A method for intracochlear drug delivery in the mouse.
The confluence of two rapidly emerging research arenas - development of mouse models of human deafness and inner ear drug therapy for treatment and prevention of hearing loss - provides an opportunity for unprecedented approaches to study and treat deafness. Toward such goals, we have developed a method for intracochlear drug delivery in the mouse. The bulla was exposed using a ventral approach and the stapedial artery cauterized. An opening made into the inferior-medial aspect of the bulla, where the basal cochlear wall fuses with tympanic bulla, provided direct access to the scala tympani without separately opening the bulla or elevating auditory response thresholds. Cochlear responses, assayed by frequency-specific effects on ABRs and DPOAEs, were stable with infusion (1 microl/h) of an artificial perilymph solution (80 min). The glutamate receptor antagonist, CNQX (100 microM; 175 min), reduced ABR responses without affecting DPOAEs. Salicylate (5mM; 165 min) altered both. Both drugs had greatest effects at high frequencies, but distributed throughout the cochlea and were reversible. The safe delivery of drugs into the cochlea by this approach has immediate application in the study and treatment of various forms of human hearing loss that can be modeled in the mouse.


Dental erosion and soft drinks: a qualitative assessment of knowledge, attitude and behaviour using focus groups of schoolchildren. A preliminary study.
This qualitative study was designed to record the perception by Newcastle children of the influences on their choice of drinks and their knowledge of the dental health problems caused by acidic drinks. Four focus groups, each involving 8 Newcastle schoolchildren (4 boys and 4 girls) formed the basis of the study. Two age groups, 13-14-year-olds and 8-9-year-olds, and two socio-economic groups were investigated, using state schools in Newcastle upon Tyne. A moderator guided the children to discuss their choice of drink and its dental effects amongst themselves. In total, 32 children participated in the focus groups and the results suggested that 8-9-year-olds preferred still, fruit-flavoured drinks whilst 13-14-year-olds preferred carbonated drinks. Taste was the most important influence on drink choice in all age groups. Parents and friends were more influential in younger children, whilst cost, availability and thirst were more important to older children. Younger children did not believe advertisements whilst older children thought they might work if seen enough times. Dental knowledge was confused in all age groups and only the 13-14-year-old-high socio-economic groups knew that acidic drinks were bad for the teeth. Different methods for addressing the problem of erosion were suggested by different age groups. There was very little difference between the socio-economic groups in the areas discussed. The children's knowledge of dental diseases and the effect of drinks on the teeth were confused. The factors that influence drink choice appear to change with age, rather than socio-economic status.


Endogenous progesterone and its cellular binding sites in wheat exposed to drought stress.
Progesterone is a basic hormone that regulates the metabolism in mammals. The presence of this compound has also been found in certain plants. It is believed that progesterone can regulate growth processes and resistance to stress, however, its precise role in plants remains unknown. The research conducted in this study was aimed at analyzing the content of endogenous progesterone and its cellular binding sites in the leaves of spring wheat exposed to drought. Changes were studied in two cultivars of wheat - a cultivar sensitive to drought (Katoda) and tolerant cultivar (Monsun). Plants had undergone periodic droughts during the seedling stage or in the phase of heading. The occurrence of free progesterone as well as its conjugated forms was observed in wheat studied. The amount of progesterone ranged from 0.2 to 5.8pmolgFW(-1) and was dependent on the cultivar, age of the plants, stage of development and fluctuated as a result of the exposure to drought. Cv. Katoda responded to a water deficit by lowering the amount of progesterone and cv. Monsun by increasing its level. Progesterone in plants grown in limited water conditions occurred primarily in a free form. While in the optimal watering conditions, some of its pool was found in the form of conjugates. In the spring wheat the occurrence of binding sites for progesterone was detected in cell membranes, cytoplasm and nuclei in the range of 10-36fmol/mg of protein. The wheat cultivars tested, Monsun and Katoda, differ in their concentration of cellular binding sites for progesterone. This number varied in the individual fractions during different stages of plant development and due to the effect of drought stress. The number of binding sites for progesterone located in the membrane fraction of seedlings and flag leaves increased significantly under drought in the cv. Katoda (35-46%), but did not change in the cv. Monsun. Whereas the number of cytoplasmic progesterone binding sites increased during the drought in the cv. Monsun (about 50%), they did not change in the cv. Katoda. Changes in the amount of progesterone and its binding sites in the cell under the influence of drought were then different depending on whether the cultivar was tolerant or sensitive to drought. The possibility of utilizing these changes as markers of drought resistance is discussed. The results obtained suggest that progesterone is a part of wheat response to stress factors (drought).


Elastic interaction between Mauna Loa and Kīlauea evidenced by independent component analysis.
The contrasting dynamics between Mauna Loa and Kīlauea have been studied over the last 100 years from multiple viewpoints. The fact that dynamic changes of one volcano trigger a dynamic response of the other volcano indicates a connection may exist. Petrological works show a direct relationship between the magmatic systems of these two volcanoes is not possible. We analysed DInSAR data and GPS measurements of ground deformation patterns associated with the activity of Mauna Loa and Kīlauea volcanoes. The DInSAR SBAS dataset spans the interval between 2003 and 2010, and was acquired along ascending and descending orbits of the ENVISAT (ESA) satellite under different look angles. Of the 10 tracks that cover the Big Island (Hawai'i), 4 cover both volcanic edifices. Using GPS measurements, we computed the areal strain on 15 triplets of stations for Kīlauea volcano and 11 for Mauna Loa volcano. DInSAR data was analysed by applying Independent Component Analysis (ICA) to decompose the time-varying ground deformation pattern of both volcanoes. The results revealed anticorrelated ground deformation behaviour of the main calderas of Mauna Loa and Kīlauea, meaning that the opposite response is seen in the ground deformation of one volcano with respect to the other. At the same time, Kīlauea exhibits a more complex pattern, with an additional component, which appears not to be correlated with the dynamics of Mauna Loa. The GPS areal strain time series support these findings. To corroborate and help interpret the results, we performed inverse modelling of the observed ground deformation pattern using analytical source models. The results indicate that the ground deformation of Mauna Loa is associated with a dike-shaped source located at 6.2 km depth. In comparison, the anticorrelated ground deformation of Kīlauea is associated with a volumetric source at 1.2 km depth. This excludes a hydraulic connection as a possible mechanism to explain the anticorrelated behaviour; instead, we postulate a stress-transfer mechanism. To support this hypothesis, we performed a 3D numerical modelling of stress and strain fields in the study area, determining the elastic interaction of each source over the others. The most relevant finding is that the Mauna Loa shallow plumbing system can affect the shallowest magmatic reservoir of Kīlauea, while the opposite scenario is unlikely. Conversely, the second independent component observed at Kīlauea is associated to a sill-shaped source located at a depth of 3.5 km, which is less affected by this interaction process.


Copper-Catalyzed Enantioselective Allylic Alkylation with a γ-Butyrolactone-Derived Silyl Ketene Acetal.
Herein, we report a Cu-catalyzed enantioselective allylic alkylation using a γ-butyrolactone-derived silyl ketene acetal. Critical to the development of this work was the identification of a novel mono-picolinamide ligand with the appropriate steric and electronic properties to afford the desired products in high yield (up to 96 %) and high ee (up to 95 %). Aryl, aliphatic, and unsubstituted allylic chlorides bearing a broad range of functionality are well-tolerated. Spectroscopic studies reveal that a CuI species is likely the active catalyst, and DFT calculations suggest ligand sterics play an important role in determining Cu coordination and thus catalyst geometry.


Effect of cresol isomers on reproduction and gene expression in Daphnia magna.
Cresols are frequently detected in freshwater systems due to their wide use as disinfectants. However, there is limited knowledge regarding their adverse long-term toxicity effects on reproduction and gene expression patterns of aquatic species. Therefore, this study aimed to investigate the chronic toxic effects on reproduction and gene expression using D. magna. In addition, the bioconcentration behaviour of cresol isomers was also investigated. Based on the 48 h EC50 value, p-cresol's toxicity unit (TU) (13.77 TU, very toxic) was higher than o-cresol (8.05 TU, toxic) and m-cresol (5.52 TU, toxic). Regarding population-level effects, cresols resulted in a decrease in offspring and a delay in reproduction. However, cresols did not significantly affect daphnia's body weight throughout the course of the exposure period of 21 day, while third brood neonates' average body length (m-cresol and p-cresol) was significantly affected in sub-lethal concentrations. In addition, the gene transcription did not vary significantly across treatments. For bioconcentration exposure experiments, D. magna quickly eliminated all cresols from their body, suggesting that cresol isomers are unlikely to bioaccumulate in aquatic species.


An efficacy trial of 'Steps to Your Health', a health promotion programme for adults with intellectual disability.
Although there are evaluation and effectiveness studies of health promotion interventions for adults with intellectual disabilities (ID), randomized efficacy trials of such interventions are lacking. A randomized active control intervention trial. The participants attended the health promotion classes in local disability agency service facilities. Method: We enrolled 443 individuals and randomly assigned them to one of two eight-week participatory classes. The 'Steps to Your Health' (STYH) classes emphasized moderate to vigorous physical activity (MVPA), healthy eating and body mass index (BMI) reduction. The control intervention focused on hygiene and safety. We did not find a statistically significant difference in mean MVPA or BMI change between completers of the STYH group compared to the control group one year after the intervention was completed. We did find that participation in STYH classes had a non-significant association with odds of reduction in BMI (odds ratio [OR] 2.87, 95% confidence interval [CI] 0.91-9.11) and completers who lived in group homes were more likely than their counterparts who lived with families or in apartments to decrease their BMI (OR 4.61; 95% CI 1.14-18.64). This trial did not demonstrate a significant effect of STYH participation on change in mean minutes of MVPA or mean BMI 12 months after classes ended, although there was a non-significant association with odds of reduction of BMI (p = 0.07). This study has implications for design of intervention studies in people with intellectual disability (ID).


The presubicular region in Alzheimer's disease: topography of amyloid deposits and neurofibrillary changes.
Specific silver impregnation techniques for extracellular amyloid and intraneuronal neurofibrillary changes were used to examine the presubiculum in Alzheimer victims. Extended amyloid clouds in the absence of neurofibrillary changes were noted in the parvopyramidal layer of the presubiculum proper. The corresponding layer in the parasubiculum, in contrast, showed many neurofibrillary tangles and neuropil threads in the absence of amyloid. The transsubicular parvopyramidal layer contained both amyloid deposits and neurofibrillary changes. This severe involvement of all subdivisions of the presubicular region in Alzheimer's disease is considered to impair functions of the Papez circuit.


Nitric oxide regulation of plant metabolism.
Nitric oxide (NO) has emerged as an important signal molecule in plants, having myriad roles in plant development. In addition, NO also orchestrates both biotic and abiotic stress responses, during which intensive cellular metabolic reprogramming occurs. Integral to these responses is the location of NO biosynthetic and scavenging pathways in diverse cellular compartments, enabling plants to effectively organize signal transduction pathways. NO regulates plant metabolism and, in turn, metabolic pathways reciprocally regulate NO accumulation and function. Thus, these diverse cellular processes are inextricably linked. This review addresses the numerous redox pathways, located in the various subcellular compartments that produce NO, in addition to the mechanisms underpinning NO scavenging. We focus on how this molecular dance is integrated into the metabolic state of the cell. Within this context, a reciprocal relationship between NO accumulation and metabolite production is often apparent. We also showcase cellular pathways, including those associated with nitrate reduction, that provide evidence for this integration of NO function and metabolism. Finally, we discuss the potential importance of the biochemical reactions governing NO levels in determining plant responses to a changing environment.


Intraperitoneal deferoxamine therapy for iron overload in children undergoing CAPD.
We treated three children with renal failure and chronic iron overload with intraperitoneal deferoxamine therapy. Each child had an elevated serum ferritin level, a dense liver as measured by computerized tomography (Hounsfield Units) and one had dialysis related porphyria cutanea tarda. Deferoxamine therapy (10 to 17.5 mg/kg) was given in the overnight exchange for three to six months. Prior to therapy, iron was not detected in the dialysate; during the course of therapy, daily dialysate iron removal averaged 5652 micrograms, 2241 micrograms and 4028 micrograms in the three children. The serum ferritin level fell during the course of therapy in two children who were estimated to be in negative iron balance, and was unchanged in the third who was estimated to be in positive iron balance due to frequent transfusions. In 10 children with chronic renal failure, there was a linear correlation (r = 0.855; P less than 0.01) between the serum ferritin and the liver density, suggesting that an increased serum ferritin correlates with hepatic iron content. Interestingly, in each of the three children who received deferoxamine therapy, the liver density increased during therapy regardless of the estimated iron balance and the change in the serum ferritin level. We conclude that intraperitoneal deferoxamine therapy results in substantial iron losses in peritoneal dialysate, can result in negative iron balance but, in this study, did not result in lower liver iron content as measured by density on computerized tomography scan.


Successful transfemoral aortic valve implantation through aortic stent graft after endovascular repair of abdominal aortic aneurysm.
The patient was a 91-year-old woman presenting with severe aortic valve stenosis. Pre-procedural computed tomography scan revealed a 45-mm abdominal aortic aneurysm (AAA). Transfemoral transcatheter aortic valve implantation (TF-TAVI) was performed after endovascular aortic repair (EVAR) of the AAA. The 23-mm Edwards Sapien XT system passed through the aortic stent graft smoothly. This is the first case report showing that successful TF-TAVI can be performed through a prior abdominal aortic stent graft. TF-TAVI after EVAR of AAA is a feasible option for patients with extremely poor access.


Sex-Associated SNP Confirmation of Sex-Reversed Male Farmed Japanese Flounder Paralichthys olivaceus.
Female Japanese flounder Paralichthys olivaceus grow more rapidly than the male. The goal of all-female commercial production requires an efficient method of genetic sex identification. We conducted genome-wide association analysis of female and male farmed Japanese flounder (n = 24 per phenotypic sex) and found all regions of chromosome 24 to be significantly associated with phenotypic sex, suggesting it as the sex chromosome. Genetic sex was identified based on single nucleotide polymorphisms (SNP) on chromosome 24 (n = 3568) using multidimensional scaling analysis, and individuals were clearly separated according to sex by the first dimension. The 61 SNPs most highly associated with sex were selected, and an amplicon-based SNP panel was developed. This was used to determine genetic sex of 39 females and 40 males. Eleven phenotypic males were assigned as female with XX genotype, suggesting sex reversal. Genetic sex was also assessed based on the indel of the amh gene promoter, which is the major candidate sex gene of Japanese flounder. We found four SNPs perfectly associated with genotypic sex in the sex-associated SNP panel, one of which was located in exon 2 of the amh gene. Along with the indel of the amh gene promoter, the sex-associated SNP panel will be of value in identifying genetic sex of farmed Japanese flounder. Molecular sexing will facilitate all-female production by breeding sex-reversed males.


Gun carrying among US adolescents: the mutual impact of violence experiences, safety concerns, and substance use behaviors.
Youth firearm carriage significantly contributes to firearm-related injuries and deaths in the United States (US). This study examined the sex-specific patterns and cumulative effects of violence experiences, safety concerns, and substance use behaviors on youth firearm carriage. Cross-sectional study. Based on a nationally representative sample (N = 13,526), the multigroup structural equation modeling (SEM) was used to examine the interplay of violence experiences (weapon threats, physical fights, and sexual violence), safety concerns, and substance use behaviors (cigarette, electronic vapor, alcohol, marijuana, and prescription opioid), and their direct, indirect, and total effects on youth gun carrying behavior. About one in 50 females and one in 15 males reported firearm carriage in the past year. Sex-specific patterns existed. Among female adolescents, gun carrying was strongly correlated with violence experiences (standardized coefficient (β) = 0.77, P < 0.001), but no direct connection was observed with substance use behaviors. Among males, both violence experiences (β = 0.56, P < 0.001) and substance use behaviors (β = 0.26, P < 0.001) were significantly correlated with gun carrying. Although safety concerns did not show a direct effect on gun carrying, a significant indirect effect was observed via the pathway of violence experiences. Collectively, the three clusters of predictors explained about 59.9% of variance in gun carrying among females and 54.6% of variance among males. Violence experiences have a robust impact on gun carrying behavior in both female and male adolescents. Effective violence prevention programs and sex-specific strategies (e.g., substance use intervention for males) are needed to reduce youth firearm carriage.


Histopathological perspective on bone marrow oedema, reactive bone change and haemorrhage.
This article presents a systematic review of the current biomedical literature surrounding the aetiopathogenesis and histopathological features of bone marrow oedema, reactive bone change and haemorrhage. Bone marrow oedema is generally demonstrated as a non-specific finding on magnetic resonance imaging in association with infections, tumours and avascular necrosis. When it occurs in isolation as a primary event not triggered by any obvious bony pathology in the clinical setting of debilitating joint pain, it constitutes the "bone marrow oedema syndrome". Although the latter diagnosis is based on magnetic resonance (MR) imaging, showing the lesion as areas of signal hyperintensity within the marrow, recent radiology-histology correlational studies have shown variably interstitial marrow oedema, necrosis, fibrosis and trabecular bone abnormalities. In light of these facts, the use of the term bone marrow oedema syndrome in a radiological context might be considered questionable, but histopathological techniques are not sensitive in detecting increased extracellular fluid. Reactive bone changes may be focal or diffuse and usually amount to increased bone formation. Bone marrow haemorrhage, due to trauma, results in bone bruising, a condition in which the size of the bruise and associated osteochondral injury determines the outcome, although the natural history of these lesions is still being researched.


Crystal structure of Prp16 in complex with ADP.
DEAH-box helicases play a crucial role in pre-mRNA splicing as they are responsible for major rearrangements of the spliceosome and are involved in various quality-ensuring steps. Prp16 is the driving force during spliceosomal catalysis, remodeling the C state into the C* state. Here, the first crystal structure of Prp16 from Chaetomium thermophilum in complex with ADP is reported at 1.9 Å resolution. Comparison with the other spliceosomal DEAH-box helicases Prp2, Prp22 and Prp43 reveals an overall identical domain architecture. The β-hairpin, which is a structural element of the RecA2 domain, exhibits a unique position, punctuating its flexibility. Analysis of cryo-EM models of spliceosomal complexes containing Prp16 reveals that these models show Prp16 in its nucleotide-free state, rendering the model presented here the first structure of Prp16 in complex with a nucleotide.


Placebo effects in children: a review.
Of more than 155,000 PubMed citations found with the search term "placebo," only ~9,000 (5.8%) included the terms "children" or "adolescents." When all these papers were screened, only ~2,000 of them investigated the placebo effect per se, and of those, only ~50 (2.5%) discussed the placebo effect in children and adolescents. In this narrative review, we explore four aspects of the placebo response in children and adolescents: (i) the legal and ethical limitations and restrictions for the inclusion of children in clinical trials as well as in experimental (placebo) research that may explain the poor knowledge base; (ii) the question of whether or not the placebo effect is larger in children and adolescents as compared with adults; (iii) whether the mechanisms underlying the placebo effect are similar between children and adults; and (iv) whether mediators and moderators of the placebo effect are comparable between children and adults. We finally discuss some of the consequences from the current placebo research in adults that may affect both experimental and clinical research in children and adolescents.


Somatosensory Response to Trigeminal Stimulation: A Functional Near-Infrared Spectroscopy (fNIRS) Study.
Functional near-infrared spectroscopy (fNIRS) is an optical imaging technique measuring relative hemodynamic changes in superficial cortical structures. It has successfully been applied to detect a hemodynamic response in the somatosensory cortex evoked by irritating mechanical, electrical, and heat stimulations of limbs or the face. The aim of the current study was to explore the feasibility of fNIRS to detect respective responses evoked by irritating chemical stimulations of the nasal divisions of the trigeminal nerve. In two experiments, healthy subjects were exposed to acetic acid and ethyl acetate presented using a respiration-synchronized olfactometer. Results demonstrated that fNIRS can detect a signal in both hemispheres after birhinal (experiment 1: n = 14) and monorhinal (experiment 2: n = 12) stimulations using acetic acid but not ethyl acetate. This is a first evidence that fNIRS might be a suitable imaging technique to assess chemosensory neuronal correlates in the somatosensory cortex thereby offering a new, portable method to evaluate the irritating properties of certain volatiles in an objective, nonverbal, easy, and comparably inexpensive manner.


Solid-phase radioimmunoassay for substance P.
The solid-phase immunoassay for quantification of substance P has been developed. The assay is based on the repartition of anti-substance P antibodies between the insoluble phase-immobilized substance P and the free peptide. The immobilized substance P-antibody complex is then quantified with 125I-protein A. The method allowed detection of 10 pg of substance P. The values of substance P concentration obtained by the present method in different regions of the rat brain were comparable to those obtained by standard radioimmunoassay with 125I-tyr-8-substance P as tracer. The described solid-phase radioimmunoassay is a simple, sensitive, and reliable technique for quantification of substance P-like immunoreactivity in biological samples.


Nanoparticle platform comprising lipid-tailed pH-sensitive carbon dots with minimal drug loss.
Herein, we synthesized a lipid-mimicking organic material (PCD_FA) that can surpass the efficacy of lipid-based nanoparticles and demonstrated its potential as a delivery vehicle for various hydrophilic drugs. PCD_FA is a conjugate of pH-sensitive carbon dots (PCDs) and fatty acids (FAs) and has potential applications in several fields owing to various combinations of carbon dots (CDs) and FAs. Similar to phospholipids, PCD-FAs have hydrophilic heads and hydrophobic tails that allow them to self-form nanoparticles (Coposomes) in the aqueous phase. Coposomes can easily combine various hydrophilic head and hydrophobic tail combinations, and several drugs can be encapsulated, or drug release patterns can be controlled according to each property. We analyzed the differences in size, drug loading efficiency, and drug release patterns of Coposomes depending on the type of FAs and characteristics of the encapsulated drugs. Additionally, cell entry and intracellular drug release mechanisms of the Coposomes were identified. The applicability of Coposomes as drug delivery carriers for tumor treatment has been demonstrated in comparison with that of liposomes formulation in tumor-bearing mouse models. Consequently, this study presents possibilities for the synthesis and application of various amphiphilic lipid-mimicking organic materials via the combination of CDs and FAs with various functions.


Identification and characterization of key genes in insulin signaling pathway as molecular targets for controlling the fall webworm, Hyphantria cunea.
The insulin signaling pathway is closely related to metabolism, growth, reproductive capacity and lifespan of insects. However, the physiological function of the insulin signaling pathway is little known in Hyphantria cunea. Five insulin signaling pathway genes (HcInR, HcPI3K, HcAKT, HcFOXO and HcTOR) in H. cunea were identified and characterized in this study. The spatiotemporal expression profiles of the genes showed that HcInR, HcAKT, HcPI3K and HcTOR expressions were higher at the egg stage than those in other development stages, whereas HcFOXO was highly expressed in the adult stage; all of these genes were highly expressed in the larval digestive system, especially in the midgut and hindgut. After RNA interference (RNAi) of the five genes in 5th instar H. cunea larvae, weight gain and survival rate (except in the siHcAKT-injected group) were significantly decreased, and the developmental duration of larval and pupal stages were prolonged. In addition, knockdown of five genes in 7th instar larvae decreased the pupation rate, survival rate and oviposition capacity, and resulted in abnormal development during larval-pupal transition. Our findings indicate that the insulin signaling pathway plays essential roles in growth and development and the molting process in H. cunea, providing an important basis for developing new potentially molecular targets for RNAi-based pest control and understanding the mechanism of H. cunea outbreak. © 2022 Society of Chemical Industry.


[Sonographic determination of thyroid volume in subjects with healthy thyroids].
Echography of the thyroid was performed on 542 persons with thyroid glands normal to palpation. Thyroid volume in men ranged between 9 and 38 ml, in females between 6 and 25 ml; median 16.7 ml and 13.5 ml, respectively. This sex difference is significant. There was only a weakly positive correlation between thyroid size, on one hand, and age or surface area, on the other. In future, thyroid echography should be used as reliable and yet simple method in any epidemiological study of the incidence of goitre.


EMG activities of neck muscles underlying lateral flexion of the neck during head-turning induced by electrical stimulation of the caudate nucleus in cats.
Patterns of EMG activities of neck muscles underlying the initiation of head-turning, induced by stimulation of the caudate nucleus, were analyzed with special reference to temporal relations between the onset of head-turning and that of changes in EMG activities. These patterns were compared with those associated with the initiation of lateral flexion of the neck which occurred without electrical stimulation of the caudate nucleus in order to examine whether the caudate-induced head-turning was initiated via the same muscular system as that used in non-caudate-induced head movements. Experiments were carried out using 5 awake, unrestrained cats which were trained to stand still with one limb on each of 4 footplates. Trains of stimulating current pulses were applied to several stimulation points in the caudate nucleus while the animal maintained a stable standing posture with its neck extended. Head movements in the horizontal plane and EMGs of 6 neck muscles (splenius, longissimus cervicis, obliquus capitis caudalis, biventer cervicis, complexus and cervical multifidus) were recorded. Patterns of EMG activities of neck muscles around the onset of the caudate-induced head-turning were characterized by an increase in activity of the splenius, the longissimus cervicis and the obliquus capitis caudalis muscles, and by a decrease in activity of the complexus, the biventer cervicis and the cervical multifidus on the side of flexion. It is suggested that an increase in activity of the splenius, the longissimus cervicis and the obliques capitis caudalis muscles was responsible for the initiation of this evoked response. In non-caudate-induced lateral flexion of the neck, patterns of activities of neck muscles were similar to those in caudate-induced head-turning. It is therefore concluded that the caudate-induced head-turning as an evoked behavioral response was initiated through a muscular system similar to that utilized for similar head movements occurring without electrical stimulation of the caudate nucleus, although the pathways involved are thought to be different.


Assessment of adherence to asthma controllers in children and adolescents.
Low adherence to asthma controllers is known to increase the risk of uncontrolled disease and poor health outcomes. We aimed to study risk factors of long-term adherence to preventive medications in children and adolescents with asthma. Adherence was assessed during a two-year period in 155 children with asthma followed in a tertiary pediatric asthma outpatient clinic using percentage of days covered (PDC) based on physician prescriptions and pharmacy claims data. The risk factor analysis included age, sex, ethnicity, BMI, atopic comorbidity, spirometry incentives, and fractional exhaled nitric oxide (FeNO). Ninety-five children, 50 (53%) males, mean age of 16.3 years (SD, 2.36), received at least one prescription for asthma controllers in the study period. Fifty-two (54%) children were classified as non-adherent with a PDC cutoff at 80%. Adherence was negatively associated with age: adherence ratio (AR) 0.84 (95% CI, 0.73-0.95), P = .008; forced expiratory volume in 1 second (FEV1): AR per L 0.6 (0.91-1.0), P = .03; unfilled inhaled beta-2-agonist prescription: AR 0.45 (0.23-0.89), P = .02; and FeNO level: AR per ppb 0.98 (0.97-0.99), P = .03, where age and FeNO retained significance in multivariate analysis. Type and number of asthma controllers were not associated with adherence. This study shows low adherence to preventive medication among half of the children with asthma, which is associated with increasing age and FeNO level. Therefore, an extra effort should be directed toward teenagers transitioning from pediatric to adult medicine and toward inhaled corticosteroid-treated patients with elevated FeNO to increase their adherence to asthma controllers.


Role of selected amino acids on plasma IGF-I concentration in infants.
Insulin-like growth factor-I (IGF-I) is related to growth and its secretion is modified by protein intake in early infancy. We examined the relationship of dietary protein and circulating amino acids on plasma IGF-I levels and early growth. Healthy formula-fed infants (n = 213) were randomly assigned to receive either a protein-reduced infant formula with alpha-lactalbumin-enriched whey and free tryptophan and phenylalanine (IF) or an isocaloric standard formula without free amino acids (CF) for the first 120 days of life. A group of breastfed (BF) infants was studied as a non-randomized reference cohort. Biochemical variables were measured shortly after birth (subpopulation) and at an age of 120 days. A path analysis was used to explore the relationship between IGF-I, insulin and amino acids. Results are derived from secondary analyses of a randomized controlled trial. Plasma concentrations of IGF-I at 120 days were significantly higher in IF than in CF infants [58.5 (15.0) vs. 53.7 (9.95) ng/mL; p = 0.020]. BF infants showed lower IGF-I concentrations of 41.6 (10.7) ng/mL. All amino acids but Thr and Cit had a more marked effect on insulin than on IGF-I level. Considering weight, sex and feeding group, Trp explained an equal percentage of variance of IGF-I and insulin (total R 2 12.5 % of IGF-I and 12.3 % of insulin), while branched-chain AA explained an up to twofold higher variance of insulin than IGF-I. Compared to CF, IF explained 18.9 % of the IGF-I level (p = 0.03), while for insulin no direct effect was detectable. Higher IGF-I concentrations and growth velocities in infants receiving protein-reduced IF indicate that the protein concentration of an infant formula alone does not control IGF-I levels and growth. Other components (e.g., selected amino acids) of infant formulae might control directly or indirectly via insulin influence IGF-I.


Establishment and biological activity of a proliferative anti-idiotype-activated T cell line.
Antisera were raised in rabbits against a monoclonal antibody (McAb 103) of C3H.SW origin which is specific to the synthetic polypeptide (T,G)-A-L and was shown to express the major idiotypic determinants of conventional anti-(T,G)-A-L antibodies. Antibodies were purified and were shown in a binding assay to recognize McAb 103 as well as C3H.SW anti-(T,G)-A-L antibodies. C57BL/6 mice were immunized with the purified rabbit anti-McAb 103 (Ra 103) and their lymph nodes were studied in a proliferation assay. Proliferation was observed in the presence of both Ra 103 and (T,G)-A-L, although the latter stimulated the cells to a lesser extent, suggesting the induction in vivo of (T,G)-A-L-specific clones in low frequency. A T cell line was established from these lymph node cells. The line is kept in continuous growth in the presence of IL-2 and periodic triggering with Ra 103. A significant proliferative response was obtained with Ra 103 only. This proliferation could be almost completely inhibited by either McAb 103 or by conventional anti-(T,G)-A-L antibodies of C3H.SW origin, indicating the cross reaction between the idiotypes expressed on the T cell line and the (T,G)-A-L-specific antibodies. No proliferation could be detected in the presence of either normal rabbit IgG or rabbit anti-mouse IgG. Thus, the T cell line TId 103 allows the analysis of the role of idiotype in T cell recognition and regulation.


Optimized precooling combined with SO2-released paper treatment improves the storability of longan (Dimocarpus longan Lour.) fruits stored at room temperature.
Precooling and sulfur dioxide fumigation were proved as effective methods for the preservation of longan (Dimocarpus longan Lour.) fruits. However, inadequate precooling and sulfur dioxide fumigation resulted in unexpected losses and short shelf life. A L9(34) orthogonal test was conducted to screen out ideal dosage of sodium metabisulfite (factor A), precooling method (factor B), and precooling duration (factor C) to improve the storability of longan fruit stored for 48 hr at room temperature (RT) (25℃). The overall qualities of all of the treated longan fruits after a 48-hr storage (OQST) and during the 5-day shelf at 25℃ (OQSF) were better than those of the control fruits. The treated fruits showed brighter fresh color (higher L*, b*, C*, and h° values but lower a* value), higher flavonoid, and chlorophyll contents. Moreover, the SO2 residue was concentrated in pericarp but little in aril for any of the 12 treatments. The multivariate variance analysis showed that factor A was dominant to determine both of the OQST and OQSF, while factor B affected the OQST, and factor C affected the OQSF. In total, "0.22% sodium metabisulfite + 4 hr precooling + uncovered precooling" was considered to be an ideal treatment. These results would contribute to improving longan postharvest preservation technology.


Surgical removal of adipose tissue alters feeding behavior and the development of obesity in rats.
Lipectomized and sham-operated rats were fed a high-fat diet to induce hyperphagia and rapid fat accumulation. Lipectomized rats with 25% fewer adipocytes were less hyperphagic and accumulated less fat, but their adipocytes remained equal in size to adipocytes of controls. A role for adipocyte size in fat storage regulation and food intake control is postulated.


Evaluation of functional capacity during exercise radionuclide angiography.
This study compared functional capacity during treadmill exercise testing and during bicycle exercise radionuclide angiography. 262 patients performed maximal upright bicycle exercise and also performed maximal graded exercise testing using either the Bruce (n = 158) or Naughton (n = 104) treadmill protocols. The functional capacity was well correlated between bicycle and treadmill for Bruce (r = 0.89), Naughton (r = 0.93), or combined treadmill (r = 0.90) protocols. However, the functional capacity was significantly lower during bicycle than during treadmill testing for Bruce (8.3 vs. 10.5 METs), Naughton (7.8 vs. 8.7 METs), or combined treadmill (8.1 vs. 9.8 METs) protocols. Treadmill functional capacity could be predicted from bicycle functional capacity using the following equations: Bruce METs = 1.00 X (bike METs) + 2.23, Naughton METs = 0.94 X (bike METs) + 1.40, and combined treadmill METs = 0.98 X (bike METs) + 1.85.


Dose escalation of 3D radiotherapy is effective for esophageal squamous cell carcinoma: a multicenter retrospective analysis (3JECROG R-03).
To evaluate the impact of radiation dose escalation on overall survival (OS) in patients with non-metastatic esophageal squamous cell carcinoma (ESCC) treated with radical radiotherapy. The clinical data of ESCC patients treated with three-dimensional (3D) radiotherapy alone or chemoradiotherapy were collected from multiple institutes and retrospectively analyzed. Patients who received radiation dose ≥40 Gy were included. Radiation dose as a continuous variable was entered into the Cox regression model by using penalized spline regression to allow for a nonlinear relationship between radiation dose and OS to be identified. Patients were stratified into five groups according to EQD2. The Kaplan-Meier method was used to assess the OS in different dose groups. Univariate and multivariate analyses were performed to evaluate the factors associated with OS. A total of 2,469 patients were included from 10 institutes across China. The median follow-up time was 58.3 months [95% confidence interval (CI): 56.4-60.2 months]. The median OS and PFS time were 24.3 months (95% CI: 22.5-26.2 months) and 18.0 months (95% CI: 16.4-19.6 months), respectively. The risk of death decreased sharply with a dose up to 60 to 62 Gy, before increasing slightly after the dose was elevated beyond 62 Gy. Multivariate analysis indicated that the chance of death was significantly decreased in patients who received radiotherapy doses of 60-62 Gy [P=0.028, hazard ratio (HR) 0.85, 95% CI: 0.73-0.98)], compared with those who received radiotherapy doses of 40-60 Gy. Our results reveal radiation dose is a significant prognostic factor of survival for ESCC patients. Higher radiation dose contributes to much more favorable survival outcomes for ESCC patients receiving radical radiotherapy by modern techniques, and 60 Gy or above might be the most optimal radiation dose.


Composition and DNA-binding properties of the nuclear matrix proteins from mammalian cell nuclei.
A rapidly sedimenting DNA-protein complex was isolated from nuclear lysates in 2 M NaCl and characterized with regard to its polypeptide composition and the DNA-binding properties of the purified proteins. The complex consists of the nuclear matrix with attached DNA. Electrophoresis in SDS-polyacrylamide gels revealed two major and five minor polypeptide bands, mainly in the 60 to 75 kDa molecular weight region. The DNA-matrix complex dissociated into free DNA and proteins in the presence of 2 M NaCl and 5 M urea. The proteins could be purified by chromatography on hydroxyapatite and showed a strong tendency to reassociate at 0.15 M NaCl concentration in the absence of urea. DNA was bound to the reassociated proteins at 0.15 M NaCl concentration. Part of the DNA-protein complex was stable at 1 M NaCl concentration. The binding appeared to be random with regard to the DNA sequence.


Human endometrial endothelial cells generate distinct inflammatory and antiviral responses to the TLR3 agonist, Poly(I:C) and the TLR8 agonist, viral ssRNA.
Human endometrial endothelial cell (HEEC) innate immunity remains poorly characterized. Based on their direct contact with the circulation, HEECs are uniquely positioned to be exposed to viral infections. This study evaluated the innate immune response generated by HEECs after exposure to the TLR3 agonist, Poly(I:C) and the TLR8 agonist, viral ssRNA. HEECs were treated with or without Poly(I:C) or ssRNA. Culture supernatants were measured for cytokines by multiplex analysis. RNA was analyzed by qRT-PCR for type I interferons and antiviral factors. Treatment of HEECs with Poly(I:C) rapidly upregulated the secretion of IL-2, IL-6, IL-8, IFN-γ, G-CSF, GM-CSF, MCP-1, MIP-1β, RANTES, and GRO-α after 12 hr, while ssRNA treatment induced the slower secretion of IL-6, IL-8, IFN-γ, G-CSF, VEGF, and GRO-α after 24 hr. Both viral components induced HEEC IFN-α and IFN-β expression. While treatment with Poly(I:C) induced APOBEC3G and OAS expression, treatment with ssRNA upregulated APOBEC3G and M×A mRNA. Our findings demonstrate that HEECs can differentially sense and respond to viral components by generating distinct inflammatory and antiviral immune responses, indicating that these cells likely play an active role in the immune protection of the uterus toward viral infections.


Overtight nappy precipitating thrombosis in antithrombin III deficiency.
An antithrombin III deficient infant presented with iliac vein thrombosis, apparently precipitated by an overtight nappy. Venous thrombosis is unusual, both in normal and in antithrombin III deficient children, but children with venous thrombosis should have their natural anticoagulants assayed and obvious risk factors avoided.


A comprehensive appraisal of HER2 heterogeneity in HER2-amplified and HER2-low colorectal cancer.
This study aimed to elucidate the clinicopathological and molecular features of HER2-amplified and HER2-low colorectal cancers (CRCs). We also characterised HER2 expression statuses in CRCs focusing on their intratumoral heterogeneity and alterations in metastatic lesions to establish practical HER2 status assessment. We evaluated 1009 CRCs for HER2 expression and HER2 amplification by immunohistochemistry and FISH, respectively, and correlated the results to clinicopathological and molecular data. For HER2-positive tumours, HER2 expression in metastatic lesions was also assessed. Twenty-five HER2-amplified (2.5%) and 46 HER2-low tumours (4.6%) were identified. HER2-amplified tumours consistently lacked a mucinous component and HER2-low tumours tended to be in the right colon, but no other clinicopathological features were noted. KRAS, NRAS or BRAF mutations were detected in only two HER2-amplified tumours (8%), whereas 23 HER2-low tumours (50%) had one of these mutations. Most HER2-amplified and HER2-low tumours showed a homogeneous or mosaic HER2 expression pattern and a clustered heterogeneous expression pattern was rather rare. HER2 expression was maintained in most metastatic lesions in both HER2-amplified (93%) and HER2-low tumours (81%). These results suggest that biopsy-based assessment of primary lesions is appropriate for the identification of CRC patients eligible for systemic HER2-targeted therapy.


Attitudes Toward Research During Residency: A Survey of Canadian Residents in Obstetrics and Gynecology.
Obstetrics and Gynecology (Ob/Gyn) residency programs in Canada mandate participation in scholarly research activity, yet there remains a lack of literature on trainees' opinions regarding its value, feasibility, and perceived effect on future practice. An understanding of resident attitudes toward research during residency is essential in effectively engaging trainees and fostering a robust research community in the field. We sought to identify factors reported to influence involvement in resident research, including perceived barriers. Anonymous data were collected via an online survey distributed to all residents enrolled in accredited Ob/Gyn residency programs throughout Canada. The 10-minute, previously piloted questionnaire covered questions related to demographic information, research experience, career goals, current research activities, opinions on research environment, and opinions regarding the effect of research on future practice. Descriptive statistics were used to describe demographics, research background, and current research activities. Categorical variables were compared using the chi-square analysis and continuous variables were compared using the Mann-Whitney rank sum tests. A total of 175 residents completed the survey; 61% agreed/strongly agreed that they participate in research solely because it is mandated by their program, 22% felt that their training environment did not promote research, 19% disagreed/strongly disagreed that research is a positive experience, while 70% agreed/strongly agreed that they would prefer to complete another educational activity other than a research project. Time constraints owing to residency duties, time constraints owing to personal reasons, and lack of statistical knowledge were reported as barriers to research involvement by 97%, 90%, and 74% of trainees, respectively. Residents with graduate degrees were less likely to report lack of training on research design as a moderate/extreme barrier (7% vs 32%, p = 0.007). There exists considerable disparity in enthusiasm for scholarly research activity among Ob/Gyn residents. Curricular development should focus on addressing resident-reported barriers, including the provision of protected time for research and access to statistical support and education, particularly for residents without graduate degrees.


Methods for assessing artificial thermal refuges: Spatiotemporal analysis more informative than averages.
1: Thermal refuges are widely used by animals of all taxonomic groups and are critical to survival in severe weather. 2: Human activities are reducing the availability of natural refuges; consequently, artificial refuges are used as conservation management tools, particularly for bats. 3: Published box evaluations are generally incomplete, omitting thermal physiology and relevant thermal properties. 4: Here, we compare methods for evaluating the potential utility of bat box designs for bats and present a graphical spatiotemporal method that provides more complete information. 5: For illustration, we compare the original to three modified versions of the "rocket box" style bat box. 6: Box internal temperatures and generalized thermal physiology models are combined in two suitability indices appropriate to the mother, and to pups. 7: Results revealed that daily and seasonal averages of these indices obscured important processes and showed insignificant differences among bat box design modifications. 8: In contrast, graphical analysis highlighted the presence and spatiotemporal structure of significant differences among boxes, which were most evident in sunny weather. 9: Differences among boxes were sensitive to assumptions about bat thermal physiology and behavior. 10: We found that an external water jacket mitigated temperature extremes and extended favorable temperatures into the night, which could enhance pup development while the mothers foraged. 11: Further experiments are needed to evaluate the relation between metabolic heating by box occupants and thermal conditions within bat boxes.


Motion corrected silent ZTE neuroimaging.
To develop self-navigated motion correction for 3D silent zero echo time (ZTE) based neuroimaging and characterize its performance for different types of head motion. The proposed method termed MERLIN (Motion Estimation & Retrospective correction Leveraging Interleaved Navigators) achieves self-navigation by using interleaved 3D phyllotaxis k-space sampling. Low resolution navigator images are reconstructed continuously throughout the ZTE acquisition using a sliding window and co-registered in image space relative to a fixed reference position. Rigid body motion corrections are then applied retrospectively to the k-space trajectory and raw data and reconstructed into a final, high-resolution ZTE image. MERLIN demonstrated successful and consistent motion correction for magnetization prepared ZTE images for a range of different instructed motion paradigms. The acoustic noise response of the self-navigated phyllotaxis trajectory was found to be only slightly above ambient noise levels (<4 dBA). Silent ZTE imaging combined with MERLIN addresses two major challenges intrinsic to MRI (i.e., subject motion and acoustic noise) in a synergistic and integrated manner without increase in scan time and thereby forms a versatile and powerful framework for clinical and research MR neuroimaging applications.


Automatic recognition and measurement of butterfly eyespot patterns.
A favorite wing pattern element in butterflies that has been the focus of intense study in evolutionary and developmental biology, as well as in behavioral ecology, is the eyespot. Because the pace of research on these bull's eye patterns is accelerating we sought to develop a tool to automatically detect and measure butterfly eyespot patterns in digital images of the wings. We used a machine learning algorithm with features based on circularity and symmetry to detect eyespots on the images. The algorithm is first trained with examples from a database of images with two different labels (eyespot and non-eyespot), and subsequently is able to provide classification for a new image. After an eyespot is detected the radius measurements of its color rings are performed by a 1D Hough Transform which corresponds to histogramming. We trained software to recognize eyespot patterns of the nymphalid butterfly Bicyclus anynana but eyespots of other butterfly species were also successfully detected by the software.


Aflatoxin in human and camel milk in Abu Dhabi, United Arab Emirates.
During an initial survey, using thin layer chromatography, 10 of 64 samples of mothers' breast milk, collected from donors at the Corniche Maternity Hospital and the Al-Nehyan Clinic for Maternity and Childhood, were found to contain Aflatoxin M1 at concentrations ranging from 0.3 to 1.3 ng mL(-1). A second survey using HPLC showed Aflatoxin M1 at concentrations ranging from 7 to 23 pg mL(-1) in all of the 15 samples collected. 6 of 20 samples of camel milk collected from several sources in Abu Dhabi were also found to contain Aflatoxin M1 at levels ranging from 0.25 to 0.8 ng mL(-1).


Fungal endocarditis in bone marrow transplantation: case report and review of literature.
We report a case of fungal endocarditis due to Aspergillus terreus in a leukaemia patient who received a bone marrow allograft from a matched unrelated donor. He presented with persistent fever. microangiopathic haemolytic anaemia but there was no cardiac signs and symptoms. He died despite intravenous amphotericin B. Review of the English literature showed five other patients with fungal endocarditis in the setting of bone marrow transplantation and revealed the same features of difficult diagnosis and poor outcome.


Magnetic resonance epidurography with gadolinium-DTPA.
The aim of this study was to evaluate and describe MRI epidurography as a new imaging tool. Five volunteers and one patient were investigated with MR epidurography after injection of 20 ml Gd-DPTA solution (1:250/1 ml Gd-DPTA/250 ml normal saline). Magnetic resonance epidurography is possible. With fat-suppression techniques, the contrast between Gd-DPTA solution in the epidural space and surrounding soft tissue proved adequate. Using the multiplanar capability of MRI with MR epidurography coronal and sagittal projections similar to conventional epidurography, axial slices comparable to CT epidurography can be obtained. Magnetic resonance epidurography is superior to conventional and CT epidurography. Presently, due to high costs as compared with conventional and CT epidurography, MRI is not suitable for the routine monitoring of peridural catheters, but it may have a place in the future with decreasing costs for MRI and for the evaluation of patients with spine pathology, especially in describing epidural processes.


Ski-geometric parameters do not differ between ACL injury mechanisms in recreational alpine skiing.
It is not known so far if ski-equipment-related factors differ between the ACL injury mechanisms, potentially influencing the circumstances and causes of falling, finally resulting in ACL injury. More specifically focusing on the injury mechanisms will provide a deeper understanding of injury causation. The aim of the study was to evaluate whether ACL injury mechanisms in recreational alpine skiing differ with regard to ski-geometric parameters, self-reported circumstances and causes of accident and injury severity. Among a cohort of 392 ACL-injured (57.9% females) skiers, age, sex, height, weight, skill level, risk-taking behavior, circumstances and causes of accident, and ACL injury severity were collected by questionnaire. Additionally, patients had to recall their type of fall (ACL injury mechanism) by classifying forward and backward falls with and without body rotation. Ski length, side cut radius and widths of the tip, waist and tail were directly notated from the ski. The forward fall with body rotation was the most common reported ACL injury mechanism (63%). A riskier behavior was associated with forward falls without body rotation. Ski-geometric parameters did not significantly influence the type of ACL injury mechanism. Regarding accident characteristics, catching an edge of the ski was more frequent (p < 0.001) the cause for forward falls (75% and 67%) when compared to the backward falls (46 and 15%) and executing a turn was the most frequent action in all falls (39-68%). A complete rupture of the ACL (66-70%) was more commonly reported than a partial tear (30-34%) among all four non-contact ACL injury mechanisms (n.s.). In contrast to risk-taking behavior and accident characteristics, ski-geometric parameters and injury severity do not significantly differ between ACL injury mechanisms in recreational skiing. Thus, an individual skiing style seems to have more impact on ACL injury mechanisms than ski equipment. Future studies should evaluate potential effects of ski geometry on the incidence of ACL injury. III.


Stoichiometric C-H arylation of tricarbonyl(arene)chromium complexes bearing pyridine directing groups.
Differentially substituted Cr(CO)3-complexed aryl pyridines have been shown to readily undergo stoichiometric palladation and subsequent arylation using boronic acid nucleophiles. The positioning of the aryl substituents has been shown to be key in governing substrate reactivity, whereby sterically congested compounds prevent the geometry required for cyclometallation.


Response to steroids in Budd-Chiari syndrome caused by idiopathic granulomatous venulitis.
A 31-yr-old man presented with the Budd-Chiari syndrome. A liver biopsy specimen demonstrated noncaseating centrilobular granulomas and an idiopathic necrotizing granulomatous venulitis involving hepatic vein radicles with superimposed thrombotic occlusion. High-dose prednisone therapy produced dramatic clinical improvement with resolution of the hepatomegaly, ascites, and portal hypertension and normalization of the hepatic venous angiogram. A repeat liver biopsy specimen showed resolution of the venulitis and disappearance of the hepatic vein thrombosis. Idiopathic granulomatous venulitis that is reversible with prednisone therapy should be considered in the differential diagnosis of the Budd-Chiari syndrome.


Intensified tuberculosis case finding among HIV-infected persons using a WHO symptom screen and Xpert(®) MTB/RIF.
Human immunodeficiency virus (HIV) clinic in Addis Ababa, Ethiopia. The World Health Organization (WHO) recommends active tuberculosis (TB) case-finding among people living with HIV (PLHIV) in high-burden settings. To evaluate the effectiveness of combining a WHO-recommended symptom screen and the Xpert(®) MTB/RIF test to enhance TB case finding. In this cross-sectional study, PLHIV were screened for TB using a WHO-recommended symptom-based algorithm (cough, fever, night sweats, weight loss). Those with a positive symptom screen (⩾1 symptom) underwent diagnostic testing with smear microscopy, culture, and Xpert. Of 828 PLHIV (89% on antiretroviral therapy), 321 (39%) had a positive symptom screen. In multivariate analysis, an unscheduled clinic visit (aOR 3.78, 95%CI 2.69-5.32), CD4 count <100 cells/μl (aOR 2.62, 95%CI 1.23-5.59) and previous history of TB (aOR 1.62, 95%CI 1.12-2.31) were predictors of a positive symptom screen. Among those with a positive symptom screen, 6% had active pulmonary TB. Smear microscopy sensitivity for TB was poor (30%) compared to culture and Xpert. A positive symptom screen was common among PLHIV, creating a substantial laboratory burden. Smear microscopy had poor sensitivity for active TB disease. Given the high rate of positive symptom screen, substantial additional resources are needed to implement intensified TB case finding among PLHIV in high-burden areas.


Unravelling the complexity of lncRNAs in autophagy to improve potential cancer therapy.
Autophagy is well-known as an internal catabolic process that is evolutionarily conserved and performs the key biological function in maintaining cellular homeostasis. It is tightly controlled by several autophagy-related (ATG) proteins, which are closely associated with many types of human cancers. However, what has remained controversial is the janus roles of autophagy in cancer progression. Interestingly, the biological function of long non-coding RNAs (lncRNAs) in autophagy has been gradually understood in different types of human cancers. More recently, numerous studies have demonstrated that several lncRNAs may regulate some ATG proteins and autophagy-related signaling pathways to either activate or inhibit the autophagic process in cancer. Thus, in this review, we summarize the latest advance in the knowledge of the complicated relationships between lncRNAs and autophagy in cancer. Also, the in-depth dissection of the lncRNAs-autophagy-cancers axis involved in this review would shed new light on discovery of more potential cancer biomarkers and therapeutic targets in the future.


Effects of e-vapour and high-fat diet on the immunohistochemical staining of nicotinic acetylcholine receptors, apoptosis, microglia and astrocytes in the adult male mouse hippocampus.
The use of e-cigarettes/e-vapour, and the consumption of a high-fat diet (HFD), are two popular lifestyle choices associated with alterations in the hippocampus. This study, using a mouse model, investigated the effects of exposure to e-vapour (± nicotine) and HFD (43% fat) consumption, on the expression of nicotinic acetylcholine receptor (nAChR) subunits α3, α4, α7 and β2, apoptosis markers caspase-3 and TUNEL, microglial marker Iba-1, and astrocyte marker GFAP, in hippocampal subregions of dentate gyrus (DG) and cornu ammonis (CA) 1-3. The major findings included: (1) HFD alone had minimal effect with no consistent pattern or interaction between the markers, (2) E-vapour (± nicotine) predominantly affected the CA2 subregion, decreasing α7 and β2 nAChR subunits and Iba-1, (3) Nicotine e-vapour increased TUNEL across all subregions, and (4) HFD, in the presence of nicotine-free e-vapour, decreased caspase-3 and increased TUNEL across all regions, and decreased Iba-1 in the CA subregions, while HFD and nicotine-containing e-vapour, subregion specifically affected the α3, α4 and α7 nAChR subunits, with a protective effect against change in GFAP in the DG and Iba-1 in the CA1 and CA3. These findings highlight that e-vapour itself alters nAChRs, particularly in the CA2 subregion, associated with a decrease in neuroinflammatory response (Iba-1) across the whole hippocampus, and the addition of nicotine increases cell apoptosis across the whole hippocampus. HFD alone was not detrimental in our model, but in the presence of nicotine-free e-vapour, it differentially affected apoptosis, while the addition of nicotine increased nAChR subunits.


Regression of established hepatocellular carcinoma is induced by chemoimmunotherapy in an orthotopic murine model.
The high rate of mortality and frequent incidence of recurrence associated with hepatocellular carcinoma (HCC) reveal the need for new therapeutic approaches. In this study we evaluated the efficacy of a novel chemoimmunotherapeutic strategy to control HCC and investigated the underlying mechanism that increased the antitumor immune response. We developed a novel orthotopic mouse model of HCC through seeding of tumorigenic hepatocytes from SV40 T antigen (Tag) transgenic MTD2 mice into the livers of syngeneic C57BL/6 mice. These MTD2-derived hepatocytes form Tag-expressing HCC tumors specifically within the liver. This approach provides a platform to test therapeutic strategies and antigen-specific immune-directed therapy in an immunocompetent murine model. Using this model we tested the efficacy of a combination of oral sunitinib, a small molecule multitargeted receptor tyrosine kinase (RTK) inhibitor, and adoptive transfer of tumor antigen-specific CD8(+) T cells to eliminate HCC. Sunitinib treatment alone promoted a transient reduction in tumor size. Sunitinib treatment combined with adoptive transfer of tumor antigen-specific CD8(+) T cells led to elimination of established tumors without recurrence. In vitro studies revealed that HCC growth was inhibited through suppression of STAT3 signaling. In addition, sunitinib treatment of tumor-bearing mice was associated with suppression of STAT3 and a block in T-cell tolerance. These findings indicate that sunitinib inhibits HCC tumor growth directly through the STAT3 pathway and prevents tumor antigen-specific CD8(+) T-cell tolerance, thus defining a synergistic chemoimmunotherapeutic approach for HCC.


Silica-titania xerogel for solid phase spectrophotometric determination of salicylate and its derivatives in biological liquids and pharmaceuticals.
Salicylic acid and its derivatives are widely used drugs with potential toxicity. The main areas of salicylate derivatives determination are biological liquids and pharmaceuticals analysis. Silica-titania xerogel has been used for solid phase spectrophotometric determination of various salicylate derivatives (salicylate, salicylamide, methylsalicylate). The reaction conditions influence on the interaction of salicylate derivatives with silica-titania xerogels has been investigated; the characteristics of titanium(IV)-salicylate derivatives complexes in solid phase have been described. The simple solid phase spectrophotometric procedures are based on the formation of xerogel incorporated titanium(IV) colored complexes with salicylate derivatives. A linear response has been observed in the following concentration ranges 0.1-5, 0.5-10 and 0.05-4.7 mM for salicylate, salicylamide, and methylsalicylate, respectively. The proposed procedures have been applied to the analysis of human urine, synthetic serum, and pharmaceuticals. The simple solid phase spectrophotometric procedures of salicylate derivatives determination based on the new sensor materials have been proposed for biological liquids and pharmaceuticals analysis. Graphical abstractComplexation of titanium (IV), incorporated in silica-titania xerogels (Si-Ti), with salicylate derivatives (L) resulting in yellow-colored xerogels (Si-Ti/Ln) has been proposed for salicylate derivatives determination in biological liquids and pharmaceuticals.


UV-blocking potential of oils and juices.
Sunscreens are commonly used to protect the body from damage caused by UV light. Some components of organic sunscreens have been shown to pass through the skin during wear which could raise toxicity concerns for these compounds. This study explores the potential for oils and fruit and vegetable juices to be substitutes for these compounds. The absorptivity of various oils (canola oil, citronella oil, coconut oil, olive oil, soya bean oil, vitamin E, as well as aloe vera) and fruit and vegetable juices (acerola, beet, grape, orange carrot, purple carrot and raspberry) was measured in vitro. The mean absorptivity was compared with FDA-approved UV absorbers to gauge the potential of the natural products. The most promising candidates were incorporated into formulations, and the UV transmittance of a 20-μm-thick film of the formulation was measured. The formulations were also imaged by light microscopy and scanning electron microscopy. The absorptivity of oils was at least two orders of magnitude lower compared to the commercial UV blockers. The fruit juice powders were more effective at UV blocking but still showed an order of magnitude lower absorptivity compared to commercial UV blockers. The UV blocking from most natural oils is insufficient to obtain a significant UV protection. Formulations containing 50wt% purple carrot showed good UV-blocking capabilities and represent a promising ingredient for sunscreen and cosmetic applications.


Measuring child functioning: Assessing correlation and agreement between caregiver and child responses at the Iganga-Mayuge health and demographic surveillance site in Uganda.
Empirical data is scare on assessment of concordance between caregiver-child responses on child functioning. To assess correlation and agreement between children (11-17 years old) and their caregivers' responses to the UNICEF/Washington Group Child Functioning Module (CFM) at the Iganga-Mayuge Health and Demographic Surveillance Site (IM-HDSS) in Uganda. CFM with 24-questions corresponding to 13 domains of functioning was administered to children between 11 and 17 years of age and their caregivers. Descriptive analyses of the child/caregiver responses were conducted. Correlation and agreement between caregiver and child responses were assessed. Of the 217 caregiver/child pairs eligible for this study, 181 pairs agreed to participate (83.4%). The mean age of children was 13.9 ± 1.9 years, and 56.4% were males. Cronbach's alpha was 0.892 and 0.886 for the caregiver and child versions of CFM respectively, showing good internal consistency in both. There was a significant overall agreement between mean score of caregiver (5.36 ± 5.63 out of 39) and child (5.45 ± 5.34) pairs. Spearman's rank correlation between the pairs was 0.806 (strong positive correlation). Bland-Altman plots for CFM scores showed greater agreement between caregiver and child at lower scores. Percentage agreement between the pairs for overall disability was greater for mild (83.53%) and moderate (79.37%) categories as compared to the severe (66.67%) category. There was substantial agreement (kappa 0.623) for overall disability between the pairs. This study indicates that there is significant correlation and agreement between self-reported caregiver-child pair responses, opening the way for considering children as CFM respondents, when possible.


Time-resolved 3D contrast-enhanced MRA of an extended FOV using continuous table motion.
A method is presented for acquiring 3D time-resolved MR images of an extended (>100 cm) longitudinal field of view (FOV), as used for peripheral MR angiographic runoff studies. Previous techniques for long-FOV peripheral MRA have generally provided a single image (i.e., with no time resolution). The technique presented here generates a time series of 3D images of the FOV that lies within the homogeneous volume of the magnet. This is achieved by differential sampling of 3D k-space during continuous motion of the patient table. Each point in the object is interrogated in five consecutive 3D image sets generated at 2.5-s intervals. The method was tested experimentally in eight human subjects, and the leading edge of the bolus was observed in real time and maintained within the imaging FOV. The data revealed differential bolus velocities along the vasculature of the legs.


Anti-parkinsonian activity of the adenosine A2A receptor antagonist/inverse agonist KW-6356 as monotherapy in MPTP-treated common marmosets.
KW-6356 is a novel adenosine A2A receptor antagonist/inverse agonist that not only blocks binding of adenosine to adenosine A2A receptor but also inhibits the constitutive activity of adenosine A2A receptor. The efficacy of KW-6356 as both monotherapy and an adjunct therapy to L-3,4-dihydroxyphenylalanine (L-DOPA)/decarboxylase inhibitor in Parkinson's disease (PD) patients has been reported. However, the first-generation A2A antagonist istradefylline, which is approved for use as an adjunct treatment to L-DOPA/decarboxylase inhibitor in adult PD patients experiencing OFF episodes, has not shown statistically significant efficacy as monotherapy. In vitro pharmacological studies have shown that the pharmacological properties of KW-6356 and istradefylline at adenosine A2A receptor are markedly different. However, the anti-parkinsonian activity and effects on dyskinesia of KW-6356 in PD animal models and the differences in the efficacy between KW-6356 and istradefylline are unknown. The present study investigated the anti-parkinsonian activity of KW-6356 as monotherapy in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets, and its efficacy was directly compared with that of istradefylline. In addition, we investigated whether or not repeated administration of KW-6356 induced dyskinesia. Oral administration of KW-6356 reversed motor disability in a dose-dependent manner up to 1 mg/kg in MPTP-treated common marmosets. The magnitude of anti-parkinsonian activity induced by KW-6356 was significantly greater than that of istradefylline. Repeated administration of KW-6356 induced little dyskinesia in MPTP-treated common marmosets primed to exhibit dyskinesia by prior exposure to L-DOPA. These results indicate that KW-6356 can be a novel non-dopaminergic therapy as monotherapy without inducing dyskinesia in PD patients.


Immunopathogenesis, Diagnosis, and Treatment of Multiple Sclerosis: A Clinical Update.
Multiple sclerosis (MS) is the most prevalent nontraumatic disabling neurologic condition among young adults worldwide. The diagnosis and management of MS is complex. The goal of this review is to provide an updated and practical approach to the diagnosis and treatment approaches in MS, emphasizing current understanding of immunopathogenesis, recent advances, and future directions, for both MS and non-MS clinicians.


Assessment of marginal nutrition and means of preventing communicable diseases in twins: an implication for intensive follow-up.
Of the 101 mothers who delivered twins at the Ife State Hospital in 1979, 58 mothers were traceable. The twins were assessed for growth by weighing; mothers were interviewed as to feeding practices, means of protecting children from common diseases. Seventy-six percent of the children were underweight for age; 9 of the children died of preventable diseases. Corn pap (maize gruel) in addition to breast milk was the major weanling food among the lower socio-economic mothers. Sixty-two percent of the mothers employed traditional methods, either singly or combined with immunization, to protect their infants from preventable disease. The role of regular home visits by the health workers in developing countries to monitor the growth progress and health status of twins in the first 18 months is emphasized.


A Comparative Study of the Use of Dexamethasone, N-acetyl Cysteine, and Theophylline to Ameliorate Renal Ischemia-Reperfusion Injury in Experimental Rat Models: A Biochemical and Immuno-histochemical Approach.
Renal ischemia-reperfusion injury (IRI) is commonly encountered in clinical practice during renal transplantation. In a trial to find the drug that best safeguards the kidney against IRI, dexamethasone (Dex), N-acetyl cysteine (NAC), and theophylline (Theo) were tested in experimental rat models. This study included 105 adult male albino rats, which were randomly assigned to the following five groups: Group I - sham-operated, n = 5, Group II - IRI n = 25, Group III - IRI + Dex n = 25, Group IV - IRI + NAC n = 25, and Group V -IRI + Theo n = 25. IRI was induced for 40 min followed by reperfusion. Rats were sacrificed 1, 2, 4, 6, and 24 h after reperfusion. This was preceded by blood and urine sampling for biochemical study of serum Cystatin C (Cys C), serum creatinine, and urinary Cys C. Kidneys were processed for histopathological evaluation and immune-histochemical staining for Cys C. The expression of Cys C in the proximal tubular cells was significantly lower in the IRI group compared to that of the sham group. There was a significant rise in the levels of serum and urinary Cys C after 1 h in the IRI group, while the rise in creatinine occurred later. Dex was superior to NAC and Theo 24 h after the IR insult, and the serum levels of creatinine and Cys C were significantly lower in this group than the other two drug groups (P <0.001 in both cases). Our study revealed a clear benefit for the use of Dex to ameliorate IRI over NAC and Theo if used immediately following the insult. The effect is evident 24-h after its use. The role of serum Cys C as an early marker of acute kidney injury compared to serum creatinine is confirmed.


Controlled comparison of topical anesthetic agents in flexible upper gastrointestinal endoscopy.
Topical anesthetics are generally part of the premedication associated with upper gastrointestinal endoscopy. Selection is not usually based on objective criteria. We performed a randomized study comparing six anesthetic agents: three sprays (Cetacaine, Hurricaine, and 10% Xylocaine spray) and three gargles (2% lidocaine, and two combinations of 2% lidocaine diluted 1:1 with mouthwash). Normal subjects, experienced in undergoing gastroscopy, underwent repeated upper gastrointestinal endoscopic examinations with a 34 F Pentax fiberscope. Topical anesthetic was the only premedication used. The parameters evaluated by the subjects were taste, effectiveness of anesthesia, and ease of scope passage. At the end of the trial each subject ranked the agents in order of preference. Although subjects differed in their preference for the different anesthetic agents (sometimes significantly), there was no single parameter such as taste, degree of anesthesia, or ease of passage of the endoscope that could be correlated with overall preference. All agents gave acceptable levels of local anesthesia, although there was a distinct subjective preference for spray forms. We recommend that if a local anesthetic is used, it should be one of the spray formulations. This recommendation is based on safety, the relative ease of application, and the lack of profound differences between agents.


The social logic of naloxone: Peer administration, harm reduction, and the transformation of social policy.
This paper examines overdose prevention programs based on peer administration of the opioid antagonist naloxone. The data for this study consist of 40 interviews and participant observation of 10 overdose prevention training sessions at harm reduction agencies in the Bronx, New York, conducted between 2010 and 2012. This paper contends that the social logic of peer administration is as central to the success of overdose prevention as is naloxone's pharmacological potency. Whereas prohibitionist drug policies seek to isolate drug users from the spaces and cultures of drug use, harm reduction strategies like peer-administered naloxone treat the social contexts of drug use as crucial resources for intervention. Such programs utilize the expertise, experience, and social connections gained by users in their careers as users. In revaluing the experience of drug users, naloxone facilitates a number of harm reduction goals. But it also raises complex questions about responsibility and risk. This paper concludes with a discussion of how naloxone's social logic illustrates the contradictions within broader neoliberal trends in social policy.


Preload dependence of right ventricular blood flow: I. The normal right ventricle.
Right ventricular (RV) failure is commonly treated with intravascular volume expansion to increase the RV-left atrial pressure gradient and improve left-sided filling. As RV pressure rises, chamber distention occurs and wall tension increases. These studies were designed to determine if increased wall tension might impede RV myocardial blood flow in the normal canine right ventricle and thus contribute to RV failure. Hemodynamic data, the septal-RV free wall dimension, and RV myocardial blood flow were obtained at low and high levels of preload and in both the autoregulated and vasodilated (adenosine, 2 mg per kilogram of body weight per minute) states. Elevated filling pressure decreased RV myocardial blood flow in both the autoregulated (0.85 +/- 0.18 to 0.67 +/- 0.15 ml/min/gm; p less than .05) and vasodilated (2.25 +/- 0.50 to 0.85 +/- 0.25 ml/min/gm; p less than .05) states but did not change the transmural distribution of blood flow to the right ventricle. Vasodilator reserve was markedly impaired in the high-preload state. These observations suggest that preload is an important determinant of RV myocardial blood flow. Volume loading to treat RV dysfunction may be limited by impairment of RV myocardial blood flow.


Cilengitide inhibits osteoclast adhesion through blocking the αvβ3-mediated FAK/Src signaling pathway.
The remodeling of actin cytoskeleton of osteoclasts on the bone matrix is essential for osteoclastic resorption activity. A specific regulator of the osteoclast cytoskeleton, integrin αvβ3, is known to provide a key role in the degradation of mineralized bone matrixes. Cilengitide is a potent inhibitor of integrins and is capable of affecting αvβ3 receptors, and has anti-tumor and anti-angiogenic and apoptosis-inducing effects. However, its function on osteoclasts is not fully understood. Here, the cilengitide role on nuclear factor κB ligand-receptor activator (RANKL)-induced osteoclasts was explored. Cells were cultured with varying concentrations of cilengitide (0,0.002,0.2 and 20 μM) for 7 days, followed by detected via Cell Counting Kit-8, staining for tartrate resistant acid phosphatase (TRAP), F-actin ring formation, bone resorption assays, adhesion assays, immunoblotting assays, and real-time fluorescent quantitative PCR. Results demonstrated that cilengitide effectively restrained the functionality and formation of osteoclasts in a concentration-dependent manner, without causing any cytotoxic effects. Mechanistically, cilengitide inhibited osteoclast-relevant genes expression; meanwhile, cilengitide downregulated the expression of key signaling molecules associated with the osteoclast cytoskeleton, including focal adhesion kinase (FAK), integrin αvβ3 and c-Src. Therefore, this results have confirmed that cilengitide regulates osteoclast activity by blocking the integrin αvβ3 signal pathway resulting in diminished adhesion and bone resorption of osteoclasts.


Hypofractionated stereotactic radiotherapy for medically inoperable stage I non-small cell lung cancer--report on clinical outcome and dose to critical organs.
We report 20 cases using hypofractionation stereotactic radiotherapy in medically inoperable stage I non-small cell lung cancer with dose escalation of 45-54 Gy prescribed at 85 or 90% isodose level in 3-4 fractions. Two-year local control and cancer-specific survival were 94.7 and 77.6%, respectively, with minimal toxicity. Though, large fraction size can be safely given to peripheral lung tumors, normal tissue tolerance to hypofractionated radiotherapy to esophagus, trachea, main bronchi, aorta and heart remains unknown. Therefore we also reported the maximum point doses to these critical organs to contribute information to extend this technique to more centrally located lung tumors in future.


Structure of intracorneal femtosecond laser pulse effects in conical incision profiles.
As the applicative potential of femtosecond lasers is to be extended from LASIK-flap creation into intrastromal ablation uses, the interdependency of influencing factors has to be understood. We therefore evaluated the relationship between focus depth, energy level, spatial distribution and morphology of fs-Laser pulse effects at a given repetition rate in corneal tissue. The experimental study included five porcine corneae obtained from slaughterhouse pigs. Using a prototype of a femtosecond laser (FEMTEC; 20/10 Perfect Vision AG, Heidelberg, Germany), a conical circular cut was performed in posterior-anterior direction through the entire corneal profile. The laser energy applied ranged from 4.0 to 8.5 microJ. Histological sections (n = 337) of a thickness of 7 microm were obtained, stained with hematoxylin/eosin, and morphometrically evaluated. The intrastromal femtosecond laser effects were aligned throughout the corneal stroma in a line that followed the dissection line programmed for the laser. The lesions were mostly of roughly elliptic shape with a fine dense lining at the inner wall, without evidence of a collateral damage beyond the disruption cavity. The mean maximal diameter of the intrastromal laser effects was 34.2 +/- 18.6 microm (range: 9-120 microm), and the mean maximal lesion diameter was 60.8 +/- 42.6 microm. In multivariate analysis, the lesion type (single shot cavity, partly confluent lesions, and fully confluent lesions) was significantly associated with the laser energy applied (P = 0.027) and the lesion diameter (P = 0.01). At higher laser energies, the intrastromal laser lesions were larger and more confluent, suggesting that, with the prototype of femtosecond laser used, a higher laser energy may lead to more confluent intrastromal laser effects. It may facilitate the complete cutting of the corneal tissue with the laser. Neither discernable debris nor stainable collateral damage were detected, suggesting a purely mechanical action of the laser.


Enzymic differentiation of human liver: comparison with the rat model.
The quantitative pattern of enzymes in the second trimester human fetal liver is significantly different from that of adult liver. For some 20 enzymes, the activity quotient (AQ, i.e., activity of immature liver divided by that in adult liver) is appreciably different from 1.0. Most of the enzymes increase their concentrations with age but, as one would expect, some contribute to differentiation by diminishing in amount. In developing human liver the concentrations of the various enzymes tend to change in the same direction as they do in rat liver. Those that increase in rat liver have been classified into three main clusters, according to whether their rise begins on about the 17th day of gestation (B), the first neonatal day (C), or just before weaning (D), respectively. The distribution of these enzymes among these three clusters correlates with their AQ's in the human fetal liver. In general, enzymes with AQ around 0.5 belong to cluster (B) in rat liver whereas those with 0-0.16 belong to cluster C or D. Gross malformations resulting from the teratogenic action of drugs, hormones, or vitamins on the early embryo attract much attention. The harmful impacts of such agents at late stages of gestation are less spectacular. They may be more frequent, however, and manifest themselves in permanent inadequacies in metabolism or growth with a tendency to succumb to minor childhood diseases. The underlying causes may not be mirrored in the cytocomposition or even the subcellular morphology of autopsy specimens. Only deviations from the organ characteristic quantitative pattern of gene products would provide sensitive enough indictors of the metabolic lesions and of the aberrant aspects of differentiation that were responsible for them. In both the presence and absence of detectable morphologic abnormalities, the study of enzymes, this most varied and largest class of specific chemical constituents, would greatly extend the resolving power of the usual diagnostic procedures postmortem.


Catalytic microwave torrefaction of microalga Chlorella vulgaris FSP-E with magnesium oxide optimized via taguchi approach: A thermo-energetic analysis.
Biochar is a promising material and fuel for environmental sustainability. Microalgal biochar is produced using catalytic microwave torrefaction of Chlorella vulgaris FSP-E residue with magnesium oxide as a microwave absorber to enhance heating. Using Taguchi experimental design (TED) and Analysis of Variance (ANOVA), the effects of microwave power, catalyst concentration, and duration on energy yield are investigated. Both TED and ANOVA confirm the significant effects of microwave power and catalyst concentration, while only a slight effect from duration. The calorific values of produced biochar (21.12-26.22 MJ⋅kg-1) are close to coal. The maximum deoxygenation and carbonization extents are 56.69% and 35.23%, respectively. The optimal parameter combination of low microwave power (450 W), low duration (25 min), and high catalyst concentration (10 wt% MgO) poses the highest upgrading energy index (UEI) value. This confirms that better energy efficiency leans towards light torrefaction conditions with maximized catalyst concentration to produce the maximum energy yield while consuming the least electricity input.


Perishock Pause Intervals and Rearrest after Out-of-Hospital Cardiac Arrest.
The loss of pulses after successful return of spontaneous circulation (ROSC) in out-of-hospital cardiac arrest (OHCA) is known as rearrest (RA). The causes of RA are not well understood. To investigate the association between shock pause intervals and RA. Data from treated OHCA with ROSC and one or more defibrillation attempts were obtained from one site of the Resuscitation Outcomes Consortium. All analyses were conducted internally. Data available for analysis included cases spanning 2006-2008 and 2010-2011. Defibrillator tracings were used to calculate both components of the perishock pause (PSP) interval: the pre- (preSP) and the postshock pauses (postSP). RA and no-RA shock pauses were compared and independent associations between shock pause intervals, patient characteristics, and RA were assessed with the appropriate statistical tests. Analysis included 241 shocks from 101 cases. Forty-one cases (41%) had RA. RA vs. no-RA median (interquartile range) shock pauses in seconds were: preSP 13.5 (6.0-18.0) vs. 15.0 (10.9-21.5) (p = 0.121); postSP 6.0 (3.5-8.2) vs. 8.7 (4.5-13.9) (p = 0.053); and PSP 18.0 (12.3-24.0) vs. 24.0 (16.7-30.2) (p = 0.022). Considering all possible shock pause durations, shock pause lengths and various patient characteristics were not associated with RA. If 30 s or shorter, the preSP (odds ratio [OR] 0.90, 955 confidence interval [CI] 0.82-0.98) and postSP (OR 0.89, 95% CI 0.79-0.99) were related to RA. Shock pause length was inversely associated with RA when shock pause intervals were limited to 30 s or less. Shock pauses and RA were not associated when all durations of shock pauses were considered.


External Validation of the Simplified Preoperative Assessment for Low-Grade Mucinous Adenocarcinoma of the Appendix.
MD Anderson Cancer Center developed a computed tomography (CT)-based preoperative assessment tool simplified preoperative assessment for appendix tumor (SPAAT) for predicting incomplete cytoreduction (IC) in low-grade mucinous adenocarcinoma (LGMA) of the appendix, based on preoperative CT scans. This study independently evaluates the tool's performance. Seventy-six preoperative CT scans of LGMA patients were evaluated by two surgeons unfamiliar with the patients' medical history. Scores were assigned based on SPAAT criteria, with a SPAAT ≥3 predictive of IC. Binary regression analyses and area under the receiver operating characteristic (AUROC) curve analyses were performed. Patients with splenic resection were excluded due to the structure of the SPAAT assessment tool. Seventy-six LGMA patients underwent attempted cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Of 68 patients, 58 had complete cytoreduction and 10 had IC; 8 patients were ineligible due to prior splenectomy. The mean SPAAT score was 0.8, with six patients having SPAAT scores ≥3. SPAAT scores ≥3 were predictive of IC, with a hazard ratio (HR) of 19 (95% confidence interval 2.8-124.1) (p = 0.002). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were 40, 97, 50, and 90%, respectively. A SPAAT score ≥3 was not associated with worse survival prognosis. Median follow-up was 2.4 years and AUROC curve was 71%. SPAAT components with respective HR and p-values were foreshortening of the bowel mesentery (29.5; p = 0.004), and scalloping of the pancreas (9; p = 0.008), spleen (4.3; p = 0.04), portal vein (3.1; p = 0.4), and liver (2.1; p = 0.3). A SPAAT score ≥3 predicted IC based on a binary regression model. The clinical value of this score is controversial due to low sensitivity and PPV.


Laparoscopy versus laparotomy in management of abdominal trauma.
A majority of abdominal injuries (AIs) are associated with shock, hence most of the patients are hemodynamically unstable, which limits the use of video-assisted laparoscopy (VAL) in their management. The purpose of this study is to demonstrate the possibility of using VAL in management of stable and unstable patients with abdominal trauma. In a period of six years 2,695 patients with AIs were evaluated. The subjects were evaluated retrospectively and divided into two groups. Group 1, consisting of 1,363 patients, had conventional routine investigations following which they underwent laparotomy for confirmatory diagnosis and definitive management. The second group, consisting of 1,332 patients, underwent diagnostic laparoscopy in addition to the conventional investigations in the first group; 411 patients of this group had therapeutic laparoscopy. Demographic information, incidence of organs injuries and operative findings, success rate of VAL and laparotomy repair, complications, associated injuries, and hospital mortality were evaluated. The age of 62.6% of our patients was 20-50 years, while 10.6% and 14.5% were less than 19 and greater than 50 years, respectively. Associated injuries were head, chest, musculoskeletal, and vertebral column. Most of the victims presented with shock; 50.7%, 24.7%, and 15.9% of the patients were in mild, moderate, and severe shock respectively, and 8.7% of the subjects had stable hemodynamic status. In the first group 47.1% of the laparotomies were absolutely indicated and 24.4% were negative. Of the patients who had laparotomy, 26.0% would have been managed confidently by VAL. In the second group following VAL 42.5% of the patients did not require surgical intervention. VAL surgery was performed in 30.8% of patients. Conversion to laparotomy was performed in 26.7% of the patients. The VAL technique can be confidently used as a main tool to expedite evaluation and treatment of patients with abdominal trauma in cases of both stable and unstable hemodynamic status.


[Spasm of the adductor muscles, pre-dislocation and dislocations of the hip joints in children and adolescents with cerebral palsy. Clinical observations on aetiology, pathogenesis, therapy and rehabilitation. Part I: The effect of open myotenotomy of the gracilis muscle and of the long and short adductor muscles in connection with total extrapelvine resection of the obturator nerve, on the hip joints and static function (author's transl)].
Spasm and contraction of the adductor muscles involve, on the one hand, danger in respect of the development of a dislocation of the hip, and are a serious impediment to a walking ability on the other. Hence, surgery is often necessary. The article reports on the results of consequent weakening of the adductor muscles as a result of open myotenotomy in association with complete extrapelvine resection of the obturator nerve. 27 patients were subjected to surgery--in most cases bilaterally--at an age between 2 years and 5 months and 18 years, with a follow-up period of up to 15 years. The study does not include patients with spastic dislocation of the hip in whom this method was applied on the non-dislocated side and on the dislocated side in combination with iliopsoas tenotomy. This method makes it possible to achieve regression of existing defective positions of the hip joints. In a few cases, the valgus position of the neck of the femur was corrected to some extent. In two patients it was not possible to prevent the progress of a developing dislocation of the hip. These results show that, whereas the adductor muscles represent an essential factor for the occurrence of a spastic dislocation of the hip, other forces are most probably also involved. In the majority of cases, results were favourable in respect of the static function, although in some cases the success became evident after several years only, especially in mentally retarded patients and in apathetic individuals. Important for therapeutic success is the follow-up. The principles of its therapy are thoroughly discussed. Surgery is indicated only in special cases. Indications must be observed very strictly, since the risk of excessive weakening of the adductor muscles should not be underestimated.


Two decades of proteomics in Latin America: a personal view.
Proteomics is the charming young daughter of classical protein chemistry. It was conceived in 1975, year of invention of the first proteomic technique, the procedure to separate Escherichia coli and mouse tissue proteins in a two-dimensional polyacrylamide gel. Pregnancy, however, lasted for over 10years and deliverance occurred together with sister protein mass spectrometry. Jointly, the two techniques changed protein chemistry moving it from the study of single molecular entities to whole cell extracts and fluids. This review does not propose to report state-of-the art in proteomics in Latin America but rather to describe its development with emphasis on leading Brazil and Cuba as well as discuss proteomic research in these and other countries exposing the history and stories of researchers and selected laboratories that contributed to its establishment and development in the last 20years. This manuscript accounts for the fact that proteomics was present in Latin America since its birth. However, because the political and the economic situation in the region during the eighties and nineties were not favorable for science expansion, its beginning was shy. This changed at the dawn of the 21st century in such a way that a Latin American country, Brazil, became number 10 in manuscripts published in high impact journals as the Journal of Proteomics and Proteomics in 2012/2013. Interestingly, actual prevailing research themes come from centenary protein areas of study - e.g. neglected diseases - that quickly migrated from classical protein chemistry to proteomics, especially human parasites and snake, scorpion and spider venoms. This article is part of a Special Issue entitled: "20years of Proteomics" in memory of Viatliano Pallini" Guest Editors: Luca Bini, Juan J. Calvete, Natacha Turck, Denis Hochstrasser and Jean-Charles Sanchez.


Arixanthomycins A-C: Phylogeny-guided discovery of biologically active eDNA-derived pentangular polyphenols.
Soil microbiomes are a rich source of uncharacterized natural product biosynthetic gene clusters. Here we use short conserved biosynthetic gene sequences (natural product sequence tags) amplified from soil microbiomes as phylogenetic markers to correlate genotype to chemotype and target the discovery of novel bioactive pentangular polyphenols from the environment. The heterologous expression of an environmental DNA-derived gene cluster (the ARX cluster), whose ketosynthase beta (KSβ) sequence tag was phylogenetically distinct from any known KSβ sequence, led to the discovery of the arixanthomycins. Arixanthomycin A (1) exhibits potent antiproliferative activity against human cancer cell lines.