into HIT for this purpose may be warranted.


Telling stories about illness and disability: the limits and lessons of narrative.
Autobiographical narratives of illness and disability are influential in popular and medical discourses of illness and disability, in part because these narratives represent illness and disability within a sociocultural context, intersecting with other categories of difference. Clinicians can benefit patients through a critical understanding of the formal and social conventions that shape illness and disability narratives and the effect these conventions can have on the lived experience of illness and disability. I analyze the 2003 edition of Lucy Grealy's Autobiography of a Face to illustrate these socio-narrative conventions, especially in light of an afterword that significantly revises the ending to Grealy's narrative. I explore the parallels between narrative conventions-such as the "recovery narrative"-and caregivers' expectations that shape the role of the "good patient," as well as the resistance to conventions of closure, represented by the "renegotiated ending."


Retrospective study of efficacy and toxicity on patients older than 70 years within a randomized clinical trial of two cisplatin-based combinations in patients with small-cell lung cancer.
A retrospective analysis based on the Spanish Lung Cancer Group (SLCG) clinical trial of high-dose epirubicin/cisplatin in patients with small-cell lung cancer (SCLC) was performed. Patients younger than 70 years vs. older than 70 years old were analyzed to evaluate the influence of age on response to treatment, toxicity, time to progression (TTP) and overall survival (OS) of the chemotherapy schedule. Three hundred and thirty eight patients <70 years and sixty-four >70 years, were analyzed. Objective responses were similar in both groups. In patients less than 70 years higher TTP (36 weeks vs. 32 weeks) and OS (47 weeks vs. 42 weeks) were seen, attributable to the improved results observed in the subgroup of patients with limited disease (LD). No significant differences were observed when toxicity profile of both groups was compared, except for a higher rate of febrile neutropenia observed in the elderly group with extensive disease (4.6% vs. 8.8%, p=0.01). In the subgroup of patients with LD, elderly patients received less total cisplatin dose (401 vs. 508 mg/m(2), p=0.01) although less treatment delays were reported (10 days vs. 15 days, p=0.05). Age was likely to be a negative prognostic factor for OS of elderly patients with LD. It also seemed to be related to a greater dose reduction, which may explain that toxic episodes and delays occurred more frequently in the younger patients receiving the full scheduled dose. However, the definitive reason to explain this could not be established due to the characteristics of our analysis.


[The abnormalities of carbohydrate and lipid metabolism in uremia. A study in 20 hemodialyzed patients (author's transl)].
The glucose tolerance and serum lipids pattern were studied in 20 hemodialyzed patients after 8 and 12 hours of fasting. They all were non-obese uremics under 40 years of age. The test was conducted according to the nutritional conditions of the protocol of de Gennes. Fasting hyperglycemia and an abnormal glucose tolerance test were observed in 75% of the patients. The basal serum insulin levels were increased in 80% of the cases. 40% of the population studied exhibited significant hypertriglyceridemia after 12 hours and 65% after only 8 hours of fasting. Thus, this protocol was useful for detecting abnormalities in the metabolism of triglycerides in hemodialyzed patients with few baseline disturbances. The normal levels of serum triglycerides at 12 hours could be explained by 1) the relatively young age of the population studied and 2) dialysis with glucose free solutions.


Immediate ridge reconstruction with a composite tuberosity graft after removal of failing implants.
When a dental implant is discovered to be failing, the implant must be removed, resulting in a defect. Immediate reconstruction of the defect using an autogenous composite tuberosity graft has been reported following the removal of a single implant. Ridge reconstruction after the removal of more than one failing dental implant poses an even greater challenge, given the substantial loss of hard and soft tissue. To the author's knowledge, this is the first report to describe the use of an autogenous composite tuberosity graft for the reconstruction of hard and soft tissue for multiple sites. Three patients with failing implants and ridge defects received a composite tuberosity graft comprising the bone, periosteum, connective tissue, and epithelium of the maxillary tuberosity for simultaneous hard and soft tissue reconstruction. Bone from the maxillary tuberosity was positioned between the bony borders of the defect or fixed buccally to augment the ridge. Smaller bone pieces from the tuberosity were used to fill the gaps. The soft tissue portion of the graft was allowed to heal spontaneously, thus eliminating the need for further surgery to increase keratinized gingiva and vestibular depth. All sites recovered uneventfully, and the ridge dimensions were re-established. For patients with sufficient tuberosity bone volume, using a one-piece composite tuberosity bone graft appears to be a promising approach for rebuilding the ridge in a single surgery. Why are these cases new information? Large hard and soft tissue defects are reconstructed immediately after the removal of one or more failed implants. Keratinized gingival width and vestibular depth are improved. What are the keys to the successful management of these cases? Cone-beam computed tomography for tuberosity and defect evaluation Careful handling of tuberosity bone Proper graft shaping Composite tuberosity graft fixation Fixed provisional prosthesis for grafted area protection What are the key limitations to the success of these cases? Unavailability of tuberosity A technique-sensitive approach.


Induction of centrosome amplification and chromosome instability in p53-deficient lung cancer cells exposed to benzo[a]pyrene diol epoxide (B[a]PDE).
Benzo[a]pyrene diol epoxide (B[a]PDE), the ultimate carcinogenic metabolite of benzo[a] pyrene, has been implicated in the mutagenesis of the p53 gene involved in smoking-associated lung cancer. To further understand the role of B[a]PDE in lung tumour progression, we investigated its effect on the numerical integrity of centrosomes and chromosome stability in lung cancer cells lacking p53. Exposure of p53-deficient H1299 lung cancer cells to B[a]PDE resulted in S-phase arrest, leading to abnormal centrosome amplification. Analysis of H1299 cells stably expressing fluorescence-tagged centrin (a known centriolar marker) revealed that the centrosome amplification was primarily attributable to excessive centrosome duplication rather than to centriole splitting. Forced expression of POLK DNA polymerase, which has the ability to bypass B[a]PDE-guanine lesions in an error-free manner, suppressed the B[a]PDE-induced centrosome amplification. Fluorescence in situ hybridization analyses with probes specific for chromosomes 2, 3, and 16 revealed that B[a]PDE exposure also led to chromosome instability, which was likely to have resulted from centrosome amplification. We extended these findings to primary lung carcinomas containing non-functional p53, and found a strong association between centrosome amplification and a high level of B[a]PDE-DNA accumulation. Therefore B[a]PDE contributes to neoplasia by inducing centrosome amplification and consequent chromosome destabilization as well as its mutagenic activity.


Does normal pulmonary impedance constitute the optimum load for the right ventricle?
Right ventricular performance of isolated supported cat hearts was experimentally characterized by a relationship among ventricular pressure (P), volume (V), and time after onset of systole. This characterization was combined with a hypothetical load network consisting of lumped central and peripheral lung vascular resistances (Rc and Rp), inertance (L), and compliance (C). We calculated ventricular and load pressure, flow, external ventricular work (Wext), static ventricular P-V energy (Wstat), and pump efficiency Q = Wext/Wstat over a broad range of load conditions. Magnitudes of load network variables resulting in a maximum value of Q would define the load impedance matching the ventricle. A practical optimum magnitude of lumped vascular compliance was obtained at C = 150 x 10(-6) g-1 . cm4, above which no substantial change in Q took place. We obtained maximum Q at approximately 4 ml stroke volume (heart rate = 2 Hz) and at characteristic impedance between 0.75 and 1.1 x 10(3)g . cm-1 . s-1. As these values are quite close to those encountered in the intact animal, we conclude that the right ventricular and the pulmonary arterial tree appear to constitute a matched pump-load system.


NMR imaging of acute experimental cerebral ischemia: time course and pharmacologic manipulations.
Nuclear magnetic resonance (NMR) imaging was used to evaluate the intracerebral changes over time in gerbils after unilateral carotid artery ligation. Each animal was imaged during one of three stated periods 3-28 hr after surgery and again after administration of dexamethasone, morphine, or naloxone, agents reported to affect the clinical outcome of ischemic cerebral lesions. Asymptomatic animals exhibited no differences between the occluded and control hemispheres in relative signal intensity or in T1 or T2 relaxation times, but symptomatic animals demonstrated significant differences in these parameters between hemispheres. The ischemic lesion was detected at the earliest imaging time, 3 hr after surgery. A linear increase was observed in the relative interhemispheric signal intensity in three of four intensity images and in T1 and T2 relaxation times over the 24 hr experiment. No effect was noted on any image parameter as a result of pharmacologic manipulations. The results suggest that NMR may be of significant diagnostic importance for acute cerebral ischemia and infarction in man.


gamma2-COP, a novel imprinted gene on chromosome 7q32, defines a new imprinting cluster in the human genome.
We describe a novel imprinted gene, gamma 2-COP (nonclathrincoatprotein), identified in a search for expressed sequences in human chromosome 7q32 where the paternally expressed MEST gene is located. gamma 2-COP contains 24 exons and spans >50 kb of genomic DNA. Like MEST, gamma 2-COP is ubiquitously transcribed in fetal and adult tissues. In fetal tissues, including skeletal muscle, skin, kidney, adrenal, placenta, intestine, lung, chorionic plate and amnion, gamma 2-COP is imprinted and expressed from the paternal allele. In contrast to the monoallelic expression observed in these fetal tissues, biallelic expression was evident in fetal brain and liver and in adult peripheral blood. Biallelic expression in blood is supported by the demonstration of gamma 2-COP transcripts in lymphoblastoid cell lines with maternal uniparental disomy 7. Absence of paternal gamma 2-COP transcripts during embryonic development may contribute to Silver-Russell syndrome. However, on mutation scanning the only gamma 2-COP mutation detected was maternally derived. Amino acid comparison of gamma2-COP protein revealed close relation to gamma-COP, a subunit of the coatomer complex COPI, suggesting a role of gamma2-COP in cellular vesicle traffic. The existence of distinct coatomer complexes could be the basis for the functional heterogeneity of COPI vesicles in retrograde and anterograde transport and/or in cargo selection. Together, gamma 2-COP and MEST constitute a novel imprinting cluster in the human genome that may contain other, as yet unknown, imprinted genes.


Identification and characterization of glucocorticoid receptors in B16 mouse melanoma cells.
To gain better insight into the role of glucocorticoids as modulators of cell growth, as well as to investigate the presence and characteristics of glucocorticoid receptors (GR) in mouse melanoma cells. In two different B16 mouse melanoma cell clones (B16/F10 and B16/C3) the role of synthetic glucocorticoids (triamcinolone acetonide, TA) as cell growth modulators was investigated. The inhibitory effect of TA on B16/F10 cell growth after 8 days in culture was observed. The same hormonal treatment applied on B16/C3 melanoma cells also provoked changes in the cell growth. Dot blot analysis, using monoclonal antirodent glucocorticoid receptor antibodies showed the presence of receptor protein in both cell clones. The analysis of glucocorticoid receptors in B16/F10 and B16/C3 cell cytosol by Scatchard assay and ion-exchange chromatography on DEAE-Sephadex A-50 minicolumn indicated that the changes in melanoma cell growth may be mediated by glucocorticoid receptors and may relieve changes in the GR itself. It was found that B16/C3 melanoma cells exhibited different growth pattern under TA treatment when compared to the results obtained with B16/F10 cells. Such differences may be mediated by glucocorticoid receptors.


3D treatment planning and intensity-modulated radiation therapy.
Three-dimensional (3D) image-based treatment planning and new delivery technologies have spurred the implementation of external beam radiation therapy techniques, in which the high-dose region is conformed much more closely to the target volume than previously possible, thus reducing the volume of normal tissues receiving a high dose. This form of external beam irradiation is referred to as 3D conformal radiation therapy (3DCRT). 3DCRT is not just an add-on to the current radiation oncology process; it represents a radical change in practice, particularly for the radiation oncologist. Defining target volumes and organs at risk in 3D by drawing contours on CT images on a slice-by-slice basis, as opposed to drawing beam portals on a simulator radiograph, can be challenging, because radiation oncologists are generally not well trained in cross-sectional imaging. Currently, the 3DCRT approach will increase the time and effort required by physicians inexperienced with 3D treatment planning. Intensity-modulated radiation therapy (IMRT) is a more advanced form of 3DCRT, but there is considerable developmental work remaining. The instrumentation and methods used for IMRT quality assurance procedures and testing are not well established. Computer optimization cost functions are too simplistic, and thus time-consuming. Subjective plan evaluation by the radiation oncologist is still the norm. In addition, many fundamental questions regarding IMRT remain unanswered. For example, the radiobiophysical consequences of altered time-dose-fraction are unknown. Also, the fact that there is much greater dose heterogeneity for both the target and normal critical structures with IMRT compared to traditional irradiation techniques challenges current radiation oncology planning principles. However, this new process of planning and treatment delivery shows significant potential for improving the therapeutic ratio. In addition, while inefficient today, these systems, when fully developed, will improve the efficiency with which external beam radiation therapy can be planned and delivered, thus lowering costs.


Determination of glyphosate, AMPA and glufosinate by high performance liquid chromatography with fluorescence detection in waters of the Santarém Plateau, Brazilian Amazon.
Herbicide use, mainly glyphosate, has been intense in worldwide agriculture, including in the Brazilian Amazon region. This study aimed to validate a method for determining glyphosate and its degradation product, AMPA, and glufosinate by HPLC-FL in 58 water samples collected at the Santarém plateau region (Planalto Santareno), in the western of Pará state, Brazil. The method involves filtration and direct injection in the HPLC-FL for AMPA analysis, or previous concentration (10×) by lyophilization for glufosinate and glyphosate analysis. Analytes were oxidized and complexed with o-phthalaldehyde and 2-mercaptoethanol in a post-column reaction before fluorescence detection. LOQs for AMPA, glyphosate and glufosinate were established at 0.5, 0.2 and 0.3 μg L-1, respectively. A total of 58 samples were collected. Glyphosate and glufosinate were not detected in any of the 30 surface water samples collected in 2015 (<LOQ), and AMPA was detected in 6 samples (0.65-1.93 μg L-1). A total of 28 ground and surface water samples were collected in 2017 and analyzed for glyphosate, which was detected in 11 samples (7 ground water samples), with concentrations between 1.5 and 9.7 μg L-1. A continuous pesticide monitoring of the Amazonian water system is essential to guarantee the preservation of this important ecosystem.


Prevalence and significance of cardiovascular disease and hypertension in elderly patients with dementia and depression.
The prevalence and significance of clinical heart disease and hypertension were compared in three groups of elderly patients. One group was diagnosed as dementia of an Alzheimer's type (AD), another as multiinfarct dementia (MID), and the third as major depression. Clinical heart disease and hypertension were uncommon in the AD group with the prevalence being lower than that reported in most epidemiologic studies. Four percent of the AD patients had a history of myocardial infarction, 5% angina, 1% arrhythmias, and 3% heart failure. Electrocardiographic changes of an old myocardial infarction were present in 9%, atrial fibrillation in 1%, and left ventricular hypertrophy in 3%. A history of hypertension was present in 24% of the AD patients. In comparison, a history of myocardial infarction, angina, and heart failure was five times greater, and electrocardiographic abnormalities were twice as prevalent in the MID group. A history of hypertension was three times more common and actual blood pressure readings were higher. In the depression group heart disease was not uncommon and the prevalence, in general, was comparable with the MID group. However, a history of increased blood pressure and actual increased blood pressure readings were statistically less than in the MID group.


Medical response of a physician and two nurses to the mass-casualty event resulting in the Phi Phi Islands from the tsunami.
The Phi Phi Islands are isolated islands located about one hour by ship from the mainland in Krabi province of Thailand. There is a small medical facility where the director is the one physician that provides care to residents and tourists. This small medical facility faced an enormous mass casualty incident due to the 2004 Tsunami. The hospital was damaged by the Tsunami wave and was not functional, one crew member died and another was injured. Medical care and evacuation posed a unique problem in the Phi Phi Islands due to remoteness, limited medical resources, lack of effective communication with the main land and the large number of victims. An alternative medical facility was located in a nearby hotel. The crew included the medical director, two nurses, two additional staff members, 10 local volunteers, and hotel staff members. The medical crew had to treat 600-700 casualties in 24 hours. Most of the victims were mildly injured, but approximately 100 (15%) of the victims could not walk due to their injuries. The medical director, made a conscious decision to initially treat only circulation ("C") problems, by controlling external hemorrhages. This decision was driven by the lack of equipment and personnel to deal with airway ("A") and breathing ("B") problems. In the post-disaster debriefing, the Phi Phi Island hospital physician noted five major lessons concerning disaster management in such extreme situation in a small facility located in a remote area: (1) effective resistant communication facilities must be ensured; (2) clear, simple "evacuation plans" should be made in advance; (3) plans should be made to ensure automatic reinforcement of remote areas with evacuation vehicles, medical equipment and medical personnel; (4) efficient cooperation with medical volunteers must be planned and drilled; and (5) every team member of such a hospital must participate in an educational program and periodic drills should be done to improve the disaster and emergency medicine capabilities. This case report is an example for caregivers all over the world, of an amazing lesson of leadership and courage.


Pathway analysis of a genome-wide gene by air pollution interaction study in asthmatic children.
We aimed to investigate the role of genetics in the respiratory response of asthmatic children to air pollution, with a genome-wide level analysis of gene by nitrogen dioxide (NO2) and carbon monoxide (CO) interaction on lung function and to identify biological pathways involved. We used a two-step method for fast linear mixed model computations for genome-wide association studies, exploring whether variants modify the longitudinal relationship between 4-month average pollution and post-bronchodilator FEV1 in 522 Caucasian and 88 African-American asthmatic children. Top hits were confirmed with classic linear mixed-effect models. We used the improved gene set enrichment analysis for GWAS (i-GSEA4GWAS) to identify plausible pathways. Two SNPs near the EPHA3 (rs13090972 and rs958144) and one in TXNDC8 (rs7041938) showed significant interactions with NO2 in Caucasians but we did not replicate this locus in African-Americans. SNP-CO interactions did not reach genome-wide significance. The i-GSEA4GWAS showed a pathway linked to the HO-1/CO system to be associated with CO-related FEV1 changes. For NO2-related FEV1 responses, we identified pathways involved in cellular adhesion, oxidative stress, inflammation, and metabolic responses. The host lung function response to long-term exposure to pollution is linked to genes involved in cellular adhesion, oxidative stress, inflammatory, and metabolic pathways.


Encapsulation of proteins in transparent porous silicate glasses prepared by the sol-gel method.
Novel sol-gel synthetic techniques were used to immobilize copper-zinc superoxide dismutase (CuZnSOD), cytochrome c, and myoglobin (Mb) by encapsulation in stable, optically transparent, porous silica glass matrices under mild conditions such that the biomolecules retained their characteristic reactivities and spectroscopic properties. The resulting glasses allowed transport of small molecules into and out of the glasses at reasonable rates but nevertheless retained the protein molecules within their pores. Chemical reactions of the immobilized proteins could be monitored by means of changes in their visible absorption spectra. Silica glasses containing the immobilized proteins were observed to have similar reactivities and spectroscopic properties to those found for the proteins in solution. For example, encapsulated CuZnSOD was demetallated and remetallated, encapsulated ferricytochrome c was reduced and then reoxidized, and encapsulated met Mb was reduced to deoxy Mb and then reacted either with dioxygen to make oxy Mb or with carbon monoxide to make carbonyl Mb.


Development of a transformation system for Hirsutella spp. and visualization of the mode of nematode infection by GFP-labeled H. minnesotensis.
Hirsutella rhossiliensis and H. minnesotensis are endoparasitic fungi of the second-stage juvenile (J2) of the soybean cyst nematode (Heterodera glycines) in nature. They also parasitize both H. glycines J2 and Caenorhabditis elegans on agar plates. Agrobacterium tumefaciens-mediated transformation conditions were established for these Hirsutella spp. The resulting transformants were similar to the corresponding wild-type strains. The infection processes of H. glycines J2 and C. elegans second larval stage (L2) by H. minnesotensis expressing ZsGreen were microscopically analyzed. Conidia of H. minnesotensis adhered to passing nematodes within 8 h post-inoculation (hpi), formed an infection peg between 8 and 12 hpi, and penetrated the nematode cuticle between 12 and 24 hpi for C. elegans L2 and between 12 and 32 hpi for H. glycines J2. Hyphal proliferation inside of the nematode coelom was observed at approximately 32 hpi for C. elegans L2 and at approximately 40 hpi for H. glycines J2. The fungus consumed the whole body and grew out to produce conidia at approximately 156 and 204 hpi for C. elegans L2 and H. glycines J2, respectively. The efficient transformation protocol and a better understanding of infection process provide a solid foundation for studying the molecular and cellular mechanisms underlying fungal parasitism of nematodes.


Extensive colonic pneumatosis. Conservative or Surgical approach?
Intestinal pneumatosis is a radiologic finding that consists of the presence of air in the intestinal wall. The etiology is extensive and can range from a benign entity to one that compromises the patients´ life. It is important to know and recognize the differences between them as the surgical management will depend on it. We report the case of an 82-year-old male diagnosed with a metastatic castration resistant prostate carcinoma, under chemotherapy with disease progression in treatment with high doses of intravenous morphics. The patient reported abdominal distension with constipation and no vomiting in the emergency department and a distended and tympanic abdomen, without generalized peritonitis was identified during physical examination. A blood analysis showed lactate levels of 0.9 mmol/L and a PCR of 4.2 mg/L without leukocytosis. An extensive colonic pneumatosis with minimum pneumoperitoneum without free fluid was confirmed by a computed tomography (CT) scan (Fig 1). A conservative approach with intravenous antibiotic and clinical surveillance was decided due to the fact that the patient was clinically stable without generalized peritonitis nor pathological findings in the supplementary blood tests. The clinical evolution was uneventful and the patient was discharged from hospital De la Serna et al. opted for a conservative approach for a patient with stage IV lung adenocarcinoma under chemotherapy treatment, who presented asymptomatic intestinal pneumatosis and subsequently made a full recovery. We also believe that the use of some chemotherapeutic agents may cause an increase in the permeability of the intestinal capillaries, allowing air to flow into the intestinal walls. Thus, resulting in this radiologic image, which is more a radiological finding than a disease. We think that a conservative initial attitude should be recommended in hemodynamically stable cases, without peritonitis and non-pathological blood analysis.


The epidemiology of malignant giant cell tumors of bone: an analysis of data from the Surveillance, Epidemiology and End Results Program (1975-2004).
Malignant giant cell tumor (GCT) of bone is a rare tumor with debilitating consequences. Patients with GCT of bone typically present with mechanical difficulty and pain as a result of bone destruction and are at an increased risk for fracture. Because of its unusual occurrence, little is known about the epidemiology of malignant GCT of bone. This report offers the first reliable population-based estimates of incidence, patient demographics, treatment course and survival for malignancy in GCT of bone in the United States. Using data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program, we estimated the overall incidence and determinants of survival among patients diagnosed with malignant GCT of bone from 1975-2004. Cox proportional hazards regression was used to evaluate demographic and clinical determinants of survival among malignant GCT cases. Based on analyses of 117 malignant GCT cases, the estimated annual incidence in the United States was 1.6 per 10,000,000 persons per year. Incidence was highest among adults aged 20 to 44 years (2.4 per 10,000,000 per year) and most patients were diagnosed with localized (31.6%) or regional (29.9%) disease compared to distant disease (16.2%). Approximately 85% of patients survived at least 5 years, with survival poorest among older patients and those with evidence of distant metastases at time of diagnosis. The current study represents the largest systematic investigation examining the occurrence and distribution of malignancy in GCT of bone in the general U.S. population. We confirm its rare occurrence and suggest that age and stage at diagnosis are strongly associated with long-term survival.


The acute effects of a caffeine-containing supplement on bench press strength and time to running exhaustion.
The purpose of the present study was to examine the acute effects of a caffeine-containing supplement (SUPP) on one-repetition maximum (1-RM) bench press strength and time to running exhaustion (TRE) at a velocity that corresponded to 85% of the peak oxygen uptake ([latin capital V with dot above]O2peak). The study used a double-blinded, placebo-controlled, crossover design. Thirty-one men (mean +/- SD age = 23.0 +/- 2.6 years) were randomly assigned to take either the SUPP or placebo (PLAC) first. The SUPP contained 201 mg of caffeine, and the PLAC was microcrystalline cellulose. All subjects were tested for 1-RM bench press strength and TRE at 45 minutes after taking either the SUPP or PLAC. After 1 week of rest, the subjects returned to the laboratory and ingested the opposite substance (SUPP or PLAC) from what was taken during the previous visit. The 1-RM bench press and TRE tests were then performed in the same manner as before. The results indicated that the SUPP had no effect on 1-RM bench press strength or TRE at 85% [latin capital V with dot above]O2peak. It is possible that the acute effects of caffeine are affected by differences in training status and/or the relative intensity of the exercise task. Future studies should examine these issues, in addition to testing the acute effects of various caffeine doses on performance during maximal strength, power, and aerobic activities. These findings do not, however, support the use of caffeine as an ergogenic aid in untrained to moderately trained individuals.


Anti-inflammatory and antitumor promotional effects of a novel urinary metabolite, 3',4'-didemethylnobiletin, derived from nobiletin.
We reported previously that 3',4'-didemethylnobiletin (DDMN) is the major metabolite of nobiletin in mouse urine. In this study, we examined DDMN's molecular mechanism of action and its anti-inflammatory and antitumor properties. We demonstrated that topical application of DDMN effectively inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated transcription of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and ornithine decarboxylase (ODC) messenger RNA and protein expression in mouse skin. Pretreatment with DDMN has resulted in the reduction of TPA-induced nuclear translocation of the nuclear factor-kappa B (NF-kappaB) subunit. DDMN also reduced DNA binding by blocking phosphorylation of inhibitor kappaB (IkappaB) alpha and p65 and caused subsequent degradation of IkappaBalpha. DDMN inhibited TPA-induced phosphorylation and nuclear translocation of the signal transducer and activator of transcription 3. Moreover, DDMN suppressed TPA-induced activation of extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase, phosphatidylinositol 3-kinase/Akt and protein kinase C that are upstream of NF-kappaB and activator protien-1. We also found that DDMN significantly inhibited TPA-induced mouse skin inflammation by decreasing inflammatory parameters. Furthermore, DDMN significantly inhibited 7,12-dimethylbenz[a]anthracene/TPA-induced skin tumor formation measured by the tumor multiplicity of papillomas at 20 weeks. Presented data for the first time reveal that DDMN is an effective antitumor agent that functions by downregulating inflammatory iNOS, COX-2 and ODC gene expression in mouse skin. It is suggested that DDMN is a novel functional agent capable of preventing inflammation-associated tumorigenesis.


Human serum protein fractionation by gel filtration.
The development of a quantitative immunological technique using polyvalent antiserum permits a more logical approach to the fractionation of complex protein mixtures. In this study whole serum was separated by conventional gel filtration and the fractions obtained were analysed. This demonstrates over 60 immunologically distinct serum proteins. Because the current terminology is inadequate to describe this number of proteins, a temporary numerical nomenclature has been used.


The effect of intrathecal administration TRPA1 antagonists in a rat model of neuropathic pain.
The fact that transient receptor potential ankyrin 1 (TRPA1) on the peripheral terminals could attenuate hyperalgesia is widely accepted, but the effect of spinal TRPA1 in the modulation of hyperalgesia has not been fully demonstrated. In the present study, we investigated the effect of intrathecal (i.t.) administration TRPA1 antagonists on chronic pain and expression of TRPA1 and phosphorylation N-methyl-D-aspartate receptor 2B subunit (p-NR2B) in the spinal cord with chronic compression of the dorsal root ganglia (CCD) in rats. The study was conducted in 2 parts. Part 1: Sixteen rats were divided into 2 groups (n = 8 each): a sham group and CCD group. Paw withdrawal mechanical thresholds (PWMT) were measured at baseline and 1, 3, 7, 10, 14, and 21 days after CCD. Sixteen other rats were used to evaluate expression of TRPA1 and p-NR2B in spinal cord on the seventh and 14th days after CCD; Western blotting was used to evaluate expression levels (n = 4 each). Part 2: 40 rats were divided into 5 groups (n = 8 each): CCD group, CCD + Vehicle group, CCD + HC-030031(10 μg, i.t.) group, CCD + HC-030031(25 μg, i.t.) group, and CCD + HC-030031(50 μg, i.t.) group. PWMTs were measured at baseline and 0.5, 1, 2, 4, and 6 hours after i.t. HC-030031 on the third, seventh, 10th, and 14th days after CCD. Another 48 rats were used to evaluate expression of TRPA1 and p-NR2B in spinal cord 2 hours after injection on the seventh and 14th days after CCD in groups CCD, CCD + Vehicle, and CCD+ HC-030031(50 μg, i.t.) using Western blotting (n = 4 each). Compared with the sham group, PWMT was significantly decreased, and protein expression of TRPA1 and p-NR2B were upregulated, in spinal cord on the seventh and 14th days after CCD operation. TRPA1 antagonists (HC-030031, 50 μg, i.t.) increased the PWMT after CCD and downregulated the protein level of TRPA1 and p-NR2B in spinal cord at 2 hours after the injection on the seventh and 14th days after CCD. These data demonstrated that the i.t. administration of TRPA1 antagonists could attenuate neuropathic pain in CCD rats, and this effect could be partially reduced by p-NR2B receptor expression in spinal cord.


Purification and Characterization of Antioxidant Peptides from Alcalase-Hydrolyzed Soybean ( Glycine max L.) Hydrolysate and Their Cytoprotective Effects in Human Intestinal Caco-2 Cells.
This study aimed to purify and identify antioxidant peptides from the low-molecular-weight fraction (SPH-I, MW < 3 kDa) of Alcalase-hydrolyzed soybean ( Glycine max L.) hydrolysate and further evaluate the cytoprotective effects of synthesized peptides against oxidative stress in human intestinal Caco-2 cells. After purification by gel filtration chromatography and reversed-phase HPLC, four major peptides were sequenced by nano-LC-ESI-MS/MS as VVFVDRL (847 Da, SPH-IA), VIYVVDLR (976 Da, SPH-IB), IYVVDLR (877 Da, SPH-IC), and IYVFVR (795 Da, SPH-ID). The antioxidant peptides were synthesized and displayed desirable DPPH radical-scavenging activity (from 16.5 ± 0.5 to 20.3 ± 1.0 μM Trolox equivalent (TE)/μM), ABTS•+ radical-scavenging activity (from 3.42 ± 0.2 to 4.24 ± 0.4 mM TE/μM), ORAC (from 143 ± 2.1 to 171 ± 4.8 μM TE/μM), and FRAP (from 54.7 ± 1.2 to 79.0 ± 0.6 mM Fe2+/μM). Moreover, the synthesized peptides protected Caco-2 cells against H2O2-induced oxidative damage via significantly downregulating intracellular ROS generation and lipid peroxidation ( p < 0.05). Additionally, SPH-IC and SPH-ID statistically upregulated total reduced glutathione synthesis, enhanced activities of catalase and glutathione reductase, and suppressed ROS-mediated inflammatory responses via inhibiting interleukin-8 secretion ( p < 0.05).


A comprehensive evaluation of a polymeric zwitterionic hydrophilic monolith for nucleotide separation.
Rapid and effective separation of nucleotides (NTs) and their derivatives is crucial for studying their physiological functions. In this work, we comprehensively evaluated the separation ability of a zwitterionic hydrophilic monolith, i.e., poly(N,N-dimethyl-N-(3-methacrylamidopropyl)-N-(3-sulfopropyl)ammonium betaine-co-N,N'-methylenebisacrylamide) (poly(SPP-co-MBA)) for NTs analysis, including its selectivity, chemical stability under extremely basic condition and compatibility with hydrophilic interaction liquid chromatography (HILIC) coupled with mass spectrometry (HILIC-MS). The poly(SPP-co-MBA) monolith exhibited excellent chemical stability, as evidenced by the low relative standard deviation of retention time (0.16-1.05%) after 4000 consecutive injections over one month under strong alkaline elution condition (pH 10). After optimizing the separation conditions, including buffer pH and concentration, organic solvent content and column temperature, four nucleoside triphosphates, five nucleoside diphosphates and five nucleoside monophosphates were baseline separated within 7 min. Additionally, the mixtures containing one nucleoside and its corresponding mono-, di-, and triphosphates were baseline separated within only 3 min, respectively. It is good HILIC-MS compatibility was also confirmed by the satisfactory peak shape and high response of nine NTs. Overall, the proposed poly(SPP-co-MBA) monolith exhibited good mechanical stability and compatibility of HILIC-MS, making it a promising technique for NTs analysis.


Evaluation of depression, anxiety and stress levels in patients with oral lichen planus.
The pathogenesis of oral lichen planus (OLP) remains to be fully elucidated; however, certain psychoneurological factors may influence the onset and exacerbation of OLP. The aim of the present study is to evaluate the intensity of negative emotions in patients with OLP. A cross-sectional, questionnaire-based study was performed. The sample consisted of 52 subjects, comprising 26 patients with OLP (OLP group) and 26 controls (CTRL group). The Depression Anxiety Stress Scale 21 (DASS-21) was used for psychometric evaluation. The patients were also asked about their attitude toward the disease, treatment, and interference of the disease on daily life. The mean level of depression was 12.54 ± 6.6 in the OLP group and 7.69 ± 5.22 in the CTRL group (P = 0.006). The mean level of anxiety was 11.15 ± 7.95 in the OLP group and 6.62 ± 4.86 in the CTRL group (P = 0.018). The mean stress levels were 8.69 ± 7.06 and 3.85 ± 3.18 in the OLP and CTRL groups, respectively (P = 0.003). Severe and very severe scores of depression and very severe scores of anxiety and stress were present in the OLP group, whereas these emotions were normal in the majority of controls. Depression, stress, and anxiety may be involved in the pathogenesis and course of OLP.


Search for a fourth-generation quark more massive than the Z0 boson in p&pmacr; collisions at radicals = 1.8 TeV
We present the results of a search for pair production of a fourth-generation charge -1 / 3 quark (b(')) in sqrt[s] = 1.8 TeV p&pmacr; collisions using 88 pb(-1) of data obtained with the Collider Detector at Fermilab. We assume that both quarks decay via the flavor-changing neutral current process b(')-->bZ(0) and that the b(') mass is greater than m(Z)+m(b). We studied the decay mode b(')b(');-->Z(0)Z(0)b&bmacr; where one Z0 decays into e(+)e(-) or &mgr;(+)&mgr;(-) and the other decays hadronically, giving a signature of two leptons plus jets. An upper limit on the sigma(p&pmacr;-->b(')b(');)x[B(b(')-->bZ(0))](2) is established as a function of the b(') mass. We exclude at 95% confidence level a b(') quark with mass between 100 and 199 GeV/c(2) for B(b(')-->bZ(0)) = 100%.


Driving sustainable circular economy in electronics: A comprehensive review on environmental life cycle assessment of e-waste recycling.
E-waste, encompassing discarded materials from outdated electronic equipment, often ends up intermixed with municipal solid waste, leading to improper disposal through burial and incineration. This improper handling releases hazardous substances into water, soil, and air, posing significant risks to ecosystems and human health, ultimately entering the food chain and water supply. Formal e-waste recycling, guided by circular economy models and zero-discharge principles, offers potential solutions to this critical challenge. However, implementing a circular economy for e-waste management due to chemical and energy consumption may cause environmental impacts. Consequently, advanced sustainability assessment tools, such as Life Cycle Assessment (LCA), have been applied to investigate e-waste management strategies. While LCA is a standardized methodology, researchers have employed various routes for environmental assessment of different e-waste management methods. However, to the authors' knowledge, there lacks a comprehensive study focusing on LCA studies to discern the opportunities and limitations of this method in formal e-waste management strategies. Hence, this review aims to survey the existing literature on the LCA of e-waste management under a circular economy, shedding light on the current state of research, identifying research gaps, and proposing future research directions. It first explains various methods of managing e-waste in the circular economy. This review then evaluates and scrutinizes the LCA approach in implementing the circular bioeconomy for e-waste management. Finally, it proposes frameworks and procedures to enhance the applicability of the LCA method to future e-waste management research. The literature on the LCA of e-waste management reveals a wide variation in implementing LCA in formal e-waste management, resulting in diverse results and findings in this field. This paper underscores that LCA can pinpoint the environmental hotspots for various pathways of formal e-waste recycling, particularly focusing on metals. It can help address these concerns and achieve greater sustainability in e-waste recycling, especially in pyrometallurgical and hydrometallurgical pathways. The recovery of high-value metals is more environmentally justified compared to other metals. However, biometallurgical pathways remain limited in terms of environmental studies. Despite the potential for recycling e-waste into plastic or glass, there is a dearth of robust background in LCA studies within this sector. This review concludes that LCA can offer valuable insights for decision-making and policy processes on e-waste management, promoting environmentally sound e-waste recycling practices. However, the accuracy of LCA results in e-waste recycling, owing to data requirements, subjectivity, impact category weighting, and other factors, remains debatable, emphasizing the need for more uncertainty analysis in this field.


Human type 1 diabetes is associated with T cell autoimmunity to zinc transporter 8.
Recently we demonstrated that zinc transporter 8 (ZnT8) is a major target of autoantibodies in human type 1 diabetes (T1D). Because the molecules recognized by T1D autoantibodies are typically also targets of autoreactive T cells, we reasoned that this would likely be the case for ZnT8. To test this hypothesis, IFN-γ-producing T cells specific for ZnT8 in the peripheral blood of 35 patients with T1D (<6 mo after onset at blood draw) and 41 age-matched controls were assayed by ELISPOT using a library of 23 overlapping dipeptide pools covering the entire 369 aa primary sequence. Consistent with our hypothesis, patients showed significantly higher T cell reactivity than the matched controls, manifest in terms of the breadth of the overall response and the magnitude of responses to individual pools. Therefore, the median number of pools giving positive responses (stimulation index ≥ 3) in the control group was 1.0 (range, 0-7) compared with 6.0 (range, 1-20; p < 0.0001) for the patients. Similarly, the median stimulation index of positive responses in controls was 3.1 versus 5.0 in the patients (p < 0.0001). Individually, 7 of 23 pools showed significant disease association (p < 0.001), with several of the component peptides binding the disease associated HLA-DR3 (0301) and -DR4 (0401) molecules in vitro. We conclude that ZnT8 is also a major target of disease-associated autoreactive T cells in human T1D, and we suggest that reagents that target ZnT8-specific T cells could have therapeutic potential in preventing or arresting the progression of this disease.


Recognition of psychogenic non-epileptic seizures: a curable neurophobia?
Diagnosing psychogenic non-epileptic seizures (PNES) remains challenging. The majority of 'PNES status' cases are likely to be seen in the emergency department or similar non-specialised units, where patients are initially assessed and managed by physicians of varying expertise in neurology. 216 participants including medical students and doctors of all grades from a wide range of medical disciplines were shown video recordings of six patients with PNES and six other patients with convulsive epileptic seizures (ES). Participants were asked to choose between PNES and ES as a diagnosis and to rate their confidence in each diagnosis, both before and after a 15-minute teaching presentation on PNES and ES. Pre-teaching sensitivity for diagnosing PNES was 0.77, specificity 0.55. The positive predictive value (PPV) of diagnosing PNES was 0.63, and was 0.7 for ES. Diagnostic accuracy increased with increasing clinical grades (p=0.022), as did clinical confidence (p<0.0005). Clinical accuracy and clinical confidence increased post-teaching (p<0.0005). Sensitivity for diagnosing PNES post-teaching improved to 0.88, specificity to 0.67. The PPV of diagnosing PNES increased to 0.72, and to 0.84 for ES. Diagnosing PNES can be improved by clinical experience in neurology and focussed teaching interventions.


Microblog use and student engagement in the large-classroom setting.
Encouraging student engagement in the large-classroom setting can be difficult. Challenges include the depersonalized nature of the environment and the fact that students frequently find asking questions and participating in class discussion intimidating. Social media has the potential to address these barriers, but this has not yet been formally evaluated. Our study analyzed the impact of microblog use on students' question-asking behaviors (an indicator of student engagement) in a large-classroom setting. Formative evaluation of a large-classroom medical humanities course identified microblog use as a potential tool to facilitate greater student engagement. A microblog was thereafter incorporated into the course. Student engagement was operationalized as question-asking behaviors before and after microblog incorporation. Paired t tests showed that the total number of questions asked was significantly greater in the microblog-available classes, t (2)=12.12. In addition, significantly more individual students asked questions in the microblog-available classes, t (2)=17.39. Our study, demonstrating an increase in question-asking behavior after incorporation of a microblog, has important implications for educators who seek to enhance student engagement and learning in the large-classroom setting. In addition, innovative use of emerging technologies (such as microblogs) as educational tools requires continuous assessment and iterative change to maximize benefit. More research is needed to evaluate what specific barriers to engagement are overcome by microblog use and whether microblog use can similarly benefit other courses.


Targeting Hif1a rescues cone degeneration and prevents subretinal neovascularization in a model of chronic hypoxia.
Degeneration of cone photoreceptors leads to loss of vision in patients suffering from age-related macular degeneration (AMD) and other cone dystrophies. Evidence, such as choroidal ischemia and decreased choroidal blood flow, implicates reduced tissue oxygenation in AMD pathology and suggests a role of the cellular response to hypoxia in disease onset and progression. Such a chronic hypoxic situation may promote several cellular responses including stabilization of hypoxia-inducible factors (HIFs). To investigate the consequence of a chronic activation of the molecular response to hypoxia in cones, von Hippel Lindau protein (VHL) was specifically ablated in cones of the all-cone R91W;Nrl -/- mouse. Retinal function and morphology was evaluated by ERG and light microscopy, while differential gene expression was tested by real-time PCR. Retinal vasculature was analyzed by immunostainings and fluorescein angiography. Two-way ANOVA with Šídák's multiple comparison test was performed for statistical analysis. Cone-specific ablation of Vhl resulted in stabilization and activation of hypoxia-inducible factor 1A (HIF1A) which led to increased expression of genes associated with hypoxia and retinal stress. Our data demonstrate severe cone degeneration and pathologic vessel growth, features that are central to AMD pathology. Subretinal neovascularization was accompanied by vascular leakage and infiltration of microglia cells. Interestingly, we observed increased expression of tissue inhibitor of metalloproteinase 3 (Timp3) during the aging process, a gene associated with AMD and Bruch's membrane integrity. Additional deletion of Hif1a protected cone cells, prevented pathological vessel growth and preserved vision. Our data provide evidence for a HIF1A-mediated mechanism leading to pathological vessel growth and cone degeneration in response to a chronic hypoxia-like situation. Consequently, our results identify HIF1A as a potential therapeutic target to rescue hypoxia-related vision loss in patients.


Imaging Calcium in Drosophila at Egg Activation.
Egg activation is a universal process that includes a series of events to allow the fertilized egg to complete meiosis and initiate embryonic development. One aspect of egg activation, conserved across all organisms examined, is a change in the intracellular concentration of calcium (Ca(2+)) often termed a 'Ca(2+) wave'. While the speed and number of oscillations of the Ca(2+) wave varies between species, the change in intracellular Ca(2+) is key in bringing about essential events for embryonic development. These changes include resumption of the cell cycle, mRNA regulation, cortical granule exocytosis, and rearrangement of the cytoskeleton. In the mature Drosophila egg, activation occurs in the female oviduct prior to fertilization, initiating a series of Ca(2+)-dependent events. Here we present a protocol for imaging the Ca(2+) wave in Drosophila. This approach provides a manipulable model system to interrogate the mechanism of the Ca(2+) wave and the downstream changes associated with it.


VRK3 depletion induces cell cycle arrest and metabolic reprogramming of pontine diffuse midline glioma - H3K27 altered cells.
We previously identified VRK3 as a specific vulnerability in DMG-H3K27M cells in a synthetic lethality screen targeting the whole kinome. The aim of the present study was to elucidate the mechanisms by which VRK3 depletion impact DMG-H3K27M cell fitness. Gene expression studies after VRK3 knockdown emphasized the inhibition of genes involved in G1/S transition of the cell cycle resulting in growth arrest in G1. Additionally, a massive modulation of genes involved in chromosome segregation was observed, concomitantly with a reduction in the level of phosphorylation of serine 10 and serine 28 of histone H3 supporting the regulation of chromatin condensation during cell division. This last effect could be partly due to a concomitant decrease of the chromatin kinase VRK1 in DMG following VRK3 knockdown. Furthermore, a metabolic switch specific to VRK3 function was observed towards increased oxidative phosphorylation without change in mitochondria content, that we hypothesized would represent a cell rescue mechanism. This study further explored the vulnerability of DMG-H3K27M cells to VRK3 depletion suggesting potential therapeutic combinations, e.g. with the mitochondrial ClpP protease activator ONC201.


Mobile phone access and comfort: implications for HIV and tuberculosis care in India and South Africa.
SETTING: India and South Africa shoulder the greatest burden of tuberculosis (TB) and human immunodeficiency virus (HIV) infection respectively, but care retention is suboptimal.OBJECTIVE: We conducted a study in Pune, India, and Matlosana, South Africa, 1) to identify the factors associated with mobile phone access and comfort of use, 2) to assess access patterns.DESIGN: A cross-sectional study assessed mobile phone access, and comfort; a longitudinal study assessed access patterns.RESULTS: We enrolled 261 participants: 136 in India and 125 in South Africa. Between 1 week and 6 months, participant contact decreased from 90% (n = 122) to 57% (n = 75) in India and from 93% (n = 116) to 70% (n = 88) in South Africa. In the latter, a reason for a clinic visit for HIV management was associated with 63% lower odds of contact than other priorities (e.g., diabetes mellitus, maternal health, TB). In India, 57% (n = 78) reported discomfort with texting; discomfort was higher in the unemployed (adjusted OR [aOR] 4.97, 95%CI 1.12-22.09) and those aged ≥35 years (aOR 1.10, 95%CI 1.04-1.16) participants, but lower in those with higher education (aOR 0.04, 95% CI 0.01-1.14). In South Africa, 91% (n = 114) reported comfort with texting.CONCLUSION: Mobile phone contact was poor at 6 months. While mHealth could transform TB-HIV care, alternative approaches may be needed for certain subpopulations.


The Neptune System in Voyager's Afterglow.
Any time the view of a planet leaps from a fuzzy dot accompanied by two pinpoints of light to the riveting details of swirling clouds, rings, cratered moonlets, and even individual dust particles, planetary science is going to be in for some upheaval. Voyager 2's encounter with Neptune was no exception. Something as seemingly innocuous as an hour or two shift in the new length of a Neptunian day is giving meteorologists and physicists fits. And Neptune's canted, complex magnetic field found by Voyager knocks into a cocked hat most ideas about why a similar field at Uranus was unique. But there were more reassuring discoveries as well. Here are samplings of both sorts of findings.


A rehabilitation program for patients with gastroesophageal cancer--a pilot study.
Gastroesophageal carcinoma has a 5-year survival rate of 20%. Esophagogastrectomy is a significant life-altering operation which interferes with a patient's ability to eat food as a normal social interaction. Dumping syndrome, delayed gastric emptying, and reflux are encountered after surgery. In addition, loss of appetite and body weight occurs. Fatigue is universally encountered. We conducted this study to evaluate whether a structured cancer nutrition and rehabilitation program has an effect on the symptoms and quality of life of patients with gastroesophageal cancer. Fifty-three patients with histologically documented gastroesophageal carcinoma were evaluated before and after an 8-week multidisciplinary program consisting of physicians, oncology nurse, dietitian, physical and occupational therapists, social worker, and psychologist. Twenty-two patients completed all the following questionnaires pre- and post-program: The Edmonton Symptom Assessment Scale (ESAS), Patient-Generated Subjective Global Assessment (PG-SGA), Brief Fatigue Inventory (BFI), and the Distress Thermometer. There were 42 male and 11 female patients. The median age was 63 years (22-80 years). Thirty patients had gastric cancer and 23 had esophageal cancer. On the ESAS, appetite, strength, shortness of breath, and constipation all improved (p = 0.01). The PG-SGA score decreased significantly (p = 0.05). Fatigue and general activity as measured on the BFI improved significantly. The 6-min walk increased from 384 to 435 m (p = 0.01). The Cancer Nutrition and Rehabilitation program offers a multidimensional, holistic treatment approach emphasizing the patient as an individual. Participation in a cancer rehabilitation program ameliorates symptoms, improves nutrition, decreases global distress, and increases physical activities.


The effect of medial longitudinal arch height and medial longitudinal arch support insoles on postural balance in perimenopausal women
Changes in balance and postural control have been reported during the perimenopausal period. We investigated the effect of medial longitudinal arch height and medial arch support insoles on postural sway and balance in middle-aged perimenopausal women. 29 women with normal arches and 29 women with low arches were included in the study. The foot arches of the participants were determined using the arch height index. The static balance index (SBI) measured by Kinesthetic Ability Trainer 3000 and functional reach test were used to evaluate postural balance. Measurements were obtained from all participants with and without medial arch support insoles. The SBI-total scores without the insoles were found to be significantly higher in the lower arch group than in the normal arch group. SBI-total, SBI-anteroposterior, and SBI-mediolateral scores significantly improved in the low arch group in the presence of insoles, whereas the usage of insoles resulted in no difference in the normal arch group. In the presence of insoles, the reach distances to left and right sides increased in both groups, while the forward functional reach distances decreased. Medial longitudinal arch height and medial arch support insoles affect the balance parameters in perimenopausal women.


Fifth-order field aberration coefficients for an optical surface of rotational symmetry.
The approximate formulas for the principal ray parameters, such as directional cosines and heights of incidence, as well as for the paraxial sagittal quantities h(s) and H (s) have been expressed by paraxial quantities and Seidel aberrations to fifth-order accuracy. On the basis of these relations an expression for the sagittal radius of curvature r(s), (for a given y ) has been obtained. These quantities are used to derive fifth-order field aberration coefficients for arbitrary surfaces of rotational symmetry by using the wave aberration formula for sagittal focus {M. Gaj, Opt. Spectrosk. 21, 373 (1966) [Opt. Spectrosc. 21, 209 (1966)]}. The resulting expression has four terms. The first one depends only on asphericity and tends to equal zero when the surface becomes spherical. The second is a disturbance term and disappears in the Seidel region. The third and fourth terms may be treated as a generalization of the Petzval curvature and of the Seidel astigmatism, respectively. The limits of the terms, when h tends to zero, has been examined.


The 100 most influential manuscripts in andrology: a bibliometric analysis.
As the specialty of Andrology expands it is important to establish the most important studies that have shaped, and continue to shape, current research and clinical practice. Bibliometric analysis involving a citation rank list is an established means by which to identify the published material within a given field that has greatest intellectual influence. This bibliometric analysis sought to identify the 100 most influential manuscripts in Andrology, as well as the key research themes that have shaped contemporary understanding and management of andrological conditions. The Thompson Reuters Web of Science citation indexing database was interrogated using a number of search terms chosen to reflect the full spectrum of andrological practice. Results were ranked according to citation number and further analysed according to subject, first and senior author, journal, year of publication, institution and country of origin. The Web of Science search returned a total of 24,128 manuscripts. Citation number of the top 100 articles ranged from 2819 to 218 (median 320). The most cited manuscript (by Feldman et al., The Journal of Urology 1994; 2819 citations) reported the prevalence and risk factors for erectile dysfunction (ED) in the Massachusetts Male Ageing Study. The Journal of Urology published the highest number of manuscripts (n = 11), followed by the New England Journal of Medicine (n = 10). The most common theme represented within the top 100 manuscripts was erectile dysfunction (n = 46), followed jointly by hypogonadism and male factor infertility (n = 24 respectively). Erectile dysfunction should be considered the most widely researched, published and cited field within andrological practice. This study provides a list of the most influential manuscripts in andrology and serves as a reference of what comprises a 'highly citable' paper for both researchers and clinicians.


Acute renal failure of obstetrical origin during 1994 at one center.
Although preventable, acute renal failure (ARF) of obstetrical origin continues to be common in developing countries. During the year 1994, we treated a total of 238 cases of ARE. Of these cases, 43 (18%) were of obstetrical origin. All of the patients were known to be previously healthy. Acute renal failure occurred in association with antepartum hemorrhage in 15, postpartum hemorrhage in 10, intrauterine death of fetus in 11, preeclampsia or eclampsia in 9, and septic abortions or puerperal sepsis in 7. Thirty-six patients required dialysis therapy because of moderate to severe azotemia. Renal histology was studied in 12 cases. Acute cortical necrosis was present in 9, extensive tubular necrosis in 2, and 1 patient had membranoproliferative glomerulonephritis. Twenty-two (51%) patients recovered normal renal function, while 11 (26%) developed irreversible renal dysfunction and 10 (23%) expired. Mortality and morbidity in this region is still quite high in obstetrical situations. Poor health infrastructure and lack of antenatal health clinics leads to development of major complications at the time of childbirth, which is mostly conducted at home by untrained personnel in quite a few cities of the country.


Residual Inflammation Indicated by High-Sensitivity C-Reactive Protein Predicts Worse Long-Term Clinical Outcomes in Japanese Patients after Percutaneous Coronary Intervention.
The aim of this study was to investigate the long-term clinical impact of residual inflammatory risk (RIR) by evaluating serial high-sensitivity C-reactive protein (hs-CRP) in Asian patients with coronary artery disease (CAD). We evaluated 2032 patients with stable CAD undergoing percutaneous coronary intervention (PCI) with serial hs-CRP measurements (2 measurements, 6-9 months apart) from the period 2000 to 2016. A high-RIR was defined as hs-CRP > 0.9 mg/L according to the median value. Patients were assigned to four groups: persistent-high-RIR, increased-RIR, attenuated-RIR, or persistent-low-RIR. Major adverse cardiac events (MACE) and all-cause death were evaluated. MACE rates in patients with persistent high, increased and attenuated RIR were significantly higher than in patients with persistent low RIR (p < 0.001). Moreover, the rate of all-cause death was significantly higher among patients with persistent high and increased RIR than among patients with attenuated and persistent low RIR (p < 0.001). After adjustment, the presence of persistent high RIR (hazard ratio (HR) 2.22; 95% confidence interval (CI) 1.37-3.67, p = 0.001), increased RIR (HR 2.25, 95%CI 1.09-4.37, p = 0.029), and attenuated RIR (HR 1.94, 95%CI 1.14-3.32, p = 0.015) were predictive for MACE. In addition, presence of persistent high RIR (HR 2.07, 95%CI 1.41-3.08, p < 0.001) and increased RIR (HR 1.94, 95%CI 1.07-3.36, p = 0.029) were predictive for all-cause death. A high RIR was significantly associated with MACE and all-cause death among Japanese CAD patients. An evaluation of changes in inflammation may carry important prognostic information and may guide the therapeutic approach.


Multilevel rhythms in multimodal communication.
It is now widely accepted that the brunt of animal communication is conducted via several modalities, e.g. acoustic and visual, either simultaneously or sequentially. This is a laudable multimodal turn relative to traditional accounts of temporal aspects of animal communication which have focused on a single modality at a time. However, the fields that are currently contributing to the study of multimodal communication are highly varied, and still largely disconnected given their sole focus on a particular level of description or their particular concern with human or non-human animals. Here, we provide an integrative overview of converging findings that show how multimodal processes occurring at neural, bodily, as well as social interactional levels each contribute uniquely to the complex rhythms that characterize communication in human and non-human animals. Though we address findings for each of these levels independently, we conclude that the most important challenge in this field is to identify how processes at these different levels connect. This article is part of the theme issue 'Synchrony and rhythm interaction: from the brain to behavioural ecology'.


Rhizobium meliloti insertion element ISRm2 and its use for identification of the fixX gene.
Two of the three plasmids of the wild-type Rhizobium meliloti 41 (pRme41a and pRme41c) carry a copy of ISRm2, a 2.7-kilobase-long transposable element. ISRm2 is terminated by 22-base-pair (bp) inverted repeat sequences, exhibiting some homology to the inverted repeats of elements generating 9-bp target sequence duplication. Transposition of ISRm2 results in a duplication of 8 bp in length, rather rare among transposable elements. DNA sequences homologous to an internal fragment of ISRm2 were found in several Rhizobium species. Transposition of ISRm2 into fixation and nodulation genes located on the symbiotic plasmid pRme41b was detected at a high frequency. Exact locations of two copies of ISRm2 which transposed into the nod-nif region on the megaplasmid were determined. In one case, integration into the protein-coding region of the hsnD gene that determines a host specificity function of nodulation occurred. In the other mutant, ISRm2 was localized upstream of nifA, where a short open reading frame coding for a new fix gene (fixX) was identified. The product of fixX is a ferredoxin carrying a characteristic cluster of cysteine residues. On the basis of the observation that the arrangement of the ISRm2 copies is identical in the free-living wild-type cells and in nitrogen-fixing nodules, we concluded that the involvement of ISRm2 transposition in the development of nitrogen-fixing symbiosis is unlikely.