Phloretin ameliorates chemokines and ICAM-1 expression via blocking of the NF-κB pathway in the TNF-α-induced HaCaT human keratinocytes.
Previous studies found that phloretin had anti-oxidant, anti-inflammatory, and anti-tumor properties. In this study, we investigated whether phloretin could suppress the production of the intercellular adhesion molecule (ICAM)-1 and chemokines through downregulation of the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in TNF-α-stimulated HaCaT human keratinocytes. HaCaT cells were treated with phloretin and then the cells were stimulated by TNF-α. Phloretin treatment decreased the production of IL-6, IL-8, CCL5, MDC, and TARC. Phloretin decreased ICAM-1 protein and mRNA expression, and also suppressed the adhesion of monocyte THP-1 cells to inflammatory HaCaT cells. Phloretin inhibited NF-κB translocation into the nucleus and also suppressed the phosphorylation of Akt and MAPK signal. In addition, phloretin increased heme oxygenase-1 production in a concentration-dependent manner. These results demonstrated that phloretin has anti-inflammatory effects to inhibit chemokines and ICAM-1 expressions through suppression of the NF-κB and MAPK pathways in human keratinocytes.


Cardiovascular abnormalities in progeria. Case report and review of the literature.
The cardiovascular findings in cases of progeria are similar in many respects to the changes associated with aging. These changes include prominent atherosclerosis and calcification of the aortic and mitral valves, coronary arteries, and aorta. The coronary artery disease leads to ischemic changes in the myocardium, including well-defined infarcts. In addition, the present case demonstrates narrowing of the small intramural arteries, which may have contributed to myocardial fibrosis.


Adiponectin levels in patients with bipolar disorder: A systematic review and meta-analysis.
Bipolar disorder (BD) is associated with high prevalence rates of obesity-related conditions and subclinical inflammation. Adiponectin is produced by adipose tissue and exerts anti-inflammatory activities. We aimed to perform a systematic review and meta-analysis of studies investigating adiponectin levels in BD patients and healthy controls. Electronic databases were searched from their inception until 15th Jan 2019. Random-effects models with the Hedges' g as the effect size (ES) estimate were used. We included 11 studies, representing 477 patients and 380 controls. Pooled data analysis revealed no significant differences in adiponectin levels between BD patients and controls (ES = 0.28, 95%CI: -0.34 - 0.90, p = 0.372). The levels of adiponectin were significantly higher during euthymia (ES = 1.09, 95%CI: 0.03-2.16, p = 0.044). The levels of adiponectin in depressed patients were lower, but this result did not reach statistical significance (ES = -0.90, 95%CI: -1.85 - 0.05, p = 0.063). Due to low number of studies, the subgroup analysis of manic patients was not performed; however, a severity of manic symptoms was not associated with the ES estimates. Longer illness duration and a higher percentage of BD type I (BD-I) patients were associated with higher ES estimates. A higher severity of depressive symptoms was associated with lower ES estimates. Heterogeneity was significant in all analyses. Results of the Egger's test were insignificant, showing no publication bias. Our results indicate that adiponectin might be a state marker of BD as it appears to be elevated in euthymia and decreased in depression. Illness progression and a diagnosis of BD-I might contribute to higher adiponectin levels.


Prefrontal activity during koh-do incense discrimination.
Whenever we make reasoned decisions we must refer to relevant knowledge obtained through past experience. Our brains test multiple premises and select whichever conclusion serves as the best explanation of the current conditions. In the present study we examined the prefrontal activity of koh-do experts with near infrared spectroscopy while they reasoned about odours during an incense discrimination task. These practitioners of the Japanese incense ceremony have been trained to form and manipulate abstract images of complex olfactory stimuli represented in a multidimensional symbolic space in the mind. In koh-do experts, the right PFC showed a consistent stimulus-non-selective response during discrimination and the left PFC showed phasic stimulus-selective responses modulated by the internal subjective state of the reasoning process. These two dissociated functions appeared to cooperate with each other during reasoning. In contrast, koh-do beginners did not show the organized response pattern found in experts. The results suggest that both PFCs contribute to abductive reasoning, but do so differently through different stages of the process.


Hand movement asymmetry during speech: no effect of speaking topic.
Right-handed subjects were videotaped as they spoke on verbal, spatial and neutral topics and the frequencies of their spontaneous hand movements were analyzed. Although subjects made more free movement gestures during the spatial topics than during the other topics, there was a consistent level of right hand preference for free movements across topics. Self-touching movements showed no hand preference in any topic. The results suggest that free movements are generated by a left-hemisphere motor control system which exerts consistently greater influence over the right than the left hand regardless of the source of processing preceding activation of this system.


Effects of angiotensin II on [3H]noradrenaline release and phosphatidylinositol hydrolysis in the parietal cortex and locus coeruleus of the rat.
Angiotensin II (ANGII) (3-100 nM) facilitated the potassium-evoked (22.5 mM) release of [3H]-noradrenaline ([3H]NA) from slices of parietal cortex in a concentration-dependent manner, but did not significantly alter the release of [3H]NA evoked in a similar manner from locus coeruleus slices. The facilitatory action of ANGII was blocked by saralasin (0.1-3 microM). Neither nimodipine (10-30 microM) nor phenylmethylsulphonyl fluoride (1 mM) altered either [3H]NA release or the facilitatory action of ANGII in the parietal cortex. Carbachol (0.01-3 mM) and raised potassium (22.5 mM), but not ANGII (3-100 nM), stimulated the production of inositol phosphates in parietal cortex slices. The potassium-evoked increase in inositol phosphate production was unaffected by ANGII (3-100 nM). In the locus coeruleus, ANGII (3-100 nM) did not stimulate inositol phosphate production. The mechanism underlying the ANGII facilitation of [3H]NA release from the parietal cortex does not appear to involve either nimodipine-sensitive calcium channels, or, as far as we have been able to determine, the release of calcium from intracellular stores following the breakdown of phosphoinositides.


MicroRNA-18a-5p mitigates oxygen-glucose-deprivation/reoxygenation-induced injury through suppression of TLRs/NF-κB signaling by targeting TLR8 in PC12 cells.
This work aimed to assess the role of TLR8 in cerebral I/R injury and its in-depth pathogenesis. Bioinformatics analysis indicated that TLR8 was up-regulated in patients with ischemic stroke than that in healthy control, and miR-18a-5p was the upstream regulatory of TLR8. Then, the rat pheochromocytoma PC12 cells were exposed in oxygen-glucose-deprivation/reoxygenation (OGD/R) conditions to construct a model in vitro. The functional experiments indicated that OGD/R can decline the viability and elevate the apoptosis of PC12 cells, while up-regulation of miR-18a-5p can alleviate OGD/R-induced cell injury. Notably, overexpression of TLR8 reverses the miR-18a-5p-mediated protection on OGD/R-induced cells injury. Finally, we found that up-regulation of miR-18a-5p obviously declined the protein levels of TLR4 and TLR7 as well as the phosphorylation of NF-κB, while overexpression of TLR8 canceled the decrease caused by miR-18a-5p up-regulation. In summing, our results illustrated that miR-18a-5p/TLR8 axis can mitigate OGD/R-induced cells injury through TLRs and NF-κB pathway.


Spin-Orbit Charge-Transfer Intersystem Crossing (ISC) in Compact Electron Donor-Acceptor Dyads: ISC Mechanism and Application as Novel and Potent Photodynamic Therapy Reagents.
Spin-orbit charge-transfer intersystem crossing (SOCT-ISC) is useful for the preparation of heavy atom-free triplet photosensitisers (PSs). Herein, a series of perylene-Bodipy compact electron donor/acceptor dyads showing efficient SOCT-ISC is prepared. The photophysical properties of the dyads were studied with steady-state and time-resolved spectroscopies. Efficient triplet state formation (quantum yield ΦT =60 %) was observed, with a triplet state lifetime (τT =436 μs) much longer than that accessed with the conventional heavy atom effect (τT =62 μs). The SOCT-ISC mechanism was unambiguously confirmed by direct excitation of the charge transfer (CT) absorption band by using nanosecond transient absorption spectroscopy and time-resolved electron paramagnetic resonance (TREPR) spectroscopy. The factors affecting the SOCT-ISC efficiency include the geometry, the potential energy surface of the torsion, the spin density for the atoms of the linker, solvent polarity, and the energy matching of the 1 CT/3 LE states. Remarkably, these heavy atom-free triplet PSs were demonstrated as a new type of efficient photodynamic therapy (PDT) reagents (phototoxicity, EC50 =75 nm), with a negligible dark toxicity (EC50 =78.1 μm) compared with the conventional heavy atom PSs (dark toxicity, EC50 =6.0 μm, light toxicity, EC50 =4.0 nm). This study provides in-depth understanding of the SOCT-ISC, unveils the design principles of triplet PSs based on SOCT-ISC, and underlines their application as a new generation of potent PDT reagents.


A contribution to a new test method for dandruff-inhibiting and "keratolytic" action of drugs.
Free cholesterol in lipids from the scalp and hair is predominantly a constituent of epidermal lipids. Therefore, a reduction in cholesterol content induced by a drug indicates a reduction in cell turnover in the epidermis. As, according to the literature, increased cell turnover in the epidermis results in formation of dandruff, a reduction in the proportion of cholesterol should indicate inhibition of the formation of dandruff. Conversely, an increase in free cholesterol should generally indicate a "keratolytic" effect. So unequivocal an interpretation has not so far been possible in persons with dandruff, as it was not known whether free cholesterol was increased or decreased. In addition, this interpretation was not possible after use of antimicrobial substances, as in vitro investigations had failed to exclude microbial esterification of cholesterol on the scalp. The present investigation has shown that correlation of free cholesterol level with cell turnover is permissible in patients with dandruff, even if antimicrobial drugs are being tested.


Biologically-Active Gold(III) Complexes.
A review is given of the background to and results of the succesful pharmacological testing of [AuX(2)(damp)] (X = Cl, OAc; damp = 2-Me(2) NCH(2)C(6) H(4)) against a range of microbes, fungi and tumouts, culminating in in vivo xenografts of ZR-1-75. These are the first fully evaluated gold(III) complexes. The activity and reactions of the diacetato-complex bear a resemblance to cisplatin, and some of the relevant chemistry is discussed. Preliminary screening data for C,P-chelated tertiary phosphine derivatives of gold(III) are presented.


Effects of inhibiting protein synthesis on the secretion of surfactant by type II cells in primary culture.
Pulmonary surfactant is isolated from the alveolar lumen as a complex of lipid and protein (King, R.J., Martin, H., Mitts, D. and Holmstrom, F.M. (1977) J. Appl. Physiol. 42, 483-491). We wished to determine whether the secretion of this complex was dependent upon cellular activities associated with the synthesis of protein, and whether the pre-formed lipids of surfactant would be released from the cell even though the synthesis of newly-formed protein was inhibited. Alveolar epithelial Type II cells were isolated from adult rat lung and grown to confluency in primary culture. The synthesis and secretion of the apolipoprotein of surfactant and its principal lipid, dipalmitoyl phosphatidyl-choline, were followed by isotopic precursor techniques. The synthesis of the apolipoprotein was reduced to 14% of control by 1 . 10(-4) M cycloheximide and to 2.5% of control by 4 . 10(-4) M cycloheximide. These concentrations of cycloheximide, however, had no effect on the rate of synthesis or release of DPPC. The secretion of the apolipoprotein which had been synthesized before the addition of 1 . 10(-4) M cycloheximide was not inhibited by this compound. Cells maintained at 5 degrees C neither synthesized nor released surfactant. We conclude, therefore, that the synthesis of cellular protein is not required for the secretion of surfactant, but that the continuous generation of metabolic energy may be essential. These results, together with those of previous kinetic studies (see above references), suggest that the lipid and protein constituents of surfactant may be contained within lamellar bodies prior to their release into the extracellular environment.


Current status and future trends of clinical diagnoses via image-based deep learning.
With the recent developments in deep learning technologies, artificial intelligence (AI) has gradually been transformed from cutting-edge technology into practical applications. AI plays an important role in disease diagnosis and treatment, health management, drug research and development, and precision medicine. Interdisciplinary collaborations will be crucial to develop new AI algorithms for medical applications. In this paper, we review the basic workflow for building an AI model, identify publicly available databases of ocular fundus images, and summarize over 60 papers contributing to the field of AI development.


Limited potential of AAV-mediated gene therapy in transducing human mesenchymal stem cells for bone repair applications.
Adeno-associated viral vectors (AAV) are unique in their ability to transduce a variety of both dividing and nondividing cells, with significantly lower risk of random genomic integration and with no known pathogenicity in humans, but their role in ex vivo regional gene therapy for bone repair has not been definitively established. The goal of this study was to test the ability of AAV vectors carrying the cDNA for BMP-2 to transduce human mesenchymal stem cells (MSCs), produce BMP-2, and induce osteogenesis in vitro as compared with lentiviral gene therapy with a two-step transcriptional amplification system lentiviral vector (LV-TSTA). To this end, we created two AAV vectors (serotypes 2 and 6) expressing the target transgene; eGFP or BMP-2. Transduction of human MSCs isolated from bone marrow (BMSCs) or adipose tissue (ASCs) with AAV2-eGFP and AAV6-eGFP led to low transduction efficiency (BMSCs: 3.57% and 8.82%, respectively, ASCs: 6.17 and 20.2%, respectively) and mean fluorescence intensity as seen with FACS analysis 7 days following transduction, even at MOIs as high as 106. In contrast, strong eGFP expression was detectable in all of the cell types post transduction with LV-TSTA-eGFP. Transduction with BMP-2 producing vectors led to minimal BMP-2 production in AAV-transduced cells 2 and 7 days following transduction. In addition, transduction of ASCs and BMSCs with AAV2-BMP-2 and AAV6-BMP-2 did not enhance their osteogenic potential as seen with an alizarin red assay. In contrast, the LV-TSTA-BMP-2-transduced cells were characterized by an abundant BMP-2 production and induction of the osteogenic phenotype in vitro (p < 0.001 vs. AAV2 and 6). Our results demonstrate that the AAV2 and AAV6 vectors cannot induce a significant transgene expression in human BMSCs and ASCs, even at MOIs as high as 106. The LV-TSTA vector is significantly superior in transducing human MSCs; thus this vector would be preferable when developing an ex vivo regional gene therapy strategy for clinical use in orthopedic surgery applications.


Pd-catalyzed tandem C-N/C-C coupling of gem-dihalovinyl systems: a modular synthesis of 2-substituted indoles.
2-substituted indoles were synthesized via a Pd-catalyzed tandem C-N/Suzuki-Miyaura coupling from readily prepared ortho-gem-dihalovinylanilines. Optimal conditions used a Pd(OAc)(2)/S-Phos catalyst in the presence of K(3)PO(4).H(2)O and an organoboron reagent, which included boronic acids, esters, alkyl 9-BBN derivatives, and trialkylboranes. Yields of the desired indoles were good to excellent using low catalyst loadings (typically 1 mol %). [reaction: see text]


Divergent functional effects of sazetidine-a and varenicline during nicotine withdrawal.
Smoking is the largest preventable cause of death in the United States. Furthermore, a recent study found that <10% of quit attempts resulted in continuous abstinence for 1 year. With the introduction of pharmacotherapies like Chantix (varenicline), a selective α4β2 nicotinic partial agonist, successful quit attempts have significantly increased. Therefore, novel subtype-specific nicotinic drugs, such as sazetidine-A, present a rich area for investigation of therapeutic potential in smoking cessation. The present studies examine the anxiety-related behavioral and functional effects of the nicotinic partial agonists varenicline and sazetidine-A during withdrawal from chronic nicotine in mice. Our studies indicate that ventral hippocampal-specific infusions of sazetidine-A, but not varenicline, are efficacious in reducing nicotine withdrawal-related anxiety-like phenotypes in the novelty-induced hypophagia (NIH) paradigm. To further investigate functional differences between these partial agonists, we utilized voltage-sensitive dye imaging (VSDi) in ventral hippocampal slices to determine the effects of sazetidine-A and varenicline in animals chronically treated with saline, nicotine, or undergoing 24 h withdrawal. These studies demonstrate a functional dissociation of varenicline and sazetidine-A on hippocampal network activity, which is directly related to previous drug exposure. Furthermore, the effects of the nicotinic partial agonists in VSDi assays are significantly correlated with their behavioral effects in the NIH test. These findings highlight the importance of drug history in understanding the mechanisms through which nicotinic compounds may be aiding smoking cessation in individuals experiencing withdrawal-associated anxiety.


Influence of the sickle cell trait on Plasmodium falciparum infectivity from naturally infected gametocyte carriers.
Sickle cell trait (SCT) refers to the carriage of one abnormal copy of the β-globin gene, the HbS allele. SCT offers protection against malaria, controlling parasite density and preventing progression to symptomatic malaria. However, it remains unclear whether SCT also affects transmission stages and mosquito infection parameters. Deciphering the impact of the SCT on human to mosquito malaria transmission is key to understanding mechanisms that maintain the trait in malaria endemic areas. The study was conducted from June to July 2017 among asymptomatic children living in the locality of Mfou, Cameroon. Blood samples were collected from asymptomatic children to perform malaria diagnosis by microscopy, Plasmodium species by PCR and hemoglobin typing by RFLP. Infectiousness of gametocytes to mosquitoes was assessed by membrane feeding assays using blood from gametocyte carriers of HbAA and HbAS genotypes. A zero-inflated model was fitted to predict distribution of oocysts in mosquitoes according to hemoglobin genotype of the gametocyte source. Among the 1557 children enrolled in the study, 314 (20.16%) were of the HbAS genotype. The prevalence of children with P. falciparum gametocytes was 18.47% in HbAS individuals and 13.57% in HbAA, and the difference is significant (χ2 = 4.61, P = 0.032). Multiplicity of infection was lower in HbAS gametocyte carriers (median = 2 genotypes/carrier in HbAS versus 3.5 genotypes/carrier in HbAA, Wilcoxon sum rank test = 188, P = 0.032). Gametocyte densities in the blood donor significantly influenced mosquito infection prevalence in both HbAS and HbAA individuals. The HbAS genotype had no significant effect on mosquito infection outcomes when using immune or naïve serum in feeding assays. In AB replacement feeding experiments, the odds ratio of mosquito infection for HbAA blood as compared to HbAS was 0.56 (95% CI 0.29-1.10), indicating a twice higher risk of infection in mosquitoes fed on gametocyte-containing blood of HbAS genotype. Plasmodium transmission stages were more prevalent in SCT individuals. This may reflect the parasite's enhanced investment in the sexual stage to increase their survival rate when asexual replication is impeded. The public health impact of our results points the need for intensive malaria control interventions in areas with high prevalence of HbAS. The similar infection parameters in feeding experiments where mosquitoes received the original serum from the blood donor indicated that immune responses to gametocyte surface proteins occur in both HbAS and HbAA individuals. The higher risk of infection in mosquitoes fed on HbAS blood depleted of immune factors suggests that changes in the membrane properties in HbAS erythrocytes may impact on the maturation process of gametocytes within circulating red blood cells.


Enhanced incorporation of 3-hydroxy-4-methylvalerate unit into biosynthetic polyhydroxyalkanoate using leucine as a precursor.
Ralstonia eutropha PHB-4 expressing Pseudomonas sp. 61-3 polyhydroxyalkanoate (PHA) synthase 1 (PhaC1Ps) synthesizes PHA copolymer containing 3-hydroxybutyrate (3HB) and a small amount (0.5 mol%) of 3-hydroxy-4-methylvalerate (3H4MV) from fructose as a carbon source. In this study, enhanced incorporation of 3H4MV into PHA was investigated using branched amino acid leucine as a precursor of 3H4MV. Leucine has the same carbon backbone as 3H4MV and is expected to be a natural and self-producible precursor. We found that the incorporation of 3H4MV was enhanced by the supplementation of excess amount (10 g/L) of leucine in the culture medium. This finding indicates that 3H4MV can be derived from leucine. To increase metabolic flux to leucine biosynthesis in the host strain by eliminating the feedback inhibition, the cells were subjected to N-methyl-N'-nitro-N-nitrosoguanidine (NTG) mutagenesis and leucine analog resistant mutants were generated. The mutants showed statistically higher 3H4MV fraction than the parent strain without supplementing leucine. Additionally, by supplying excess amount of leucine, the mutants synthesized 3HB-based PHA copolymer containing 3.1 mol% 3H4MV and 1.2 mol% 3-hydroxyvalerate (3HV) as minor constituents, which significantly affected the thermal properties of the copolymer. This study demonstrates that it is possible to enhance the monomer supply of 3H4MV into PHA by manipulating leucine metabolism.


How should continence and incontinence after radical prostatectomy be evaluated? A prospective study of patient ratings and changes with time.
We examined prevalence rates, and changes in continence and incontinence before and after radical prostatectomy for prostate cancer by comparing different definitions. We also studied the descriptive validity of the grading system of Ellison et al for post-prostatectomy incontinence and baseline predictors of post-prostatectomy incontinence at 12 months. This national prospective study included 844 patients treated with radical prostatectomy between 2005 and 2009. Adverse effects, including urinary dysfunction and bother, were reported by 735 patients (88%) using the EPIC-50 and UCLA-PCI validated questionnaires at baseline and 12-month followup. Linear regression analysis was done to examine baseline predictors and the degree of post-prostatectomy incontinence at followup. At 12 months after radical prostatectomy 74% of patients reported post-prostatectomy incontinence, of whom 40% used pads daily, 34% reported occasional dribbling without pads and 26% had total urinary control. When defined as total incontinence/no urinary control, severe post-prostatectomy incontinence was reported by 3% of the men but 25% had severe post-prostatectomy incontinence according to the stratification of Ellison et al. Of patients with preoperative incontinence 14% improved postoperatively. Predictors of post-prostatectomy incontinence were age 65 years or greater, not working, sexual dysfunction and incontinence preoperatively. The latter 2 remained the strongest predictors on multivariate analysis. Prostate cancer related variables were not associated with post-prostatectomy incontinence. The prevalence of post-prostatectomy incontinence varied considerably according to the definition applied. In our opinion incontinence may be reported as any leakage and not only as pad use with grading done on a symptom scale. Preoperative sexual dysfunction and urinary incontinence were the strongest predictors of post-prostatectomy incontinence at 12-month followup.


Effect of age on decisions about the numbers of embryos to transfer in assisted conception: a prospective study.
Elective single-embryo transfer has been proposed as a strategy to reduce the risk of multiple birth and adverse pregnancy outcomes after in-vitro fertilisation (IVF). Whether this approach should be restricted to young women is unclear. In a prospective study of UK Human Fertilisation and Embryology Authority data, we investigated whether perinatal livebirth outcomes varied by the number of embryos transferred in relation to maternal age. We compared rates of livebirth, multiple births, low birthweight (<2·5 kg), preterm birth (<37 weeks), and severe preterm birth (<33 weeks) in women younger than 40 years and those aged 40 years or older. We used logistic and binomial regression methods to assess, respectively, relative risk and absolute differences in risk. We assessed 124,148 IVF cycles overall, which yielded 33,514 livebirths. The odds ratios of livebirth were higher in women aged 40 years or older than in those younger than 40 years when two embryos were transferred compared with one embryo (3·12, 95% CI 2·58-3·77 [corrected] vs 2·33, 2·20-2·46; p=0·0006 for interaction), but the absolute difference in risk of livebirth was smaller (0·090, 0·080-0·099 for women ≥40 years vs 0·156, 0·148-0·163 for those <40 years; p<0·0001). The odds ratios and absolute risk differences for multiple birth, preterm birth, and low birthweight were all smaller in older than in younger women (analyses were done in 32,732 cycles in which a livebirth had resulted and data on gestational age and birthweight were complete). Livebirth rates did not increase with transfer of three embryos, but the risk of adverse perinatal outcomes did increase. Transfer of three or more embryos at any age should be avoided. The decision to transfer one or two embryos should be based on prognostic indicators, such as age. None.


The productive and reproductive biology of flowering plants X. Reproductive energy allocation and propagule output of five congeners of the genus Setaria (Gramineae).
The energy allocation patterns to reproductive structures (RA) and the propagule output (PN) of five annual weedy or ruderal fox-tail species (Gramineae)-Setaria viridis (2x) (including var. pachystachys (2x)), S. X pycnocoma (2x), S. faberi (4x), S. glauca (4x, 8x), and S. pallide-fusca (8x)-were studied in relation to their biomass on the materials from ten different wild populations in Toyama and Fukui Prefectures, Japan. In addition, the relationship between the RA and PN was also critically examined.For all five fox-tail species, proportional partitioning of dry matter into total reproductive structures (caryopses, bristles, inflorescence axis and other persistent floral organs at the fruiting stage) (RA) shows considerable overlaps, but more or less constant within each taxon and independent of the biomass. On the other hand, the number of propagules produced per plant (PN) is remarkably dependent on the size of plants and thus a function of the biomass. This high efficiency of energy allocation to propagules is evidently determined by the breeding system (i.e., predominant inbreeding) of these weedy annual species. However, the relationship between the RA and PN showed no conspicuous trend, and thus the reproductive output is also independent of RA. The reproductive strategy found in Setaria is perhaps typical in such weedy annuals which grow chiefly in frequently disturbed, unpredictable environments. Another notable discovery was that, in spite of differences in ploidy levels (from 2x to 8x), all five species showed a very similar reproductive strategy, although slight but clear decrease was noted in the RA in response to the increase in ploidy levels, ranging from 49.52% (in diploids) to 27.53% (in tetraploids and octoploids). Seed weight (per gram), on the contrary, clearly increases in response to the increase in ploidy levels, i.e., ranging from 7.09×10-4 g (in diploids) to 41.87×10-4g (in octoploids).


Management of a Primary Retroperitoneal Yolk Sac Tumor.
BACKGROUND Existing literature has detailed occurrences of retroperitoneal yolk sac tumors (YSTs) as the result of metastasis from a primary gonadal site. However, primary retroperitoneal YSTs are extremely rare, thus remaining a challenge to diagnose and treat. We present a complex case of a large primary retroperitoneal YST in a man treated with neoadjuvant chemotherapy followed by surgical resection. CASE REPORT A 31-year-old man presented with a chief symptom of severe lower abdominal pain. Diagnostic imaging revealed a large, rapidly progressing neoplasm in the retroperitoneal region, initially thought to be a sarcoma. However, the pathological results from further biopsies found the mass to be a retroperitoneal YST, which was tethered to a large portion of the small bowel. A testicular ultrasound was used to confirm that the mass was a primary tumor with no origins in the gonads. The tumor progressed to involve several fistulas connected to the small intestine and anterior abdominal wall. The patient was treated with 3 cycles of bleomycin, etoposide, and cisplatin, followed by surgical excision of the residual mass. The patient retained normal gastrointestinal functions, and subsequent imaging revealed no evidence of recurrence 2.5 years following resection. CONCLUSIONS Owing to the rarity of extragonadal primary YSTs, diagnostic and treatment standards have not yet been sufficiently explored. Our case demonstrates that a combination of chemotherapy and surgical resection should be considered for select patients with primary YST in the retroperitoneal region.


Structure of the rotor of the bacterial flagellar motor revealed by electron cryomicroscopy and single-particle image analysis.
The FliF ring is the base for self-assembly of the bacterial flagellum and the FliF/FliG ring complex is the core of the rotor of the flagellar motor. We report the structures of these two ring complexes obtained by electron cryomicroscopy and single-particle image analysis at 22A and 25A resolution, respectively. Direct comparison of these structures with the flagellar basal body made by superimposing the density maps on the central section reveals many interesting features, such as how the mechanically stable connection between the ring and the rod is formed, how directly FliF domains are involved in the near axial density of the basal body forming the proximal end of the central channel for a potential gating mechanism, some indication of flexibility in the connection of FliF and FliG, and structural and functional similarities to the head-to-tail connectors of bacteriophages.


Patient preferences in treatment of erectile dysfunction: the continuing importance of patient education.
Understanding patient preferences can be important in ensuring full benefit is derived from treatment for erectile dysfunction (ED). They seem to be important in determining whether patients continue treatment in the medium and long term. In clinical practice, discontinuation rates beyond a year are relatively high. Factors such as spontaneity, "naturalness", and onset and duration of action may all influence preference. This article discusses a number of studies looking into patient preferences for a particular class of treatment method over another, and also for individual treatments within classes. In general, patients appear to prefer oral treatments to others such as penile implant surgery, vacuum-pump therapy, apomorphine, and intracavernosal injection. In some studies, men have also shown preferences for particular oral phosphodiesterase-5 (PDE5) inhibitors over others. Providing patients with full information on the pros and cons of treatment options can help ensure patients are treated with a therapy that fits more closely with their wishes, and ensure continuation of treatment for optimal efficacy.


Intraoperative control by Schanz-screws is inaccurate to achieve the exact amount of correction in de-rotational osteotomies.
The accuracy of intraoperative control of correction commonly is achieved by K-wires or Schanz-screws in combination with goniometer in de-rotational osteotomies. The purpose of this study is to investigate the accuracy of intraoperative torsional control in de-rotational femoral and tibial osteotomies. It is hypothesized, that intraoperative control by Schanz-screws and goniometer in de-rotational osteotomies around the knee is a safe and well predictable method to control the surgical torsional correction intraoperatively. 55 consecutive osteotomies around the knee joint were registered, 28 femoral and 27 tibial. The indication for osteotomy was femoral or tibial torsional deformity with the clinical occurrence of patellofemoral maltracking or PFI. Pre- and postoperative torsions were measured according to the method of Waidelich on computed tomography (CT) scan. The scheduled value of torsional correction was defined by the surgeon preoperatively. Intraoperative control of torsional correction was achieved by 5 mm-Schanz-screws and goniometer. The measured values of torsional CT scan were compared to the preoperative defined and intended values and deviation was calculated separately for femoral and tibial osteotomies. The surgeon's intraoperative measured mean value of correction in all osteotomies was 15.2° (SD 4.6; range 10-27), whereas the postoperatively measured mean value on CT scan was 15.6 (6.8; 5.0-28.5). Intraoperatively the femoral mean value measured 17.9° (4.9; 10-27) and 12.4° (1.9; 10-15) for the tibia. Postoperatively the mean value for femoral correction was 19.8 (5.5; 9.0-28.5) and 11.3 (5.0; 5.0-26.0) for tibial correction. When considering a deviation of plus or minus 3° to be acceptable femorally 15 osteotomies (53.6%) and tibially 14 osteotomies (51.9%) fell within these limits. Nine femoral cases (32.1.%) were overcorrected, four cases undercorrected (14.3%). Four tibial cases of overcorrection (14.8%) and 9 tibial cases of undercorrection (33.3%) were observed. However, the observed difference between femur and tibia regarding the distribution of cases between the three groups did not reach significance. Moreover, there was no correlation between the extent of correction and the deviation from the intended result. The use of Schanz-screws and goniometer in de-rotational osteotomies as an intraoperative control of correction is an inaccurate method. Every surgeon performing derotational osteotomies must consider this and include postoperative torsional measurement in his postoperative algorithm until new tools or devices are available to guarantee a better intraoperative accuracy of torsional correction. Observational study. III.


Calibration transfer for excitation-emission fluorescence measurements.
The main part of the wide array of different calibration transfer methods found in literature is dedicated to two-way data arrangements (m×n matrices). Less work has been done within the area of calibration transfer for three-way data structures (m×n×l tensors) such as calibrations made for excitation-emission-matrix (EEM) fluorescence spectra. There are two possible ways to attack the problem for EEM transfer. Either the tensors are unfolded to two-way data, whereby the existing methods can be applied, or new methods dedicated to three-way calibration transfer have to be developed. This paper presents and compares both. It was possible to make a local linear pixel-based model that could be used for transfer of EEM's. This new method has a similar performance to the classical methods found in literature, direct- and piecewise direct standardization. The three-way advantages made it possible to use as few as four samples to build useable transfer models. Care has to be taken though when choosing the samples. When subset recalibration of the systems is compared to calibration transfer, better performance is seen for the transferred calibrations. Overall the three-way calibration transfer methods have a slightly better performance than the two-way methods.


The disulfide bond pattern of catrocollastatin C, a disintegrin-like/cysteine-rich protein isolated from Crotalus atrox venom.
The disulfide bond pattern of catrocollastatin-C was determined by N-terminal sequencing and mass spectrometry. The N-terminal disintegrin-like domain is a compact structure including eight disulfide bonds, seven of them in the same pattern as the disintegrin bitistatin. The protein has two extra cysteine residues (XIII and XVI) that form an additional disulfide bond that is characteristically found in the disintegrin-like domains of cellular metalloproteinases (ADAMs) and PIII snake venom Zn-metalloproteinases (SVMPs). The C-terminal cysteine-rich domain of catrocollastatin-C contains five disulfide bonds between nearest-neighbor cysteines and a long range disulfide bridge between CysV and CysX. These results provide structural evidence for a redefinition of the disintegrin-like and cysteine-rich domain boundaries. An evolutionary pathway for ADAMs, PIII, and PII SVMPs based on disulfide bond engineering is also proposed.


Choledochal cyst disease in children and adults: a 30-year single-institution experience.
The reported incidence of choledochal cyst (CC) disease varies greatly based on geography. Most large series on CC originate from East Asia. So our understanding of the presentation and natural history of CC disease in western societies is less well characterized. Recognition and surgical treatment are important because of the significant longterm risks of developing cholangiocarcinoma. We report here the largest single-institution western experience with CC disease. Ninety-two patients with CC disease who were seen at our institution between 1976 and 2006 were included in this study. Potential differences between children and adults (defined as 16 years old or older) were specifically evaluated. There were 19 children and 73 adults; 90% were girls/women with type I cysts. Adults were more likely to present with abdominal pain (97% versus 63%, p < 0.001), and children were more likely to present with jaundice (71% versus 25%, p=0.001). Surgical management most commonly involved cyst excision and Roux-en-Y hepaticojejunostomy reconstruction. Four adults (three with cholangiocarcinoma and one with gall bladder cancer) and one child (with embryonal rhabdomyosarcoma) had malignancies associated with their CC at the time of excision. Two patients (with type IV and type V disease) developed cholangiocarcinoma after surgical management. Another patient died of pancreatic adenocarcinoma 21 years after excision of her type I cyst. There was no operative or hospital mortality, and no patient who underwent complete cyst excision developed cholangiocarcinoma during a mean followup of 10 years. Western CC disease has a similar demographic profile as that seen in Asia. CCs are more frequently found in adults and girls/women and are associated with a longterm risk of developing cholangiocarcinoma. Presentation differs between adults and children. After complete cyst excision, no patients developed cholangiocarcinoma.


Severe Weakness of Hip Flexor after Iliopsoas Tenotomy: Two Case Reports.
Hip arthroscopies are becoming a standard surgical technique, with psoas tenotomy being a relatively common procedure during this operation. A 37-year-old male and a 42-year-old female with internal hip snapping came to our department. Arthroscopic partial psoas tenotomy of the iliopsoas portion of the conjoint tendon was performed, but its results were bad. Patients reported preoperative unilateral low-back pain and weakness when flexing the hip. Unilateral atrophy of the lumbar psoas and fatty multifidus were detected in both cases. Patients at risk of unsatisfactory outcomes after psoas tenotomy should be ideally identified prior to surgery. Warning symptoms, physical examination, and imaging studies should be considered to avoid unsatisfactory results.


Effect of penicillin on nitrite-oxidizing bacteria in activated sludge.
The effects of penicillin G on the number and activity of nitrite-oxidizing bacteria were investigated in laboratory-scale reactors and batch tests. At a concentration of 100 mg L(-1), addition of penicillin G for short periods did not significantly affect nitrite oxidation, while addition for more than 2 months suppressed nitrite oxidation. Fluorescence in situ hybridization with 16S ribosomal RNA-targeted probes revealed a slight decrease in the abundance of Nitrospira, while Nitrobacter was not affected by addition of penicillin G for more than 39 days. The resistance of nitrite-oxidizing bacteria to penicillin appeared to be positively affected by intermittent aeration only when accompanied by denitrification; otherwise, the aeration mode (continuous or intermittent aeration) did not significantly affect the abundance of Nitrobacter and Nitrospira.


Does weight-related stigmatisation and discrimination depend on educational attainment and level of income? A systematic review.
Obesity is considered a global health issue, because of its health-related consequences and also because of its impact on social status as a result of stigma. This study aims to review the quantitative state of research regarding socioeconomic characteristics' influence on weight-related stigmatisation and discrimination. Based on Bourdieu's Theory of Class and his concept of 'habitus', it is assumed that people with a higher level of education and income show stronger negative attitudes towards people with obesity. A narrative systematic literature review was conducted in 2017 using PubMed, PsychINFO, Web of Science and the Cochrane Library. Seventeen studies that measured weight bias and either educational attainment or level of income were included in the analysis. The results of the studies included were inconsistent: six of these studies were found to support the hypothesis, whereas two of the studies contradicted it. The remaining seven studies did not show any significant correlation between weight bias and either education or income. In light of the inconsistent and heterogeneous results of the studies that report a significant association between weight bias and socioeconomic variables, the findings must be discussed concerning their cultural context, that is, cultural and governmental differences. Furthermore, educational attainment seems to be more likely to predict weight bias than income. The review revealed a lack of research when it came to examining the impact of socioeconomic capital on weight bias.


The pharmacological profile of L-glutamate transport in human NT2 neurones is consistent with excitatory amino acid transporter 2.
The human teratocarcinoma cell line NTera2/D1 can be differentiated to produce post-mitotic neurones (NT2-N cells) by prolonged (> 3 week) exposure to retinoic acid. In this study, we describe the characterisation of high-affinity Na+-dependent L-glutamate transport activity in post-mitotic differentiated NT2-N cells. NT2-N cells, but not the undifferentiated precursor cells, transported L-glutamate in a Na+-dependent manner, as determined by equimolar replacement of Na+ with choline. L-glutamate uptake was saturable and Eadie-Hofstee transformation of the saturation data revealed a Km of 10.6+/-0.8 microM, and a maximum transport capacity (Vmax) of 100.3+/-12.3 pmol min(-1) mg(-1) protein. Pharmacological characterisation of the transport activity in NT2-N cells produced a rank order of inhibitory activity which was identical to that determined for the human excitatory amino acid transporter 2 which we have analysed in a stable mammalian cell line (Madin Darby Canine Kidney (MDCK) cells). Of particular note, L-glutamate transport by NT2-N cells was sensitive to both dihydrokainate and kainate. The expression of human excitatory amino acid transporter mRNAs was studied using reverse transcriptase polymerase chain reaction. NT2-N cells expressed transcripts for excitatory amino acid transporters 2 and 3, but not for the subtypes 1, 4 and 5. We conclude that although the mRNA expression studies suggest the presence of transcripts for both excitatory amino acid transporter 2 and 3 in NT2-N cells, the sensitivity to dihydrokainate and kainate determined in the pharmacological analysis indicates that, of the known transporter subtypes, excitatory amino acid transporter 2 contributes to the bulk of the L-glutamate transport activity present in these cells.


Systematic reviews can be produced and published faster.
As part of a larger project on updating systematic reviews, we studied the currency of reviews at the time of publication to determine typical and achievable times to publication for systematic reviews published in journals, Health Technology Assessment technical reports or Cochrane Collaboration reviews, and examined differences in publication speed between these document types. A cohort of systematic reviews of treatment interventions originally published between 1995 and 2005 and indexed in ACP Journal Club was assembled. Dates of search, manuscript submission, acceptance, publication and indexing in MEDLINE were extracted. One hundred fifty-six reviews meet inclusion criteria. The median time from final search to publication was 61 weeks with an interquartile range of 33-87 weeks. Best (first quartile) performances were for the final search updated to occur within 10 weeks of submission, acceptance for publication within 11 weeks of submission, and publication, print or electronic, within 12 weeks of acceptance. Efforts to reduce the time spent in production of systematic reviews can improve currency. Both authors and publishers can contribute to more rapid production of health care evidence syntheses.


Thiazohalostatin, a new cytoprotective substance produced by Actinomadura. I. Taxonomy, production, isolation and biological activities.
Thiazohalostatin has been isolated from the culture broth of Actinomadura sp. by a screening program designed to find novel cytoprotective substances. It was purified by use of column chromatography on silica gel, reversed phase HPLC and then isolated as colorless powder. Thiazohalostatin prevented cell death caused by calcium overload and exhibited an inhibitory activity against lipid peroxidation.


Effect of moisture content, aeration rate, and C/N on maturity and gaseous emissions during kitchen waste rapid composting.
To determine factors affecting compost maturity and gaseous emissions during the rapid composting of kitchen waste, an orthogonal test was conducted with three factors: moisture content (MC) (55%, 60%, 65%), aeration rate (AR) (0.3,0.6 and 0.9 L·kg-1DM·min-1) and C/N ratio (21, 24, 27). The results showed that the importance of factors affecting compost maturity was: C/N > AR > MC, optimal conditions were: C/N of 24, AR of 0.3 L·kg-1DM·min-1and MC of 65%. For gaseous emissions, the sequence of essential factors affecting NH3 emissions was: C/N > MC > AR, and the optimal parameters for NH3 reduction were: C/N of 27, MC of 65%, and AR of L·kg-1DM·min-1. The important factors affecting N2O and H2S emissions are both: MC > C/N > AR, while their best parameters were different. The optimal parameters for N2O emission reduction were MC of 60%, AR of 0.3 L·kg-1DM·min-1 and C/N of 24, while these for H2S were MC of 55%, AR of 0.3 L·kg-1DM·min-1 and C/N of 21. The C/N mainly affected the compost maturity and AR further affected the maturity and pollutant gas emissions by influencing the temperature and O2 content. Considering comprehensively the maturity and gaseous reduction, the optimal control parameters were: MC of 60%-65%, AR of L·kg-1DM·min-1, and C/N of 24-27.


Anatomical and visual outcome after vitrectomy with triamcinolone acedonide-assisted epiretinal membrane removal in highly myopic eyes with retinal detachment due to macular hole.
To determine the effectiveness of staining an epiretinal membrane (ERM) with triamicinolone acedonide (TA) during vitrectomy for a retinal detachment (RD) due to a macular hole (MH) in highly myopic eyes. Thirty-four highly myopic eyes (>-6.0 dioptres) of 34 patients with an RD caused by an MH underwent vitrectomy with TA-assisted ERM removal. The excised ERMs from five eyes were examined by transmission electron microscopy (TEM). The main outcome measures were the retinal status and best-corrected visual acuity (BCVA). The anatomic status of the MH was determined by optic coherence tomography (OCT) in 24 successfully retinal-reattached eyes. The follow-up periods ranged from 5 to 20 months. The granules of TA adhered to the ERM and the residual posterior hyaloid, which made them more visible and facilitated their removal. Tissues resembling the internal limiting membrane were not detected in any of the five excised tissues. The retinal reattachment rate was 88% after the first surgery. The mean log MAR BCVA significantly improved from 1.83+/-0.50 (mean+/-SD) before surgery to 1.22+/-0.35 at the final follow-up (P<0.001, Wilcoxon signed rank test). OCT showed a normal concave appearance in 11 of 24 eyes (46%), but a central neural epithelial defect was present in 13 of 24 eyes (54%). TA facilitates the complete removal of both the ERM and residual posterior hyaloid, thus ensuring high anatomical and visual success rates in highly myopic eyes with an RD due to MH.


Fabrication of Cd(II)-MOF-based ternary photocatalytic composite materials for H2 production via a gel-to-crystal approach.
Cd(II)-MOF-based ternary composite materials of CdS@Cd(II)-MOF@TiO2 were prepared by a unique TiO2 induced gel-to-crystal approach. CdS@Cd(II)-MOF@TiO2 was demonstrated to be a highly active photocatalyst for hydrogen production under visible light based on water photolysis.


A general framework to support cost-efficient survey design choices for the control of soil-transmitted helminths when deploying Kato-Katz thick smear.
To monitor and evaluate soil-transmitted helminth (STH) control programs, the World Health Organization (WHO) recommends screening stools from 250 children, deploying Kato-Katz thick smear (KK). However, it remains unclear whether these recommendations are sufficient to make adequate decisions about stopping preventive chemotherapy (PC) (prevalence of infection <2%) or declaring elimination of STHs as a public health problem (prevalence of moderate-to-heavy intensity (MHI) infections <2%). We developed a simulation framework to determine the effectiveness and cost of survey designs for decision-making in STH control programs, capturing the operational resources to perform surveys, the variation in egg counts across STH species, across schools, between and within individuals, and between repeated smears. Using this framework and a lot quality assurance sampling approach, we determined the most cost-efficient survey designs (number of schools, subjects, stool samples per subject, and smears per stool sample) for decision-making. For all species, employing duplicate KK (sampling 4 to 6 schools and 64 to 70 subjects per school) was the most cost-efficient survey design to assess whether prevalence of any infection intensity was above or under 2%. For prevalence of MHI infections, single KK was the most cost-efficient (sampling 11 to 25 schools and 52 to 84 children per school). KK is valuable for monitoring and evaluation of STH control programs, though we recommend deploying a duplicate KK on a single stool sample to stop PC, and a single KK to declare the elimination of STHs as a public health problem.


Posterior sub-Tenon's triamcinolone injections in the treatment of uveitis.
This is the first study reported in the United Kingdom to investigate the efficacy and safety of posterior, sub-Tenon's triamcinolone acetonide injections in the treatment of posterior and intermediate uveitis. Twenty-eight posterior sub-Tenon's triamcinolone injections (40 mg) were given and the results analysed with a 6 month prospective follow-up in 13 cases. At 6 weeks follow-up, objective improvement in visual acuity occurred in 25 eyes (p < 0.05). Vitreous cellular activity was diminished in 21 eyes (p < 0.05). In most cases improvement was observed within 2 weeks of injection. No patient required repeat triamcinolone injection within 3 months and all patients previously treated with systemic immunosuppression were able to decrease or discontinue this treatment. Complications included transient elevation of intraocular pressure in 4 patients and persistent mild ptosis in 2 patients. We have demonstrated that posterior sub-Tenon's triamcinolone injection significantly decreases cystoid macular oedema, with a corresponding increase in visual acuity, in patients with posterior uveitis. Systemic immunosuppression may be reduced or discontinued with the avoidance of associated systemic side effects, and the technique has a high level of patient acceptability.


Arbovirus-mosquito interactions: RNAi pathway.
Arthropod-borne (arbo) viruses infect hematophagous arthropods (vectors) to maintain virus transmission between vertebrate hosts. The mosquito vector actively controls arbovirus infection to minimize its fitness costs. The RNA interference (RNAi) pathway is the major antiviral response vectors use to restrict arbovirus infections. We know this because depleting RNAi gene products profoundly impacts arbovirus replication, the antiviral RNAi pathway genes undergo positive, diversifying selection and arboviruses have evolved strategies to evade the vector's RNAi responses. The vector's RNAi defense and arbovirus countermeasures lead to an arms race that prevents potential virus-induced fitness costs yet maintains arbovirus infections needed for transmission. This review will discuss the latest findings in RNAi-arbovirus interactions in the model insect (Drosophila melanogaster) and in specific mosquito vectors.


Regulatory elements can be essential for maintaining broad chromatin organization and cell viability.
Increasing evidence shows that promoters and enhancers could be related to 3D chromatin structure, thus affecting cellular functions. Except for their roles in forming canonical chromatin loops, promoters and enhancers have not been well studied regarding the maintenance of broad chromatin organization. Here, we focused on the active promoters/enhancers predicted to form many 3D contacts with other active promoters/enhancers (referred to as hotspots) and identified dozens of loci essential for cell growth and survival through CRISPR screening. We found that the deletion of an essential hotspot could lead to changes in broad chromatin organization and the expression of distal genes. We showed that the essentiality of hotspots does not result from their association with individual genes that are essential for cell viability but rather from their association with multiple dysregulated non-essential genes to synergistically impact cell fitness.


Hepatic arterial infusion chemotherapy following simultaneous metallic stent placement and iodine-125 seed strands for advanced cholangiocarcinoma causing malignant obstructive jaundice: a propensity score matching study.
This study aims to evaluate the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) following the simultaneous placement of self-expandable metallic stent (SEMS) and iodine-125 (125I) seed strands for the management of advanced cholangiocarcinoma (CCA) patients presenting with malignant obstructive jaundice (MOJ). Data from 74 patients with MOJ caused by advanced CCA treated with stent placement with 125I seed strands with or without HAIC between November 2015 and October 2020 were analysed retrospectively. Eighteen patients received 5 sessions of HAIC after SEMS placement with 125I seed strands (HAIC group), and 56 patients only underwent SEMS placement with 125I seed strands and served as controls (control group). HAIC consisted of infusions of gemcitabine (600-1000 mg/m2 given over 30 min) followed by oxaliplatin (60-100 mg/m2 given over 2 h), with an interval of 4 weeks. Propensity score matching (PSM) analysis was used to adjust for differences in the baseline characteristics of the groups (including age, total bilirubin, and serum alanine aminotransferase level). Overall survival (OS), stent patency, and adverse events were compared between the two groups. OS and stent patency were significantly better in patients in the HAIC group than in those in the control group (median survival time: before PSM, 362 vs. 185 days, p = 0.005; after PSM, 357 vs. 183 days, p = 0.012; median duration of stent patency: before PSM, 294 vs. 156 days, p = 0.001; after PSM, 287 vs. 183 days, p = 0.039). All adverse reactions were controllable by temporary symptomatic treatment. Serious complications and treatment-related deaths were not observed. Our preliminary study showed that HAIC following SEMS placement with 125I seed strands is effective and safe for the management of advanced CCA patients presenting with MOJ and could improve stent patency and patient survival.


Intramedullary spinal cord metastasis from endometrioid adenocarcinoma.
Intramedullary spinal cord metastases are rare .The majority of these metastases reportedly spread from lung cancer in the cervical region; however, they have been seen to arise from a variety of other primary sources. Here, we report what is, to the best of our knowledge, the first known case of an intramedullary spinal cord metastatic lesion in the conus region arising from primary endometrioid adenocarcinoma.


Investigation of the subcellular distribution of cyclic-AMP phosphodiesterase in rat hepatocytes, using a rapid immunological procedure for the isolation of plasma membrane.
The distribution of cyclic-AMP phosphodiesterase was investigated in subcellular fractions prepared from homogenates of rat liver or isolated hepatocytes. When measured at 1 mM or 1 microM substrate concentration, approx. 35% or 50%, respectively, of enzyme activity was particulate. The soluble activity appeared to be predominantly a 'high Km' form, whereas the particulate activity had both 'high Km' and 'low Km' components. The recovery of cyclic-AMP phosphodiesterase was measured using 1 microM substrate concentraiton, in plasma membrane-containing fractions prepared either by centrifugation or by the use of specific immunoadsorbents. The recovery of phosphodiesterase was lower than that of marker enzymes for plasma membrane, and comparable with the recovery of markers for intracellular membranes. It was concluded that regulation of both 'high Km' and 'low Km' phosphodiesterase could potentially make a significant contribution to the control of cyclic AMP concentration, even at microM levels, in the liver. the 'low Km' enzyme, for which activation by hormones has been previously described, appears to be located predominantly in intracellular membranes in hepatocytes. The immunological procedure for membrane isolation allowed the rapid preparation of plasma membranes in high yield. Liver cells were incubated with rabbit anti-(rat erythrocyte) serum and homogenized. The antibody-coated membrane fragments were then extracted onto an immunoadsorbent consisting of sheep anti-(rabbit IgG) immunoglobulin covalently bound to aminocellulose. Plasma membrane was obtained in approx. 40% yield within 50 min of homogenizing cells.


Genetic counseling services and development of training programs in Malaysia.
Genetic counseling service is urgently required in developing countries. In Malaysia, the first medical genetic service was introduced in 1994 at one of the main teaching hospitals in Kuala Lumpur. Two decades later, the medical genetic services have improved with the availability of genetic counseling, genetic testing and diagnosis, for both paediatric conditions and adult-onset inherited conditions, at four main centers of medical genetic services in Malaysia. Prenatal diagnosis services and assisted reproductive technologies are available at tertiary centres and private medical facilities. Positive developments include governmental recognition of Clinical Genetics as a subspecialty, increased funding for genetics services, development of medical ethics guidelines, and establishment of support groups. However, the country lacked qualified genetic counselors. Proposals were presented to policy-makers to develop genetic counseling courses. Challenges encountered included limited resources and public awareness, ethical dilemmas such as religious and social issues and inadequate genetic health professionals especially genetic counselors.


Buying time: Drug repurposing to treat the host in COVID-19H.
In 2016 Fedson stated …. "For almost two decades, leading scientists and health officials have warned that we must prepare for a potentially devastating global pandemic of an infectious disease. Initial concern was focused on …H5N1…. More recently…a devastating outbreak of Ebola virus..(and) several other emerging viruses are believed to seriously threaten global health and global security. To prepare, scientists have been urged to discover new vaccines and treatments for these emerging viruses. At the same time, political leaders have been urged by global health experts to invest millions in a "top down" restructuring of the global health system. This article takes a different view. It focuses on an alternative approach to the scientific discovery of treatments for individual patients, reviews the mechanisms of action and clinical experience with specific drugs that might be useful, and considers whether or not recent lessons regarding this "bottom up" approach to treatment have been learned". Now with a new virus and pandemic upon us, Fedson's 2016 comments appear chilling, are cause for reflection on what we have learnt and importantly offer focus on an immediate opportunity in the area of treating the host (Fedson DS, Ann Transl Med, 2016;4:421).


Acinar cell responsiveness to urecholine in the rat pancreas during fetal and early postnatal growth.
These studies were performed to determine when, during fetal or postnatal life, rat pancreatic acinar cells acquire their capacity to respond to cholinergic drugs. The release of amylase, lipase, and chymotrypsin from rat pancreas in response to urecholine was measured in vitro. Fetal and newborn pancreas did not respond to 10(-5) M urecholine; 3-day- to 15-day-old pancreas demonstrated an increasing response to this dose. Peak sensitivity when compared to adult pancreas was present between days 15 and 21. Our results indicate that the exocrine pancreas acquired a responsiveness to urecholine on the 3rd day of postnatal life and becomes more sensitive to stimulation from the 15th day.


Inclusion body myositis in a patient with chronic myeloid leukemia treated with dasatinib: a case report.
Chronic myelogenous leukemia is often treated using tyrosine kinase inhibitors such as dasatinib. Here we describe a rare case of inflammatory myopathy in a patient with chronic myelogenous leukemia treated with the tyrosine kinase inhibitor dasatinib. A 69-year-old Caucasian man with imatinib-resistant chronic myelogenous leukemia achieved complete molecular remission in response to dasatinib therapy. However, from a normal initial serum creatine kinase level, he developed elevated serum creatine kinase levels and gradual-onset progressive muscle weakness after dasatinib therapy was initiated. Our patient was eventually diagnosed with inclusion body myositis. However, we were unable to determine the mechanism underlying the dasatinib-associated muscle weakness. Given the efficacy of dasatinib in the treatment of chronic myelogenous leukemia and our patient's mild symptoms of inclusion body myositis, he continued to receive dasatinib under close clinical and laboratory observation. Despite the wide use of dasatinib and its documented safety, we report a case of severe muscle injury of unknown etiology. Therefore, patients with chronic myelogenous leukemia receiving dasatinib and perhaps all tyrosine kinase inhibitors should be carefully monitored for signs of muscle injury, especially if this is associated with significant elevations in serum creatine kinase levels.


Genetic lineage tracing identifies in situ Kit-expressing cardiomyocytes.
Cardiac cells marked by c-Kit or Kit, dubbed cardiac stem cells (CSCs), are in clinical trials to investigate their ability to stimulate cardiac regeneration and repair. These studies were initially motivated by the purported cardiogenic activity of these cells. Recent lineage tracing studies using Kit promoter to drive expression of the inducible Cre recombinase showed that these CSCs had highly limited cardiogenic activity, inadequate to support efficient cardiac repair. Here we reassess the lineage tracing data by investigating the identity of cells immediately after Cre labeling. Our instant lineage tracing approach identifies Kit-expressing cardiomyocytes, which are labeled immediately after tamoxifen induction. In combination with long-term lineage tracing experiments, these data reveal that the large majority of long-term labeled cardiomyocytes are pre-existing Kit-expressing cardiomyocytes rather than cardiomyocytes formed de novo from CSCs. This study presents a new interpretation for the contribution of Kit(+) cells to cardiomyocytes and shows that Kit genetic lineage tracing over-estimates the cardiogenic activity of Kit(+) CSCs.


From electronic health records to terminology base: A novel knowledge base enrichment approach.
Enriching terminology base (TB) is an important and continuous process, since formal term can be renamed and new term alias emerges all the time. As a potential supplementary for TB enrichment, electronic health record (EHR) is a fundamental source for clinical research and practise. The task to align the set of external terms in EHRs to TB can be regarded as entity alignment without structure information. Conventional approaches mainly use internal structural information of multiple knowledge bases (KBs) to map entities and their counterparts among KBs. However, the external terms in EHRs are independent clinical terms, which lack of interrelations. To achieve entity alignment in this case, we proposed a novel automatic TB enrichment approach, named semantic & structure embeddings-based relevancy prediction (S2ERP). To obtain the semantic embedding of external terms, we fed them with formal entity into a pre-trained language model. Meanwhile, a graph convolutional network was used to obtain the structure embeddings of the synonyms and hyponyms in TB. Afterwards, S2ERP combines both embeddings to measure the relevancy. Experimental results on clinical indicator TB, collected from 38 top-class hospitals of Shanghai Hospital Development Center, showed that the proposed approach outperforms baseline methods by 14.16% in Hits@1.


Analysis of bacterial community during the fermentation of pulque, a traditional Mexican alcoholic beverage, using a polyphasic approach.
In this study, the characterization of the bacterial community present during the fermentation of pulque, a traditional Mexican alcoholic beverage from maguey (Agave), was determined for the first time by a polyphasic approach in which both culture and non-culture dependent methods were utilized. The work included the isolation of lactic acid bacteria (LAB), aerobic mesophiles, and 16S rDNA clone libraries from total DNA extracted from the maguey sap (aguamiel) used as substrate, after inoculation with a sample of previously produced pulque and followed by 6-h fermentation. Microbiological diversity results were correlated with fermentation process parameters such as sucrose, glucose, fructose and fermentation product concentrations. In addition, medium rheological behavior analysis and scanning electron microscopy in aguamiel and during pulque fermentation were also performed. Our results showed that both culture and non-culture dependent approaches allowed the detection of several new and previously reported species within the alpha-, gamma-Proteobacteria and Firmicutes. Bacteria diversity in aguamiel was composed by the heterofermentative Leuconostoc citreum, L. mesenteroides, L. kimchi, the gamma-Proteobacteria Erwinia rhapontici, Enterobacter spp. and Acinetobacter radioresistens. Inoculation with previously fermented pulque incorporated to the system microbiota, homofermentative lactobacilli related to Lactobacillus acidophilus, several alpha-Proteobacteria such as Zymomonas mobilis and Acetobacter malorum, other gamma-Proteobacteria and an important amount of yeasts, creating a starting metabolic diversity composed by homofermentative and heterofermentative LAB, acetic and ethanol producing microorganisms. At the end of the fermentation process, the bacterial diversity was mainly composed by the homofermentative Lactobacillus acidophilus, the heterofermentative L. mesenteroides, Lactococcus lactis subsp. lactis and the alpha-Proteobacteria A. malorum. After a 6-h fermentation, 83.27% of total sugars detected after inoculation were consumed (228.4 mM hexose equivalents) and a carbon (C) recovery of 66.18% in fermentation products was estimated. They were produced 284.4 mM C as ethanol, 71.5 mM C as acetic acid and 19 mM C as lactic acid, demonstrating the presence of homo- and heterofermentative, acetic and alcoholic metabolisms in the final product. It was also found, after hydrolysis, that the exopolysaccharide produced during the fermentation was mainly composed by fructose residues, probably inulin or levan.


The outcomes of using high oxygen concentration in pediatric patients.
Oxygen reserve index, available as part of Masimo Rainbow SET pulse oximetry, is a noninvasive and continuous variable intended to provide insight into a patient's oxygen status in the moderate hyperoxic range (PaO2 > 100 and ≤ 200 mm Hg), defined as a patient's oxygen "reserve". When used in conjunction with pulse oximetry, ORi extends the knowledge on a patient's oxygen status providing clinically important information helping to prevent hyperoxemia and hypoxemia. There are limited data on patients undergoing craniosynostosis surgery. Our primary goal was to evaluate the effects of different concentrations of inspiratory oxygen (FiO2) on patient oxygenation status by monitoring ORi. Thirty patients scheduled for craniosynostosis were included in this observational cohort study. Patients were randomized into two equal groups: Group 1 received a fraction of inspired oxygen of 0.8 and group 2 received a FiO2 of 0.6 during induction of anaesthesia. In addition to standard haemodynamic variables with ORi were recorded at baseline 1 min, 5 min, 60 min, and 120 min after intubation. Postoperative complications, length of stay in the intensive care unit and hospital were recorded. In total, 14 patients were evaluated in each group. Gender, age, BMI, ASA scores were similar between groups (p > 0.05). In Group 1, ORi values were significantly higher when compared to group 2 at baseline (0.86 ± 0.21 vs 0.45 ± 0.32, p = 0.001), one minute (0.61 ± 0.24 vs 0.27 ± 0.21, p = 0.001), and 5 min (0.34 ± 0.31 vs 0.10 ± 0.13, p = 0.033). High inspired oxygen concentration during induction of anesthesia in pediatric patients is associated with higher levels of ORi. Therefore, ORi may provide the means to safely reduce the inspired oxygen fraction during inhalational induction in paediatric patients.


Full calcium jacket: Conservative management of a traumatic aortic injury.
We describe the case of an elderly male patient who presented with a proximal descending aortic aneurysm after a motorcycle accident in 1977. We concluded that the aorta had been transected at that time. In a rather unconventional manner, the aneurysm developed a circumferential layer of calcification that provided mechanical stability and likely prevented further degeneration. We chose not to pursue surgical intervention at the late stage of his presentation. The patient has been followed up for a period of 30 years, with no change in the size and shape of the now completely calcified aneurysm.


Cancer stem cells: The adventurous journey from hematopoietic to leukemic stem cells.
This year's Gairdner Foundation Award for Biomedical Research is awarded to John Dick for the discovery of leukemic stem cells and the hierarchical organization of acute myeloid leukemias. His work laid the foundation for the cancer stem cell model with numerous clinical implications for hematopoietic malignancies and solid tumors.


Complications of Anterior Cervical Discectomy and Fusion.
Anterior cervical discectomy and fusion (ACDF) is the most common surgery performed on the cervical spine, and the number of its cases has tripled over the last two decades. Although this intervention is typically safe and effective, it carries an inherent complication risk, which should not be underestimated. Improvements in surgical techniques and advances in interbody fusion devices and plating systems have certainly reduced the rate of postoperative morbidity, but despite such progress, surgeons need to beware consistently of the potential complications, inform the patient of their possibility, and have a management strategy as they develop. This review discusses postoperative morbidity encountered in recently reported large studies on ACDF and highlights the senior author's own single-surgeon experience with 2579 such procedures performed between 1998 and 2017. In his clinical series, which is the largest one reported to date, the overall complication rate was 7.0% (180 cases), and dysphagia (1.9% of cases), graft/hardware failures (1.3% of cases), and postoperative hematomas (0.9% of cases) were noted most frequently. Understanding of the risk and clinical impact of complications after ACDF is very important and every effort should be put on their possible avoidance and on appropriate management when they do occur.


[Seroepidemiological aspects of onchocerciasis in Liberia, West Africa (author's transl)].
Sera of 1292 persons were examined for their antibodies to onchocercal antigen. The results were correlated with epidemiological data and microfilarial rates. They show that demonstration of antibodies is suitable for epidermiological studies although the frequency of antibodies does not increase in that degree like age and endemicity.


Intracranial calcification and seizures: a case of central neurofibromatosis.
Periventricular calcification was found in an eight-year-old boy with seizures. The diagnosis of tuberous sclerosis was considered, but (like his mother) he has central neurofibromatosis. This condition must be considered in the differential diagnosis of children with intracranial calcification and seizures.


Biotransformation of Acetaminophen by intact cells and crude enzymes of bacteria: A comparative study and modelling.
Acetaminophen (APAP), which is an active ingredient of many analgesic drugs, is one of the contaminants of emerging concern in the environment. Although APAP is biodegradable, it is frequently detected in treatment plant effluents, surface water and soil suggesting that there are factors affecting the fate of APAP in the environment. In this study, four strains of bacteria that can degrade APAP were isolated from soil. Those strains belonged to Rhodococcus, Pseudomonas, Flavobacterium, and Sphingobium genera of Bacteria. A series of kinetic experiments were performed on the isolates in shake-flasks to determine biodegradation rate constant as well as the effect of temperature, APAP concentration and cell density on the biodegradation rates. APAP biodegradation follows the first order reaction kinetics which is coupled with cell growth. The specific APAP biodegradation rate constant (k) for all strains was similar and equal to 0.19 ± 0.01 h-1. The temperature, at which APAP biodegradation rate was maximum, was 35 °C. APAP biodegradation rate was linearly correlated with both the initial APAP concentration and the cell density. Initial step of the APAP biodegradation was hydrolysis of the amide bond which resulted in formation and accumulation of p-aminophenol suggesting that aryl acylamidase enzyme is responsible for the biotransformation. In addition, free and immobilized crude enzymes of the isolates transformed APAP at similar rates, comparable to the intact cells. This study showed that APAP biodegradation is achieved by a diverse group of bacteria having a similar enzyme operating at a constant kinetics which is very slow at environmentally relevant APAP concentrations. Natural removal of APAP in the environment is limited by kinetics, therefore APAP-bearing waste streams should be treated in adsorption enhanced biological systems before discharged into the environment.


Determination of professional job burnout and temperament (Mizaj) from the viewpoint of Traditional Persian Medicine and work-related variables among Iranian dentists: a cross-sectional study.
Dentists are prone to professional burnout due to the nature of their work but this phenomenon could be prevented. Professional burnout has a great impact on different aspects of human life. No study has been published on determination of professional job burnout and temperament (Mizaj) from the viewpoint of Traditional Persian Medicine (TPM). The current study intends to touch upon this issue for the first time. In order to conduct this Cross-Sectional study based on a randomized sampling method, 145 dentists completed the 22-item Maslach Burnout Inventory questionnaires (MBI), and the 20-item Salmannejad Mizaj questionnaire. The study started since February, 2020 and ended in August, 2020 in Yazd, Iran. A total of 120 valid questionnaires were collected, with a response rate of 82.76%. Data analysis was performed using descriptive statistics, mean and standard deviation, analytical tests (including student t-test, one-way analysis of variance) by Spss17 (Chicago, USA) software. Overall, 8.3% of responders had high emotional exhaustion, while 65.8% and 33.3% had moderate depersonalization and reduced personal accomplishment, respectively. With respect to the results, dentists with cold and dry temperaments experienced a higher level of burnout in emotional exhaustion while dentists with warm and wet temperaments had a higher level of burnout in depersonalization and reduced personal accomplishment dimensions. There was an insignificant difference between age, gender, work experience, number of working days per week, number of patients per day with the dimensions of burnout. Pearson correlation coefficient indicated there was a positive correlation between avoidance job and emotional exhaustion (r = - 0.22, p = 0.016). Based on the findings, it may conclude there was no significant difference in professional burnout between different temperaments among dentists.


'Health is wealth and wealth is health'--perceptions of health and ill-health among female sex workers in Savannakhet, Laos.
Female sex workers (FSWs) are vulnerable to sexually transmitted infections (STIs) and other types of health problems and they also encounter socio-economic difficulties. Efforts to develop effective health intervention programs for FSWs have been hampered by a lack of information on why FSWs do not seek or delay seeking treatment for STIs. To further understand their reasons, our study applied a qualitative approach to explore perceptions of health and ill-health among FSWs in Savannakhet province in Laos. Fifteen in-depth interviews were conducted with FSWs in Savannakhet province. Latent content analysis was used for analysis. Sex workers' definitions of health and wealth are intertwined. Thus, good health was described as strongly related to wealth, and wealth was needed in order to be healthy. This is explained in two sub-themes: health is necessary for work and income and ill-health creates social and economic vulnerability. Female sex workers' beliefs and perceptions about health and ill-health were dominated by their economic need, which in turn was influenced by expectations and demands from their families.


Impact of the introduction of a combined Haemophilus B conjugate vaccine and hepatitis B recombinant vaccine on vaccine coverage rats in a large West Coast health maintenance organization.
We evaluated the effect of introduction of a combined hepatitis B-Haemophilus influenzae b vaccine on vaccine coverage rates in a large health maintenance organization and found a modest improvement in up-to-date immunization status.


The effects of Rhodopseudomonas palustris PSB06 and CGA009 with different agricultural applications on rice growth and rhizosphere bacterial communities.
In recent years, the photosynthetic bacteria have been used widely in agriculture, but the effects of different agricultural applications on crop rhizosphere microorganism and crops are lack. In this study, we provide new insights into the structure and composition of the rice root-associated microbiomes as well as the effect on crop of the Rhodopseudomonas palustris(R. palustris) PSB06 and CGA009 at the rice seedling stage with seed immersion and root irrigation. Compare with CK group, the length of stem, the peroxidase (POD), and superoxide dismutase (SOD) activities in PSB06 treatment group was significantly higher, while the length of stem in CGA009 treatment group was significantly higher. The POD and SOD activities in CGA009 treatment groups only were higher slightly than the CK group. In the study, the dominant phyla were Proteobacteria (51.95-61.66%), Bacteroidetes (5.40-9.39%), Acidobacteria (4.50-10.52%), Actinobacteria (5.06-8.14%), Planctomycetes (2.90-4.48%), Chloroflexi (2.23-5.06%) and Firmicutes (2.38-7.30%), accounted for 87% bacterial sequences. The principal coordinate analysis (pCoA) and mantel results showed the two application actions of R. palustris CGA009 and PSB06 had significant effects on rice rhizosphere bacterial communities (p < 0.05). The PSB06 can significantly promote the rice growth and enhance stress resistance of rice at the seedling stage, while the R. palustris CGA009 has no significant effect on rice. Dissimilarity test and canonical correspondence analysis (CCA) results showed that the TN and pH were the key factors affecting rice rhizosphere bacterial community in the seedling stage. This study will provide some guidance advices for the study of the microecological regulation of photosynthetic bacteria on crops.


Correlation of CD4 counts and CD4/CD8 ratio with HIV-infection associated oral manifestations.
The relationship between oral lesions arising from HIV infection and CD4/CD8 cell ratios is of relevance in clinical assessment of immune suppression. To correlate the prevalence of oral manifestations arising from HIV infection and the levels of CD4/CD8 cell ratios. A cross-sectional study. Kenyatta National Hospital, Nairobi, Kenya. Two hundred and seven HIV-infected patients in medical wards were recruited in the study. Seventy eight (37.7%) were male and 129 (62.3%) female, with an age range of 18-73 years (mean=34.81 years). Oral manifestations encountered with highest prevalence in the oral cavity included: hyperplastic candidosis (labial mucosa) 15%, erythematous candidosis (gingival) 5%, angular cheilitis 32.4%, herpes simplex (corner of the mouth) 0.5%, persistent oral ulceration (labial mucosa) 0.5%, Parotid enlargement 2% and Kaposis sarcoma (hard/soft palate) 2.9%. The prevalence of oral manifestations was higher with low CD4 count <200 cell/mm3 and mean CD4/CD8<0.39(95%CI 0.32-0.48).


Models, mechanisms and clinical evidence for cancer dormancy.
Patients with cancer can develop recurrent metastatic disease with latency periods that range from years even to decades. This pause can be explained by cancer dormancy, a stage in cancer progression in which residual disease is present but remains asymptomatic. Cancer dormancy is poorly understood, resulting in major shortcomings in our understanding of the full complexity of the disease. Here, I review experimental and clinical evidence that supports the existence of various mechanisms of cancer dormancy including angiogenic dormancy, cellular dormancy (G0-G1 arrest) and immunosurveillance. The advances in this field provide an emerging picture of how cancer dormancy can ensue and how it could be therapeutically targeted.


Long-term renal function after hemopoietic stem cell transplantation in children.
Glomerular function of all long-term survivors who underwent hemopoietic stem cell transplantation (HSCT) from 1991 to 1998 (study I, n=121) was studied retrospectively. In addition, we prospectively analyzed glomerular and tubular function of all long-term surviving children who received an HSCT between 1998 and 2000 (study II, n=41). We found a lower prevalence of children with chronic renal failure (CRF) post-HSCT in our more recent cohort (study II: 10%) as compared to the older cohort (study I: 24%) 5.0 (0.7 s.d.) and 7.6 (2.4 s.d.) year's post-HSCT, respectively. Furthermore, it seems that renal function may stabilize after 1-year post-HSCT. None of the patients required dialysis or antihypertensive medication at long-term follow-up. The sole predictor of CRF in our study was high serum creatinine pre-HSCT (P=0.007), while acute renal failure within 3 months after HSCT (P=0.08) only showed a trend towards predicting CRF. We could not confirm a relation of conditioning with irradiation with CRF post-HSCT, as was shown in several other pediatric and adult studies. Proximal and distal tubular dysfunction only occurred in a minority of long-time survivors of HSCT (3-12 and 9-13%, respectively) and had no clinical consequences.


How to limit the burden of data collection for Quality Indicators based on medical records? The COMPAQH experience.
Our objective was to limit the burden of data collection for Quality Indicators (QIs) based on medical records. The study was supervised by the COMPAQH project. Four QIs based on medical records were tested: medical record conformity; traceability of pain assessment; screening for nutritional disorders; time elapsed before sending copy of discharge letter to the general practitioner. Data were collected by 6 Clinical Research Assistants (CRAs) in a panel of 36 volunteer hospitals and analyzed by COMPAQH. To limit the burden of data collection, we used the same sample of medical records for all 4 QIs, limited sample size to 80 medical records, and built a composite score of only 10 items to assess medical record completeness. We assessed QI feasibility by completing a grid of 19 potential problems and evaluating time spent. We assessed reliability (kappa coefficient) as well as internal consistency (Cronbach alpha coefficient) in an inter-observer study, and discriminatory power by analysing QI variability among hospitals. Overall, 23 115 data items were collected for the 4 QIs and analyzed. The average time spent on data collection was 8.5 days per hospital. The most common feasibility problem was misunderstanding of the item by hospital staff. QI reliability was good (kappa: 0.59-0.97 according to QI). The hospitals differed widely in their ability to meet the quality criteria (mean value: 19-85%). These 4 QIs based on medical records can be used to compare the quality of record keeping among hospitals while limiting the burden of data collection, and can therefore be used for benchmarking purposes. The French National Health Directorate has included them in the new 2009 version of the accreditation procedure for healthcare organizations.


Methyl 2-(3-chloro-2-methyl-anilino)pyridine-3-carboxyl-ate.
The title compound, C14H13ClN2O2, was obtained during an attempt to grow single crystals of 4-acetyl-phenyl 2-[(3-chloro-2-methyl-phen-yl)amino]-nicotinate in methanol, and was probably generated by alcoholysis. Two intra-molecular hydrogen bonds are formed, one between the N-H group and the carbonyl O atom of the ester and the other between the ortho sp 2CH group of the benzene ring and the pyridine N atom. Aromatic π-π stacking [shortest centroid-centroid separation = 3.598 (2) Å] is observed in the extended structure.


Application of essential oils in packaging films for the preservation of fruits and vegetables: A review.
Fruits and vegetables are highly perishable in nature. Several factors could affect the quality and shelf life of fruits and vegetables. Packaging materials (usually made up of polymers, proteins, lipids, polysaccharides, etc.,) are incorporated with essential oil (EO) which is high in antimicrobial and antioxidant compounds that can enhance the shelf life of fruits and vegetables without affecting their quality. However, the use of EO for postharvest preservation can alter the organoleptic properties of fresh produce. Exploiting synergistic interactions between several EOs, encapsulation of EO, or combining EO with non-thermal techniques such as irradiation, UV-C, cold plasma, ultrasound, etc., may help in preventing the spoilage of food products at lower concentrations without altering their organoleptic properties. This review aims to discuss the overview and current scenario of packaging film with EO for the preservation of fruit and vegetables. We have also discussed the spoilage mechanism of fruits and vegetables, mode of action of EOs, and the effect of EO with packaging film on antimicrobial and sensory properties of fruits and vegetables.


[Factors determining the subjective closeness of vowel-like stimuli].
Conditions for two formants combined into one spectral cue or giving rise to two spectral cues were studied by psychoacoustical methods. Critical distance between formant frequencies corresponding to perceptual separation of the formants was measured. Interdependence between the formant amplitudes and the equivalent frequency was revealed for stimuli with closely spaced formants. For stimuli with widely spaced formants formant amplitudes appeared to be unimportant for vowel quality.


[Bilateral shortening of the m. rectus femoris due to complications after injection].
A case of bilateral shortening of the muscle rectus femoris--developed as complication of the injection--is reported. The mechanisms of the development of the alteration and the examination method are described. The possibility of the prevention of the extension knee constractures--developing as complication of the injection--is similarly discussed.


Erratum: Progression Of Physical Inactivity In COPD Patients: The Effect Of Time And Climate Conditions - A Multicenter Prospective Cohort Study [Corrigendum].
[This corrects the article DOI: 10.2147/COPD.S208826.].


Steroidogenic Factor-1 Lineage Origin of Skin Lesions in Carney Complex Syndrome.
Carney complex is a rare familial multineoplastic syndrome predisposing to endocrine and nonendocrine tumors due to inactivating mutations of PRKAR1A, leading to perturbations of the cAMP‒protein kinase A signaling pathway. Skin lesions are the most common manifestation of Carney complex, including lentigines, blue nevi, and cutaneous myxomas in unusual locations such as oral and genital mucosa. Unlike endocrine disorders, the pathogenesis of skin lesions remains unexplained. In this study, we show that embryonic invalidation of the Prkar1a gene in steroidogenic factor-1‒expressing cells leads to the development of familial skin pigmentation alterations, reminiscent of those in patients with Carney complex. Immunohistological and molecular analyses, coupled with genetic monitoring of recombinant cell lineages in mouse skin, suggest that familial lentiginosis and myxomas occur in skin areas specifically enriched in dermal melanocytes. In lentigines- and blue nevi‒prone areas from mutant mice and patients, Prkar1a/PRKAR1A invalidation occurs in a subset of dermal fibroblasts capable of inducing, under the influence of protein kinase A signaling, the production of promelanogenic EDN3 and hepatocyte GF signals. Our model strongly suggests that the origin of the typical Carney complex cutaneous lesions is the result of noncell-autonomous promelanogenic activity of a dermal fibroblast population sharing a community of origin with steroidogenic factor-1 lineage.


The calcium hypothesis and modulation of transmitter release by hyperpolarizing pulses.
Small presynaptic conditioning hyperpolarizing pulses reduce transmitter release to a depolarizing stimulus by a substantial amount, with little effect on release by a subsequent depolarization. This result, obtained at neuromuscular junctions and the squid giant synapse, has been offered as a disproof of the calcium hypothesis of transmitter release or the residual calcium hypothesis of synaptic facilitation. However, calculations based on several formulations of these hypotheses are shown to be consistent with the experimental results, and no fundamental modification of the hypotheses is necessary.


Contrast-enhanced proton radiographic sensitivity limits for tumor detection.
Purpose: Proton radiography may guide proton therapy cancer treatments with beam's-eye-view anatomical images and a proton-based estimation of proton stopping power. However, without contrast enhancement, proton radiography will not be able to distinguish tumor from tissue. To provide this contrast, functionalized, high- Z nanoparticles that specifically target a tumor could be injected into a patient before imaging. We conducted this study to understand the ability of gold, as a high- Z , biologically compatible tracer, to differentiate tumors from surrounding tissue. Approach: Acrylic and gold phantoms simulate a tumor tagged with gold nanoparticles (AuNPs). Calculations correlate a given thickness of gold to levels of tumor AuNP uptake reported in the literature. An identity, × 3 , and × 7 proton magnifying lens acquired lens-refocused proton radiographs at the 800-MeV LANSCE proton beam. The effects of gold in the phantoms, in terms of percent density change, were observed as changes in measured transmission. Variable areal densities of acrylic modeled the thickness of the human body. Results: A 1 - μ m -thick gold strip was discernible within 1 cm of acrylic, an areal density change of 0.2%. Behind 20 cm of acrylic, a 40 - μ m gold strip was visible. A 1-cm-diameter tumor tagged with 1 × 10 5 50-nm AuNPs per cell has an amount of contrast agent embedded within it that is equivalent to a 65 - μ m thickness of gold, an areal density change of 0.63% in a tissue thickness of 20 cm, which is expected to be visible in a typical proton radiograph. Conclusions: We indicate that AuNP-enhanced proton radiography might be a feasible technology to provide image-guidance to proton therapy, potentially reducing off-target effects and sparing nearby tissue. These data can be used to develop treatment plans and clinical applications can be derived from the simulations.


The efficacy of atypical antipsychotics in bipolar disorders.
Current treatment options for patients with bipolar spectrum disorders are expanding. New evidence in the treatment of various phases of illness of bipolar disorder is emerging. Atypical antipsychotic medications, used as monotherapy or as adjunctive therapy with mood stabilizers, have shown efficacy as well as well-tolerated side effect profiles, thus becoming valuable new resources in the treatment of bipolar disorder.


MicroRNAs in hematological malignancies.
MicroRNAs (miRNAs) have become one of the hottest topics in biology over recent years, but remarkably have only been formally recognized for just over 10 years. These endogenously produced short (19-24 nt) non-coding RNAs have introduced an entirely new paradigm in our understanding of gene control and it is now evident that miRNAs play a crucial regulatory role in many, if not all, physiological and pathological processes. In this review we provide an overview of the role and potential clinical utility for miRNAs in hematological malignancies and their function in normal hematopoiesis. Although still in its infancy, the miRNA field has already added much to our understanding of hematological processes, and provides us with novel tools as both biomarkers and therapeutic agents for hematological malignancies.


Nurses' knowledge and implementation of antimicrobial stewardship and infection prevention strategies in acute paediatric settings.
Nurses are the first point of contact for patients and are responsible for monitoring and reporting signs of infection. The COVID-19 pandemic cemented nurses' leadership role in infection prevention. Despite this, nurses' contribution to antimicrobial stewardship initiatives remains under-recognized. To determine how paediatric nurses understood their role and contribution to antimicrobial stewardship and infection prevention and control practices in three different acute paediatric wards. Forty-three nurses were recruited from an adolescent ward, an oncology ward, and a surgical ward in a metropolitan tertiary children's hospital for a qualitative exploratory descriptive study. Thematic and content analysis derived three themes from the data: understanding of preventable infections; embracing evidence-based guidelines to protect the patient; and roles in preventing and controlling infections and antimicrobial stewardship. Associated subthemes were: desensitized to COVID-19; understanding infection prevention and control precautions; correct use of hospital policy and guidelines; restrictions associated with the use of electronic medical records; understanding of sepsis management and the importance of timely microbiological testing; ambivalence on antimicrobial stewardship roles; and high priority placed on consumer education. Nurses' understanding of their role focused on practices such as performing hand hygiene, standard precautions, and reporting the use of high-risk antimicrobials. A lack of understanding of paediatric COVID-19 transmission and presentations was also reported. Education on best practice in infection prevention and AMS was recognized as crucial for both nurses and parents.