Control of familywise errors in multiple endpoint assessments via stepwise permutation tests.
We describe permutation based sequentially rejective multiple comparison procedures useful in multiple endpoint assessments. We used Monte Carlo methods to compare the power of these newly devised tests to that of tests due to Holm and Rom as well as to the classical Bonferroni method. We illustrate applications of the methods with analysis of visual field data collected from optic neuritis patients. We conclude that the new methods are particularly useful when there are many endpoints involved, the data are significantly correlated, and/or the distributional assumptions are questionable.


Specificity of human antibodies reactive with pneumococcal C polysaccharide.
Antibodies reactive with C polysaccharide (PS) were found in healthy adults, pneumococcal patients, and vaccinees. These antibodies were not directed to the phosphocholine determinant of the C PS, as they appear to be in mice, since the human antibodies were inhibitable only with C PS. We found another population of phosphocholine-specific antibodies inhibitable only by phosphocholine and related compounds.


Personality Traits Modulate the Effect of tDCS on Reading Speed of Social Sentences.
In this case, 62 university students participated in the study, in which a between-subjects design was adopted. Participants were also given the behavioral approach system (BAS) and behavioral inhibition system (BIS) scales. Participants had to read a list of 60 sentences with interpersonal and neutral content: 20 approach ("Pedro accepted Rosa in Whatsapp"), 20 avoidance ("Pedro Blocked Rosa in Whatsapp") and 20 neutral ("Marta thought about the causes of the problem"). After reading them, they were subjected to 20 min of transcranial direct current stimulation (tDCS) in one of the two conditions: anodal (31) or sham (31). After tDCS, they had to read other list of 60 sentences matched in approach, avoidance and neutral contents with the former list. We found significant improvement in reading speed after anodal stimulation for social and neutral sentences. Regarding affective traits, we found that anodal stimulation benefitted reading speed in low-BIS and low-BAS participants and had no effect in either high BAS or high BIS participants. In addition, tDCS improvement in reading speed was significantly lower in avoidance sentences in low-BIS (avoidance) participants. We discuss these results at the light of previous research and highlight the importance of approach and avoidance traits as moderators of tDCS effects.


Spinal intraosseous arteriovenous fistulas with perimedullary drainage associated with vertebral compression fracture: illustrative case.
Although osseous involvement is occasionally observed in spinal epidural arteriovenous fistulas (AVFs) or seen as a part of diseases of spinal arteriovenous metameric syndrome, purely intraosseous spinal AVFs are extremely rare. Their clinical and imaging characteristic features are not well known. The authors present a case of purely intraosseous AVFs associated with compression fracture. A 76-year-old man presented with back pain and progressive myelopathy. Computed tomography showed compression fracture of the T12 vertebral body and dilatation of perimedullary veins. Spinal angiography revealed an intraosseous AVF at the T12 spine level, which was fed by multiple feeders of ventral somatic branches and drained into the paravertebral and perimedullary veins. The intraosseous AVF was completely occluded by the combined techniques of transarterial and transvenous embolization with glue and a coil. The symptoms disappeared within 1 month after embolization. Although extremely rare, spinal intraosseous AVFs can develop after compression fracture and cause congestive myelopathy. Combined transarterial and transvenous embolization is useful for the specific case of spinal intraosseous AVFs with both paravertebral and perimedullary drainage.


Neurobiological and behavioral mechanisms of circadian rhythm disruption in bipolar disorder: A critical multi-disciplinary literature review and agenda for future research from the ISBD task force on chronobiology.
Symptoms of bipolar disorder (BD) include changes in mood, activity, energy, sleep, and appetite. Since many of these processes are regulated by circadian function, circadian rhythm disturbance has been examined as a biological feature underlying BD. The International Society for Bipolar Disorders Chronobiology Task Force (CTF) was commissioned to review evidence for neurobiological and behavioral mechanisms pertinent to BD. Drawing upon expertise in animal models, biomarkers, physiology, and behavior, CTF analyzed the relevant cross-disciplinary literature to precisely frame the discussion around circadian rhythm disruption in BD, highlight key findings, and for the first time integrate findings across levels of analysis to develop an internally consistent, coherent theoretical framework. Evidence from multiple sources implicates the circadian system in mood regulation, with corresponding associations with BD diagnoses and mood-related traits reported across genetic, cellular, physiological, and behavioral domains. However, circadian disruption does not appear to be specific to BD and is present across a variety of high-risk, prodromal, and syndromic psychiatric disorders. Substantial variability and ambiguity among the definitions, concepts and assumptions underlying the research have limited replication and the emergence of consensus findings. Future research in circadian rhythms and its role in BD is warranted. Well-powered studies that carefully define associations between BD-related and chronobiologically-related constructs, and integrate across levels of analysis will be most illuminating.


Impact of opportunistic testing in a systematic cervical cancer screening program: a nationwide registry study.
Systematic screening for precancerous cervical lesions has resulted in decreased incidence and mortality of cervical cancer. However, even in systematic screening programs, many women are still tested opportunistically. This study aimed to determine the spread of opportunistic testing in a systematic cervical cancer screening program, the impact of opportunistic testing in terms of detecting cytological abnormalities and examine the associations between sociodemography and opportunistic testing. A nationwide registry study was undertaken including women aged 23-49 years (n = 807,624) with a cervical cytology between 2010 and 2013. The women were categorised into: 1) screening after invitation; 2) routine opportunistic testing, if they were either tested more than 9 months after the latest invitation or between 2.5 years and 3 years after the latest cervical cytology and 3) sporadic opportunistic testing, if they were tested less than 2.5 years after the latest cervical cytology. Cytological diagnoses of women in each of the categories were identified and prevalence proportion differences (PPD) and 95% confidence intervals (CIs) were used to explore group differences. Associations between sociodemography and undergoing opportunistic testing were established by multinomial logistic regression. In total, 28.8% of the cervical cytologies were due to either routine (20.7%) or sporadic (8.1%) opportunistic testing. Among women undergoing routine opportunistic testing, a larger proportion had high-grade squamous intraepithelial abnormalities than invited women (PPD: 0.6%, 95 % CI: 0.03-1.17%). A similar proportion of cytological abnormalities among women undergoing sporadic opportunistic testing and invited women was found. In multivariate analyses, younger age, being single or a social welfare recipient and residence region (North Denmark) were especially associated with opportunistic testing (routine or sporadic). One fourth of cervical cytologies in this study were collected opportunistically. Compared to invited women, women undergoing routine opportunistic testing were more likely to be diagnosed with abnormal cytologies. Hence, routine opportunistic testing might serve as an important supplement to the systematic screening program by covering non-participating women who may otherwise be tested with a delay or not tested at all. Among women tested more often than recommended (sporadic testing), no benefits in terms of detecting more cytological abnormalities were identified.


Perception and Signaling of Strigolactones.
Strigolactones (SLs), a recently discovered class of phytohormones, are important regulators of plant growth and development. While the biosynthetic pathway of these molecules is well documented, until recently there was not much known about the molecular mechanisms underlying SL perception and signal transduction in plants. Certain aspects of their perception and signaling, including the hormone-mediated interaction between receptor and F-box protein, degradation of suppressor proteins and activation of transcription factors, are also found in other phytohormones. However, some of SL signaling features seem to be specific for the SL signaling pathway. These include the enzymatic activity of the SL receptor and its destabilization caused by SLs. This review summarizes the current knowledge about SL signaling pathway in plants.


Catalytic asymmetric epoxidation of alpha,beta-unsaturated amides: efficient synthesis of beta-aryl alpha-hydroxy amides using a one-pot tandem catalytic asymmetric epoxidation-Pd-catalyzed epoxide opening process.
The catalytic asymmetric epoxidation of alpha,beta-unsaturated amides using Sm-BINOL-Ph3As=O complex was succeeded. Using 5-10 mol % of the asymmetric catalyst, a variety of amides were epoxidized efficiently, yielding the corresponding alpha,beta-epoxy amides in up to 99% yield and in more than 99% ee. Moreover, the novel one-pot tandem process, one-pot tandem catalytic asymmetric epoxidation-Pd-catalyzed epoxide opening process, was developed. This method was successfully utilized for the efficient synthesis of beta-aryl alpha-hydroxy amides, including beta-aryllactyl-leucine methyl esters. Interestingly, it was found that beneficial modifications on the Pd catalyst were achieved by the constituents of the first epoxidation, producing a more suitable catalyst for the Pd-catalyzed epoxide opening reaction in terms of chemoselectivity.


Applicability of non-halogenated methyl propionate to microencapsulation.
Applicability of methyl propionate to microencapsulation was evaluated with regard to volatility, capability of forming emulsions, and their quality. An emulsion-based technique was then developed to encapsulate progesterone into poly-d,l-lactide-co-glycolide microspheres. Their characteristics were compared with those prepared using ethyl acetate. Our results demonstrated that methyl propionate had greater evaporative tendency and less water miscibility than ethyl acetate did. The former allowed us to prepare good microspheres. Their average volume mean diameter was 68.3 ± 1.7 μm with a span index of 0.91 ± 0.13. Progesterone did not undergo polymorphic transition during microencapsulation, and its encapsulation efficiency ranged from 41.80 ± 1.83 to 85.64 ± 1.95%. Residual methyl propionate in various microspheres was found to be 0.97 ± 0.03 to 1.54 ± 0.07%. Such microsphere characteristics were quite similar to those prepared by the ethyl acetate-based microencapsulation process. Overall, our findings reflect that methyl propionate has a potential to become an invaluable solvent for microencapsulation.


Increased serum osteocalcin levels in patients with lactase deficiency.
Serum levels of osteocalcin, a noncollagenous bone matrix protein, have been found to be a specific biochemical parameter of bone formation. In the literature in subjects with osteoporosis, an increased incidence of lactase deficiency has been described. We therefore determined the serum levels of osteocalcin in 10 patients with lactase deficiency and in 20 control subjects by radioimmunoassay. The patients with lactase deficiency were dietary treated and had a very low daily calcium intake. Serum osteocalcin levels were significantly higher in the patients with lactase deficiency than in the control subjects. In contrast, serum levels of parathyroid hormone, alkaline phosphatase, calcium, and phosphorus were not statistically different in the two groups. Our data suggest an increased rate of bone turnover in patients with lactase deficiency on a low calcium diet; possibly calcium supplementation is indicated in dietary-treated patients with lactase deficiency.


Formulation and physiologic factors affecting the pharmacology of carrier-mediated anticancer agents.
Major advances in carrier-mediated agents (CMAs), which include nanoparticles and conjugates, have revolutionized drug delivery capabilities over the past decade. While providing numerous advantages such as increased exposure duration, greater solubility and delivery to tumor sites over their small molecule counterparts, there is substantial variability in how individual CMA formulations affect the pharmacology, pharmacokinetics and pharmacodynamics (efficacy and toxicity) of these agents. CMA formulations are complex in nature compared to their small molecule counterparts and consist of multiple components and variables that can affect the pharmacological profile. This review provides an overview of factors that affect the pharmacologic profiles observed in CMA-formulated chemotherapy, primarily in liposomal formulations, that are currently in preclinical or early clinical development. Despite the numerous advantages that CMA formulations provide, their clinical use is still in its infancy. It is critical that we understand the mechanisms and effects of CMAs in navigating biological barriers and how these factors affect their biodistribution and delivery to tumors. Future studies are warranted to better understand the complex pharmacology and interaction between CMA carriers and biological systems, such as the mononuclear phagocyte system and tumor microenvironment.


A Review of Natural Products for Prevention of Acute Kidney Injury.
acute kidney injury (AKI), formerly called acute renal failure (ARF), is commonly defined as an abrupt decline in renal function, clinically manifesting as a reversible acute increase in nitrogen waste products-measured by blood urea nitrogen (BUN) and serum creatinine levels-over the course of hours to weeks. AKI occurs in about 20% of all hospitalized patients and is more common in the elderly. Therefore, it is necessary to prevent the occurrence of AKI, and to detect and treat early, since it is known that a prolonged period of kidney injury increases cardiovascular complications and the risk of death. Despite advances in modern medicine, there are no consistent treatment strategies for preventing the progression to chronic kidney disease. Through many studies, the safety and efficacy of natural products have been proven, and based on this, the time and cost required for new drug development can be reduced. In addition, research results on natural products are highly anticipated in the prevention and treatment of various diseases. In relation to AKI, many papers have reported that many natural products can prevent and treat AKI. in this paper, the results of studies on natural products related to AKI were found and summarized, and the mechanism by which the efficacy of AKI was demonstrated was reviewed. Many natural products show that AKI can be prevented and treated, suggesting that these natural products can help to develop new drugs. In addition, we may be helpful to elucidate additional mechanisms and meta-analysis in future natural product studies.


Navicular Stress Fractures.
Navicular stress fractures are multifactorial injuries due to chronic overload on the navicular, particularly in young athletes. The navicular is subject to unique stresses and has a complex blood supply, making it susceptible to stress fractures and potentially delayed union or nonunion. Expeditious diagnosis is critical to prevent a delay in treatment and a poor outcome. Advanced imaging is essential in making the diagnosis and monitoring healing. Both nonsurgical and surgical treatments have demonstrated good results. Nonsurgical management consists of a period of immobilization and nonweight bearing, and surgical management typically involves open reduction and internal fixation. Patients need to be appropriately counseled regarding expectations for these challenging injuries.


Hereditary risk of women's cancers.
The characterization of specific genes responsible for the hereditary risk of common cancers has enabled the development of clinical tests designed to identify at-risk individuals and to significantly improve the clinical outcome of such individuals. Two of the most important syndromes associated with a hereditary risk of cancer in women are hereditary breast and ovarian cancer, resulting from the BRCA1 and BRCA2 genes, and hereditary non-polyposis colorectal cancer, caused primarily by the MLH1 and MSH2 genes. As testing for the hereditary risk of breast, ovarian, endometrial and colorectal cancer enters the clinical mainstream, physicians responsible for the health care of women are increasingly required to assess and provide guidance to healthy patients with a strong family history, cancer survivors who may be at risk of a second cancer and women who discover that a family member carries a specific mutation identified through genetic testing. Obstetricians and gynaecologists must therefore become familiar with the principles of assessing the family history for specific hereditary cancer syndromes, with the appropriate use of tests to confirm such syndromes and with the management options for women who have inherited a greatly increased risk of cancer.


Potential utility of DNA sequence analysis of long-term-stored plant leaf fragments for forensic discrimination and identification.
This study examined the potential utility of DNA sequence analysis to discriminate and identify plant material in forensic investigations. DNA was extracted from plant leaf fragments of 11 species stored for 5 to 22 years after collection. The trnH-psbA intergenic spacer and 316 bp of the rbcL gene were successfully amplified and sequenced for all fragments except for the trnH-psbA spacer of one sample. All of the plant samples were discriminated in pairwise comparisons of the sequences. Using a combination of local and global genetic databases is likely to provide greater reliability in search results to identify forensic samples from sequence data.


Cerebral palsy update.
A common language on CP has been developed for the European registers by the SCPE (Surveillance of Cerebral Palsy in Europe) working group and the common database allows prevalence analyses on a larger basis. CP prevalence increases with lower birthweight and higher immaturity. Increase of survival after preterm birth has first also increased CP rates. But already in the 80s this trend was reversed for LBW infants, and in the 90 s also for VLBW or very immature infants. The outcome with respect to CP in the group of extremely LBW or immature infants remains a matter of specific concern, as prevalence seems to be rather stable on a high level. CP is caused in more than 80% by brain lesions or maldevelopments which can be attributed to different timing periods of the developing brain. Extent and topography determine the clinical subtype of CP and are related also to the presence and severity of associated disabilities. CP, thus, offers a model to study plasticity of the developing brain. Reorganisation following unilateral lesions is mainly interhemispheric and homotopic. In the motor system, it involves the recruitment of ipsilateral tracts; functionality seems to be limited and decreases already towards the end of gestation. There is no clear evidence for substantial reorganisation in the sensory system. The best compensatory potential is described concerning language function following left hemispheric lesions. Language function reorganized to the right hemisphere eventually seems not to be impaired, this occurs, however, on the expense of primary right hemispheric functions.


Alerting the immune system to DNA damage: micronuclei as mediators.
Healthy cells experience thousands of DNA lesions per day during normal cellular metabolism, and ionizing radiation and chemotherapeutic drugs rely on DNA damage to kill cancer cells. In response to such lesions, the DNA damage response (DDR) activates cell-cycle checkpoints, initiates DNA repair mechanisms, or promotes the clearance of irreparable cells. Work over the past decade has revealed broader influences of the DDR, involving inflammatory gene expression following unresolved DNA damage, and immune surveillance of damaged or mutated cells. Subcellular structures called micronuclei, containing broken fragments of DNA or whole chromosomes that have been isolated away from the rest of the genome, are now recognized as one mediator of DDR-associated immune recognition. Micronuclei can initiate pro-inflammatory signaling cascades, or massively degrade to invoke distinct forms of genomic instability. In this mini-review, we aim to provide an overview of the current evidence linking the DDR to activation of the immune response through micronuclei formation, identifying key areas of interest, open questions, and emerging implications.


A novel photomultiplier tube neutron time-of-flight detector.
A traditional neutron time-of-flight (nTOF) detector used in inertial confinement fusion consists of a scintillator coupled with a photomultiplier tube (PMT). The instrument response function (IRF) of such a detector is dominated by the scintillator-light decay. In DT implosions with neutron yield larger than 1013, a novel detector consisting of a microchannel-plate (MCP) photomultiplier tube in a housing without a scintillator (PMT nTOF) can be used to measure DT yield, ion temperature, and neutron velocity. Most of the neutron signals in PMT nTOF detectors are produced from neutron interaction with a PMT window. The direct interaction of neutrons with the MCP provides negligible contribution. The elimination of the scintillator removes the scintillator decay from the instrument response function and makes the IRF of the PMT nTOF detector faster, which makes the ion temperature and neutron velocity measurements more accurate. Three PMT nTOF detectors were deployed in the OMEGA laser system for the first time to diagnose inertial confinement fusion plasma. The design details, characteristics, and calibration results of these detectors in DT implosions on OMEGA are presented. Recommendations on the use of different PMTs for specific applications are provided.


Adalimumab in the treatment of pediatric Behçet's disease: case-based review.
Behçet's disease (BD) is a systemic vasculitis affecting prominently the veins, which is usually diagnosed in adulthood, but can occur in children younger than 16 years in about 4-26% of cases. The therapy is based on several immune-suppressive drugs; in case of inadequate control and/or complications, the biologic therapy with anti-TNF drugs has been successfully used in adults. Here, we reported one pediatric case of BD with systemic (persistent/recurrent high fever), skin and mucosal manifestations (recurrent aphthous stomatitis, anal/penile ulcers, erythema nodosum and papulo-pustules), that were unresponsive to the conventional treatment with steroids and colchicine; however, he was successfully treated with adalimumab. Compared to adult patients, the experience with adalimumab in the treatment of pediatric BD is very limited. Indeed, through a systematic search in the medical literature, we retrieved 4 case reports and 2 case series, describing BD pediatric patients treated with adalimumab, in addition to three clinical studies including some BD children. The analysis and discussion of these available clinical experiences may indicate adalimumab as an effective and safe option to treat several forms of BD, in addition to BD-related chronic uveitis.


Measuring access to urban health services using Geographical Information System (GIS): a case study of health service management in Bandar Abbas, Iran.
The current distribution of and access to health services along with the future health needs of the population have prompted wide application of Geographic Information Systems (GISs). During recent years, GIS has been used in public health management for planning and organization of healthcare services. This study investigates geographical accessibility of residential areas in Bandar Abbas, Iran to healthcare services. Accessibility was evaluated by using Floating Catchment Area (FCA), minimum distance methods and Response Time (RT) accessibility technique. More accurate measures of distances in Bandar Abbas, illustrated that Euclidean distances were not strongly correlated with network distances. The RT accessibility technique that utilizes shortest network path and time distances, presented detailed information about all the possible positions of the patients with respect to available healthcare services based on optimum and critical response times. Locations of public health services in Bandar Abbas were not related to the sites of populations. The RT accessibility technique provides a reasonably sensitive and robust evaluation of accessibility.


Presumptive renal tubular acidosis secondary to topiramate administration in a cat.
To describe renal tubular acidosis (RTA) and secondary acquired hyperaldosteronism in a cat as an adverse effect of topiramate therapy. An 8-year-old neutered female cat on chronic oral topiramate therapy at a recommended dose (11.9 mg/kg q 8 h) for seizure control was presented with severe metabolic acidosis and hypokalemia. Plasma electrolyte and acid-base analysis identified a severe metabolic acidosis (pH 7.153, reference interval: 7.31-7.46), hypokalemia (2.08 mmol/L [2.08 mEq/L], reference interval: 3.5-4.8 mmol/L [3.5-4.8 mEq/L]), and ionized hypercalcemia (1.85 mmol/L [1.85 mEq/L], reference range: 1.1-1.4 mmol/L [1.1-1.4 mEq/L]). Urinalysis revealed a urine specific gravity of 1.021 and a pH of 7.0. Diagnostic workup suggested distal RTA as a cause of the cat's acid-base and electrolyte disturbances. Aldosterone concentration was moderately increased, suggestive of secondary hyperaldosteronism. The metabolic abnormalities resolved with supportive care and discontinuation of topiramate. Topiramate is suggested to have led to the development severe RTA in a cat.


Roles of TauT and system A in cytoprotection of rat syncytiotrophoblast cell line exposed to hypertonic stress.
The purpose of this study was to clarify the cytoprotective mechanism(s) induced in a conditionally immortalized syncytiotrophoblast cell line (TR-TBT 18d-1) exposed to hypertonic conditions. Hypertonicity-induced apoptosis of TR-TBT 18d-1 cells, but this was blocked by addition of 1 mM taurine to the culture medium. TauT-knockdown using siRNA revealed that TauT is a major contributor to taurine uptake by TR-TBT 18d-1 cells, at least under normal conditions. Cellular uptake of [(3)H]taurine and [(14)C]betaine by TR-TBT 18d-1 cells cultured under hypertonic conditions was increased compared to that under normal conditions. TauT, BGT-1, ATA2 and HSP70 mRNAs were upregulated by hypertonicity, while OCTN2, ENT1 and CNT1 mRNAs were downregulated. [(3)H]Taurine uptake was strongly inhibited by TauT inhibitors such as hypotaurine and β-alanine. MeAIB, a system A specific substrate, inhibited hypertonic stress-induced [(14)C]betaine uptake. These results suggest that TauT and system A play cytoprotective roles in syncytiotrophoblasts exposed to hypertonic stress.


Ligustilide: a novel TRPA1 modulator.
TRPA1 is activated by electrophilic compounds such as mustard oil (MO). Here, we demonstrate a bimodal sensitivity of TRPA1 to ligustilide (Lig), an electrophilic volatile dihydrophthalide of dietary and medicinal relevance. Lig is a potent TRPA1 activator and is also capable to induce a modest block of MO activated currents. Aromatization to dehydroligustilide (DH-Lig), as occurs during aging of its botanical sources, reversed this profile, enhancing TRPA1 inhibition and reducing activation. Mutation of the reactive cysteines in mouseTRPA1 (C622S, C642S, C666S) dramatically reduced activation by MO and significantly reduced that by Lig, but had an almost negligible effect on the action of DH-Lig, whose activation mechanism of TRPA1 is therefore largely independent from the alkylation of cysteine residues. Taken together, these observations show that the phthalide structural motif is a versatile platform to investigate the modulation of TRPA1 by small molecules, being tunable in terms of activation/inhibition profile and mechanism of interaction. Finally, the action of Lig on TRPA1 may contribute to the gustatory effects of celery, its major dietary source, and to the pharmacological action of important plants from the Chinese and native American traditional medicines.


Assessing the Influence of an Individual Event in Complex Fault Spreading Network Based on Dynamic Uncertain Causality Graph.
Identifying the pivotal causes and highly influential spreaders in fault propagation processes is crucial for improving the maintenance decision making for complex systems under abnormal and emergency situations. A dynamic uncertain causality graph-based method is introduced in this paper to explicitly model the uncertain causalities among system components, identify fault conditions, locate the fault origins, and predict the spreading tendency by means of probabilistic reasoning. A new algorithm is proposed to assess the impacts of an individual event by investigating the corresponding node's time-variant betweenness centrality and the strength of global causal influence in the fault propagation network. The algorithm does not depend on the whole original and static network but on the real-time spreading behaviors and dynamics, which makes the algorithm to be specifically targeted and more efficient. Experiments on both simulated networks and real-world systems demonstrate the accuracy, effectiveness, and comprehensibility of the proposed method for the fault management of power grids and other complex networked systems.


Correlation and differences in cervical sagittal alignment parameters between cervical radiographs and magnetic resonance images.
Although cervical alignment is better assessed using standing radiography than supine magnetic resonance imaging (MRI), few studies have investigated this. This study aimed to investigate the difference in alignment between standing radiographs and supine MRI images, and assess whether neck position affects the cervical parameters and neurological changes. We analyzed 53 patients, measuring the O-C2 angle, C2-7 angle (the distinction between the lordotic and kyphotic groups), T1 slope, neck tilt, thoracic inlet angle, and the C2-7 sagittal vertical axis. Inter- and intra-group analyses were conducted to identify any difference between standing radiography and supine MRI. Statistical differences between the cervical parameters were compared. Strong correlations were noted between the equivalent parameters in the radiographs and MRI images, whereas no significant difference was observed in C2-7 angle in the kyphotic group between the radiographs and MRI images, or for neck tilt between the radiographs and MRI images. However, in the lordotic group, the C2-7 angle was significantly different between the two types of images and larger in the radiographs than in the MRI images (C2-7 angle in the radiographs: C2-7 angle in the MRI images: 4.49°, p < 0.001). Neck tilt was a constant parameter. The C2-7 angle in the kyphotic group was similar between the standing radiographs and the supine MRI images; however, the C2-7 angle in the lordotic group was different. Therefore, we recommend that standing cervical radiographs should be preoperatively obtained for all surgical patients. The slides can be retrieved under Electronic Supplementary Material.


Case-control genome-wide association study of rheumatoid arthritis from Genetic Analysis Workshop 16 using penalized orthogonal-components regression-linear discriminant analysis.
Currently, genome-wide association studies (GWAS) are conducted by collecting a massive number of SNPs (i.e., large p) for a relatively small number of individuals (i.e., small n) and associations are made between clinical phenotypes and genetic variation one single-nucleotide polymorphism (SNP) at a time. Univariate association approaches like this ignore the linkage disequilibrium between SNPs in regions of low recombination. This results in a low reliability of candidate gene identification. Here we propose to improve the case-control GWAS approach by implementing linear discriminant analysis (LDA) through a penalized orthogonal-components regression (POCRE), a newly developed variable selection method for large p small n data. The proposed POCRE-LDA method was applied to the Genetic Analysis Workshop 16 case-control data for rheumatoid arthritis (RA). In addition to the two regions on chromosomes 6 and 9 previously associated with RA by GWAS, we identified SNPs on chromosomes 10 and 18 as potential candidates for further investigation.


Challenges to Detecting and Addressing Intimate Partner Violence Among Roma Women in Spain: Perspectives of Primary Care Providers.
The objective of this study is to identify challenges and facilitators for detecting and addressing cases of intimate partner violence (IPV) against Roma women, from the perspectives of health personnel and representatives of Roma organizations, and to compare both perspectives. A total of 28 semi-structured interviews were carried out between November 2014 and February 2015 in different Spanish cities. A thematic analysis was carried out, guided by Aday and Andersen's model regarding barriers to access to health services. Both groups signaled the following as principal challenges: (a) consideration of IPV as a private problem among the Roma population, (b) little use of primary care providers for prevention, (c) distrust of Roma women toward primary care professionals as resources for seeking help, (d) the inexistence of Roma professionals in health services, (e) health professionals' lack of cultural sensitivity related to Roma people, and (f) the focus of health protocols for action against IPV on filing a police report. Potential facilitating factors included Roma women's trust in nurses, social workers, and pediatricians and ethnic heterogeneity. There is need to promote action to address the identified challenges through a health equity approach that includes greater training and awareness raising among health professionals about Roma culture and the specific needs of Roma women.


Outcomes and predictors of response from an optimised, multidisciplinary intervention for chronic fatigue states.
Medically unexplained chronic fatigue states are prevalent and challenging to manage. Cognitive behavioural therapy (CBT) and graded exercise therapy (GET) are effective in clinical trials. The evaluation of delivery in a standard healthcare setting is rare. An integrated treatment programme with individualised allocation of resources to patients' needs was developed and implemented through an academic outpatient clinic. It was hypothesised that the programme would result in similar responses to those observed in the clinical trials. To evaluate the outcomes of an integrated, 12-week CBT and GET programme delivered by exercise physiologists and clinical psychologists. Consecutive eligible patients (n = 264) who met the diagnostic criteria for chronic fatigue syndrome or post-cancer fatigue were evaluated with self-report measures of fatigue, functional capacity and mood disturbance at baseline, end-of-treatment (12 weeks) and follow-up (24 weeks). A semi-structured interview recording the same parameters was conducted pre- and post-treatment by an independent clinician. Primary outcome was analysed by repeated measures analysis of variance and predictors of response were analysed by logistic regression. The intervention produced sustained improvements in symptom severity and functional capacity. A substantial minority of patients (35%) gained significant improvement, with male gender and higher pain scores at baseline predicting non-response. A small minority of patients (3%) worsened. The manualised protocol of integrated CBT and GET was successfully implemented, confirming the generally positive findings of clinical trials. Assessment and treatment protocols are available for dissemination to allow standardised management. The beneficial effects described here provide the basis for ongoing studies to optimise the intervention further and better identify those most likely to respond.


Formation of Aminocyclopentadienes from Silyldihydropyridines: Ring Contractions Driven by Anion Stabilization.
Highly functionalized aminocyclopentadienes can be formed through the rearrangement of anions generated from readily prepared 6-silyl-1,2-dihydropyridines by desilylation with fluoride. The scope and generality of the reaction was defined, and diverse transformations were performed on the highly functionalized products. A mechanism and driving force for the rearrangement were identified from experiments and DFT calculations.


The German CML study, comparison of busulfan vs. hydroxyurea vs. interferon alpha and establishment of prognostic score 1.
From July 1983 to January 1991 a total of 622 patients were randomized (585 eligible) to compare the effects of hydroxyurea, interferon alpha (IFN), and busulfan on the duration of chronic phase, and survival. Further goals included the determination of prognostic parameters. 598 CML patients were documented and 575 evaluable. The Ph-status was known for 547 patients. 89.4% of the patients were Ph-positive (+). 11% had additional chromosome aberrations. The median survival of Ph+ patients by now is 4.2 years, that of Ph-patients 1.4 years. Ph-negative patients are older, tend to have lower cell counts and, as a group are more ill at diagnosis. A survival difference of about one year is expected between busulfan and hydroxyurea treated patients. Prospectively evaluated age, organomegaly related symptoms, Karnofsky index, extramedullary manifestations, number of erythroblasts and percent of circulating blasts proved to be of prognostic significance. A prognostic score (score 1) was determined which was superior to Sokal's score in the study population. 164 patients were randomized to receive IFN. In 54 patients (33%) IFN had to be terminated because of adverse effects, therapy resistance or other reasons. Clinically relevant neutralizing antibodies were detected in 9 cases. Most frequent adverse events were flu-like symptoms in 74%, gastrointestinal symptoms in 52%, and neurologic-psychiatric symptoms in 30% of patients. Reduction of the Ph-chromosome was observed in 13% of evaluable patients (10 of 75). In 4 patients complete cytogenetic remissions were observed, in three of these ongoing. Cytogenetic responders have a survival advantage. Interferon treated Philadelphia-negative CML patients have no survival disadvantage. The study is expected to allow statements as to the advantages or disadvantages of the use of busulfan, hydroxyurea and IFN in the treatment of CML as well as to the reliability of prognostic markers.


Effect of the Lymphocyte Activation Gene 3 Polymorphism rs951818 on Mortality and Disease Progression in Patients with Sepsis-A Prospective Genetic Association Study.
(1) Background: Sepsis is a leading cause of death and a global public health problem. Accordingly, deciphering the underlying molecular mechanisms of this disease and the determinants of its morbidity and mortality is pivotal. This study examined the effect of the rs951818 SNP of the negative costimulatory lymphocyte-activation gene 3 (LAG-3) on sepsis mortality and disease severity. (2) Methods: 707 consecutive patients with sepsis were prospectively enrolled into the present study from three surgical ICUs at University Medical Center Goettingen. Both 28- and 90-day mortality were analyzed as the primary outcome, while parameters of disease severity served as secondary endpoints. (3) Results: In the Kaplan-Meier analysis LAG-3 rs951818 AA-homozygote patients showed a significantly lower 28-day mortality (17.3%) compared to carriers of the C-allele (23.7%, p = 0.0476). In addition, these patients more often received invasive mechanical ventilation (96%) during the course of disease than C-allele carriers (92%, p = 0.0466). (4) Conclusions: Genetic profiling of LAG-3 genetic variants alone or in combination with other genetic biomarkers may represent a promising approach for risk stratification of patients with sepsis. Patient-individual therapeutic targeting of immune checkpoints, such as LAG-3, may be a future component of sepsis therapy. Further detailed investigations in clinically relevant sepsis models are necessary.


A functionalized gold nanoparticles and Rhodamine 6G based fluorescent sensor for high sensitive and selective detection of mercury(II) in environmental water samples.
A gold-nanoparticles (Au NPs)-Rhodamine 6G (Rh6G) based fluorescent sensor for detecting Hg(II) in aqueous solution has been developed. Water-soluble and monodisperse gold nanoparticles (Au NPs) has been prepared facilely and further modified with thioglycolic acid (TGA). Free Rh6G dye was strongly fluorescent in bulk solution. The sensor system composing of Rh6G and Au NPs fluoresce weakly as result of fluorescence resonance energy transfer (FRET) and collision. The fluorescence of Rh6G and Au NPs based sensor was gradually recovered due to Rh6G units departed from the surface of functionalized Au NPs in the presence of Hg(II). Based on the modulation of fluorescence quenching efficiency of Rh6G-Au NPs by Hg(II) at pH 9.0 of teraborate buffer solution, a simple, rapid, reliable and specific turn-on fluorescent assay for Hg(II) was proposed. Under the optimum conditions, the fluorescence intensity of sensor is proportional to the concentration of Hg(II). The calibration graphs are linear over the range of 5.0x10(-10) to 3.55x10(-8) mol L(-1), and the corresponding limit of detection (LOD) is low as 6.0x10(-11) mol L(-1). The relative standard deviation of 10 replicate measurements is 1.5% for 2.0x10(-9) mol L(-1) Hg(II). In comparison with conventional fluorimetric methods for detection of mercury ion, the present nanosensor endowed with higher sensitivity and selectivity for Hg(II) in aqueous solution. Mercury(II) of real environmental water samples was determined by our proposed method with satisfactory results that were obtained by atomic absorption spectroscopy (AAS).


Adult vaccination in 11 Central European countries - calendars are not just for children.
As Europe's population ages, disease morbidity and treatment costs in the adult population are likely to rise substantially, making this a pertinent time to review and revise preventive strategies such as vaccination. Vaccine uptake remains a problem for adults and there is a lack of coordinated programmes for vaccination of adults. Countries in Western Europe have begun to identify the need to increase adult vaccination, but the situation in Central European countries remains poorly identified and inadequately described. This paper summarises the evidence to support the development of an adult vaccination calendar in the Central European Vaccination Awareness Group (CEVAG) member countries (Bulgaria, Croatia, the Czech Republic, Estonia, Hungary, Latvia, Lithuania, Romania, Slovakia, Slovenia and Turkey). CEVAG recommends the introduction of an adult vaccination calendar, which should include vaccination against diseases that represent a large burden in adults in terms of mortality and morbidity. This calendar could be modified to meet the priorities of individual countries.


Factors affecting the compliance of patients with preventive dental regimens.
The common dental problems of caries and periodontal disease can be controlled by patients who are prepared to adopt the appropriate dietary and oral hygiene behaviours. However compliance with dental surgery based health education programmes is often disappointing. The failure of these interventions is due to the fact that the majority of the dental profession are naive and have a rather insular approach to patient education. There are two key influences on the patient. First there is the 'macro environment' whereby behaviour is shaped by the norms on lifestyle which exist in a patient's social environment. Behaviour changes which are a variance with these norms will not be successful, therefore health education programmes must take cognisance of these norms. It may be necessary to change certain oral health behaviours slowly over an extended period of time. Second there is the 'micro environment' in the dental office. All too often patient education is unplanned, haphazard, not relevant to a particular patient and difficult to understand. Dental professionals should give prevention the same status as clinical care so that it is well planned and carefully evaluated.


Computerized O.R. scheduling: is it an accurate predictor of surgical time?
The goal of this project was to determine whether a standardized surgical time, generated by the Operating Room Information System (ORIS), could be used as an accurate predictor of actual surgical time. Utilizing retrospective, quantitative data from the ORIS database, frequency distributions by surgical speciality, were completed. Chi-square analysis was applied to determine the significance of the frequency distributions. The study outcome indicates that ORIS computer generated procedure times were not an accurate predictor of actual surgical time. Further follow-up will be required to determine if alternate scheduling methodologies would lead to higher accuracy rates.


Synthesis of Gold(I) Complexes Containing Cinnamide: In Vitro Evaluation of Anticancer Activity in 2D and 3D Spheroidal Models of Melanoma and In Vivo Angiogenesis.
A series of alkynylgold(I) phosphine complexes containing methoxy-substituted cinnamide moieties (3a-3c and 4a-4c) have been synthesized and characterized. All of the synthesized complexes were evaluated for their cytotoxicity against three human cancer cell lines A549 (lung), D24 (melanoma), and HT1080 (fibrosarcoma) and the human embryonic kidney 293 cell line (Hek293T) as a proxy model for noncancer cells. Most of the synthesized compounds showed antiproliferative activity against cancer cell lines at low micromolar concentrations. Among these, complex 3c showed a broad spectrum of anticancer activity with IC50 values in the range of 1.53-6.05 μM against all tested cancer lines. Complex 3c possessed 20 times higher cytotoxicity than the reference drug cisplatin against D24 melanoma cells and showed significant anticancer activity in 3D spheroidal models of melanoma cells. Mechanistic investigations of 3c activity indicate thioredoxin reductase inhibition through steric and hydrogen-bonding interactions, followed by the induction of oxidative stress and a mitochondrial pathway of cell death. Compound 3c also showed significant antiangiogenic properties in a transgenic zebrafish Tg(fli1a:EGFP) in vivo model.


Characterization of extended-spectrum β-lactamase-producing Escherichia coli harboring mcr-1 and toxin genes from human fecal samples from China.
To characterize extended-spectrum β-lactamase-producing Escherichia coli harboring the colistin resistance gene mcr-1 from human fecal samples collected in 2012 in a rural area of Shandong province, PR China. Whole-genome sequencing and antimicrobial susceptibility testing was performed on 25 mcr-1-positive isolates to determine carriage of antibiotic resistance and virulence genes, diversity and antibiotic resistance profiles. The isolates were highly genetically diverse and carried a large variety of different antibiotic resistance genes. The multidrug-resistance rate was high (96%). Virulence genes associated with intestinal pathogenic E. coli were carried by 32% of the isolates. Further monitoring of the epidemiological situation is necessary to ensure a preparedness for potential emergence of novel, difficult-to-treat strains and awareness of available treatment options.


Post-Renal Transplant Metabolic Acidosis: A Neglected Entity.
Metabolic acidosis is a prevalent yet overlooked entity among renal transplant recipients (RTRs) and incurs adverse effects on graft function. Although graft dysfunction and calcineurin inhibitor usage have been linked with renal tubular acidosis (RTA), there is no Indian data on prevalence or risk factors of post-transplant acidosis. A cross-sectional study was conducted on 106 adult RTRs, with a transplant duration of >6 months and an estimated glomerular filtration rate (GFR) >40 ml/min/1.73 m2. Acidosis was diagnosed on basis of plasma bicarbonate and arterial pH. Serum and urine electrolytes with anion gap were determined to diagnose and type RTA. Acidosis was diagnosed in 44 of 106 patients (41.5%) with 23 (52.27%) having severe acidosis. Type I RTA was the most common subtype (52.5%) followed by type IV (30.9%) and type II RTA (7.5%). The correlation between estimated glomerular filtration rate and acidosis was minimally linear (r = 0.1088), with multivariate analysis revealing previous acute rejection episodes, current serum tacrolimus levels, cotrimoxazole usage and intake of animal proteins to be independent risk factors. The serum albumin levels were low in the acidosis group and showed linear correlation with bicarbonate levels (r = 0.298). There is a high prevalence of metabolic acidosis in RTRs with type I RTA being most common subtype. Screening of RTRs on a regular basis is a feasible approach for early diagnosis and intervention. However, prospective studies are needed to demonstrate the effect of acidosis on graft survival and benefit of bicarbonate therapy in RTRs.


Dual-Energy Lung Perfusion in Portal Venous Phase CT-A Comparison with the Pulmonary Arterial Phase.
Pulmonary arterial dual-energy (aDE) CT is an established technique for evaluating pulmonary perfusion blood volume (PBV). As DECT protocols are increasingly used for thoraco-abdominal CT, this study assessed image quality and clinical findings in portal-venous phase dual-energy (vDE) CT and compared it to aDE. In 95 patients, vDE-CT was performed using a dual-source scanner (70/Sn150 kV, 560/140 ref.mAs). Pulmonary triggered aDE-CT served as reference (n = 94). PBV was reconstructed using a dedicated algorithm. Mean relative attenuation was measured in the pulmonary trunk, aorta, and segmented lung parenchyma. A distribution ratio (DL) between vessels and parenchyma was calculated to assess the iodine uptake of the lung parenchyma. Subjective overall diagnostic image quality was assessed for PBV images on a five-point Likert scale. Image artifacts were classified into five groups based on scale rating and compared between vDE and aDE. Pathological findings were correlated with the anatomical image datasets. Mean relative attenuation of the lung parenchyma was comparable in both groups (vDE: 23 ± 6 HU and aDE: 22 ± 7 HU), but significantly lower in the vessels of vDE. Therefore, iodine uptake of the lung parenchyma was significantly higher in vDE (DL: 10% vs. 8%, p < 0.01). The subjective overall image quality of the PBV images was comparable (p = 0.5). Rotation and streak artifacts were found in most of the patients (>86%, both p > 0.6). Dual-source artifacts were found in only a few patients in both groups (vDE 5%, aDE 7%, p = 0.5). Recess and subpleural artifacts were increased in vDE (vDE 53/27%, aDE 24/7%, both p < 0.001). Pathological findings were found in 19% of the vDE patients and 59% of the aDE patients. Comparable objective and subjective image quality of lung perfusion can be obtained in vDE and aDE. Iodine uptake of the lung parenchyma is increased in vDE compared to aDE, suggesting an interstitial pooling effect. Knowledge of the different appearances of artifacts will aid in the interpretation of the images. Additional clinical information about the lung parenchyma can be provided by PBV evaluation in vDE.


Patient- and physician-reported radiation-induced toxicity of short-course radiotherapy with a prolonged interval to surgery for rectal cancer.
A prolonged interval (>4 weeks) between short-course radiotherapy (25 Gy in five fractions) (SCRT-delay) and total mesorectal excision for rectal cancer has been associated with a decreased postoperative complication rate and offers the possibility of organ preservation in the case of a complete tumour response. This prospective cohort study systematically evaluated patient-reported bowel dysfunction and physician-reported radiation-induced toxicity for 8 weeks following SCRT-delay. Patients who were referred for SCRT-delay for intermediate risk, oligometastatic or locally advanced rectal cancer were included. Repeated measurements were done for patient-reported bowel dysfunction (measured by the low anterior resection syndrome [LARS] questionnaire and categorized as no, minor or major LARS) and physician-reported radiation-induced toxicity (according to Common Terminology Criteria for Adverse Events version 4.0) before start of treatment (baseline), at completion of SCRT and 1, 2, 3, 4, 6 and 8 weeks thereafter. Fifty-one patients were included; 31 (61%) were men and the median age was 67 years (range 44-91). Patient-reported bowel dysfunction and physician-reported radiation-induced toxicity peaked at weeks 1-2 after completion of SCRT and gradually declined thereafter. Major LARS was reported by 44 patients (92%) at some time during SCRT-delay. Grade 3 radiation-induced toxicity was reported in 17 patients (33%) and concerned predominantly diarrhoea. No Grade 4-5 radiation-induced toxicity occurred. During SCRT-delay, almost every patient experiences temporary mild-moderate radiation-induced toxicity and major LARS, but life-threatening toxicity is rare. SCRT-delay is a safe alternative to SCRT-direct surgery that should be proposed when counselling rectal cancer patients on neoadjuvant strategies.


[Effect of co-inhibition of MCT1 gene and NHE1 gene on proliferation and growth of human lung adenocarcinoma cells].
The authors previously discovered that the intracellular pH values (pHi) of tumor cells could be decreased, which led tumor cells to acidify and die, when the expressions of the first subtype of monocarboxylate transporter (MCT1) gene and the first subtype of Na+/H+ exchanger (NHE1) gene in tumor cell membranes had been inhibited by each corresponding antisense gene respectively. However it was not clear whether there were co-effects on the pHi, proliferation, and growth of tumor cells, after two genes were inhibited at the same time. pLXSN-MCT1 and pLXSN-NHE1, the corresponding antisense gene expression vectors of MCT1 and NHE1 genes, were introduced into human lung adenocarcinoma A549 cells at the same time with electroporation. The positive colonies were selected by G418. Using PCR and RT-PCR technique, it was confirmed that antisense genes of MCT1 and NHE1 genes integrated with A549 genomic DNA. The pHi and lactate content were detected with spectrophotometry. Cell growth cycle was measured with flow cytometer. The cells co-transfected antisense genes, cells transfected MCT1 antisense gene and A549 cells were respectively inoculated in nude mouse subcutaneous to observe the growth of transplantation tumors. Compared with A549 cells, the pHi of cells co-transfected antisense genes was remarkably decreased (P < 0.05), while lactate content was remarkably increased (P < 0.001). The cell cycle was blocked at G0-G1 period. And the transplantation tumors of nude mice inoculated co-transfected antisense gene-cells and inoculated MCT1-antisense-gene-transfected cells were significantly lighter and smaller than ones inoculated A549 cells (P < 0.001). MCT1 and NHE1 genes play important regulation roles in proliferation and growth of tumor cells, probably by affecting pHi.


Guiding visual attention during acquisition of matching-to-sample.
Matching-to-sample skills are involved in language acquisition and the development of basic reading and counting abilities. The rapid, even errorless, induction of matching performances in young children and individuals with mental retardation was demonstrated here through the structuring of a visual array so as to promote detection of the relevant stimulus. Implications for theory and application are discussed.


External validity of phase III trials on vaccines against SARS-CoV-2 to a middle-aged and elderly Western European population.
Initial results from various phase-III trials on vaccines against SARS-CoV-2 are promising. For proper translation of these results to clinical guidelines, it is essential to determine how well the general population is reflected in the study populations of these trials. This study was conducted among 7162 participants (age-range: 51-106 years; 58% women) from the Rotterdam Study. We quantified the proportion of participants that would be eligible for the nine ongoing phase-III trials. We further quantified the eligibility among participants at high risk to develop severe COVID-19. Since many trials were not explicit in their exclusion criterion with respect to 'acute' or 'unstable preexisting' diseases, we performed two analyses. First, we included all participants irrespective of this criterion. Second, we excluded persons with acute or 'unstable preexisting' diseases. 97% of 7162 participants was eligible for any trial with eligibility for separate trials ranging between 11-97%. For high-risk individuals the corresponding numbers were 96% for any trial with separate trials ranging from 5-96%. Importantly, considering persons ineligible due to 'acute' or 'unstable pre-existing' disease drastically dropped the eligibilities for all trials below 43% for the total population and below 36% for high-risk individuals. The eligibility for ongoing vaccine trials against SARS-CoV-2 can reduce by half depending on interpretation and application of a single unspecified exclusion criterion. This exclusion criterion in our study would especially affect the elderly and those with pre-existing morbidities. These findings thus indicate the difficulty as well as importance of developing clinical recommendations for vaccination and applying these to the appropriate target populations. This becomes especially paramount considering the fact that many countries worldwide have initiated their vaccination programs by first targeting the elderly and most vulnerable persons.


Revisiting the role of acids and hydrogen bond acceptors in enamine formation.
A systematic investigation into the effects of acids and hydrogen bond acceptors on the reaction rates and equilibria of enamine formation is reported. Acids can accelerate the reaction but do not change the reaction equilibria. In comparison, hydrogen bond acceptors facilitate the enamine formation via their strong hydrogen bonding interaction with the water generated in the reaction.


Characterization of the light reaction in promoting the mobilizing ability of rose shoot tips.
Mixed fluorescent and incandescent light increased growth and sink strength of the uppermost young shoot of rose plants (Rosa hybrida cv. Marimba) in comparison to pure fluorescent light. This was manifested by increased apical dominance. Monochromatic low-energy red light, given by means of optic fibers for 24 hours to shoot tips that had been previously darkened for 5 days, increased the transport of (14)C-labeled assimilates to the intact tips and the uptake of [(14)C]sucrose by detached tips. Far-red had little or no effect, and blue was not effective at all in these reactions. Red light given directly to detached shoot tips, in vitro, increased the uptake of [(14)C]sucrose by the isolated tips. Adding far-red to the red greatly promoted the uptake, whereas blue and blue plus far-red were not active. The main character of the light reaction promoting sink activity in the shoot is that it is perceived by the shoot tip itself. It is operated by red light; far-red promotes the red effect but has little or no effect when alone. Light apparently promotes shoot sink activity by increasing the unloading process.


Symbolic expression of feelings and depressive symptoms in high-risk pregnant women.
Pregnant women using rural health departments for prenatal care often experience chronic stressors (minority status, poor education, low income, young age, and single parenting of young children) that contribute to depression. Yet these same women may be reluctant to express their feelings. Because depression has been related to negative patterns of motherchild interaction and even newborn irritability, it is important to identify symptoms in high-risk mothers. For years, symbolic methods of expression have been used to reveal psychological traits or to identify clinical diagnoses, but few have been used to evaluate pregnant women. Women attending a rural health department were administered a comprehensive health and psychosocial questionnaire, including the Center for Epidemiologic Studies-Depression Scale (CES-D). They were then asked to complete a drawing expressing their feelings regarding their pregnancy. The relationship between CES-D scores and drawing ratings determined by two different methods of interpretation (expert, non-expert) was then examined. Non-expert art analysis was able to distinguish those women with the highest scores on the depression index, while expert analysis was able to discern racial differences consistent with risk status. Suggestions for the use of this drawing measure in the clinical setting are discussed. Alternative (non-verbal) methods of assessment that may improve communication with pregnant women are important for optimizing maternal and infant health and well-being and child development.


Elevated CO2 did not affect the hydrological balance of a mature native Eucalyptus woodland.
Elevated atmospheric CO2 concentration (eCa ) might reduce forest water-use, due to decreased transpiration, following partial stomatal closure, thus enhancing water-use efficiency and productivity at low water availability. If evapotranspiration (Et ) is reduced, it may subsequently increase soil water storage (ΔS) or surface runoff (R) and drainage (Dg ), although these could be offset or even reversed by changes in vegetation structure, mainly increased leaf area index (L). To understand the effect of eCa in a water-limited ecosystem, we tested whether 2 years of eCa (~40% increase) affected the hydrological partitioning in a mature water-limited Eucalyptus woodland exposed to Free-Air CO2 Enrichment (FACE). This timeframe allowed us to evaluate whether physiological effects of eCa reduced stand water-use irrespective of L, which was unaffected by eCa in this timeframe. We hypothesized that eCa would reduce tree-canopy transpiration (Etree ), but excess water from reduced Etree would be lost via increased soil evaporation and understory transpiration (Efloor ) with no increase in ΔS, R or Dg . We computed Et , ΔS, R and Dg from measurements of sapflow velocity, L, soil water content (θ), understory micrometeorology, throughfall and stemflow. We found that eCa did not affect Etree , Efloor , ΔS or θ at any depth (to 4.5 m) over the experimental period. We closed the water balance for dry seasons with no differences in the partitioning to R and Dg between Ca levels. Soil temperature and θ were the main drivers of Efloor while vapour pressure deficit-controlled Etree , though eCa did not significantly affect any of these relationships. Our results suggest that in the short-term, eCa does not significantly affect ecosystem water-use at this site. We conclude that water-savings under eCa mediated by either direct effects on plant transpiration or by indirect effects via changes in L or soil moisture availability are unlikely in water-limited mature eucalypt woodlands.


Insight into structural diversity of influenza virus haemagglutinin.
Influenza virus infects host cells through membrane fusion, a process mediated by the low pH-induced conformational change of the viral surface glycoprotein haemagglutinin (HA). We determined the structures and biochemical properties of the HA proteins from A/Korea/01/2009 (KR01), a 2009 pandemic strain, and A/Thailand/CU44/2006 (CU44), a seasonal strain. The crystal structure of KR01 HA revealed a V-shaped head-to-head arrangement, which is not seen in other HA proteins including CU44 HA. We isolated a broadly neutralizing H1-specific monoclonal antibody GC0757. The KR01 HA-Fab0757 complex structure also exhibited a head-to-head arrangement of HA. Both native and Fab complex structures reveal a different spatial orientation of HA1 relative to HA2, indicating that HA is flexible and dynamic at neutral pH. Further, the KR01 HA exhibited significantly lower protein stability and increased susceptibility to proteolytic cleavage compared with other HAs. Our structures provide important insights into the conformational flexibility of HA.


Formation of obstructing blood clot in the ureter in a patient with Glanzmann's thrombasthenia.
Glanzman thrombasthenia is a rare hematologic disorder characterized by qualitative thrombocyte abnormality. Patients present with episodic mucocutaneous bleeding. Thrombosis is a paradox phenomenon observed in patients with Glanzman thrombasthenia and generally considered as a treatment complication. We present a 16-year-old girl referred for severe flank pain beginning after treatment of hematuria due to Glanzman thrombasthenia. The patient underwent endoscopy for further diagnosis and treatment because of the failure of radiologic evaluation. Although the resolution of the large clots was obtained with streptokinase instillation via the ureteral catheter, clot was mobilized with gentle insertion of ureteral catheter in the present case.


Modulation of liver-intestine cadherin (Cadherin 17) expression, ERK phosphorylation and WNT signaling in EPHB6 receptor-expressing MDA-MB-231 cells.
Aberrant expression of erythropoietin-producing hepatocellular carcinoma cell (EPH) receptors has been reported in a variety of human cancer types. In addition to modulating cell proliferation and migration, EPH receptors are also involved in tumor progression. The transcriptional activation and silencing of EPH receptors are also associated with tumorigenesis. However, the mechanisms underlying the involvement of EPH receptors in tumorigenesis have not been completely deciphered. We have investigated and described the role of EPHB6, a kinase-deficient receptor, in modulating the abundance of cadherin 17 and activation of other intracellular signaling proteins. We previously showed that EPHB6 alters the tumor phenotype of breast carcinoma cells. However, the mechanisms underlying these phenotypic changes had not previously been investigated. Herein we demonstrated the downstream effects of EPHB6 expression on the abundance of cadherin 17, mitogen-activated protein kinase (MEK2), extracellular signal-regulated kinase (ERK), phospho-ERK, β-catenin, phospho- glycogen synthase kinase 3 beta (GSK3β) (ser21/9), cell morphology and actin cytoskeleton. These comparisons were made between EPHB6-deficient MDA-MB-231 cells transfected with an empty pcDNA3 vector and cells stably transfected with an expression construct of EPHB6. The results indicate elevated levels of MEK2 and phospho-ERK. While there was no change in the amount of ERK, the abundance of cadherin 17, β-catenin and phospho-GSK3β was significantly reduced in EPHB6-transfected cells. These studies clearly demonstrate an inverse relationship between the levels of phospho-ERK and the abundance of cadherin 17, β-catenin and phospho-GSK3β in EPHB6-expressing MDA-MB-231 cells. From these data we conclude that EPHB6-mediated alterations arise due to changes in abundance and localization of cadherin 17 and activation of WNT signaling pathway. Transcriptional silencing of EPHB6 in native MDA-MB-231 cells and consequent effects on cadherin 17 and WNT pathway may, thus, be responsible for the invasive behavior of these cells.


Highly fluorinated 2,2'-biphenols and related compounds: relationship between substitution pattern and herbicidal activity.
A broad range of halogenated 2,2'-biphenols was tested for applicability as crop protection agents. The activity of these compounds toward four typical pest plants was observed after application by spraying of diluted solutions. Despite their rather simple structure, it was found that the studied compounds reveal a surprisingly high herbicidal impact. To gain a better understanding of the structure-activity relationship, specific sites of the molecule were chemically modified and the core structures thus gradually changed. The influence of the substitution pattern on the herbicidal properties is discussed, and conclusions on the active site of the biphenol structure are drawn. It was observed that type and position of the halogen substituents have a significant influence on the activity of the core structure. The hydroxy functionalities play a crucial role for the effectiveness of the tested compounds. Because the blocking of the hydroxy moiety leads to dramatically deteriorated performances, the presence of these functionalities on the aromatic ring seems to be indispensable.


Image-guided radio-frequency gain calibration for high-field MRI.
High-field (≥ 3T) MRI provides a means to increase the signal-to-noise ratio, due to its higher tissue magnetization compared with 1.5T. However, both the static magnetic field (B(0)) and the transmit radio-frequency (RF) field (B 1+) inhomogeneities are comparatively higher at higher field strengths than those at 1.5T. These challenging factors at high-field strengths make it more difficult to accurately calibrate the transmit RF gain using standard RF calibration procedures. An image-based RF calibration procedure was therefore developed, in order to accurately calibrate the transmit RF gain within a specific region-of-interest (ROI). Using a turbo fast low-angle shot (TurboFLASH) pulse sequence with centric k-space reordering, a series of 'saturation-no-recovery' images was acquired by varying the flip angle of the preconditioning pulse. In the resulting images, the signal null occurs in regions where the flip angle of the preconditioning pulse is 90°. For a given ROI, the mean signal can be plotted as a function of the nominal flip angle, and the resulting curve can be used to quantitatively identify the signal null. This image-guided RF calibration procedure was evaluated through phantom and volunteer imaging experiments at 3T and 7T. The image-guided RF calibration results in vitro were consistent with standard B(0) and B 1+ maps. The standard automated RF calibration procedure produced approximately 20% and 15-30% relative error in the transmit RF gain in the left kidney at 3T and brain at 7T, respectively. For initial application, a T(2) mapping pulse sequence was applied at 7T. The T(2) measurements in the thalamus at 7T were 60.6 ms and 48.2 ms using the standard and image-guided RF calibration procedures, respectively. This rapid, image-guided RF calibration procedure can be used to optimally calibrate the flip angle for a given ROI and thus minimize measurement errors for quantitative MRI and MR spectroscopy.


Potential cross-talk between muscle and tendon in Duchenne muscular dystrophy.
To describe potential signaling (cross-talk) between dystrophic skeletal muscle and tendon in Duchenne muscular dystrophy. Review of Duchenne muscular dystrophy and associated literature relevant to muscle-tendon cross-talk. Duchenne muscular dystrophy results from the absence of the protein dystrophin and the associated dystrophin - glycoprotein complex, which are thought to provide both structural support and signaling functions for the muscle fiber. In addition, there are other potential signal pathways that could represent cross-talk between muscle and tendon, particularly at the myotendinous junction. Duchenne muscular dystrophy is characterized by multiple pathophysiologic mechanisms. Herein, we explore three of these: (1) the extracellular matrix, fibrosis, and fat deposition; (2) satellite cells; and (3) tensegrity. A key signaling protein that emerged in each was transforming growth factor - beta one (TGF-β1).].


Early formation of the vascular system in quail embryos.
The relation between vascular development and translocation of the splanchnic mesodermal layers was studied in presomite to 20-somite quail embryos by scanning electron microscopy. In addition, serially sectioned embryos were stained immunohistochemically with monoclonal antibodies (alpha QH1 or alpha MB1) specific for endothelial and hemopoietic cells. By the formation of the foregut the anterior borders of the two splanchnic mesodermal layers of a presomite embryo are translocated to the lateral and ventral sides of the foregut and fuse in the ventral midline of a 4-somite embryo. Meanwhile the splanchnic mesoderm differentiates into a splanchnic mesothelial layer and a plexus of endothelial cells, facing the endoderm. From 4 somites onward the foregut is covered by a single endothelial plexus. At first the endothelial precursors bordering the anterior intestinal portal and those in the area of the ventral mesocardium lumenize, subsequently giving rise to the endocardium of the heart tube. Hereafter, the pharyngeal arch arteries and the dorsal aortae develop from the remaining precursors. During formation of the pharyngeal arches, the pharyngeal arch arteries maintain their connections with the splanchnic plexus through the developing ventral pharyngeal veins. After disappearance of the dorsal mesocardium, the midpharyngeal endothelial strand, which is a longitudinal strand of proendocardial cells, remains connected to the foregut. This strand will contribute to the formation of the pulmonary venous drainage into the left atrium. A bilateral accumulation of cardiac jelly developing between the promyocardium and proendocardial plexus only suggests that the heart develops from two tubes. The proendocardial layer, however, is not divided by the ventral mesocardium but initially forms just one endocardial heart tube.


Morphological affinities of the Sal'a 1 frontal bone.
The human frontal bone from Sal'a, Slovak Republic, has previously entered into discussions of the morphological patterns of Central European Neandertals and the origins of early modern humans in that region. A morphological reassessment of its supraorbital region and a morphometric analysis of its overall proportions indicate that it falls well within expected ranges of variation of Late Pleistocene Neandertals and is separate from European earlier Upper Paleolithic early modern human crania. It is similar to the Qafzeh-Skhul sample in some metrical and supraorbital robusticity measures, but it contrasts with them in mid-sagittal curvature and supraorbital torus morphology. In the context of its probable oxygen isotope stage 5 age based on inferred biostratigraphic associations, it should not be employed directly for arguments relating to the emergence of modern humans in Central Europe.


Endoluminal radiofrequency ablation in patients with malignant biliary obstruction: a randomised trial.
Endoluminal radiofrequency ablation (RFA) has been promoted as palliative treatment for patients with cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC) in order to improve biliary drainage and eventually prolong survival. No high level evidence is, however, available on this technique. In this randomised controlled study, we compared endoluminal RFA plus stenting with stenting alone (control group) in patients with malignant biliary obstruction; metal stents were primarily placed. Primary outcome was overall survival; secondary outcomes were stent patency, quality of life and adverse events. In a superiority design, survival was assumed to be doubled by RFA as compared with 6.4 months in the control group (n=280). A total of 161 patients (male:female 90:71, mean age 71±9 years) were randomised before recruitment was terminated for futility after an interim analysis. Eighty-five patients had CCA (73 hilar, 12 distal) and 76 had pancreatic cancer. There was no difference in survival in both subgroups: for patients with CCA, median survival was 10.5 months (95% CI 6.7 to 18.3) in the RFA group vs 10.6 months (95% CI 9.0 to 24.8), p=0.58)) in the control group. In the subgroup with pancreatic cancer, median survival was 6.4 months (95% CI 4.3 to 9.7) for the RFA vs 7.7 months (95% CI 5.6 to 11.3), p=0.73) for the control group. No benefit was seen in the RFA group with regard to stent patency (at 12 months 40% vs 36% in CCA and 66% vs 65% in PDAC), and quality of life was unchanged by either treatment and comparable between the groups. Adverse events occurred in seven patients in each groups. A combination of endoluminal RFA and stenting was not superior to stenting alone in prolonging survival or improving stent patency in patients with malignant biliary obstruction. NCT03166436.


Immunotherapy for sarcomas: new frontiers and unveiled opportunities.
Sarcomas are a rare malignancy of mesenchymal tissues, comprizing a plethora of unique subtypes, with more than 60 types. The sheer heterogeneity of disease phenotype makes this a particularly difficult cancer to treat. Radiotherapy, chemotherapy and surgery have been employed for over three decades and, although effective in early disease (stages I-II), in later stages, where metastatic tumors are present, these treatments are less effective. Given the spectacular results obtained by cancer immunotherapy in a variety of solid cancers and leukemias, there is now a great interest in appliying this new realm of therapy for sarcomas. The widespread use of immunotherapy for sarcoma relies on immuno-profiling of subtypes, immunomonitoring for prognosis, preclinical studies and insight into the safety profile of these novel therapies. Herein, we discuss preclinical and clinical data highlighting how immunotherapy is being used in soft tissue sarcoma and bone sarcomas.


Effects of temperature gradient correction of carbon dioxide absorbent on carbon dioxide absorption.
The effects of temperature gradients in CO(2) absorbents on water content and CO(2) absorption are not clear. We constructed a novel temperature gradient correction (TGC) canister, and investigated the effects of temperature gradient correction on the water content and longevity (time to exhaustion) of CO(2) absorbent using a simulated anaesthesia circuit. Experiments were divided into two groups according to the type of canister used: the TGC canister (n=6) or the conventional canister (n=6). One kilogram of fresh CO(2) absorbent was placed into the canister. The anaesthetic ventilator was connected to a 3 litre bag and 300 ml min(-1) of CO(2) was introduced. Oxygen (500 ml min(-1)) was used as fresh gas. The anaesthetic ventilator was set at a ventilatory frequency of 12 bpm, and tidal volume was adjusted to 700 ml. Before the experiment, the water content of the fresh CO(2) absorbent in the conventional canister and TGC canister was 16.1 (0.9)% and 15.7 (1.1)%, respectively. After the experiment, the water content of CO(2) absorbent near the upper outer rim of the canister increased to 32.4 (0.7)% in the conventional canister, but increased to only 20.6 (1.3)% in the TGC canister (P<0.01). The longevity of CO(2) absorbent in the conventional canister and TGC canister was 434 (9) min and 563 (13) min (P<0.01). Temperature gradient correction prevented a local excessive increase in water content and improved the longevity of CO(2) absorbent.


An examination of interrater reliability for scoring the Rorschach Comprehensive System in eight data sets.
In this article, we describe interrater reliability for the Comprehensive System (CS; Exner. 1993) in 8 relatively large samples, including (a) students, (b) experienced re- searchers, (c) clinicians, (d) clinicians and then researchers, (e) a composite clinical sample (i.e., a to d), and 3 samples in which randomly generated erroneous scores were substituted for (f) 10%, (g) 20%, or (h) 30% of the original responses. Across samples, 133 to 143 statistically stable CS scores had excellent reliability, with median intraclass correlations of.85, .96, .97, .95, .93, .95, .89, and .82, respectively. We also demonstrate reliability findings from this study closely match the results derived from a synthesis of prior research, CS summary scores are more reliable than scores assigned to individual responses, small samples are more likely to generate unstable and lower reliability estimates, and Meyer's (1997a) procedures for estimating response segment reliability were accurate. The CS can be scored reliably, but because scoring is the result of coder skills clinicians must conscientiously monitor their accuracy.


The introduction of emergency cricothyroidotomy simulation training in Zimbabwe contributed to the saving of two lives.
In developing countries with limited access to ENT services, performing emergency cricothyroidotomy in patients with upper airway obstruction may be a life-saving last resort. An established Danish-Zimbabwean collaboration of otorhinolaryngologists enrolled Zimbabwean doctors into a video-guided simulation training programme on emergency cricothyroidotomy. This paper presents the positive effect of this training, illustrated by two case reports. A 56-year-old female presented with upper airway obstruction due to a rapidly progressing infectious swelling of the head and neck progressing to cardiac arrest. Cardiopulmonary resuscitation was initiated and a secure surgical airway was established via an emergency cricothyroidotomy, saving the patient. A 70-year-old male presented with upper airway obstruction secondary to intubation for an elective procedure. When extubated, the patient exhibited severe stridor followed by respiratory arrest. Re-intubation attempts were unsuccessful and emergency cricothyroidotomy was performed to secure the airway, preserving the life of the patient. Emergency cricothyroidotomy training should be considered for all surgeons, anaesthetists and, eventually, emergency and recovery room personnel in developing countries. A video-guided simulation training programme on emergency cricothyroidotomy in Zimbabwe proved its value in this regard.


5-Aminolevulinic Acid-based Photodynamic Intense Pulsed Light Therapy Shows Better Effects in the Treatment of Skin Photoaging in Asian Skin: A Prospective, Single-blinded, Controlled Trial.
To investigate the effects of photodynamic intense pulsed light therapy on skin photoaging in Asian skin. This was a prospective, single-blinded, controlled, clinical trial with 40 patients enrolled. The enrolled patients applied 5% 5-aminolevulinic acid on the left side of the face while a placebo was applied on the right side of the face. After a one-hour incubation, the patients received intense pulsed light therapy. After four treatment cycles, the pH values, transepidermal water loss of the dermis of the forehead and canthus skin, as well as the moisture capacity of stratum corneum and the global score of photoaging were assessed. The pH value of forehead and canthus skin, moisture capacity of stratum corneum, and the dermis of forehead and canthus skin of the photodynamic intense pulsed light therapy treated sides were significantly higher than those of the control sides in all of the patients. The photoaging score decreased after the therapy on both sides, with the photodynamic intense pulsed light therapy treated sides decreasing more than the control sides (P<0.01). 5-aminolevulinic acid photodynamic intense pulsed light therapy showed better effects in the treatment of skin photoaging compared to intense pulsed light therapy alone.


In-Hospital and 1-Year Mortality Trends in a National Cohort of US Veterans with Acute Kidney Injury.
AKI, a frequent complication among hospitalized patients, confers excess short- and long-term mortality. We sought to determine trends in in-hospital and 1-year mortality associated with AKI as defined by Kidney Disease Improving Global Outcomes consensus criteria. This retrospective cohort study used data from the national Veterans Health Administration on all patients hospitalized from October 1, 2008 to September 31, 2017. AKI was defined by Kidney Disease Improving Global Outcomes serum creatinine criteria. In-hospital and 1-year mortality trends were analyzed in patients with and without AKI using Cox regression with year as a continuous variable. We identified 1,688,457 patients and 2,689,093 hospitalizations across the study period. Among patients with AKI, 6% died in hospital, and 28% died within 1 year. In contrast, in-hospital and 1-year mortality rates were 0.8% and 14%, respectively, among non-AKI hospitalizations. During the study period, there was a slight decline in crude in-hospital AKI-associated mortality (hazard ratio, 0.98 per year; 95% confidence interval, 0.98 to 0.99) that was attenuated after accounting for patient demographics, comorbid conditions, and acute hospitalization characteristics (adjusted hazard ratio, 0.99 per year; 95% confidence interval, 0.99 to 1.00). This stable temporal trend in mortality persisted at 1 year (adjusted hazard ratio, 1.00 per year; 95% confidence interval, 0.99 to 1.00). AKI associated mortality remains high, as greater than one in four patients with AKI died within 1 year of hospitalization. Over the past decade, there seems to have been no significant progress toward improving in-hospital or long-term AKI survivorship.


Chirality dependence of quantum thermal transport in carbon nanotubes at low temperatures: a first-principles study.
We study the transport properties of single-walled carbon nanotubes (SWCNTs) using the nonequilibrium Green's function method based on first-principles calculations. We compared three SWCNTs with different chiralities (3, 3), (5, 0), and (4, 2), and found that the thermal conductance varies significantly with the chirality, especially at low temperatures. Such differences are attributed to the dependence on the chirality of the frequency of the lowest optical mode and phonon-phonon interaction with the semi-infinite leads. To obtain accurate low-vibrational frequencies, a force constant correction based on the Lagrange undetermined multiplier method was employed. The phonon-phonon interaction was analyzed in terms of the projection of the phonon coupling with the semi-infinite leads onto the normal modes of the center region. Our result indicates that high optical mode frequency and weak phonon coupling on the armchair (3, 3) SWCNT are the origin of the long quantized plateau found in the experimental thermal conductance.


Isolation and purification of leaf starch components.
A procedure was developed for the separation and purification of amylose and amylopectin isolated from cotton leaves. Cotton leaves were homogenized in 0.02 molar phosphate buffer at pH 7.0 containing HgCl(2) plus toluene. Crude starch granules were collected by centrifugation and partially purified by treating with acetone and toluene. The starch granules were then dispersed in dimethylsulfoxide and precipitated with ethyl alcohol. The precipitate was suspended in boiling water. Amylose was separated from amylopectin and cell wall particles on a Sepharose 2B column and further purified with thymol and butanol. Amylopectin was then separated from the colloidal cell wall contaminants by its specific interaction with concanavalin A. Purities of starch components were verified by specific biochemical and enzymic tests in addition to their iodine-binding capacity. This procedure should also be suitable for purification of starch components from other plant sources.


Ceftobiprole: First reported experience in osteomyelitis.
A 74-year-old man with long-standing diabetes presented with advanced infection of the right forefoot associated with septic arthritis and osteomyelitis involving the second and third metatarsophalangeal joints. Polymicrobial infection, which included methicillin-resistant Staphylococcus aureus, was documented. First-line antibiotic therapy, which included vancomycin, was not tolerated. A durable cure was obtained following a six-week course of intravenous ceftobiprole medocaril combined with local surgery. The present report is the first to administer intravenous ceftobiprole medocaril to a patient with methicillin-resistant S aureus-associated septic arthritis and osteomyelitis.


Novel mechanisms underlying anti-polycystic ovary like syndrome effects of electroacupuncture in rats: suppressing SREBP1 to mitigate insulin resistance, mitochondrial dysfunction and oxidative stress.
Acupuncture, a therapy of traditional Chinese medicine, is confirmed to exert the therapeutic action on polycystic ovary syndrome (PCOS). However, the detailed therapeutic mechanisms of acupuncture in PCOS remain ambiguous. In this study, we further investigated whether electroacupuncture (EA) alleviated PCOS-like symptoms in rats via regulating a metabolic regulator, sterol regulatory element binding protein-1 (SREBP1). The PCOS-like rat model was built by hypodermic injection with dehydroepiandrosterone (DHEA). The rats were subjected to EA intervention (ST29 and SP6 acupuncture points) for 5 weeks. Primary granulosa cells were isolated from control and PCOS-like rats for evaluating insulin resistance, mitochondrial dysfunction and oxidative stress in vitro. The expression of SREBP1 was increased in PCOS-like rats, which was suppressed by EA treatment. In addition, lentivirus-mediated overexpression of SREBP1 restrained EA treatment-induced improvement in pathological changes, serum hormone levels and insulin resistance in rats. In addition, overexpression of SREBP1 repressed insulin-stimulated phosphorylation of insulin receptor β (IR) and AKT in primary granulosa cells. Moreover, upregulation of SREBP1 further exacerbated mitochondrial dysfunction and oxidative stress in granulosa cells isolated from PCOS-like rats. Mechanically, EA treatment suppressed SREBP1 expression through inducing the activation of AMP-activated protein kinase (AMPK) signaling pathway in PCOS-like rats. EA intervention alleviated PCOS-like symptoms in rats via improving IR, mitochondrial dysfunction and oxidative stress through regulating SREBP1, a lipid metabolism regulator. Our findings illuminate the novel protective mechanisms of EA in the treatment of PCOS.


Understanding noncovalent bonds and their controlling forces.
The fundamental underpinnings of noncovalent bonds are presented, focusing on the σ-hole interactions that are closely related to the H-bond. Different means of assessing their strength and the factors that control it are discussed. The establishment of a noncovalent bond is monitored as the two subunits are brought together, allowing the electrostatic, charge redistribution, and other effects to slowly take hold. Methods are discussed that permit prediction as to which site an approaching nucleophile will be drawn, and the maximum number of bonds around a central atom in its normal or hypervalent states is assessed. The manner in which a pair of anions can be held together despite an overall Coulombic repulsion is explained. The possibility that first-row atoms can participate in such bonds is discussed, along with the introduction of a tetrel analog of the dihydrogen bond.


Effects of lightning on trees: A predictive model based on in situ electrical resistivity.
The effects of lightning on trees range from catastrophic death to the absence of observable damage. Such differences may be predictable among tree species, and more generally among plant life history strategies and growth forms. We used field-collected electrical resistivity data in temperate and tropical forests to model how the distribution of power from a lightning discharge varies with tree size and identity, and with the presence of lianas. Estimated heating density (heat generated per volume of tree tissue) and maximum power (maximum rate of heating) from a standardized lightning discharge differed 300% among tree species. Tree size and morphology also were important; the heating density of a hypothetical 10 m tall Alseis blackiana was 49 times greater than for a 30 m tall conspecific, and 127 times greater than for a 30 m tall Dipteryx panamensis. Lianas may protect trees from lightning by conducting electric current; estimated heating and maximum power were reduced by 60% (±7.1%) for trees with one liana and by 87% (±4.0%) for trees with three lianas. This study provides the first quantitative mechanism describing how differences among trees can influence lightning-tree interactions, and how lianas can serve as natural lightning rods for trees.


Problems with the American College of Radiology Standard for Diagnostic Mammography.
In an effort to help assure quality, the American College of Radiology (ACR) has developed standards for many imaging procedures. One of the most recent standards adopted is the ACR Standard for Diagnostic Mammography and Problem-Solving Breast Evaluation. Despite the fact that this Standard apparently went through a lengthy review process (although this author, a member of the Breast Cancer Task Force of the ACR, never gave his approval), it contains many unsupportable recommendations.


The Role of MRI Pancreatic Protocol in Assessing Response to Neoadjuvant Therapy for Patients With Borderline Resectable Pancreatic Cancer.
Borderline Resectable Pancreatic Cancer (BRPC) remains a unique entity that is difficult to categorize due to variance in definitions and the small number of patients. The ultimate goal is to achieve a free resection (R0) after a favorable response to neoadjuvant therapy that is somewhat difficult to assess by current radiological parameters. To evaluate the role of Magnetic Resonance Imaging (MRI) pancreatic protocol, including Diffusion-Weighted Imaging (DWI), in patients with BRPC receiving neoadjuvant therapy, and further compare it to RECIST criteria and outcome. Histologically confirmed BRPC patients were prospectively included. DWI-MRI was performed pre- and post-therapy. Clinical characteristics with ensuing operability were recorded and correlated to radiological RECIST/apparent diffusion coefficient (ADC) change, preoperative therapy administrated, surgical resection status, and survival. Out of 30 BRPC cases, only 11 (36.7%) ultimately underwent pancreaticoduodenectomy. Attaining a stationary or stable disease via ADC/RECIST was achieved in the majority of cases (60%/53.3% respectively). Of the 12 patients (40%) who achieved a regression by ADC, 11 underwent surgery with an R0 status. These surgical cases showed variable RECIST responses (PR=5, SD=4, PD=3). Responders by ADC to neoadjuvant therapy were significantly associated to presenting with abdominal pain (p =0.07), a decline in post-therapy CA19-9 (p<0.001), going through surgery (p<0.001), and even achieving better survival (p<0.001 vs. 0.66). DWI-MRI ADC picked up patients most likely to undergo a successful operative procedure better than traditional RECIST criteria. An algorithm incorporating novel radiological advances with CA19-9 deserves further assessment in future studies.


Long-term management of recurrent papillary thyroid carcinoma treated with lenvatinib for over 5 years: a case report.
Few reports exist of the long-term management of recurrent and progressive papillary thyroid carcinoma (PTC) with a tyrosine kinase inhibitor for over 5 years. A 57-year-old woman was referred to a psychiatric hospital for the treatment of schizophrenia. The patient had been diagnosed with a PTC at the age of 40 and subsequently underwent a left thyroid lobectomy. At 47, completion total thyroidectomy and lymph node dissection were performed and the patient assessed as radioactive iodine refractory postoperatively. External radiation therapy was performed for Rouviere lymph nodes. At 57, neck and mediastinal lymph nodes, and lung metastases had progressed, and the trachea became narrowed by para-tracheal lymph node compression. After 2 weeks of sorafenib therapy on an outpatient basis, the patient was discovered unconsciousness at home and transferred to hospital by ambulance; sorafenib therapy was stopped. The patient was diagnosed with reversible posterior leukoencephalopathy syndrome by brain magnetic resonance imaging. External radiation therapy to the site of the tracheal stenosis in the neck and mediastinum was performed. The patient's mental symptoms worsened, and she was referred to a psychiatric hospital, Kachi Memorial Hospital, in July 2015. In September, the patient's mental state stabilized and in November, after computed tomography revealed rapid disease progression, lenvatinib was commenced at a daily dose of 24 mg. Measurable solid recurrence sites were neck lymph nodes in the pre-laryngeal subcutaneous space, right lobe of the lung, and left adrenal. After 3 months, the tumors shrank in a partial response (PR). Because of several adverse events, occasional dose reductions or discontinuations of lenvatinib were sometimes necessary. Since re-starting lenvatinib, treatment with this for 51 consecutive months was achieved while maintaining a PR. Although a new bone metastasis was noted after 57 months of lenvatinib, treatment was continued for another 9 months. The patient subsequently passed away in June 2021. The long-term treatment of recurrent PTC with lenvatinib was feasible, with manageable adverse events, for more than 5 years.