A large-scale experiment finds no consistent evidence of change in mortality or commercial productivity in silverlip pearl oysters (Pinctada maxima) exposed to a seismic source survey.
High-intensity, impulsive sounds are used to locate oil and gas reserves during seismic exploration of the seafloor. The impacts of this noise pollution on the health and mortality of marine invertebrates are not well known, including the silverlip pearl oyster (Pinctada maxima), which comprises one of the world's last remaining significant wildstock pearl oyster fisheries, in northwestern Australia. We exposed ≈11,000 P. maxima to a four-day experimental seismic survey, plus one vessel-control day. After exposure, survival rates were monitored throughout a full two-year production cycle, and the number and quality of pearls produced at harvest were assessed. Oysters from two groups, on one sampling day, exhibited reduced survival and pearl productivity compared to controls, but 14 other groups receiving similar or higher exposure levels did not. We therefore found no conclusive evidence of an impact of the seismic source survey on oyster mortality or pearl production.


Shexiang Baoxin Pills for Coronary Heart Disease in Animal Models: Preclinical Evidence and Promoting Angiogenesis Mechanism.
Shexiang Baoxin Pill (SBP) originated from a classical TCM Fufang Suhexiang Pill for chest pain with dyspnea in the Southern Song Dynasty (1107-110 AD). Here, we aimed to evaluate preclinical evidence and possible mechanism of SBP for experimental coronary heart disease (CHD). Studies of SBP in animal models with CHD were identified from 6 databases until April 2016. Study quality for each included article was evaluated according to the CAMARADES 10-item checklist. Outcome measures were myocardial infarction area, vascular endothelial growth factor (VEGF) and microvessel count (MVC). All the data were analyzed by using RevMan 5.1 software. As a consequence, 25 studies with 439 animals were identified. The quality score of studies ranged from 2 to 5, with the median of 3.6. Meta-analysis of seven studies showed more significant effects of SBP on the reduction of the myocardial infarction area than the control (P < 0.01). Meta-analysis of eight studies showed significant effects of SBP for increasing VEGF expression compared with the control (P < 0.01). Meta-analysis of 10 studies indicated that SBP significantly improved MVC compared with the control (P < 0.01). In conclusion, these findings preliminarily demonstrated that SBP can reduce myocardial infarction area, exerting cardioprotective function largely through promoting angiogenesis.


Driving under the influence of cannabis versus alcohol: A mixed-methods study examining perceptions and related risk behaviors among US and Israeli adults.
Despite the dangers of driving under the influence (DUI), little is known about DUI substance-specific risk perceptions or risk factors for riding with drunk/drugged drivers (RDD). In this sequential exploratory mixed-methods study, we conducted: 1) multivariable analyses of cross-sectional survey data from 2222 US and Israeli adults to identify correlates of perceived cannabis- vs. alcohol-related DUI risks (linear regression) and past-month RDD involving alcohol-only, cannabis-only, or both (alcohol-cannabis) (multinomial logistic regression); and 2) deductive-inductive thematic analyses of qualitative interview data from 84 participants to identify themes elaborating on survey findings regarding DUI-related risk perceptions. 54.0 % reported past-month alcohol use, 16.7 % cannabis use, 4.2 % alcohol-only RDD, 5.5 % cannabis-only RDD, and 7.9 % alcohol-cannabis RDD. Being from the US, not having children at home, and cannabis non-use correlated with lower perceived cannabis vs. alcohol DUI risk. Lower perceived cannabis vs. alcohol DUI risk correlated with cannabis-only and alcohol-cannabis (vs. no) RDD, and with alcohol-cannabis (vs. cannabis-only) RDD. Alcohol use correlated with alcohol-only (vs. no) RDD and alcohol-cannabis (vs. cannabis-only) RDD. Cannabis use correlated with cannabis-only and alcohol-cannabis (vs. no) RDD, and with alcohol-cannabis (vs. alcohol-only) RDD. Being from the US correlated with alcohol-only (vs. alcohol-cannabis and none) RDD and cannabis-only (vs. alcohol-cannabis) RDD; being from Israel correlated with alcohol-cannabis (vs. no) RDD. Qualitative data indicated most participants perceived greater risk of DUI of alcohol vs. cannabis and desired more effective DUI-related prevention and regulatory efforts. Prevention interventions targeting DUI- and RDD-related risk perceptions are needed, particularly for high-risk populations.


The REC2 gene encodes the homologous pairing protein of Ustilago maydis.
Amino acid sequence analysis has established that the homologous pairing protein of Ustilago maydis, known previously in the literature as rec1, is encoded by REC2, a gene essential for recombinational repair and meiosis with regional homology to Escherichia coli RecA. The 70-kDa rec1 protein is most likely a proteolytic degradation product of REC2, which has a predicted mass of 84 kDa but which runs anomalously during sodium dodecyl sulfate-gel electrophoresis with an apparent mass of 110 kDa. To facilitate purification of the protein product, the REC2 gene was overexpressed from a vector that fused a hexahistidine leader sequence onto the amino terminus, enabling isolation of the REC2 protein on an immobilized metal affinity column. The purified protein exhibits ATP-dependent DNA renaturation and DNA-dependent ATPase activities, which were reactions characteristic of the protein as purified from cell extracts of U. maydis. Homologous pairing activity was established in an assay that measures recognition via non-Watson-Crick bonds between identical DNA strands. A size threshold of about 50 bp was found to govern pairing between linear duplex molecules and homologous single-stranded circles. Joint molecule formation with duplex DNA well under the size threshold was efficiently catalyzed when one strand of the duplex was composed of RNA. Linear duplex molecules with hairpin caps also formed joint molecules when as few as three RNA residues were present.


Post-caesarean necrotizing soft tissue infection leading to maternal death: A case report.
Necrotizing soft tissue infection is lethal and can lead to sepsis, multi-organ failure, and death. Here we describe a case, which reported to us within 24 hours of Caesarean section, with acute abdominal pain, tachycardia, and tachypnoea. Local examination revealed a large area of necrotic subcutaneous tissue involving a Caesarean section scar. Immediate debridement was carried out and repeated twice after the initial procedure but she could not survive.


Emotion skills training for medical students: a systematic review.
To identify emotion skills training methods and outcomes using a systematic review of medical student curricula studies. We searched the English language literature listed in the PubMed, Educational Resources Information Center (ERIC), PsycINFO and Web of Science databases, from 1980 to the present, using a comprehensive list of emotion skills keywords and subsequent hand searches. A total of 828 articles were initially identified. A manual search yielded 161 articles on broadly defined emotion skills educational programmes for medical students. A more stringent review and hand search of reference lists yielded a final 26 articles that included 'other-directed' emotion skills (i.e. cognitive and behavioural skills intended to manage the emotions of others), a description of the training programme, and assessment data. Emotion skills courses varied by total number of contact hours (2-64 hours), session frequency (from 1 session per day to 1 session every 6 months), duration (2 weeks to 2 years), pedagogy, patients targeted and educational outcomes. Student evaluation data were positive. Fifteen of 26 studies used objective emotion skills measures. Only 6/26 studies included a control or comparison condition and 5/26 used a randomised, controlled trial (RCT) design. All 5 RCTs showed positive outcomes with modest improvements in emotion communication skills, empathy, use of emotion words, supportive behaviours and enriched patient understanding. The heterogeneity of emotion skills curricular studies makes direct comparisons difficult. However, all controlled trials showed positive outcomes, suggesting the importance and effectiveness of 'other-directed' emotion skills training. No specific recommendations about curricular amount and frequency, timing and pedagogy can be made.


Drug and Therapeutics Bulletin at 40.
In April 1962, Consumers' Association published the first issue of a British edition of the American Medical Letter on Drugs and Therapeutics. A year later, formal ties with the parent journal were severed, the title was changed, and Drug and Therapeutics Bulletin (DTB) was launched. Initially, articles in DTB were brief (each around 500 words), references few (rarely more than five) and the circulation around 5,000. Gradually, articles and reference lists have lengthened, and our circulation has grown to 130,000 (a figure bolstered by bulk purchasing agreements with Departments of Health, or their equivalents, in the UK and Eire).


The role of chlorhexidine in caries prevention.
The use of chlorhexidine for caries prevention has been a controversial topic among dental educators and clinicians. In several reviews, it has been concluded that the most persistent reduction of mutans streptococci have been achieved by chlorhexidine varnishes, followed by gels and, lastly, mouth rinses. Also, the evidence for using different chlorhexidine modes or a combination of chlorhexidine-fluoride therapy for caries prevention has been "suggestive but incomplete". Variable study designs and lack of data in high-risk children and adults support the need to continue conducting randomized, well-controlled clinical trials and to search for a practical, effective mode of antimicrobial treatment that augments the known effect of fluoride treatments. Currently, the only chlorhexidine-containing products marketed in the United States (US) are mouthrinses containing 0.12 percent chlorhexidine. Based on the available reviews, chlorhexidine rinses have not been highly effective in preventing caries, or at least the clinical data are not convincing. Due to the current lack of long-term clinical evidence for caries prevention and reported side effects, chlorhexidine rinses should not be recommended for caries prevention. Due to the inconclusive literature and sparse clinical data on gels and varnishes, their use for caries prevention should also be studied further to develop evidence-based recommendations for their clinical role in caries prevention. Since dental caries is a disease with a multifactoral etiology, it is currently more appropriate to use other established, evidence-based prevention methods, such as fluoride applications, diet modifications and good oral hygiene practices. Recent findings also indicate that the effect of an antimicrobial agent for reducing the levels of mutans streptococci or plaque reduction may not always correlate with eventual caries reduction. The clinically important outcome is proven reductions in caries. Many advances in the treatment and prevention of dental caries have been introduced over the past century. The use of chlorhexidine in caries prevention has been referred to as a nonsurgical management of dental caries and has represented the modern medical model of caries treatment. However, there is a lack of consensus on evidence-based treatment protocols and controversy regarding the role of chlorhexidine in caries prevention among dental educators and clinicians. There is a need to standardize guidelines to optimize evidence-based non-surgical disease management to provide appropriate care. This paper reviewed the literature on the effectiveness of different modes of chlorhexidine delivery for caries prevention and provides guidelines for chlorhexidine use in caries management. A literature search was conducted using the PubMed and Evidence-Based Medicine Reviews databases and the keywords "chlorhexidine" and "caries", limiting the search to "humans", "reviews" and "English". Based on the published reviews, it was concluded that chlorhexidine rinses, gels and varnishes or combinations of these items with fluoride have variable effects. Additionally, the sparse clinical data that was reported weakens the conclusions. Due to the current lack of evidence on long-term clinical outcomes and reported side effects, chlorhexidine rinse, which is currently the only treatment mode available in the US, should not be recommended for caries prevention. Clinical evidence on gels and varnishes is also inconclusive. For the treatment of dental caries, there are alternative evidence-based prevention methods available, such as fluoride applications, diet modifications and good oral hygiene practices.


Work characteristics and emotional exhaustion among young workers: a latent class analysis.
This study aims to assess the heterogeneity of psychosocial working conditions of young workers by identifying subgroups of work characteristic configurations within young workers and to assess these subgroups' associations with emotional exhaustion. Latent class analysis. Groups were formed based on 12 work characteristics (8 job demands and 4 job resources), educational level and sex. Differences in emotional exhaustion between subgroups were analysed using analysis of variance and post hoc comparisons. Data from the 2019 wave of the Netherlands Working Conditions Survey. 7301 individuals between the age of 18 and 30 years, who worked more than 16 hours per week. Emotional exhaustion. Five subgroups of work characteristics could be identified and were labelled as: (1) 'low-complexity work' (24.4%), (2) 'office work' (32.3%), (3) 'manual and non-interpersonal work' (12.4%), (4) 'non-manual and interpersonal work' (21.0%), and (5) 'manual and interpersonal work' (9.9%). Mean scores for emotional exhaustion in the two interpersonal work groups (M=3.11, SD=1.4; M=3.45, SD=1.6) were significantly higher than in the first three groups (M=2.05, SD=1.1; M=1.98, SD=1.0; M=2.05, SD=1.1) (all 95% CIs excluding 0). Further, mean scores for emotional exhaustion were significantly higher in the 'manual and interpersonal work' group than in the 'non-manual and interpersonal work' group (95% CI 0.24, 0.45). All results could be replicated in the 2017 and 2021 waves of the Netherlands Working Conditions Survey. Young workers reported heterogeneous work characteristic configurations with substantial differences in degrees of emotional exhaustion between the identified subgroups. Preventing emotional exhaustion should focus on the two interpersonal work subgroups, which showed a high degree of emotional exhaustion. In prevention efforts, these groups' configurations of work characteristics should be taken into account.


Genes Involved in Long-Term Memory Are Expressed in Testis of Cryptorchid Boys and Respond to GnRHa Treatment.
It has been known for many years that boys with unilateral or bilateral undescended testis (cryptorchidism) tend to have a low IQ, and those who belong to the high infertility risk (HIR) group perform less well at school than low infertility risk (LIR) patients. However, the molecular biological processes underlying this phenomenon are not understood. In this study, we report the outcome of testicular RNA profiling for genes involved in long-term memory formation. We analyzed the histology and the transcriptome of testicular biopsies from bilateral HIR cryptorchid boys, comparing those who received GnRHa treatment for 6 months after the first surgery with those who did not receive GnRHa before the second surgery. We found that GnRHa treatment alters the testicular mRNA levels of neuronal genes that are involved in long-term memory and testosterone synthesis. These data highlight a possible molecular link between cryptorchidism, impaired mini-puberty, and diminished cognitive functions. Our results are consistent with the hypothesis that hypogonadotropic hypogonadism in cryptorchid boys with altered mini-puberty may affect neuronal genes important for memory and learning, which could help explaining the negative correlation between cryptorchidism and intellectual abilities.


Somatosympathetic reflex and acupuncture-related analgesia.
Both acute and chronic pains correspond to nociceptive substances (NSs), which are naturally produced and metabolized by the organism experiencing the pains. The accumulation of NSs in regional tissues triggers a series of pathophysiological reactions and initiates certain threats to the health and the quality of human life. Pharmacological intervention is the most popular treatment for pain relief, which is achieved by either reducing the production of NSs or blocking the transmission of nociceptive signals through the nervous system, but no drug has been developed for the elimination of NSs. Therefore, improving blood circulation to eliminate NSs in painful tissues is an alternative strategy for pain relief. Acupuncture has been proved to be effective for the treatment of certain kinds of pain, but the mechanisms therein remain unclear. The effectiveness of acupuncture analgesia is also variable owing to the uncertainty surrounding the mechanism and the poor standardization of the technique. There is some evidence that acupuncture may induce pain relief by changing the regional blood flow through somatosympathetic reflex (SSR). Therefore, when exploring the mechanisms of SSR in detail, it is helpful to clarify the mechanisms of acupuncture analgesia and to develop a more standardized and effective protocol for acupuncture analgesia. Increasing evidence has suggested that both sympathetic activity and stimulation-induced SSR are differentially controlled in an organ-specific and activity-dependent manner. Vasomotor outflow, which involves the regulation of impaired regional blood circulation, is also differentially controlled in response to specific somatic stimulation. Therefore, we vigorously review the relations between SSR and acupuncture-related analgesia so that we can develop a targeted pain therapy where in certain areas of the body undergo site-specific somatic stimulation, which in turn, can adjust the impaired regional blood circulation.


Brief communication: MRGPRX2, atopic dermatitis and red man syndrome.
Vancoymycin causes red man syndrome, an itchy erythematous eruption involving the face, neck and upper torso. Atopic dermatitis also manifests itch and erythema, and staphylococcus δ-toxin contributes to this process. The antibiotic and toxin each provoke mast cell degranulation but the mechanism had not been understood. We have determined that these compounds evoke degranulation via interaction with the same receptor, MRGPRX2, on mast cells. A receptor antagonist inhibits this process. Antagonists of this receptor may have therapeutic potential.


Taking the lead from premature babies regarding their care.
William was born at 26 weeks' gestation and, three weeks later, he is in a high-dependency ward breathing with the help of a continuous positive airway pressure (CPAP) machine. On the whiteboard next to his incubator, a nurse has written 'minimal handling'.


Effects of Chinese Medicine on the Survival of AIDS Patients Administered Second-Line ART in Rural Areas of China: A Retrospective Cohort Study Based on Real-World Data.
Chinese medicine (CM) improves the symptoms of patients with acquired immune deficiency syndrome (AIDS) and prolongs their survival. This real-world study aimed to evaluate the effects of CM on the survival of AIDS patients administered second-line antiretroviral therapy (ART). We conducted a retrospective cohort study of the medical records of patients with AIDS who switched to second-line ART between January 2009 and December 2014. Patients were divided into ART and CM + ART groups. Propensity score matching (PSM) was performed to correct for biases between groups. Kaplan-Meier analysis and the log-rank test were used to compare survival rates, and Cox regression models were employed to identify factors significantly associated with survival. The study population (n = 4180) was comprised of the CM + ART group (n = 855) and the ART group (n = 3325). After 1 : 2 PSM, 855 patients in the CM + ART group and 1699 in the ART group were selected for analysis. Patients in the CM + ART group were followed for 4246.8 person-years, and the mortality rate was 2.12/100 person-years. Patients in the ART group were followed for 8381.2 person-years, and the mortality rate was 2.91/100 person-years. Cox regression model analysis revealed that patients in the CM + ART group survived significantly longer than those in the ART group (hazard ratio: 0.73 and 95% confidence interval: 0.57-0.93). Gender, age, symptoms, CD4 cell counts, and viral loads were independently associated with the survival of AIDS patients treated with second-line ART. CM significantly improved the survival rate of AIDS patients treated with second-line ART.


Actions of mercurials on cell volume regulation of dissociated MDCK cells.
The mercurial, p-chloromercuribenzoylsulfonate (PCMBS), blocks volume recovery of dissociated, osmotically swollen, Madin-Darby canine kidney cells (MDCK) and, at higher concentrations, induces substantial swelling. In the absence of Na+ the rate of volume recovery is, in contrast, substantially increased. PCMBS does not inhibit the "normal" volume-regulating pathways, K+ and Cl- conductances. Rather, its blocking action is due to substantial activation of Na+ and K+ permeabilities, especially the former. Consequently, the normal reshrinking mechanism, loss of KCl, is counterbalanced by PCMBS-induced gains of NaCl. In isotonic cells, PCMBS, at higher concentrations, induces cell swelling, indicating that Cl- permeability is also increased, a conclusion confirmed by direct measurement of 36Cl- fluxes. HgCl2 produces similar effects except that it is more potent and more rapid in its action. Activation of conductive ion permeabilities to Na+, K+, and Cl- are associated with appropriate changes in membrane potential. A small bumetanide-sensitive swelling component (Na(+)-Cl- cotransport) is activated by HgCl2 but not by PCMBS. Another effect is elevation of cytoplasmic Ca2+, apparently by mobilization from internal stores. Some of the functional sites (Na+ and K+) appear to be located externally, rapidly accessible to both HgCl2 and PCMBS, whereas others (Cl- and Ca2+) appear to be internal, rapidly accessible to the permeant HgCl2 but slowly to relatively impermeant PCMBS. In conclusion, the disturbances of volume regulation are largely due to the increases in conductive ion fluxes.


Synaptophysin and postsynaptic density protein 95 in the human prefrontal cortex from mid-gestation into early adulthood.
Previous studies of postnatal synaptic development in human frontal cortex have shown that synaptic density rises after birth, reaches a plateau in childhood and then decreases to adult levels by late adolescence. A similar pattern has been seen in nonhuman primate cortex. These earlier studies in human cortex are limited, however, by significant age gaps in study subjects at critical inflection points of the developmental curve. Additionally, it is unclear if synaptic development occurs in different patterns in different cortical layers in prefrontal cortex (PFC). The purpose of this study was to examine synaptic density in human PFC across development by measuring two synaptic marker proteins: synaptophysin (presynaptic), and postsynaptic density protein 95 (PSD-95; postsynaptic). Western blotting was used to assess the relative levels of synaptophysin and PSD-95 in dorsolateral PFC of 42 subjects, distributed in age from 18 weeks gestation to 25 years. In addition, synaptophysin immunoreactivity was examined in each layer of areas 9 and 46 of PFC in 24 subjects, ranging in age from 0.1-25 years. Synaptophysin levels slowly increased from birth until age 5 and then increased more rapidly to peak in late childhood around age 10. Synaptophysin subsequently decreased until the adult level was reached by mid-adolescence, around age 16. PSD-95 levels increased postnatally to reach a stable plateau by early childhood with a slight reduction in late adolescence and early adulthood. The pattern of synaptophysin immunoreactivity seen with immunohistochemistry was similar to the Western experiments but the changes across age were more subtle, with little change by layer within and across age. The developmental patterns exhibited by these synaptic marker proteins expand upon previous studies of developmental synaptic changes in human frontal cortex; synaptic density increases steadily from birth to late childhood, then decreases in early adolescence to reach adult levels by late adolescence.


Hierarchical superstructures with control of helicity from the self-assembly of chiral bent-core molecules.
Herein, two asymmetric chiral bent-core molecules, 3-[(4-{[4-(heptyloxy)benzoyl]oxy}benzoyl)oxy]-phenyl-4-[(4-{[(1R)-1-methylheptyl]oxy}benzoyl)oxy] benzoate (BC7R) and 3-[(4-{[4-(heptyloxy)benzoyl]oxy}benzoyl)oxy]-phenyl-4-[(4-{[(1S)-1-methylheptyl]oxy}benzoyl)oxy] benzoate (BC7S), were synthesized to demonstrate control of the helicity of their self-assembled hierarchical superstructures. Mirror-imaged CD spectra showed a split-type Cotton effect after the formation of self-assembled aggregates of BC7R and BC7S, thereby suggesting the formation of intermolecular exciton couplets with opposite optical activities. Both twisted and helical ribbons with preferential helicity that corresponded to the twisting character of the intermolecular exciton couplet were found in the aggregates. The formation of helical ribbons was attributed to the merging of twisted ribbons through an increase in width to improve morphological stability. As a result, control of the helicity of hierarchical superstructures from the self-assembly of bent-core molecules could be achieved by taking advantage of the transfer of chiral information from the molecular level onto the hierarchical scale.


OLDER AND YOUNGER ADULTS' STRATEGIC CONTROL OF METACOGNITIVE MONITORING: THE ROLE OF CONSEQUENCES, TASK EXPERIENCE, AND PRIOR KNOWLEDGE.
Background/Study Context: Although explicit memory abilities decline during older adulthood, there is evidence that suggests that metacognitive capabilities are relatively well preserved. However, it is unclear what effect aging, consequences of forgetting, prior knowledge, and task experience have on the strategic control and use of one's metacognitive capabilities. In the current study, older and younger adults were presented with six unique lists of words (Experiment 1), related and unrelated word pairs (Experiment 2), or items within specific scenarios (e.g., items to bring on a picnic; Experiment 3). For each item, participants assigned it a point value (from 0 to 10) that was akin to "betting" on the likelihood the item would be remembered. If the item was recalled (free recall in Experiments 1 and 3, cued recall in Experiment 2), participants received the points they had assigned to it, but if the item was forgotten they lost those points. Participants were told to maximize their point score and were told their score at the end of each list. Although younger adults remembered more words in Experiment 1, older and younger adults were equally able to remember items assigned higher values, and accuracy of predictions and point scores increased with task experience. In Experiments 2 and 3, when participants were able to rely on semantic knowledge, age-related differences in memory performance were eliminated. The results suggest that both younger and older adults achieve accurate metacognitive insight and are able to use this knowledge strategically in order to maximize goal-related memory outcomes and performance.


Haloalkaliphilic microorganisms assist sulfide removal in a microbial electrolysis cell.
Several industrial processes produce toxic sulfide containing streams that are often scrubbed using caustic solutions. An alternative, cost effective sulfide treatment method is bioelectrochemical sulfide removal. For the first time, a haloalkaliphilic sulfide-oxidizing microbial consortium was introduced to the anodic chamber of a microbial electrolysis cell operated at alkaline pH and with 1.0 M sodium ions. Under anode potential control, the highest sulfide removal rate was 2.16 mM/day and chemical analysis supported that the electrical current generation was from the sulfide oxidation. Biotic operation produced a maximum current density of 3625 mA/m2 compared to 210 mA/m2 while under abiotic operation. Furthermore, biotic electrical production was maintained for a longer period than for abiotic operation, potentially due to the passivation of the electrode by elemental sulfur during abiotic operation. The use of microorganisms reduced the energy input in this study compared to published electrochemical sulfide removal technologies. Sulfide-oxidizing populations dominated both the planktonic and electrode-attached communities with 16S rRNA gene sequences aligning within the genera Thioalkalivibrio, Thioalkalimicrobium, and Desulfurivibrio. The dominance of the Desulfurivibrio-like population on the anode surface offered evidence for the first haloalkaliphilic bacterium able to couple electrons from sulfide oxidation to extracellular electron transfer to the anode.


Sequential Presentation of Bilateral Brown Syndrome: Report of a Case with an Interesting Imaging Finding.
To present a case of bilateral Brown syndrome who presented as a unilateral disease and then showed the disease in the fellow eye in an older age. A 4-year-old girl presented with congenital Brown syndrome of the left eye and underwent a superior oblique weakening procedure in that eye, but then developed Brown syndrome in the right eye which required two more surgeries on the right eye to attain an acceptable alignment. Her orbital computed tomography scan revealed that the distance between the annulus of Zinn and trochlea (Z-T distance) was 41.2 mm in both sides, which was comparatively longer than her age- and sex-matched cases. This finding can suggest a possible mechanism of Brown syndrome development in some patients. Bilateral Brown syndrome can present as a sequential disease, and its radiologic finding may be associated with increased Z-T distance.


[Preventive contralateral mastectomy despite absence of gene mutation; management and treatment of women with no medical indication].
Recently, there has been an increase in the rate of contralateral prophylactic mastectomies (CPM) as a therapy for breast cancer. The CPM is performed to achieve a reduction in the risk of developing asecond breast cancer. However, evidence is lacking for beneficial survival outcomes after a CPM in patients without a gene mutation, and complications of surgery are inevitable. Currently there are no evidence-based clinical practice guidelines available for clinicians to decide upon the right treatment for patients without a gene mutation. Our hospitals have therefore implemented their own clinical pathway to achieve a comprehensive treatment for this group of patients. In this article we will provide an overview of the existing literature and illustrate our clinical pathway by presenting three patients treated in our hospitals in the last two years.


Differentiating Transudative From Exudative Ascites Using Quantitative B-Mode Gray-Scale Ultrasound Histogram.
The purpose of this article is to differentiate exudative from transudative ascites using B-mode gray-scale ultrasound histogram analysis. Sixty-two consecutive patients with ascites were prospectively studied from June 2014 through June 2015. All underwent ultrasound (US) and paracentesis in the radiology department. Five patients were excluded (three with hemorrhage and two with peritoneal carcinomatosis). The remaining 57 patients were divided into those with exudative and transudative ascites according to results of paracentesis. Electronically recorded US images were transferred to a workstation, and gray-scale histograms were generated. The ascites-to-rectus abdominis muscle echogenicity ratio (ARAER) was obtained from ascites adjacent to the rectus abdominis muscle. ROC curves were used to evaluate the sensitivity and specificity of this method in differentiating exudative from transudative ascites. ARAERs for exudative ascites were significantly higher than those for transudative ascites (p < 0.001). ROC was done to evaluate ARAERs for exudative ascites. The best cutoff value for ARAER histogram was 0.002. The sensitivity and specificity of ARAER were 87.5% and 79.2% (AUC = 0.843), respectively. ARAER is an easily applicable noninvasive quantitative sonographic method with high sensitivity and specificity in differentiating exudative from transudative ascites.


Extrapiscine development of Myxobolus drjagini Akhmerov, 1954 (Myxosporea: Myxobolidae) in oligochaete alternative hosts.
The extrapiscine development of Myxobolus drjagini, a myxosporean parasite of the head, operculum and buccal cavity of the silver carp (Hypophthalmichthys molitrix), was studied in experimentally infected oligochaetes, Tubifex tubifex. After infection of uninfected tubificids with mature spores of M. drajagini, development of actinosporean stages was first observed by light microscopy 27 days after infection. Triactinomyxon stages of M. drjagini emerged from the worms after 91 days of intraoligochaete development. In histological sections, early pansporocysts were found in the gut epithelium of the experimental oligochaetes 42 days after infection. Mature pansporocysts, each containing 8 triactinomyxons, appeared 79 days after infection. After rupture of the epithelial cell and the pansporocyst, free actinosporean stages were found in the gut lumen of the oligochaete. Actinosporean stages released from oligochaetes appeared in the water 91 days after infection. They were floating in the water and showed a typical triactinomyxon form. Each triactinomyxon had three pyriform polar capsules, a sporoplasm with 14 secondary cells inside the spore body, a moderately long style and slightly bent, trifurcated, conically ending tails. The total length of the triactinomyxon measured approximately 198 microns. The prevalence of infection in 51 oligochaetes proved to be 9.8%. No infection was found in the control oligochaetes.


Acute myeloid leukemia with t(3;21)(q26.2;q22) developing following low-dose methotrexate therapy for rheumatoid arthritis and expressing two AML1/MDS1/EVI1 fusion proteins: A case report.
The t(3;21)(q26.2;q22) translocation is a rare chromosomal abnormality exhibited almost exclusively in therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/AML) or in the blastic crisis phase of chronic myelogenous leukemia, which results in the fusion of the runt related transcription factor 1 (RUNX1, also called AML1) gene at 21q22 to the myelodysplasia syndrome 1 (MDS1)-ecotropic virus integration site 1 (EVI1) complex locus (MECOM) at 3q26.2, generating various fusion transcripts, including AML1/MDS1/EVI1 (AME). The present study examined the case of an 84-year-old Japanese woman who developed t-MDS/AML with t(3;21)(q26.2;q22) subsequent to receiving low-dose methotrexate (MTX) treatment for rheumatoid arthritis. Following treatment with MTX for 6 years, the patient developed anemia and neutropenia, and MTX was discontinued. A total of 3 years later, the patient was diagnosed with MDS with t(3;21)(q26.2;q22) and del (5q), which progressed rapidly to AML within 3 months. The patients was subsequently treated with azacitidine and cytarabine chemotherapy, but succumbed to the disease 6 months after diagnosis. Sequencing analysis of the nested reverse transcription-PCR products from the leukemic cells revealed the expression of two types of alternatively-spliced AME transcripts with or without RUNX1 exon 6 sequences. Western blot analysis of the leukemic cells of the patient additionally revealed that the corresponding AME fusion protein products were expressed at high levels, and that these cells also prominently expressed CCAAT/enhancer-binding protein α, the repression of which has been reported to be involved in leukemogenesis mediated by AME. To the best of our knowledge, the case discussed in the present study represents the first report of MDS/AML with t(3;21)(q26.2;q22) developing following low-dose MTX therapy for rheumatoid arthritis. Nonetheless, the clinical and molecular features of the patient in the present study were representative of those patients who typically develop this disease following exposure to chemotherapy or radiotherapy for primary malignancy, which implicates MTX in the pathogenesis of t-MDS/AML. Moreover, we confirmed the expression of two AME fusion proteins for the first time in primary leukemic cells and analyzed several cellular factors implicated in AME-mediated leukemogenesis to gain some insight into its molecular mechanisms.


Micelle-Assisted Formation of Nanoparticle Superlattices and Thermally Reversible Symmetry Transitions.
Nanoparticle superlattices (NPSLs) are of great interest as materials with designed emerging properties depending on the lattice symmetry as well as composition. The symmetry transition of NPSLs depending on environmental conditions can be an excellent ground for making new stimuli-responsive functional materials. Here, we report a spherical micelle-assisted method to form exceptionally ordered NPSLs which are inherently sensitive to environmental conditions. Upon mixing functionalized gold nanoparticles (AuNPs) with a nonionic surfactant spherical micellar solution, NPSLs of different symmetries such as NaZn13, MgZn2, and AlB2-type are formed depending on the size ratio between micelles and functionalized AuNPs and composition. The NPSLs formed by the spherical micelle-assisted method show thermally reversible order-order (NaZn13-AlB2) and order-disorder (MgZn2-isotropic) symmetry transitions, which are consistent with the Gibbs free energy calculations for binary hard-sphere model. This approach may open up new possibilities for NPSLs as stimuli-responsive functional materials.


[Bending resistance of composites after storage in water from 1 day to 3 months].
The resistance to bending of paste-paste composites decreases with one exception after prolonged storage in water. The UV-hardened artificial filling materials show no uniform picture in this respect. The bending module of three paste-paste composites is at its peak after 24 hours with values of 40 to 50 kN/mm2, and then drops to 1/3 of this value. The value of the bending module of photopolymerising composites lies considerably lower-between 4 and 13 kN/mm2.


Effect of ankle position and a plaster cast on intramuscular pressure in the human leg.
Intramuscular pressure was measured with transducer-tipped catheters that had been inserted into the anterior and deep posterior compartments of the leg in seven healthy adults. Intramuscular pressure increased three to sevenfold (depending on the position of the ankle) in both compartments after the application of a plaster cast from the proximal part of the thigh to the malleoli. While the cast was in place, the baseline intramuscular pressure was elevated by the inflation of a tourniquet, which was located on the proximal part of the thigh, to a pressure of sixty millimeters of mercury (8.00 kilopascals). The intramuscular pressure in both the anterior and the deep posterior compartments was found to be lowest when the ankle joint was between the neutral and the resting positions (between 0 and 37 degrees of flexion). After the cast was bivalved and the opening on each side was spread approximately one-half centimeter, there was a significant decrease in intramuscular pressure of 47 per cent in the anterior compartment and of 33 per cent in the deep posterior compartment (p < 0.05 for both).


The origins of altruism in offspring care.
The current review aims to unify existing views of altruism through an examination of the biological bases of a fundamental form of giving: altruistic responding. Altruistic responding is most salient during heroic acts of helping but is also observed any time one perceives another's distress or need, which in turn motivates one to help at a current cost to the self. Such aid is simple, observable across species, and rooted in the instincts and circuits that evolved to maximize inclusive fitness through the care of helpless offspring. By design, the system already biases aid to both kin and nonkin under conditions that are largely adaptive. These inherent benefits are also buttressed in primates and humans by known, later-arriving benefits to helping in group-living animals. Evidence for the proposed homology between altruistic responding and offspring retrieval is presented through 10 key shared factors. Conceptually, both require (a) participation by nonmothers, (b) motor competence and expertise, (c) an adaptive opponency between avoidance and approach, and a facilitating role of (d) neonatal vulnerability, (e) salient distress, and (f) rewarding close contact. Physiologically, they also share neurohormonal support from (g) oxytocin, (h) the domain-general mesolimbocortical system, (i) the cingulate cortex, and (j) the orbitofrontal cortex. The framework intermixes ultimate and proximate levels of analysis and unifies existing views by assuming that even complex human behaviors reflect ancient mammalian neural systems that evolved to solve key problems in adaptive ways, with far-reaching consequences for even our most venerated human traits.


Polymer Competitive Solvation Reduced Propylene Carbonate Cointercalation in a Graphitic Anode.
Polymer electrolytes have been studied as an alternative to organic liquid electrolytes but suffer from low ionic conductivity. Propylene carbonate (PC) proves to be an interesting solvent but is incompatible with graphitic anodes due to its cointercalation effect. In this work, adding poly(ethylene oxide) (PEO) into a PC-based electrolyte can alter the solvation structure as well as transform the solution into a polymer electrolyte with high ionic conductivity. By spectroscopic techniques and calculations, we demonstrate that PEO can compete with PC in solvating the Li+ ions, reducing the Li+-PC bond strength, and making it easier for PC to be desolvated. Due to the unique solvation structure, PC-cointercalation-induced graphite exfoliation is inhibited, and the reduction stability of the electrolyte is improved. This work will extend the applications of the PC-based electrolytes, deepen the understandings of the solvation structure, and spur designs of advanced electrolytes.


Normal and abnormal fMRI activation patterns in the visual cortex after recovery from optic neuritis.
Recovery to normal or near normal visual acuity after an optic neuritis episode is common, despite frequent persistence of conduction abnormalities, evident in prolonged visual evoked potential (VEP) latencies. Improvement of visual function is commonly attributed to peripheral nerve recovery. However, central reorganization processes may also be involved. To assess this, we compared the patterns of fMRI activation, elicited by stimulation of the affected and the normal eye, along the visual cortical hierarchy. Activation was assessed in 8 subjects, which recovered clinically from an episode of optic neuritis but still had prolonged VEP latencies. In all patients, reduced fMRI activation was seen in V1 during stimulation of the affected eye, compared to the normal eye. The fMRI signal difference decreased in magnitude with progression along the visual hierarchy, and in some regions within the lateral occipital complex even showed the opposite preference (for the affected eye). These results may indicate a built-in robustness of the object-related areas to disruption of the visual input. Alternatively, it could reflect an adaptive functional reorganization of the cortical response to an abnormal input.


Clinical evaluation of analgesic activity of guduchi (tinospora cordifolia) using animal model.
Pain is a very well-known signal of ill health and analgesics are the drugs that are used to relieve pain. The main problem with these drugs remains that of side effects. Safer alternatives are natural herbs. Guduchi (Tinospora cordifolia) is one such plant with analgesic potential but few studies are there. To evaluate the analgesic activity of commercially available extract of Guduchi (T. cordifolia). For this purpose commercially available extract of Guduchi (T. cordifolia) by Himalaya Drug Company, Bangalore was used. Albino rats were divided randomly in three groups of six rats each. Group 1 (control) received distilled water orally, group 2 (test) received T. cordifolia extract in dose of 300 mg/kg orally and group 3(standard) received Pentazocine in dose 10mg/kg intraperitoneally. Analgesic activity was evaluated using hot plate and abdominal writhing method. All the observations were analysed statistically using student's t-test. T. cordifolia extract significantly (p<0.05) increased the response time and decreased the number of writhes in hot plate method and abdominal writhing method respectively, on comparison with the control group. The above findings suggest that this commercially available extract of Guduchi (T. cordifolia) possess analgesic activity. This analgesic activity probably involves peripheral as well as central mechanisms as the extract showed analgesic activity in both hot plate and abdominal writhing method.


Lower Bone Density, Impaired Microarchitecture, and Strength Predict Future Fragility Fracture in Postmenopausal Women: 5-Year Follow-up of the Calgary CaMos Cohort.
The aim of this prospective study was to use high-resolution peripheral quantitative computed tomography (HR-pQCT) to determine if baseline skeletal parameters can predict incident fragility fracture in women and, secondly, to establish if women that fracture lose bone at a faster rate than those who do not fracture. Women older than 60 years who experienced a fragility fracture during the 5-year follow-up period (incident fracture group, n = 22) were compared with those who did not experience a fragility fracture during the study (n = 127). After image registration between baseline and follow-up measures, standard and cortical morphological analyses were conducted. Odds ratios were calculated for baseline values and annualized percent change of HR-pQCT and finite element variables. At the radius, baseline HR-pQCT results show women who fractured had lower total bone mineral density (Tt.BMD; 19%), trabecular bone mineral density (Tb.BMD; 25%), and trabecular number (Tb.N; 14%), with higher trabecular separation (Tb.Sp; 19%) than women who did not fracture. At the tibia, women with incident fracture had lower Tt.BMD (15%), Tb.BMD (12%), cortical thickness (Ct.Th; 14%), cortical area (Ct.Ar; 12%), and failure load (10%) with higher total area (Tt.Ar; 7%) and trabecular area (Tb.Ar; 10%) than women who did not fracture. Odds ratios (ORs) at the radius revealed every SD decrease of Tt.BMD (OR = 2.1), Tb.BMD (OR = 2.0), and Tb.N (OR = 1.7) was associated with a significantly increased likelihood of fragility fracture. At the tibia, every SD decrease in Tt.BMD (OR = 2.1), Tb.BMD (OR = 1.7), Ct.Th (OR = 2.2), Ct.Ar (OR = 1.9), and failure load (OR = 1.7) were associated with a significantly increased likelihood of fragility fracture. Irrespective of scanning modality, the annualized percent rate of bone loss was not different between fracture groups. The results suggest baseline bone density, microarchitecture, and strength rather than change in these variables are associated with incident fragility fractures in women older than 60 years. Furthermore, irrespective of fragility fracture status, women experienced changes in skeletal health at a similar rate. © 2017 American Society for Bone and Mineral Research.


Characterization of Tigecycline-Heteroresistant Klebsiella pneumoniae Clinical Isolates From a Chinese Tertiary Care Teaching Hospital.
Tigecycline has been used as one of the therapeutic choices for the treatment of infections caused by multidrug-resistant Klebsiella pneumoniae. However, the emergence of tigecycline heteroresistance has led to great challenges in treating these infections. The purpose of this study was to investigate whether tigecycline-heteroresistant K. pneumoniae (TGCHR-Kp) exists in clinical isolates, and to further characterize the underlying molecular mechanisms involved in the development of tigecycline-resistant subpopulations. Of the 268 tigecycline-susceptible clinical K. pneumoniae isolates, 69 isolates were selected as tigecycline-heteroresistant candidates in the preliminary heteroresistant phenotypic selection by a modified disk diffusion method, and only 21 strains were confirmed as TGCHR-Kp by the population analysis profile (PAP). Pulsed-field gel electrophoresis (PFGE) analysis demonstrated that all the parental TGCHR-Kp isolates were clonally unrelated, and colonies confirmed as the heteroresistant subpopulation showed no significant differences from their respective parental TGCHR-Kp isolates. Efflux pump inhibitors reversed the tigecycline susceptibility in heteroresistant subpopulations. Mutations in the ramR and soxR genes lead to upregulation of the ramA and soxS transcriptional regulators, which in turn induced overexpression of the AcrAB-TolC efflux pump genes in TGCHR-Kps-resistant subpopulations. Moreover, mutations of rpsJ were also found in resistant subpopulations, which suggested that the rpsJ mutation may also lead to tigecycline resistance. Time-kill assays showed that the efficacy of tigecycline against TGCHR-Kps was weakened, whereas the number of resistant subpopulations was enriched by the presence of tigecycline. Our findings imply that the presence of TGCHR-Kps in clinical strains causes severe challenges for tigecycline therapy in clinical practice.


Immunomodulatory activities associated with beta-glucan derived from Saccharomyces cerevisiae.
In this study we investigated the effect of beta-glucan derived from Saccharomyces cerevisiae on fungicidal activity, cytokine production and natural killer activity. Spleen and peritoneal cells from female C57BL/6 mice, previously injected (24 or 48 h) with 20 or 100 microg of glucan by i.p. route, were assayed. In vivo beta-glucan administration primed spleen cells for a higher production of IL-12 and TNF-alpha when S. aureus was used as a stimulus. In addition, beta-glucan increased NK spleen cells activity against YAC target cells. Some immunomodulatory activities not yet described for beta-glucan were observed in this work.


Response of Kampuchean strains of Plasmodium falciparum to antimalarials: in-vivo assessment of quinine and quinine plus tetracycline; multiple drug resistance in vitro.
Forty-three patients were enlisted in the in-vivo test for sensitivity of Kampuchean strains of Plasmodium falciparum to quinine. The mean parasite density count on day 0 was 32,398 asexual parasites per microliter of blood. With a dosage of 1.5 g quinine base daily for 10 days the average parasite clearance time was 5.6 days, and the average duration of fever 3.4 days. The in-vivo test was evaluated at 7 and 10 days after the start of therapy. After 7 days only 16 patients were parasite negative by microscopic examination (S); 20 patients had an RI recrudescence, four patients responded at the RII level and three at the RIII level. Evaluating the in-vivo test at 10 days, the number of patients parasite negative increased to 18, the number of those with an RI level of resistance increased to 21, two patients gave an RII response and two had an RIII level of resistance. Twenty-two adult males were included in an in-vivo test of the sensitivity of P. falciparum to quinine plus tetracycline. The course of treatment was: quinine 3 x 500 mg daily for 10 days, tetracycline 3 x 500 mg for 7 days. Parasite density counts on day 0 averaged 11,393 asexual parasites per microliter of blood. The average parasite clearance time was 5.9 days, and the average duration of fever was 3.8 days. After 7 days of treatment, 81.8% of patients were parasite negative, while one patient had a recrudescence after 17 days (RI). Three infections were resistant at the RII level. By prolongation of the observations to day 10, the parasitaemia was cleared in all patients, i.e. all infections were sensitive to quinine plus tetracycline. Thirty-four patients with falciparum malaria were screened for in-vitro resistance to chloroquine, mefloquine and quinine using the WHO standard micro-test.(ABSTRACT TRUNCATED AT 250 WORDS)


Short communication: Molecular epidemiology of HIV type 1 in the Republic of Dagestan, Russian Federation: virtually uniform circulation of subtype A, former Soviet Union variant, with predominance of the V77I(PR) subvariant.
We examine the distribution of viral genetic forms and the presence of antiretroviral drug resistance mutations in HIV-1 infections in the Republic of Dagestan, in the North Caucasus area of Russia, where a recent large increase in HIV-1 infections has been documented. Samples were collected from 41 HIV-1-infected individuals from Dagestan, most of them from the cities of Derbent (n = 21) and Mahachkala (n = 18). Thirty six were injecting drug users and five were infected by heterosexual contact. None was on antiretroviral drug treatment. HIV-1 protease and a segment of reverse transcriptase were amplified by RT-PCR from plasma RNA and sequenced, and phylogenetic trees were constructed via maximum likelihood. Forty (97.6%) of 41 samples were of subtype A, former Soviet Union variant (A(FSU)), of which 27 (67.5%) clustered with the subvariant containing the V77I substitution in protease (V77I(PR)). Within this cluster, 13 viruses formed a local subcluster, 10 of which were from Derbent. Four viruses clustered with the A(SP2) subcluster, recently identified in St. Petersburg, two with a virus from Georgia and one with a virus from Azerbaijan. No mutations associated with antiretroviral drug resistance were detected. The results, therefore, show the relationship of the HIV-1 epidemic in Dagestan with that of other areas of Russia and of neighboring countries, and reveal the spread of the A(FSU) V77I(PR) variant in the North Caucasus area.


How Extracellular Nano-Vesicles Can Play a Role in Sepsis? An Evidence-Based Review of the Literature.
Sepsis is a systemic inflammatory reaction caused by infection. Severe sepsis can lead to multiple organ dysfunction, with a high incidence rate and mortality. The molecular pathogenesis of sepsis is complex and diverse. In recent years, with further study of the role of extracellular vesicles (EVs) in inflammatory diseases, it has been found that EVs play a dual role in the imbalance of inflammatory response in sepsis. Due to the great advantages such as lower toxicity, lower immunogenicity compared with stem cells and better circulation stability, EVs are increasingly used for the diagnosis and treatment of sepsis. The roles of EVs in the pathogenesis, diagnosis and treatment of sepsis were summarized to guide further clinical studies.


Microwave-assisted fibrous decoration of mPE surface utilizing Aloe vera extract for tissue engineering applications.
Developing multifaceted, biocompatible, artificial implants for tissue engineering is a growing field of research. In recent times, several works have been reported about the utilization of biomolecules in combination with synthetic materials to achieve this process. Accordingly, in this study, the ability of an extract obtained from Aloe vera, a commonly used medicinal plant in influencing the biocompatibility of artificial material, is scrutinized using metallocene polyethylene (mPE). The process of coating dense fibrous Aloe vera extract on the surface of mPE was carried out using microwaves. Then, several physicochemical and blood compatibility characterization experiments were performed to disclose the effects of corresponding surface modification. The Fourier transform infrared spectrum showed characteristic vibrations of several active constituents available in Aloe vera and exhibited peak shifts at far infrared regions due to aloe-based mineral deposition. Meanwhile, the contact angle analysis demonstrated a drastic increase in wettability of coated samples, which confirmed the presence of active components on glazed mPE surface. Moreover, the bio-mimic structure of Aloe vera fibers and the influence of microwaves in enhancing the coating characteristics were also meticulously displayed through scanning electron microscopy micrographs and Hirox 3D images. The existence of nanoscale roughness was interpreted through high-resolution profiles obtained from atomic force microscopy. And the extent of variations in irregularities was delineated by measuring average roughness. Aloe vera-induced enrichment in the hemocompatible properties of mPE was established by carrying out in vitro tests such as activated partial thromboplastin time, prothrombin time, platelet adhesion, and hemolysis assay. In conclusion, the Aloe vera-glazed mPE substrate was inferred to attain desirable properties required for multifaceted biomedical implants.


Design, characterization and applications of nanocolloidal hydrogels.
Nanocolloidal gels (NCGs) are an emerging class of soft matter, in which nanoparticles act as building blocks of the colloidal network. Chemical or physical crosslinking enables NCG synthesis and assembly from a broad range of nanoparticles, polymers, and low-molecular weight molecules. The synergistic properties of NCGs are governed by nanoparticle composition, dimensions and shape, the mechanism of nanoparticle bonding, and the NCG architecture, as well as the nature of molecular crosslinkers. Nanocolloidal gels find applications in soft robotics, bioengineering, optically active coatings and sensors, optoelectronic devices, and absorbents. This review summarizes currently scattered aspects of NCG formation, properties, characterization, and applications. We describe the diversity of NCG building blocks, discuss the mechanisms of NCG formation, review characterization techniques, outline NCG fabrication and processing methods, and highlight most common NCG applications. The review is concluded with the discussion of perspectives in the design and development of NCGs.


Epstein-Barr virus (EBV) and X-linked lymphoproliferative syndrome (XLP).
XLP was first described in 1975, when EBV was still focused on as an immediate oncogenic agent, but with some uncertainties raised by the absence of EBV in most non-endemic Burkitt lymphoma. The discovery of XLP refreshingly evidenced and popularized the concept, "EBV pathogenicity (oncogenicity) in immunocompromised hosts", which was later vastly substantiated by EBV-carrying lymphomas in organ-transplanted and AIDS patients. Fatal (or severe) IM, acquired hypogammaglobulinemia (AH) and malignant lymphoma (MH) are 3 major phenotypes in XLP. Fatal IM occurs in 2/3 with a mortality rate of 85%. Lymphocyte infiltration (T cells and EBV-positive B cells) followed by their depletion with the appearance of macrophages. EBV-associated hemophagocytic syndrome in the bone marrow leads to hematocytopenia, ML, AH and ML with AH usually occur after EBV infection, but can occur before it. Reactivation pattern of EBV serology (high VCA, high EA, low EBNA), impaired generation of EBV-specific killer cell (poor regression), lowered NK activity, lowered 4/8 ratio and failure to mount IgG response to phi X174 have been recorded in XLP and carrier females. However, some or all of these are also found in non-XLP congenital immunodeficiencies as well as acquired immunodeficient states like advanced lymphoma or AIDS. In order to record XLP-specific defects, impaired help of autologous Ia-stimulated T4 cells or exaggerated suppression by T cells exposed to MA-pulsed macrophages is now being tested (Purtilo, personal communication). Fewer V region genes of T receptor may be a possibility. Restriction fragment length polymorphism (RFLP) by using probes from X chromosome may substantiate the precise genetics of this disease.


Approaching criticality in polymer-polymer systems.
The interfacial width of polyolefins blends has been probed as a function of distance away from the critical point by using neutron reflectivity. For strongly immiscible polymer pairs, the width of the interface increases slowly when the degree of immiscibility is decreased and the interfacial width varies with the interaction parameter chi of the polymers. Closer to the critical point the dependence on the degree of miscibility becomes stronger and the way in which the interfacial width diverges, as criticality is approached, is related to both the chain length and chi. The self-consistent field theory numerical calculations, with the additional contribution due to capillary waves, provides a good description of the width of the interface between two polymer bulk phases in particular at intermediate values of the degree of immiscibility.


Triage for the neurosurgeon.
Triage for the neurosurgeon is a misnomer. The neurosurgeon's role within a mass-casualty situation is one of a subspecialist surgeon instead of a triage officer. Unfortunately because of the events of September 11, 2001, civilian neurosurgeons and other medical specialists have been questioning their role within a mass-casualty situation or, worse, a situation created by biological, chemical, or nuclear weapons. There is no single triage system used exclusively within the United States, and different systems have differing sensitivities, specificities, and labeling methods. The purpose of this article is to discuss varying aspects of triage for both military personnel and civilians and suggest how the neurosurgeon may help shape this process within his or her community. Furthermore, the effects of biological, chemical, and nuclear weapons will be discussed in relation to the triage system.


Local and systemic regulation of plant root system architecture and symbiotic nodulation by a receptor-like kinase.
In plants, root system architecture is determined by the activity of root apical meristems, which control the root growth rate, and by the formation of lateral roots. In legumes, an additional root lateral organ can develop: the symbiotic nitrogen-fixing nodule. We identified in Medicago truncatula ten allelic mutants showing a compact root architecture phenotype (cra2) independent of any major shoot phenotype, and that consisted of shorter roots, an increased number of lateral roots, and a reduced number of nodules. The CRA2 gene encodes a Leucine-Rich Repeat Receptor-Like Kinase (LRR-RLK) that primarily negatively regulates lateral root formation and positively regulates symbiotic nodulation. Grafting experiments revealed that CRA2 acts through different pathways to regulate these lateral organs originating from the roots, locally controlling the lateral root development and nodule formation systemically from the shoots. The CRA2 LRR-RLK therefore integrates short- and long-distance regulations to control root system architecture under non-symbiotic and symbiotic conditions.


Misoprostol use as a method of medical abortion.
The aim of our study was to verify with the use of ultrasound (US) scanning the effectiveness of misoprostol in medical abortion. The study population included women with a medical miscarriage attending the 2nd Department of Obstetrics and Gynecology, University of Athens in Aretaieion Hospital, Athens, Greece. All women < 49 days since their last menstruation received 800 microg vaginal misoprostol. The diagnosis of complete abortion was possible by the US measurements as endometrial thickness of 15 mm by transvaginal US was used as a cutoff level for successful abortion. The mean age of the study population was 27 years (ranging from 19 up to 37 years). Complete evacuation with misoprostol was performed in 149 women. The success rate was 85.2% (127/149). Twenty-two women experienced intrauterine echogenic structures with a diameter > 15 mm and all of them underwent surgical evacuation (14.8%). Vaginal bleeding was present in 17 patients after the procedure (11.4%). Less usual reported side-effects included nausea, vomiting, pain, or diarrhea. Misoprostol use is an effective, safe and acceptable method of medical abortion for women.


Obstructive sleep apnea and hypertension.
There has long been a recognized link between obstructive sleep apnea (OSA) and the cardiovascular system, no aspect of which has been more studied than blood pressure. Research in OSA has not only demonstrated dysregulation of homeostatic cardiovascular mechanisms but also has furthered our understanding of blood pressure regulatory control. Acute nocturnal blood pressure elevations associated with disordered breathing events have been reproduced from a number of observational studies, the accrual of which has also made an increasing argument for the importance of OSA in the pathogenesis of diurnal hypertension, as suggested by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), which implicated OSA as a secondary cause of hypertension. Accumulating data from randomized controlled treatment trials in OSA, particularly with continuous positive airway pressure, though sometimes inconsistent, suggest a potential role in blood pressure reduction. Further research is needed to better clarify indications for OSA treatment as well as its role as an adjunct to other antihypertensive treatments.


Cloning and sequence analysis of a class A beta-lactamase from Mycobacterium tuberculosis H37Ra.
A cosmid library from Mycobacterium tuberculosis H37Ra was introduced into Mycobacterium smegmatis, and eight recombinant clones with increased resistance to cefoxitin were identified. Isoelectric focusing detected an M. tuberculosis-derived beta-lactamase in one of these recombinant clones. A sequence analysis identified it as a class A beta-lactamase whose expression correlated with the increased resistance phenotype.


c-di-AMP Is Essential for the Virulence of Enterococcus faecalis.
Second messenger nucleotides are produced by bacteria in response to environmental stimuli and play a major role in the regulation of processes associated with bacterial fitness, including but not limited to osmoregulation, envelope homeostasis, central metabolism, and biofilm formation. In this study, we uncovered the biological significance of c-di-AMP in the opportunistic pathogen Enterococcus faecalis by isolating and characterizing strains lacking genes responsible for c-di-AMP synthesis (cdaA) and degradation (dhhP and gdpP). Using complementary approaches, we demonstrated that either complete loss of c-di-AMP (ΔcdaA strain) or c-di-AMP accumulation (ΔdhhP, ΔgdpP, and ΔdhhP ΔgdpP strains) drastically impaired general cell fitness and virulence of E. faecalis. In particular, the ΔcdaA strain was highly sensitive to envelope-targeting antibiotics, was unable to multiply and quickly lost viability in human serum or urine ex vivo, and was virtually avirulent in an invertebrate (Galleria mellonella) and in two catheter-associated mouse infection models that recapitulate key aspects of enterococcal infections in humans. In addition to evidence linking these phenotypes to altered activity of metabolite and peptide transporters and inability to maintain osmobalance, we found that the attenuated virulence of the ΔcdaA strain also could be attributed to a defect in Ebp pilus production and activity that severely impaired biofilm formation under both in vitro and in vivo conditions. Collectively, these results demonstrate that c-di-AMP signaling is essential for E. faecalis pathogenesis and a desirable target for drug development.


Pixuna virus modifies host cell cytoskeleton to secure infection.
Pixuna virus (PIXV) is an enzootic member of the Venezuelan Equine Encephalitis Virus complex and belongs to the New World cluster of alphaviruses. Herein we explore the role of the cellular cytoskeleton during PIXV replication. We first identified that PIXV undergoes an eclipse phase consisting of 4 h followed by 20 h of an exponential phase in Vero cells. The infected cells showed morphological changes due to structural modifications in actin microfilaments (MFs) and microtubules (MTs). Cytoskeleton-binding agents, that alter the architecture and dynamics of MFs and MTs, were used to study the role of cytoskeleton on PIXV replication. The virus production was significantly affected (p < 0.05) after treatment with paclitaxel or nocodazole due to changes in the MTs network. Interestingly, disassembly of MFs with cytochalasin D, at early stage of PIXV replication cycle, significantly increased the virus yields in the extracellular medium (p < 0.005). Furthermore, the stabilization of actin network with jasplakinolide had no effect on virus yields. Our results demonstrate that PIXV relies not only on intact MTs for the efficient production of virus, but also on a dynamic actin network during the early steps of viral replication.


C3a modulates IL-1β secretion in human monocytes by regulating ATP efflux and subsequent NLRP3 inflammasome activation.
Interleukin-1β (IL-1β) is a proinflammatory cytokine and a therapeutic target in several chronic autoimmune states. Monocytes and macrophages are the major sources of IL-1β. IL-1β production by these cells requires Toll-like receptor (TLR) and adenosine triphosphate (ATP)-mediated P2X purinoceptor 7 (P2X7) signals, which together activate the inflammasome. However, how TLR signals and ATP availability are regulated during monocyte activation is unclear and the involvement of another danger signal system has been proposed. Here, we demonstrate that both lipopolysaccharide (LPS) and the anaphylatoxin C3a are needed for IL-1β production in human macrophages and dendritic cells, while in monocytes, C3a enhanced the secretion of LPS-induced IL-1β. C3a and LPS-stimulated monocytes increased T helper 17 (Th17) cell induction in vitro, and human rejecting, but not nonrejecting, kidney transplant biopsies were characterized by local generation of C3a and monocyte and Th17 cell infiltration. Mechanistically, C3a drives IL-1β production in monocytes by controlling the release of intracellular ATP into the extracellular space via regulation of as-yet unidentified ATP-releasing channels in an extracellular signal-regulated kinase 1/2-dependent fashion. These data define a novel function for complement in inflammasome activation in monocytes and suggest that C3aR-mediated signaling is a vital component of the IL-1β-Th17 axis.


Geographic disparity in premature mortality in Ontario, 1992-1996.
BACKGROUND: Standardized mortality ratios are used to identify geographic areas with higher or lower mortality than expected. This article examines geographic disparity in premature mortality in Ontario, Canada, at three geographic levels of population and considers factors that may underlie variations in premature mortality across geographic areas. All-cause, sex and disease chapter specific premature mortality were analyzed at the regional, district and public health unit level to determine the extent of geographic variation. Standardized mortality ratios for persons aged 0-74 years were calculated to identify geographic areas with significantly higher or lower premature mortality than expected, using Ontario death rates as the basis for the calculation of expected deaths in the local population. Data are also presented from the household component of the 1996/97 National Population Health Survey and from the 1996 Statistics Canada Census. RESULTS: Results showed approximately 20% higher than expected all-cause premature mortality for males and females in the North region. However, disparity in all-cause premature mortality in Ontario was most pronounced at the public health unit level, ranging from 20% lower than expected to 30% higher than expected. Premature mortality disparities were largely influenced by neoplasms, circulatory diseases, injuries and poisoning, respiratory diseases and digestive diseases, which accounted for more than 80% of all premature deaths. Premature mortality disparities were also more pronounced for disease chapter specific mortality. CONCLUSION: Geographic disparities in premature mortality are clearly greater at the small area level. Geographic disparities in premature mortality undoubtedly reflect the underlying distribution of population health determinants such as health related behaviours, social, economic and environmental influences.


[Survival analysis on liver failure patients treated with an artificial liver support system].
To evaluate the efficacy of artificial liver support system (ALSS) in the treatment of liver failure patients. This is a prospective, multi-center, controlled, large sample clinic trial. 518 patients with liver failure from 5 hospitals were studied and followed. All the patients received similar pharmacological manipulation according to one and the same protocol but were divided into an ALSS treatment group and a control group without ALSS treatment. The ALSS treatment procedures included plasma exchange, molecular adsorbent recirculating system (MARS), plasma exchange plus hemofiltration and other combined nonbioartificial methods. The analysis of survival time was computed using the Kaplain-Maier method, and comparison among groups was done using Log-Rank, Breslow and/or the Tarone-Ware test. Survival time of acute liver failure patients was prolonged from 4.0+/-0.2 days to 8.0+/-0.4 days (P=0.004). ALSS was shown to be two times more effective. ALSS increased the survival time of acute on chronic (A on C) liver failure patients from 27.0+/-1.6 days to 39.0+/-4.0 days (P less than 0.01). In addition, it increased the survival time of the patients in the middle and end stage of subacute liver failure and A on C liver failure, but had no significant effects on early stage patients. The survival time of middle stage patients was 38.0+/-17.5 days in the control group vs 66.0+/-18.6 days in the ALSS group (P less than 0.05). The survival time of end stage patients of the control group and the ALSS group was 18.0+/-4.0 days vs 26.0+/-2.5 days (P less than 0.01). Multi ALSS treatment is more effective than the standard medicinal liver care treatment. Multi-ALSS treatment could increase survival time of patients suffering from acute liver failure or A on C liver failure, especially in their middle and end stages. It is important and necessary to treat these patients with ALSS.


Activation of human T cells by major histocompatability complex class II expressing neutrophils: proliferation in the presence of superantigen, but not tetanus toxoid.
The primary function of polymorphonuclear neutrophils (PMN) in the immune response appears to be acute phagocytic clearance of foreign pathogens and release of inflammatory mediators. Consistent with their assumed lack of major histocompatibility complex (MHC) class II expression, PMN have not been considered to play a role in antigen presentation and T-cell activation. However, recent reports have shown that human PMN can express MHC class II molecules both in vitro and in vivo after stimulation with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interferon-gamma (IFN-gamma). Thus, under appropriate conditions, PMN could play a significant role in immune regulation, including T-cell activation. In this report, we demonstrate that human class II-expressing PMN can serve as accessory cells in superantigen (SAg)-mediated T-cell activation. This accessory activity for SAg presentation was present only after induction of MHC class II expression, and was especially pronounced following culture of PMN with GM-CSF plus IFN-gamma, which acted synergistically to induce MHC class II molecules on PMN. Moreover, the level of MHC class II expression and the magnitude of SAg-induced T-cell responses were found to be highly correlated and distinctly donor dependent, with PMN from some donors repeatedly showing fivefold higher responses than PMN from other donors. On the other hand, culture of PMN with GM-CSF plus IFN-gamma under conditions that resulted in optimal MHC class II expression did not enable them to function as antigen-presenting cells for either intact tetanus toxoid (TT) or for a TT peptide. These results delineate a new pathway for T-cell activation by SAg that may play an important role in the severity of SAg-induced inflammatory responses. They also identify a donor-specific polymorphism for induction of PMN MHC class II expression which may be of significance for therapies involving GM-CSF and IFN-gamma.


Coping with palliative chemotherapy.
Comparatively little is known about how patients with advanced cancer cope with palliative chemotherapy. This study uses grounded theory to analyse the coping responses of 24 women with advanced breast or ovarian cancer. Half the sample received chemotherapy at home, and the remainder were treated in hospital. The results suggest that four predominant coping styles are used; think positive/fighter (n = 8), acceptance (n = 8), fearfulness (n = 5) and hopelessness (n = 3). In addition, a range of coping strategies that reduced the threat of chemotherapy are identified. The findings have implications for the provision of quality patient care in palliative therapy, especially in relation to individualizing patient education.


Evolution of cytochrome bc complexes: from membrane-anchored dehydrogenases of ancient bacteria to triggers of apoptosis in vertebrates.
This review traces the evolution of the cytochrome bc complexes from their early spread among prokaryotic lineages and up to the mitochondrial cytochrome bc1 complex (complex III) and its role in apoptosis. The results of phylogenomic analysis suggest that the bacterial cytochrome b6f-type complexes with short cytochromes b were the ancient form that preceded in evolution the cytochrome bc1-type complexes with long cytochromes b. The common ancestor of the b6f-type and the bc1-type complexes probably resembled the b6f-type complexes found in Heliobacteriaceae and in some Planctomycetes. Lateral transfers of cytochrome bc operons could account for the several instances of acquisition of different types of bacterial cytochrome bc complexes by archaea. The gradual oxygenation of the atmosphere could be the key evolutionary factor that has driven further divergence and spread of the cytochrome bc complexes. On the one hand, oxygen could be used as a very efficient terminal electron acceptor. On the other hand, auto-oxidation of the components of the bc complex results in the generation of reactive oxygen species (ROS), which necessitated diverse adaptations of the b6f-type and bc1-type complexes, as well as other, functionally coupled proteins. A detailed scenario of the gradual involvement of the cardiolipin-containing mitochondrial cytochrome bc1 complex into the intrinsic apoptotic pathway is proposed, where the functioning of the complex as an apoptotic trigger is viewed as a way to accelerate the elimination of the cells with irreparably damaged, ROS-producing mitochondria. This article is part of a Special Issue entitled: Respiratory complex III and related bc complexes.


Selection of surgical procedures for treatment of failed back surgery syndrome (FBSS).
The paper presents the definition of failed back surgery syndrome (FBSS), current surgical treatment options and other pain control options. Available data indicates an occurrence rate of FBSS in 5-50% of cases. A steep increase of the number of performed spinal procedures has also led to an increase in the number of FBSS cases. FBSS is caused by a complex relation of different causes: biological, psychological. social and economic. Patient selection and correct indications are of key importance for successful surgical treatment of FBSS. The pathology to be addressed must be clearly defined in imaging studies, in order to perform the procedure that will yield optimal results. In over 50% with FBSS a psychological or behavioral dysfunction can be noted, and identification of such condition is part of FBSS prevention protocols. Surgical techniques for FBSS treatment include decompression, stabilization and fusion and dynamic neutralization procedures. These techniques are discussed in the paper.


MetaOmics: analysis pipeline and browser-based software suite for transcriptomic meta-analysis.
The rapid advances of omics technologies have generated abundant genomic data in public repositories and effective analytical approaches are critical to fully decipher biological knowledge inside these data. Meta-analysis combines multiple studies of a related hypothesis to improve statistical power, accuracy and reproducibility beyond individual study analysis. To date, many transcriptomic meta-analysis methods have been developed, yet few thoughtful guidelines exist. Here, we introduce a comprehensive analytical pipeline and browser-based software suite, called MetaOmics, to meta-analyze multiple transcriptomic studies for various biological purposes, including quality control, differential expression analysis, pathway enrichment analysis, differential co-expression network analysis, prediction, clustering and dimension reduction. The pipeline includes many public as well as >10 in-house transcriptomic meta-analytic methods with data-driven and biological-aim-driven strategies, hands-on protocols, an intuitive user interface and step-by-step instructions. MetaOmics is freely available at https://github.com/metaOmics/metaOmics. Supplementary data are available at Bioinformatics online.


A decomposition product of a contaminant implicated in L-tryptophan eosinophilia myalgia syndrome affects spinal cord neuronal cell death and survival through stereospecific, maturation and partly interleukin-1-dependent mechanisms.
The L-tryptophan eosinophilia myalgia syndrome (L-TRP-EMS), an inflammatory syndrome characterized by eosinophilia, myalgias, perimyositis, fasciitis and neuropathies, occurred in epidemic proportions in the United States in the summer and fall of 1989. The neuropathic clinical features in L-TRP EMS are complex and mixed. In the present study, one of the impurities most highly associated with development of L-TRP EMS, 1,1'-ethylidenebis[L-tryptophan] (EBT), and two of its diastereoisomeric breakdown products, were compared for evidence of neurotoxicity in vitro. In 1-month-old spinal cord cultures derived from fetal mice, synthetic (-)-(1S,3S)-1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (1S-beta-C) produced a 30 to 35% loss in numbers of neurons. Toxicity was not apparent after treatment with the R-isomer of the same compound or with the parent compound, EBT. Cotreatment of cultures with 1S-beta-C and neutralizing antiserum to interleukin-1 alpha (IL-1 alpha), or with 1S-beta-C and neutralizing antiserum against the murine IL-1 receptor, prevented neuronal cell death associated with 1S-beta-C. Recombinant IL-1 alpha also produced neuronal killing that was not additive to that observed with the 1S-beta-C treatment. In contrast, in immature spinal cord neuronal cultures, the 1S-beta-C, but not the 1R-beta-C or EBT, prevented the 30% cell death which normally occurs in these cultures. Neither neutralizing anti-IL-1 antibody, nor anti-IL-1 receptor antibody blocked the neuronal survival effect, suggesting that 1S-beta-C induces neuronal survival through a receptor-mediated mechanism independent of IL-1.(ABSTRACT TRUNCATED AT 250 WORDS)


Safety and efficacy of endovascular recanalization in patients with mild anterior stroke due to large-vessel occlusion exceeding 24 hours.
Endovascular recanalization (ER) has demonstrated efficacy as a treatment modality for patients presenting with acute ischemic stroke (AIS) caused by large-vessel occlusion (LVO) within a 24-hour timeframe. Nevertheless, the safety and effectiveness of ER in patients with a time of onset exceeding 24 h remain uncertain. To evaluate the safety and efficacy of ER treatment for mild ischemic stroke beyond 24-h from symptom onset. A retrospectively maintained database of mild AIS due to LVO from March2018 to September 2022 at a comprehensive stroke center was screened.Patients received ER or standard medical therapies (SMT) for anterior circulation AIS due to LVO > 24-h were selected. We included 47 LVO patients with mild AIS beyond 24-h who suffered neurological deterioration (ND). 34 of these patients underwent ER, the other 13 received SMT. The technical success rate of recanalization was 82.4% (28/34). Patients received ER had significantly lower NIHSS score at discharge and 90-day mRS score (p = 0.028, p = 0.037, respectively) compared to SMT. In addition, they had significantly lower 90-day recurrence of ischemic stroke and lower incidence of moderate-severe stroke (with a NIHSS score at least 5) (p = 0.037, p = 0.033). There were 4 patients (11.7%) had perioperative complications, and no symptomatic intracranial hemorrhage occurred. ER treatment for mild AIS due to LVO encountered ND was generally safe and effective, even beyond 24-h, and resulted in a good prognosis and lower 90-day recurrence compared to SMT.


Greater activation of smooth muscle alpha-2 adrenoceptors by epinephrine in distal than in proximal segments of rat tail artery.
The effects of selective blockade of alpha-1 and alpha-2 adrenoceptors on the vasoconstrictor responses to epinephrine (EPI) and norepinephrine (NOR) were compared in perfused/superfused proximal and distal segments of rat tail artery. The influence of neuronal uptake and of activation of beta adrenoceptors was also investigated. EPI was more potent in distal than in proximal segments. The antagonistic effect of idazoxan (100 nM) against EPI was greater in distal than in proximal segments, whereas the opposite result was obtained with prazosin (0.1-10 nM). No such difference were observed when NOR was used as agonist. Reducing the calcium ion concentration had a greater inhibitory effect on EPI in distal than in proximal segments. Cocaine (4 microM) increased responses to EPI and NOR to a greater extent in proximal than in distal segments. In the presence of cocaine, in proximal segments, antagonism of EPI by prazosin was reduced, whereas in distal segments, antagonism by idazoxan and the inhibitory effect of a reduction in calcium ion concentration were reduced. Propranolol (1 microM) increased responses to EPI and NOR to a greater extent in proximal than in distal segments. In the presence of propranolol, antagonism of EPI by both prazosin and idazoxan was reduced in proximal segments, and the inhibitory effect of a reduction in calcium ion concentration was lost. Forskolin (1 microM) inhibited responses to EPI and prevented the antagonistic effect of idazoxan, but not that of prazosin. From the results obtained it is suggested that smooth muscle alpha-2 adrenoceptors are distributed differently in the proximal and distal ends of the rat tail artery.(ABSTRACT TRUNCATED AT 250 WORDS)


Virtual sonography for novice sonographers: usefulness of SYNAPSE VINCENT® with pre-check imaging of tumor location.
To evaluate the usefulness of a virtual ultrasound (US) imaging device as a tool to assist novice sonographers. A prospective blinded pilot study was conducted involving patients with liver lesions. Two sonographers and 2 medical doctors with less than 5 years of experience performed US examinations. The time needed to detect liver lesions on US and the success rate for detecting liver lesions with and without using the virtual US imaging device SYNAPSE VINCENT® (Fujifilm Medical Co., Tokyo, Japan) before US examination were evaluated. Thirty-two patients with the following 42 liver lesions were included: liver cyst (n = 24), hemangioma (n = 8), hepatocellular carcinoma (n = 6), and liver metastasis (n = 4). The maximal diameter of these lesions ranged from 0.3 to 1.5 cm (mean ± SD, 0.8 ± 0.4). The average time for detecting liver lesions on US was 47.8 s (range, 7-113) with VINCENT and 112.9 s (range, 14-313) without VINCENT before US examination. There were significant differences in the duration of US examination with and without VINCENT (p = 0.0002, Student's t test). The rates for accurately detecting liver lesions were 100 and 76.2% (16/21) in US beginners with and without VINCENT, respectively. Significantly higher detection rates were found in the US beginners who used VINCENT compared to those who did not use VINCENT (p = 0.047, Fisher's exact test). Before US examination, a reference with VINCENT could contribute to the successful detection of liver lesions and could be time-saving for US beginners.


Controversies in the assessment of HER-2: more questions than answers.
Human epidermal growth factor receptor 2 (HER-2) is over-expressed in 15% to 30% of breast cancers and is a poor prognostic marker in node-positive patients. HER-2 expression is an indicator of greater sensitivity to anthracycline-based chemotherapy and is the major criterion for selection for treatment with the anti-HER-2 antibody trastuzumab (Herceptin). Fluorescence in situ hybridization and immunohistochemistry (IHC) are the 2 most commonly used methods for detection of the gene and protein, respectively. Criticisms have been levied at the IHC method of identifying HER-2 overexpression but convenience and costs of this technique cannot be overlooked. Modifications to the IHC technique and scoring accommodate for many of the problems that derive from variables in preanalytical and analytic factors that influence results but standardization is currently impossible to attain. Deficiencies in fluorescence in situ hybridization assay also exist and alternative molecular methods of assay are explored in this review.


Firearm suicides and homicides in the United States: regional variations and patterns of gun ownership.
Among industrialized countries, the United States has the highest rates of firearm suicide and homicide, as well as the highest rate of gun ownership. The present study compares the differential impact of gun availability on firearm suicides and homicides in the U.S. Using data from the NCHS Mortality Detail Files (1989-1991), the 1990 U.S. census population estimates, and the General Social Surveys (1989-1991) for nine geographic divisions, we computed rates of firearm and non-firearm suicides and homicides as well as rates of gun ownership for four gender-race groups. We tested the strength of the associations between gun availability and firearm suicide and homicide rates by computing the Spearman correlation coefficients. To help elucidate the role of method substitution, we conducted similar analyses on non-firearm suicide and homicide. The results show that gun ownership has a stronger impact on firearm suicides than homicides. These findings held up after stratifying by gender and race. The study suggests that reducing the aggregate level of gun availability may decrease the risk of firearm-related deaths.


Photochemistry of proteins: a review.
Proteins are an important target of photochemical damage to the eye. The wavelength of irradiation is a major determinant of the initial mechanisms. The effects of ultraviolet radiation are initiated by absorption in the aromatic amino acid residues and cystine. Photoionization of tyrosine and tryptophan residues leads to aromatic free radicals. The ejected electrons are stabilized in the aqueous medium as hydrated electrons and may be temporarily trapped by cystyl bridges. N-formylkynurenine is an important tryptophan photoproduct, which can act as an endogenous photosensitizer of near-ultraviolet radiation by generating singlet oxygen and superoxide. Singlet oxygen is produced also by exogenous sensitizers absorbing in the visible and near ultraviolet regions. The mechanisms are illustrated by porphyrins and furocoumarins, in which dark binding interactions influence the photosensitization pathways.


Laparoscopic adjustable silicone gastric banding: complications.
Laparoscopic adjustable gastric banding is a procedure that is now approved by the Federal Drug Administration for use in the United States to treat morbid obesity. Numerous complications can occur as a result of the device. These include both early technical complications as well as long-term problems such as esophageal dilatation and failed weight loss. While improvements in surgical technique may decrease early technical complications such as gastric prolapse, long-term follow-up studies will be required to determine the ultimate success of this device in controlling severe obesity.


Line mixing in parallel and perpendicular bands of CO2: A further test of the refined Robert-Bonamy formalism.
Starting from the refined Robert-Bonamy formalism [Q. Ma, C. Boulet, and R. H. Tipping, J. Chem. Phys. 139, 034305 (2013)], we propose here an extension of line mixing studies to infrared absorptions of linear polyatomic molecules having stretching and bending modes. The present formalism does not neglect the internal degrees of freedom of the perturbing molecules, contrary to the energy corrected sudden (ECS) modelling, and enables one to calculate the whole relaxation matrix starting from the potential energy surface. Meanwhile, similar to the ECS modelling, the present formalism properly accounts for roles played by all the internal angular momenta in the coupling process, including the vibrational angular momentum. The formalism has been applied to the important case of CO2 broadened by N2. Applications to two kinds of vibrational bands (Σ → Σ and Σ → Π) have shown that the present results are in good agreement with both experimental data and results derived from the ECS model.


Spontaneous and repetitive calcium transients in C2C12 mouse myotubes during in vitro myogenesis.
Fluorescence videomicroscopy was used to monitor changes in the cytosolic free Ca2+ concentration ([Ca2+]i) in the mouse muscle cell line C2Cl2 during in vitro myogenesis. Three different patterns of changes in [Ca2+]i were observed: (i) [Ca2+]i oscillations; (ii) faster Ca2+ events confined to subcellular regions (localized [Ca2+]i spikes) and (iii) [Ca2+]i spikes detectable in the entire myotube (global [Ca2+]i spikes). [Ca2+]i oscillations and localized [Ca2+]i spikes were detectable following the appearance of caffeine-sensitivity in differentiating C2Cl2 cells. Global [Ca2+]i spikes appeared later in the process of myogenesis in cells exhibiting coupling between voltage-operated Ca2+ channels and ryanodine receptors. In contrast to [Ca2+]i oscillations and localized [Ca2+]i spikes, the global events immediately stopped when cells were perfused either with a Ca2+-free solution, or a solution with TTX, TEA and verapamil. To explore further the mechanism of the global [Ca2+]i spikes, membrane currents and fluorescence signals were measured simultaneously. These experiments revealed that global [Ca2+]i spikes were correlated with an inward current. Moreover, while the depletion of the Ca2+ stores blocked [Ca2+]i oscillations and localized [Ca2+]i spikes, it only reduced the amplitude of global [Ca2+]i spikes. It is suggested that, during the earlier stages of the myogenesis, spontaneous and repetitive [Ca2+]i changes may be based on cytosolic oscillatory mechanisms. The coupling between voltage-operated Ca2+ channels and ryanodine receptors seems to be the prerequisite for the appearance of global [Ca2+]i spikes triggered by a membrane oscillatory mechanism, which characterizes the later phases of the myogenic process.


A pause in nucleus accumbens neuron firing is required to initiate and maintain feeding.
Nucleus accumbens (NAc) inactivation increases food intake, indicating that NAc neurons exert ongoing inhibition of feeding. We previously described a subpopulation of NAc neurons that pause during sucrose licking and proposed that the pause permits consumption. We tested this hypothesis by first recording NAc neurons during sucrose consumption, and then electrically stimulating through the same electrodes. A large proportion of NAc shell and core neurons were inhibited during sucrose consumption, and local electrical stimulation abruptly interrupted licking. Effective stimulation sites were more anterior than ineffective sites in NAc. At low stimulus intensities, licking resumed immediately on stimulation offset. The latency to lick resumption from NAc neuron inhibition onset ( approximately 460 ms) was very similar to that after electrical stimulation offset ( approximately 440 ms). These results directly support the hypothesis that a significant subpopulation of NAc neurons inhibit palatable food consumption and that a pause in their firing is required to initiate and maintain consumption.


Water-Mediated Interactions between Hydrophilic and Hydrophobic Surfaces.
All surfaces in water experience at short separations hydration repulsion or hydrophobic attraction, depending on the surface polarity. These interactions dominate the more long-ranged electrostatic and van der Waals interactions and are ubiquitous in biological and colloidal systems. Despite their importance in all scenarios where the surface separation is in the nanometer range, the origin of these hydration interactions is still unclear. Using atomistic solvent-explicit molecular dynamics simulations, we analyze the interaction free energies of charge-neutral model surfaces with different elastic and water-binding properties. The surface polarity is shown to be the most important parameter that not only determines the hydration properties and thereby the water contact angle of a single surface but also the surface-surface interaction and whether two surfaces attract or repel. Elastic properties of the surfaces are less important. On the basis of surface contact angles and surface-surface binding affinities, we construct a universal interaction diagram featuring three different interaction regimes-hydration repulsion, cavitation-induced attraction-and for intermediate surface polarities-dry adhesion. On the basis of scaling arguments and perturbation theory, we establish simple combination rules that predict the interaction behavior for combinations of dissimilar surfaces.