Reduced physical activity level was associated with poorer quality of life during the early phase of the COVID-19 pandemic: a sub-study of the last-long trial.
To assess how physical activity levels changed in a stroke cohort during the COVID-19 (SARS-CoV-2) pandemic, and how these changes were associated with quality of life (QoL). Between March and July 2021, 150 patients with stroke already included in the Life after Stroke (LAST-long) trial in Norway were invited to participate in this cross-sectional survey. Participants were asked to complete a questionnaire assessing changes in physical activity and self-reported health following the pandemic. Univariate and multivariate logistic regression analyses were used to explore the association between physical activity, loneliness, mental health, social activity and QoL. In all, 118 (79%) participants completed the questionnaire. A total of 80 (68%) reported less physical activity, 46 (39%) felt lonelier, and 43 (37%) reported worse mental health, while 50 (42%) reported reduced QoL compared with before the lockdown. In the univariate analyses less physical activity, feeling lonelier and changes in mental health were associated with reduced QoL. In the multivariate analysis only less physical activity odds ratio (OR) = 4.04 (95% confidence interval (95% CI) 1.44-11.34, p = 0.008) was significantly associated with reduced QoL. More than two-thirds of patients with stroke reported reduced physical activity during the COVID-19 pandemic, and less physical activity was strongly associated with reduced QoL.


Outcome and complications of living donor pediatric renal transplantation: Experience from a tertiary care center.
We retrospectively reviewed the patient characteristics, outcome, and complications of renal transplantation in pediatric age group performed at our center and compared the results with various centers in India and other developed countries. Patients younger than eighteen years of age who underwent renal transplantation from 2003 to 2014 at our institute were reviewed. Demographic data of the transplant recipients and donors, etiology of ESRD, mode of dialysis, surgical details of renal transplantation, immunosuppression, medical and surgical complications, and post-transplant follow-up were assessed. Graft survival was determined at 1, 3 and 5 years post-transplant. All data collected were entered into Microsoft excel program and analyzed using SPSS 20. Kaplan-Meier method was applied to determine the graft survival at 1, 3, and 5 years. The log-rank test was applied to test the statistical significance of the difference in survival between groups. Thirty-two children underwent transplantation comprising of 18 females and 14 males. The mean age was 14.5 years (range 10-17 years). The primary cause of renal failure was glomerular diseases in 53% (17/32) of patients. Seventeen postsurgical complications were noted in our series. Two grafts were lost over a follow-up of 5 years. The 1, 3, and 5 year graft survival rates were 96.7%, 92.9%, and 85%, respectively. There was no mortality. The etiology of ESRD in our region is different from that of developed countries. The mean age at which children undergo renal transplantation is higher. Graft survival at our center is comparable to that of developed nations. Renal transplantation can be safely performed in children with ESRD.


Wider aspects of veterinary public health.
The field of public health work covered by the Veterinary Branch of the Johannesburg City Health Department is described. This comprises meat hygiene, milk hygiene and the investigation of zoonoses. Meat hygiene embraces hygienic control of wholesale meat premises and inspection of meat imported into the municipal area. Results of the bacterial monitoring of premises and the mass of meat inspected and condemned are given. Inspection of dairy herds, diseases monitored by laboratory tests and other aspects of milk hygiene are discussed. Zoonosis control includes the investigation of unusual animal behaviour and mortality. In carrying out this work the Branch co-operates closely with the Laboratory and Technical Services and Environmental Health Branches of the City Health Department.


Harnessing regulatory T cells to suppress asthma: from potential to therapy.
Regulatory T cells (Tregs) play an essential role in maintaining the homeostatic balance of immune responses. Asthma is an inflammatory condition of the airways that is driven by dysregulated immune responses toward normally innocuous antigens. Individuals with asthma have fewer and less functional Tregs, which may lead to uncontrolled effector cell responses and promote proasthmatic responses of T helper type 2, T helper 17, natural killer T, antigen-presenting, and B cells. Tregs have the capacity to either directly or indirectly suppress these responses. Hence, the induced expansion of functional Tregs in predisposed or individuals with asthma is a potential approach for the prevention and treatment of asthma. Infection by a number of micro-organisms has been associated with reduced prevalence of asthma, and many infectious agents have been shown to induce Tregs and reduce allergic airways disease in mouse models. The translation of the regulatory and therapeutic properties of infectious agents for use in asthma requires the identification of key modulatory components and the development and trial of effective immunoregulatory therapies. Further translational and clinical research is required for the induction of Tregs to be harnessed as a therapeutic strategy for asthma.


Impact of genetic polymorphisms on adenoma recurrence and toxicity in a COX2 inhibitor (celecoxib) trial: results from a pilot study.
Chemoprevention trials have shown that celecoxib reduces adenoma recurrence but can cause cardiovascular toxicity. In this pilot study, we evaluated associations between genetic variation in several candidate pathways (e.g. prostaglandin synthesis) and adenoma recurrence and cardiovascular and gastrointestinal toxicities. Genotyping analysis was carried out on 117 Israeli colorectal adenoma patients who participated in the Prevention of Colorectal Sporadic Adenomatous Polyps trial. Reassessment followed after 3 years on celecoxib and after 2 years from termination of treatment with celecoxib. Efficacy (absence of colorectal adenomas) was measured by colonoscopy at years 1, 3, and 5. Toxicities were assessed by investigators during celecoxib treatment and by self-report post-treatment. A linkage disequilibrium-based selection algorithm (r2≥0.90, MAF≥4%) identified 255 tagSNPs in 25 analyzed candidate genes. Genotyping was performed by using Illumina GoldenGate technology. Multiple genetic variants were associated with adenoma recurrence and toxicity. Genetic variability in COX1, COX2, and ALOX12/15 genes played a role in adenoma recurrence, particularly among patients on placebo. More gene variants (especially variants in PGES, CRP, SRC, and GPX3) were associated with increased risk for cardiovascular toxicity and symptoms, compared with gastrointestinal toxicity and symptoms. The increased risk for cardiovascular toxicity/symptoms associated with the SRC gene variants (rs6017996, rs6018256, rs6018257) ranged from 6.61 (95% confidence interval 1.66-26.36, P<0.01) to 10.71 (95% confidence interval 1.96-58.60, P<0.01). Genetic polymorphisms in multiple inflammation-related genes appear to interact with celecoxib on adenoma recurrence and its attendant toxicity, particularly cardiovascular toxicity/symptoms. Larger studies validating these pharmacogenetic relationships are needed.


[Genetic vulnerability of methamphetamine dependence].
Methamphetamine (METH) dependence show strong familial and genetic influences in family and twin studies. METH exerts its reinforcing effects by modulating monoaminergic transmission, of which dopamine is supposed to be important. Previously, experimental animals were being used to identify mechanisms of action of METH that are related to its abuse and toxicity, and genetic mouse models have also been used to define genes that may predict risk for the development of drug addiction. We found that genetic variances of dopamine transporter, dopamine receptor, micro-opioid receptor, serotonin 1A receptor, serotonin 6 receptor, and adenosine 2A adenosine receptor could be vulnerability factors for METH dependence or psychosis in the Japanese population. Genetic analysis with a genome-wide association study (GWAS)-based approach has been successful for investigating the genetic influences of METH dependence and other complex features. Collaborative studies with JGIDA and NIDA/NIH have obtained the results that the genetic vulnerability to METH dependence contributes to other major drug addiction. The genetic studies for METH dependence might help to identify the risk of individuals and to develop treatments that take advantage of individual genetic information in the future.


Vibro-acoustography and multifrequency image compounding.
Vibro-acoustography is an ultrasound based imaging modality that can visualize normal and abnormal soft tissue through mapping the acoustic response of the object to a harmonic radiation force at frequency Δf induced by focused ultrasound. In this method, the ultrasound energy is converted from high ultrasound frequencies to a low acoustic frequency (acoustic emission) that is often two orders of magnitude smaller than the ultrasound frequency. The acoustic emission is normally detected by a hydrophone. Depending on the setup, this low frequency sound may reverberate by object boundaries or other structures present in the acoustic paths before it reaches the hydrophone. This effect produces an artifact in the image in the form of gradual variations in image intensity that may compromise image quality. The use of tonebursts with finite length yields acoustic emission at Δf and at sidebands centered about Δf. Multiple images are formed by selectively applying bandpass filters on the acoustic emission at Δf and the associated sidebands. The data at these multiple frequencies are compounded through both coherent and incoherent processes to reduce the acoustic emission reverberation artifacts. Experimental results from a urethane breast phantom are described. The coherent and incoherent compounding of multifrequency data show, both qualitatively and quantitatively, the efficacy of this reverberation reduction method. This paper presents theory describing the physical origin of this artifact and use of image data created using multifrequency vibro-acoustography for reducing reverberation artifacts.


Emerging Infection with Elizabethkingia Meningoseptica in Neonate. A Case Report.
Elizabethkingia meningoseptica are Gram-negative rod bacteria which are commonly found in the environment. The bacteria have also been associated with nosocomial infections, having been isolated on contaminated medical equipment, especially in neonatal wards. Here, we present the case of a premature female infant born at 33 weeks' gestational age, with neonatal meningitis. The onset was marked by fever, in the 5th day of life, while in the Neonatal Intensive Care Unit. The patient was commenced on Gentamicin and Ampicillin, but her clinical condition worsened. Psychomotor agitation and food refusal developed in the 10th day of life, and a diagnosis of bacterial meningitis was made based on clinical and cerebrospinal fluid findings. A strain of Elizabethkingia meningoseptica sensitive to Vancomycin, Rifampicin and Clarithromycin was isolated from cerebrospinal fluid. First-line antibiotic therapy with Meropenem and Vancomycin was adjusted by replacing Meronem with Piperacillin/Tazobactam and Rifampicin. The patient's clinical condition improved, although some isolated febrile episodes were still present. The cerebrospinal fluid was normalized after 6 weeks of antibiotic treatment, although periventriculitis and tetraventricular hydrocephalus were revealed by imaging studies. Neurosurgical drainage was necessary. Elizabethkingia meningoseptica can cause severe infection, with high risk of mortality and neurological sequelae in neonates. Intensive care and multidisciplinary interventions are crucial for case management.


Impact of Exposure Uncertainty on the Association between Perfluorooctanoate and Preeclampsia in the C8 Health Project Population.
Uncertainty in exposure estimates from models can result in exposure measurement error and can potentially affect the validity of epidemiological studies. We recently used a suite of environmental models and an integrated exposure and pharmacokinetic model to estimate individual perfluorooctanoate (PFOA) serum concentrations and assess the association with preeclampsia from 1990 through 2006 for the C8 Health Project participants. The aims of the current study are to evaluate impact of uncertainty in estimated PFOA drinking-water concentrations on estimated serum concentrations and their reported epidemiological association with preeclampsia. For each individual public water district, we used Monte Carlo simulations to vary the year-by-year PFOA drinking-water concentration by randomly sampling from lognormal distributions for random error in the yearly public water district PFOA concentrations, systematic error specific to each water district, and global systematic error in the release assessment (using the estimated concentrations from the original fate and transport model as medians and a range of 2-, 5-, and 10-fold uncertainty). Uncertainty in PFOA water concentrations could cause major changes in estimated serum PFOA concentrations among participants. However, there is relatively little impact on the resulting epidemiological association in our simulations. The contribution of exposure uncertainty to the total uncertainty (including regression parameter variance) ranged from 5% to 31%, and bias was negligible. We found that correlated exposure uncertainty can substantially change estimated PFOA serum concentrations, but results in only minor impacts on the epidemiological association between PFOA and preeclampsia. Avanasi R, Shin HM, Vieira VM, Savitz DA, Bartell SM. 2016. Impact of exposure uncertainty on the association between perfluorooctanoate and preeclampsia in the C8 Health Project population. Environ Health Perspect 124:126-132; http://dx.doi.org/10.1289/ehp.1409044.


Longevity of an immunocontraceptive vaccine effect on fecundity in rats.
•Increases in human-wildlife conflicts alongside cultural shifts against lethal control methods are driving the need for alternative wildlife management tools such as fertility control. Contraceptive formulations suitable for oral delivery would permit broader remote application in wildlife species.•This study evaluated the contraceptive effect and immune response to two novel injectable immunocontraceptive formulations targeting the Gonadotropin Releasing Hormone (GnRH): MAF-IMX294 and MAF-IMX294P conjugates, both identified as having potential as oral contraceptives. The study also explored whether in multiparous species immunocontraceptives may either totally prevent reproduction or also affect litter size.•Female rats, chosen as a model species, were given three doses of either MAF-IMX294 or MAF-IMX294P to compare anti-GnRH immune response and reproductive output up to 310 days post-treatment.•Both formulations induced anti-GnRH antibody titres in 100% of rats and significantly impaired fertility compared to control animals. Following treatment with MAF-IMX294 and MAF-IMX294P 0 of 9 and 1 of 10 females respectively produced litters following the first mating challenge 45 days post-treatment, compared to 9 of 9 control animals.•Across the whole 310 day study period 7 of 9 females from the MAF-IMX294 group and 10 of 10 females in the MAF-IMX294P group became fertile, producing at least one litter throughout six mating challenges.•No significant differences were found between the two formulations in antibody titre response or duration of contraceptive effect, with an average time to first pregnancy of 166 days for MAF-IMX294 and 177 days for MAF-IMX294P for all females that became fertile.•Following treatment with MAF-IMX294 and MAF-IMX294P the first litter produced post-infertility in treated females was significantly smaller than in control animals. This indicates treatment with immunocontraceptives may induce an overall suppression of fecundity extending past an initial infertility effect. This increases the potential long-term impact of these immunocontraceptives in multiparous species such as commensal rodents.


Transit time kinetics in ordered and disordered vascular trees.
Imaging modalities exploit tracer-dilution methods to measure bulk haemodynamic parameters such as blood flow and volume at the level of the microcirculation. Here, we ask the question of whether the kinetics of a tracer can reveal morphological information about the vessels through which the tracers flow. The goal is to relate the acquired time-intensity characteristic to details of the vascular structure that lies below the imaging resolution. Two fractal vascular models are developed that represent organized 'kidney-like' and disorganized 'tumour-like' structures. The models are generated using simple rules of branching and fractal geometry in two dimensions. Blood flow and tracer kinetics are simulated using fundamental laws of haemodynamics. The flow conditions are matched in the two models. The fractal box dimensions of the kidney (D(B) = 1.67 +/- 0.01) and the tumour (D(B) = 1.80 +/- 0.01) vasculatures fall in the range given in the literature (D(B) = 1.61 +/- 0.06 and D(B) = 1.84 +/- 0.04, respectively). The tracer kinetic curves of the kidney and the tumour vasculatures have the same initial slope and final asymptote, corresponding to the same flow rate and vascular volume, but have different forms. The difference in the two curves is related to the distribution function of transit times of the vascular models, and is a consequence of the randomness introduced in vessel diameter and length. In principle, the form of the tracer kinetic curve from a contrast imaging study may offer information relating not only to vascular volume and flow rate, but also to the organization of a microvascular network.


Development of the breast cancer education and risk assessment program.
To provide a description of the inception and evolution of the Breast Cancer Education and Risk Assessment Program. Computerized database (e.g., Personal Family History Risk Assessment Model, Knowledge Assessment Tool, risk perception, evaluation form) and author experience. A total of 749 women participated in the group education and risk-assessment program from March 1999 through March 2002. Advanced practice nurses provided information about calculated risks, corrected misperceptions among participants, and highlighted options available to decrease breast cancer risk. Knowledge scores improved, and, in general, participants were very satisfied with the content and comprehensibility of the educational session. Results from the evaluation of the Breast Cancer Education and Risk Assessment Program suggest that group education is a viable and acceptable way to bring new advances in breast cancer prevention to large groups of women. The data sources support the conclusion that women can be effectively taught general breast cancer risk information in a group setting and be placed into specific risk categories to streamline discussion of risk-management options and relevant research studies. Advanced practice nurses are a vital link in the assessment of women at high risk for breast cancer, education, and appropriate referrals for management options and relevant clinical trials.


Hesionidae Grube, 1850 (Annelida: Polychaeta) from South-Southeastern Brazil, with descriptions of four new species.
On the basis of extensive intertidal and subtidal samplings in South-Southeastern Brazil, five hesionid species were found; four are newly described and Podarkeopsis levisfuscina Perkins, 1984 is redescribed. Micropodarke pleijeli n. sp. differs from the other species because it lacks eyes, and by having a large number of pharynx papillae and by neurochaetal features; this species differs from M. dubia (Hessle, 1925) by lacking eyes, having a pharynx with more papillae, and by the neurochaetal features. Syllidia amaralae n. sp. resembles more closely S. armata sensu Day, 1967 (non S. armata de Quatrefages, 1865) because both have dorsal and tentacular cirri annulated or moniliform, and 10-15 pharyngeal papillae. However, S. amaralae n. sp. specimens differ from Day's ones because they have a quadrangular prostomium, by the relative size and arrangement of eyes, and by a reduced number of chaetae which are disposed in two bundles; these features are consistent and present in juveniles and mature specimens. Neogyptis nonatoi n. sp. is distinguishable from the others by having four types of neurochaetae; this species resembles N. crypta (Pleijel, 1993), and N. plurisetis (Hilbig, 1992). It differs from N. crypta by having a few acicular notochaetae with blunt tip, a small number of compound neurochaetae, simple capillary neurochaetae distally curved, and much slender notopodial and neuropodial lobes. The new species also differs from N. plurisetis by having four types of neurochaetae instead of having only falciger chaetae; there are less pharyngean papillae and they are far apart to each other, conical and shorter in N. plurisetis when compared to those of N. nonatoi n. sp., which are fringed, longer and closer among them, having some other longer lateral papillae. Oxydromus lanai n. sp. resembles O. obscurus (Verrill, 1873) as recorded by Uebelacker (1984), O. pugettensis by Hilbig (1994), O. guanicus by Hoagland (1919), and O. cf. guanicus by Hartman (1951). The pharynx of O. obscurus does not have fringe or papilla on its border, and it has two types of neurochaetae, differing from O. lanai n. sp. which has a single furcate notochaeta, with its shorter tine serrated. Oxydromus pugettensis and O. cf. guanicus also have usually two, instead of one, furcate notochaeta, differing from O. lanai n. sp. Oxydromus guanicus differs from our new species in having a characteristic pigmentation pattern, to be very large, its median antenna is less than one-third as long as lateral antennae, and its cirrophores are distally constricted producing a colorless ring, whereby the cirrostyle is inserted. These species are the first Brazilian records for the genera Podarkeopsis and Syllidia, and for Micropodarke, it is newly recorded from the Atlantic Ocean. Keys are included to identify hesionid genera and the species of Syllidia, Micropodarke, Neogyptis, and Podarkeopsis.


High Porosity in Nanostructured n-Type Bi2Te3 Obtaining Ultralow Lattice Thermal Conductivity.
Porous structure possesses full potentials to develop high-performance thermoelectric materials with low lattice thermal conductivity. In this study, the n-type porous nanostructured Bi2Te3 pellet is fabricated by sintering Bi2Te3 nanoplates synthesized with a facile solvothermal method. With adequate sublimations of Bi2TeO5 during the spark plasma sintering, homogeneously distributed pores and dense grain boundaries are successfully introduced into the Bi2Te3 matrix, causing strong phonon scatterings, from which an ultralow lattice thermal conductivity of <0.1 W m-1 K-1 is achieved in the porous nanostructured Bi2Te3 pellet. With the well-maintained decent electrical performance, a power factor of 10.57 μW cm-1 K-2 at 420 K, as well as the reduced lattice thermal conductivity, secured a promising zT value of 0.97 at 420 K, which is among the highest values reported for pure n-type Bi2Te3. This study provides the insight of realizing ultralow lattice thermal conductivity by synergistic phonon scatterings of pores and nanostructure in the n-type Bi2Te3-based thermoelectric materials.


Eye movement abnormalities during reading in patients with Alzheimer disease.
This goal of this study was to evaluate reading ability by assessing eye movements during reading among patients with Alzheimer disease (AD) compared with normal elderly controls. Reading is disturbed in patients with AD. These patients may have changes in reading ability early in the course of their disease before clinical alexia or abnormalities are apparent on standard reading tasks. Reading competence was evaluated by recording eye movements during reading in 14 patients with mild to moderate clinically probable AD and 14 age- and education-matched controls. All patients with AD could recognize letters and words and could understand written material of similar difficulty. Despite successful reading comprehension among the patients with AD, their oculographs showed slowed reading and irregular eye movements. Compared with controls, the patients with AD did not differ in saccadic duration; however, they had significantly longer fixation times, more forward saccades per line of text, and more saccadic regressions. In addition, increased reading difficulty significantly correlated with a scale of dementia severity in the patients with AD. This pattern of eye movements corresponds to increased text difficulty and probably represents difficulty with lexical-semantic access in AD. These results suggest that disordered eye movements can signal difficulties in reading ability in AD even before complaints of reading difficulty or abnormalities on reading tests and may be a means of identifying linguistic impairment early in this disorder.


Efficacy of a Parent-Implemented Pivotal Response Treatment for Children with Autism Spectrum Disorder.
Pivotal response treatment (PRT) is a well-established intervention addressing core symptoms of autism spectrum disorder (ASD), with parent involvement as a key component. The current study aimed to examine the effects of PRT parent training on parent fidelity and provide descriptive analyses of parent-child interactions before and after parent training. It also probed parental acceptance and satisfaction with the program. A concurrent multiple baseline design across participants was used to evaluate the effectiveness of the parent training program. Four parents (range 32-47 years old) and their children with ASD participated in the study. The intervention comprised 12 one-on-one parent training sessions over six consecutive weeks. The visual analysis and effect size calculation (Tau-U) were used to evaluate functional relationship between independent and dependent variables. The descriptive analysis was used to analyze parent-child interaction data. The findings reveal that all parents learned and maintained PRT with a high level of fidelity, they also enhanced awareness to create more opportunities for interactions during free play, and the parents were very satisfied with the program. The results also indicate that the six-week parent training program is effective in teaching parents to implement PRT with their children. These results suggest that the parent training program may be a promising treatment model that is effective, efficient, and cost-effective. Implications for future research and practice are then discussed.


Multi-parametric MRI characterization of healthy human thigh muscles at 3.0 T - relaxation, magnetization transfer, fat/water, and diffusion tensor imaging.
Muscle diseases commonly have clinical presentations of inflammation, fat infiltration, fibrosis, and atrophy. However, the results of existing laboratory tests and clinical presentations are not well correlated. Advanced quantitative MRI techniques may allow the assessment of myo-pathological changes in a sensitive and objective manner. To progress towards this goal, an array of quantitative MRI protocols was implemented for human thigh muscles; their reproducibility was assessed; and the statistical relationships among parameters were determined. These quantitative methods included fat/water imaging, multiple spin-echo T2 imaging (with and without fat signal suppression, FS), selective inversion recovery for T1 and quantitative magnetization transfer (qMT) imaging (with and without FS), and diffusion tensor imaging. Data were acquired at 3.0 T from nine healthy subjects. To assess the repeatability of each method, the subjects were re-imaged an average of 35 days later. Pre-testing lifestyle restrictions were applied to standardize physiological conditions across scans. Strong between-day intra-class correlations were observed in all quantitative indices except for the macromolecular-to-free water pool size ratio (PSR) with FS, a metric derived from qMT data. Two-way analysis of variance revealed no significant between-day differences in the mean values for any parameter estimate. The repeatability was further assessed with Bland-Altman plots, and low repeatability coefficients were obtained for all parameters. Among-muscle differences in the quantitative MRI indices and inter-class correlations among the parameters were identified. There were inverse relationships between fractional anisotropy (FA) and the second eigenvalue, the third eigenvalue, and the standard deviation of the first eigenvector. The FA was positively related to the PSR, while the other diffusion indices were inversely related to the PSR. These findings support the use of these T1 , T2 , fat/water, and DTI protocols for characterizing skeletal muscle using MRI. Moreover, the data support the existence of a common biophysical mechanism, water content, as a source of variation in these parameters.


When hurt will not heal: exploring the capacity to relive social and physical pain.
Recent discoveries suggest that social pain is as real and intense as physical pain, and that the social-pain system may have piggybacked on the brain structure that had evolved earlier for physical pain. The present study examined an important distinction between social and physical pain: Individuals can relive and reexperience social pain more easily and more intensely than physical pain. Studies 1 and 2 showed that people reported higher levels of pain after reliving a past socially painful event than after reliving a past physically painful event. Studies 3 and 4 found, in addition, that people performed worse on cognitively demanding tasks after they relived social rather than physical pain. Implications for research on social pain and theories about social pain are discussed.


Integrative characterization of G-Quadruplexes in the three-dimensional chromatin structure.
DNA molecules are highly compacted in the eukaryotic nucleus where distal regulatory elements reach their targets through three-dimensional chromosomal interactions. G-quadruplexes, stable four-stranded non-canonical DNA structures, can change local chromatin organization through the exclusion of nucleosomes. However, the relationship between G-quadruplexes and higher-order genome organization remains unknown. Here, we found that G-quadruplexes are significantly enriched at boundaries of topological associated domains (TADs). Architectural protein occupancy, which plays critical roles in the formation of TADs, was highly correlated with the content of G-quadruplexes at TAD boundaries. Moreover, adjacent boundaries containing G-quadruplexes frequently interacted with each other because of the high enrichment of architectural protein binding sites. Similar to CCCTC-binding factor (CTCF) binding sites, G-quadruplexes also showed strong insulation ability in the separation of adjacent regions. Additionally, the insulation ability of CTCF binding sites and TAD boundaries was significantly reinforced by G-quadruplexes. Furthermore, G-quadruplex motifs on different strands were associated with the orientation of CTCF binding sites. These findings suggest a potential role for G-quadruplexes in loop extrusion. The enrichment of transcription factor binding sites (TFBSs) around regulatory elements containing G-quadruplexes led to frequent interactions between regulatory elements containing G-quadruplexes. Intriguingly, more than 99% of G-quadruplexes overlapped with TFBSs. The binding sites of CTCF and cohesin proteins were preferentially located surrounding G-quadruplexes. Accordingly, we proposed a new mechanism of long-distance gene regulation in which G-quadruplexes are involved in distal interactions between enhancers and promoters.


DAF-16/FOXO regulates homeostasis of essential sleep-like behavior during larval transitions in C. elegans.
Sleep homeostasis, which refers to the maintenance of sleep amount or depth following sleep deprivation, indicates that sleep and sleep-like states serve fundamental functions that cannot be bypassed [1]. Homeostasis of sleep-like behavior is observed during C. elegans lethargus, a 2-3 hr behavioral quiescent period that occurs during larval state transitions [2]. Here, we report a role for DAF-16/FOXO, a transcription factor that is active under conditions of stress [3], in the response to deprivation of lethargus quiescence. Forced locomotion during lethargus results in nuclear translocation of DAF-16. The formation of dauer larvae, a developmental state promoted by daf-16, is increased in response to quiescence deprivation. daf-16 mutants show an impaired homeostatic response to deprivation of lethargus quiescence and are hypersensitive to the lethal effects of forced locomotion during lethargus. DAF-16 expression in muscle cells, but not in neurons, is sufficient to restore a homeostatic response to deprivation of quiescence, pointing to a role for muscle in sleep homeostasis. These findings are relevant to clinical observations of altered metabolic signaling in response to sleep deprivation and suggest that these signaling pathways may act in nonneuronal tissue to regulate sleep behaviors.


Roles for T and NK cells in the innate immune response to Shigella flexneri.
Shigella flexneri, an enteroinvasive Gram-negative bacterium, is responsible for the worldwide endemic form of bacillary dysentery. The host response to primary infection is characterized by the induction of an acute inflammation, which is accompanied by polymorphonuclear cell (PMN) infiltration, resulting in massive destruction of the colonic mucosa. However, PMN play a major role in the recovery from primary infection, by restricting the bacterial infection at the intestinal mucosa. In this study, we assessed the roles for T and NK cells in the control of primary S. flexneri infection, using an alymphoid mouse strain (Rag null gamma(c) null) devoid of B, T, and NK cells. Using the mouse pulmonary model of Shigella infection, we showed that alymphoid Rag null gamma(c) null mice were highly susceptible to S. flexneri infection in comparison with wild-type (wt) mice. Whereas PMN recruitment upon infection was similar, macrophage recruitment and production of proinflammatory cytokines were significantly decreased in Rag null gamma(c) null mice compared with wt mice. Upon selective engraftment of Rag null gamma(c) null mice with polyclonal alphabeta T cells, but not with alphabeta T cells from IFN-gamma null , S. flexneri infection could be subsequently controlled. Rag null mice devoid of B and T cells but harboring NK cells could control infection. Local IFN-gamma production by T and NK cells recruited to the lung was demonstrated in S. flexneri-infected wt mice. These data demonstrate that both alphabeta T cells and NK cells contribute to the early control of S. flexneri infection through amplification of an inflammatory response. This cellular lymphocyte redundancy assures IFN-gamma production, which is central to innate immunity against Shigella infection.


The Biopsychosocial Model of Low Back Pain and Patient-Centered Outcomes Following Lumbar Fusion.
Lumbar fusion is a surgical procedure performed to eliminate painful motion in a spinal segment by joining, or fusing, two or more vertebrae. Although the surgery has a high rate of producing radiographic fusion, many patients report pain, functional disability, an inability to return to work, and prolonged opioid pain reliever use following the procedure. Using the biopsychosocial model of low back pain as a framework, this review of the literature describes the biological, psychological, and social factors that have been associated with these negative outcomes. The findings suggest that at least some of the variability in postoperative outcomes may be due to preoperative patient characteristics, and evidence the theorized relationship between biopsychosocial factors and low back disability. The review also highlights a gap in the literature regarding biopsychosocial predictors of prolonged opioid use following lumbar fusion.


Titanium nanoparticles fate in small-sized watersheds under different land-uses.
Surface waters from three catchments having contrasting land-uses (forested, agricultural, and urban) were sampled monthly and analysed for nanoparticulate titanium dioxide (NPs-TiO2) by single particle ICPMS and electron microscopy. We report one-year of data for NPs-TiO2 having average number and mass concentrations of 9.1 × 108 NPs-TiO2 particles L-1 and 11 µg NPs-TiO2 L-1 respectively. An increase in concentration during warmer months is observed in the forested and agricultural catchments. Both concentrations of NPs-TiO2 are within the range of recently reported values using similar analytical approaches. The positive correlations for NPs-TiO2 mass concentration or particle number with the concentration of some trace elements and DOC in the forested and agricultural catchments suggest the detected NPs-TiO2 in these two systems are mostly from geogenic origin. Additionally, microscopy imaging confirmed the presence of NPs in the three catchments. Furthermore, the land-area normalized annual flux of NPs-TiO2 (1.65 kg TiO2 year-1 km-2) was highest for the agricultural catchment, suggesting that agricultural practices have a different impact on the NPs-TiO2 dynamics and exports than other land-uses (urban or forestry). A similar trend is also found by the reanalysis of recent literature data.


Transport studies and enzyme assays in mice infected with human Giardia lamblia.
It is well established that Giardia infection causes malabsorption. However, the precise mechanism of such a malabsorption is not known. To investigate this, transport studies, using the tissue accumulation technique, were carried out in mice infected with G. lamblia obtained from human stools. There was a significant fall in the transport of D-glucose, L-alanine and glycine in the infected animals compared with the controls. Kinetics of the D-glucose and glycine transport system were examined by measuring the tissue uptake in the presence of different concentrations of the substrate. For glucose, the affinity constant (Km) for the transport site was the same (4 . 37mM) in normal and infected animals but the maximal transport rate (V max) was considerably reduced in infected animals (158 . 7 mu moles/hr/g tissue) compared with (357 . 1 microgram moles/hr/g tissue) in controls. Results with glycine were similar; the Km was similar in control and infected animals (5 . 7 mM) whereas the V max was reduced in infected animals (27 . 02 microgram moles/hr/g tissue) compared with controls (45 . 5 micrograms moles/hr/g tissue). Analysis of the intestinal enzymes showed a significant decrease in the levels of brush border sucrase, lactase and alkaline phosphatase in infected animals; the cellular enzymes, LDH, GOT and GPT remained unaffected. The observed aberrations in the transport functions and brush border enzymes suggest that G. lamblia causes malabsorption by damaging the epithelial membrane of the enterocyte.


Access to kidney transplantation: outcomes of the non-referred.
There is a concern that some, especially older people, are not referred and could benefit from transplantation. We retrospectively examined consecutive incident end stage renal disease (ESRD) patients at our center from January 2006 to December 2009. At ESRD start, patients were classified into those with or without contraindications using Canadian eligibility criteria. Based on referral for transplantation, patients were grouped as CANDIDATE (no contraindication and referred), NEITHER (no contraindication and not referred) and CONTRAINDICATION. The Charlson Comorbidity Index (CCI) was used to assess comorbidity burden. Of the 437 patients, 133 (30.4%) were CANDIDATE (mean age 50 and CCI 3.0), 59 (13.5%) were NEITHER (age 76 and CCI 4.4), and 245 (56.1%) were CONTRAINDICATION (age 65 and CCI 5.5). Age was the best discriminator between NEITHER and CANDIDATES (c-statistic 0.96, P <0.0001) with CCI being less discriminative (0.692, P <0.001). CANDIDATES had excellent survival whereas those patients designated NEITHER and CONTRAINDICATION had high mortality rates. NEITHER patients died or developed a contraindication at very high rates. By 1.5 years 50% of the NEITHER patients were no longer eligible for a transplant. There exists a relatively small population of incident patients not referred who have no contraindications. These are older patients with significant comorbidity who have a small window of opportunity for kidney transplantation.


Local reputation, local selection, and the leading eight norms.
Humans are capable of solving cooperation problems following social norms. Social norms dictate appropriate behaviour and judgement on others in response to their previous actions and reputation. Recently, the so-called leading eight norms have been identified from many potential social norms that can sustain cooperation through a reputation-based indirect reciprocity mechanism. Despite indirect reciprocity being claimed to extend direct reciprocity in larger populations where direct experiences cannot be accumulated, the success of social norms have been analysed in models with global information and evolution. This study is the first to analyse the leading eight norms with local information and evolution. We find that the leading eight are robust against selfish players within most scenarios and can maintain a high level of cooperation also with local information and evolution. In fact, local evolution sustains cooperation under a wider set of conditions than global evolution, while local reputation does not hinder cooperation compared to global reputation. Four of the leading eight norms that do not reward justified defection offer better chances for cooperation with quick evolution, reputation with noise, larger networks, and when unconditional defectors enter the population.


Circumstances and consequences of falls among people with chronic stroke.
Falls are common after stroke; however, circumstances and consequences are relatively unknown. Our objectives were to identify the differences between fallers and non-fallers among people with chronic stroke, identify the circumstances of fall events, and examine the consequences of the falls. This is a secondary data analysis; all participants included sustained a stroke. Variables included demographics, stroke characteristics, and comorbidities. Falls were collected via self-report, and circumstances and consequences were derived from participant description of the event and categorized as appropriate. Among 160 participants, 53 (33%) reported a fall during the 1 yr period. Circumstances of falls were categorized as intrinsic or extrinsic. Location and circumstance of the fall were included: 70% occurred at home and 40% were associated with impaired physical or mental state (e.g., inattention to tying shoes). Additionally, 21% of falls were associated with activities of daily living and mobility and 34% with slips or trips. The majority who fell sustained an injury (72%). Injuries ranged from bruising to fractures, and 55% of those with an injury sought medical care (32% to emergency department). Poststroke falls are associated with an alarming rate of injury and healthcare utilization. Targeting mental and physical states may be key to fall prevention.


Reinnervation of muscle fiber types in the newborn rat soleus.
We have examined the selectivity of reinnervation of fiber types in rat soleus muscle denervated by crush of the soleus nerve 2 d after birth. The fibers innervated by single, regenerated motor axons were identified by use of glycogen depletion approximately 2 weeks following denervation. The types of fibers were determined by immunohistochemistry employing anti-myosin antibodies and, in some cases, by myofibrillar ATPase staining. Two distinct types of fibers are present in soleus at 2 d and through the next 16 d of normal postnatal development. These fiber types are retained in a denervated muscle for the period of time required for reinnervation. Although 40% of the fibers are lost from the muscle during reinnervation, we find no evidence for interconversion of muscle fiber types. Nonetheless, 10 of the 12 single motor units examined had fiber type compositions that were markedly biased toward one or the other of these 2 types; the bias in these units could not be explained by chance reinnervation. On the basis of the topographical distribution of the muscle fibers in each of these units, the motor axons reinnervated a novel set of fibers. We interpret these findings to mean that neonatal soleus motor neurons reinnervate fiber types in a selective manner. This selective innervation may explain the bias in the fiber type composition of normal motor units during early postnatal development.


Maturation of the Human Intestinal Immune System Occurs Early in Fetal Development.
There are limited data on fetal and early life development of human intestinal immunity. Using mass cytometry (CyTOF) and next-generation sequencing of B and T cell receptor (BCR and TCR) repertoires, we demonstrate complex intestinal immunity from 16 weeks' gestational age (GA). Both BCR and TCR repertoires are diverse with CDRH and CDR3β length increasing with advancing GA. The difference-from-germline, CDR insertions and/or deletions, similarly occur in utero for TCR but not BCR, suggesting earlier mucosal T than B cell maturity. Innate immunity is dominated by macrophages, dendritic cells (DCs), innate lymphoid cells (ILCs), and natural killer (NK) cells. Follicular and transitional B cells are enriched in fetuses while CD69+IgM+ B cells are abundant in infants. Both CD4+ and CD8+ T cells are abundant, capable of secreting cytokines and are phenotypically of the tissue resident memory state in utero. Our data provide the foundation for a 2nd trimester and infant intestinal immune atlas and suggest that a complex innate and adaptive immune landscape exists significantly earlier than previously reported.


Osteopenia in alcoholics after tibia shaft fractures.
A marked reduction of 40-70% in regional bone mineral density (BMD) has been reported after fractures of long bones, and this post-traumatic osteopenia may to some extent persist for several years, perhaps lifelong. In this cross-sectional study, we investigated whether prolonged alcohol abuse had any effect on the degree of post-traumatic osteopenia after isolated tibia shaft fractures, the rationale for such a suspicion being the deranged bone metabolism found in alcoholics. We also wanted to investigate whether dual energy X-ray absorptiometry (DEXA) or quantitative ultrasound technique could detect differences between abusers and non-abusers in post-traumatic bone loss. We measured the BMD in 61 male patients with isolated tibia shaft fractures (1984-94) with the Lunar DPX-L and the Lunar Achilles. Twenty-four of the patients were verified to be high consumers of alcohol. After correction for differences in age and the time elapsed since the fracture event, we found significantly lower (11%; P = 0.017) BMD in the femoral neck of the fractured leg in abusers when utilizing the DEXA technique. No differences between abusers and non-abusers in BMD were detectable when using the ultrasound technique. We found a fair correlation (r = 0.63-0.81) between the DEXA and the ultrasound techniques in regions with spongious bone. Our findings suggest that alcohol abuse has some, albeit a limited, effect on the degree of post-traumatic osteopenia and that ultrasound measurements in the calcaneus are of little use in detecting an increased post-traumatic osteopenia in this patient group.


Finding genetic overlaps among diseases based on ranked gene lists.
To understand disease relationships in terms of their genetic mechanisms, it is important to study the common genetic basis among different diseases. Although discoveries on pleiotropic genes related to multiple diseases abound, methods flexibly applicable to various types of datasets generated from different studies or experiments are needed to gain big pictures on the genetic relationships among a large number of diseases. We develop a set of genetic similarity measures to gauge the genetic overlap between diseases, as well as several estimators of the number of overlapping disease genes between diseases. These methods are based on ranked gene lists so that they could be flexibly applied to different types of data. We first investigate the performance of the genetic similarity measure for evaluating the similarity between human diseases in simulation studies. Then we apply the method to diseases in the OMIM database. We show that our proposed genetic measure achieves superior performance in explaining phenotype similarities between diseases compared to simpler methods. Furthermore, we identified common genes underlying the genetic overlap between disease pairs. With an example of five vision-related diseases, we demonstrate how our methods can provide insights into the relationships among diseases based on their shared genetic mechanisms.


Epidemiological Study Assessing the Overuse of Proton Pump Inhibitors in Lebanese Population.
BACKGROUND Proton pump inhibitors (PPIs) are the most potent gastric agents for most acid-related disorders. Their effectiveness has led to their overutilization, leading to potential risks on patients and significant economic implications. The aim of this study was to determine the frequency of PPI overuse in Lebanon. Hence, the economic impact of this overutilization, if proven to be present, can be inferred. METHODS An epidemiological descriptive cross-sectional study was conducted in pharmacies all around Lebanese governorates over a 1-year period, using questionnaires handed out to 1000 participants coming to buy PPIs. Subjects taking PPIs for inappropriate indications or in inappropriate dosages or durations were considered abusing PPIs. PPIs are indicated for multiple gastric disorders and for prophylaxis of gastrointestinal injury when taking gastro-toxic medications. RESULTS 71.4% of subjects were overusing PPIs. Approximately 25 million US dollars were being wasted annually. Three categories of overuse were inferred (indication, dosage, and duration). Gastro protection was the most common reason for taking PPIs. Demographic variables and doctors' prescriptions did not influence PPI overuse. CONCLUSION PPIs are massively overused in Lebanon, leading to a huge burden on the health care system. Adhering to evidence-based guidelines and educational programs is highly recommended to enhance the quality and efficiency of prescriptions.


Improved hair restoration method for burns.
Extracted partial longitudinal follicular units can be used as complete follicular units to regenerate completely differentiated hair growth. The partial follicular units that remained in the dermis in the donor area can survive and produce hairs. This technique enables us to multiply hair follicles in vivo, while preserving the donor area and therefore is suitable in persons, who have a relative small donor area compared to the recipient area, as in scalp burns. With this study, we try to determine if partial longitudinal follicular unit transplantation (PL-FUT) can be used for facial and/or scalp burns. Four burn victims (age 22-39 years, mean 27.75 years) were treated in the face (eyebrows, and beard) and/or on the scalp with PL-FUT. The grafts were harvested with hollow wave-tipped needles with an inner diameter of 0.6mm from the occipital area of the scalp. The suitable longitudinal partial follicular units were impregnated with a preservative medium, and implanted into the recipient area. Hair growth in the donor area as well as the recipient area was observed before treatment, and at intervals of 1 week, 3 months and 1 year after the treatment. After evaluation of the donor area, sometimes a few little white spots were visible, but almost all hair follicles in the donor site re-produce hairs after 2 years. All treated patients had satisfactory or very satisfactory cosmetic results in the treated area. Longitudinal partial follicular unit transplantation (LP-FUT) may represent the first reliable patient-friendly method to generate two hair follicles from one hair follicle with consistent results and preservation of the donor area. Therefore, this method is very suitable for people with facial and/or scalp burns.


Synthesis, Structures, and Photophysical Properties of a Series of Rare Near-IR Emitting Copper(I) Complexes.
Herein, we report on the synthesis and structural characterization of a series of trigonal and tetrahedral cationic copper(I) complexes, bearing phosphine or N-heterocyclic carbene ligands as donors, with benzthiazol-2-pyridine (pybt) and benzthiazol-2-quinoline (qybt) acting as π-chromophores. The compounds are highly colored due to their 1MLCT (MLCT = metal-to-ligand charge transfer) states absorbing between ca. λabs = 400-500 nm, with 1ILCT (ILCT = intraligand charge transfer) states in the UV region. The relative shifts of the S0→S1 absorption correlate with the computed highest occupied molecular orbital-lowest unoccupied molecular orbital gaps, the qybt complexes generally being lower in energy than the pybt ones due to the larger conjugation of the quinoline-based ligand. The compounds exhibit, for CuI complexes, rare intense long-lived near-IR emission with λmax ranging from 593 to 757 nm, quantum yields of up to Φ = 0.11, and lifetimes τ of several microseconds in the solid state as well as in poly(methyl methacrylate) films. Although a bathochromic shift of the emission is observed with λmax ranging from 639 to 812 nm and the lifetimes are greatly increased at 77 K, no clear indication for thermally activated delayed fluorescence was found, leaving us to assign the emission to originate from a 3(Cu→pybt/qybt)MLCT state. The red to near-IR emission is a result of incorporation of the sulfur into the chromophore ligand, as related nitrogen analogues emit in the green to orange region of the electromagnetic spectrum. The photophysical results and conclusions have further been corroborated with density functional theory (DFT)/time-dependent DFT calculations, confirming the nature of the excited states and also the trends of the redox potentials.


Bactericidal activity in whole blood as a potential surrogate marker of immunity after vaccination against tuberculosis.
The development of new tuberculosis (TB) vaccines will require the identification of correlates of human protection. This study examined the balance between immunity and virulence in a whole blood infection model in which intracellular mycobacterial survival was measured using BACTEC. In the blood of tuberculin-negative donors, counts of Mycobacterium tuberculosis H(37)Ra organisms fell by 0.14 log(10) CFU during 96 h of whole blood culture, whereas counts of Mycobacterium bovis BCG, M. tuberculosis H(37)Rv, and a clinical TB isolate's organisms increased by 0.13, 0.43, and 1.04 log(10) CFU, respectively (P < 0.001), consistent with their relative virulence. Inhibition of tumor necrosis factor alpha by the addition of methylprednisolone or pentoxifylline or removal of CD4(+) or CD8(+) T cells by magnetic beads had deleterious effects on immune control of intracellular growth only in the blood of tuberculin-positive donors. Repeated vaccination of eight tuberculin-negative volunteers with M. bovis BCG resulted in a 0.3 log (50%) reduction in BCG CFU counts in the model compared to baseline values (P < 0.05). Three of the volunteers responded only after the second vaccination. These experiments indicate that whole blood culture may be used to measure immunity to M. tuberculosis and that further studies of repeated BCG vaccination are warranted.


Associations between bullying and engaging in aggressive and suicidal behaviors among sexual minority youth: the moderating role of connectedness.
Research on the extent to which cyberbullying affects sexual minority youth is limited. This study examined associations between experiencing cyber and school bullying and engaging in aggressive and suicidal behaviors among sexual minority youth. We also explored whether feeling connected to an adult at school moderated these associations. Data came from 951 self-identified lesbian, gay, and bisexual (LGB) youth, who completed the New York City Youth Risk Behavior Survey during fall 2009. We used multiple logistic regression to examine the hypothesized associations and test for effect modification. Cyber and school bullying were associated with engaging in aggressive and suicidal behaviors among LGB youth. Youth experiencing both cyber and school bullying had the greatest odds of engaging in aggressive and suicidal behaviors. However, feeling connected to an adult at school moderated these associations such that bullied youth who felt connected were not more likely to report aggressive and suicidal behaviors. The findings highlight the challenges faced by bullied LGB youth. Practitioners should work with school administrators to establish supportive environments for sexual minority youth. Helping victimized LGB youth develop meaningful connections with adults at school can minimize the negative impacts of cyber and school bullying.


Epidemiological survey of 214 families with bladder exstrophy-epispadias complex.
We sought to identify causative nongenetic and genetic risk factors for the bladder exstrophy-epispadias complex. A total of 237 families with the bladder exstrophy-epispadias complex were invited to participate in the study, and information was obtained from 214 families, mainly from European countries. Two families showed familial occurrence. Male predominance was found among all subgroups comprising epispadias, classic bladder exstrophy and cloacal exstrophy, with male-to-female ratios of 1.4:1, 2.8:1 and 2.0:1, respectively (p = 0.001). No association with parental age, maternal reproductive history or periconceptional maternal exposure to alcohol, drugs, chemical noxae, radiation or infections was found. However, periconceptional maternal exposure to smoking was significantly more common in patients with cloacal exstrophy than in the combined group of patients with epispadias/classic bladder exstrophy (p = 0.009). Only 16.8% of mothers followed the current recommendations of periconceptional folic acid supplementation, and 17.6% had started supplementation before 10 weeks of gestation. Interestingly, in the latter group mothers of patients with cloacal exstrophy were more compliant with folic acid supplementation than were mothers of the combined group of patients with epispadias/classic bladder exstrophy (p = 0.037). Furthermore, mothers of children with cloacal exstrophy knew significantly more often prenatally that their child would have a congenital malformation than did mothers of children with epispadias/classic bladder exstrophy (p <0.0001). Our study corroborates the hypothesis that epispadias, classic bladder exstrophy and cloacal exstrophy are causally related, representing a spectrum of the same developmental defect, with a small risk of recurrence within families. Embryonic exposure to maternal smoking appears to enforce the severity, whereas periconceptional folic acid supplementation does not seem to alleviate it. There is a disproportional prenatal ultrasound detection rate between severe and mild phenotypes, possibly due to the neglect of imaging of full bladders with a focus on neural tube defects.


Pectus patient information website has improved access to care and patient reported outcomes.
Pectus is the most common congenital disorder. Awareness amongst primary care physicians and the general public is poor. NHS commissioning bodies plan to withdraw funding for this surgery because they deem a lack of sufficient evidence of benefit. The purpose of this study is to assess the effects of introducing a patient information website on referral and activity patterns and on patients reported outcomes. We produced an innovative information website, www.pectus.co.uk , accessible to the general public, providing information about pectus deformities; management options and advice about surgery. Referral patterns and number of cases where studied before and after the introduction of the website in 2010. Patients' satisfaction post-op was assessed using the Brompton's single step questionnaire (SSQ). The website had considerable traffic with 2179 hits in 2012, 4983 in 2013 and 7416 in 2014. This has led to 1421 contacts and 372 email enquiries. These emails have resulted in an increased number of patients who have been assessed and go on to have surgery. We asked 59 pectus excavatum patients who were operated from 2008 to 2014 to complete the SSQ. We received 32 replies. Eighty-four percent (16/19) of patients who visited the website and then underwent surgery, found the website useful. All patients scored satisfactorily in SSQ. Even though those who visited the website tended to be more satisfied with the surgical outcomes this did not reach statistical significance. This group of patients said that would have the operation again given the option compared to 76.9 % of the group who did not visit the website before surgery (p=0.031). Despite the fact that patients who visited the website experienced more post-operative complications were equally or more satisfied with post-operative outcomes. The overall SSQ obtainable score was not different for the two subgroups, being more widespread in the group that did not visit the website. The introduction of a pectus patient information website has significantly improved access to specialised services. Patients are overall highly satisfied with the surgical outcomes.


[Fetus papyraceus. Case report].
The term fetus papyraceus is used to describe a mummified fetus associated to a multi-fetal gestation. We present the case of a of 20 years old patient who entered under the diagnosis of pregnancy of 41.1 weeks of gestation by last menstrual period, and effective labor work. It was conducted labor and delivery obtaining a live, male product. The uterine cavity was revised due to suspicion of retention of placenta and/or fetal membranes and it was obtained a product of approximated 15 weeks of gestation; the patient presented uterine atony and postpartum hemorrhage (PPH) quantified in approx 1,500 cc. Therefore it was decided to perform an obstetrical abdominal hysterectomy, which took place without incidents. The patient cursed pathological puerperium and received blood transfusion for 4 U. She was discharged at the 7th day after surgery. The histopathologic result was fetus papyraceus.


Disturbed Fatty Acid Oxidation, Endoplasmic Reticulum Stress, and Apoptosis in Left Ventricle of Patients With Type 2 Diabetes.
Chronic heart failure is a common complication in patients with type 2 diabetes mellitus (T2DM). T2DM is associated with disturbed metabolism of fat, which can result in excessive accumulation of lipids in cardiac muscle. In the current study, we assessed mitochondrial oxidation of carbohydrates and fatty acids, lipid accumulation, endoplasmic reticulum (ER) stress, and apoptosis in diabetic left ventricle. Left ventricular myocardium from 37 patients (a group of patients with diabetes and a group of patients without diabetes [ejection fraction >50%]) undergoing coronary artery bypass graft surgery was obtained by subepicardial needle biopsy. The group with diabetes had a significantly decreased rate of mitochondrial respiration fueled by palmitoyl-carnitine that correlated with blood glucose dysregulation, while there was no difference in oxidation of pyruvate. Diabetic myocardium also had significantly decreased activity of hydroxyacyl-CoA dehydrogenase (HADHA) and accumulated more lipid droplets and ceramide. Also, markers of ER stress response (GRP78 and CHOP) and apoptosis (cleaved caspase-3) were elevated in diabetic myocardium. These results show that, even in the absence of contractile failure, diabetic heart exhibits a decreased mitochondrial capacity for β-oxidation, increased accumulation of intracellular lipids, ER stress, and greater degree of apoptosis. Lower efficiency of mitochondrial fatty acid oxidation may represent a potential target in combating negative effects of diabetes on the heart.


Dapagliflozin, an oral sodium glucose cotransporter type 2 inhibitor for the treatment of type 2 diabetes mellitus.
Dapagliflozin (BMS-512148), a specific inhibitor of the sodium-glucose cotransporter SGLT2, is under development by AstraZeneca plc and Bristol-Myers Squibb Co for the potential oral treatment of type 2 diabetes mellitus (T2DM); a fixed-dose combination of dapagliflozin and metformin is also being developed by the companies for the potential treatment of diabetes mellitus. Phlorizin, a naturally occurring O-glucoside, inhibits renal glucose transport and induces glucosuria in rodent models of diabetes; however, phlorizin inhibits other glucose transporters in addition to SGLT2 and thus is not suitable for oral administration. The chemical synthesis of more specific SGLT2 inhibitors led to the identification of dapagliflozin, a C-aryl glucoside that was highly selective for SGLT2 compared with SGLT1. In phase II clinical trials in patients with T2DM, once-daily dapagliflozin induced dose-dependent increases in glucosuria and efficiently reduced HbA1c, fasting and postprandial glucose levels. Dapagliflozin was not associated with significant hypoglycemic episodes or weight gain; rather, the caloric losses related to renal glucose wasting induced a net weight loss. In addition, the diuretic effect observed with dapagliflozin may help to control hypertension, an associated finding in patients with T2DM. The major adverse effect associated with dapagliflozin appears to be an increased occurrence of mycotic genital infections.


Thyroid Ultrasound: State of the Art. Part 2 - Focal Thyroid Lesions.
Accurate differentiation of focal thyroid nodules (FTL) and thyroid abnormalities is pivotal for proper diagnostic and therapeutic work-up. In these two part articles, the role of ultrasound techniques in the characterization of FTL and evaluation of diffuse thyroid diseases is described to expand on the recently published World Federation in Ultrasound and Medicine (WFUMB) thyroid elastography guidelines and review how this guideline fits into a complete thyroid ultrasound exam.


Small/Kiddie Cigarette Packaging Size and Its Impact on Smoking: A Systematic Review.
Background: Small cigarette pack sizes contain less than 20 cigarette sticks in a pack. Smaller packs may suggest lower costs, increasing affordability among lower-income users, especially the younger generation, which could lead to tobacco-related diseases and economic costs, including human capital lost results from tobacco-attributable morbidity and mortality. This concern has caused many countries to ban the sale of single cigarette sticks or kiddie packs. However, small cigarette pack sizes were proposed recently to be reintroduced by the tobacco industry with an excuse to prevent consumers from buying illicit cigarettes. This would demean efforts in combating tobacco consumption based on the existing tobacco control policies to prevent minors from purchasing cigarettes. Given the competing influences of affordability and availability of tobacco on consumption and the dearth of evidence-based review on the impact of pack size on smoking, this systematic review was conducted to identify the link between kiddie packs and smoking specifically on the initiation of smoking, urge/tendency to buy cigarettes among the general population and attempt to reduce cigarette consumption and prevalence of smoking using kiddie packs among current smokers. Methods: We include all studies except for reviews, guidelines, conference papers, commentaries, editorials, or opinion pieces. A database search was conducted in PubMed, EMBASE, CENTRAL, Web of Science and Scopus on 27 November 2021. The results were presented in the form of narrative synthesis under four groups: initiation of smoking; urge/tendency to buy cigarettes; the prevalence of smoking, and attempt to reduce cigarette consumption. The literature search identified 1601 articles, of which 21 articles had met the inclusion criteria. The methodological quality of all included articles was determined using a validated 16-item quality assessment tool (QATSDD). The average quality score for all papers was 34.8%. Discussion: Given the diverse study settings of the articles and despite the challenges of the methodological quality of some articles, this review provides some evidence that kiddie packs may increase the urge/tendency to buy cigarettes and mixed evidence on the attempt to reduce cigarette consumption. This review also found some evidence that kiddie pack purchasing among teenage smokers was higher compared to adults. However, we are uncertain about the link between kiddie packs and smoking initiation. Nevertheless, since most studies were of low quality, further high-quality studies are needed to conclude about the impact of kiddie packs on smoking to assist the policymakers and stakeholders in formulating new policies and strengthening existing strategies related to the kiddie packs.


Neuronal shot noise and Brownian 1/f2 behavior in the local field potential.
We demonstrate that human electrophysiological recordings of the local field potential (LFP) from intracranial electrodes, acquired from a variety of cerebral regions, show a ubiquitous 1/f(2) scaling within the power spectrum. We develop a quantitative model that treats the generation of these fields in an analogous way to that of electronic shot noise, and use this model to specifically address the cause of this 1/f(2) Brownian noise. The model gives way to two analytically tractable solutions, both displaying Brownian noise: 1) uncorrelated cells that display sharp initial activity, whose extracellular fields slowly decay in time and 2) rapidly firing, temporally correlated cells that generate UP-DOWN states.


Deep Variational and Structural Hashing.
In this paper, we propose a deep variational and structural hashing (DVStH) method to learn compact binary codes for multimedia retrieval. Unlike most existing deep hashing methods which use a series of convolution and fully-connected layers to learn binary features, we develop a probabilistic framework to infer latent feature representation inside the network. Then, we design a struct layer rather than a bottleneck hash layer, to obtain binary codes through a simple encoding procedure. By doing these, we are able to obtain binary codes discriminatively and generatively. To make it applicable to cross-modal scalable multimedia retrieval, we extend our method to a cross-modal deep variational and structural hashing (CM-DVStH). We design a deep fusion network with a struct layer to maximize the correlation between image-text input pairs during the training stage so that a unified binary vector can be obtained. We then design modality-specific hashing networks to handle the out-of-sample extension scenario. Specifically, we train a network for each modality which outputs a latent representation that is as close as possible to the binary codes which are inferred from the fusion network. Experimental results on five benchmark datasets are presented to show the efficacy of the proposed approach.


Nas-Walras equilibria of a large economy.
Individuals exchange contracts for the delivery of commodities in competitive markets and, simultaneously, act strategically; actions affect utilities across individuals directly or through the payoffs of contracts. This encompasses economies with asymmetric information. Nash-Walras equilibria exist for large economies, even if utility functions are not quasi-concave and choice sets are not convex, which is the case in standard settings; the separation of the purchase from the sale of contracts and the pooling of the deliveries on contracts guarantee that the markets for commodities clear.


A system for the high-throughput analysis of acute thermal avoidance and adaptation in C. elegans.
Nociception and its plasticity are essential biological processes controlling adaptive behavioral responses in animals. These processes are also linked to different pain conditions in human and have received considerable attention, notably via studies in rodent models and the use of heat-evoked withdrawal behavior assays as a readout of unpleasant experience. More recently, invertebrates have also emerged as useful complementary models, with their own set of advantages, including their amenability to genetic manipulations, the accessibility and relative simplicity of their nervous system and ethical concerns linked to animal suffering. Like humans, the nematode Caenorhabditis elegans (C. elegans) can detect noxious heat and produce avoidance responses such as reversals. Here, we present a methodology suitable for the high-throughput analysis of C. elegans heat-evoked reversals and the adaptation to repeated stimuli. We introduce two platforms: the INFERNO (for infrared-evoked reversal analysis platform), allowing the quantification of the thermal sensitivity in a petri dish containing a large population (> 100 animals), and the ThermINATOR (for thermal adaptation multiplexed induction platform), allowing the mass-adaptation of up to 18 worm populations at the same time. We show that wild type animals progressively desensitize in response to repeated noxious heat pulses. Furthermore, analyzing the phenotype of mutant animals, we show that the mechanisms underlying baseline sensitivity and adaptation, respectively, are supported by genetically separable molecular pathways. In conclusion, the presented method enables the high-throughput evaluation of thermal avoidance in C. elegans and will contribute to accelerate studies in the field with this invertebrate model.


Spin coating mediated morphology modulation in self assembly of peptides.
Controlling the morphology and nanostructure of self-assembled peptide molecules is of fundamental importance to chemistry and material science due to their bioactivity in both in vivo and in vitro settings, ability to act as templates for conjugating bio-recognition elements, hybrid supramolecular assembly, possible detection and treatment of diseases and so on. In this article, we show that spin coating, a widely utilized method for obtaining ultra-thin polymer films, has been utilised to modulate the self-assembly of peptide molecules, which has traditionally been achieved by chemical functionalisation of the molecules. With the specific example of diphenylalanine-based peptide molecules, we show that a variety of self-assembled architectures such as long fibrils, short fibrils, globules, nanodots, and so on, spanning over large areas can be obtained by simultaneously varying the spinning speed (RPM) and the solution concentration (Cp) during spin coating. We correlate the variation in morphology to a transition from spin dewetting at very low Cp (or high RPM) to the formation of continuous films at high Cp (or low RPM) during the initial stage of spin coating. We further show the generality of the approach by achieving distinct self-assembled morphologies with diphenylalanine analogues with different C-terminal and N-terminal groups by modulation of spin coating parameters, though the exact morphology obtained under identical coating conditions depends on the chemical nature of the peptide molecules. The work opens up a new possible route for creating complex peptide assemblies on demand by simultaneous control of molecular functionalisation and spin coating parameters vis - a - vis the applied centrifugal force.


Cisplatin-Mediated Upregulation of APE2 Binding to MYH9 Provokes Mitochondrial Fragmentation and Acute Kidney Injury.
Cisplatin chemotherapy is standard care for many cancers but is toxic to the kidneys. How this toxicity occurs is uncertain. In this study, we identified apurinic/apyrimidinic endonuclease 2 (APE2) as a critical molecule upregulated in the proximal tubule cells (PTC) following cisplatin-induced nuclear DNA and mitochondrial DNA damage in cisplatin-treated C57B6J mice. The APE2 transgenic mouse phenotype recapitulated the pathophysiological features of C-AKI (acute kidney injury, AKI) in the absence of cisplatin treatment. APE2 pulldown-MS analysis revealed that APE2 binds myosin heavy-Chain 9 (MYH9) protein in mitochondria after cisplatin treatment. Human MYH9-related disorder is caused by mutations in MYH9 that eventually lead to nephritis, macrothrombocytopenia, and deafness, a constellation of symptoms similar to the toxicity profile of cisplatin. Moreover, cisplatin-induced C-AKI was attenuated in APE2-knockout mice. Taken together, these findings suggest that cisplatin promotes AKI development by upregulating APE2, which leads to subsequent MYH9 dysfunction in PTC mitochondria due to an unrelated role of APE2 in DNA damage repair. This postulated mechanism and the availability of an engineered transgenic mouse model based on the mechanism of C-AKI provides an opportunity to identify novel targets for prophylactic treatment of this serious disease. SIGNIFICANCE: These results reveal and highlight an unexpected role of APE2 via its interaction with MYH9 and suggest that APE2 has the potential to prevent acute kidney injury in patients with cisplatin-treated cancer. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/3/713/F1.large.jpg.


Pervasive reinforcement and the role of sexual selection in biological speciation.
Sexual selection has been widely implicated as a driver of speciation. However, allopatric forms are often defined as species based on divergence in sexually selected traits and it is unclear how much such trait differences affect reproductive isolation upon secondary contact, the defining feature of biological species. We show that in birds, divergence in song and plumage in allopatry corresponds poorly with whether species mate assortatively in hybrid zones and argue that this is because many other factors besides trait divergence affect propensity to hybridize, including rarity of conspecific mates and choice based on territory rather than male traits. We then present a general model for the establishment of sympatry that assumes a period of differentiation in allopatry followed by secondary contact and often hybridization, with hybridization subsequently reduced by reinforcement of mate preferences. We suggest that reinforcement commonly operates by a narrowing of a "window of recognition" for traits that are different between the species, rather than evolution of the traits themselves. Our arguments imply that it is important to study postmating as well as premating reproductive isolation in limiting sympatry and suggest that studies of reinforcement should focus on evolution of female preferences for diagnostic traits, rather than evolution of traits per se.


Physical activity levels and counseling by health care providers in cancer survivors.
Physical activity guidelines for cancer survivors issued by the American Cancer Society and the American College of Sports Medicine emphasize the essential role of a health care provider (HCP) in counseling cancer survivors to achieve healthier lifestyles. However, research has not established whether HCP's recommendations to engage in physical activity are associated with increased physical activity levels of cancer survivors. The study examines this potential association using the 2005 and 2010 National Health Interview Survey data. The final analytic sample consisted of 3320 cancer survivors and 38,955 adults without cancer who reported seeing or talking to a HCP and if or not they had received a physical activity recommendation in the prior year. Consistent with the aforementioned guidelines, physical activity levels were categorized as inactive, insufficiently active, and sufficiently active (i.e., meeting guidelines). Average adjusted predictions and marginal effects were estimated from generalized ordered logit models. Multivariable regressions controlled for socio-demographic and health-related characteristics and survey year. On average, receipt of a HCP's physical activity recommendation was associated with a lower adjusted prevalence of inactivity by 8.3 percentage points and a higher adjusted prevalence of insufficient and sufficient activity by 4.6 and 3.7 percentage points, respectively, regardless of cancer diagnosis (P's<0.05). A HCP's recommendation is associated with higher levels of leisure-time aerobic physical activity among cancer survivors and adults without cancer. The communication between cancer survivors and their HCPs may act as a 'window' of opportunity to increase physical activity levels among the U.S. cancer survivors.


Quantitative real-time PCR and fluorescence in situ hybridization approaches for enumerating Brevundimonas diminuta in drinking water.
Brevundimonas diminuta is a small Gram-negative bacterium used for validation of membranes and filters used in the pharmaceutical and drinking water treatment industries. Current assays are time consuming, nonselective, and may be subject to interference by competing indigenous microorganisms. The focus of this study is to develop rapid and specific enumeration methodologies for B. diminuta. Quantitative real-time polymerase chain reaction (qPCR) and fluorescence in situ hybridization (FISH) assays were developed based on the gyrB (1,166 bp) and rpoD (829 bp) gene sequences of B. diminuta ATCC 19146. Species-specific primers and probes were designed, and a 100-200 bp segment of each gene was targeted in the qPCR studies. For both the qPCR and FISH assays, an internal 25 bp sequence was selected for use as a TaqMan probe (labeled with 6-FAM and a Black Hole Quencher). Probe specificity studies, conducted against Gram-negative and Gram-positive reference strains as well as environmental strains, revealed high specificity of the primer/probe pairs to B. diminuta. Sensitivities of the qPCR reactions using purified genomic DNA from B. diminuta were determined to be 0.89 pg for rpoD and 8.9 pg for gyrB. The feasibility of using whole-cell B. diminuta suspensions directly with the rpoD qPCR protocol was also evaluated. The greatest sensitivity observed for B. diminuta was 1 x 10(3) colony forming units (CFU) per mL when tryptic soy broth was used as the growth medium. When compared with direct microscopic enumeration using a 5' 6-FAM FISH probe, traditional plating methods showed significant underestimation of B. diminuta concentration (P = 0.01) when this organism was cultivated in saline lactose broth. The results of this investigation demonstrate that qPCR and FISH are effective methods for rapid (<4 h) enumeration of B. diminuta and may be viable alternatives to plating when validating drinking water filtration systems.


Characterization of alpha-adrenoceptors in canine mesenteric vein.
The alpha-adrenergic receptors (alpha-ARs) in canine mesenteric vein (DMV) were studied by using nonselective agonists and selective antagonists in functional studies and in ligand binding to classify the subtypes present. Based on functional studies of phenylephrine (PE)-induced contractions and ligand-binding interactions of [3H]-prazosin with prazosin (PR), WB 4101 (WB), 5-methylurapidil (5-MU), BMY 7378, and SK&F 105854, and pretreatment with chloroethylclonidine (CEC), DMV alpha1-ARs resembled the alpha1D subtype. However, the affinity of PR assessed in functional and ligand-binding studies was less (pK(B,D,i) < or = 9) than expected from previous characterization of cloned rat or human alpha1-AR (pKi > or = 10). Interactions with 5-MU, BMY 7378, or SK&F 105854 suggested the presence of some alpha1-ARs that were not typical of alpha1D-AR and that binding and functional interactions did not yield corresponding results. PR binding was abolished by treatment with CEC, contractile responses to PE were reduced in Emax, and the concentration-effect curve shifted to the left, as previously reported. DMVs contracted in response to alpha2-AR agonists and were studied when contractions were potentiated by increasing extracellular KCl to 20 mM. Rauwolscine (RAU) had K(B) values at these sites consistent with K(D) values in binding studies. CEC had no effect on RAU binding in DMV. Ligand-binding studies to [3H]-RAU sites did not reveal a clear identification of subtype, but these alpha2-ARs were clearly not alpha2B-ARs. We conclude that canine mesenteric vein contains alpha1D-like ARs, but with significant differences, and an unclassifiable alpha2-AR. There may also be a smaller population of other, not alpha1D-like ARs, receptors, mediating responses to PE and binding of prazosin.


Genomic and biotechnological insights on stress-linked polyphosphate production induced by chromium(III) in Ochrobactrum anthropi DE2010.
The resistance of microorganisms to heavy metals in polluted environments is mediated by genetically determined mechanisms. One such mechanism includes the intracellular sequestration of heavy metals in polyphosphate (polyP) inclusions. In Cr(III) contaminated mediums, Ochrobactrum anthropi DE2010 is able to bind and sequester Cr(III) in polyP inclusions. In order to further study the relationship between Cr(III) tolerance and polyP production in O. anthropi DE2010, we carried out whole genomic sequencing, analysis of single nucleotide polymorphisms (SNPs), polyP chemical quantification, and determination of the relative abundance and morphometry of polyP inclusions. In the O. anthropi DE2010 genome, six polyP and pyrophosphate (PPi) metabolic genes were found. Furthermore, genomic analysis via SNPs calling revealed that O. anthropi ATCC49188 and DE2010 strains had average variations of 1.51% in their whole genome sequences and 1.35% variation associated with the principal polyP metabolic gene cluster. In addition, the accumulation of polyP in the DE2010 strain and number of polyP inclusions found were directly correlated with the concentration of Cr(III) in contaminated cultures. The results presented in this study may enhance the understanding of polyP production in response to Cr(III) toxicity in the O. anthropi DE2010 strain. This knowledge may facilitate the successful removal of Cr(III) from the natural environment.


Retrospective growth analysis of Atlantic salmon Salmo salar and implications for abundance trends.
Scale archives of Atlantic salmon Salmo salar from Maine, U.S.A., were examined to determine whether ocean conditions affected the long-term trends in S. salar populations in the southern tier of the species' range in North America. To date, scale analyses of southern tier populations have been limited to hatchery fish; previous studies suggest that post-smolt growth does not influence recruitment, with the exception that winter growth may play a role in stock maturation rate. A time series of scales from the Machias and Narraguagus Rivers spanning the years 1946 to 1999 was analysed. Image analysis was used to measure intercirculi spacing, which provided proxy variables of growth rate. Post-smolt growth increment has increased since the early 1990s, as returns have decreased, suggesting that survival factors act on post-smolts independent of growth. The data support the hypothesis of a decoupling between freshwater size and early marine growth. Growth during the second sea winter was independent of post-smolt growth, suggesting that individuals are capable of significant compensatory growth. Southern tier North American stocks exhibit a similar pattern of independence between growth and survival as observed for northern tier North American stocks. These data support the inference that the recruitment of the North American and European subspecies is governed by fundamentally different mechanisms.


Nitric oxide confers cisplatin resistance in human lung cancer cells through upregulation of aldo-keto reductase 1B10 and proteasome.
In this study, we show that exposure of human lung cancer A549 cells to cisplatin (cis-diamminedichloroplatinum, CDDP) promotes production of nitric oxide (NO) through generation of reactive oxygen species (ROS) and resulting upregulation of inducible NO synthase (iNOS). The incubation of the cells with a NO donor, diethylenetriamine NONOate, not only reduced the CDDP-induced cell death and apoptotic alterations (induction of CCAAT-enhancer-binding protein homologous protein and caspase-3 activation), but also elevated proteolytic activity of 26S proteasome, suggesting that the activation of proteasome function contributes to the reduction of CDDP sensitivity by NO. Monitoring expression levels of six aldo-keto reductases (AKRs) (1A1, 1B1, 1B10, 1C1, 1C2, and 1C3) during the treatment with the NO donor and subsequent CDDP sensitivity test using the specific inhibitors also proposed that upregulation of AKR1B10 by NO is a key process for acquiring the CDDP resistance in A549 cells. Treatment with CDDP and NO increased amounts of nitrotyrosine protein adducts, indicative of peroxynitrite formation, and promoted the induction of AKR1B10, inferring a relationship between peroxynitrite formation and the enzyme upregulation in the cells. The treatment with CDDP or a ROS-related lipid aldehyde, 4-hydroxy-2-nonenal, facilitated the iNOS upregulation, which was restored by increasing the AKR1B10 expression. In contrast, the facilitation of NO production by CDDP treatment was hardly observed in AKR1B10-overexpressing A549 cells and established CDDP-resistant cancer cells (A549, LoVo, and PC3). Collectively, these results suggest the NO functions as a key regulator controlling AKR1B10 expression and 26S proteasome function leading to gain of the CDDP resistance.


Microtubule transport and assembly during axon growth.
There is controversy concerning the mechanisms by which the axonal microtubule (MT) array is elaborated, with some models focusing on MT assembly and other models focusing on MT transport. We have proposed a composite model in which MT assembly and transport are both important (Joshi, H.C., and P.W. Baas. 1993. J. Cell Biol. 121:1191-1196). In the present study, we have taken a novel approach to evaluate the merits of this proposal. Biotinylated tubulin was microinjected into cultured neurons that had already grown short axons. The axons were then permitted to grow longer, after which the cells were prepared for immunoelectron microscopic analyses. We reasoned that any polymer that assembled or turned over subunits after the introduction of the probe should label for biotin, while any polymer that was already assembled but did not turnover should not label. Therefore, the presence in the newly grown region of the axon of any unlabeled MT polymer is indicative of MT transport. In sampled regions, the majority of the polymer was labeled, indicating that MT assembly events are active during axon growth. Varying amounts of unlabeled polymer were also present in the newly grown regions, indicating that MT transport also occurs. Together these findings demonstrate that MT assembly and transport both contribute to the elaboration of the axonal MT array.


Forty-four-hour interdialytic ambulatory blood pressure monitoring and cardiovascular risk in pediatric hemodialysis patients.
Children undergoing chronic hemodialysis are at risk of cardiovascular disease and often develop left ventricular hypertrophy (LVH). Twenty-four-hour ambulatory blood pressure monitoring (ABPM) is known to better predict cardiovascular morbidity than casual blood pressure (BP) measurement. Given the BP variability attributed to interdialytic fluid overload, 44-h ABPM should better delineate cardiovascular morbidity in pediatric hemodialysis patients. In this cross-sectional study, 17 children (16.7 ± 2.9 years) on chronic hemodialysis underwent 44-h interdialytic ABPM and routine echocardiogram. Left ventricular mass index (LVMI) was calculated by height-based equation; LVH was defined as an LVMI in the ≥95th percentile for height-age and gender. Hypertension was defined by the recommendations of the Fourth Report of the National High Blood Pressure Education Program for casual measurements, and by those of the American Heart Association for ABPM. Twenty-four percentage of patients were hypertensive by casual post-dialytic systolic BP, whereas 59% were hypertensive by ABPM. Eighty-eight percentage of patients had abnormal cardiac geometry: 53% had LVH. Thirty-five percentage (6 of 17) had masked hypertension, including four with abnormal cardiac geometry, of which, three had LVH. LVMI correlated with ABPM, but not with casual measurements. Strongest correlations with an increased LVMI were with 44-h diastolic BP: at night (r = 0.53, P = 0.03) and total load (r = 0.57, P = 0.02). LVH was similarly associated with 44-h nighttime BP: systolic (P = 0.02), diastolic (P = 0.01) and mean arterial (P = 0.01). Casual BP measurement underestimates hypertension in pediatric hemodialysis patients and does not correlate well with indicators of cardiovascular morbidity. In contrast, 44-h interdialytic ABPM better characterizes hypertension, with nighttime parameters most strongly predicting increased LVMI and LVH.


Effect of frequency of multimodal coma stimulation on the consciousness levels of traumatic brain injury comatose patients.
To evaluate the effectiveness of multimodal coma stimulation on the conscious levels of head injury comatose patients and to find out which of the two protocols of coma stimulation, i.e. administrating twice a day or 5-times a day is more beneficial. Thirty comatose patients with traumatic head injury (GCS < 8) were selected and were divided into three groups randomly. Group A (n = 10) received multimodal coma stimulation 5-times a day (20 minutes each session), Group B (n = 10) received stimulation twice a day (50 minutes each session) and Group C (n = 10) received conventional physiotherapy twice daily. Subjects in all the three groups received treatment for 2 weeks. The results showed a significant difference (p < 0.01) for Glasgow Coma Scale as well as Western Neuro Sensory Stimulation Profile scores between Groups A & C and B & C, i.e. multimodal coma stimulation is effective as compared to the control group. The results also revealed a significant difference (p < 0.01) between Groups A, B and C on the Western Neuro Sensory Stimulation Profile but a non-significant difference (p > 0.01) on the Glasgow coma scale. This indicates that short sessions of high frequency can be more beneficial.


Anticancer potential of Conium maculatum extract against cancer cells in vitro: Drug-DNA interaction and its ability to induce apoptosis through ROS generation.
Conium maculatum extract is used as a traditional medicine for cervix carcinoma including homeopathy. However, no systematic work has so far been carried out to test its anti-cancer potential against cervix cancer cells in vitro. Thus, in this study, we investigated whether ethanolic extract of conium is capable of inducing cytotoxicity in different normal and cancer cell lines including an elaborate study in HeLa cells. Conium's effects on cell cycle, reactive oxygen species (ROS) accumulation, mitochondrial membrane potential (MMP) and apoptosis, if any, were analyzed through flow cytometry. Whether Conium could damage DNA and induce morphological changes were also determined microscopically. Expression of different proteins related to cell death and survival was critically studied by western blotting and ELISA methods. If Conium could interact directly with DNA was also determined by circular dichroism (CD) spectroscopy. Conium treatment reduced cell viability and colony formation at 48 h and inhibited cell proliferation, arresting cell cycle at sub-G stage. Conium treatment lead to increased generation of reactive oxygen species (ROS) at 24 h, increase in MMP depolarization, morphological changes and DNA damage in HeLa cells along with externalization of phosphatidyl serine at 48 hours. While cytochrome c release and caspase-3 activation led HeLa cells toward apoptosis, down-regulation of Akt and NFkB inhibited cellular proliferation, indicating the signaling pathway to be mediated via the mitochondria-mediated caspase-3-dependent pathway. CD-spectroscopy revealed that Conium interacted with DNA molecule. Overall results validate anti-cancer potential of Conium and provide support for its use in traditional systems of medicine.


Commissural NTS lesions and cardiovascular responses in aortic baroreceptor-denervated rats.
Both acute (1 day) lesions of the commissural nucleus of the solitary tract (commNTS) and aortic baroreceptor denervation increase pressor responses to bilateral common carotid occlusion (BCO) during a 60-second period in conscious rats. In this study, we investigated the following: (1) the effects of commNTS lesions on basal mean arterial pressure (MAP) and heart rate (HR) of aortic denervated (ADNx) rats; (2) the effects of acute commNTS lesions on pressor responses to BCO in ADNx rats; and (3) the effects of chronic (10 days) commNTS lesions on the pressor response to BCO. ADNx increased basal MAP and HR in sham-lesioned rats. Acute commNTS lesions abolished the MAP and HR increases observed in ADNx rats. Acute commNTS lesions increased the pressor responses to BCO in rats with intact-baroreceptor innervation but produced no additional change in the pressor response to BCO in ADNx rats. Chronic commNTS lesions did not change the pressor responses to BCO in rats with intact-baroreceptor innervation. The data show that acute commNTS lesions abolish the MAP increase produced by aortic baroreceptor denervation. They also suggest that acute commNTS lesions enhance the pressor response to BCO by partial withdrawal of aortic baroreceptor inputs into the NTS. Chronically, reorganization in the remaining aortic baroreceptor or in the baroreflex function as a whole might produce normalization of the cardiovascular responses to BCO.