Spiroconjugated intramolecular charge-transfer emission in non-typical spiroconjugated molecules: the effect of molecular structure upon the excited-state configuration.
A set of terfluorenes and terfluorene-like molecules with different pendant substitutions or side groups were designed and synthesized, their photophysical properties and the excited-state geometries were studied. Dual fluorescence emissions were observed in compounds with rigid pendant groups bearing electron-donating N atoms. According to our earlier studies, in this set of terfluorenes, the blue emission is from the local π-π* transition, while the long-wavelength emission is attributed to a spiroconjugation-like through-space charge-transfer process. Herein, we probe further into how the molecular structures (referring to the side groups, the type of linkage between central fluorene and the 2,2'-azanediyldiethanol units, and-most importantly-the amount of pendant groups), as well as the excited-state geometries, affect the charge-transfer process of these terfluorenes or terfluorene-like compounds. 9-(9,9,9'',9''-tetrahexyl-9H,9'H,9''H-[2,2':7',2''-terfluoren]-9'-yl)-1,2,3,5,6,7-hexahydropyrido[3,2,1-ij]quinolone (TFPJH), with only one julolidine pendant group, was particularly synthesized, which exhibits complete "perpendicular" conformation between julolidine and the central fluorene unit in the excited state, thus typical spiroconjugation could be achieved. Notably, its photophysical behaviors resemble those of TFPJ with two pendant julolidines. This study proves that spiroconjugation does happen in these terfluorene derivatives, although their structures are not in line with the typical orthogonal π fragments. The spiroconjugation charge-transfer emission closely relates to the electron-donating N atoms on the pendant groups, and to the rigid connection between the central fluorene and the N atoms, whereas the amount of pendant groups and the nature of the side chromophores have little effect. These findings may shed light on the understanding of the through-space charge-transfer properties and the emission color tuning of fluorene derivatives.


Alexithymia predicts poorer social and everyday functioning in schizophrenia and bipolar disorder.
Alexithymia, or the inability to identify and describe one's emotions, is significantly higher in bipolar disorder (BD) and schizophrenia (SZ), compared to healthy controls (HC). Alexithymia has also been observed to predict psychosocial functioning in SZ. We investigated whether alexithymia predicted social and everyday functioning in BD, as well as transdiagnostically in HC, BD, and SZ patients. 56 BD, 45 SZ, and 50 HC were administered and compared on tests measuring neurocognition, social cognition, functioning and alexithymia. We conducted linear regressions assessing whether alexithymia predicted functional outcomes in BD. Next, we conducted hierarchical stepwise linear regressions investigating the predictive ability of neurocognition, social cognition and alexithymia on everyday and social functioning in our overall sample. BD and SZ patients were comparable on most demographics and demonstrated higher alexithymia compared to HCs. In BD, alexithymia predicted social functioning only. In the overall sample, difficulty identifying and describing feelings predicted everyday functioning; difficulty describing feelings predicted social functioning. Results suggest that aspects of alexithymia significantly predict functioning among these psychiatric groups, above and beyond the contributions of previously identified factors such as neurocognition and social cognition. Results may aid in developing proper interventions aimed at improving patients' ability to articulate their feelings.


Endotoxin and cytokine removal in sepsis.
Sepsis, the leading cause of mortality in intensive care units, is a complex series of interrelated effects caused by the overproduction of multiple mediators and their unrestrained biological activity. Both proinflammatory and antiinflammatory mediators participate in the high complexity of sepsis and explain the failure of specific therapies to improve survival. Continuous extracorporeal therapies have been proposed as therapeutic options and as tools for blood purification in sepsis. Along these lines and in order to achieve higher clearances and mass removal rates, we studied the effects of plasmafiltration coupled with adsorption and provided in vitro and in vivo evidence that adsoprtion of multiple cytokines, activated complement components, and lipid mediators such as the platelet-activating factor occurs. We also showed that such treatment may lead to improved survival in a rabbit model of sepsis and to improved hemodynamics, reduced norepinephrine dose, and restoration of near-to-normal responsiveness of blood leukocytes to endotoxin in humans. It is anticipated that treatment of plasma, as a modular device to conventional hemofiltration, may pave the way to innovative approaches in the extracorporeal treatment of septic patients.


Cardiovascular Prognosis of Subclinical Chronic Obstructive Pulmonary Disease in Patients with Suspected or Confirmed Coronary Artery Disease.
Chronic obstructive pulmonary disease (COPD) worsens prognosis in patients with coronary artery disease (CAD). However, the cardiovascular prognosis in patients with stable or mildly symptomatic COPD remains unclear. Here, we sought to determine the long-term cardiovascular events in patients with subclinical or early-stage COPD with concomitant CAD. This was a longitudinal analytical study involving 117 patients with suspected or established CAD who underwent assessment of pulmonary function by spirometry and who were followed up for six years (March 2015-January 2021). The patients were divided into two groups, one comprising COPD (n=44) and the other non-COPD (n=73) patients. Cox regression was used to evaluate the association between COPD and cardiovascular events, with adjustment for the established CAD risk factors, and the effect size was measured by the Cohen test. COPD patients were older (p=0.028), had a greater frequency of diabetes (p=0.026), were more likely to be smokers (p<0.001), and had higher modified Medical Research Council scores (p<0.001). There was no difference between the groups regarding gender, body mass index, hypertension, dyslipidemia, family history of CAD, and type of angina. CAD frequency and the proportion of patients with severe and multivessel CAD were significantly higher among COPD than among non-COPD patients (all p<0.001). At six-year follow-up, patients with COPD were more likely to have experienced adverse cardiovascular events than those without COPD (p<0.001; effect size, 0.720). After adjusting for established CAD risk factors, COPD occurrence remained an independent predictor for long-term adverse cardiovascular events (OR: 5.13; 95% CI: 2.29-11.50; p<0.0001). COPD was associated with increased severity of coronary lesions and a greater number of adverse cardiovascular events in patients with suspected or confirmed CAD. COPD remained a predictor of long-term cardiovascular events in stable patients with subclinical or early-stage of COPD, independently of the established CAD risk factors.


Micronutrient fortification of caffeinated energy drinks and supplemented foods marketed in Canada.
To examine the micronutrient content of discretionarily fortified products marketed under Canada's current regulations, we conducted an in-store and online search for products granted Temporary Marketing Authorizations in 2018. We located 129 caffeinated energy drinks and 98 other beverage products. Most were fortified at levels well below permitted maximums, but 82.2% of energy drinks and 35.7% of other beverage products contained nutrients above 100% of Daily Values, suggesting that current fortification practices are largely gratuitous. Novelty The micronutrients in a sample of discretionarily fortified products marketed under Canada's current regulations were generally below permitted maximum levels, but many greatly exceeded nutrient requirements.


In vitro evaluation of nasal mucociliary clearance using excised rat nasal septum.
Mucus on the nasal mucosa is translocated to the pharynx by ciliary beating, which is an important nonspecific defense mechanism called mucociliary clearance (MC). MC is one of the important factors determining the rate and extent of drug absorption after nasal application. The purpose of this study is to evaluate MC using rat nasal septum under physiological condition in an in vitro system. The nasal septum was excised from rats anesthetized with urethane and the movement of fluorescent microspheres (FMS) applied on the nasal septum was observed with a fluorescence microscope. FMS were transported at a constant velocity in the same direction for a few minutes, but addition of 4% mucin solution on the nasal septum maintained MC for at least 90 min after excision. With our evaluation system established by modifying the method of Saldiva, MC was determined to be around 1 mm/min. Furthermore, the ciliostatic effect of benzalkonium chloride was observed, and it was confirmed that β-adrenergic antagonists and a cholinergic antagonist decreased MC, and that β-adrenergic agonists and a cholinergic agonist tended to increase MC, indicating that our system is valid and useful for evaluating MC function and the effect of drugs and pharmaceutical additives for nasal application on MC.


Detection of aryl hydrocarbon receptor agonists in human samples.
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor with important functions in the immune response and cancer. AHR agonists are provided by the environment, the commensal flora and the metabolism. Considering AHR physiological functions, AHR agonists may have important effects on health and disease. Thus, the quantification of AHR agonists in biological samples is of scientific and clinical relevance. We compared different reporter systems for the detection of AHR agonists in serum samples of Multiple Sclerosis (MS) patients, and assessed the influence of transfection methods and cell lines in a reporter-based in vitro assay. While the use of stable or transient reporters did not influence the measurement of AHR agonistic activity, the species of the cell lines used in these reporter assays had important effects on the reporter readings. These observations suggest that cell-specific factors influence AHR activation and signaling. Thus, based on the reported species selectivity of AHR ligands and the cell species-of-origin effects that we describe in this manuscript, the use of human cell lines is encouraged for the analysis of AHR agonistic activity in human samples. These findings may be relevant for the analysis of AHR agonists in human samples in the context of inflammatory and neoplastic disorders.


Prevalence of disabilities and associated health conditions--United States, 1991-1992.
An estimated 35-49 million persons in the United States have a disability; estimated direct and indirect annual costs related to disability (including medical expenses and lost workdays) total $170 billion. Because of definitions of disability used in previous analyses generally contained limited measures of disability, the prevalence of disability in the United States may have been underestimated. The Survey of Income and Program Participation (SIPP), a subsample of the 1990 U.S. census, collected comprehensive data about disability using several measures. The U.S. Bureau of the Census and CDC analyzed data from SIPP to provide more precise prevalence estimates of disability and health conditions associated with disability in the United States during 1991-1992. This report summarizes the findings from that analysis.


Bullous pemphigoid treated by topical corticosteroids.
Three patients with bullous pemphigoid have been successfully treated with topical corticosteroids (clobetasol propionate) alone. Another patient required adjuvant systemic corticosteroid therapy. In view of its minimal side effects, we confirm a previous report that topical corticosteroid therapy could represent a valuable alternative in the treatment of limited bullous pemphigoid, although for its extensive forms, such therapy may be incomplete.


The effect of concentration of phenols on their batch methanogenesis.
The biodegradability of phenol and six other phenolic compounds (o-, m-, and p-cresol, 2-, 3-, and 4-ethylphenol) was examined in batch methanogenic cultures. The effect of concentration of these alkyl phenols on the anaerobic biodegradation of phenol was also evaluated. The inoculum used in this study was cultivated in a continuous flow laboratory fermenter with phenol as the primary substrate. Phenol, at initial concentrations as high to 1400 mg/L was completely degraded to methane and carbondioxide after 350 hours incubation. Complete degradation of m- and p-cresol was also observed while the ethylphenols and o-cresol were not significantly degraded.At initial concentrations exceeding 600 mg/L, phenol inhibited the phenol-degrading microorganisms but not the methanogens. At about 600 mg/L, cresols reduced the rate of phenol degradation to 50% of that observed in a control culture containing only 200 mg/L phenol. Ethylphenols were more inhibitory than cresols. Phenol degrading microorganisms were more susceptible to inhibition by cresols and ethylphenols than were the methanogens. The inhibitory effects of the three isomers of cresol and ethylphenol did not vary with the isomer but rather with the substituted functional group.


Lipidomics analysis of mesenteric lymph after trauma and hemorrhagic shock.
After trauma and hemorrhagic shock (T/HS), a variety of inflammatory mediators enter the systemic circulation through mesenteric lymph ducts, leading to acute lung injury and multiple-organ dysfunction syndrome. Recent studies have demonstrated that post-HS mesenteric lymph (PHSML) activates polymorphonuclear leukocytes (PMNs) and causes vascular endothelial cell and red blood cell dysfunction. Furthermore, PHSML contains proinflammatory mediators, such as biologically active lipids. The purpose of this study was to identify the lipid mediators in PHSML and plasma by liquid chromatography/electrospray ionization mass spectrometry and then estimate the biologic activities of the identified lipids on PMNs. PHSML was collected from male Sprague-Dawley rats undergoing trauma (laparotomy) plus HS (40 mm Hg, 30 minutes) or sham shock (SS). The lipids in PHSML and plasma were extracted using the methods of Bligh and Dyer, and liquid chromatography/electrospray ionization mass spectrometry was performed. The biologic activities (superoxide production and elastase release) of identified lipids on human PMNs were tested. Phosphatidylcholine, lysophosphatidylcholine (LPC), phosphatidylethanolamine, lysophosphatidylethanolamine (LPE), and sphingomyelin were detected in the PHSML. Furthermore, linoleoyl, arachidonoyl, and docosahexaenoyl LPCs and LPEs significantly increased in the PHSML of the T/HS group as compared with those of the T/SS group. In the plasma, arachidonoyl and docosahexaenoyl LPCs of the T/HS group also significantly increased in comparison with that of the T/SS group. Linoleoyl and arachidonoyl LPCs and LPEs showed the priming activity on N-formyl-methionyl-leucyl-phenylalanine-activated PMNs. The elastase release was also induced by linoleoyl and arachidonoyl LPCs. Mesenteric lymph after T/HS contains biologically active lipids, such as LPCs and LPEs with polyunsaturated fatty acids, which may be involved in the pathogenesis of acute lung injury/multiple-organ dysfunction syndrome.


Inhibition of NO3- and NO2- reduction by microbial Fe(III) reduction: evidence of a reaction between NO2- and cell surface-bound Fe2+.
A recent study (D. C. Cooper, F. W. Picardal, A. Schimmelmann, and A. J. Coby, Appl. Environ. Microbiol. 69:3517-3525, 2003) has shown that NO(3)(-) and NO(2)(-) (NO(x)(-)) reduction by Shewanella putrefaciens 200 is inhibited in the presence of goethite. The hypothetical mechanism offered to explain this finding involved the formation of a Fe(III) (hydr)oxide coating on the cell via the surface-catalyzed, abiotic reaction between Fe(2+) and NO(2)(-). This coating could then inhibit reduction of NO(x)(-) by physically blocking transport into the cell. Although the data in the previous study were consistent with such an explanation, the hypothesis was largely speculative. In the current work, this hypothesis was tested and its environmental significance explored through a number of experiments. The inhibition of approximately 3 mM NO(3)(-) reduction was observed during reduction of a variety of Fe(III) (hydr)oxides, including goethite, hematite, and an iron-bearing, natural sediment. Inhibition of oxygen and fumarate reduction was observed following treatment of cells with Fe(2+) and NO(2)(-), demonstrating that utilization of other soluble electron acceptors could also be inhibited. Previous adsorption of Fe(2+) onto Paracoccus denitrificans inhibited NO(x)(-) reduction, showing that Fe(II) can reduce rates of soluble electron acceptor utilization by non-iron-reducing bacteria. NO(2)(-) was chemically reduced to N(2)O by goethite or cell-sorbed Fe(2+), but not at appreciable rates by aqueous Fe(2+). Transmission and scanning electron microscopy showed an electron-dense, Fe-enriched coating on cells treated with Fe(2+) and NO(2)(-). The formation and effects of such coatings underscore the complexity of the biogeochemical reactions that occur in the subsurface.


Anti-Inflammatory and Antioxidant Activities of the Methanolic Extract of Cyrtocarpa procera Bark Reduces the Severity of Ulcerative Colitis in a Chemically Induced Colitis Model.
Cyrtocarpa procera is a plant used in traditional Mexican medicine to treat different gastrointestinal problems. Here, we investigated the effects of a C. procera methanolic extract in DSS-induced colitis mice. Ulcerative colitis (UC) was induced by administering 4% DSS in drinking water to female BALB/c mice. Compared to untreated mice with UC, the treatment group receiving the C. procera extract presented less severe UC symptoms of diarrhea, bleeding, and weight loss. Additionally, colon shortening was significantly reduced, and at the microscopic level, only minor damage was observed. Levels of proinflammatory cytokines such as TNF-α, IL-1β, and IFNγ in serum as well as the MPO activity in the colon were significantly reduced in the C. procera methanolic extract-treated group. Moreover, the extract of C. procera reduced oxidative stress during UC, preventing the deterioration of the activity of antioxidant enzymes such as SOD, CAT, and GPx. Additionally, the extract decreased lipid peroxidation damage and its final products, such as malondialdehyde (MDA). In agreement with this, in vitro assays with the C. procera extract displayed good antioxidant capacity, probably due to the presence of polyphenolic compounds, in particular the flavonoids that were identified, such as chrysin, naringenin, kaempferol, and catechin, which have been reported to have anti-inflammatory and antioxidant activities. Therefore, the improvement of UC by the C. procera methanolic extract may be related to the action mechanisms of these compounds.


Novel Target Study to Cure Cardiovascular Disease regarding Proprotein Converse Subtilisin/Kexin Type 9.
This study is aimed at screening the potential ideal lead compounds from natural drug library (ZINC database), which had potential inhibition effects against proprotein converse subtilisin/kexin type 9 (PCSK9), and contributing to enrich the practical basis of PCSK9 inhibitor screening. A series of computer-aided virtual screening techniques were used to identify potential inhibitors of PCSK9. Structure-based virtual screening by LibDock was carried out to calculate the LibDock scores, followed by ADME (absorption, distribution, metabolism, and excretion) and toxicity predictions. Molecule docking was next employed to demonstrate the binding affinity and mechanism between the candidate ligands and PCSK9 macromolecule. Finally, molecular dynamics simulation was performed to evaluate the stability of ligand-PCSK9 complex under natural circumstance. Two novel natural compounds ZINC000004099069 and ZINC000014952116 from the ZINC database were found to bind with PCSK9 with a higher binging affinity together with more favorable interaction energy. Also, they were predicted to be non-CYP2D6 inhibitors, together with low rodent carcinogenicity and AMES mutagenicity as well as hepatotoxicity. Molecular dynamics simulation analysis demonstrated that these two complex ZINC000004099069- and ZINC000014952116-PCSK9 had more favorable potential energy compared to the reference ligand, which could exist stably whether in vivo or in vitro. This study elucidated that ZINC000004099069 and ZINC000014952116 were finally screened as safe and potential drug candidates, which may have great significance in the development of PCSK9 inhibitor development.


Feeding Strategies in Newborns and Infants During the COVID-19 Pandemic-Polish Cross-Sectional Study.
Objective: We aimed to analyze factors affecting feeding strategies of newborns and infants during the COVID-19 pandemic in Poland. Methods: The cross-sectional study using a self-developed CAWI questionnaire was conducted between February and April 2021 among Polish mothers. The analysis included responses from 1,485 women who delivered during the COVID-19 pandemic restrictions. The inferential analysis uses Parson's chi-square test and the series of logistic models. The data were weighted to adjust age and educational level distribution. Results: When hospitalized, lack of skin-to-skin contact (OR = 0.094; p < 0.001, 95% CI [0.057 0.156]), not being informed about direct breastfeeding in the pandemic (OR = 0.195, p = 0.006, 95% CI [0.61 0.62]) and being suspected for COVID-19 (OR = 0.379, p < 0.001, 95% CI [0.223 0.642]) reduced the probability of breastfeeding. Feeding plans and feeding after leaving the hospital were impacted only by the educational level (OR = 2.463, p = 0.028, 95% CI [1.1 5.518]). Conclusion: While the mother's education level plays a key role in the nutrition plans and long-term feeding strategy, PUI status and hospital practices (lack of skin-to-skin and proper information) had a major negative impact on breastfeeding rates in the hospital.


Copper-Mediated Cross-Coupling of Diazo Compounds with Sulfinates.
A copper-mediated cross-coupling reaction between a diazo compound and a sodium alkane(arene)sulfinate gives a sulfone as the product. This reaction proceeds under mild conditions and features excellent functional group compatibility. A wide range of sodium alkane(arene)sulfinates were successfully applied in this chemistry. Mechanistic studies revealed that the overall reaction efficiency of the sulfinates was in line with their nucleophilicity in this reaction.


Simultaneous confidence intervals for quantile differences of several heterogeneous normal populations: With application to vitamin D supplement treatment on colorectal cancer patients.
In many applications, comparing the q-quantiles of several normal populations are more advantageous than comparing their means. In this paper, we consider the problem of constructing simultaneous confidence intervals (SCIs) for quantile differences of several heterogeneous normal distributions. To the best of our knowledge, this problem remains unsolved. We propose a novel method for constructing a set of SCI. We propose two new sets of SCI by using the proposed technique and discuss two classic and two simulation-based SCIs. We show that the proposed classic SCIs are conservative for all population parameters configuration. We also show that the simulation-based SCIs have correct coverage probability asymptotically. We then compare these six sets of SCI in terms of average volume and coverage probability via an extensive simulation study. Results show that one of the proposed classic SCI can be recommended. Finally, the proposed methods are illustrated by a real example that is a vitamin D study on colorectal cancer patients.


Mechanism of Amyloidogenesis of a Bacterial AAA+ Chaperone.
Amyloids are fibrillar protein superstructures that are commonly associated with diseases in humans and with physiological functions in various organisms. The precise mechanisms of amyloid formation remain to be elucidated. Surprisingly, we discovered that a bacterial Escherichia coli chaperone-like ATPase, regulatory ATPase variant A (RavA), and specifically the LARA domain in RavA, forms amyloids under acidic conditions at elevated temperatures. RavA is involved in modulating the proper assembly of membrane respiratory complexes. LARA contains an N-terminal loop region followed by a β-sandwich-like folded core. Several approaches, including nuclear magnetic resonance spectroscopy and molecular dynamics simulations, were used to determine the mechanism by which LARA switches to an amyloid state. These studies revealed that the folded core of LARA is amyloidogenic and is protected by its N-terminal loop. At low pH and high temperatures, the interaction of the N-terminal loop with the folded core is disrupted, leading to amyloid formation.


Energy balance during an ironman triathlon in male and female triathletes.
Energy balance of 10 male and 8 female triathletes participating in an Ironman event (3.8-km swim, 180-km cycle, 42.2-km run) was investigated. Energy intake (EI) was monitored at 7 designated points by dietary recall of food and fluid consumption. Energy expenditure (EE) during cycling and running was calculated using heart rate-VO, regression equations and during swimming by the multiple regression equation: Y = 3.65v+ 0.02W- 2.545 where Yis VO,in L x min(-1), v is the velocity in m s(-1), Wis the body weight in kilograms. Total EE (10,036 +/- 931 and 8,570 +/- 1,014 kcal) was significantly greater than total EI (3,940 +/- 868 and 3,115 +/- 914 kcal, p <.001) for males and females, respectively, although energy balance was not different between genders. Finishing time was inversely related to carbohydrate (CHO) intake (g x kg(-1) x h(-1)) during the marathon run for males (r = -.75,p <.05), and not females, suggesting that increasing CHO ingestion during the run may have been a useful strategy for improving Ironman performance in male triathletes.


Peripheral T lymphocytes recirculating back into the thymus can mediate thymocyte positive selection.
The thymus continuously produces T lymphocytes that contribute to the maintenance of the peripheral T cell pool. Since peripheral recirculating T cells represent a very minor population among total thymocytes in normal animals, the relationship between the thymus and secondary lymphoid organs is generally considered unidirectional. Recently, several reports have described the presence of recirculating T cells in the thymus, raising issues regarding their possible function. In this article, we show that the niche for recirculating T cells in the thymus, i.e., their absolute number, is the same in lymphopenic and normal mice. Using a novel combination of TCR-transgenic mice in which the ligand necessary for positive selection of host T cells is only expressed by transferred donor T cells, we show that mature T cells recirculating back to the thymus can mediate positive selection.


The Psychosocial Impact of COVID-19 on health care workers.
At the end of 2019, a disease was identified, COVID-19, caused by a new type of easy and fast spreading virus, which led to the beginning of a worldwide pandemic. One of the most exposed groups to the virus and its psychosocial consequences is the healthcare workers, due to their implication in caring for affected people. Health workers are exposed to a fast and unpredictable situation that requires more human resources and materials than usual, however, the lack of means on account to this situation entails an increased probability of suffering different consequences, including the burnout syndrome, to which, generally, this professionals are already vulnerable. In addition, quarantine is added as a measure to prevent the spread of the pandemic, which is another handicap for healthcare workers. Quarantine means these professionals are more likely to suffer the foreseeable psychological consequences in general population, specifically, it has been observed that Post-Traumatic Stress Disorder (PTSD) is more prevalent, because of the stress load of the situation experienced.


Schizosaccharomyces japonicus: A Distinct Dimorphic Yeast among the Fission Yeasts.
Genomic sequencing data and morphological properties demonstrate evolutionary relationships among groups of the fission yeast, Schizosaccharomyces Phylogenetically, S. japonicus is the furthest removed from other species of fission yeast. The basic characteristics of cell proliferation are shared among all fission yeast, including the process of binary fission during vegetative growth, conjugation and karyogamy with horsetail movement, mating-type switching, and sporulation. However, S. japonicus also exhibits characteristics that are unique to filamentous fungi. S. japonicus is a nonpathogenic yeast that exhibits dimorphism. Depending on the environmental conditions, S. japonicus transforms from yeast cells into filamentous cells (hyphae), and blue light triggers synchronous septation of hyphal cells. A rough version of the whole-genome sequence is now available, facilitating genetic manipulation of S. japonicus. Furthermore, the extensive genetic knowledge available for S. pombe is aiding the development of genetic tools for analyzing S. japonicus. S. japonicus will help shed light on the evolutionary relationships among the fission yeast.


Dyslexic students have more everyday cognitive lapses.
There is a dearth of information about the everyday performance difficulties of adult dyslexic people. This study investigates the empirical support for anecdotal reports of increased vulnerability to distraction in dyslexia, using the self-report Cognitive Failures Questionnaire (CFQ). Two groups of university students, a dyslexic group and a non-dyslexic control group, were asked to complete the CFQ. The dyslexic group reported a higher frequency of everyday lapses in cognition, scoring significantly higher on a number of CFQ items. Representative problems include distractibility, over-focusing (so that relevant peripheral information is missed), and word-finding difficulties. A similar measure administered to close friends of dyslexic people, the CFQ-for-others, yielded results consistent with those of the CFQ, with major findings being that their friends considered them to be more disorganised, more distractible, and more absent-minded than normal. The results indicate clearly the continuing effects of dyslexia on cognition in adulthood and demonstrate that dyslexic impairments are not limited to "artificial" laboratory tasks or even literacy tasks but, instead, pervade everyday life.


Inflammatory plasma markers and pancreatic cancer risk: a prospective study of five U.S. cohorts.
Chronic inflammation may play a role in the development of pancreatic cancer. However, few prospective studies have examined the association between plasma inflammatory markers and pancreatic cancer risk. Therefore, we investigated the association of prediagnostic circulating C-reactive protein (CRP), interleukin-6 (IL-6), and TNF-α receptor II (TNF-αR2) with subsequent pancreatic cancer risk in a prospective, nested case-control study of 470 cases and 1,094 controls from Health Professionals Follow-up Study, Nurses' Health Study, Physicians' Health Study, Women's Health Initiative, and Women's Health Study. The median follow-up time of cases was 7.2 years (range 1-26 years). No association was observed between plasma CRP, IL-6, and TNF-αR2 and the risk of pancreatic cancer. Comparing extreme quintiles, the multivariate ORs were 1.10 [95% confidence interval (CI), 0.74-1.63; Ptrend = 0.81] for CRP, 1.19 (95% CI, 0.81-1.76; Ptrend = 0.08) for IL-6, and 0.88 (95% CI, 0.58-1.33; Ptrend = 0.57) for TNF-αR2. In conclusion, prediagnostic levels of circulating CRP, IL-6, and TNF-αR2 were not associated with the risk of pancreatic cancer, suggesting that systemic inflammation as measured by circulating inflammatory factors is unlikely to play a major role in the development of pancreatic cancer.


Computational resources to define alleles and altered regulatory motifs at genomically edited candidate response elements.
Unequivocal functional assessment of candidate genomic regulatory regions, such as transcriptional response elements, requires genetic alteration at their native chromosomal loci. Targeted DNA cleavage by Cas9 or other programmable nucleases enables analysis at virtually any genomic region, and diverse alleles generated by editing can be defined by deep sequencing for functional analysis. Interpretation of disrupted response elements, however, presents a special challenge, as these regions typically comprise clustered DNA binding motifs for multiple transcriptional regulatory factors (TFs); DNA sequence differences, natural or engineered, that affect binding by one TF can confer loss or gain of binding sites for other TFs. To address these and other analytical complexities, we created three computational tools that together integrate, in a single experiment, allele definition and TF binding motif evaluation for up to 9216 clones isolated, sequenced and propagated from Cas9-treated cell populations. We demonstrate 1) the capacity to functionally assess edited TF binding sites to query response element function, and 2) the efficacy and utility of these tools, by analyzing cell populations targeted by Cas9 for disruption of example glucocorticoid receptor (GR) binding motifs near FKBP5, a GR-regulated gene in the human adenocarcinoma cell line A549.


Diagnostic and prognostic value of T-cell receptor gamma alternative reading frame protein (TARP) expression in prostate cancer.
T-cell receptor gamma chain alternative reading frame protein (TARP) has recently been proposed as being up-regulated in prostate cancer (PCA). Additionally, TARP has been proposed as a potential therapeutic target for cancer therapy. We analysed the protein expression of TARP in a large well characterised prostate cancer cohort to assess its diagnostic and prognostic value. Methodologically, we constructed a tissue microarray comprising more than 600 PCA cases including matching benign prostate tissue. TARP protein expression was carefully analysed and associated with clinico-pathological parameters, PSA-relapse free survival and expression data of established and proposed diagnostic markers (AMACR, p63, GOLPH2). Our results show that TARP is significantly over-expressed in the vast majority (approximately 85%) of PCA in comparison to non neoplastic prostate tissue. Its expression was associated with conventional markers of unfavourable and more aggressive tumour behaviour. However, a prognostic value of TARP could not be found. The diagnostic value of TARP is limited in comparison to AMACR, p63 or GOLPH2. Since TARP specific immunologic therapy regimen are currently being tested, the high frequency of TARP over-expression in PCA conveys a high potential for a predictive and potentially therapeutic use of this biomarker.


Isolation and Characterization of the Novel Phage JD032 and Global Transcriptomic Response during JD032 Infection of Clostridioides difficile Ribotype 078.
Insights into the interaction between phages and their bacterial hosts are crucial for the development of phage therapy. However, only one study has investigated global gene expression of Clostridioides (formerly Clostridium) difficile carrying prophage, and transcriptional reprogramming during lytic infection has not been studied. Here, we presented the isolation, propagation, and characterization of a newly discovered 35,109-bp phage, JD032, and investigated the global transcriptomes of both JD032 and C. difficile ribotype 078 (RT078) strain TW11 during JD032 infection. Transcriptome sequencing (RNA-seq) revealed the progressive replacement of bacterial host mRNA with phage transcripts. The expressed genes of JD032 were clustered into early, middle, and late temporal categories that were functionally similar. Specifically, a gene (JD032_orf016) involved in the lysis-lysogeny decision was identified as an early expression gene. Only 17.7% (668/3,781) of the host genes were differentially expressed, and more genes were downregulated than upregulated. The expression of genes involved in host macromolecular synthesis (DNA/RNA/proteins) was altered by JD032 at the level of transcription. In particular, the expression of the ropA operon was downregulated. Most noteworthy is that the gene expression of some antiphage systems, including CRISPR-Cas, restriction-modification, and toxin-antitoxin systems, was suppressed by JD032 during infection. In addition, bacterial sporulation, adhesion, and virulence factor genes were significantly downregulated. This study provides the first description of the interaction between anaerobic spore-forming bacteria and phages during lytic infection and highlights new aspects of C. difficile phage-host interactions.IMPORTANCE C. difficile is one of the most clinically significant intestinal pathogens. Although phages have been shown to effectively control C. difficile infection, the host responses to phage predation have not been fully studied. In this study, we reported the isolation and characterization of a new phage, JD032, and analyzed the global transcriptomic changes in the hypervirulent RT078 C. difficile strain, TW11, during phage JD032 infection. We found that bacterial host mRNA was progressively replaced with phage transcripts, three temporal categories of JD032 gene expression, the extensive interplay between phage-bacterium, antiphage-like responses of the host and phage evasion, and decreased expression of sporulation- and virulence-related genes of the host after phage infection. These findings confirmed the complexity of interactions between C. difficile and phages and suggest that phages undergoing a lytic cycle may also cause different phenotypes in hosts, similar to prophages, which may inspire phage therapy for the control of C. difficile.


Automated Synapse Detection Method for Cerebellar Connectomics.
The connectomic analyses of large-scale volumetric electron microscope (EM) images enable the discovery of hidden neural connectivity. While the technologies for neuronal reconstruction of EM images are under rapid progress, the technologies for synapse detection are lagging behind. Here, we propose a method that automatically detects the synapses in the 3D EM images, specifically for the mouse cerebellar molecular layer (CML). The method aims to accurately detect the synapses between the reconstructed neuronal fragments whose types can be identified. It extracts the contacts between the reconstructed neuronal fragments and classifies them as synaptic or non-synaptic with the help of type information and two deep learning artificial intelligences (AIs). The method can also assign the pre- and postsynaptic sides of a synapse and determine excitatory and inhibitory synapse types. The accuracy of this method is estimated to be 0.955 in F1-score for a test volume of CML containing 508 synapses. To demonstrate the usability, we measured the size and number of the synapses in the volume and investigated the subcellular connectivity between the CML neuronal fragments. The basic idea of the method to exploit tissue-specific properties can be extended to other brain regions.


Psychophysical and physiological forward masking studies: probe duration and rise-time effects.
To determine if the amount of forward masking observed in single auditory-nerve fibers of the chinchilla was sufficient to account for the amount of masking observed behaviorally in humans, thresholds for the detection of several types of probe signals following a forward masker were measured in both behavioral and physiological experiments. It is necessary to use the same probe stimulus characteristics in both behavioral and physiological experiments to make valid comparisons between the two measures of forward masking. Experiment 1 was behavioral and used human listeners. Two types of probe signals were used, differing in overall duration and rise/fall times. The two probes yielded different growth of masking functions. These results further demonstrate that forward masking characteristics in behavioral experiments are critically dependent upon the parameters of the probe signal used. Experiment 2 was physiological and used chinchillas. The amount of masking for high-level maskers using the same two probe types in a physiological "forced-choice" experiment are presented. In contrast with the behavioral results, there was little or no difference in the amounts of masking observed for the two probes. In addition, the amounts of masking observed in some auditory-nerve fibers were considerably smaller than those observed behaviorally. These experiments further demonstrate that the amount of forward masking observed in single auditory-nerve fibers is inconsistent with that observed behaviorally.


Covalent attachment of the plant natural product naringenin to small glass and ceramic beads.
Natural products have numerous medicinal applications and play important roles in the biology of the organisms that accumulate them. Few methods are currently available for identifying proteins that bind to small molecules, therefore the discovery of cellular targets for natural products with pharmacological activity continues to pose a significant challenge in drug validation. Similarly, the identification of enzymes that participate in the biosynthesis or modification of natural products remains a formidable bottleneck for metabolic engineering. Flavonoids are one large group of natural products with a diverse number of functions in plants and in human health. The coupling of flavonoids to small ceramic and glass beads provides a first step in the development of high-throughput, solid-support base approaches to screen complex libraries to identify proteins that bind natural products. The utilization of small glass and ceramic beads as solid supports for the coupling of small molecules was explored. Initial characterization of the beads indicated uniform and high capacity loading of amino groups. Once the beads were deemed adequate for the linking of small molecules by the coupling of NHS-fluorescein followed by microscopy, chemical hydrolysis and fluorometry, the flavonoid naringenin was modified with 1,4-dibromobutane, followed by the attachment of aminopropyltriethoxysilane. After NMR structural confirmation, the resulting 7-(4-(3-(triethoxysilyl)propylamino)butoxy) naringenin was attached to the ceramic beads. Our results demonstrate that ceramic and glass beads provide convenient solid supports for the efficient and facile coupling of small molecules. We succeeded in generating naringenin-coupled ceramic and glass beads. We also developed a convenient series of steps that can be applied for the solid-support coupling of other related flavonoids. The availability of solid-support coupled naringenin opens up new opportunities for the identification of flavonoid-binding proteins.


Drug uptake, lipid rafts, and vesicle trafficking modulate resistance to an anticancer lysophosphatidylcholine analogue in yeast.
The ether-phospholipid edelfosine, a prototype antitumor lipid (ATL), kills yeast cells and selectively kills several cancer cell types. To gain insight into its mechanism of action, we performed chemogenomic screens in the Saccharomyces cerevisiae gene-deletion strain collection, identifying edelfosine-resistant mutants. LEM3, AGP2, and DOC1 genes were required for drug uptake. Edelfosine displaced the essential proton pump Pma1p from rafts, inducing its internalization into the vacuole. Additional ATLs, including miltefosine and perifosine, also displaced Pma1p from rafts to the vacuole, suggesting that this process is a major hallmark of ATL cytotoxicity in yeast. Radioactive and synthetic fluorescent edelfosine analogues accumulated in yeast plasma membrane rafts and subsequently the endoplasmic reticulum. Although both edelfosine and Pma1p were initially located at membrane rafts, internalization of the drug toward endoplasmic reticulum and Pma1p to the vacuole followed different routes. Drug internalization was not dependent on endocytosis and was not critical for yeast cytotoxicity. However, mutants affecting endocytosis, vesicle sorting, or trafficking to the vacuole, including the retromer and ESCRT complexes, prevented Pma1p internalization and were edelfosine-resistant. Our data suggest that edelfosine-induced cytotoxicity involves raft reorganization and retromer- and ESCRT-mediated vesicular transport and degradation of essential raft proteins leading to cell death. Cytotoxicity of ATLs is mainly dependent on the changes they induce in plasma membrane raft-located proteins that lead to their internalization and subsequent degradation. Edelfosine toxicity can be circumvented by inactivating genes that then result in the recycling of internalized cell-surface proteins back to the plasma membrane.


[On the beginnings of sixteen-century science in Hungary].
Among the 222 letters by Gáspár Fraxinus to Count Nádasdy that have been recently published by T. Vida and T. Grynaeus (Budapest 1988), some 88 are concerned with or at least mention medical therapies and pharmaceutical practice. The authors examined the scientific terms and usage of the correspondence, and corroborate and detail the findings of Botta about the emergence of pharmaco-botanical education in the Nádsdys chateau at Sárvár during the first half of the XVIth century. The first scientific writer of this school interested in botany and medicine was the Hungarian humanist and teacher, the translator of the New Testament, Johannes Sylvester (Erdosi Sylvester János). In his book, the Grammatica Hungaro-Latina (1539) and in his translation of the New Testament (1541) he was the first to publish texts in Hungarian that referred to plants and maladies. The leading figure of the school, however, was Caspar Fraxinus (Szegedi Korös Gáspár), the humanist physician and friend of the Italian A. Fracantianus and P. Matthiolus. According to his letters, the authors suppose that he might have been the tutor of Peter Melius (Somogyi Juhász Péter), and Georg Lenczius (Váradi Lencsés György), whom both became respected scholars later on. Melius made name for himself as the writer of the first pharmaco-botanical monograph in Hungarian (Herbarium, Kolozsvár, 1578). Lenczius, on the other hand, wrote exhaustively in his six-volume Ars medica (Gyulafehévár, 1570-90) about theoretical and practical medicine. Though inventively arguing in favour of the connections between Fraxinus, Melius and Lencsés, the main contribution of the article is rather the collection of pharmaceutical and botanical terms that appeared in letters of these persons who visited Sárvár, or even stayed there. The authors give a set of thoroughly elaborated indices, about medical plants and herbs, (either in Latin or Hungarian), about medicaments and drugs, names of illnesses and anatomical terms; about the suggested or used therapies, the names of famous physicians and scientists, etc. By the use of these lists the detailed scientific knowledge and medical education of these late Renaissance characters are perfectly raised.


Feasibility of venous thromboembolism prophylaxis during inflammatory bowel disease flares in the outpatient setting: a decision analysis.
Inflammatory bowel disease (IBD) patients are at increased risk of venous thromboembolism (VTE), which is most pronounced during a disease flare. We explored the cost-effectiveness of pharmacological VTE prophylaxis in an outpatient setting. Markov decision analysis was conducted from a societal perspective to compare the relative costs and effectiveness of pharmacological VTE prophylaxis versus no anticoagulation during ambulatory IBD flares among a hypothetical cohort of 10,000 IBD patients. The time horizon was from time of IBD diagnosis until death. Univariate and probabilistic sensitivity analyses were performed. In base case analysis, VTE prophylaxis was, compared with no anticoagulation, associated with higher average costs (U.S. $141,036 versus $90,338) and quality-adjusted life-years (QALYs) (22.29 versus 22.25), yielding an incremental cost-effectiveness ratio of $1,267,450/QALY. Venous thromboembolism prophylaxis resulted in higher unadjusted life-years (47.76 life-years versus 46.67 life-years) and lower lifetime risk of VTE (6.2% versus 9.3%). The number needed to treat to prevent one VTE event over a lifetime was 32.3. Univariate sensitivity analysis showed that the incremental cost-effectiveness ratio was most sensitive to variations in the efficacy of VTE prophylaxis. In probabilistic sensitivity analysis, only 20% of 1000 simulated trials showed that VTE prophylaxis increased QALYs. In the remaining 80%, it was associated with both higher costs and fewer QALYs. Although the administration of pharmacological VTE prophylaxis during IBD flares in the outpatient setting was associated with increased life-years and reduced VTE events, it was not cost effective. Moreover, the benefits of VTE prophylaxis were not robust to probabilistic sensitivity analysis.


Exploring the experiences of high-risk groups during the first UK Covid-19 lockdown through creative methods.
Background: Groups at high risk of severe illness/death from COVID-19 (older people and those identified as clinically extremely vulnerable: CEV) experienced increased restrictions, poor mental health and loneliness during the first UK lockdown. Methods: Seventeen older adults, eight CEV adults, one parent of a CEV child, and two family carers of CEV adults, shared their experiences of the first UK lockdown through various media: written reflections, interviews, poetry, videos, photographs, and visual artwork. Results: Through a positive psychology lens, five themes were identified: experiencing loss; community and connection; finding joy, hope and optimism; adapting to change; and sense- and meaning-making. Conclusion: High-risk groups fostered wellbeing and flourishing and formed a sense of coherence in a time of great loss. Engagement with artistic, creative, and cultural activities facilitated this. The arts not only provided a creative means of collecting data but was also identified as a central thread in the findings.


General characteristics of protein degradation in diabetes and starvation.
The enhanced protein degradation associated with diabetes and starvation is fundamentally different from normal protein catabolism. In normal eukaryotic cells large molecular weight proteins tend to be degraded more rapidly than small proteins, acidic proteins tend to be degraded more rapidly than neutral or basic proteins, and glycoproteins tend to be degraded more rapidly than nonglycoproteins. All three of these general correlations are absent or markedly reduced in liver and muscle of diabetic and starved rats. In contrast, the correlations between proteins size and half-life, between protein net charge and half-life, and between protein carbohydrate content and half-life are not affected in brain of diabetic or starved animals. These results suggest that diabetes and starvation alter the general characteristics of intracellular protein degradation in target tissues of insulin. Degradation of serum proteins is also affected in diabetes and starvation. In normal animals a general correlation exists between isoelectric points of serum proteins and their degradative rates. This relationship is abolished in diabetes and starvation, as it is among liver and muscle proteins. The implications of our findings are discussed with regard to possible mechanisms of the enhanced protein breakdown.


Development of a visual inspection programme for cervical cancer prevention in Bangladesh.
Cervical cancer is the most common reproductive cancer in women in Bangladesh, and most women come for diagnosis and treatment when it is too late. To support early detection of pre-cancerous conditions and prevent cervical cancer, Bangladesh undertook a screening programme using visual inspection of the cervix with acetic acid (VIA) and cryotherapy through a public sector programme. The programme was launched in 2004-05 in a phased manner, starting with a pilot programme in 16 of the 64 districts in the country and scaled up to 44 districts as of the end of 2007. Evaluation of the pilot programme's performance showed that VIA can be carried out by trained doctors, nurses, and paramedical workers in Bangladesh, even though the level of resources is poor, and women, their partners and families are often not aware of the disease and its consequences. The programme now needs to move from opportunistic screening to population-based, systematic screening of women over age 30. More providers need to be trained, and clinics better equipped. The links between screening, diagnosis and treatment need to be improved and the false-positive rate of VIA tests greatly reduced. It is only when we have achieved high coverage that reduced rates of cancer can be ensured.


[Profile and course of cardiovascular morbidity and mortality in Conakry. Apropos of 268 cases seen at the Cardiology Department of the Ignace-Deen University Hospital 1986-1987].
Over a period of two years (1986-1987), the authors have studied the morbidity and mortality of various cardiovascular diseases in a hospital population of 268 patients. By comparing it with a previous similar study conducted over 5 years (1981-1985), they have reached the following conclusions: the prevalence of the main nosological groups is equivalent (H.B.P., rheumatoid valvulopathies, chronic pulmonary heart, ischemic cardiopathies; severity of the valvulopathies and their prognosis which raise social and medical problems especially that of cardiac surgery, still inexistent in Guinea; increased prevalence of diseases such as hypertension and rheumatoid valvulopathies. They suggest early screening, especially for rheumatoid valvulopathies and hypertension, which cause major social problems because of their complications. Besides, it would be desirable that visits at regular intervals be made mandatory in schools and universities and at preemployment examinations and in all SMI (?) centers in the country.


Ultrasound-guided pulse-dose radiofrequency: treatment of neuropathic pain after brachial plexus lesion and arm revascularization.
Neuropathic pain following brachial plexus injury is a severe sequela that is difficult to treat. Pulsed radiofrequency (PRF) has been proved to reduce neuropathic pain after nerve injury, even though the underlying mechanism remains unclear. This case report describes the use of ultrasound-guided PRF to reduce neuropathic pain in a double-level upper extremity nerve injury. A 25-year-old man who sustained a complete left brachial plexus injury with cervical root avulsion came to our attention. Since 2007 the patient has suffered from neuropathic pain (NP) involving the ulnar side of the forearm, the proximal third of the forearm, and the thumb. No pain relief was obtained by means of surgery, rehabilitation, and medications. Ultrasound-guided PRF was performed on the ulnar nerve at the elbow level. The median nerve received a PRF treatment at wrist level. After the treatment, the patient reported a consistent reduction of pain in his hand. We measured a 70% reduction of pain on the VAS scale. PRF treatment allowed our patient to return to work after a period of absence enforced by severe pain. This case showed that PRF is a useful tool when pharmacological therapy is inadequate for pain control in posttraumatic neuropathic pain.


Short-term stress enhances individuals' adaptive behaviors: a near-infrared spectroscopy study.
Few studies have examined the influence of short-term stress on neural networks underlying impulsivity in reward/punishment behavior. The influence of short-term stress on neural networks in a sample of female participants was investigated. Participants in the experimental group first completed a speech task intended to induce stress. Next, all participants performed a reward (R)/punishment (P) Go/NoGo task, while near-infrared spectroscopy was used to assess brain activation. Results indicated that Δdeoxy-Hb in the right ventrolateral prefrontal cortex increased in the R condition compared to the P condition. Moreover, false alarm reaction times during the R condition increased in the experimental group compared to the control group. Also, commission errors in the control group increased significantly in the R condition compared to the P condition. These results suggest that individuals make more careful and adaptive actions to obtain rewards when exposed to short-term stress. Long-term and short-term stress appear to have different influences on human reward-based decision making. In the future, fMRI can be used to precisely examine the possible impulsivity-related changes in functional connectivity caused by short-term stress.


Emergence of Frequency-Dependent Motor Variability Within Supra-Second Auditory Cueing.
Motor variability (MV) is an essential feature of the sensory motor system, and it plays an important role in sensory-motor learning. MV facilitates motor adaptation during auditory-motor synchronization (AMS). In AMS, individuals receive a series of similar auditory stimuli that come in a periodic manner at a fixed interval called an inter-stimulus interval (ISI). Peri-second ISI (1 second range) and supra-second ISI (>1 second) are differently processed, since these intervals involve different amount of cognitive resources. Supra-second ISI involves more top-down attention as compared to peri-second ISI. In this study we examined the effect of tone frequency (perceptual property of auditory stimuli) on predictive tapping and MV under peri-second and supra-second ranges. We examined the effect of tone frequency (a perceptual property of auditory stimuli) on predictive tapping and motor variability (MV) under short (peri-second) and long (supra-second) inter-stimulus intervals. Among 30 healthy participants (aged 18-35 years, M = 24.6 years), we randomly assigned equal numbers of these two inter-stimulus conditions to isochronous sound sequences. In their attempt to synchronize their motor responses with the tone, participants reproduced the ISI in their inter-tap intervals (ITIs). We analyzed their predictive tapping in terms of negative asynchrony (in which the tap occurs before the tone) and small positive asynchrony (0-100 ms), whereas we analyzed MV using the coefficient of variation (CV) of the ITI. We found that participants showed predictive tapping under short ISI, irrespective of the tone frequency. Moreover, their MV was unaffected by tone frequency. These findings imply that participants expressed MV in a predictive rather than reactive manner under short, but not long, ISI. Under long ISI, tone frequency had a significant effect on MV such that there was higher MV with the low-frequency than with the high-frequency tone. Thus, low-frequency tones are most suitable for auditory-motor learning in the supra-second range.


Comparison Between an Oral Sulfate Solution and a 2 L of Polyethylene Glycol/Ascorbic Acid as a Split Dose Bowel Preparation for Colonoscopy.
This study aimed to compare the efficacy and tolerability of an oral sulfate solution (OSS) versus 2 L of polyethylene glycol/ascorbic acid (2L-PEG/Asc) for bowel cleansing before colonoscopy. A prospective, single-center, single-blinded, noninferiority, randomized, controlled trial was performed. The primary outcome was the rate of successful bowel cleansing, evaluated using the Boston Bowel Preparation Scale (BBPS). Secondary outcomes were examination time, polyp, and adenoma detection rate (PDR and ADR), tolerability, and safety. Ease of use, palatability, intention to reuse, and satisfaction were evaluated using a questionnaire. A total of 187 participants were randomized to receive either OSS (n=93) or 2L-PEG/Asc (n=94). Successful bowel cleansing was achieved in 86.0% (80/93) of the OSS group, which was noninferior to the 2L-PEG/Asc group (88.3%, 83/94), with a difference of -2.3% by ITT analysis [95% confidence interval (CI) -12.0 to +7.4]. The withdrawal time of the OSS group was significantly shorter than that of the 2L-PEG/Asc group (11.8±5.2 vs. 14.3±8.5; P=0.016). Ease of use, palatability, intention to reuse, and satisfaction were similar between the 2 groups. Adverse events were also similar between the 2 groups. Mucosal erythema (4.3%) and aphthous lesions (2.1%) were found only in the 2L-PEG/Asc group. OSS was as effective as 2L-PEG/Asc for successful bowel cleansing and had acceptable tolerability. OSS is a promising and safe low-volume preparation alternative for colonoscopy. (Clinical trial registration number: NCT02761213.).


Cutting depth-oriented ductile machining of infrared micro-lens arrays by elliptical vibration cutting.
Infrared micro-lens arrays (MLAs) are widely used in advanced optical systems due to their advantages such as low focusing depth and high sensitivity. Elliptical vibration cutting (EVC) is a promising approach for the fabrication of MLAs on infrared brittle materials. However, the mechanism of ductile machining of MLAs prepared by EVC has not been fully elucidated so far. In this paper, based on the vibration intermittent cutting characteristics and the transient material removal state, a ductile machining model of MLAs on brittle material by EVC was established. This model effectively calculates the subsurface damage of the machined surface and realizes the prediction of the critical depth for ductile machining of MLAs. Furthermore, the concave micro-lenses were prepared on single crystal silicon by EVC and ordinary cutting (OC) to verify this model. The results demonstrated that EVC could significantly enhance the critical depth by approximately 4.3 times compared to OC. Microstructural surface damage predominantly occurs at the exit side of the tool cutting. This proposed model accurately predicts the actual critical depth, with an average error of about 7.5%. Additionally, elevating the amplitude in the depth of cut direction could increase the critical depth, but a larger amplitude would inhibit the increase of the critical depth. This study contributes to a better understanding of ductile machining of microstructure on brittle materials and facilitates the process optimization of MLAs fabrication using EVC.


The Confucian relational concept of the person and its modern predicament.
The Confucian relational concept of the person has been proposed as an epistemically more cogent and ethically more attractive alternative to that of liberal individualism. Two arguments are raised against this proposal without defending liberal individualism. Ethically, Confucianism is vitiated by certain unattractive features that cannot be removed without reducing the Confucian relational concept of the person to an abstract and not very helpful notion of human relatedness. Epistemically, Confucianism commits the essentialist fallacy of treating its own concept of human relations as reflecting the nature of things. In view of these limitations, the Confucian relational concept of the person does not provide a viable framework for dealing with social issues including bioethics.


Adjuvant effect of CIA07, a combination of Escherichia coli DNA fragments and modified lipopolysaccharides, on the immune response to hepatitis B virus surface antigen.
CIA07 is an immunostimulatory agent composed of bacterial DNA fragments and modified lipopolysaccharide, which has antitumor activity against bladder cancer in mice. In this study, the adjuvant activity of CIA07 was evaluated using hepatitis B virus surface antigen (HBsAg) as the immunogen. Mice were immunized intramuscularly three times at 1-week intervals with HBsAg alone or in combination with alum, bacterial DNA fragments, modified lipopolysaccharide, CIA07 or CpG1826, and immune responses were assessed. At 1 week after the final injection, the HBsAg-specific total serum IgG antibody titer in CIA07-treated mice was 14 times higher than that in animals administered antigen alone, six times higher than in mice given alum or bacterial DNA fragments and twice as high as those treated with modified lipopolysaccharide or CpG1826, and remained maximal until 8 weeks postimmunization. Animals receiving antigen alone or plus alum displayed barely detectable HBsAg-specific serum IgG2a antibody responses. However, coadministration of CIA07 with antigen led to markedly enhanced serum IgG2a antibody titer and IFN-gamma(+) production in splenocytes, indicating that CIA07 effectively induces Th1-type immune responses. In addition, the number of HBsAg-specific CD8(+) T cells in peripheral blood mononuclear cells was elevated in CIA07-treated mice. These data clearly demonstrate that CIA07 is able to induce both cellular and humoral immune responses to HBsAg, and confirm its potential as an adjuvant in therapeutic vaccines for hepatitis B virus infections.


Advances in siRNA therapeutics and synergistic effect on siRNA activity using emerging dual ribose modifications.
Nucleic acid-based therapeutics that control gene expression have been steadily progressing towards achieving their full clinical potential throughout the last few decades. Rapid progress has been achieved in RNAi-based therapy by optimizing high specificity and gene silencing efficiency using chemically modified siRNAs. Since 2018, four siRNA drugs - patisiran, givosiran, lumasiran, and inclisiran, were approved by the US FDA, providing a testament to the promise of RNAi therapeutics. Despite these promising results, safe and efficient siRNA delivery at the target site remains a major obstacle for efficient siRNA-based therapeutics. In this review, we have outlined the synergistic effects of emerging dual ribose modifications, including 2',4'- and 2',5'-modifications, 5'-E/Z-vinylphosphonate, and northern methanocarbacyclic (NMC) modifications that have contributed to drug-like effects in siRNA. These modifications enhance nuclease stability, prolong gene silencing efficiency, improve thermal stability, and exhibit high tissue accumulation. We also highlight the current progress in siRNA clinical trials. This review will help to understand the potential effects of dual ribose modifications and provides alternative ways to use extensive 2'-modifications in siRNA drugs. Moreover, the minimal number of these dual ribose modifications could be sufficient to achieve the desired therapeutic effect. In future, detailed in vivo studies using these dual ribose modifications could help to improve the therapeutic effects of siRNA. Rational design could further open doors for the rapid progress in siRNA therapeutics. [Figure: see text].


An analytical study of the changing health of a hospice population 1978-89.
This study explores the changing characteristics of patients admitted to Sir Michael Sobell House, Oxford, between 1978-89. These dates represent the period between the first available records and the first computerized records. Analysis is between these dates and has been undertaken to enable future comparison between the early life of the unit with more recent developments. Using secondary sources the following areas were compared statistically: information related to general characteristics such as sex and age; information related to referral such as the number of referrals; diagnosis on referral and reasons for referral; information related to problems presented and place of death. Significant findings included an increase in referrals and patient survival; an increase in patients dying at home; a decrease in symptoms presented on referral and fewer referrals for terminal care; and an increase in referral for rehabilitation, assessment and support. Reasons for these changes are suggested.


Echocardiographic subtypes of heart failure in consecutive hospitalised patients with dyspnoea.
Heart failure with preserved ejection fraction (HFpEF) involves half of hospitalised patients with heart failure (HF), but estimates vary due to unclear diagnostic criteria. We performed a prospective observational study of hospitalised patients admitted with dyspnoea. The aim was to apply contemporary guidelines to diagnose HF due to valvular disease (HFvhd), HF due to reduced ejection fraction (HFrEF), HF due to midrange EF (HFmrEF) and HFpEF in relation to presumed cardiac or non-cardiac dyspnoea. We included consecutive hospitalised patients with presumed HF or dyspnoea and excluded patients with acute coronary syndrome, estimated glomerular filtration rate <30 mL/min/1.73 m² or low NT-proBNP (<296 ng/L). Higher age-adjusted NT-proBNP values excluded patients with presumptive non-cardiac dyspnoea. Contemporary criteria for HFpEF and diastolic dysfunction were assessed, and we adjudicated whether acute decompensated HF (ADHF) had been the primary diagnosis. Of 707 eligible patients, we included 370 patients of whom 75 had non-cardiac dyspnoea. Of these, 10% (38/370) had no cardiac dysfunction. Cardiac dysfunction consisted of 18.4%, HFvhd, 30.1% HFrEF, 10.2% HFmrEF and 41.3% HFpEF. HFpEF was twice as common in presumptive non-cardiac dyspnoea versus cardiac dyspnoea (71% vs 34%, p<0.0001). However, adjudicated ADHF was the primary diagnosis in 80% of HFrEF, 62% of HFmrEF and just 28% of HFpEF. HF according to contemporary criteria applied to 90% of patients admitted with dyspnoea and elevated NT-proBNP irrespective of the presumptive cause of dyspnoea, of whom 10% had HFmrEF and 41% HFpEF. However, significant non-cardiac diagnoses related to 9 out of 10 with HFpEF with pulmonary disease as the predominant adjudicated problem.


Viscoelastic rheology of colloid-liquid crystal composites.
Gelation in colloidal suspensions is mostly induced by attractive interparticle potentials. Beside these interactions, the mechanical properties of the gel are influenced by morphological aspects like fractality. In suspensions of liquid crystal (LC) and polymeric colloids, solvent-particle interactions dominate and can be changed when the mesogen undergoes phase transition from isotropic to nematic. In case of poly(methyl methacrylate) colloids and 4-pentyl-4'-cyanobiphenyl (5CB), cooling through the isotropic-nematic phase transition results in a cellular network. Such network formation is accompanied by a strong evolution of the mechanical properties. Shear moduli reach values up to 10(6) Pa for temperatures of 15 K below the transition. Until now, the mechanical response of the gel was attributed to the elastic interactions of the LC with the colloids. However, the dynamic viscoelastic stiffening with decreasing temperature could not be explained satisfactorily. We used a homemade piezorheometer to measure the complex shear modulus of the sample in parallel plate geometry. Since the applied strains are very small, only the linear viscoelastic regime was tested. This limit guarantees a high degree of reproducibility. We gained insight into the underlying processes by measuring the frequency response for the whole cooling process. Temperature and frequency showed a strong correlation allowing for a superposition of the frequency spectra to form a single master curve similar to time-temperature-superposition. We propose that this superposition behavior is connected to the thermodynamics of the isotropic-nematic phase transition of 5CB located in the network walls. Additional experimental observations, such as hysteresis effects, support this assumption. Morphological aspects were found to be of minor relevance.


Bioresponsive albumin-conjugated paclitaxel prodrugs for cancer therapy.
The efficacy of traditional chemotherapy often suffers from rapid clearance and off-target toxicity. Drug delivery systems and controlled release are applied to improve the therapeutic efficiencies of small-molecule drugs. In this work, two novel oxidative/reductive (Ox/Re) -sensitive and one non-sensitive Paclitaxel (PTX) prodrugs were synthesized with a maleimide group, which rapidly conjugates with albumin in vivo. Albumin serves as a good vehicle to deliver more prodrug to tumors due to the enhanced permeation and retention (EPR) effect. PTX was then released from the prodrugs in glutathione(GSH)/ reactive oxygen species(ROS)-rich tumor microenvironments. This bioresponsive prodrug strategy demonstrates potent chemotherapeutic efficiency in vivo and may be utilized in clinical cancer therapy.


[Surgical treatment for Crohn's disease].
No medical on surgical treatment exists that is ideal for the patient afflicted Crohn's disease. During the chronic course of disease various complications or significant side effect of medications will develop. At this point, the patient is offered an operation. Indication for surgery rarely absolute in Crohn's disease with the exception of life threatening emergencies such as free perforation or massive hemorrhage. Common indications are bowel obstruction due to stenosis, fistula in various sites, abscess and perianal complications. It is well known that future likelihood of postoperative "recurrence" of the disease, and to learn various operative procedures described in this article. Therefore surgeon should be alert to understand the pathophysiology of the disease and to learn various operative procedures described in this article. It is important to determine proper indication and to choose best timing for operation and select the appropriate operative procedures.


HIV-1 does not alter in vitro and in vivo IL-10 production by human monocytes and macrophages.
The present study analyses the ability of HIV-1 to modulate IL-10 production in cells of monocyte-macrophage lineage cultured in the presence of macrophage colony-stimulating factor (M-CSF). Both monocytes and macrophages spontaneously produced low amount of IL-10. Lipopolysaccharide (LPS) induced a strong IL-10 response in fresh monocytes and in M-CSF-treated macrophages. In contrast, macrophages cultured in the absence of M-CSF exhibited a marked decrease in their susceptibility to LPS stimulation. M-CSF increased the IL-10 response of macrophages to LPS by enhancing both the expression of membrane-bound CD14, the protein that serves as LPS receptor, and the sensibility of CD14-expressing cells to LPS stimulation. Neither spontaneous nor LPS-induced expression of IL-10 was modulated in monocytes and macrophages by infection with eight monocytotropic strains, as demonstrated by ELISA and cytofluorimetric analysis. In contrast, all the HIV-1 strains primed macrophages for an increased IL-6 response to LPS stimulation. To determine whether IL-10 production was associated with in vivo infection, monocytes from AIDS individuals were analysed for IL-10 production. We found that neither spontaneous nor LPS-induced IL-10 production were different between healthy controls and HIV-infected patients. Taken together, these data strongly suggest that HIV-1 infection of monocytes-macrophages does not play a significant role in the regulation of IL-10 in infected patients. This study also emphasizes the role of M-CSF activation in the regulation of the cytokine response in macrophages.


[Tick-born encephalitis in southeastern Bavaria (F.R. of Germany) (author's transl)].
In 1976 blood samples from 748 patients were tested for complement fixation antibodies against the virus of tickborne encephalitis. Of these, 38 had antibodies in a serum dilution of 1:8, 18 also in a dilution of 1:32 or higher. Clinical symptoms, laboratory results, time and place of illness are presented in more detailed analysis for 14 cases. From these data, it appears than tick-borne encephalitis is more wide-spread in southeastern Bavaria than has been previously supposed. In most of the cases, tick-borne encephalitis was not suspected because the patients generally did not have a bi-pattern of illness, only 6 of the 14 had a definite history of a tick-bite, and, moreover, atypical features frequently occurred in addition to CNS symptoms. The number of juvenile patients (4 out of 14) was also unexpected. Attention is drawn to the present situation with regard to passive and active immunization.


Dengue Symptoms Significance in Anti-Dengue Drug Development: Road Less Travelled.
Dengue outbreak has affected rural areas of Delhi-NCR, Haryana widely but it lacks in surveillance. High cases of dengue symptoms were reported in these regions whereas dengue symptoms have been a neglected issue in the anti-dengue drug development. Therefore, this study aims to analyze the status of the dengue infection, a rural issue of Delhi-NCR, Haryana and to identify the significance of dengue symptoms in anti-dengue drug development. The study was conducted when there is high chance of dengue infection i.e. from August 2015 to October 2015 at OPD Unit of PR Institute of Medical Science & Research, Delhi-NCR, Sonepat. It includes 158 patients from 24 rural areas of Haryana comprising both males and females from different age groups. Out of 20% cases, 6% were IgG-Positive, 9% were IgMPositive and 88% were NS1-Positive and rest 80% was normal. It includes 44% cases of thrombocytopenia. Badkhalsa village (28%), age group 18-24 (34%) and males (63%) reported cases of high infection. It was found that people with fewer platelet counts (Rai village) were not suffering from dengue whereas people with more platelet count reported dengue infection (Badkhalsa village). This study focuses on new research directions by highlighting the dengue symptoms importance in anti-dengue drug development also it is a first attempt to investigate the status of dengue, a rural issue of Delhi-NCR, Haryana and suggests that health authorities and people living in these regions should take initiatives for better health.


miR-652 Promotes Tumor Proliferation and Metastasis by Targeting RORA in Endometrial Cancer.
Endometrial cancer is the most common gynecologic malignancy, whose incidence rate is on the rise. However, the underlying mechanisms of endometrial cancer are not very clear yet. miRNAs have been considered to be playing important roles in malignant behavior. Here, miR-652 was significantly upregulated in endometrial cancer, which correlated with shorter overall survival and earlier recurrence. Moreover, overexpression of miR-652 in endometrial cancer cells promoted proliferation, migration, and invasion in vitro and facilitated tumor growth and metastasis in vivo. In contrast, downregulation of miR-652 in endometrial cancer cells inhibited these processes both in vitro and in vivo. Mechanistically, miR-652 promotes proliferation and metastasis through directly targeting RORA. Both mRNA and protein level of RORA were negatively related with miR-652 and overexpression of RORA can rescue the promotion effect of miR-652. Further experiments indicated miR-652 overexpression can activate the Wnt/β-catenin pathway and RORA can downregulate β-catenin and function as a tumor suppressor in endometrial cancer. Collectively, these findings demonstrate that miR-652 functions as an oncomir in endometrial cancer. IMPLICATIONS: This study suggests that the miR-652 is a critical regulator of proliferation and metastasis in endometrial cancer and may serve as a therapeutic target.


[Ultrastructure of the sympathetic ganglia in hypoxia].
Short-term hypoxia produces ultrastructural alterations in ganglions of rats in the form of dilatation of some membrane neuron compartments and sinuous plasmatic membrane. More long-term hypoxia produces structural changes of membrane cell components. An increase of lysosome number and lipofuscin granules alternations in chronic hypoxia (1 year) are similar to the age changes and are characterized by intensive accumulation of lipofuscin and Nissl bodies hypertrophy.


[Anterolateral thigh flap for limb reconstructive surgery: four case reports].
We report four cases of anterolateral thigh flap reconstructions, searching for the different advantages and disadvantages of this type of flap. A pure skin flap was used to cover tissue loss on the plantar surface of the foot both in weight-bearing and non-weight-bearing zones as well as to cover the dorsal aspect of the first commissura of the hand. A musculocutaneous flap (fragment of the vastus lateralis) was associated with an iliac cancellous graft to treat septic nonunion of the tibia. A composite tendinocutaneous flap (fragment of the iliotibial band) was used to reconstruct extensor tendon and skin loss on the dorsal aspect of the hand. A perforating artery measuring more than 1 mm was used in all cases, but in one flap it was in the position described by Song. Side-to-side anastomosis was used in one case. For three cases, the sutured circumflex artery had the same caliber as the radial artery at the wrist level. In one case the circumflex artery had a diameter greater than the posterior tibial artery. Closure of the donor site was not possible immediately in one case. A thin skin graft was required in three cases. Skin healing after microsurgery was satisfactory in all cases, occurring within the usual delay. Bone healing in the patient with septic nonunion of the tibia was achieved at four months. The flap was reliable. In three cases the skin graft of the donor site only healed partially. The advantages of the antero lateral thigh flap are: surgery in the supine position, spinal anesthesia when the recipient site is on the lower limb, flap reliability, use of the flap as a bridging element, use as a composite flap. The disadvantages are: variable position of usable perforants, requirement for wide skin grafts > 6 cm to cover the donor site. The antero lateral thigh flap is a reliable flap that can be most useful when a bridging element is required and when the donor site can be closed directly.


[Predictive value of baseline plasma midregional fragment of pro-adrenomedullin level on long-term outcome of postural tachycardia syndrome children treated with midodrine hydrochloride].
To explore the predictive value of baseline plasma midregional fragment of pro-adrenomedullin level (MR-proADM) on long-term survival of postural tachycardia syndrome (POTS) children treated with midodrine hydrochloride. Fifty-three children (male 26, mean age (14.5 ± 4.5) years old) with POTS were included in this study, and all of them were diagnosed as POTS in our department from December 2007 to January 2010. Fifty-three children with POTS were divided into two groups according to the baseline plasma content of MR-proADM. Group I consisted of 35 POTS children with plasma content of MR-proADM > 61.5 ng/L, and the group II consisted of 18 POTS children with plasma content of MR-proADM ≤ 61.5 ng/L. The mean follow-up time was (67 ± 7) months. The orthostatic intolerance symptom score and the symptom free survival were compared between the 2 groups. At the 60 months follow-up, the symptom score of children in group I was significantly lower than that in group II (χ(2) = 4.985, P < 0.05). At 72 months follow up, the symptom score was similar between the 2 groups (χ(2) = 0.004, P > 0.05) while the symptom free survival of group I was significantly higher than that in group II (χ(2) = 4.566, P < 0.05). The baseline plasma MR-proADM level is value in predicting the long-term survival of POTS children treated with midodrine hydrochloride.


Adult Shigatoxin-mediated hemolytic uremic syndrome masked by alcohol use and inflammatory bowel disease.
Diagnosing uncommon diseases in individuals with underlying medical conditions can be challenging. Cognitive bias can lead to delayed or missed disease management. We present a case of Shiga-toxin mediated hemolytic uremic syndrome (ST-HUS) in a 46-year-old man with ulcerative colitis and alcohol use disorder who presented with acute alcohol intoxication, non-bloody diarrhoea and coffee ground emesis. He was admitted to the hospital for alcoholic ketoacidosis, alcohol withdrawal and possible upper gastrointestinal bleed, but ultimately, he developed severe thrombocytopaenia, hemolytic anaemia, acute renal failure and prolonged altered mentation. Given that ST-HUS is uncommon in adults, his initial report of diarrhoea was attributed to alcohol use or underlying active ulcerative colitis and not connected to his haematologic abnormalities. He was initially started on plasmapheresis; however, thrombotic microangiopathy work up revealed Shiga-toxin in his stool and ADAMST13 levels within normal limits. Subsequently, he was transitioned to supportive care for management of ST-HUS.


The Emergence and Spread of Novel SARS-CoV-2 Variants.
Since severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) began to spread in late 2019, laboratories around the world have widely used whole genome sequencing (WGS) to continuously monitor the changes in the viral genes and discovered multiple subtypes or branches evolved from SARS-CoV-2. Recently, several novel SARS-CoV-2 variants have been found to be more transmissible. They may affect the immune response caused by vaccines and natural infections and reduce the sensitivity to neutralizing antibodies. We analyze the distribution characteristics of prevalent SARS-CoV-2 variants and the frequency of mutant sites based on the data available from GISAID and PANGO by R 4.0.2 and ArcGIS 10.2. Our analysis suggests that B.1.1.7, B.1.351, and P.1 are more easily spreading than other variants, and the key mutations of S protein, including N501Y, E484K, and K417N/T, have high mutant frequencies, which may have become the main genotypes for the spread of SARS-CoV-2.


Comparison of the cell envelope structure of a lipopolysaccharide-defective (heptose-deficient) strain and a smooth strain of Salmonella typhimurium.
The cell envelope structure of Salmonella typhimurium LT2, which has a heptose-deficient lipopolysaccharide (LPS), is significantly different from that of an isogenic strain with a normal LPS. The rough strain, when examined by freeze-etching, lacks most surface structures that are routinely present in the smooth strain (surface particles and flagella) and has few transmemberane studs in the cytoplasmic membrane (those present are generally found in aggregates), and the outer membrane cleavage is substantially stronger than that of the smooth strain. These envelope differences were independent of both growth temperature and culture age. Examination of ultrathin sections indicated that the rough strain has an outer membrane which forms a much more defined double-track artifact than the smooth strain. The addition of MgCl2 to the growth medium of the rough strain decreased the extent of outer membrane cleavage, and flagella became evident in freeze-etched preparations. The presence of supplemental MgCl2 in the growth medium, which resulted in these morphological changes in the rough strain, also produced growth at a previously restrictive temperature and a decrease in the leakage of periplasmic enzymes. The smooth strain was unaltered morphologically or physiologically by MgCl2 under identical conditions. It is suggested that the outer membrane of the rough strain is more planar.


Whole cell vaccination for meningococcus: Lessons from an idea whose time has gone.
Endotoxin in vaccines has long been recognized as a cause of adverse events and is generally regarded as a contaminant. However there are now a number of vaccine candidates that contain endotoxin as either antigen or adjuvant, particularly vaccines for Neisseria meningitidis based on native outer membrane vesicles (NOMV). Vaccines containing meningococcal endotoxin are not new. From 1907 to 1939 approximately 400,000 individuals were immunized with whole cell vaccines against meningococcus. We reviewed reports of meningococcal vaccinations from this period to characterize the adverse events in order to draw a baseline for evaluating meningococcal NOMV vaccines. The majority of these investigators conclude that whole cell vaccination was well tolerated with an adverse event profile comparable to other whole cell vaccines for Gram negative pathogens. There is insufficient data to draw conclusions on the duration of protection, if any, induced by whole cell meningococcal vaccines.


A threshold approach to understanding the origins of attachment disorganization.
Disorganized attachment in infancy is known to predict a wide range of maladaptive outcomes, but its origins are poorly understood. Parental lack of resolution concerning loss or trauma has been proposed to result in atypical parenting behaviors, which in turn have a disorganizing effect on the parent-child relationship. The authors review the evidence for this transmission pathway, considering other factors (e.g., social environment, child characteristics) that might enrich understanding of the antecedents of disorganization. A threshold approach is proposed to explain (a) why different parental behaviors are linked to disorganization depending on prevailing social conditions and (b) why certain children appear more vulnerable to forming a disorganized attachment relationship.


A comparison of intrathecal morphine/fentanyl and patient-controlled analgesia with patient-controlled analgesia alone for analgesia after liver resection.
Continuous epidural anesthesia and analgesia may be considered in liver resection, but is often avoided because of the potential development of coagulopathies and the risk of epidural hematoma. In this prospective, randomized, double-blind study we compared postoperative morphine consumption via patient-controlled analgesia after liver surgery between two groups of patients: patients receiving a preoperative dose of intrathecal morphine (0.5 mg) and fentanyl (15 microg) (treatment group) and patients receiving a sham intrathecal injection (placebo group). Forty patients scheduled for major liver resection (> or = two segments) were enrolled. The primary outcome measure was patient-controlled analgesia morphine consumption. Secondary outcomes were evaluation of pain at rest and with movement, scored on a visual analog scale with assessment of sedation, nausea, pruritus, and respiratory frequency. Outcome measures were recorded at 6, 12, 18, 24, and 48 h postspinal anesthesia or simulation. Patients in the placebo group consumed approximately three times more morphine during each time interval than patients in the treatment group (at 48 h: 124 +/- 30 vs 47 +/- 21 mg, P < 0.0001). Pain evaluation on the visual analog scale was lower for the first 18 h in the treatment group. There was no difference in the incidence of side effects in both groups. Intrathecal morphine (0.5 mg) and fentanyl (15 microg) given before liver surgery significantly decreased postoperative morphine consumption compared to placebo without any increase in side effects.


Time course of effects of unilateral lesions of the nucleus basalis of Meynert on glucose utilization by the cerebral cortex. Positron tomography in baboons.
In order to investigate the effects of a partial cholinergic deafferentation on the functional activity of the cortex, the cerebral metabolic rate of glucose (CMRGlu) was measured with positron emission tomography and 18F-2-fluoro-2-deoxy-D-glucose in 5 baboons (Papio anubis) both before and serially following stereotaxic electrocoagulation of the left nucleus basalis of Meynert (NbM). Four days postlesion, significant metabolic depression was present in the entire ipsilateral cerebral cortex, most marked in the frontotemporal region, and which slowly recovered close to normal within 6-13 weeks. Postmortem studies showed that the lesions were located largely in the NbM, and that a significant decrease in choline-acetyltransferase (ChAT) activity was present in the ipsilateral frontal, temporal and parietal cortices. The animal with the most limited histological lesion showed the least decrease in both ChAT activity and CMRGlu. There was a highly significant linear correlation between the regional cortical decreases in CMRGlu (early postlesion data) and in ChAT activity. These results indicate that cholinergic deafferentation induces a proportional metabolic depression in the cortex. However, compensatory mechanisms operate to restore the cortical metabolic activity gradually despite sustained cholinergic denervation, pointing to pre- and/or postsynaptic adaptation (plasticity). Moreover, unilateral NbM lesions also induced a significant reduction in contralateral CMRGlu, which also demonstrated recovery. Several mechanisms are discussed to explain this contralateral effect, but the most likely implicates a transcallosal depression of function as a result of ipsilateral effects of the NbM lesion. These metabolic effects of cholinergic deafferentation in the primate provide new insight into the mechanisms of cortical dysfunction, and the recovery thereof, following subcortical lesions. In addition, our findings have some relevance to the cortical consequences of cholinergic deafferentation observed in dementia of Alzheimer type.


Microprocessor-based speech processing system.
Durational measurements of frication, aspiration, prevoicing, and voice onset are often difficult to perform from the spectrogram, and the resolution is limited to about 5 ms. In many instances, a higher resolution can be obtained from a study of waveforms than from a study of spectrum. We present a microprocessor-based speech acquisition and processing system which uses waveform analysis techniques to extract measurements from the acoustic signal. The system is low cost and portable; it operates in "real time" and employs noninvasive data-capturing techniques. The usefulness of the system is demonstrated in the VOT measurement of CV clusters and in the measurement of fundamental frequency.


Endoscopic radiofrequency ablation for cholangiocarcinoma.
To describe the use of endobiliary radiofrequency ablation (RFA) in the treatment of malignant disease of the bile duct and offer a comprehensive review of the emerging evidence on the safety and effectiveness of this new technique. Ex-vivo and in-vivo porcine studies have been reported, confirming the feasibility of the technique, gathering preliminary safety data and defining appropriate power settings for human studies. Moderate-sized case series have now reported the use of RFA in mixed cohorts of human individuals with pancreatic cancer, cholangiocarcinoma and other malignant diseases of the bile duct. Endoscopic and percutaneous approaches have both been investigated. Small case series of blocked self-expanding metal stent clearance using RFA have been published. Intraductal RFA, via both endoscopic and percutaneous approaches, is feasible. Complication rates appear to be comparable with the current standard endoscopic and percutaneous approaches to palliation of malignant strictures of the bile duct. The current body of literature is germinal, but warrants the further investigation of planned clinical trials.


Endoscopic stenting of minor papilla for symptomatic pancreas divisum.
Pancreatitis is one of the presentations of pancreas divisum. Endoscopic treatment by dorsal pancreatic duct stenting relieves symptoms in a majority of patients. We report a patient with pancreas divisum and calcific chronic pancreatitis in whom successful drainage of the dorsal duct with a stent through the minor papilla relieved the pain.


Biochemistry, function, and deficiency of vitamin B12 in Caenorhabditis elegans.
Caenorhabditis elegans is a nematode that has been widely used as an animal for investigation of diverse biological phenomena. Vitamin B12 is essential for the growth of this worm, which contains two cobalamin-dependent enzymes, methylmalonyl-CoA mutase and methionine synthase. A full complement of gene homologs encoding the enzymes associated with the mammalian intercellular metabolic processes of vitamin B12 is identified in the genome of C elegans However, this worm has no orthologs of the vitamin B12-binders that participate in human intestinal absorption and blood circulation. When the worm is treated with a vitamin B12-deficient diet for five generations (15 days), it readily develops vitamin B12 deficiency, which induces worm phenotypes (infertility, delayed growth, and shorter lifespan) that resemble the symptoms of mammalian vitamin B12 deficiency. Such phenotypes associated with vitamin B12 deficiency were readily induced in the worm.


Streptomyces cameroonensis sp. nov., a Geldanamycin Producer That Promotes Theobroma cacao Growth.
The taxonomy of an actinobacterial strain, designated JJY4T, was established using a polyphasic approach. JJY4T was isolated from the rhizosphere of Chromolaena odorata in Yaoundé (Cameroon) during a project for the selection of biological control agents. Strain JJY4T exhibited antimicrobial activities against bacteria, fungi, and oomycetes. Strain JJY4T also exhibited the traits of plant growth-promoting rhizobacteria such as the solubilization of inorganic phosphate, production of siderophores and indole-3-acetic acid, and 1-aminocyclopropane-1-carboxylate deaminase activity. In planta assays performed on cocoa plantlets confirmed that strain JJY4T exhibited strong abilities to promote plant growth and protect against Phytophthora megakarya, the main causal agent of cocoa pod rot. The formation of rugose-ornamented spores in spiral spore chains by strain JJY4T is a typical feature of members found in the Streptomyces violaceusniger clade and, similar to some members of the clade, strain JJY4T produces geldanamycin. A phylogenetic analysis based on 16S rRNA gene sequences confirmed this classification and suggests that strain JJY4T be added to the subclade constituted of the type strains Streptomyces malaysiensis DSM 41697T and Streptomyces samsunensis DSM 42010T. However, DNA-DNA relatedness and physiological characteristics allowed for the differentiation of strain JJY4T from its closest phylogenetic relatives. Based on these results, strain JJY4T (=NRRL B-65369, =NBRC 112705) appears to represent a novel species in the S. violaceusniger clade for which the proposed name is Streptomyces cameroonensis sp. nov.