'This is the place where I can be alone, no tension:' Photovoice evidence for adolescent perceptions of their microsystem and psychological adjustment.
Adolescents experience myriad emotions which occur in relation to their immediate social space which may shape their perceptions of members within the microsystem. The photovoice method uniquely provides participants with the means to capture their life through the lens of a camera while also enabling them to express emotions and meanings they attach to their particular life situations. We explore the various emotions adolescents attach to the spaces they occupy and how they link them to socialization in the context of the microsystem. This study was conducted in rural and urban areas of Udupi taluk, southern India. A total of 21 participants, ranging from early to late adolescence participated and provided multiple forms of data with 112 photographs, 21 journals on their daily interactions and one-on-one interviews facilitated using the SHOWeD model. The analytical method involved compiling visual data from photographs, journal content and interview data pertaining to each participant as a single data file, developing codes using ATLAS.ti, version 8, and further developing sub-themes and themes as they emerged into narratives. Our study was able to elicit emotions and meanings that adolescents attached to social interactions with gendered nuances specific to the Indian cultural setting. Future applications of the photovoice methodology on research among adolescents have also been discussed.


The predictive brain: temporal coincidence and temporal order in synaptic learning mechanisms.
Some forms of synaptic plasticity depend on the temporal coincidence of presynaptic activity and postsynaptic response. This requirement is consistent with the Hebbian, or correlational, type of learning rule used in many neural network models. Recent evidence suggests that synaptic plasticity may depend in part on the production of a membrane permeant-diffusible signal so that spatial volume may also be involved in correlational learning rules. This latter form of synaptic change has been called volume learning. In both Hebbian and volume learning rules, interaction among synaptic inputs depends on the degree of coincidence of the inputs and is otherwise insensitive to their exact temporal order. Conditioning experiments and psychophysical studies have shown, however, that most animals are highly sensitive to the temporal order of the sensory inputs. Although these experiments assay the behavior of the entire animal or perceptual system, they raise the possibility that nervous systems may be sensitive to temporally ordered events at many spatial and temporal scales. We suggest here the existence of a new class of learning rule, called a predictive Hebbian learning rule, that is sensitive to the temporal ordering of synaptic inputs. We show how this predictive learning rule could act at single synaptic connections and through diffuse neuromodulatory systems.


Psychometrics and event-related potentials in the diagnosis of dementia.
This study attempted to increase the reliability of predicting the normal latency of the P3 component in elderly adults. It was hypothesized this would allow a more accurate distinction to be made between normal adults (n = 20) and patients with dementia (n = 19) on the basis of observed P3 latencies. Two models for predicting latency were assessed. The first, which used age alone as a predictor, explained 18% of the normal variation in latency and misclassified 40% of the patients. The second model, which incorporated scores on psychometric tests, explained 74% of latency variation and misclassified 20% of the patients. Scores on the Similarities subtest of the WAIS and the Rey Auditory Verbal Learning Test, however, correctly identified 92% of the patients. This finding casts doubt on the justification of the P3 latency measures to diagnose dementia.


The factor structure of the Reckless Behavior Questionnaire.
In this study, the relative fits of three different factor-structure models of adolescent reckless behavior were examined using the Reckless Behavior Questionnaire (RBQ) with individual samples of college and high school students. Both one- and two-factor models were found to be satisfactory representations of the RBQ with both samples. In order to test the construct validity of the one- and two-factor models, relations between instruments generally associated with reckless behavior were examined by gender. Using the two-factor model, gender differences were found for both the college and high school samples; thus, it was determined to be the more parsimonious fit of the data given previous research supporting gender differences. Findings are discussed in terms of current conceptualizations of factor patterns of adolescent problem behavior and implications for future investigations.


Cortico-Thalamo-Cortical Circuits of Mouse Forelimb S1 Are Organized Primarily as Recurrent Loops.
Cortical projections to the thalamus arise from corticothalamic (CT) neurons in layer 6 and pyramidal tract-type (PT) neurons in layer 5B. We dissected the excitatory synaptic connections in the somatosensory thalamus formed by CT and PT neurons of the primary somatosensory (S1) cortex, focusing on mouse forelimb S1. Mice of both sexes were studied. The CT neurons in S1 synaptically excited S1-projecting thalamocortical (TC) neurons in subregions of both the ventral posterior lateral and posterior (PO) nuclei, forming a pair of recurrent cortico-thalamo-cortical (C-T-C) loops. The PT neurons in S1 also formed a recurrent loop with S1-projecting TC neurons in the same subregion of the PO. The PT neurons in the adjacent primary motor (M1) cortex formed a separate recurrent loop with M1-projecting TC neurons in a nearby subregion of the PO. Collectively, our results reveal that C-T-C circuits of mouse forelimb S1 are primarily organized as multiple cortical cell-type-specific and thalamic subnucleus-specific recurrent loops, with both CT and PT neurons providing the strongest excitatory input to TC neurons that project back to S1. The findings, together with those of related studies of C-T-C circuits, thus suggest that recurrently projecting thalamocortical neurons are the principal targets of cortical excitatory input to the mouse somatosensory and motor thalamus.SIGNIFICANCE STATEMENT Bidirectional cortical communication with the thalamus is considered an important aspect of sensorimotor integration for active touch in the somatosensory system, but the cellular organization of the circuits mediating this process is not well understood. We used an approach combining cell-type-specific anterograde optogenetic excitation with single-cell recordings targeted to retrogradely labeled thalamocortical neurons to dissect these circuits. The findings reveal a consistent pattern: cortical projections to the somatosensory thalamus target thalamocortical neurons that project back to the same cortical area. Commonalities of these findings to previous descriptions of related circuits in other areas suggest that cortico-thalamo-cortical circuits may generally be organized primarily as recurrent loops.


[Benchmarking and other functions of ROM: back to basics].
Since 2011 outcome data in the Dutch mental health care have been collected on a national scale. This has led to confusion about the position of benchmarking in the system known as routine outcome monitoring (rom). To provide insight into the various objectives and uses of aggregated outcome data. A qualitative review was performed and the findings were analysed. Benchmarking is a strategy for finding best practices and for improving efficacy and it belongs to the domain of quality management. Benchmarking involves comparing outcome data by means of instrumentation and is relatively tolerant with regard to the validity of the data. Although benchmarking is a function of rom, it must be differentiated form other functions from rom. Clinical management, public accountability, research, payment for performance and information for patients are all functions of rom which require different ways of data feedback and which make different demands on the validity of the underlying data. Benchmarking is often wrongly regarded as being simply a synonym for 'comparing institutions'. It is, however, a method which includes many more factors; it can be used to improve quality and has a more flexible approach to the validity of outcome data and is less concerned than other rom functions about funding and the amount of information given to patients. Benchmarking can make good use of currently available outcome data.


Preliminary results: prospective clinical study to assess image-based iterative reconstruction for abdominal computed tomography acquired at 2 radiation dose levels.
The objective of this study was to compare image quality for abdominal computed tomographic (CT) images acquired at 200 and 50 mA s and reconstructed with image-based iterative reconstruction. In this institutional review board-approved prospective study, 22 patients (mean [SD] age, 64.3 [14.4] years; male-female ratio, 12:10) gave informed consent for acquisition of additional abdominal CT images on 64-slice multi-detector CT (MDCT) (Siemens Definition Flash). Standard-dose images were acquired at 200 quality reference mA s, whereas low-dose images were acquired at 50 mA s (all series: 120 kV; 5-mm section thickness; pitch, 0.9:1). The low-dose images were reconstructed with a nonlinear 3-dimensional iterative image reconstruction (3D-IIR) (SafeCT; MedicVision, Tirat Carmel, Israel) (4 settings, namely, A1, A2, A3, and A4) and were assessed by 3 abdominal radiologists for lesion detection, image noise, and visibility of small structures. CATPHAN 500 was scanned at the respective doses to obtain noise spectral density and modulation transfer function. Subjective image noise was unacceptable at 50-mA s filtered back projection and improved to average in 50-mA s A1 and minimal or no noise in 50-mA s A4. However, the visibility of small structures was similar to standard-dose filtered back projection images on 50-mA s A2. Objective image noise was reduced to 66% for the 50-mA s 3D-IIR images (9.08 [2.3]/26.75 [6.8]). The modulation transfer function curve demonstrated resolution improvement in the low-dose images with the 3D-IIR technique, whereas the noise spectral density curve confirmed noise suppression in the 50-mA s 3D-IIR images. Three-dimensional iterative image reconstruction helps to lower image noise without affecting the visibility of small structures at "moderate" settings. Diagnostically acceptable abdominal CT examinations can be acquired at 75% lower-radiation dose with the help of the image-based iterative reconstruction technique.


Default Mode Network Efficiency Is Correlated With Deficits in Inhibition in Adolescents With Inhalant Use Disorder.
It is well established that alterations in cognitive function and damage to brain structures are often found in adolescents who have substance use disorder (SUD). However, deficits in executive cognitive functioning in adolescents related to the vulnerability and consumption of such substances are not well known. In this study, we use graph theoretic analysis to compare the network efficiency in the resting state for three networks-default mode network (DMN), salience network (SN) and fronto-parietal network (FPN)-between inhalant-consuming adolescents and a control group (12 to 17 years old). We analyzed whether the efficiency of these functional networks was related to working memory, mental flexibility, inhibition of response, and sequential planning. We found that, when compared to the control group, inhalant-consuming adolescents presented with important deficits in communication among brain regions that comprise the DMN, SN, and FPN networks. DMN is the most affected network by inhalant abuse during adolescence. The mediation analyses suggested that the relationship between inhalant abuse and inhibitory control and sequential planning was partly mediated by DMN efficiency.


Contracting for food service management.
Under food service contract management, health care administrators must remain responsible for developing appropriate contracts and for supervising their on-going implementation.


Functional analysis of a breast cancer-associated FGFR2 single nucleotide polymorphism using zinc finger mediated genome editing.
Genome wide association studies have identified single nucleotide polymorphisms (SNP) within fibroblast growth factor receptor 2 (FGFR2) as one of the highest ranking risk alleles in terms of development of breast cancer. The potential effect of these SNPs, in intron two, was postulated to be due to the differential binding of cis-regulatory elements, such as transcription factors, since all the SNPs in linkage disequilibrium were located in a regulatory DNA region. A Runx2 binding site was reported to be functional only in the minor, disease associated allele of rs2981578, resulting in increased expression of FGFR2 in cancers from patients homozygous for that allele. Moreover, the increased risk conferred by the minor FGFR2 allele associates most strongly in oestrogen receptor alpha positive (ERα) breast tumours, suggesting a potential interaction between ERα and FGFR signalling. Here, we have developed a human cell line model system to study the effect of the putative functional SNP, rs2981578, on cell behaviour. MCF7 cells, an ERα positive breast cancer cell line homozygous for the wild-type allele were edited using a Zinc Finger Nuclease approach. Unexpectedly, the acquisition of a single risk allele in MCF7 clones failed to affect proliferation or cell cycle progression. Binding of Runx2 to the risk allele was not observed. However FOXA1 binding, an important ERα partner, appeared decreased at the rs2981578 locus in the risk allele cells. Differences in allele specific expression (ASE) of FGFR2 were not observed in a panel of 72 ERα positive breast cancer samples. Thus, the apparent increased risk of developing ERα positive breast cancer seems not to be caused by rs2981578 alone. Rather, the observed increased risk of developing breast cancer might be the result of a coordinated effect of multiple SNPs forming a risk haplotype in the second intron of FGFR2.


The effect of patient age on perceived resuscitation outcomes by practitioners.
When health care practitioners assist patients with decisions about advance directives, the risks and benefits of resuscitation options are often discussed. Whether practitioners have accurate perceptions about in-hospital resuscitation success rates is not known, nor is the effect of patient age on these perceptions. Age on its own has not been definitively associated with decreased inpatient survival after resuscitation. The goal of this study was to compare perceived resuscitation success rates with the actual observed rates at our hospital and to assess the effect of patient age on the perceived rates. A survey-based observational study of on-duty hospital-based faculty, internal medicine resident physicians, and critical care nurses was performed over a week-long recruitment period to estimate their perception of in-hospital resuscitation success rates for patients of different ages. The survey response rate was 100%. Patient survival to hospital discharge following in-hospital resuscitation during a three-year period at New Hanover Regional Medical Center was 29.22% for patients < 70 years old and 20.13% for patients > or = 70. The perceived in-hospital resuscitation success rates were 38.76% for patients < 70 and 21.24% for patients > or = 70. This corresponds to a statistically significant overestimation of resuscitation success rates for patients < 70 years old (p < 0.001), although predictions were fairly accurate for patients > or = 70. When posed with one of two clinical scenarios where the only different variable was patient age, participants were statistically more likely to predict success for the younger patient. Subgroup analysis showed general agreement in the estimates between the three major types of practitioners, and factors such as length of experience in their current position and time since their last Advanced Cardiac Life Support (ACLS) recertification course did not have a significant impact on these perceptions. Practitioners may overestimate resuscitation success rates in patients younger than 70. Disseminating information about ACLS success rates to clinicians, and what factors affect or do not affect these rates, seems essential.


Osilodrostat for the treatment of Cushing's disease.
The treatment of Cushing's disease (CD) has been advanced well with the introduction of treatment options like transsphenoidal surgery, radiosurgery, bilateral adrenalectomy, and various classes of medication; however, many patients still fail to achieve disease remission. Osilodrostat, an orally bioavailable adrenal steroidogenesis inhibitor, was approved in the USA and EU in 2020 for the treatment of CD. This review provides an overview of Cushing's disease and the newly FDA approved 11β-hydroxylase inhibitor, osilodrostat, for CD with a focus on pharmacodynamics, pharmacokinetics, safety and efficacy data, and phase 2 and 3 clinical trials. Osilodrostat has proven clinical efficacy and tolerability in phase 2 and 3 trials with CD patients who had an inadequate or reoccurring response to transsphenoidal surgery (TSS) and conventional first-line treatment. The phase 3 trial (LINC3) had 86% of the treatment group respond with normal urinary free cortisol (UFC) level compared to 29% in the placebo group (p < 0.001). Deemed as well-tolerated in all current pivotal trials, oral osilodrostat provides a noninvasive option for patients who cannot undergo surgery or patients who have reoccurring hypercortisolemia.


Temporomandibular malformations in the bonnet monkey (Macaca radiata) fetus following maternal ingestion of thalidomide.
Structural abnormalities of the temporomandibular region were seen and described in the fetal bonnet monkey (Macaca radiata) after maternal ingestion of thalidomide. A single oral dose of 10 mg/kg of thalidomide was given on day 24, 25, 26, 27, 28 or 29 or 30 mg/kg on day 25 or 28 of gestation to 25 pregnant monkeys (day of mating = 0). The skeletons, processed and stained with alizarin red S, were examined for gross changes in configuration of craniofacial bones. Temporomandibular defects, in varying severity, were seen in four 70-day-old and seven 100-day-old fetuses associated with a single treatment between day 24 and day 28. The highest risk appeared to occur following treatment on day 25 (4/5) and the lowest on day 28 (2/8). Characteristic expression of the defects included 1) temporo-zygomatic hyperplasia involving the articular tubercle and postglenoid process and 2) mandibular hypoplasia, primarily of the condyles and the angular and coronoid processes. Micrognathia, apertognathia, and partial extraarticular ankylosis were seen. Although the sensitivity periods of the temporomandibular and ear regions seem to overlap and the embryonic origins are similar, the defects of each region appeared to be independent. Although the ear demonstrated a definite temporal relationship characterized by a decrease in severity in the expression of the ear malformations with respect to increased gestational age at the time of thalidomide insult, the temporomandibular region failed to exhibit a specific pattern. Although the temporo-zygomatic hyperplasia was dissimilar to any reported human condition, the mandibular changes were similar.


SISTA South Africa: the adaptation of an efficacious HIV prevention trial conducted with African-American women for isiXhosa-speaking South African women.
Although new HIV treatments continue to offer hope for individuals living with HIV, behavioural interventions shown to reduce HIV risk behaviour remain one of the most powerful tools in curbing the HIV epidemic. Unfortunately, the development of evidence based HIV interventions is a resource-intensive process that has not progressed as quickly as the epidemiology of the disease. As the epidemic continues to evolve, there is a need to expedite the development of evidence-based HIV interventions for populations that are often disproportionately impacted by HIV/AIDS. One mechanism of accelerating the development process is to adapt evidence-based HIV interventions for vulnerable populations. The aim of this paper was to describe the adaptation process of a HIV intervention for African-American women for black South African Xhosa women. For African-American women the intervention was effective in increasing consistent condom use, sexual self-control, sexual communication, sexual assertiveness and partner adoption of norms supporting consistent condom use.


Development of Light-activated Pupilloconstriction in Rats as Mediated by Normal and Transplanted Retinae.
The relationship between the development of the pupilloconstriction response to changes in light levels and retinal maturation was studied in normal rats and rats that had received intracranial retinal transplants at birth. A pupillary response to light was first observed between postnatal days 7 and 9 in normal rats, and was typically of small amplitude and sluggish. By the time the eyelids first open, 2 weeks after birth, the pupillary response had improved to near adult levels. The inception of the pupillary response correlates with the first appearance of conventional synaptic contacts in the inner and outer plexiform layers of the retina, while improved responses correlate with maturation of photoreceptor outer segments and formation of synaptic ribbons in the inner plexiform layer. When embryonic retinae were transplanted to intracranial locations in newborn hosts and the transplants later illuminated as the host matured, the onset of a pupillary response to transplant illumination was delayed in proportion to the developmental disparity between the transplant and the host. The pattern of anatomical development in transplanted retinae was also similar, but delayed in time, compared to normal retinae. This indicates that the limiting factors for expression of light-activated pupilloconstriction exist within the retina, rather than being intrinsic to the central nuclei or to the output pathway subserving the response.


Mediators and Moderators of a Personalized Feedback Alcohol Intervention for Nonstudent Emerging Adult Drinkers.
The main objective of this study was to test proposed mediators and moderators of a personalized feedback alcohol intervention (PFI) on alcohol use. Data for the current investigation came from an earlier randomized controlled trial of a PFI targeted for nonstudent heavy drinkers between 18 and 25 years. Participants were 164 (65.9% men) drinkers recruited from the community. They were randomly assigned to either a single-session PFI or an assessment-only (AO) control group. Follow-up assessments at 1 and 3 months were included for analysis. Perceived drinking norms mediated the intervention effect on quantity, frequency, and peak drinking; 2 dimensions of protective behavioral strategies (PBS) mediated the intervention effect on peak drinking; and drinking to cope motives did not mediate any drinking outcomes. Of the moderating factors examined (i.e., norms, PBS, drink to cope motives, age, gender), only PBS related to serious harm reduction moderated intervention impact. Specifically, for those high in serious harm reduction PBS at baseline, postintervention reductions in drinking were stronger for the PFI group compared to AO. Overall, findings highlight the importance of correcting misperceived drinking norms and addressing the use of specific PBS in brief interventions. The knowledge gained from this study represents an important step toward minimizing drinking-related harms that are disproportionately experienced by those with lower educational attainment.


The use of the optacon as a screening device. A new technique for detecting sensory loss in individuals exposed to neurotoxins.
Periphral neuropathy is one of the most common nervous system reactions to toxic chemicals. Early detection signs of peripheral neuropathy among workers exposed to these chemicals is of paramount concern to occupational physicians. This study describes the use of the Optacon to to assess finger-tip sensation in normal and diabetic subjects. The instrument is capable of detecting the steady increase in threshold with age and is able to identify peripheral neuropathy in diabetic subjects. There was little variation upon repeated testing of the same subject. This study illustrates the usefulness of the Optacon as as a simple, reliable technique for detecting sensory loss in individuals with peripheral neuropathy, and suggests that it may be useful in detecting sensory loss in workers exposed to neurotoxins.


Calcium signals inhibition sensitizes ovarian carcinoma cells to anti-Bcl-xL strategies through Mcl-1 down-regulation.
Ovarian carcinoma is the leading cause of death from gynecologic cancer in the developed world and is characterized by acquired chemoresistance leading to an overall 5-year survival rate of about 30 %. We previously showed that Bcl-xL and Mcl-1 cooperatively protect platinum-resistant ovarian cancer cells from apoptosis. Despite BH3-mimetics represent promising drugs to target Bcl-xL, anti-Mcl-1 strategies are still in pre-clinical studies and required new investigations. Calcium is a universal second messenger and dysregulation of calcium signal is often observed during carcinogenesis. As change in cytosolic free calcium concentration [Ca(2+)]i is known to control the fate of the cell by regulating Bcl-2 family members, we wonder if calcium signal could impact on Mcl-1 expression and if its pharmacological inhibition could be useful to sensitize ovarian carcinoma cells to anti-Bcl-xL strategies. We therefore studied the effect of different calcium signals inhibitors in ovarian carcinoma cell lines SKOV3 and IGROV1-R10 and analysed their effects on proliferation and Mcl-1 expression. We also exposed these cells to these inhibitors in combination with anti-Bcl-xL strategies (siRNA or BH3-mimetic: ABT-737). We found that calcium signaling regulates Mcl-1 through translational events and a calmodulin-mediated pathway. BAPTA-AM and calmodulin inhibitor combination with ABT-737 leads to apoptosis, a process that is reversed by Mcl-1 enforced expression. As Mcl-1 represents a crucial hurdle to the success of chemotherapy, these results could open to new area of investigation using calcium modulators to directly or indirectly target Mcl-1 and thus efficiently sensitize ovarian carcinoma cells to anti-Bcl-xL strategies.


Protocols for the detection of s-glutathionylated and s-nitrosylated proteins in situ.
The oxidation of protein cysteine residues represents significant posttranslational modifications that impact a wide variety of signal transduction cascades and diverse biological processes. Oxidation of cysteines occurs through reactions with reactive oxygen as well as nitrogen species. These oxidative events can lead to irreversible modifications, such as the formation of sulfonic acids, or manifest as reversible modifications such as the conjugation of glutathione with the cysteine moiety, a process termed S-glutathionylation (also referred to as S-glutathiolation, or protein mixed disulfides). Similarly, S-nitrosothiols can also react with the thiol group in a process known as S-nitrosylation (or S-nitrosation). It is the latter two events that have recently come to the forefront of cellular biology through their ability to reversibly impact numerous cellular processes. Herein we describe two protocols for the detection of S-glutathionylated or S-nitrosylated proteins in situ. The protocol for the detection of S-glutathionylated proteins relies on the catalytic specificity of glutaredoxin-1 for the reduction of S-glutathionylated proteins. The protocol for the detection of S-nitrosylated proteins represents a modification of the previously described biotin switch protocol, which relies on ascorbate in the presence of chelators to decompose S-nitrosylated proteins. These techniques can be applied in situ to elucidate which compartments in tissues are affected in diseased states whose underlying pathologies are thought to represent a redox imbalance.


Treatment guidelines in inflammatory bowel disease: the Japanese perspectives.
The number of inflammatory bowel disease patients has been increasing in Japan and the demand for clinical practical guidelines emerged. A set of clinical practice guidelines for ulcerative colitis and Crohn's disease were thus published in 2006 and 2011, respectively. Their English versions were then published in 2000 and 2012, respectively. These guidelines aim to provide appropriate clinical indicators to Japanese practitioners to improve the outcomes of inflammatory bowel disease patients. The guidelines are based on global literature-based evidence as well as evidence from Japan. The Japanese guidelines were developed based on the existing evidence with integration of the experts' consensus. The criteria for recommendation grade were also determined by the level of evidence as well as by the experts' consensus. It is a distinct feature of the Japanese guidelines to disclose this process explicitly. This recommendation rating is thus useful to fill the gap between evidence and daily clinical practice. Since the Japanese guidelines are primarily based on global literature-based evidence, most of the clinical indicators in them are consistent with those in other guidelines from the Western world. Meanwhile, there are some distinctly different statements in the Japanese guidelines reflecting Japanese standard clinical practice, evidence, and the opinions of Japanese experts.


Exercise induced hypoglycaemic hyperinsulinism.
Hyperinsulinism in childhood is often caused by genetic defects involving the regulation of insulin secretion leading to recurrent episodes of hypoglycaemia. We report two patients with exercise induced hypoglycaemia. Standardised short exercise tests with frequent blood glucose and plasma insulin measurements were performed in the patients and young healthy controls. Short term exercise resulted in insulin induced hypoglycaemia 15 to 50 minutes after the end of exercise. A massive burst of insulin secretion was observed within a few minutes of the start of exercise in both patients. By contrast glucose and insulin concentrations remained unchanged in healthy controls. Hyperinsulinaemic hypoglycaemia after moderate physical exercise represents a rarely described phenotype of hyperinsulinism with an as yet unknown defect in the regulation of insulin secretion. It should be suspected in individuals with recurrent exercise related syncope or disturbance of consciousness.


Pediatric penetrating neck trauma: Hard signs of injury and selective neck exploration.
Selective neck exploration and computed tomography angiography (CTA) in penetrating neck trauma have been well described in adults. However, data in the pediatric population are sparse. The extent to which these practices have been adopted in pediatric patients is unknown. Retrospective, single-center cohort study of pediatric penetrating neck trauma for the years 2001 to 2014 in a dedicated children's hospital/Level 1 pediatric trauma center. Clinical data, sensitivity and specificity of hard signs (active hemorrhage, airway compromise, expanding hematoma, crepitus, and so on) and soft signs of injury (bruit, voice change, stridor, laceration less than 2 cm, nonexpanding hematoma, and so on), and trends in imaging were examined. A total of 44 patients were identified with penetrating neck trauma. The majority of these patients were male (55%) aged 8 months to 18 years and a median of 7.3 years. Sixteen patients underwent neck exploration with 13 major injuries identified in 10 patients. Nineteen patients had associated injuries. Ten patients had at least one hard sign of injury, and 16 patients had only soft signs of injury. The sensitivity and specificity of hard signs of injury were 100% (95% confidence interval [CI], 59-100%) and 94.4% (95% CI, 79-99%), respectively. Soft signs only had a sensitivity and specificity of 100% (95% CI, 39-100%) and 75.5% (95% CI, 60-86%), respectively. Positive and negative predictive values were 4.8% and 100%, respectively, for both hard and soft signs. The number of CTA studies increased over time but was not statistically significant. Forty (90%) patients were discharged home and two patients died. These results suggest that management of penetrating neck trauma in children includes selective neck exploration based on physical examination and the use of CTA in stable patients, similar to current adult recommendations. We did not observe evidence of missed injuries over the study period. Therapeutic/care management, level IV.


Population structure, antimicrobial resistance, and mutation frequencies of Streptococcus pneumoniae isolates from cystic fibrosis patients.
Forty-eight Streptococcus pneumoniae isolates recovered from sputum samples from 26 cystic fibrosis (CF) patients attending our CF unit (1995 to 2003) were studied. Mean yearly incidence of isolation was 5.5%, and all were strains recovered from young patients (< or = 12 years). The isolation was linked to clinical exacerbation in 35% of the cases, but only 27% of these were not accompanied by other CF pathogens. Fifty percent of the patients presented with two to four isolates over the studied period. Pulsed-field gel electrophoresis-SmaI digestion revealed a high heterogeneity (32 pulsotypes among 48 isolates) and the persistence over a 6-month period of a single clone (clone A) in two patients. This clone, presenting a varied multiresistance phenotype, was identified as the Spain23F-1 clone and was also recognized in six other patients, including two out of nine patients from the CF unit of Sant Joan de Deu Hospital, Barcelona, Spain. In our isolates, 16 different serotypes were recognized, the most frequent being 23F (33.3%), 19F (18.8%), 6A (6.2%), and 6B (6.2%). High overall resistance rates were observed: to penicillin, 73%; to cefotaxime, 33%; to erythromycin, 42%; to tetracycline, 58%; to chloramphenicol, 48%; and to trimethoprim-sulfamethoxazole, 67%. Resistance to fluoroquinolones was not detected. Multiresistance was a common feature (60%). The percentage of S. pneumoniae strains with increased frequencies of mutation to rifampin resistance (> or = 7.5 x 10(-8)) was significantly higher (P = 0.02) in CF (60%) than among non-CF (37%) isolates in the same institution (M. I. Morosini et al., Antimicrob. Agents Chemother. 47:1464-1467, 2003). Even though a clear association with acute exacerbations could not be observed, long-term clonal persistence and variability, high frequency of antibiotic resistance, and hypermutability indicate the plasticity for adaptation of S. pneumoniae to the CF lung environment.


The influence of intrapartum opioid use on breastfeeding experience at 6 weeks post partum: A secondary analysis.
To examine breastfeeding experiences up to 6 weeks postpartum for mothers administered intranasal fentanyl, subcutaneous fentanyl or intramuscular pethidine for intrapartum analgesia. A secondary analysis was undertaken using the per-protocol dataset to examine the third phase of a larger randomised controlled trial. This phase of the study examined breastfeeding intention and experience from the first hour of birth to 6 weeks postpartum. Medical records were audited and women were contacted at 6 weeks postpartum to complete a telephone questionnaire. Two maternity hospitals in South Australia. Healthy women birthing at term received intranasal fentanyl (n=37), subcutaneous fentanyl (n=37), or intramuscular pethidine (n=35). While maternal characteristics and birth outcomes were comparable between groups, women who received either intranasal fentanyl or subcutaneous fentanyl experienced fewer difficulties in establishing breastfeeding by 6 weeks postpartum when compared to intramuscular pethidine (p<0.01). Women who received fentanyl reported that their neonates had less difficulties establishing breastfeeding, compared to those who received pethidine. Therefore, for woman who intend to breastfeed, fentanyl should be the preferred opiate, for the relief of pain in labour. When providing education to women in relation to intrapartum pain relief it is important to consider the potential influence on breastfeeding experience. This research provides evidence that fentanyl is a suitable alternative to pethidine for women requesting parenteral analgesia in labour.


Intrahepatic arterial flow distribution after ligation of a right replaced hepatic artery. A case report.
A basic requirement for arterial chemotherapy of liver tumors is complete catheter perfusion of the liver. In cases with atypical anatomy of the hepatic artery, it is frequently impossible to obtain this goal by means of a single catheter. In a patient with a right replaced hepatic artery, the aberrant vessel was ligated and the left hepatic artery was perfused through a catheter inserted into the gastroduodenal artery. Perfusion scans performed through the catheter 14 and 135 days after arterial ligation showed a fall in the arterial flow to the right liver (right/left ratio 0.43 and 0.60). In contrast, a nearly complete perfusion of the liver (0.91 right/left ratio) was obtained 28 days after ligation, when the perfusion scan was performed immediately after catheter infusion of 90,000,000 degradable starch microspheres (DSM: diameter = 40 m). DSM administration is supposed to increase back pressure in the lobe receiving native circulation, thus activating intrahepatic collateral flow to the ischemic lobe. As regards regional treatment of liver tumors, obvious conclusions are to be drawn.


Equipment specifications for supported treadmill ambulation training.
Supported Treadmill Ambulation Training (STAT) is a mode of therapy for gait retraining for patients with spinal cord injuries or other upper motor neuron dysfunction. The STAT program involves simultaneously supporting a portion of the patient's weight while gait training on a treadmill. STAT has been successful in improving the gait of many research subjects, but has not been widely applied in clinical practice. The goal of this study was to acquire practical, clinically useful information regarding this therapeutic intervention in order to remove barriers to its use. This manuscript enumerates equipment specifications for the treadmill, body weight support (BWS) system, and harness. The ergonomics of the work space are also considered, since the therapist(s) will need access to the patient's legs during therapy. The specific recommendations were determined through prior clinical experience, consultation of anthropometric tables, and application of engineering principles. The guidelines listed are intended to facilitate safe and effective application of the therapy at minimum hardware cost.


The fibroblast growth factor receptor substrate 3 adapter is a developmentally regulated microtubule-associated protein expressed in migrating and differentiated neurons.
Fibroblast growth factor (FGF) mediated signaling is essential to many aspects of neural development. Activated FGF receptors signal primarily through the FGF receptor substrate (Frs) adapters, which include Frs2/Frs2alpha and Frs3/Frs2beta. While some studies suggest that Frs3 can compensate for the loss of Frs2 in transfected cells, the lack of an effective Frs3 specific antibody has prevented efforts to determine the role(s) of the endogenous protein. To this end, we have generated a Frs3 specific antibody and have characterized the pattern of Frs3 expression in the developing nervous system, its subcellular localization as well as its biochemical properties. We demonstrate that Frs3 is expressed at low levels in the ventricular zone of developing cortex, between E12 and E15, and it co-localizes with nestin and acetylated alpha-tubulin in radial processes in the ventricular/subventricular zones as well as with betaIII tubulin in differentiated cortical neurons. Subcellular fractionation studies demonstrate that endogenous Frs3 is both soluble and plasma membrane associated while Frs3 expressed in 293T cells associates exclusively with lipid rafts. Lastly, we demonstrate that neuronal Frs3 binds microtubules comparable to the microtubule-associated protein, MAP2, while Frs2 does not. Collectively, these data suggest that neuronal Frs3 functions as a novel microtubule binding protein and they provide the first biochemical evidence that neuronal Frs3 is functionally distinct from Frs2/Frs2alpha.


Comparison of the polypeptide composition of Escherichia coli outer membranes prepared by two methods.
Escherichia coli outer membranes were prepared by centrifugation to equilibrium in sucrose gradients and then treated with Sarkosyl in the presence of ethylenediaminetetraacetate. The polypeptide profiles of the two outer membrane preparations were compared by two-dimensional polyacrylamide gel electrophoresis. The patterns obtained were not identical, and Sarkosyl removed several minor proteins from the outer membrane.


Selected immunohistochemical prognostic factors in endometrial cancer.
The objectives of this study were to assess the immunohistochemical expression of p53, bcl-2, c-erbB-2, Ki-67, estrogen (ER) and progesterone (PR) receptors, matrix metalloproteinase-7 and -26 (MMP-7 and MMP-26) in endometrial cancer patients and to assess the relation between steroid receptor positivity and other markers. Experimental prospective study. Department of Obstetrics and Gynecology, Department of Genetics, Department of Pathology, Palacký University Medical School and University Hospital Olomouc. We studied 144 cases of primary untreated endometrial carcinoma in which the p53, bcl-2, c-erbB-2, Ki-67, ER, PR, MMP-7, and MMP-26 antigens were investigated with the use of immunohistochemical methods. We evaluated the correlations among immunohistochemical staining and the age, International Federation of Gynecology and Obstetrics stage, grading, depth of invasion, and metastatic spread to lymph nodes. Mean age was 65.7 years (range, 34-90 years). p53, bcl-2, c-erbB-2, Ki-67, ER, and PR were positive in 35 (24.3%), 100 (69.4%), 41 (28.4%), 65 (45.1%), 115 (79.8%), and 127 (88.1%) cases, respectively. Matrix metalloproteinases were evaluated in a group of 70 patients, wherein MMP-7 was positive in 33 patients (47.1%) and MMP-26 was positive in 40 patients (57.1%). The expression of MMP-7 decreased with higher patient age. p53 and Ki-67 overexpression was found to be related to poor differentiation. Immunostaining for bcl-2 correlated with the positivity of steroid receptors status, whereas immunostaining for c-erbB-2 correlated inversely with ER-positive group of cases. The overexpression of p53 and Ki-67 seems to indicate a more malignant phenotype, whereas bcl-2 expression in dependence of steroid receptor positivity could contribute to the identification of high-risk tumors.


A complex prediction: three-dimensional model of the yeast exosome.
We present a model of the yeast exosome based on the bacterial degradosome component polynucleotide phosphorylase (PNPase). Electron microscopy shows the exosome to resemble PNPase but with key differences likely related to the position of RNA binding domains, and to the location of domains unique to the exosome. We use various techniques to reduce the many possible models of exosome subunits based on PNPase to just one. The model suggests numerous experiments to probe exosome function, particularly with respect to subunits making direct atomic contacts and conserved, possibly functional residues within the predicted central pore of the complex.


Migrant Asian Indians in New Zealand; prediction of metabolic syndrome using body weights and measures.
The aim of this study of Asian Indian migrants in New Zealand was to determine cut-off points for body mass index, waist circumference, waist-to-hip ratio, and waist-to-height ratio that best discriminate for increased risk of type 2 diabetes and cardiovascular disease. One hundred and seventy-five (90F, 85M) Asian Indian volunteers (aged >50 y) were recruited from urban Auckland, New Zealand. Body weight, height and waist and hip circumferences were measured using standard techniques. Waist-to-hip ratio, waist-to-height ratio and body mass index were derived. Total and percent body fat by dual energy X-ray absorptiometry, and fasting glucose, insulin and lipids were measured. Three measures of metabolic risk were determined: the homeostasis model assessment of insulin resistance, the McAuley score for insulin sensitivity and metabolic syndrome by International Diabetes Federation criteria. Body mass index, percent body fat and anthropometric measurements of central adiposity generally did not perform well as indicators of metabolic risk in this high risk population of Asian Indian migrants. Our data support the use of lower ethnic specific body mass index and waist circumference for Asian Indian women and men. The discriminatory power of waist-to-height ratio was similar to that of body mass index. Hence, waist-to-height ratio could be used as a simple screening tool. A recommendation, of a waist-to- height ratio of less than 0.5 that would underpin the simple public health message of "your waist circumference should be less than half your height".


Rationale and design of MARQUEE: a phase III, randomized, double-blind study of tivantinib plus erlotinib versus placebo plus erlotinib in previously treated patients with locally advanced or metastatic, nonsquamous, non-small-cell lung cancer.
We present the rationale and design for MARQUEE, a phase III, randomized, double-blind, placebo-controlled study of ARQ 197 plus erlotinib versus placebo plus erlotinib in previously treated subjects with locally advanced or metastatic, nonsquamous, non-small-cell lung cancer (NSCLC). The design of MARQUEE is based on preclinical data, the current understanding of the role of cellular N-methyl-N'-nitroso-guanidine human osteosarcoma (MNNG HOS) transforming gene (MET) in NSCLC, and clinical data from a randomized phase II study. The available evidence suggests that dual inhibition of MET and the epidermal growth factor receptor (EGFR) may overcome resistance to EGFR inhibitors. In the phase II study, the combination of tivantinib plus erlotinib significantly improved progression-free survival (PFS) and overall survival (OS) compared with placebo plus erlotinib in the subset of patients with nonsquamous histology, a population enriched for MET overexpression. The primary endpoint in MARQUEE is OS. Secondary and exploratory objectives include determination of PFS, OS in molecular subgroups (defined by EGFR and KRAS mutation status, amplification or overexpression of MET, and serum hepatocyte growth factor), and safety. All patients will be tested for biomarkers, and the results will provide a wealth of information on the role of tivantinib in treating nonsquamous NSCLC.


[Anti-ulcer therapy after eradication of Helicobacter pylori].
Helicobacter pylori (H. pylori) infection is the cause of the frequent relapse of peptic ulcer disease. Successful eradication therapy of H. pylori is associated with a decline in the recurrence of peptic ulcer. In this paper, we discussed the significance of anti-ulcer therapy after H. pylori eradication therapy. In patients with duodenal ulcer, maintenance therapy for preventing ulcer recurrence is not necessary because the rate of ulcer recurrence after eradication therapy is very low. However, in patients with gastric ulcer, the rate of ulcer relapse and reflux esophagitis ranges between 5-10% in the Japanese population even after successful eradication therapy; therefore, maintenance therapy for 1 year may be permissible in patients with gastric ulcer even after successful eradication therapy.


Pooling Morphometric Estimates: A Statistical Equivalence Approach.
Changes in hardware or image-processing settings are a common issue for large multicenter studies. To pool MRI data acquired under these changed conditions, it is necessary to demonstrate that the changes do not affect MRI-based measurements. In these circumstances, classical inference testing is inappropriate because it is designed to detect differences, not prove similarity. We used a method known as statistical equivalence testing to address this limitation. Equivalence testing was carried out on 3 datasets: (1) cortical thickness and automated hippocampal volume estimates obtained from healthy individuals imaged using different multichannel head coils; (2) manual hippocampal volumetry obtained using two readers; and (3) corpus callosum area estimates obtained using an automated method with manual cleanup carried out by two readers. Equivalence testing was carried out using the "two one-sided tests" (TOST) approach. Power analyses of the TOST were used to estimate sample sizes required for well-powered equivalence testing analyses. Mean and standard deviation estimates from the automated hippocampal volume dataset were used to carry out an example power analysis. Cortical thickness values were found to be equivalent over 61% of the cortex when different head coils were used (q < .05, false discovery rate correction). Automated hippocampal volume estimates obtained using the same two coils were statistically equivalent (TOST P = 4.28 × 10(-15) ). Manual hippocampal volume estimates obtained using two readers were not statistically equivalent (TOST P = .97). The use of different readers to carry out limited correction of automated corpus callosum segmentations yielded equivalent area estimates (TOST P = 1.28 × 10(-14) ). Power analysis of simulated and automated hippocampal volume data demonstrated that the equivalence margin affects the number of subjects required for well-powered equivalence tests. We have presented a statistical method for determining if morphometric measures obtained under variable conditions can be pooled. The equivalence testing technique is applicable for analyses in which experimental conditions vary over the course of the study.


Dynamic Kv4.3-CaMKII unit in heart: an intrinsic negative regulator for CaMKII activation.
Reduction of transient outward current (I(to)) and excessive activation of Ca(2+)/Calmodulin-dependent kinase II (CaMKII) are general features of ventricular myocytes in heart failure. We hypothesize that alterations of I(to) directly regulate CaMKII activation in cardiomyocytes. A dynamic coupling of I(to) channel subunit Kv4.3 and inactive CaMKII was discovered in cardiomyocytes with the membrane predominant distribution by co-immunoprecipitation and fluorescence resonance energy transfer techniques. CaMKII dissociation from Kv4.3-CaMKII units caused a significant increase in CaMKII autophosphorylation and L-type calcium current (I(Ca)) facilitation. I(Ca) facilitation was blunted by the compartmental Ca²(+) chelator BAPTA but unaffected by bulk Ca²(+) chelator EGTA, implicating membrane-localized CaMKII. Kv4.3 overexpression reduced basal CaMKII autophosphorylation in myocytes and eliminated Ca²(+)-induced CaMKII activation. Kv4.3 blocks CaMKII activation by binding to the calmodulin binding sites, whereas Kv4.3 uncoupling releases these sites and leads to a substantial CaMKII activation. Our results uncovered an important mechanism that regulates CaMKII activation in the heart and implicate I(to) channel alteration in pathological CaMKII activation.


Active Surveillance of Carbapenemase-Producing Organisms (CPO) Colonization With Xpert Carba-R Assay Plus Positive Patient Isolation Proves to Be Effective in CPO Containment.
Background: Rapid screening of patients for colonization with carbapenemase-producing organisms (CPO), coupled with implementation of infection prevention strategies, has the potential to contain the spread of CPO. Methods: We first evaluated the performance of Xpert Carba-R assay (in comparison with other phenotypic methods) for carbapenemase detection using clinical isolates, and then used it to determine the intestinal CPO colonization in hospitalized patients. We then assessed the effectiveness of patient isolation in controlling the spread of CPO in a medical intensive care unit. Results: The Xpert Carba-R assay required the least processing time to reveal results and showed a 94.5% sensitivity and specificity in carbapenemase detection, except for IMP-8 (n = 4). During a 6-month study period, 134 patients in one ward were studied for CPO colonization and infection. Fifteen patients (11.2%) were colonized by CPO as detected by Xpert Carba-R assay, including three NDM, three IMP, and nine KPC possessing strains. The overall colonization and CPO infection rates were both 11.2% each. Isolation of patients with CPO led to a reduction in both colonization (from 28.6 to 5.6%) and infection rates (from 35.7 to 2.8%) during the study period (p < 0.05). Conclusion: Active surveillance of CPO utilizing the Xpert Carba-R assay supplemented with immediate patient isolation, proved to be an effective strategy to limit the spread of CPO in a health care setting.


Prediction of Antioxidant Activity of Cherry Fruits from UAS Multispectral Imagery Using Machine Learning.
In this research, a model for the estimation of antioxidant content in cherry fruits from multispectral imagery acquired from drones was developed, based on machine learning methods. For two consecutive cultivation years, the trees were sampled on different dates and then analysed for their fruits' radical scavenging activity (DPPH) and Folin-Ciocalteu (FCR) reducing capacity. Multispectral images from unmanned aerial vehicles were acquired on the same dates with fruit sampling. Soil samples were collected throughout the study fields at the end of the season. Topographic, hydrographic and weather data also were included in modelling. First-year data were used for model-fitting, whereas second-year data for testing. Spatial autocorrelation tests indicated unbiased sampling and, moreover, allowed restriction of modelling input parameters to a smaller group. The optimum model employs 24 input variables resulting in a 6.74 root mean square error. Provided that soil profiles and other ancillary data are known in advance of the cultivation season, capturing drone images in critical growth phases, together with contemporary weather data, can support site- and time-specific harvesting. It could also support site-specific treatments (precision farming) for improving fruit quality in the long-term, with analogous marketing perspectives.


Regulation of the DPP1-encoded diacylglycerol pyrophosphate (DGPP) phosphatase by inositol and growth phase. Inhibition of DGPP phosphatase activity by CDP-diacylglyceron and activation of phosphatidylserine synthase activity by DGPP.
The regulation of the Saccharomyces cerevisiae DPP1-encoded diacylglycerol pyrophosphate (DGPP) phosphatase by inositol supplementation and growth phase was examined. Addition of inositol to the growth medium resulted in a dose-dependent increase in the level of DGPP phosphatase activity in both exponential and stationary phase cells. Activity was greater in stationary phase cells when compared with exponential phase cells, and the inositol- and growth phase-dependent regulations of DGPP phosphatase were additive. Analyses of DGPP phosphatase mRNA and protein levels, and expression of beta-galactosidase activity driven by a P(DPP1)-lacZ reporter gene, indicated that a transcriptional mechanism was responsible for this regulation. Regulation of DGPP phosphatase by inositol and growth phase occurred in a manner that was opposite that of many phospholipid biosynthetic enzymes. Regulation of DGPP phosphatase expression by inositol supplementation, but not growth phase, was altered in opi1Delta, ino2Delta, and ino4Delta phospholipid synthesis regulatory mutants. CDP-diacylglycerol, a phospholipid pathway intermediate used for the synthesis of phosphatidylserine and phosphatidylinositol, inhibited DGPP phosphatase activity by a mixed mechanism that caused an increase in K(m) and a decrease in V(max). DGPP stimulated the activity of pure phosphatidylserine synthase by a mechanism that increased the affinity of the enzyme for its substrate CDP-diacylglycerol. Phospholipid composition analysis of a dpp1Delta mutant showed that DGPP phosphatase played a role in the regulation of phospholipid metabolism by inositol, as well as regulating the cellular levels of phosphatidylinositol.


Optometric intraprofessional referral of visual dysfunctions.
Every optometrist has the professional responsibility to detect visual dysfunctions. If optometrists do not wish to provide vision therapy in their offices they have an obligation to refer. Simple screening tests and guidelines for referral are described.


Effective and timely evaluation of pulmonary congestion: qualitative comparison between lung ultrasound and thoracic bioelectrical impedance in maintenance hemodialysis patients.
The assessment of pulmonary congestion in maintenance hemodialysis (MHD) patients is challenging. Bioelectrical impedance analysis (BIA) can estimate body water compartments. Natriuretic peptides are markers of hemodynamic stress, neurohormonal activation and extracellular volume overload. Lung ultrasound (LUS) has been proposed for the non-invasive estimation of extravascular lung water through B-lines assessment. Up to now, no study evaluated the correlation between B-lines, segmental thoracic BIA, and natriuretic peptides in MHD patients. The aims of this study were: (1) To validate LUS as a tool for an effective and timely evaluation of pulmonary congestion in MHD patients, in comparison with segmental thoracic BIA, and with natriuretic peptides; (2) To compare a comprehensive whole chest ultrasound scanning with a simplified and timely scanning scheme limited to the lateral chest regions.Thirty-one MHD adult patients were examined. LUS, total body and thoracic BIA, and natriuretic peptides were performed immediately before and after a mid-week dialysis session. The number of B-lines assessed by LUS was compared with total body and thoracic impedance data and with natriuretic peptides.Pre-HD B-lines ranged 0-147 (mean 31) and decreased significantly post-HD (mean 16, P < 0.001). A significant correlation was found between the number of B-lines and extra-cellular water index (ECWI, r = 0.45, P < 0.001), with thoracic impedance (r = 0.30, P < 0.05), and with BNP (r = 0.57, P < 0.01). The dynamic changes in B-lines correlated better with thoracic impedance than with total body impedance, and correlated with extra-cellular but not with intra-cellular water index. The correlation between B-lines and ECWI was similar when LUS was limited to the lateral chest regions or performed on the whole chest. Multivariate analysis showed that only segmental thoracic impedance was an independent predictor of residual pulmonary congestion.The dynamic changes in B-lines after hemodialysis are correlated to the changes in total body and extra-cellular water, and particularly to lung fluids removal. B-line assessment in MHD patients is highly feasible with a simplified and timely scanning scheme limited to the lateral chest regions. These premises make B-lines a promising biomarker for a bedside assessment of pulmonary congestion in MHD patients.


Statistical analysis of a lung cancer spectral histopathology (SHP) data set.
We report results on a statistical analysis of an infrared spectral dataset comprising a total of 388 lung biopsies from 374 patients. The method of correlating classical and spectral results and analyzing the resulting data has been referred to as spectral histopathology (SHP) in the past. Here, we show that standard bio-statistical procedures, such as strict separation of training and blinded test sets, result in a balanced accuracy of better than 95% for the distinction of normal, necrotic and cancerous tissues, and better than 90% balanced accuracy for the classification of small cell, squamous cell and adenocarcinomas. Preliminary results indicate that further sub-classification of adenocarcinomas should be feasible with similar accuracy once sufficiently large datasets have been collected.


Physiology and pharmacology of iodized oil in goiter prophylaxis.
Thyroid complications resulting from excess iodide such as thyrotoxicosis, thyroiditis, sialadenitis, or hypothyroidism are much rarer after iodine supplementation with Lipiodol than with KI. They do not militate against its widespread use in endemic goiter populations, especially in pregnant women. However, patients with multinodular goiter should not be treated or should be treated only under careful observation. When Lipiodol-induced thyrotoxicosis occurs it tends to be mild or even subclinical and self-limited. If treatment is required, potassium perchlorate with or without thionamides is recommended. Iodide goiter has not been seen after Lipiodol supplementation, nor has thyroiditis. Sialadenitis occurs rarely. Iodide derived from Lipiodol readily enters the fetus, possibly by active transport, and theoretically endangers the fetus because autoregulation of the fetal thyroid occurs late during gestation. Despite the difficulty in distinguishing iodide goiter from iodide deficiency goiter of the newborn, no cases of neonatal iodide goiter have been reported. Possible mechanisms of thyroid inhibition by excess iodide are briefly discussed. The use of locally produced iodized plant oils is recommended for financial reasons as well as for the benefits derived from local participation.


Evaluation of propofol for repeated prolonged deep sedation in children undergoing proton radiation therapy.
The aim of this study is to evaluate the safety and sufficiency of a fixed dose rate propofol infusion for repeated prolonged deep sedation in children for proton radiation therapy (PRT). With ERB approval, we recorded anaesthesia monitoring data in children undergoing repeated prolonged propofol sedation for PRT. Sedation was introduced with a single bolus of i.v. midazolam 0.1 mg kg(-1) followed by repeated small boluses of propofol until sufficient depth of sedation was obtained. Sedation was maintained with fixed dose rate propofol infusion of 10 mg kg(-1) h(-1) in all patients up to the end of the radiation procedure. Patient characteristics, number and duration of sedation, propofol induction dose, necessity to alter propofol infusion rate, and heart rate, mean arterial pressure, respiratory rate were noted at the end of the radiation procedure before cessation of the propofol infusion. Data are mean (sd) or range (median) as appropriate. Eighteen children aged from 1.4 to 4.2 yr (2.6 yr) had 27.6 (sd 2.0) (497 in total) radiation procedures within 44.1 (4.0) days lasting 55.7 (8.8) min. Propofol bolus dose for induction, monitoring, and positioning was 3.7 (1.0) mg kg(-1). Propofol bolus requirements were quite stable over the successive weeks of treatment and variability was larger between individuals than over time. In none of the children did propofol infusion rate need to be changed from the pre-set 10 mg kg(-1) h(-1) flow rate because of haemodynamic state, respiratory conditions or inadequate anaesthesia. Repeated prolonged deep sedation over several weeks in very young children using a fixed rate propofol infusion was safe and adequate for all patients.


Biochemical Analysis Reveals the Multifactorial Mechanism of Histone H3 Clipping by Chicken Liver Histone H3 Protease.
Proteolytic clipping of histone H3 has been identified in many organisms. Despite several studies, the mechanism of clipping, the substrate specificity, and the significance of this poorly understood epigenetic mechanism are not clear. We have previously reported histone H3 specific proteolytic clipping and a protein inhibitor in chicken liver. However, the sites of clipping are still not known very well. In this study, we attempt to identify clipping sites in histone H3 and to determine the mechanism of inhibition by stefin B protein, a cysteine protease inhibitor. By employing site-directed mutagenesis and in vitro biochemical assays, we have identified three distinct clipping sites in recombinant human histone H3 and its variants (H3.1, H3.3, and H3t). However, post-translationally modified histones isolated from chicken liver and Saccharomyces cerevisiae wild-type cells showed different clipping patterns. Clipping of histone H3 N-terminal tail at three sites occurs in a sequential manner. We have further observed that clipping sites are regulated by the structure of the N-terminal tail as well as the globular domain of histone H3. We also have identified the QVVAG region of stefin B protein to be very crucial for inhibition of the protease activity. Altogether, our comprehensive biochemical studies have revealed three distinct clipping sites in histone H3 and their regulation by the structure of histone H3, histone modifications marks, and stefin B.


NPPB and ACAN, two novel SHOX2 transcription targets implicated in skeletal development.
SHOX and SHOX2 transcription factors are highly homologous, with even identical homeodomains. Genetic alterations in SHOX result in two skeletal dysplasias; Léri-Weill dyschondrosteosis (LWD) and Langer mesomelic dysplasia (LMD), while no human genetic disease has been linked to date with SHOX2. SHOX2 is, though, involved in skeletal development, as shown by different knockout mice models. Due to the high homology between SHOX and SHOX2, and their functional redundancy during heart development, we postulated that SHOX2 might have the same transcriptional targets and cofactors as SHOX in limb development. We selected two SHOX transcription targets regulated by different mechanisms: 1) the natriuretic peptide precursor B gene (NPPB) involved in the endochondral ossification signalling and directly activated by SHOX; and 2) Aggrecan (ACAN), a major component of cartilage extracellular matrix, regulated by the cooperation of SHOX with the SOX trio (SOX5, SOX6 and SOX9) via the protein interaction between SOX5/SOX6 and SHOX. Using the luciferase assay we have demonstrated that SHOX2, like SHOX, regulates NPPB directly whilst activates ACAN via its cooperation with the SOX trio. Subsequently, we have identified and characterized the protein domains implicated in the SHOX2 dimerization and also its protein interaction with SOX5/SOX6 and SHOX using the yeast-two hybrid and co-immunoprecipitation assays. Immunohistochemistry of human fetal growth plates from different time points demonstrated that SHOX2 is coexpressed with SHOX and the members of the SOX trio. Despite these findings, no mutation was identified in SHOX2 in a cohort of 83 LWD patients with no known molecular defect, suggesting that SHOX2 alterations do not cause LWD. In conclusion, our work has identified the first cofactors and two new transcription targets of SHOX2 in limb development, and we hypothesize a time- and tissue-specific functional redundancy between SHOX and SHOX2.


Prognostic usefulness of ACTH in the postoperative period of Cushing's disease.
To analyze the usefulness of plasma ACTH in predicting CD remission after surgery and to evaluate the prognostic usefulness of ACTH measurement after the cortisol and ACTH nadir (48 h prior to discharge). A prospective study was made of 65 patients with CD operated upon between 2005 and 2016. Postsurgery plasma ACTH and cortisol were measured every 6 h, in the absence of corticosteroid coverage. Hydrocortisone was started in the presence of adrenal insufficiency or cortisol <55.2 nmol/L. Plasma ACTH was again determined before discharge. Usefulness of plasma ACTH in predicting CD remission. Remission at 3 months of CD was achieved in 56 of 65 cases, with late recurrence in 18 of 58 cases. Following resection, the ACTH nadir was significantly lower referred to late remission (2.8 vs 6.5 pmol/L; P = 0.031) and higher for recurrence (2.1 vs 4.8 pmol/L; P < 0.001), and identical results were obtained for the ACTH values before discharge. In the analysis of the ROC curves, nadir and before discharge ACTH values <1.9 pmol/L and <2.6 pmol/L were respectively indicative of early remission (AUC 0.827; P < 0.001); <6.2 pmol/L of remission at 3 months (AUC 0.847; P = 0.001) and >3.2 pmol/L of recurrence (AUC 0.810; P < 0.001) in both ACTH values. A time to ACTH nadir <46 h was indicative of early remission (AUC 0.751; P = 0.001), while a time >39 h was indicative of recurrence (AUC 0.773; P = 0.001). We propose an ACTH value <3.3 pmol/L as a good long-term prognostic marker in the postoperative period of CD. Reaching the ACTH nadir in less time is associated to a lesser recurrence rate.


Pope Leo XII's death: the twist to a longstanding dispute by novel historical documents and paleopathographic analysis.
Although the practice of autopsy on the Pope's corpse was performed from the 16th century, autopsy reports are only rarely analysed, and never with the aim of investigating the real causes of the death from a concomitant medical and historical point of view. Here, for the first time, we report on the discovery of new unpublished documents from the Vatican Secret Archives and their investigation by a scientific and inter-disciplinary approach. This analysis allows us to draw new conclusions on the true cause of Leo XII's mysterious death. His sudden death, that occurred on February 10th, 1829 after a short illness, particularly struck the public. Suspicions of poisoning or surgeon's guilt or inexperience and even the shadow of a venereal disease, contributed to create a "black legend" on his pontificate and death. On the contrary, the present paleopathographic analysis points toward a new conclusion. The regular use of catheterization with a silver syringe provided an easy access for bacterial superinfection, confirmed by the observed early emphysematous stage of the corpse. So, the most substantiated hypothesis concerning the cause of Leo XII's death indicates a severe form of sepsis, exacerbated by a weakened state due to chronic hemorrhoids.


Involving vendors in continuous quality improvement efforts.
In the hospital environment, vendors supply a wide range of items, from surgical sutures to the latest in high-cost technological equipment. Also, many clinical and support services, such as respiratory therapy, transcription, and computer databanks are now outsourced to commercial vendors. Interaction with such vendors is often less than satisfactory, with prolonged timelines and disruption of an important process that is being computerized. Although hospitals deal with very few vendors in long-term relationships, such as those seen in manufacturing, this should not preclude the formation of a supplier-customer relationship that goes beyond management's interaction with the sales representative in response to a request for proposal. This is especially true when a process improvement team has studied an internal process and defined a key quality characteristic.


Changes in energy cost and total external work of muscles in elite race walkers walking at different speeds.
The aim of the study was to assess energy cost and total external work (total energy) depending on the speed of race walking. Another objective was to determine the contribution of external work to total energy cost of walking at technical, threshold and racing speed in elite competitive race walkers. The study involved 12 competitive race walkers aged 24.9 4.10 years with 6 to 20 years of experience, who achieved a national or international sports level. Their aerobic endurance was determined by means of a direct method involving an incremental exercise test on the treadmill. The participants performed three tests walking each time with one of the three speeds according to the same protocol: an 8-minute walk with at steady speed was followed by a recovery phase until the oxygen debt was repaid. To measure exercise energy cost, an indirect method based on the volume of oxygen uptake was employed. The gait of the participants was recorded using the 3D Vicon opto-electronic motion capture system. Values of changes in potential energy and total kinetic energy in a gate cycle were determined based on vertical displacements of the centre of mass. Changes in mechanical energy amounted to the value of total external work of muscles needed to accelerate and lift the centre of mass during a normalised gait cycle. The values of average energy cost and of total external work standardised to body mass and distance covered calculated for technical speed, threshold and racing speeds turned out to be statistically significant (p 0.001). The total energy cost ranged from 51.2 kJ.m-1 during walking at technical speed to 78.3 kJ.m-1 during walking at a racing speed. Regardless of the type of speed, the total external work of muscles accounted for around 25% of total energy cost in race walking. Total external work mainly increased because of changes in the resultant kinetic energy of the centre of mass movement.


The ontogeny of independent ingestion in mice: or, why won't infant mice feed?
Unlike infant rats, which show deprivation-related ingestion in several different test situations, infant mice appeared to be relatively unwilling to feed independently of suckling until 12 days of age. We tested mouse pups that were deprived (of food, water, suckling, and maternal care) for 1, 7, or 24 hr in ingestive tests in which a milk diet was spread on the floor of their test container (Experiment 1). Pups at 3, 6, and 9 days of age consumed small amounts of the diet and showed little increase in intake when deprivation was increased. In contrast (and like rat pups of all ages), mouse pups 12 and 15 days of age actively ingested the diet and increased their intake with increased deprivation. Six-day-old mouse pups were similarly unwilling to ingest a 5% sucrose solution, though 12-day-old pups showed deprivation-related intake (Experiment 2). Cellular dehydration (produced by hypertonic saline injection), a potent stimulus for ingestion in infant rats, did not stimulate ingestion in mice younger than 12 days of age (Experiment 3). Finally, when ingestion was tested with diet infusions made through oral cannulas, mouse pups at 6 and 9 days of age showed only a slight increase in intake with increased deprivation. However, by 12 days of age, pups' ingestion increased markedly with deprivation (Experiment 4). Thus, mouse pups seem to be very different from rat pups with respect to the early existence of ingestive systems. The neural substrates for the ingestive responses that subserve independent ingestion are only minimally present in infant mice or are somehow inhibited.


[Surgical treatment of tracheal obstruction in children].
47 infants and children with tracheobronchial obstruction requiring surgical treatment are reported. 10 had subglottic stenosis; 17 severe tracheomalacia; 19 intraluminal tracheal stenosis (in 2 of whom it was congenital); 12 granulation tissue or webs; 4 both tracheal stenosis and tracheal fistula; and 1 had a tear of the right main bronchus. The anterior cricoid splitting procedure for the management of severe acquired subglottic stenosis was performed in 10, in 2 of whom it failed and tracheostomy was required. Aortopexy was performed in 14 cases and pulmonary arteriopexy in 1. A rib cartilage graft and a prosthetic splint fabricated from Marlex mesh were applied in 2 cases after failed aortopexy. The 19 patients with tracheal stenosis were treated as follows: tracheal splitting with autologous free tibial periosteal graft was used in 2 infants; transbronchoscopic resection was successful in 12 children; wedge resection of the tracheal fistula and anterior anastomosis was done in 4; segmental tracheal resection with end-to-end anastomosis in 1; and suture of a bronchial tear was performed in 1. There was no operative mortality; 2 patients died; but the deaths were not directly related to surgery. In our experience, the surgical approach is both safe and expedient in relieving tracheal obstruction in most infants and children.


Effects of Peer Support Interventions on the Communication of Preschoolers with Autism Spectrum Disorder: A Systematic Review.
Many young children with autism spectrum disorders (ASDs) experience difficulty in the development of communication skills. Teaching peers to make use of communication support behaviors has been investigated as a strategy to increase communication for young children with ASD in early childhood settings. The purpose of this systematic review was to examine (1) the overall effects of peer support interventions on the communication of young children with ASD and (2) any possible moderating variables related to participant and intervention characteristics. The social support model was used as a framework for the study of intervention components. Eighteen single-case experimental design studies (48 children with ASD) met the inclusion criteria and were advanced to the full coding and analysis phase of the investigation. Descriptive analyses and effect size estimations using the improvement rate difference (IRD) metric were conducted. Overall, peer support interventions were found to be effective across a range of young children with ASD and intervention approaches. Evidence was also identified for the use of the social support model as a framework to guide the development of peer interventions in early childhood settings. The use of friendship groups, the selection of play materials based on the interests of the child with ASD, and the provision of augmentative and alternative communication appeared to be associated with positive communication outcomes.


Giant hysteromyoma after vaginoplasty in a woman with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: case report and review of the literature.
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital disorder characterized by congenital absence of both the uterus and vagina. Some patients require surgery to create a neovagina, however, the preservation of a nonfunctional rudimentary uterus after surgery may lead to long-term complications. Herein, a rare case of a giant hysteromyoma after vaginoplasty, in a 31-year-old Chinese female patient who was diagnosed with MRKH syndrome, is reported. The patient, who had undergone vaginal reconstruction 4 years previously, presented with abdominal distension for the previous 2 weeks. Transabdominal ultrasonography showed a firm mass of approximately 10 × 10 cm in the lower abdomen. The patient subsequently underwent an exploratory laparotomy, and a leiomyoma from her rudimentary uterus was removed. Beside this case, seven cases, published between 2004 and 2020, were identified during a literature search. Findings of the present and previously published cases suggest that gynaecologists should pay particular attention to the risks of pelvic complications in female patients with MRKH syndrome who have previously undergone surgery, and select appropriate therapeutic methods.


Irinotecan/gemcitabine combination chemotherapy in pancreatic cancer.
Gemcitabine (Gemzar) and irinotecan (CPT-11, Camptosar) are active cytotoxic drugs against pancreatic cancer. Preclinical data evaluating the combination of gemcitabine and irinotecan suggest dose-dependent synergistic interactions in SCOG small-cell lung cancer and MCF-7 breast cancer cell lines. Two phase I trials of this combination have been reported to date: the day 1 and 8 every-3-week schedule (IrinoGem trial), and the day 1, 8, and 15 every-4-week schedule (MSKCC trial). Both trials aimed to determine the maximum tolerated dose of irinotecan when administered as a 90-minute i.v. infusion either immediately after (IrinoGem) or before or immediately after (MSKCC) gemcitabine at 1,000 mg/m2 by 30-minute i.v. infusion in patients with solid tumors. The achieved maximum tolerated dose of IrinoGem has a higher dose intensity of irinotecan (100 mg/m2 on days 1 and 8, every-3-week cycle) compared with the MSKCC schedule (60 mg/m2 on days 1, 8, and 15, every-4-week trial). In IrinoGem, two of three previously untreated metastatic pancreas cancer patients had durable radiologic partial responses. The third had stable disease with clinical benefit for eight cycles. In addition, a patient with metastatic adenocarcinoma of unknown primary--potentially pancreatic--has had a durable response and is alive more than 30 months after the diagnosis. Preliminary results of a 45-patient multicenter phase II trial with IrinoGem in advanced and metastatic pancreas cancer were recently reported. Toxicity was modest, with no toxic deaths or neutropenic fever. Radiologic response rate was 20% of patients (9 out of 45), and a CA 19-9 decrease of more than 50% from baseline values occurred in 32.5% of patients (13 out of 40). Median survival was 6 months (range: 0.9 to 12.2+ months) and median time to treatment failure was 2.9 months (range: 0.1 to 11.3+ months). A pivotal international multicenter phase III trial comparing IrinoGem to single-agent gemcitabine in advanced and metastatic pancreas cancer is ongoing.


HB-EGF but not amphiregulin or their receptors HER1 and HER4 is altered in endometrium of women with unexplained infertility.
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) and its receptors (HER1 and HER4) play a role in the human implantation process. Amphiregulin is a member of the EGF family but with unknown function in human fertility. It has been suggested that some women with unexplained infertility have defective endometrial development. The aim of this study is to determine the presence of amphiregulin and the receptors HER1 and HER4 in normal human endometrium throughout the menstrual cycle. In addition, the present study aims to compare endometrium from women with unexplained infertility with endometrium from women with male factor infertility and healthy fertile controls. Immunohistochemistry and real-time polymerase chain reaction were used to determine the expression of HB-EGF, HER1, HER4, and amphiregulin. The stromal staining of HER1 and the epithelial staining of HER4 were most intense in the mid- and late-secretory-phase endometrium. Amphiregulin did not vary during the menstrual cycle. In the mid-secretory phase, the protein expression of HB-EGF was lower in endometrium from women with unexplained infertility versus normal endometrium and endometrium from women with male factor infertility. HB-EGF and HER4 mRNA expression in mid-secretory endometrium of women with unexplained and male factor infertility were increased compared with normal controls. Impaired endometrial expression of certain members of the EGF family may contribute to infertility in some women with unexplained infertility.


Improved prognosis of thoracic aortic aneurysms: a population-based study.
Managing thoracic aortic aneurysms identified incidentally by increased use of computed tomography, echocardiography, and magnetic resonance imaging is problematic, especially in the elderly. To ascertain whether the previously reported poor prognosis for individuals with thoracic aortic aneurysms has changed with better medical therapies and improved surgical techniques that can now be applied to aneurysm management. Population-based cohort study. All 133 patients with the diagnosis of degenerative thoracic aortic aneurysms among Olmsted County, Minnesota, residents between 1980 and 1994 compared with a previously reported cohort of similar patients between 1951 and 1980. The primary clinical end points were incidence, cumulative rupture risk, rupture risk as a function of aneurysm size, and survival. In contrast to abdominal aortic aneurysms, for which men are affected predominately, 51% of thoracic aortic aneurysms were identified in women who were considerably older at recognition than men (mean age, 75.9 vs 62.8 years, respectively; P= .01). The overall incidence rate of 10.4 per 100000 person-years (95% confidence interval [CI], 8.6-12.2) between 1980 and 1994 was more than 3-fold higher than the rate from 1951 to 1980. The cumulative risk of rupture was 20% after 5 years. Seventy-nine percent of ruptures occurred in women (P= .01). The 5-year risk of rupture as a function of aneurysm size at recognition was 0% for aneurysms less than 4 cm in diameter, 16% (95% CI, 4%-28%) for those 4 to 5.9 cm, and 31% (95% CI, 5%-56%) for aneurysms 6 cm or more. Overall 5-year survival improved to 56% (95% CI, 48%-66%) between 1980 and 1994 compared with only 19% between 1951 and 1980 (P<.01). In this population, elderly women represent an increasing portion of all patients with clinically recognized thoracic aortic aneurysms and constitute the majority of patients whose aneurysm eventually ruptures. Overall survival for thoracic aortic aneurysms has improved significantly in the past 15 years.


Predicting the receptive range of olfactory receptors.
Although the family of genes encoding for olfactory receptors was identified more than 15 years ago, the difficulty of functionally expressing these receptors in an heterologous system has, with only some exceptions, rendered the receptive range of given olfactory receptors largely unknown. Furthermore, even when successfully expressed, the task of probing such a receptor with thousands of odors/ligands remains daunting. Here we provide proof of concept for a solution to this problem. Using computational methods, we tune an electronic nose to the receptive range of an olfactory receptor. We then use this electronic nose to predict the receptors' response to other odorants. Our method can be used to identify the receptive range of olfactory receptors, and can also be applied to other questions involving receptor-ligand interactions in non-olfactory settings.


Attending to adult ADHD: a review of the neurobiology behind adult ADHD.
Attention deficit hyperactivity disorder (ADHD) is a common disorder in childhood, which progresses to adulthood in about a fifth of cases. For various reasons, adult ADHD is a disorder not comprehensively assessed by psychiatrists, not least because the biological underpinnings are only recently being unmasked.AimsThis selective review targets psychiatrists without a background in neuroscience and aims to describe the neurobiological basis of ADHD. In total, 40 articles from a PubMed search were selected for inclusion based on sample population and methodology (neuroimaging studies). Studies focussing on adult participants were selected preferentially for inclusion. Seminal articles relevant to childhood populations were included for the purpose of understanding general concepts around ADHD. The neuropathology of ADHD is not rooted in a single anatomical area, but in multiple parallel and intersecting pathways, which have demonstrated impaired functional connectivity in ADHD brains. Dysfunction in executive function, reward processing, attention networks and default networks play major roles in the neuropathology of this condition. Biological findings vary between individuals, with some showing greater dysfunction at cortical levels and others at subcortical levels, which is in keeping with its clinical heterogeneity. Improved symptomatology in adulthood is linked to a number of factors. Maturation of the prefrontal cortex in early adulthood contributes to symptom attenuation in many cases, meaning that individuals with cortical dysfunction are more likely to grow out of symptoms, whereas individuals with subcortical dysfunction may be less likely to do so. There is emerging evidence for a similar but distinct disorder arising de novo in adulthood.


The Enhancement Mechanism of Different Single-Transition Metal Atomic Catalysts/Sulfur Cathode on High-Performance of Li-S Batteries.
Materials with various single-transition metal atoms dispersed in nitrogenated carbons (M─N─C, M = Fe, Co, and Ni) are synthesized as cathodes to investigate the electrocatalytic behaviors focusing on their enhancement mechanism for performance of Li-S batteries. Results indicate that the order of both electrocatalytic activity and rate capacity for the M─N─C catalysts is Co > Ni > Fe, and the Co─N─C delivers the highest capacity of 1100 mAh g-1 at 1 C and longtime stability at a decay rate of 0.05% per cycle for 1000 cycles, demonstrating excellent battery performance. Theoretical calculations for the first time reveal that M─N─N─C catalysts enable direct conversion of Li2 S6 to Li2 S rather than Li2 S4 to Li2 S by stronger adsorption with Li2 S6 , which also has an order of Co > Ni > Fe. And Co─N─C has the strongest adsorption energy, not only rendering the highest electrocatalytic activity, but also depressing the polysulfides' dissolution into electrolyte for the longest cycle life. This work offers an avenue to design the next generation of highly efficient sulfur cathodes for high-performance Li-S batteries, while shedding light on the fundamental insight of single metal atomic catalytic effects on Li-S batteries.


Complications of Minimally Invasive Surgery in Children: A Prospective Morbidity and Mortality Analysis Using the Clavien-Dindo Classification.
There is a lack of information about evaluation of pediatric minimal access surgery complications; the Clavien-Dindo classification was never used for a large series of laparoscopic and thoracoscopic pediatric procedures. With a prospective Morbidity and Mortality database, all the minimal access surgical procedures carried out between 2012 and 2016 were included in this study. Statistical analyses were used to valuate modification of surgical techniques in to 2 periods (period 1: January 2012 to February 2014; period 2: February 2014 to February 2016). A total of 1374 minimal access procedures were performed on 1371 patients. The overall complication rate was 2.9%. No differences, in terms of complications, were observed between elective and emergency procedures (P=0.3). There was a significant difference between the complication rate of thoracoscopic surgery (P=0.027). These results provide the relevance of adequate recording system and standardized classification for analyses and reduction of complications for pediatric minimal access procedures.


Irrigation and Crop Load Management Lessen Rain-Induced Cherry Cracking.
The combined effects of deficit irrigation and crop load level on sweet cherry (Prunus avium L.) physiological and agronomic response were evaluated during the 2019 season in a commercial orchard located in southeastern Spain. Two irrigation treatments were imposed: (i) control treatment (CTL) irrigated above crop water requirements at 110% of crop evapotranspiration (ETC) and (ii) a deficit irrigation treatment (DI) irrigated at 70% ETC. Within each irrigation treatment, crop load was adjusted to three levels: 100% (natural crop load-high), 66% (medium crop load), and 33% (low crop load). The water relations results were more affected by the irrigation strategies applied than by the crop load management. The deficit irrigation strategy applied reduced soil water availability for DI trees, which led to a continuous decrease in their gas exchange and stem water potential. At harvest, the fruit water potential and osmotic potential of cherries from the DI treatment resulted in significantly lower values than those measured in cherries from CTL trees. On the other hand, both the irrigation strategies imposed and the crop load management used impacted fruit quality. Trees with the lowest level of crop load had fruits of greater size, regardless of the irrigation treatment assayed, and in the DI treatment, cherries from the trees with the lowest crop load were darker and more acidic than those from the trees with the highest crop load. Our results emphasize the different effects that rainfall before harvest has on mature cherries. Thus, cracked cherries at harvest represented 27.1% of the total yield of CTL trees while they were 8.3% of the total yield in DI trees. Cherries from CTL trees also showed a greater cracking index than those from DI trees. Moreover, a linear relationship between crop load and fruit cracked at harvest was observed, particularly for the CTL treatment; thus, the lower the crop load, the greater the proportion of cracked cherries.


Discrimination of acoustic patterns in rats using the water T-maze.
The extraction of abstract rules and their generalization to new items has been proposed to be at the heart of higher cognitive functions such as language. Research with animals has shown that various species can extract rather complex patterns from the input, as well as establish abstract same/different relations. However, much of these findings have been observed after extensive training procedures. Here, we tested rats' capacity to discriminate and generalize tone triplets that entailed a repetition from triplets that followed an ordinal, non-repeating pattern following a relatively short discrimination training procedure in a water T-maze. Our findings demonstrate that, under this procedure and after only 12 sessions, rats can learn to discriminate both patterns when a reliable difference in pitch variations is present across them (Experiment 1). When differences in pitch are eliminated (Experiment 2), no discrimination between patterns is found. Results suggest a procedure based on a water T-maze might be used to explore discrimination of acoustic patterns in rodents.


Chrysin attenuates carrageenan-induced pleurisy and lung injury via activation of SIRT1/NRF2 pathway in rats.
Chrysin, a natural polyphenol plentifully contained in honey, propolis, vegetables and fruits, it has been reported to exert a variety of pharmacological activities. In the present study, we mainly investigated the protective effects and underlying molecular mechanisms of chrysin on carrageenan-induced lung injury in rats. The results showed that chrysin inhibited the neutrophils infiltration, attenuated histological injury of lung tissues, decreased PMNs markers level and oxidative stress markers levels of lungs in rats. Further studies showed chrysin can inhibit the NF-кB activation in neutrophils cells, activate SIRT1/NRF2 pathway and reduce the expression of adhesion molecule in lung tissues. Taken together, these results suggested that chrysin can attenuate carrageenan-induced lung injury via inhibition of neutrophils activation and oxidative stress response, and that this attenuation is, at least partially, related to up-regulation of SIRT1/NRF2 signaling pathway. This study also validates SIRT1/NRF2 is an effective pharmacological target to protect against carrageenan-induced lung injury.


Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in human lung and liver microsomes and cytochromes P-450 expressed in hepatoma cells.
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent tobacco-specific carcinogen in animals, has been linked to tobacco-related cancers in humans. The cytochrome(s) P-450 (P-450) responsible for the metabolic activation of NNK in humans has not been identified. The present work investigated the ability of human lung and liver microsomes and 12 forms of human P-450, expressed in Hep G2 (hepatoma) cells, to metabolize NNK. Of the 12 P-450 forms, P-450 1A2 had the highest activity in catalyzing the conversion of NNK to the keto alcohol, 4-hydroxy-1-(3-pyridyl)-1-butanone. P-450s 2A6, 2B7, 2E1, 2F1, and 3A5 also had measurable activities in the formation of keto alcohol. The apparent Km and Vmax for the formation of keto alcohol in the P-450 1A2-expressed Hep G2 cell lysate were 309 microM and 55 pmol/min/mg protein, respectively. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol, a reductive product, was the major metabolite formed, whereas the formation of keto alcohol and its aldehyde and acid derivatives (all alpha-hydroxylation products) constituted approximately 1% of the initial amount of NNK in P450-expressed Hep G2 cell lysate. A similar metabolite pattern was observed with human lung or liver microsomes. In human lung microsomes, the apparent Kms for the formation of 4-hydroxy-4-(3-pyridyl)butyric acid, 4-oxo-1-(3-pyridyl)-1-butanone, NNK-N-oxide, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol were 526, 653, 531, and 573 microM, respectively; the formation of keto alcohol was not observed. For human lung microsomes, there was no sex-related difference in NNK metabolism. Carbon monoxide (90% atmosphere) significantly inhibited the metabolism of NNK in human lung and liver microsomes. 7,8-Benzoflavone, an inhibitor of P-450s 1A1 and 1A2, had no effect on NNK metabolism in human lung microsomes but decreased the formation of keto alcohol by 47% in human liver microsomes. Similarly, antibodies against human P-450s 1A2 and 2E1 decreased keto alcohol formation by 42% and 53%, respectively, in human liver microsomes but did not affect NNK metabolism in lung microsomes. Inhibitory antibodies against P-450s 2A1, 2C8, 2D1, or 3A4 had little or no effect on the metabolism of NNK in human liver or lung microsomes.(ABSTRACT TRUNCATED AT 400 WORDS)


Awareness, attitudes, and practices related to the swine influenza pandemic among the Saudi public.
During an infectious disease outbreak, it is critical to learn as much as possible about the concerns, knowledge, attitudes, and behavior of the public. Such information can be crucial to the improvement of communication efforts by public health officials and clinicians. The aim of this study was to identify awareness, attitudes, and practices related to influenza A (H1N1) among the Saudi public. A cross-sectional study of 1,548 adult subjects recruited from various shopping malls in Riyadh and Jeddah was conducted. All of the subjects were interviewed using a questionnaire that tested their knowledge, attitudes, and use of precautionary measures in relation to the H1N1 influenza pandemic. More than half (54.3%, 840/1548) of the participants showed high concern, 43.7%(677/1548) showed a low level of knowledge, and 60.8%(941/1548) had taken minimal or no precautionary measures. After adjusting for other variables, education level was the only significant predictor of the level of concern (p < 0.001), while greater precautionary measures were taken by participants who were male (p < 0.001), older (p = 0.047), better educated (p = 0.04), and more knowledgeable (p < 0.001). More than one-third (38.3%) of participants were not convinced that the MOH reports about the disease were true, and only 16.1% of the participants reported receiving information from health providers. High concern did not translate into a higher compliance with precautionary recommendations, possibly due to the low level of knowledge about the disease among the public. Frequent communication between physicians and the public is recommended to help dispel myths about the disease and to spread better information about the role that the public can play in limiting the spread of the disease.