The impact of depression and post-traumatic stress symptoms on physical health perceptions and functional impairment among sexual minority men living with HIV with histories of trauma.
Mental health symptoms may compromise health-related quality of life (HRQOL), including among men who have sex with men (MSM) living with HIV, who experience high rates of trauma and other stressors. This study sought to examine the relative contributions of post-traumatic stress disorder (PTSD) symptoms, depression symptoms, and biological indices of HIV disease status on HRQOL in this population. Participants were 79 MSM with HIV (49% White; 35% Black; 8% Hispanic/Latinx) with trauma histories (52% met current PTSD diagnostic criteria). HRQOL outcomes were general perceptions of health (0-100 visual analog scale) and functional disability (WHODAS 2.0). Dominance analysis was applied to examine the relative share of variance in these outcomes accounted for by PTSD symptom severity, depression symptom severity, viral suppression status, and CD4 count. Depression symptom severity accounted for 70% and 92% of variance in perceived health, respectively, across models (p's < 0.05). Both PTSD symptom severity (45%) and depression symptom severity (43%) scores also accounted for significant variance in functional disability (p's < 0.05). Medical indices of HIV disease progression did not explain significant variance in HRQOL in any model. A trauma-informed approach may aid clinicians in interpreting reports of health and physical functioning in MSM with HIV.


The taxonomic status of Myotis aelleni Baud, 1979 (Chiroptera, Vespertilionidae).
Myotis aelleni Baud, 1979 was described based on a large series from Chubut, Argentina, and is known only from the type locality and Río Negro, also in Argentina. According to the original description, M. aelleni is closest morphologically to M. chiloensis (Waterhouse, 1840), but can be distinguished based on the tricolored dorsal hairs and skull size and shape. The taxonomic status of M. aelleni has been questioned but the species is still treated as valid. Based on qualitative and quantitative analyses of the type series of M. aelleni, and series of M. chiloensis, including the neotype, we recognize M. aelleni as a junior synonym of M. chiloensis. M. aelleni and M. chiloensis have bicolor dorsal hairs and cannot be distinguished on the basis of the skull size and shape. After synonymy, M. chiloensis occur from Central Chile and western Argentina to central Patagonia and Tierra del Fuego archipelago. Twenty-one species of Myotis occur in South America, including Trinidad and Tobago.


CRISPR-based screens uncover determinants of immunotherapy response in multiple myeloma.
Cancer cells commonly develop resistance to immunotherapy by loss of antigen expression. Combinatorial treatments that increase levels of the target antigen on the surface of cancer cells have the potential to restore efficacy to immunotherapy. Here, we use our CRISPR interference- and CRISPR activation-based functional genomics platform to systematically identify pathways controlling cell surface expression of the multiple myeloma immunotherapy antigen B-cell maturation antigen (BCMA). We discovered that pharmacologic inhibition of HDAC7 and the Sec61 complex increased cell surface BCMA, including in primary patient cells. Pharmacologic Sec61 inhibition enhanced the antimyeloma efficacy of a BCMA-targeted antibody-drug conjugate. A CRISPR interference chimeric antigen receptor T cells (CAR-T cells) coculture screen enabled us to identify both antigen-dependent and antigen-independent mechanisms controlling response of myeloma cells to BCMA-targeted CAR-T cells. Thus, our study shows the potential of CRISPR screens to uncover mechanisms controlling response of cancer cells to immunotherapy and to suggest potential combination therapies.


Interaction between handedness and the attentional bias during tests of dichotic listening performance.
Perceptual advantages are typically interpreted as direct expressions of underlying hemispheric functional asymmetries. However, many other confounding factors including the asymmetric distribution of attention may also contribute to either the magnitude or direction of any of these advantages. In a series of experiments, Mondor and Bryden (1991, 1992a, 1992b) found that right-handed subjects bias their attention toward the right ear when faced with a difficult dichotic listening task. The present study was undertaken to determine whether the direction of the attentional bias is associated with handedness. The focus of auditory spatial attention was manipulated in a dichotic listening paradigm by presenting a pretrial tone cue to the ear from which the subject was required to report. The time period between the onset of the cue and the onset of the dichotic trial (Stimulus Onset Asynchrony--SOA) was varied in order to control the time available to orient attention to the cued ear. Whereas performance for the right ear improved substantially with SOA, that for the left ear improved only marginally. In addition, because of this differential effect of the cue on right ear and left ear performance, the magnitude of the right ear advantage was inflated at 450 ms SOA from that apparent at 150 ms and 750 ms SOA. These findings are interpreted as evidence that, in contrast to right-handers, left-handers bias their attention toward the left ear. This relation between handedness and the direction of the attentional bias is shown to have important implications for the interpretation of perceptual asymmetries.


Regional hypoventilation and bronchoconstriction during pulmonary air embolism.
The hypothesis that experimental pulmonary air embolism would lead to bronchoconstriction in the upper lungs and a shift in ventilation toward the lower lung regions was tested in anaesthetized and paralyzed dogs. During constant rate air infusion (0.15 ml X kg-1 X min-1), regional distribution indices were obtained using radioactive xenon boli injected at the mouth at residual volume. The results show that there was a shift of inspired xenon toward the dependent lungs after 30 min of air infusion and that this shift was accompanied by a rise in pulmonary artery pressure, a slight decrease in vital capacity, a significant increase in closing volume and an increase in airway resistance. Inspiring 5% CO2 after the shift did not reverse the distribution of xenon boli. Intravenous injection of isoproterenol after the changes had occurred, on the other hand, invariably returned the distribution toward control values. These findings indicate that hypoventilation and bronchoconstriction occurred in the non-dependent lungs during pulmonary air embolism.


Global invasive bacterial vaccine-preventable diseases surveillance--2008-2014.
Meningitis and pneumonia are leading causes of morbidity and mortality in children globally infected with Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis, and Haemophilus influenzae causing a large proportion of disease. Vaccines are available to prevent many of the common types of these infections. S. pneumoniae was estimated to have caused 11% of deaths in children aged <5 years globally in the pre-pneumococcal conjugate vaccine (PCV) era. Since 2007, the World Health Organization (WHO) has recommended inclusion of PCV in childhood immunization programs worldwide, especially in countries with high child mortality. As of November 26, 2014, a total of 112 (58%) of all 194 WHO member states and 44 (58%) of the 76 member states ever eligible for support from Gavi, the Vaccine Alliance (Gavi), have introduced PCV. Invasive pneumococcal disease (IPD) surveillance that includes data on serotypes, along with meningitis and pneumonia syndromic surveillance, provides important data to guide decisions to introduce PCV and monitor its impact.


[COVID-19 pandemic on health professionals in a third level hospital in Spain: job changes during the first wave, mental health at 4 months, and follow-up at 9 months].
To determine the impact that the COVID-19 pandemic has had on health professionals, in terms of work changes and mental health. 1) Cross-sectional study and 2) longitudinal prospective study on health professionals who worked directly with patients affected by COVID-19 pandemic during the period between March-June 2020 in a tertiary hospital in Barcelona. Baseline (July-November 2020) and follow-up (November 2020-March 2021) data were collected. Data related to the job and toxic habits were collected with ad hoc questionnaires, and data related to perceived stress, post-traumatic stress, depression, and anxiety using validated questionnaires. In the baseline group (cross-sectional study), 90 professionals participated, 76% nurses. More than a third were on sick leave or took drugs to manage stress. Half of smokers increased tobacco use, and one in 5 increased alcohol consumption. Habitual shift change is significantly associated with depression, professional profile with anxiety, and perceived stress with age. In the longitudinal prospective study, the follow-up group (n = 64) shows high levels of stress and anxiety, which are maintained or even significantly increased over time. The structural changes that occurred in the hospital during the first wave of the COVID-19 pandemic had a strong impact on professionals, many of them presenting an increase in toxic habits, as well as impaired mental health that is maintained over time.


Perceptions of engagement in health care among patients with tuberculosis: a qualitative study.
Adherence to treatment is cited as a key challenge in fighting tuberculosis (TB). Treatment of TB requires patients to actively engage in their care. The purpose of this study was to explore the perceptions of patients with TB regarding their engagement in health care. The study was conducted in three medical wards in one hospital. Purposive sampling was used to recruit participants. Semi-structured, audiotaped interviews were conducted and analyzed using thematic analysis. Twenty-three patients participated in the study. Four major themes emerged: 1) devaluing engagement; 2) interacting with health care providers (HCPs); 3) facing inability; and 4) seeking external support. The patients' perceptions of their engagement in health care were generally negative. Paying attention to the preferences and needs of patients and making decisions accordingly are effective strategies for promoting patient engagement. Moreover, HCPs should be aware of their crucial role in helping patients make sense of what engagement is and how to engage. In the process of engagement, providers should establish effective interactions with patients and cooperate with family and peers.


Transposition of plasmid DNA segments specifying hydrocarbon degradation and their expression in various microorganisms.
The conjugative TOL plasmid (75 Mdal), specifying biodegradation of xylenes, toluene, and trimethylbenzene derivatives, undergoes dissociation in Pseudomonas aeruginosa PAO to a nonconjugative TOL(*) plasmid (28 Mdal) and a transfer plasmid termed TOLDelta (48 Mdal). The TOL(*) plasmid is rendered transmissible through introduction of a number of conjugative plasmids such as factor K, CAM, and TOLDelta but not by the FP2 derivative pR0271. Transfer of TOL(*) via factor K or TOLDelta is mediated by the formation of plasmid cointegrates; no recombination is observed with CAM. A recombinant RP4-TOL plasmid (76 Mdal), which has lost resistance to tetracycline, has been isolated. The TOL(*) segment can be transposed from this RP4-TOL recombinant plasmid to other antibiotic resistance plasmids such as R702. A segment of DNA, specifying salicylate degradation from SAL plasmid, was transposed onto pAC10, the TOL(*-) derivative of RP4-TOL recombinant plasmid, which has lost resistance to tetracycline but retains the transfer genes of RP4. Transposition of the salicylate degradative genes onto pAC10 results in the loss of kanamycin resistance. It has been possible to isolate SAL(+) segregants from pAC10[unk]SAL transposition derivatives that have lost the pAC10 plasmid. Such segregants harbor the salicylate degradative genes in the form of a nonconjugative plasmid (SAL(*)). Transfer of RP4[unk]TOL(*) or pAC10[unk]SAL(*) transposition derivatives to Escherichia coli, Salmonella typhimurium, Agrobacterium tumefaciens, or Azotobacter vinelandii results in the functional expression of the antibiotic resistance genes but not of the hydrocarbon degradative genes. Such genes, however, are fully expressed on being transferred back to Pseudomonas.


Eccentric exercise prior to hindlimb unloading attenuated reloading muscle damage in rats.
Antigravity muscles that are reloaded subsequent to hindlimb unloading (HU) are prone to injury. Similarities exist between muscle damage elicited from HU and subsequent reloading and damage induced by eccentric exercise (EE). Conditioning bouts of EE reduce muscle damage following a repeat bout of EE. Since damage to reloaded skeletal muscle is comparable to damage observed after EE, the mechanisms of damage are presumably similar. Therefore, EE prior to HU may attenuate reloading muscle damage. This study evaluated the effects of prior EE on rat soleus muscles (SOL) subsequent to 7 d of HU and 16-19 h of reloading. Sprague Dawley rats were randomly assigned to the following groups: eccentric exercise + hindlimb unloading + reloading (EEHUR; n = 9); hindlimb unloading + reloading (HUR; n = 10); eccentric exercise (EE; n = 12), or control (CON; n = 12). The exercise protocol was performed 5 d x wk(-1) for 2 wks followed by HU and reloading. Fiber areas were lower in both suspended groups vs. the EE and CON groups. There was no difference in percent interstitial area among groups. However, percent myofibrillar damage was higher in the HUR group vs. all other groups. Further, glucose-6-phospate dehydrogenase activity, an indicator of muscle damage, was higher in the HUR group compared with the EE and CON groups. These results provide some evidence that prior EE reduced muscle damage subsequent to HU and reloading. Therefore, EE may prove effective in minimizing recovery time in individuals suffering from muscle damage following periods of bed rest and spaceflight.


Patients' experiences of telenursing follow-up care after bariatric surgery.
To explore the postsurgical management experiences of bariatric patients after receiving telenursing follow-up care, using a telemonitoring platform for approximately 1 month. Obesity prevalence rates among adult Canadians are increasing, and as such the number of bariatric surgeries. Adapting to life following bariatric surgery is challenging, and patients are often experiencing difficulties to adhere to the postsurgical behavioural recommendations. The use of technology has been introduced in bariatric aftercare programmes, yet patients voiced a desire to communicate with a clinician between routine visits to improve continuity of care. To our knowledge, there is a lack of research on emerging practice of telenursing to provide monitoring, support and aftercare to bariatric patients remotely. A qualitative descriptive design was used. A total of 22 semi-structured interviews were thematically analysed. The SRQR checklist was used. Participants embraced the idea of integrating telenursing care in bariatric aftercare programmes, as they viewed this novel approach to care as a way to overcome the current challenges of accessing bariatric services. The most salient benefit reported by participants was the timely advice and care provided by the telenurse. The provision of tailored nursing care and the accessibility to a first-line professional empowered participants to exercise greater control over their recovery process, which promotes self-management and enhances feelings of security and reassurance. Lastly, participants voiced areas of improvement to better the system and to render it most accessible and user-friendly. Despite its novelty in bariatric aftercare, our findings indicated that patients are eager to integrate telenursing in mainstream services. Discussions are needed regarding patient adherence to telemonitoring, and the need to develop clinical follow-up protocols. Results provide new insights into the importance of a telenurse in providing individualised care to bariatric patients.


PARENTAL EFFECTS ON PROGENY PHENOTYPE IN PLANTS: DISTINGUISHING GENETIC AND ENVIRONMENTAL CAUSES.
The experimental measurement of additive genetic variation in plant populations is complicated by the potential for non-Mendelian inheritance. Maternal influences on progeny phenotype resulting from the cytoplasmic inheritance of plastids or RNA transcripts and effects of the maternal environment have consequently been the focus of much research. To exclude or to control for these sources of variation, breeding designs (e.g., cross-factored, nested, or diallel) in which genetically unrelated pollen donors are mated to maternal genotypes have been adopted. Using these designs, some empirical studies have detected statistically significant differences among pollen donors in the mean performance of their pollen (the mature male gametophytes) or in the mean phenotype of their progeny. These statistical effects of pollen-donor identity on pollen performance or progeny phenotype have frequently been interpreted as evidence for additive genetic variance among pollen donors, although patrilineal cytoplasmic inheritance or effects of the paternal environment on pollen performance or gene expression are recognized as alternative explanations. We note that environment-specific selection among developing gametophytes-in which the environment experienced by developing pollen grains (or ovules) provides a selective force causing the differential survival of gametophyte genotypes (analagous to meiotic drive)-is an additional process that may cause genetically based paternal (or maternal) effects on gametophyte performance. If genes selected during this process are expressed in the sporophyte (postfertilization), this process could also influence the phenotype of the diploid progeny. Here, we review the potential causes of statistically significant differences in mean phenotype among the gametophytes or progeny of maternal (seed-bearing) or paternal (pollen-donating) parental plants. We suggest an experimental approach that permits the detection or elimination of selection among developing gametophytes as one such cause. Specifically, the replication of homozygous parental genotypes within and across environments allows the detection and measurement of paternal and maternal environmentally induced effects on gametophyte or offspring phenotype, while eliminating meiotic drive as a source of the phenotypic variation.


Manipulating target size influences perceptions of success when learning a dart-throwing skill but does not impact retention.
Positive feedback or experiences of success during skill acquisition have been shown to benefit motor skill learning. In this study, our aim was to manipulate learners' success perceptions through a minor adjustment to goal criterion (target size) in a dart-throwing task. Two groups of novice participants practiced throwing at a large (easy) or a small (difficult) target from the same distance. In reference to the origin/center of the target, the practice targets were alike in objective difficulty and indeed participants in both groups were not different in their objective practice performance (i.e., radial error from the center). Although the groups experienced markedly different success rates, with the large target group experiencing more hits and reporting greater confidence (or self-efficacy) than the small target group, these practice effects were not carried into longer-term retention, which was assessed after a 1-week delay. For success perceptions to moderate or benefit motor learning, we argue that unambiguous indicators of positive performance are necessary, especially for tasks where intrinsic feedback about objective error is salient.


Antibiotic resistance, virulence gene, and molecular profiles of Shiga toxin-producing Escherichia coli isolates from diverse sources in Calcutta, India.
Antibiotic resistance, virulence gene, and molecular profiles of Shiga toxin-producing Escherichia coli (STEC) non-O157 strains isolated from human stool samples, cow stool samples, and beef samples over a period of 2 years in Calcutta, India, were determined. Resistance to one or more antibiotics was observed in 49.2% of the STEC strains, with some of the strains exhibiting multidrug resistance. The dominant combinations of virulence genes present in the strains studied were stx(1) and stx(2) (44.5% of strains) and stx(1), stx(2), and hlyA (enterohemorrhagic E. coli hemolysin gene) (19% of strains). Only 6.4% of the STEC strains harbored eae. The diversity of STEC strains from various sources was assessed by random amplification of polymorphic DNA (RAPD). STEC strains that gave identical or nearly similar DNA fingerprints in RAPD-PCR and had similar virulence genotypes were further characterized by pulsed-field gel electrophoresis (PFGE). Identical RAPD and PFGE profiles were observed in four sets of strains, with each set comprising two strains. There was no match in the RAPD and PFGE profiles between strains of STEC isolated from cows and those isolated from humans. It appears that the clones present in bovine sources are not transmitted to humans in the Calcutta setting although these strains showed evolutionary relatedness. Maybe for this reason, STEC has still not become a major problem in India.


[Body image disturbances in patients with anorexia nervosa 12 years after clinical consultation].
Of 103 patients with anorexia nervosa, 50 women and 5 men were followed-up on the average 11.8 year after clinical presentation with a differentiated method for body awareness according to Askevold. A considerable number of women with body image disturbances, however, largely corresponded to those of a healthy female control group. Both the male anorexia nervosa patients and the healthy male controls had normal findings. Applying to touch-induced stimulus, the body assessment indices only increased in former male anorexia patients but remained the same in female anorexia patients, while they clearly normalized in the sense of a realistic assessment in the two healthy control groups. Surprisingly, there was only little correlation between the visually measured body perception disorder and the self (EDI) and expert assessment (Sianex) at the time of follow-up (exception: the EDI scale 3 [dissatisfaction with one's own body). The global expert rating of body image disturbances at clinical presentation was important as a predictor for the severity of anorexia nervosa after 12 years. The findings were discussed under methodological and clinical aspects.


Serious bacterial infections in neonates: improving reporting and case definitions.
Neonatal infections affect about 7 million neonates causing over 600 000 deaths every year. Estimating the burden is challenging as there are multiple reporting criteria and definitions for serious bacterial infections in neonates. Essential criteria for reporting serious neonatal bacterial infections have recently been published as the STROBE-NI checklist and, in the context of maternal vaccination, definitions have been published by the Brighton Collaboration Global Alignment of Immunization safety Assessment in pregnancy (GAIA) project. Standardisation of reporting criteria is essential to allow data comparability. This an important step in providing a clearer picture of the burden of serious bacterial infections in neonates and a welcome progress for guiding new investments in interventions.


Effect of Procedure and Coronary Lesion Characteristics on Clinical Outcomes Among Atrial Fibrillation Patients Undergoing Percutaneous Coronary Intervention: Insights From the PIONEER AF-PCI Trial.
This study sought to assess whether there were significant interactions of procedural access strategies and lesion characteristics with bleeding and ischemic events among atrial fibrillation (AF) patients anticoagulated with rivaroxaban or warfarin following a percutaneous coronary intervention. Among stented AF patients, the impact of procedural access strategies or lesion characteristics on antithrombotic safety and efficacy outcomes is unclear. In the PIONEER AF-PCI (An Open-label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention) trial, 2,124 patients were randomized to 3 groups and followed for 12 months: 1) rivaroxaban 15 mg once daily plus a P2Y12 inhibitor (n = 709); 2) rivaroxaban 2.5 mg twice a day plus dual antiplatelet therapy (DAPT) (n = 709); and 3) dose-adjusted warfarin plus DAPT (n = 706). Kaplan-Meier rates of clinically significant bleeding and major adverse cardiovascular events were compared between treatments stratified by subgroups of procedure type and lesion characteristics. Compared with warfarin, both rivaroxaban regimens consistently reduced clinically significant bleeding across subgroups of radial versus femoral arterial access and by vascular closure device use. Treatment effect of rivaroxaban on major adverse cardiovascular events did not vary when stratified by ischemia-driven revascularization, urgency of revascularization, location of culprit artery, presence of bifurcation lesion, presence of thrombus, type, and length of stent or number of stents (interaction p > 0.05 for all subgroups). Among stented AF patients requiring long-term oral anticoagulation, there was no effect modification by procedure or lesion characteristics of either clinically significant bleeding or major adverse cardiovascular events. Rivaroxaban-based therapy was superior to warfarin plus DAPT in bleeding outcomes regardless of the type of stent or arterial access during the index coronary revascularization. (A Study Exploring Two Strategies of Rivaroxaban [JNJ39039039; BAY-59-7939] and One of Oral Vitamin K Antagonist in Patients With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention [PIONEER AF-PCI]; NCT01830543).


[The half-board is a current model for formation of the health-preseving environment for junior schoolchildren].
The investigations have established that the hygienically founded organization of schooling and extraschool performance of gymnasia pupils levels increase educational and psychoemotional burdens. The contents and structure of a half-board have been developed and substantiated as a current health formation system for junior schoolchildren in the innovational institutions. The introduction of the structural elements of a half-board into a gymnasium provides an efficient organization of a teaching-and-educational process and vital activity in junior schoolchildren, which in turn promotes better adaptability and qualitative academic achievement in the pupils.


Estrogen increases galanin immunoreactivity in hyperplastic prolactin-secreting cells in Fisher 344 rats.
Galanin is a widely distributed regulatory peptide which modulates the pituitary secretion of PRL and GH. Estrogen administration strongly stimulates galanin gene expression in the rat anterior pituitary. In adult female Fischer 344 rats, estrogen also induces hyperplasia of lactotropes. We used immunocytochemical analysis to assess the effects of estrogen on galanin-like immunoreactivity (Gal-IR) in the rat pituitary and hypothalamus during sc diethylstilbestrol (DES) implantation and after its removal at 30 days. In the anterior pituitary, DES implantation increased the portion of Gal-IR-containing cells from less than 2% in the control rats to 18.3% after 3 days of DES and 36% after 30 days. These changes paralleled the lactotrope hyperplasia exhibited in response to DES exposure. Ten and 30 days after removal of the DES capsules, the percentage of Gal-IR-containing cells in the anterior pituitary decreased to 6.3% and 1.5%, respectively. Colocalization studies revealed that Gal-IR-containing cells were predominantly lactotropes. Immunoelectron microscopy demonstrated that Gal-IR was concentrated in the Golgi region of these hyperplastic lactotropes and suggests that little of the synthesized galanin is secreted. The distribution of Gal-IR in the hypothalamus, median eminence, and neurohypophysis was unaffected by DES treatment. These data demonstrate that galanin is synthesized by hyperplastic pituitary lactotropes of Fischer 344 rats and that peptide accumulation is dependent on the presence of circulating estrogens. In contrast, neuronal galanin synthesis in the hypothalamus does not appear to be regulated by estrogen.


Reduced expression of Jak-1 and Tyk-2 proteins leads to interferon resistance in hepatitis C virus replicon.
Alpha interferon in combination with ribavirin is the standard therapy for hepatitis C virus infection. Unfortunately, a significant number of patients fail to eradicate their infection with this regimen. The mechanisms of IFN-resistance are unclear. The aim of this study was to determine the contribution of host cell factors to the mechanisms of interferon resistance using replicon cell lines. HCV replicons with high and low activation of the IFN-promoter were cultured for a prolonged period of time in the presence of interferon-alpha (IFN-alpha2b). Stable replicon cell lines with resistant phenotype were isolated and characterized by their ability to continue viral replication in the presence of IFN-alpha. Interferon resistant cell colonies developed only in replicons having lower activation of the IFN promoter and no resistant colonies arose from replicons that exhibit higher activation of the IFN promoter. Individual cell clones were isolated and nine IFN resistant cell lines were established. HCV RNA and protein levels in these cells were not altered by IFN- alpha2b. Reduced signaling and IFN-resistant phenotype was found in all Huh-7 cell lines even after eliminating HCV, suggesting that cellular factors are involved. Resistant phenotype in the replicons is not due to lack of interferon receptor expression. All the cell lines show defect in the JAK-STAT signaling and phosphorylation of STAT 1 and STAT 2 proteins were strongly inhibited due to reduced expression of Tyk2 and Jak-1 protein. This in vitro study provides evidence that altered expression of the Jak-Stat signaling proteins can cause IFN resistance using HCV replicon cell clones.


Strategy for Accurate Detection of Escherichia Coli O157:H7 in Ground Pork Using a Lateral Flow Immunoassay.
Escherichia coli O157:H7 is known to cause serious diseases including hemorrhagic colitis and hemolytic uremic syndrome. A gold nanoparticle lateral flow immunoassay (Au-LFIA) was used to detect Escherichia coli O157:H7 in ground pork samples. False-positive results were detected using Au-LFIA; a Citrobacterfreundii strain was isolated from the ground pork samples and identified by using CHROmagarTM plates, API 20E, and 16S RNA sequencing. Since C.freundii showed cross-reactivity with E. coli O157:H7 when Au-LFIA test strips were used, a novel method combining modified enrichment with a lateral flow immunoassay for accurate and convenient detection of E. coli O157:H7 in ground pork was developed in this study to minimize these false positives. MacConkey broth was optimized for E. coli O157:H7 enrichment and C.freundii inhibition by the addition of 5 mg/L potassium tellurite and 0.10 mg/L cefixime. Using the proposed modified enrichment procedure, the false-positive rate of ground pork samples spiked with 100 CFU/g C.freundii decreased to 5%.


Sustained release gel (polymer-free) of itraconazole-loaded microemulsion for oral candidiasis treatment: time-kill kinetics and cellular uptake.
Itraconazole (ICZ) was prepared in a self-microemulsifying (SM) gel. This gel was intended for use in the oral mucosa, where low volume and flow of saliva result in limited solubility and absorption of drugs that are poorly water-soluble. The drug-loaded gel formulation (ICZ-SM) was selected as a clear solution in the ternary phase diagram to improve the solubility of ICZ. Seven ratios (S1-S7) were prepared by mixing polyoxyl 35 castor oils (P35), a medium chain with a blend of mono-, di-, and triglycerides (MCT), and water. Phase separation of large-sized emulsions by countering with artificial saliva were observed in dilution tests for the formulation contained MCT, P35, and water at the ratios of 70:20:10 (S1), 10:80:10 (S3), and 20:60:20 (S4). Formulations in the ratios of 15:50:35 (S5) and 19:43:38 (S6) produced strong ICZ-SM gels, as shown by rheology tests, whereas the formulations at the ratios of 30:60:10 (S2) and 10:43:47 (S7) exhibited no elasticity. A model of zero-order kinetic (S5) and first-order kinetic (S6) were found to best fit the release kinetics of ICZ from the gels. Time-killing assays revealed that S5 and S6 required less time compared with S2 and the ICZ solution. Furthermore, S5 exhibited the highest increase in cell uptake compared with S2, S6, and the ICZ solution. These findings suggest that the ICZ-SM gel was a free polymer capable of delivering an ICZ for the treatment of oral candidiasis, and that ICZ-SM gels applied locally exhibit enhanced absorption into cells.


Species and hybrid differences in frequencies of play and agonistic actions in canids.
Developmental changes in the frequency of occurrence of some 23 action patterns were studied in pairs of coyotes, wolves, dogs and their hybrids. Over 4,300 entries were recorded from days 24--42 (85.5 h observations in toto). All subjects showed a decrease in contactual behaviors from 24--30 days, and a subsequent increase in play fighting and chasing. In all species, with the exception of the coyotes, the bite was inhibited and play behavior was recorded from 24 days onwards, but only after the 30th day in the coyotes. Species differences in occurrence and frequency of certain action patterns were evident in the wolves, coyotes and dogs, and these differences were also reflected in their hybrids.


[Evaluation of the clinical effect of fluoride varnish in preventing caries of primary teeth].
To evaluate the clinical effect of fluoride varnish in preventing caries of primary teeth, and to compare the caries prevention effects of fluoride varnish with two different concentrations. 150 children whose ages were three year-old were randomly chosen from one of nurseries of Chongqing, and were randomly divided into four groups with 37 children in 0.5% fluoride varnish group, 38 children in 0.1% fluoride varnish group, 39 children in 0.5% sodium fluoride group and 36 children in blank group. The groups included 71 'girls and 79 boys. Protective measure was applied every half an year and the research has lasted for two years. The research was designed by double-blinded methods, and was carried out with the dental caries standard suggested by World Health Organization. All the data were collected and the clinical effects of four groups were compared. The average caries index and caries surface index of 0.1% fluoride varnish group and those of control groups were significantly higher than that of 0.5% fluoride varnish group. There were no significant difference between the average caries index and caries surface index of 0.1% fluoride varnish group and those of control groups. 0.5% fluoride varnish was effective in preventing caries of primary teeth.


Five cases of contact dermatitis to a trendy pet.
Skin contact with animal hair may induce contact urticaria (syndrome) or protein contact dermatitis. We report here 5 cases of dermatitis due to contact with ferrets kept as pets. The nature of the skin lesions, i.e. eczematous dermatitis, as well as the history of our 5 cases point to protein contact dermatitis. Further studies are requested to confirm this hypothesis and to identify the mechanisms and allergens. Physicians must be aware of the possibility of contact dermatitis with ferrets, especially when the patient has no previous history of atopic dermatitis and presents dermatitis of the neck, arm and around mouth.


Apoptosis-induced proteinase 3 membrane expression is independent from degranulation.
Proteinase 3 (PR3) and human neutrophil elastase (HNE) are serine proteinases stored in the azurophilic granules of neutrophils. In contrast to HNE, PR3 is the target of antineutrophil cytoplasm antibodies (ANCA) in Wegener's granulomatosis. The mechanisms leading to the membrane expression of PR3 and HNE are still unclear and appear to be critical to understand the pathophysiological role of ANCA. Stably transfected rat basophilic cell lines (RBL) with PR3 or HNE were used to analyze the PR3 and HNE secretion mechanisms and differentiate between them. RBL cells were lacking endogenous PR3 and HNE. They were stably transfected with HNE or PR3 or an inactive mutant of PR3 (PR3S203A). Using the calcium ionophore A23187 as a secretagogue, higher serine proteinase activity was secreted in the supernatant of RBL/HNE than in RBL/PR3. It is interesting that PR3 and PR3/S203A were also expressed at the plasma membrane, thus demonstrating that serine protease activity was not required for plasma membrane expression. In contrast, no expression of plasma membrane HNE could be detected in RBL/HNE. Apoptosis induced by etoposide was evaluated by DNA fragmentation, the presence of cytoplasmic histone-associated DNA fragments, and annexin V labeling. No membrane HNE was detected in RBL/HNE. In contrast, in RBL/PR3 and in RBL/PR3S203A, the membrane expression of PR3 and PR3S203A increased with etoposide concentrations and appeared closely related to annexin V labeling. Our data suggest that membrane PR3 originates from two distinct pools, the granular pool mobilized following degranulation or a plasma membrane pool mobilized upon apoptosis.


Production of gastrin-releasing peptide-(18-27) and a stable fragment of its precursor in small cell lung carcinoma cells.
The production and postsecretory stability of gastrin-releasing peptide (GRP) and the C-terminal part of the GRP precursor were studied in small cell lung cancer cell lines using RIAs developed against these two parts of the precursor. In three otherwise different cell lines (NIC-H345, NIC-H69, and NIC-H510), similar chromatographic patterns of mainly GRP-(18-27) and some GRP-(14-27) along with large fragments of the C-terminal counterpart of the precursor were found to be stored in the cells. In tissue culture medium, gel filtration chromatography indicated that postsecretory limited proteolysis of the GRP precursor fragments occurred. The amount of accumulated immunoreactivity varied among the three cell lines and between the two parts of the precursor. In medium in which only low amounts of GRP immunoreactivity accumulated, the radiolabeled GRP was degraded rapidly. When incubated with plasma, GRP-(14-27) disappeared within a few hours, whereas the C-terminal precursor fragments were stable. It is concluded that the postsecretory stability of peptides excised from the GRP precursor in small cell lung cancer cells varies under tissue culture conditions, but epitopes in the C-terminal part of the precursor are more stable in plasma than the small GRP peptides and, thus, may serve as a better indicator than GRP itself for expression of the GRP precursor in cancer cells.


Abdominal bloating is the most bothersome symptom in irritable bowel syndrome with constipation (IBS-C): a large population-based Internet survey in Japan.
Abdominal bloating is a common symptom in patients with irritable bowel syndrome with constipation (IBS-C). However, it is not included among the required items in the Rome III diagnostic criteria for IBS. Little is known about an impact of abdominal bloating seen in patients with IBS-C. Using a large population-based sample, the aim of the present study was to investigate what is the most bothersome symptom in subjects with IBS-C. An Internet survey of 30,000 adults drawn from the general public throughout Japan was conducted to identify subtypes of IBS using the Rome III diagnostic questionnaire. Consecutively, the screened subjects with IBS-C and the same number of age- and sex-matched non-IBS subjects who were randomly selected as controls were asked to answer a questionnaire on the degree of anxiety they experienced in their daily lives, thoughts about bowel habit, and their dominant gastrointestinal symptoms together with exacerbation factors (for IBS-C only). The screening survey showed that the prevalence of overall IBS was 16.5 % (female 17.4 %, male 15.5 %) and that 2.8 % met the criteria for IBS-C, 4.5 % for IBS with diarrhea (IBS-D) and 8.2 % for mixed IBS (IBS-M). Seven hundred and fifty-nine of 835 (90.9 %) subjects with IBS-C and 746 of 830 (89.9 %) control subjects completed the consecutive questionnaire. IBS-C subjects felt a higher degree of anxiety in their daily lives (p < 0.01) and considered bowel habit to be an indicator of health (p < 0.01) to a greater extent than control subjects. In IBS-C, the degree of anxiety was significantly associated with abdominal discomfort (p < 0.01), pain (p < 0.01) and bloating (p = 0.02), but not with the frequency of bowel habit (p > 0.1). Abdominal bloating was the most bothersome symptom (27.5 %), which was more likely to occur after a meal (52.2 %), at work/school (29.2 %) and during times of stress (26.8 %). Only 4.5 % of IBS-C subjects reported abdominal pain as the 'most bothersome' symptom. A large population-based Internet survey suggests that abdominal bloating has a great impact on the daily lives of subjects diagnosed with IBS-C. Not only bowel movement/abdominal pain but also abdominal bloating should be evaluated in patients with IBS-C.


Gradient Lithium Metal Infusion in Ag-Decorated Carbon Fibers for High-Capacity Lithium Metal Battery Anodes.
Lithium (Li) metal is a promising anode material for high-energy-density Li batteries due to its high specific capacity. However, the uneven deposition of Li metal causes significant volume expansion and safety concerns. Here, we investigate the impact of a gradient-infused Li-metal anode using silver (Ag)-decorated carbonized cellulose fibers (Ag@CC) as a three-dimensional (3D) current collector. The loading level of the gradient-infused Li-metal anode is controlled by the thermal infusion time of molten Li. In particular, a 5 s infusion time in the Ag@CC current collector creates an appropriate space with a lithiophilic surface, resulting in improved cycling stability and a reduced volume expansion rate. Moreover, integrating a 5 s Ag@CC anode with a high-capacity cathode demonstrates superior electrochemical performance with minimal volume expansion. This suggests that a gradient-infused Li-metal anode using Ag@CC as a 3D current collector represents a novel design strategy for Li-metal-based high-capacity Li-ion batteries.


Validation and cross-cultural adaptation of the arabic version of the nasal obstruction symptom evaluation scale.
Validation and cross-cultural adaptation of the Nasal Obstruction Symptom Evaluation (NOSE) scale into the Arabic language with studying of its psychometric properties. Prospective instrument-validation study. Guidelines for the cross-cultural adaptation process from the original English language scale into the Arabic language version were followed. We assessed the psychometric properties of the Arabic version of the NOSE scale (A-NOSE) (feasibility, reproducibility, internal consistency, reliability, discriminatory validity, responsiveness to change) in 101 consecutive patients who underwent septal surgery (preoperatively and 3 months postoperatively) and 102 asymptomatic controls. The Mann-Whitney test showed a statistically significant difference for the mean score between the patients and the control group denoting good clinical validity. The Cronbach's α coefficient value for the A-NOSE scale for 101 cases was 0.995, demonstrating good internal consistency. The Wilcoxon signed rank test showed a marked improvement in the patients score 3 months postoperatively. Correlation and level of agreement of the mean score of the A-NOSE scale for each question were studied using Spearman's rank correlation for each question, and Pearson's correlation for the total score showed statistically significant results. The A-NOSE scale is a valid instrument for evaluating the subjective severity of nasal obstruction and is recommended to be used in rhinology research and daily practice. 3b. Laryngoscope, 127:2455-2459, 2017.


Classification and comparison of biomechanical response strategies for accommodating landing impact.
The purposes of this study were to (a) present a theoretical model to explain the methods by which individuals accommodate impact force in response to increases in an applied stressor, (b) use the model and a correlation procedure to classify a sample of individuals based on their observed response patterns, and (c) statistically evaluate the classification process. Ten participants performed landings from three heights while video and force platform data were being collected. Magnitudes of impact-force characteristics from ground reaction force and lower extremity joint moments were evaluated relative to changes in landing momentum. Correlation between impact force and landing momentum was used to classify participant responses into either a positive or negative biomechanical strategy, as defined by the model. Positive and negative groups were compared using the Mann-Whitney U test. Results indicated that all responses fit within the categories defined by the model. Some individuals preferred positive strategies while others preferred negative ones depending on the specific variable. Only one participant consistently exhibited the negative strategy for all variables. Positive and negative groups were determined to be statistically different, p < or = 0.05, for 61% of the comparisons, suggesting actual differences between groups. The proposed model appeared robust and accounted for all responses in the current experiment. The model should be evaluated further using landing and other impact activities; it should be refined and used to help researchers understand individual impact-response strategies in order to identify those who may be at risk for impact related injuries.


Surgical treatment of non-ruptured giant occipital arteriovenous malformations with frequent migraine-like headache.
Two patients with giant occipital arteriovenous malformation (AVM) underwent microsurgical treatment among 294 patients with intracranial AVM treated between 1981 and 2004. The patients were aged 52 and 65 years and showed common symptoms consisting of long-term frequent migraine-like headaches with visual aura and recent homonymous hemianopia. Common neuroimaging findings were abundant dural feeders plus feeders from the posterior, middle, and anterior cerebral arteries, and deep drainers to the galenic system. Both patients underwent preoperative staged embolization and total microsurgical removal of the nidus with a neuronavigation system. Both patients returned to ordinary life without the need for assistance. These findings emphasize that giant occipital AVM, even if unruptured, is surgically treatable with acceptable morbidity.


A Redox Stimulation-Activated Amphiphile for Enhanced Photodynamic Therapy.
The development of more efficient photosensitizers with minimal damage to surrounding normal tissues has been a valuable and challenging subject during photodynamic therapy (PDT). Herein, a stimuli-activated porphyrinic photosensitizer (PEG-TPP-DNB; PEG = poly(ethylene glycol); TPP = 5,10,15,20-tetraphenylporphyrin; DNB = 2,4-dinitrobenzene) with capabilities of fluorescence and, remarkably, singlet oxygen quenching was prepared successfully for photodynamic therapy with high efficiency and biosecurity. The amphiphilic PEG-TPP-DNB could be self-assembled into nanomicelles in aqueous media and dissociated in response to reductive thiol such as glutathione. Meanwhile, the fluorescence and singlet oxygen generation of porphyrinic photosensitizer would be activated to regenerate. Moreover, the intracellular uptake and localization effectively confirmed the redox-responsive and activated behavior of PEG-TPP-DNB micelles. The cytotoxicity in vitro revealed that the micelles had low dark toxicity and great phototoxicity, and in vivo bioimaging and antitumor evaluation further indicated that the micelles possessed selective tumor imaging and targeted PDT antitumor effect as well as low systemic toxicity. Overall, this tumor microenvironment-activated photosensitizer system may provide a useful strategy for precise photodynamic therapy.


Synthesis of a tritium-labeled, fipronil-based, highly potent, photoaffinity probe for the GABA receptor.
3-[4-[1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazolo]]-3-(trifluoromethyl)diazirine is a fipronil-based (i.e. fiprole), high-affinity probe for the GABA receptor. For synthesis of the tritium-labeled version of this trifluoromethyldiazirinylfiprole ([(3)H]TDF) the required intermediate, 3-[4-[1-(2,6-dichloro-3-iodo-4-trifluoromethylphenyl)-5-iodopyrazolo]]-3-(trifluoromethyl)diazirine, was prepared in 10 steps from pyrazole and 3,5-dichloro-4-fluorobenzotrifluoride. One of the key transformations was lithiation and subsequent iodination of the 4-(2,2,2-trifluoro-1-hydroxyethyl)pyrazole intermediate. The last step involved reduction of the diiodofiprole with tritium, Pd/C, and triethylamine in ethyl acetate and afforded [(3)H]TDF with a specific activity of 15 Ci/mmol and 99% radiopurity.


Development of novel real-time PCR methodology for quantification of COL11A1 mRNA variants and evaluation in breast cancer tissue specimens.
Collagen XI is a key structural component of the extracellular matrix and consists of three alpha chains. One of these chains, the α1 (XI), is encoded by the COL11A1 gene and is transcribed to four different variants at least (A, B, C and E) that differ in the propensity to N-terminal domain proteolysis and potentially in the way the extracellular matrix is arranged. This could affect the ability of tumor cells to invade the remodeled stroma and metastasize. No study in the literature has so far investigated the expression of these four variants in breast cancer nor does a method for their accurate quantitative detection exist. We developed a conventional PCR for the general detection of the general COL11A1 transcript and real-time qPCR methodologies with dual hybridization probes in the LightCycler platform for the quantitative determination of the variants. Data from 90 breast cancer tissues with known histopathological features were collected. The general COL11A1 transcript was detected in all samples. The developed methodologies for each variant were rapid as well as reproducible, sensitive and specific. Variant A was detected in 30 samples (33 %) and variant E in 62 samples (69 %). Variants B and C were not detected at all. A statistically significant correlation was observed between the presence of variant E and lymph nodes involvement (p = 0.037) and metastasis (p = 0.041). With the newly developed tools, the possibility of inclusion of COL11A1 variants as prognostic biomarkers in emerging multiparameter technologies examining tissue RNA expression should be further explored.


Audiological findings in individuals exposed to organic solvents: case studies.
Millions of people around the world are exposed to industrial organic solvents such as toluene and xylene in the manufacturing sectors. Solvents are neurotoxic substances that are detrimental to the functioning of the nervous system, including the central auditory nervous system (CANS). This study investigated hearing and auditory processing in seven individuals with a history of exposure to industrial solvents. A battery of audiological tests was administered to all subjects: pure tone, speech, and impedance audiometry, otoacoustic emissions tests, auditory brainstem responses, middle latency responses, as well as the SCAN-A and R-SPIN tests with low predictability sentence lists. All individuals in this study exhibited findings consistent with retrocochlear and/or central abnormality. Two of the seven subjects in this study had normal pure tone thresholds at all frequencies bilaterally, yet showed abnormal retrocochlear/central results on one or more tests. The auditory test battery approach used in this study appears to be valuable in evaluating the pathological conditions of the CANS in solvent-exposed individuals.


[Experimental study of the synthesis of lysosomal enzymes by the synovial membrane: acid phosphatases].
In a system consisting of synovial samples taken surgically and maintained in culture, the authors studied the regulation of enzyme synthesis by taking acid phosphatase as the test enzyme. By means of double labelling and the use of protein synthesis inhibitors, they were able to demonstrate that this synthesis was stimulated by the addition of rheumatoid factor to the culture medium and that it depended on the transcription activity of the genome and on the translation of the information molecules.


Regulation of the human cellular glutathione peroxidase gene during in vitro myeloid and monocytic differentiation.
We have used the HL-60 and PLB-985 myeloid leukemia cell lines to examine the regulation of expression of the important intracellular antioxidant enzyme, glutathione peroxidase (GSH-Px), during phagocytic cell differentiation in vitro. Induction of differentiation along the monocytic pathway by phorbol ester results in an approximately twofold rise in enzyme activity and a parallel increase in the rate of 75Se incorporation into immunoprecipitable GSH-Px protein. Induction along the granulocytic pathway by dimethyl formamide (DMF) results in similar changes in steady-state enzyme levels and rates of GSH-Px protein synthesis. Steady-state levels of GSH-Px gene transcripts also increase more than twofold, approximately in parallel with the enzyme levels. Nuclear run-on transcription assays of GSH-Px mRNA synthesis show ratios of induced to uninduced transcript levels of 2.24 and 1.59 with phorbol myristate acetate (PMA) induction and DMF, respectively, in HL-60 cells, and ratios of 1.34 and 3.46 with PMA and DMF, respectively, in PLB-985 cells. Half lives of GSH-Px mRNA are unchanged or slightly shorter after differentiation of HL-60 cells, and slightly longer after induction of PLB-985. Overall, the present studies show that GSH-Px activity rises during in vitro-induced monocytic or granulocytic differentiation of myeloid cell lines and that the increased expression of the cellular GSH-Px gene occurs through complex mechanisms that include transcriptional up-regulation. This pattern contrasts with the nearly complete cotranslational regulation of GSH-Px expression by exogenous selenium.


Electric infusion pole adjuster.
A newly developed electric motorized infusion pole stand permits the surgeon to rapidly and accurately alter the rate and pressure of infusion during intraocular surgery.


Increased susceptibility to apoptosis and growth arrest of human breast cancer cells treated by a snake venom-loaded silica nanoparticles.
The development of effective treatments against metastatic cancers, including breast cancer, is among the most important challenges in current experimental and clinical cancer research. We recently demonstrated that Walterinnesia aegyptia venom (WEV), either alone or in combination with silica nanoparticles (WEV+NP), resulted in the growth arrest and apoptosis of different cancer cell lines. In the present study, we evaluated the impact of WEV alone and WEV+NP on human breast cancer cells isolated from cancer biopsies. The potential effects of WEV alone and WEV+NP on the proliferation, induction of apoptosis and generation of free radicals in breast cancer cells isolated from 80 patients clinically diagnosed with breast cancer were evaluated by flow cytometry and ELISA. WEV alone and WEV+NP inhibited the proliferation, altered the cell cycle and enhanced the induction of apoptosis of the breast cancer cells by increasing the activities of caspase-3, caspase-8 and caspase-9. In addition, the combination of WEV and NP robustly sensitized the breast cancer cells to growth arrest and apoptosis by increasing the generation of free radicals, including reactive oxygen species (ROS), hydroperoxide and nitric oxide. The combination of WEV with NP significantly enhanced the anti-tumor effect of WEV in breast cancer cells. Our data indicate the therapeutic potential of the nanoparticle-sustained delivery of snake venom for the treatment of breast cancer.


The Teenage Terrible Triad A Case Report.
Anterior shoulder dislocation in the athlete may result in an assortment of injuries that often benefit from surgical stabilization procedures. These injury patterns can be complex, requiring a multimodal approach to treatment. We present a rare case of a traumatic anterior shoulder dislocation in a teenage athlete that resulted in humeral avulsion of the glenohumeral ligament, rotator cuff tear, and axillary nerve palsy. Surgical treatment enabled return to football within 1 year of injury, and full function was restored.


A Conserved Core of Programmed Cell Death Indicator Genes Discriminates Developmentally and Environmentally Induced Programmed Cell Death in Plants.
A plethora of diverse programmed cell death (PCD) processes has been described in living organisms. In animals and plants, different forms of PCD play crucial roles in development, immunity, and responses to the environment. While the molecular control of some animal PCD forms such as apoptosis is known in great detail, we still know comparatively little about the regulation of the diverse types of plant PCD. In part, this deficiency in molecular understanding is caused by the lack of reliable reporters to detect PCD processes. Here, we addressed this issue by using a combination of bioinformatics approaches to identify commonly regulated genes during diverse plant PCD processes in Arabidopsis (Arabidopsis thaliana). Our results indicate that the transcriptional signatures of developmentally controlled cell death are largely distinct from the ones associated with environmentally induced cell death. Moreover, different cases of developmental PCD share a set of cell death-associated genes. Most of these genes are evolutionary conserved within the green plant lineage, arguing for an evolutionary conserved core machinery of developmental PCD. Based on this information, we established an array of specific promoter-reporter lines for developmental PCD in Arabidopsis. These PCD indicators represent a powerful resource that can be used in addition to established morphological and biochemical methods to detect and analyze PCD processes in vivo and in planta.


Sedation by the use of inhalation agents in dental care.
Nitrous oxide/oxygen has long been the mixture of gases used in dental practice to produce light sedation. The main indication for use of nitrous oxide/oxygen sedation is fear-anxiety. The equipment used is a continuous flow machine with a fail safe system set at a minimum of 30 or 40 per cent oxygen. A standardized sedation technique starting with administration of 100 per cent oxygen, is recommended. The concentration of nitrous oxide is then slowly increased and individually set, mostly between 30 and 50 per cent. In most cases the analgesia produced by nitrous oxide is not sufficient to ensure pain-free dental treatment. The sedation must therefore be supplemented by local anaesthesia. Side effects, e.g. restlessness, vomiting, and nausea are infrequent. About 90 per cent patients, who have difficulty in co-operating during dental treatment, mainly because of anxiety, show excellent or fair co-operation during nitrous oxide/oxygen sedation. Occupational exposure to nitrous oxide can be minimized by the use of scavenging systems, local exhaust systems, careful sedation technique, and equipment management.


Novel phenolate salts of bioactive agents: Cannabidiol phenolate salts.
Bioactive phenolic compounds are commonly found in medications, with examples including apomorphine, estrone, thymol, estradiol, propofol, o-phenylphenol, l-Dopa, doxorubicin, tetrahydrocannabinol (THC), and cannabidiol (CBD). This study is the first to explore the creation and assessment of metal and ammonium phenolate salts using CBD as an example. CBD is used in medicine to treat anxiety, insomnia, chronic pain, and inflammation, but its bioavailability is limited due to poor water solubility. In this study exploit a synthetic route to convert CBD into anionic CBD-salts to enhance water solubility. Various CBD-salts with metal and ammonium counterions such as lithium (Li+), sodium (Na+), potassium (K+), choline hydroxide ([(CH3)3NCH2CH2OH]+), and tetrabutylammonium ([N(C4H9)4]+) have been synthesized and characterized. These salts are obtained in high yields, ranging from 74 % to 88 %, through a straightforward dehydration reaction between CBD and alkali metal hydroxides (LiOH, NaOH, KOH) or ammonium hydroxides (choline hydroxide, tetrabutylammonium hydroxide). These reactions are conducted in either ethanol, methanol, or a methanol:water mixture, maintaining a 1:1 molar ratio between the reactants. Comprehensive characterization using Fourier-Transform Infrared Spectroscopy (FT-IR), Nuclear Magnetic Resonance (NMR) spectroscopy, and elemental (CHN) analysis confirms the formation of CBD-salts, as evidenced by the absence of aromatic hydroxyl resonances or stretching frequencies. The molecular formulas of CBD salts were determined based on CHN analysis, and CBD quantification from acid regeneration experiments. Characterization data confirms that each CBD phenolate in a specific CBD salt was electrostatically stabilized by one of the either alkali metal or ammonium ion. The CBD-salts are highly susceptible to acidic conditions, readily reverting back to the original CBD. The percentage and purity of CBD in the CBD-metal/ammonium salts have been studied using High-Performance Liquid Chromatography (HPLC) analysis. Solubility studies indicate that the conversion of CBD into CBD salts significantly enhances its solubility in water, ranging from 110 to 1606 folds greater than pure CBD. Furthermore, the pharmacokinetic evaluation of oral administration of CBD-salts compared to CBD were determined in rats.


Radiation therapy for head and neck cancers.
A general review of the therapeutic experience of the management of carcinoma of the head and neck at the Massachusetts General Hospital and Massachusetts Eye and Ear Infirmary is presented. Early lesions are highly curable by radiation therapy alone; the advanced lesions are preferably treated by combined irradiation and surgery, with improved survival rates. Concepts of various approaches are discussed.


Allergic contact dermatitis and associated allergic dermatoses: epidemiological, allergic, and immunological characteristics.
Allergic contact dermatitis (ACD) constitutes a considerable part of allergic morbidity among the population, although its actual prevalence is unknown as it is often not properly diagnosed. To determine the incidence of ACD compared to other allergic dermatoses in patients from the Russian Federation and the People's Republic of China, as well as analyse immunological parameters of ACD. The study enrolled a total of 248 patients aged 17-63 years divided into two groups representing the population of the Russian Federation (122 patients) and the People's Republic of China (126 patients). The total male and female ratio in both groups was 183 (74%) to 58 (26%). The frequency of ACD incidence among other allergic dermatoses in the group of patients from the Russian Federation was 26.2%, while that in the group of patients representing the population of the PRC amounted to 22.2%. In the group of patients from the Russian Federation, positive reactions to allergens were most often observed for thiomersal (29.8%), nickel sulfate (25.2%), and a mixture of carbamates (20.7%), and in the group of patients from China, for nickel sulfate (30.7%), thiomersal (26.4%), and a mixture of carbamates (23.8%). The incidence rate of ACD among patients with allergic dermatoses is about a quarter of cases in groups from both regions. The increased expression of defensin and IFN-γ genes can be considered as a marker of inflammation.


The neural computation of the aperture problem: an iterative process.
The aperture problem is defined as one of integrating motion information from inside and outside of the aperture, and determination of the true direction of motion of a line. Much is known about it and many models have been proposed for its neural mechanisms. However, it is still a matter of debate whether the brain solves the problem by using only feed-forward neural connections, also known as the one-shot algorithm, or by using the iterative algorithm while utilizing feedback as well as horizontal neural connections. Here we show unequivocal evidence for the latter model. The model was tested using critically designed psychophysical experiments and the results were perfectly in line with the psychophysical performance of the observers.


Effect of bax deletion on ethanol sensitivity in the neonatal rat cerebellum.
The developing cerebellum is highly sensitive to ethanol during discrete neonatal periods. This sensitivity has been linked to ethanol-induced alterations in molecules of the Bcl-2 survival-regulatory gene family. Ethanol exposure during peak periods of cerebellar sensitivity, for example, results in increased expression of proapoptotic proteins of this family, while overexpression of the antiapoptotic Bcl-2 protein in the nervous system protects against ethanol neurotoxicity. For the present study, neonatal mice with a targeted deletion of the proapoptotic bax gene were used to determine whether elimination of this protein would mitigate ethanol toxicity. bax knock-out and wild-type mice pups were exposed to ethanol via vapor inhalation during the maximal period of neonatal cerebellar ethanol sensitivity and cerebellar tissue was subsequently assessed for Purkinje and granule cell number and ethanol-mediated generation of reactive oxygen species (ROS). The results revealed that: (1) ethanol exposure during the peak period of cerebellar vulnerability resulted in substantial loss of Purkinje cells in wild-type animals, but not in bax knock-outs; (2) granule cells in the bax gene-deleted animals were not similarly protected from ethanol effects; and (3) levels of ROS following acute ethanol exposure were appreciably enhanced in the wild-type animals but not in the bax knock-outs. These results imply that Bax is important to ethanol-induced Purkinje cell death during critical neonatal periods, but that ethanol effects on granule cells may function at least partially independent of this apoptosis agonist. Amelioration of ethanol-mediated increases in ROS production in the knock-outs may contribute to the observed effects.


Vacuolar sucrose homeostasis is critical for plant development, seed properties, and night-time survival in Arabidopsis.
Most cellular sucrose is present in the cytosol and vacuoles of plant cells; however, little is known about the effect of this sucrose compartmentation on plant properties. Here, we examined the effects of altered intracellular sucrose compartmentation in Arabidopsis thaliana leaves by heterologously expressing the sugar beet (Beta vulgaris) vacuolar sucrose loader BvTST2.1 and by generating lines with reduced vacuolar invertase activity (amiR vi1-2). Heterologous expression of BvTST2.1 led to increased monosaccharide levels in leaves, whereas sucrose levels remained constant, indicating that vacuolar invertase activity in mesophyll vacuoles exceeds sucrose uptake. This notion was supported by analysis of tobacco (Nicotiana benthamiana) leaves transiently expressing BvTST2.1 and the invertase inhibitor NbVIF. However, sucrose levels were strongly elevated in leaf extracts from amiR vi1-2 lines, and experiments confirmed that sucrose accumulated in the corresponding vacuoles. The amiR vi1-2 lines exhibited impaired early development and reduced seed weight. When germinated in the dark, amiR vi1-2 seedlings were less able to convert sucrose into monosaccharides than the wild type. Cold temperatures strongly down-regulated both VI genes, but the amiR vi1-2 lines showed normal frost tolerance. These observations indicate that increased vacuolar sucrose levels fully compensate for the effects of low monosaccharide concentrations on frost tolerance.


A proposed fluorimetric determination of unsaturated iron-binding capacity.
A completely new method for the analysis of uncombined iron-binding capacity (UIBC) in human serum is proposed. The method is based on the discovery by C. K. Luk that the fluorescence of terbium ion (Tb-3+) is enhanced enormously when it binds to an empty Fe-3+ binding site of transferrin. Tb-3+ cannot displace Fe-3+ from an occupied binding site on transferrin. The analytic procedure is to dilute the serum (in order to lower its ultraviolet absorbance), add a solution of Tb-3+, excite with ultraviolet radiation, and measure the intensity of the resulting green fluorescence. With proper calibration this intensity is a measure of UIBC. Analyses of 65 serum samples previously measured at a hospital laboratory show no obvious difficulty with the method. Its absolute accuracy has not been probed in detail.


Stealth liposomes encapsulating zoledronic acid: a new opportunity to treat neuropathic pain.
In the pathogenesis of neuropathic pain, the conversion of astrocytes in the reactive state and the ras-dependent Erk-mediated pathway play an important role. Zoledronic acid (ZOL) is a potent inhibitor of the latter pathway, but its activity in neurological diseases is hampered by its biodistribution that is almost exclusively limited to the bone. We have developed nanotechnological devices able to increase the accumulation of ZOL in extra bone sites. In this work, we have evaluated the effects of ZOL-encapsulating PEGylated liposomes (LipoZOL) on an animal model of neuropathic pain. We have found that 2 iv administrations (10 μg of ZOL, either as free or encapsulated into liposomes) at days 2 and 4 after the injury markedly reduced mechanical hypersensitivity at 3 and 7 days after nerve injury. On the other hand, free ZOL did not exert any significant alteration of the mechanical threshold. Immunohistochemical analysis of spinal cord revealed that GFAP-labeled astrocytes appeared hypertrophic activated cells in the ispilateral dorsal horn of spinal cord 7 days after SNI. LipoZOL significantly changed astrocyte morphology, by inducing a protective phenotype, without changing the total cell number. Moreover, the astrocytes of the spinal cord of LipoZOL-treated mice were positive for interleukin-10. Delivery of ZOL into the CNS was confirmed by biodistribution of fluorescently labeled liposomes. In particular, liposomes accumulated in the liver and kidney in both groups of normal and neuropathic animals; on the other hand, only in the case of neuropathic animals, a fluorescence increase in the brain and spinal cord occurred only in neuropathic animals at 30 min and 1 h. These data demonstrate that ZOL, only by using a delivery system able to cross the altered BBB, could be a new opportunity to treat neuropathic pain.


Spin excitations in systems with hopping electron transport and strong position disorder in a large magnetic field.
We discuss the spin excitations in systems with hopping electron conduction and strong position disorder. We focus on the problem in a strong magnetic field when the spin Hamiltonian can be reduced to the effective single-particle Hamiltonian and treated with conventional numerical technics. It is shown that in a 3D system with Heisenberg exchange interaction the spin excitations have a delocalized part of the spectrum even in the limit of strong disorder, thus leading to the possibility of the coherent spin transport. The spin transport provided by the delocalized excitations can be described by a diffusion coefficient. Non-homogenous magnetic fields lead to the Anderson localization of spin excitations while anisotropy of the exchange interaction results in the Lifshitz localization of excitations. We discuss the possible effect of the additional exchange-driven spin diffusion on the organic spin-valve devices.


Cycloheximide resistance can be mediated through either ribosomal subunit.
Two cycloheximide-resistant mutants of Tetrahymena thermophila were analyzed to determine the site of their cycloheximide resistance. The mutations in both strains had been previously shown to be genetically dominant and located at separate loci (denoted Chx-A and Chx-B). Strains carrying these mutations were readily distinguished by the extent to which they were resistant to the drug. The homozygous double mutant was more resistant than either single mutant. Cell-free extracts of wild type and of the three mutant strains, assayed for protein synthetic activity by both runoff of natural mRNA and poly(U)-dependent phenylalanine polymerization, demonstrated that in vitro the mutants were all more resistant than the wild type. Further fractionation of the cell-free systems into ribosomes and supernates localized cycloheximide resistance to the ribosome for both Chx-A and Chx-B homozygotes. Ribosome dissociation and pairwise subunit mixing in the in vitro system indicated that ribosome resistance was conferred by the 60S subunit from one strain whereas resistance in the other strain was mediated through the 40S subunit. This was further confirmed by reconstruction of all four cycloheximide-resistance "phenotypes" by mixing ribosomal subunits from appropriate strains. This finding suggests that the mechanisms by which these mutations confer resistance to cycloheximide are different.


Small molecular compounds inhibit HIV-1 replication through specifically stabilizing APOBEC3G.
APOBEC3G (hA3G) is a host inhibitor for human immunodeficiency virus, type 1 (HIV-1). However, HIV-1 Vif binds hA3G and induces its degradation. We have established a screening system to discover inhibitors that protect hA3G from Vif-mediated degradation. Through screening, compounds IMB-26 and IMB-35 were identified to be specific inhibitors for the degradation of hA3G by Vif. The inhibitors suppressed HIV-1 replication in hA3G-containing cells but not in those without hA3G. The anti-HIV effect correlated with the endogenous hA3G level. HIV-1 particles from hA3G(+) cells treated with IMB-26/35 contained a hA3G level higher than that from those without IMB-26/35 treatment and showed decreased infectivity. IMB-26/35 bound directly to the hA3G protein, suppressed Vif/hA3G interaction, and therefore protected hA3G from Vif-mediated degradation. The compounds were safe with an anti-HIV therapeutic index >200 in vitro. LD(50) of IMB-26 in mice was >1000 mg/kg (intraperitoneally). Therefore, IMB-26 and IMB-35 are novel anti-HIV leads working through specific stabilization of hA3G.


Peroral endoscopic myotomy for Jackhammer esophagus: to cut or not to cut the lower esophageal sphincter.
With the success of peroral endoscopic myotomy (POEM) in treatment of achalasia, its successful application to other spastic esophageal motility disorders such as Jackhammer esophagus has been noted. The question of whether the lower esophageal sphincter (LES) should be included in the myotomy for Jackhammer esophagus is a topic of current debate. Here, we report our experience and results with four patients with Jackhammer esophagus treated with POEM. The clinical and manometric results are presented and their potential implications are discussed. Between January 2014 and July 2015, four patients underwent POEM for treatment of Jackhammer esophagus at our center. Manometry was performed prior to and after POEM. All patients met the Chicago classification criteria for Jackhammer esophagus and received a barium esophagram and endoscopic examination before having POEM. All patients had uneventful procedures without any intraoperative or post-procedure complications. Patients in which the LES was included during POEM had resolution or significant improvement in symptoms. One patient in whom the LES was preserved had resolution of chest pain but developed significant dysphagia and regurgitation. Subsequently this individual received a repeat POEM which included the LES, resulting in symptom resolution. POEM is a suitable treatment for patients with Jackhammer esophagus. Until there are larger-scale randomized studies, we speculate that based on our clinical experience and physiologic and manometric observations, obligatory inclusion of the LES is justified to reduce the risk of symptom development from iatrogenic ineffective esophageal motility or subsequent progression to achalasia.


Mesoporous Metal-Organic Framework with Well-Defined Cruciate Flower-Like Morphology for Enzyme Immobilization.
Metal-organic frameworks (MOFs) have recently emerged as a promising candidates for the immobilization of enzymes due to their diversified structures and porosity. However, a lack of good size and morphological control over the as-prepared MOFs has limited their practical applications in some cases. Herein, instead of zeolitic imidazolate framework-8 (ZIF-8) with the standard rhombic dodecahedral morphology, we successfully synthesize a novel mesoporous catalase@ZIF composite with cruciate flower-like morphology by embedding catalase molecules into uniformly sized ZIF crystals. With extraordinarily large mesopore size and high protein loading capacity, the catalase@ZIF composites with cruciate flower-like morphology exhibit 400% higher activity than that of catalase@ZIF composites with conventional rhombic dodecahedral morphology, and show higher reusability than conventional rhombic dodecahedral morphology. More importantly, we demonstrate for the first time that the biomacromolecules (proteins) can not directly regulate the crystal size, morphology, and crystallinity of ZIF-8. Moreover, the crystal morphology of ZIF has primary dependence on concentrations of 2-methylimidazole and Zn2+ ions, and can be directly controlled by adjusting concentrations of Zn2+ ions while keeping the high concentration of 2-methylimidazole.


Progressive multifocal leukoencephalopathy due to John Cunningham (JC) virus following allogeneic haematopoietic cell transplantation.
Progressive multifocal leukoencephalopathy (PML) is an uncommon infectious complication post allogeneic stem cell transplant. We present a case report of a patient developing this complication with a review of the current literature. It also describes the first use of artesunate in a clinical case of PML with no beneficial effect.


Haemodynamic requirements for an ideal pulmonary vasodilator.
An ideal vasodilator should be selective for the pulmonary vascular bed, thus minimizing side-effects from reduced systemic resistance. It must achieve not only a drop in pulmonary vascular resistance but also a marked decrease in pulmonary arterial pressure. The ideal drug should increase cardiac output and pulmonary venous oxygen saturation. An increase in oxygen delivery to the peripheral tissues should be achieved at a lower right ventricular afterload both at rest and during exercise. Right ventricular function should be improved. The effects of vasodilator therapy should be so marked that it should be possible to follow them non-invasively by radionuclide methods and exercise tolerance tests. The aim of vasodilator therapy is a regression of pulmonary hypertension and of right ventricular hypertrophy, an improved quality of life, and above all a longer survival.


[Intraperitoneal chemotherapy in colorectal cancer: from the laboratory to the clinic].
Some patients operated of a colo-rectal cancer can be selected to receive a post-operative adjuvant chemotherapy to decrease the risk of recurrence. The authors report the results of experimental works on intraperitoneal chemotherapy (IPC). At the laboratory, they showed that this option significantly reduced the risk of recurrences in the most frequent sites of colo-rectal cancer recurrences: liver, lymph nodes, peritoneum and the surgical site. Moreover, the survival of the treated animals was significantly prolonged compared to the controls. In human, they proved the feasibility of a intraperitoneal chemotherapy managed into the immediate post-operative period. Low morbidity, null mortality and the interesting preliminary carcinological results suggest the interest of such an option which could be confirmed by a randomized multi-centric study currently in preparation.


Mannan-binding lectin inhibits Candida albicans-induced cellular responses in PMA-activated THP-1 cells through Toll-like receptor 2 and Toll-like receptor 4.
Candida albicans (C. albicans), the most common human fungal pathogen, can cause fatal systemic infections under certain circumstances. Mannan-binding lectin (MBL),a member of the collectin family in the C-type lectin superfamily, is an important serum component associated with innate immunity. Toll-like receptors (TLRs) are expressed extensively, and have been shown to be involved in C. albicans-induced cellular responses. We first examined whether MBL modulated heat-killed (HK) C. albicans-induced cellular responses in phorbol 12-myristate 13-acetate (PMA)-activated human THP-1 macrophages. We then investigated the possible mechanisms of its inhibitory effect. Enzyme-linked immunosorbent assay (ELISA) and reverse transcriptasepolymerase chain reaction (RT-PCR) analysis showed that MBL at higher concentrations (10-20 µg/ml) significantly attenuated C. albicans-induced chemokine (e.g., IL-8) and proinflammatory cytokine (e.g., TNF-α) production from PMA-activated THP-1 cells at both protein and mRNA levels. Electrophoretic mobility shift assay (EMSA) and Western blot (WB) analysis showed that MBL could inhibit C. albicans-induced nuclear factor-κB (NF-κB) DNA binding and its translocation in PMA-activated THP-1 cells. MBL could directly bind to PMA-activated THP-1 cells in the presence of Ca(2+), and this binding decreased TLR2 and TLR4 expressions in C. albicans-induced THP-1 macrophages. Furthermore, the binding could be partially inhibited by both anti-TLR2 monoclonal antibody (clone TL2.1) and anti-TLR4 monoclonal antibody (clone HTA125). In addition, co-immunoprecipitation experiments and microtiter wells assay showed that MBL could directly bind to the recombinant soluble form of extracellular TLR2 domain (sTLR2) and sTLR4. Our study demonstrates that MBL can affect proinflammatory cytokine and chemokine expressions by modifying C. albicans-/TLR-signaling pathways. This study supports an important role for MBL on the regulation of C. albicans-induced cellular responses.


[The results of catheterization and the x-ray angiographic assessment of cardiac contractility and volume in primary pulmonary hypertension].
To ascertain the role of invasive investigations in the diagnosis of primary pulmonary hypertension (PPH), 12 PPH patients underwent catheterization of the left and right heart compartments, contrast right and left ventriculography and oximetry. Compared to control values, the patients had high pressure in the pulmonary artery and right ventricle. Some of them exhibited elevated pressure in the right atrium. Pulmonary artery wedge pressure, left ventricular end-diastolic and systolic, diastolic pressure in the aorta did not differ significantly from those in the controls. Right and left ventriculography revealed an increase in the end-systolic and end-diastolic volumes of the right ventricle which diminished its stroke index and ejection fraction. The latter two were reduced in the left ventricle also. Because the procedure was well tolerated by the patients, it is recommended for PPH diagnosis and follow-up.


The functionalisation of saturated hydrocarbons--XXX. Model studies on the mechanism of some oxygenases.
In harmony with our studies on the activation of hydrocarbons by Gif chemistry, we have, in the first part of this paper, studied the mechanism of the lipoxygenase enzymes using soybean lipoxygenase as a model. We have shown with trimethyl phosphite that no free radical is released by the enzyme. In a second part, we have studied the mechanism of the alpha-ketoglutarate dependent enzymes and shown evidence for a mechanism involving the reduction of an intermediate hydroperoxide by the alpha-ketoglutaric acid.


Single-step genomic model improved reliability and reduced the bias of genomic predictions in Danish Jersey.
A bias in the trend of genomic estimated breeding values (GEBV) was observed in the Danish Jersey population where the trend of GEBV was smaller than the deregressed proofs for individuals in the validation population. This study attempted to improve the prediction reliability and reduce the bias of predicted genetic trend in Danish Jersey. The data consisted of 1,238 Danish Jersey bulls and 611,695 cows. All bulls were genotyped with the 54K chip, and 1,744 cows were genotyped with either 7K chips (1,157 individuals) or 54K chips (587 individuals). The trait used in the analysis was protein yield. All cows with EBV were used in a single-step approach. Deregressed proofs were used as the response variable. Four alternative approaches were compared with genomic best linear unbiased prediction (GBLUP) model with bulls in the reference data (GBLUPBull): (1) GBLUP with both bulls and genotyped cows in the reference data; (2) GBLUP including a year of birth effect; (3) GEBV from a GBLUP model that accounted for the difference of EBV between dams and maternal grandsires; and (4) using a single-step approach. The results indicated all 4 alternatives could reduce the bias of predicted genetic trend and that the single-step approach performed best. However, not all these approaches improved reliability or reduced inflation of GEBV. The reliability was 0.30 and regression coefficients of deregressed proofs on GEBV were 0.69 in the scenario GBLUPBull. When genotyped cows were included in the reference population, the regression coefficients decreased to 0.59 but the reliability increased to 0.35. If a year effect was included in the model, the prediction reliability decreased to 0.29 and the regression coefficient improved to 0.75. The method in which GEBV were adjusted for the difference between dam EBV and maternal grandsire EBV led to much lower regression coefficients though the reliability increased to 0.4. The single-step approach improved both the reliability, to 0.38 and regression coefficient to 0.78. Therefore, the bias in genetic trend was reduced. The results suggest that implementing the single-step approach is an effective way to improve genomic prediction in Danish Jersey cattle.


MYH10 protein expression in platelets as a biomarker of RUNX1 and FLI1 alterations.
RUNX1 gene alterations are associated with acquired and inherited hematologic malignancies that include familial platelet disorder/acute myeloid leukemia, primary or secondary acute myeloid leukemia, and chronic myelomonocytic leukemia. Recently, we reported that RUNX1-mediated silencing of nonmuscle myosin heavy chain IIB (MYH10) was required for megakaryocyte ploidization and maturation. Here we demonstrate that runx1 deletion in mice induces the persistence of MYH10 in platelets, and a similar persistence was observed in platelets of patients with constitutional (familial platelet disorder/acute myeloid leukemia) or acquired (chronic myelomonocytic leukemia) RUNX1 mutations. MYH10 was also detected in platelets of patients with the Paris-Trousseau syndrome, a thrombocytopenia related to the deletion of the transcription factor FLI1 that forms a complex with RUNX1 to regulate megakaryopoiesis, whereas MYH10 persistence was not observed in other inherited forms of thrombocytopenia. We propose MYH10 detection as a new and simple tool to identify inherited platelet disorders and myeloid neoplasms with abnormalities in RUNX1 and its associated proteins.


Effects of acetylcholinesterase gene silencing on its activity in cultured human skeletal muscle.
In spite of several reports demonstrating that acetylcholinesterase (AChE [EC 18.104.22.168]) expression is importantly regulated at the level of its mRNA, we still know little about the relationship between AChE mRNA level and the level of mature, catalytically active enzyme in the cell. Better insight into this relationship is, however, essential for our understanding of the molecular pathways underlying AChE synthesis in living cells. We have approached this problem previously (Grubic et al., 1995; Brank et al., 1998; Mis et al., 2003; Jevsek et al., 2004); however, recently introduced small interfering RNA (siRNA) methodology, which allows blockade of gene expression at the mRNA level, opens new possibilities in approaching the AChE mRNA-AChE activity relationship. With this technique one can eliminate AChE mRNA in the cell, specifically and at selected times, and follow the effects of such treatment at the mature enzyme level. In this study we followed AChE activity in siRNA-treated cultured human myoblasts. Our aim was to find out how the temporal profile of the AChE mRNA decrease is reflected at the level of AChE activity under normal conditions and after inhibition of preexisting AChE by diisopropyl phosphorofluoridate (DFP).AChE activity was determined at selected time intervals after siRNA treatment in both myoblast homogenates and in culture medium to follow the effects of siRNA treatment at the level of intracellular AChE synthesis and at the level of AChE secreted from the cell.


Urban eye allergy syndrome: a new clinical entity?
A significant number of patients present with conjunctivitis that is not strictly speaking of allergic, infectious, or dry eye origin. Patients affected by this pseudo-allergic form of vasomotor or idiopathic conjunctivitis usually live in urban polluted areas and may be affected by a new clinical entity called the 'urban eye allergy syndrome'. To identify the incidence, pathogenesis and therapeutic response of this condition by collecting from the literature experimental evidence on the relationship between air pollution, allergy, and conjunctival disease. Allergen susceptibility might be increased in areas with increased air pollutants. Both allergens and pollutants can directly initiate specific and nonspecific mucosal inflammation through several interweaving mechanisms. The present commentary introduces the concept of 'urban eye allergy syndrome' discussing inter-actions between air pollutants and pollens, the increase of allergic signs and symptoms by pollutants, the prevalence of urban allergy, preliminary data from a single restricted geographical area, and proposed mechanisms of action.


Characteristics of older adults experiencing periodontal attachment loss as gingival recession or probing depth.
While attachment loss currently is the best field examination indicator that periodontal disease has progressed, this measure is not disaggregated enough to differentiate between attachment loss that results in deeper pockets and attachment loss that results primarily in recession of the gingiva. If these two conditions have different etiologies, then efforts at predicting who will experience the condition from a single, general risk assessment model will be difficult. The purpose of this paper is to determine whether the characteristics of people who experience attachment loss primarily as increased probing depths are different from those people who experience attachment loss primarily as gingival recession. Baseline and 18-month follow-up periodontal measures were gathered on a representative sample of community-dwelling adults aged 65+. Based on measurement errors obtained one week apart on a reliability subsample, a threshold level of 3+mm was set to define attachment loss. Attachment loss was further characterized as resulting from mostly increased probing depth or from mostly increased gingival recession. In mesio-buccal sites, 58% of the people had attachment loss mostly due to increased probing depth with 42% having attachment loss mostly due to gingival recession. For buccal sites, the figures were 24% and 76% respectively. The logistic regression models for both sites indicated that people who had their attachment loss in the form of increased probing depths had different characteristics than people who had most of their attachment loss in the form of gingival recession.(ABSTRACT TRUNCATED AT 250 WORDS)


Imazamox-clay complexes with chitosan- and iron(III)-modified smectites and their use in nanoformulations.
Imazamox is an ionisable herbicide, weakly retained and with high soil vertical mobility, that is used for the control of the root-parasitic plants Orobanche spp. A natural smectite (SW) modified with the biopolymer chitosan (Ch) or with Fe(3+) cation was assayed as adsorbent or carrier for imazamox controlled-release formulations (CRFs). The greatest adsorption (74%) was observed for SWFe at high initial concentration (500 µM) and low pH (4.3). The interaction mechanism of imazamox on SWFe implies interlayer polar adsorption, followed by protonation of the imidazolinone ring, whereas ionic, polar and hydrophobic interactions seemed to occur in imazamox adsorption on SWCh. The herbicide release into water was inversely related to the strength of the imazamox-clay interactions and ranged in the first 10 min for imazamox-SWFe and imazamox-SWCh complexes from 27 to 75%, whereas commercial imazamox released 86%. The imazamox-SWCh weak complex (SWCh6 WC) showed similar herbicidal activity to the commercial formulation but produced a reduction of 15% in the total soil leaching losses and a reduction of 40% in the peak maximum concentration in soil column leachates. The imazamox-clay weak complex (WC) of SWFe and SWCh and the strong complex (SC) with SWCh showed appropriate behaviour as nanopesticides or smart delivery systems to be incorporated in CRFs. © 2015 Society of Chemical Industry.


Rapid Evolution of Complete Dosage Compensation in Poecilia.
Dosage compensation balances gene expression between the sexes in systems with diverged heterogametic sex chromosomes. Theory predicts that dosage compensation should rapidly evolve in tandem with the divergence of sex chromosomes to prevent the deleterious effects of dosage imbalances that occur as a result of sex chromosome divergence. Examples of complete dosage compensation, where gene expression of the entire sex chromosome is compensated, are rare, and have only been found in relatively ancient sex chromosome systems. Consequently, very little is known about the evolutionary dynamics of complete dosage compensation systems. Within the family Poeciliidae the subgenus Lebistes share the same sex chromosome system which originated 18.48-26.08 Ma. In Poecilia reticulata and P. wingei, the Y chromosome has been largely maintained, whereas the Y in the closely related species P. picta and P. parae has rapidly degraded. We recently found P. picta to be the first example of complete dosage compensation in a fish. Here, we show that P. parae also has complete dosage compensation, thus complete dosage compensation likely evolved in the short (∼3.7 Myr) interval after the split of the ancestor of these two species from P. reticulata, but before they diverged from each other. These data suggest that novel dosage compensation mechanisms can evolve rapidly, thus supporting the longstanding theoretical prediction that such mechanisms arise in tandem with rapidly diverging sex chromosomes.


Dispersive perfectly matched layers and high-order absorbing boundary conditions for electromagnetic quasinormal modes.
Resonances, also known as quasinormal modes (QNMs) in the non-Hermitian case, play a ubiquitous role in all domains of physics ruled by wave phenomena, notably in continuum mechanics, acoustics, electrodynamics, and quantum theory. The non-Hermiticity arises from the system losses, whether they are material (Joule losses in electromagnetism) or linked to the openness of the problem (radiation losses). In this paper, we focus on the latter delicate matter when considering bounded computational domains mandatory when using, e.g., finite elements. We address the important question of whether dispersive perfectly matched layer (PML) and high-order absorbing boundary conditions offer advantages in QNM computation and modal expansion of the optical responses compared with nondispersive PMLs.


Investigation on the near-field cutoff effect in a subwavelength plasma shell with near-zero permittivity.
Although the plasma-induced receiving and radiating near-field cutoff phenomena in the subwavelength regime are found of crucial importance in electromagnetic (EM) signal transmissions and plasma property studies, their mechanisms to a large extent remain unclear and undistinguished. In this paper, in the perspective of field and energy transfer, it is demonstrated that the cutoff in the near-field regime is completely different from that in the geometric optical regime. Results show that, for the receiving mode, epsilon-near-zero (ENZ) plasmas can be treated as a nearly ideal EM fluid, and thus, EM waves are restricted into the plasma channel. For the radiating mode, on the other hand, it is the destructive interference between the electric dipole fields of the antenna and the ENZ plasma that results in vanishing far-field radiation. As an important supplement to the existing cutoff theories, our results not only offer clearer physical insights into the near-field cutoff effect but also provide a helpful reference for cutoff-related practical applications in various frequency bands.


Local kallikrein and trypsin responses in the rat.
1 Locally administered commercial hog pancreatic kallikrein (Depot-Glumorin) and bovine pancreatic trypsin both increased vascular permeability in the skin and paws of rats. 2 By the use of numerous antagonists and enzyme inhibitors, this vascular response was found to be the result not of kinin formation but of a direct action mostly on histamine receptors. 3 Highly purified kallikrein did not increase vascular permeability in rats, suggesting either that the effect was due to an impurity in the commercial preparation or that a structural change in the enzyme occurred on purification. 4 Soya bean trypsin inhibitor prevented the trypsin response when both were injected locally. On intraperitoneal injection, the inhibitor was effective only against local kallikrein. 5 The kallikrein inhibitor, aprotinin (Trasylol), was not effective against local kallikrein but it reduced the trypsin response when both were injected locally.