Regulatory changes associated with the head to trunk developmental transition.
Development of vertebrate embryos is characterized by early formation of the anterior tissues followed by the sequential extension of the axis at their posterior end to build the trunk and tail structures, first by the activity of the primitive streak and then of the tail bud. Embryological, molecular and genetic data indicate that head and trunk development are significantly different, suggesting that the transition into the trunk formation stage involves major changes in regulatory gene networks. We explored those regulatory changes by generating differential interaction networks and chromatin accessibility profiles from the posterior epiblast region of mouse embryos at embryonic day (E)7.5 and E8.5. We observed changes in various cell processes, including several signaling pathways, ubiquitination machinery, ion dynamics and metabolic processes involving lipids that could contribute to the functional switch in the progenitor region of the embryo. We further explored the functional impact of changes observed in Wnt signaling associated processes, revealing a switch in the functional relevance of Wnt molecule palmitoleoylation, essential during gastrulation but becoming differentially required for the control of axial extension and progenitor differentiation processes during trunk formation. We also found substantial changes in chromatin accessibility at the two developmental stages, mostly mapping to intergenic regions and presenting differential footprinting profiles to several key transcription factors, indicating a significant switch in the regulatory elements controlling head or trunk development. Those chromatin changes are largely independent of retinoic acid, despite the key role of this factor in the transition to trunk development. We also tested the functional relevance of potential enhancers identified in the accessibility assays that reproduced the expression profiles of genes involved in the transition. Deletion of these regions by genome editing had limited effect on the expression of those genes, suggesting the existence of redundant enhancers that guarantee robust expression patterns. This work provides a global view of the regulatory changes controlling the switch into the axial extension phase of vertebrate embryonic development. It also revealed mechanisms by which the cellular context influences the activity of regulatory factors, channeling them to implement one of several possible biological outputs.


Intelligent inventory management with autonomation and service strategy.
The manufacturer's service to the customer is one of the critical factors in maximizing profit. This study proposes the innovative (Q, r) inventory policy integrated with autonomated inspection and service strategy for service-dependent demand. First, an advanced autonomated inspection makes the product error-free. Therefore, this makes customers more satisfied and increases profit. The proposed model decides the optimal investment for such autonomated inspection. Second, three types of services are considered in the study: unpaid, partially paid, and fully paid services. Each type of service has a different service level and the amount of the customer's payment. Our model finds the optimal service strategy based on the variable conditions along with the optimal quantity and reorder level of inventory policy. Numerical analyses are made for different service strategies, along with a sensitivity analyses for various critical parameters. Results show that the full paid service is 84.88% beneficial compared to the unpaid service, and the autonomated inspection policy is 5.02% beneficial compared to the traditional ones. The increase in unit servicing costs always increases the profit of the company.


Preemptive middle glenohumeral ligament release in arthroscopic rotator cuff repair does not reduce the postoperative stiffness: a retrospective comparative study.
This study aimed to evaluate the efficacy of preemptive middle glenohumeral ligament (MGHL) release in arthroscopic rotator cuff repair (ARCR) to reduce postoperative stiffness. Patients who underwent ARCR were enrolled and allocated into two groups retrospectively: the preemptive MGHL release group (n = 44) and the preemptive MGHL non-release group (n = 42). Clinical outcomes were assessed and compared between the two groups, including the range of motion, Japanese Orthopedic Association Shoulder Score, Constant Shoulder Score, and the University of California, Los Angeles Score preoperatively and 3 months, 6 months, and 12 months postoperatively and complications. The integrity of the repaired tendon was assessed at the 12-month follow-up using magnetic resonance imaging. There were no significant differences between the groups in all range of motion and all functional scores at any of the assessed time points. There was also no significant difference in the healing failure rate 2.3% in the preemptive MGHL group and 2.4% in the preemptive MGHL non-release group (p = .97), and postoperative stiffness was 2.3% in the preemptive MGHL group and 7.1% in the preemptive MGHL non-release group (p = .28). There was no postoperative instability in both group. ARCR effectively facilitates the recovery of range of motion and function in patients with a rotator cuff tear. However, preemptive MGHL release could not be an effective method to reduce postoperative stiffness.


[Retroauricular dermatofibroma in a child simulating a malignant tumour].
Dermatofibroma represents one of the commonest benign soft tissue tumours, and its diagnosis is usually straightforward if classical clinicopathologic features are evident. It occurs frequently on the extremities and trunk, often in young adults during the 3(rd) and 4(th) decades. We report a peculiar case of an aggressive cellular dermatofibroma in a child that simulated a malignant tumour. Our aim is to discuss the differential diagnosis. An 8-year-old boy presented with a retroauricular tumour. Clinically, the lesion, 2 cm in diameter, was located in the left retroauricular region. It was nodular, erythematous, infiltrating the underlying tissue with an anterior spread leading to an amputation of the auricular lobule and a retraction of the tragus. Computerized axial tomography revealed a local tissular thickening extending in soft tissues without any bone involvement. A malignant lesion was initially suspected. A biopsy was performed. It was followed by a surgical resection. The lesion had the full microscopic characteristics of a cellular dermatofibroma. Dermatofibroma is one of the major differential diagnosis of nodular cutaneous tumours in children that simulate malignancy. Histologic examination with immunohistochemical study is essential for diagnosis.


Biomechanical Performance of Hip Labral Repair Techniques.
To determine the strength of various suture techniques and the impact of suture passer size on cyclically loaded hip labra. We assigned 63 bovine hip labra to 9 simple knotless suture technique groups using OrthoCord suture: (1) penetrating grasper (2.6 mm)-placed horizontal mattress, (2) penetrating grasper-placed vertical mattress, (3) SutureLasso (1.8 mm)-placed vertical mattress, (4) penetrating grasper-placed oblique repair, (5) penetrating grasper-placed vertical mattress plus radiofrequency, (6) SutureLasso-placed horizontal mattress, (7) SutureLasso-placed oblique mattress, (8) SutureLasso-placed horizontal mattress plus radiofrequency, and (9) SutureLasso-placed oblique mattress plus radiofrequency. After 20 cycles of uniaxial tensile loading (5 to 80 N), destructive testing was performed. Penetrating grasper-placed horizontal mattress sutures showed lower ultimate failure loads than vertical and oblique mattress sutures (P < .05). Penetrating grasper-placed vertical mattress sutures had higher peak-to-peak displacement than SutureLasso-placed vertical mattress sutures (P = .04). SutureLasso-placed oblique mattress sutures had a higher ultimate load (P < .01) and stiffness (P = .04) than SutureLasso-placed horizontal mattress sutures. SutureLasso-placed horizontal mattress sutures had lower cyclic elongation than penetrating grasper-placed horizontal mattress sutures (P = .01) and lower ultimate load (P < .01) and stiffness than SutureLasso-placed vertical mattress sutures (P < .01). Horizontal mattress sutures with radiofrequency had a higher ultimate load (P = .02), stiffness, and cyclic elongation (P < .01) than without radiofrequency. A horizontal mattress hip labrum stitch shows a lower ultimate failure load than vertical or oblique mattress stitches. Smaller-diameter suture-passing devices show less cyclic displacement and elongation than larger-diameter devices. Radiofrequency labral treatment does not alter vertical stitch strength but does alter horizontal mattress stitch strength. Vertical and oblique stitches are stronger than horizontal stitches. A 1.8-mm passing device shows a better cyclic loading performance than a 2.6-mm device.


Enantioselective HPLC analysis of escitalopram oxalate and its impurities using a cellulose-based chiral stationary phase under normal- and green reversed-phase conditions.
Normal-phase and reversed-phase high-performance liquid chromatography methods for the separation of the active pharmaceutical ingredient escitalopram from its (R)-enantiomer impurity have been developed on the cellulose-based Chiralcel OJ-H chiral stationary phase. Both methods share two features: they use ethanol as a cosolvent and are able to give a complete enantioseparation without interference from other associated chiral impurities. With the green eluent mixture ethanol-water-diethylammine 70:30:0.1 (v/v/v), the resolution between escitalopram and (R)-enantiomer was 2.09 at 30°C. The limits of quantification for the (S) and (R) enantiomers were 4.5 and 3.8 μg mL-1 , respectively.


Skin Diseases Affecting High-Level Competition Sailors: Descriptive Study Carried Out During the 2012 AG2R Transatlantic Boat Race.
The primary objective of this study was to identify skin disorders encountered in a population of sport sailors. Unlike merchant mariners and fishermen, there is sparse literature on this maritime population. Secondary objectives were to uncover on-board conditions that may contribute to dermatological problems in this population. We conducted a prospective study during the 2012 AG2R transatlantic race. Sixteen two-man crews participated in this race, all using the same model of sailboat (Bénéteau Figaro 2). Clinical examinations were conducted, photographs taken, and questionnaires containing 34 questions were handed out before departure and on arrival, 22 to 24 days later. Twenty-eight of 32 skippers (88%) participated in departure data collection, and 18 (56%) completed data collection on arrival. The average age of sailors was 34 years (SD = 8). Compared with skin diseases documented on departure, there was an increased amount of folliculitis on the buttocks, fungal infections, and hyperkeratosis of the hands on arrival. Furthermore, several new skin problems were found postrace: skin scaling, skin erosions on the buttocks, dyshidrosis, thermal burns, and sunburns. The use of protective gear and sunscreen was common, but on-board hygiene was poor with infrequent bathing and clothing changes. Skin conditions are nearly universal in this maritime population. Further assessments are needed to know if long-term use of protective gear; improved hygiene; use of barrier creams; and proper on-board care of fungal infections, wounds, and burns could reduce the number and severity of skin problems encountered in sport sailors.


Predicting the prognosis of operable gastric cancer patients by dynamic changes in platelets before and after surgery: a retrospective cohort study.
Since the relationship between postoperative platelet count and prognosis is still unclear, we designed a standardized index of platelet count to predict the prognosis of gastric cancer (GC). We designed a development validation cohort for the pre/post platelet ratio. We determined the ability of PPR to predict mortality in gastric cancer patients and validated them by a separate cohort. Survival was assessed by Kaplan-Meier analysis and associations explored by multivariate and multivariate analyses. The usefulness of the prediction was estimated by measuring the time-dependent ROC. Decision-curve analysis was used to validate the net clinical benefit. The sample distribution was similar in the two cohorts, and the 1-, 3-, and 5-year OS evaluation of the postoperative/preoperative platelet ratio was the largest for AUC in the two cohorts. Meanwhile, PPR has a good predictive value and a net clinical benefit. PPR has been identified and validated to be independently concerned about OS of patients with GC and was a reliable and economic indicator to evaluate the prognosis.


Crystallization of a Complex Between MYC and Jas Motif.
In the jasmonate signaling pathway, a region of 17 amino acids within the Jas motif of JAZ proteins and a conserved region within the N-terminus of MYC proteins are sufficient for JAZ-MYC interactions. Crystal structures of Jas-MYC complexes have revealed the structural basis of this important interaction. Here, we describe methods of cloning, expression, and purification of MYC N-terminal proteins and their co-crystallization with Jas motif peptides.


Effect of verapamil on allergen-induced asthma in patients with respiratory allergy.
Specific degranulation of mast cells and basophils depends upon transmembrane calcium flow. In the present studies the protective effect of the calcium-antagonist drug verapamil against allergen-induced asthma was assessed in eight atopic patients. The results of this study showed that verapamil, administered both orally or by aerosol, can prevent the specific bronchoconstriction.


The George B. Koelle symposium on the cholinergic synapse.
The George B. Koelle Symposium on the Cholinergic Synapse described the early development of the importance of ACh as a transmitter at both cholinergic synapses of the CNS, ganglion and neuromuscular junction. While a great deal is known about the function of cholinergic transmission at the neuromuscular junction, the integrated role of cholinergic, nicotinic and muscarinic receptors in the overall process of CNS functions, i.e., behavior, motor control, abstract thinking, memory and speech remains as a challenge for future investigation. The architecture of the cholinergic synapse appears to be a dynamic process involving ARIA, Agrin and the various forms of ACh esterase. The regulation of gene expression and site directed localization of postsynaptic cholinergic receptor proteins during the life cycle involves the dynamic interactions of these agents with the postsynaptic membrane and postsynaptic gene express. The last two papers at the symposium dealt with the chemistry of the nicotinic receptor regulated channel involved in ACh binding and the consequent cationic channel conductional changes.


Secondary effects of anion exchange on chloride, sulfate, and lead release: systems approach to corrosion control.
Water treatment processes can cause secondary changes in water chemistry that alter finished water quality including chloride, sulfate, natural organic matter (NOM), and metal release. Hence, the goal of this research was to provide an improved understanding of the chloride-to-sulfate mass ratio (CSMR) with regards to chloride and sulfate variations at full-scale water treatment plants and corrosion potential under simulated premise plumbing conditions. Laboratory corrosion studies were conducted using Pb-Sn solder/Cu tubing galvanic cells exposed to model waters with low (approx. 5 mg/L Cl(-) and 10 mg/L SO(4)(2-)) and high (approx. 50 mg/L Cl(-) and 100 mg/L SO(4)(2-)) concentrations of chloride and sulfate at a constant CSMR of ≈ 0.5. The role of NOM during corrosion was also evaluated by changing the type of organic material. In addition, full-scale sampling was conducted to quantify the raw water variability of chloride, sulfate, and NOM concentrations and the changes to these parameters from magnetic ion exchange treatment. Test conditions with higher concentrations of chloride and sulfate released significantly more lead than the lower chloride and sulfate test waters. In addition, the source of NOM was a key factor in the amount of lead released with the model organic compounds yielding significantly less lead release than aquatic NOM.


Photobiomodulation and antimicrobial photodynamic therapy as adjunct in the treatment and prevention of osteoradionecrosis of the jaws: A case report.
We report on a patient with a history of radiotherapy to the head and neck region exhibiting necrotic bone exposure associated with fistula and purulent exudation in the mandible, with the diagnosis of stage 3 osteoradionecrosis, in addition to a periapical cyst in the maxillary anterior region and multiple root remnants. An antibiotic coverage protocol with amoxicillin and metronidazole was prescribed for subsequent necrotic bone removal. The surgical procedure was performed along with the aPDT using methylene blue and red light, followed by coaptation of the edges of the surgical wound and the healing protocol with LLLT. The extraction of non-rehabilitated teeth was performed two per session using antibiotic coverage, aPDT, and LLLT and mouthwash with 0.12 % chlorhexidine was prescribed until the complete closure of the surgical wound was achieved. Additionally, two aPDT sessions and four LLLT protocols were performed for complete healing of the surgical sites. Extra and intraoral examinations and panoramic and periapical radiographs were performed. No emergence or recurrence of osteonecrosis was observed after 12 months of follow-up.


Models and frameworks of patient engagement in health services research: a scoping review protocol.
Patient engagement in research is an emerging approach that involves active and meaningful collaboration between researchers and patients throughout all phases of a project, including planning, data collection and analysis, and sharing of findings. To better understand the core features (elements) that underlie patient engagement, it is useful to have a look at models and frameworks that guide its conduct. Therefore, this manuscript aims to present a protocol for a scoping review of models and frameworks of patient engagement in health services research. Methods: Our protocol design is based on an established framework for conducting scoping reviews. We will identify relevant models and frameworks through systematic searches of electronic databases, websites, reference lists of included articles, and correspondence with colleagues and experts. We will include published and unpublished articles that present models and frameworks of patient engagement in health services research and exclude those not in English or unavailable as full texts. Two reviewers will independently review abstracts and full texts of identified articles for inclusion and extract relevant data; a third reviewer will resolve discrepancies. Our primary objective is to count and describe elements of patient engagement that overlap (present in 2 or more) and diverge among included models and frameworks. Discussion: We hope this review will raise awareness of existing models and frameworks of patient engagement in health services research. Further, by identifying elements that overlap and diverge between models and frameworks, this review will contribute to a clearer understanding of what patient engagement in research is and/or could be. Background: Patients can bring an expert voice to healthcare research through their lived experience of receiving healthcare services. Patient engagement in research is an emerging approach that challenges researchers to acknowledge and utilize this expertise through meaningful and active collaboration with patients throughout the research process. In order to facilitate a clearer understanding of the core elements that underlie patient engagement, it is useful to examine existing models and frameworks that guide its conduct. Therefore, the aim of this manuscript is to present a protocol for a scoping review of models and frameworks of patient engagement in health services research. Methods: Drawing on Arksey and O'Malley's and Levac et al.'s framework for scoping reviews, we designed our protocol to identify relevant a) published articles through systematic searches of 7 electronic databases and snowball sampling and b) unpublished articles through systematic searches of databases and websites and snowball sampling. We will include published and unpublished models and frameworks of patient engagement in health services research and exclude those not in English or unavailable as full texts. Two reviewers will independently screen the abstracts and full texts of identified articles for inclusion and extract relevant data; a third reviewer will resolve disagreements. We will conduct a descriptive analysis of the characteristics (i.e., elements underlying patient engagement and those related to the study authors, publication, and model/framework) of included articles and a narrative analysis of the data concerning elements of the model or framework. Our primary objective is to count and describe elements of patient engagement that overlap (present in ≥ 2) and diverge (present in < 2) among identified models and frameworks. Discussion: Through identification of elements that overlap and diverge between existing models and frameworks, this review will provide a starting point for the critical reflection on our collective understanding of what patient engagement in health services research is and/or could be. Ultimately, we hope that the findings of this review raise awareness of existing models and frameworks and shed light on some of the complexity of conducting patient engaged research through identification of key elements that shape this approach.


MALDI-ToF mass spectrometry for studying noncovalent complexes of biomolecules.
Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been demonstrated to be a valuable tool to investigate noncovalent interactions of biomolecules. The direct detection of noncovalent assemblies is often more troublesome than with electrospray ionization. Using dedicated sample preparation techniques and carefully optimized instrumental parameters, a number of biomolecule assemblies were successfully analyzed. For complexes dissociating under MALDI conditions, covalent stabilization with chemical cross-linking is a suitable alternative. Indirect methods allow the detection of noncovalent assemblies by monitoring the fading of binding partners or altered H/D exchange patterns.


Sequence of a cDNA encoding turtle high mobility group 1 protein.
In order to understand sequence information about turtle HMG1 gene, a cDNA encoding HMG1 protein of the Chinese soft-shell turtle (Pelodiscus sinensis) was amplified by RT-PCR from kidney total RNA, and was cloned, sequenced and analyzed. The results revealed that the open reading frame (ORF) of turtle HMG1 cDNA is 606 bp long. The ORF codifies 202 amino acid residues, from which two DNA-binding domains and one polyacidic region are derived. The DNA-binding domains share higher amino acid identity with homologues sequences of chicken (96.5%) and mammalian (74%) than homologues sequence of rainbow trout (67%). The polyacidic region shows 84.6% amino acid homology with the equivalent region of chicken HMG1 cDNA. Turtle HMG1 protein contains 3 Cys residues located at completely conserved positions. Conservation in sequence and structure suggests that the functions of turtle HMG1 cDNA may be highly conserved during evolution. To our knowledge, this is the first report of HMG1 cDNA sequence in any reptilian.


The Temperature-Size Rule in Lecane inermis (Rotifera) is adaptive and driven by nuclei size adjustment to temperature and oxygen combinations.
The evolutionary implications of the Temperature-Size Rule (TSR) in ectotherms is debatable; it is uncertain whether size decrease with temperature increase is an adaptation or a non-adaptive by-product of some temperature-dependent processes. We tested whether (i) the size of the rotifer Lecane inermis affects fecundity in a way that depends on the combination of low or high temperature and oxygen content and (ii) the proximate mechanism underlying TSR in this species is associated with nuclei size adjustment (a proxy of cell size). Small-type and large-type rotifers were obtained by culturing at different temperatures prior to the experiment and then exposed to combinations of two temperature and two oxygen conditions. Fecundity was estimated and used as a measure of fitness. Nuclei and body sizes were measured to examine the response to both environmental factors tested. The results show the following for L. inermis. (i) Body size affects fecundity in response to both temperature and oxygen, supporting a hypothesis regarding the contribution of oxygen in TSR. (ii) Large individuals are generally more fecund than small ones; however, under a combination of high temperature and poor oxygen conditions, small individuals are more fecund than large ones, in accordance with a hypothesis of the adaptive significance of TSR. (iii) The body size response to temperature is realised by nuclei size adjustment. (iv) Nuclei size changes in response to temperature and oxygen conditions, in agreement with hypotheses on the cellular mechanism underlying TSR and on a contribution of oxygen availability in TSR. These results serve as empirical evidence for the adaptive significance of TSR and validation of the cellular mechanism for the observed response.


Short-term effects of a nicotine-free e-cigarette compared to a traditional cigarette in smokers and non-smokers.
A few studies have assessed the short-term effects of low-dose nicotine e-cigarettes, while data about nicotine-free e-cigarettes (NF e-cigarettes) are scanty. Concerns have been expressed about the use of NF e-cigarettes, because of the high concentrations of propylene glycol and other compounds in the e-cigarette vapor. This laboratory-based study was aimed to compare the effects of ad libitum use of a NF e-cigarette or and a traditional cigarette for 5 min in healthy adult smokers (n = 10) and non-smokers (n = 10). The main outcome measures were pulmonary function tests, fraction of exhaled nitric oxide (FeNO) and fractional concentration of carbon monoxide (FeCO) in exhaled breath. The traditional cigarette induced statistically significant increases in FeCO in both smokers and non-smokers, while no significant changes were observed in FeNO. In non-smokers, the traditional cigarette induced a significant decrease from baseline in FEF75 (81 % ± 35 % vs 70.2 % ± 28.2 %, P = 0.013), while in smokers significant decreases were observed in FEF25 (101.3 % ± 16.4 % vs 93.5 % ± 31.7 %, P = 0.037), FEV1 (102.2 % ± 9.5 % vs 98.3 % ± 10 %, P = 0.037) and PEF (109.5 % ± 14.6 % vs 99.2 % ± 17.5 %, P = 0.009). In contrast, the only statistically significant effects induced by the NF e-cigarette in smokers were reductions in FEV1 (102.2 % ± 9.5 % vs 99.5 ± 7.6 %, P = 0.041) and FEF25 (103.4 % ± 16.4 % vs 94.2 % ± 16.2 %, P = .014). The present study demonstrated that the specific brand of NF e-cigarette utilized did not induce any majoracute effects. In contrast, several studies have shown that both traditional cigarettes and nicotine-containing e-cigarettes have acute effects on lung function. Our study expands on previous observations on the effects of NF e-cigarettes, but also for the first time describes the changes induced by smoking one traditional cigarette in a group of never smokers. The short-term use of the specific brand of NF e-cigarette assessed in this study had no immediate adverse effects on non-smokers and only small effects on FEV1 and FEF25 in smokers. The long-term health effects of NF e-cigarette use are unknown but worthy of further investigations. Clinicaltrials.gov: NCT02102191.


Role of metallothionein in Helicobacter pylori-positive gastric mucosa with or without early gastric cancer and the effect on its expression after eradication therapy.
Metallothionein (MT) has a proven relationship with various kinds of cancer and reduces tissue damage. Helicobacter pylori (H. pylori) infection is associated with the alteration of gastric epithelial cell cycle events, a condition implicated in the initiation and development of gastric cancer. This study investigates the role of MT in H. pylori-induced gastritis with or without early gastric cancer (ECG) and evaluates the effect on MT expression after eradication therapy. Gastric biopsy samples were immunohistochemically examined for MT expression in 36 H. pylori-negative patients without ECG and 98 positive patients with or without ECG. Real time polymerase chain reaction was performed in 14 antral biopsy samples with or without H. pylori. The severity of gastritis was also evaluated according to the updated Sydney System. In 31 successfully eradicated patients, the above assessment was repeated for two consecutive years. MT expression was higher in H. pylori-negative patients than in positive patients (P < 0.01). Moreover, in the corpus it was higher in H. pylori-positive patients without ECG compared to those with ECG (P < 0.05). The MT labeling index had a negative correlation with the severity of gastritis (P < 0.01). A positive correlation was shown between the MT labeling index and apoptosis: proliferation ratio (r = 0.41, P < 0.01). The MT labeling index in H. pylori-positive patients was gradually recovered after eradication (P < 0.05). The decrease of MT expression cannot prevent tissue damage in H. pylori-positive gastric mucosa and leads to more severe gastritis. This phenomenon may be attributed to gastric carcinogenesis. H. pylori eradication increases MT expression and may reduce the risk of ECG.


Early assessment of the effect of map-guided transcatheter intracardiac electric shock on sustained ventricular tachycardia secondary to coronary artery disease.
Short-term efficacy of transcatheter intracardiac electric shock was evaluated in 25 patients with recurrent sustained ventricular tachycardia (VT) secondary to coronary artery disease. Pace mapping and activation sequence mapping during VT were both used to direct intracardiac electric shocks applied between the distal electrode of the catheter (cathode) and a chest wall plate (anode) using a mean total energy of 588 +/- 209 J/patient. The short-term outcome of the procedure was considered successful in 3 patients (12%) who neither developed spontaneous VT nor had sustained VT in response to programmed electrical stimulation 1 week after the procedure. The short-term outcome in the remaining 22 patients (88%) was considered unsuccessful: 7 of the 22 patients developed spontaneous sustained VT and in 19 patients, including 15 with no spontaneous VT, sustained VT was still inducible by programmed electrical stimulation 7 +/- 2 days after the intracardiac electric shock. All 22 patients were subsequently treated with other modes of antiarrhythmic therapy. Using the technique described, the short-term efficacy of map-directed transcatheter intracardiac electric shock in eliminating VT is poor.


The α' subunit of β-conglycinin and various glycinin subunits of soy are not required to modulate hepatic lipid metabolism in rats.
This study examined the effect of soy proteins with depletion of different subunits of the two major storage proteins, β-conglycinin and glycinin, on hepatic lipids and proteins involved in lipid metabolism in rats, since the bioactive component of soy responsible for lipid-lowering is unclear. Weanling Sprague Dawley rats were fed diets containing either 20% casein protein in the absence (casein) or presence (casein + ISF) of isoflavones or 20% alcohol-washed soy protein isolate (SPI) or 20% soy protein concentrates derived from a conventional (Haro) or 2 soybean lines lacking the α' subunit of β-conglycinin and the A1-3 (1TF) or A1-5 (1a) subunits of glycinin. After 8 weeks, the rats were necropsied and liver proteins and lipids were extracted and analysed. The results showed that soy protein diets reduced lipid droplet accumulation and content in the liver compared to casein diets. The soy protein diets also decreased the level of hepatic mature SREBP-1 and FAS in males, with significant decreases in diets 1TF and 1a compared to the casein diets. The effect of the soy protein diets on female hepatic mature SREBP-1, FAS, and HMGCR was confounded since casein + ISF decreased these levels compared to casein alone perhaps muting the decrease by soy protein. A reduction in both phosphorylated and total STAT3 in female livers by ISF may account for the gender difference in mechanism in the regulation and protein expression of the lipid modulators. Overall, soy protein deficient in the α' subunit of β-conglycinin and A1-5 subunits of glycinin maintain similar hypolipidemic function compared to the conventional soy protein. The exact bioactive component(s) warrant identification.


Variability in H9N2 haemagglutinin receptor-binding preference and the pH of fusion.
H9N2 avian influenza viruses are primarily a disease of poultry; however, they occasionally infect humans and are considered a potential pandemic threat. Little work has been performed to assess the intrinsic biochemical properties related to zoonotic potential of H9N2 viruses. The objective of this study, therefore, was to investigate H9N2 haemagglutinins (HAs) using two well-known correlates for human adaption: receptor-binding avidity and pH of fusion. Receptor binding was characterized using bio-layer interferometry to measure virus binding to human and avian-like receptor analogues and the pH of fusion was assayed by syncytium formation in virus-infected cells at different pHs. We characterized contemporary H9N2 viruses of the zoonotic G1 lineage, as well as representative viruses of the zoonotic BJ94 lineage. We found that most contemporary H9N2 viruses show a preference for sulphated avian-like receptor analogues. However, the 'Eastern' G1 H9N2 viruses displayed a consistent preference in binding to a human-like receptor analogue. We demonstrate that the presence of leucine at position 226 of the HA receptor-binding site correlated poorly with the ability to bind a human-like sialic acid receptor. H9N2 HAs also display variability in their pH of fusion, ranging between pH 5.4 and 5.85 which is similar to that of the first wave of human H1N1pdm09 viruses but lower than the pH of fusion seen in zoonotic H5N1 and H7N9 viruses. Our results suggest possible molecular mechanisms that may underlie the relatively high prevalence of human zoonotic infection by particular H9N2 virus lineages.


Improvement of thermal stability of polypropylene using DOPO-immobilized silica nanoparticles.
After the surface silylation with 3-methacryloxypropyltrimethoxysilane, silica nanoparticles were further modified by 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO). The immobilization of DOPO on silica nanoparticles was confirmed by Fourier transform infrared spectroscopy, UV-visible spectroscopy, magic angle spinning nuclear magnetic resonance, and thermogravimetric analysis. By incorporating the DOPO-immobilized silica nanoparticles (5 wt%) into polypropylene matrix, the thermal oxidative stability exhibited an improvement of 62 °C for the half weight loss temperature, while that was only 26 °C increment with incorporation of virgin silica nanoparticles (5 wt%). Apparent activation energies of the polymer nanocomposites were estimated via Flynn-Wall-Ozawa method. It was found that the incorporation of DOPO-immobilized silica nanoparticles improved activation energies of the degradation reaction. Based on the results, it was speculated that DOPO-immobilized silica nanoparticles could inhibit the degradation of polypropylene and catalyze the formation of carbonaceous char on the surface. Thus, thermal stability was significantly improved.


Prognosis in chronic myeloid leukaemia: biology of the disease vs. treatment.
CML is best regarded as a benign neoplasm, which regularly transforms into a rapidly fatal malignant one. Survival is determined by the timing of disease transformation. The rate of transformation and death is low initially and increases gradually to a stable annual rate, reached during the third year after diagnosis. This averages 25% per year in large populations of Ph positive patients. Transformation appears to occur randomly; a patient's risk of transformation can be defined, but the time when it will occur cannot be predicted. There is no evidence that conventional antileukaemic therapy changes the risk of transformation; thus, survival is determined principally by the intrinsic biology of the disease. A number of features recorded at the time of diagnosis correlate significantly with survival and can serve as prognostic parameters. Multivariate regression and Cox model analyses can generate hazard ratio formulae which provide quantitative estimates of patients' risk. Several Cox models have been described by different groups, and it is possible that two or more models may describe survival equally well. A four-variable model described by the International CGL Prognosis Study Group in 1984 has recently been tested in a prospective study by the Italian Cooperative Study Group on Chronic Myeloid Leukaemia, and successfully classified patients into three groups with significantly different outcomes. This model produces excellent results in analyses of large patient populations, but is less satisfactory when applied to smaller series. It is likely that current prognostic models can be improved substantially to provide more accurate definition of patient risk over a broader range of hazard ratio values. Such models should prove useful in evaluating therapeutic schedules, selecting patients for investigational or hazardous treatment and making decisions regarding bone marrow transplantation.


NICE CG178 Psychosis and Schizophrenia in Adults: Treatment and Management - an evidence-based guideline?
National Institute for Health and Care Excellence (NICE) clinical guideline (CG)178 was published in 2014. NICE guidelines occupy an important international position. We argue that CG178 overemphasises the use of cognitive-behavioural therapy for schizophrenia and those 'at risk' of psychosis, with recommendations that do not always reflect the evidence base. The CG178 recommendations on medications are limited.


Levels of l-ascorbic acid and cadmium in the saphenous vein of patients with coronary artery disease are negatively correlated.
The aim of this study was the simultaneous determination of levels of cadmium and l-ascorbic Acid (AA) in human saphenous vein (SV) used in coronary artery bypass grafting (CABG) and check whether there is a relationship between these levels. Human SV were collected from 40 patients (20 men and 20 women; age, 40-75 years) at the time of routine coronary artery surgical revascularization. The concentration of cadmium in the tissue was determined according to the GF AAS-atomic absorption method. The concentration of AA was assayed in supernatant by FIA method with spectrophotometric detection. AA concentration (mean±SD); men: 98,7±13,18μg/g tissue, women: 96,06±11,98μg/g tissue. Cadmium concentration(mean±SD); men: 309±103,71ng/g tissue, women: 348,5±255,71ng/g tissue. Correlations among concentrations of AA and cadmium were insignificant negative in the group of men (Pearson r=-0,1504, p=0,5269) and in the group women (Pearson r=-0339, p=0144). Negative correlations among concentrations of AA and cadmium in human SV obtained in our study may indicate a protective effect of this vitamin in relation to toxic cadmium.


Frameshift mutations induced by four isomeric nitroacridines and their des-nitro counterpart in the lacZ reversion assay in Escherichia coli.
Acridines are well-known as compounds that intercalate noncovalently between DNA base pairs and induce +/-1 frameshift mutations at sites of monotonous repeats of a single base. Reactive derivatives of acridines, including acridine mustards and nitroacridines, form covalent adducts in DNA and exhibit mutagenic properties different from the simple intercalators. We compared the frameshift mutagenicity of the cancer chemotherapy drug nitracrine (1-nitro-9-(3'-dimethylaminopropylamino)-acridine), its des-nitro counterpart 9-(3'-dimethylaminopropylamino)-acridine (DAPA), and its 2-, 3-, and 4-nitro isomers (2-, 3-, and 4-nitro-DAPA) in the lacZ reversion assay in Escherichia coli. DAPA is a simple intercalator, much like the widely studied 9-aminoacridine. It most strongly induced +/-1 frameshift mutations in runs of guanine residues and more weakly induced -1 frameshifts in a run of adenine residues. A nitro group in the 1, 3, or 4 position of DAPA reduced the yield of +/-1 frameshift mutations. DAPA weakly induced -2 frameshifts in an alternating CG sequence. In contrast, nitracrine and its 3-nitro isomer resembled the 3-nitroacridine Entozon in effectively inducing -2 frameshift mutations. The 2- and 4-nitro isomers were less effective than the 1- and 3-nitro compounds in -2 frameshift mutagenesis. The results are interpreted with respect to intercalation, steric interactions, effects of base strength on DNA binding, enzymatic processing, and a slipped mispairing model of frameshift mutagenesis.


Megahertz-rate ultrafast X-ray scattering and holographic imaging at the European XFEL.
The advent of X-ray free-electron lasers (XFELs) has revolutionized fundamental science, from atomic to condensed matter physics, from chemistry to biology, giving researchers access to X-rays with unprecedented brightness, coherence and pulse duration. All XFEL facilities built until recently provided X-ray pulses at a relatively low repetition rate, with limited data statistics. Here, results from the first megahertz-repetition-rate X-ray scattering experiments at the Spectroscopy and Coherent Scattering (SCS) instrument of the European XFEL are presented. The experimental capabilities that the SCS instrument offers, resulting from the operation at megahertz repetition rates and the availability of the novel DSSC 2D imaging detector, are illustrated. Time-resolved magnetic X-ray scattering and holographic imaging experiments in solid state samples were chosen as representative, providing an ideal test-bed for operation at megahertz rates. Our results are relevant and applicable to any other non-destructive XFEL experiments in the soft X-ray range.


Laser-tonsillotomy for treatment of obstructive tonsillar hyperplasia in early childhood: a retrospective review.
Tonsillar hyperplasia leading to dyspnea, dysphagia and other symptoms of obstruction represents a common problem especially in young children where tonsillectomy should be avoided in order to preserve the immunological function of the tonsils. Aim of the study was to assess carbon-dioxide-laser-tonsillotomy as a considered alternative procedure to reduce the tonsillar volume in these children. Between 1993 and 2004, 109 children with tonsillar hyperplasia without former episodes of tonsillitis received laser-tonsillotomy mostly (n=98) combined with adenoidectomy. The protruding part of the tonsil was reduced by a CO2-laser. Seventy-five children were available for follow-up with a standard questionnaire. Five patients required a subsequent tonsillectomy due to a recurrence of tonsillar hyperplasia. Histological investigations were performed. Twenty-two children were reevaluated by clinical examination. Most of the patients were relieved from obstructive symptoms. There was no occurrence of postoperative hemorrhage or peritonsillar abscesses. The histological investigations on the specimens from later performed tonsillectomy (n=5) showed no evidence of inflammation or scar formations, but open and deep crypts. The clinical examination did not reveal any signs of chronic infections. In this retrospective study tonsillotomy with CO2-laser in early childhood leads to a long-term elimination of obstructive symptoms due to tonsillar hyperplasia with minimal discomfort for the patient while preserving normally functioning immunocompetent tonsillar tissue. Further prospective studies are planned.


Leishmanicidal activity of the root bark of Erythrophleum Ivorense (Fabaceae) and identification of some of its compounds by ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF-MS/MS).
Leishmaniasis is one of the neglected tropical disease caused by a protozoan of the genus Leishmania transmitted by sandflies. High cost and lack of oral formulation of existing drugs, rapid developments of resistance by the parasite coupled with serious side effects require new treatments to augment or replace currently available therapies. The major merits of herbal medicine seem to demonstrate perceived efficacy, low incidence of serious adverse effects and low cost. Erythrophleum plants possess beneficial biological properties and, as such, characterization of the bioactive components of these plants is imperative. Previous work has shown an overwhelming presence of cassaine alkaloids in these plants. However, amongst these plants, the African based specie (Erythrophleum ivorense) is the least studied. In the current study, the in vitro anti-leishmanial activity of the crude extract, its fractions and isolated compounds were evaluated using direct counting assay of promastigotes of Leishmania donovani using amphotericin B as positive control. The anti-leishmanial activity of E. ivorense extract was evaluated in vitro against the promastigote forms of Leishmania Donovani using a direct counting assay based on growth inhibition. Different crude extracts from ethyl acetate, pet-ether, and methanol as well as pure isolated compounds of E. ivorense: Erythroivorensin, Eriodictyol and Betulinic acid were screened. To know the possible components of the active methanolic extract, attempt was made to elucidate the extract using ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS/MS). This afforded a weak pet-ether fraction, a moderately active ethyl acetate fraction and a significantly active methanol fraction (IC50 = 2.97μg/mL) compared to Amphotericin B (IC50 = 2.40±0.67μg/mL). The novel diterpene erythroivorensin, betulinic acid and the flavanone Eriodictyol, from the ethyl acetate fraction, showed weak activity. UPLC-QTOF-MS/MS was used to identify the cassaine diterpenoids from the active methanol fraction. Here, 10 compounds of this type were putatively identified from the ethanol crude extract. The fragmentation mechanism of these metabolites is also proposed and are expected to serve as reference template for identification of these and related compounds in future. The presence of these compounds is an indication that they are an inherited and evolutionary component of plants belonging to the Erythrophleum genus. Our results further present another dimension where these compounds and their relative abundances can be used as chemo-taxonomical bio-markers of the genus. The present study also successfully demonstrated/re-affirmed the use of UPLC-QTOF-MS/MS as a robust technique for the characterization of natural products.


NanoString Digital Molecular Profiling of Protein and microRNA in Rhabdomyosarcoma.
Rhabdomyosarcoma (RMS) exhibits a complex prognostic algorithm based on histologic, biologic and clinical parameters. The embryonal (ERMS) and spindle cell-sclerosing RMS (SRMS) histologic subtypes warrant further studies due to their heterogenous genetic background and variable clinical behavior. NanoString digital profiling methods have been previously highlighted as robust novel methods to detect protein and microRNA expression in several cancers but not in RMS. To identify prognostic biomarkers, we categorized 12 ERMS and SRMS tumor cases into adverse (n = 5) or favorable (n = 7) prognosis groups and analyzed their signaling pathways and microRNA profiles. The digital spatial profiling of protein and microRNA analysis was performed on formalin-fixed, paraffin-embedded (FFPE) tumor tissue using NanoString technology. The detectable expression of several component members of the PI3K/AKT, MAPK and apoptosis signaling pathways was highlighted in RMS, including INPP4B, Pan-AKT, MET, Pan-RAS, EGFR, phospho-p90 RSK, p44/42 ERK1/2, BAD, BCL-XL, cleaved caspase-9, NF1, PARP and p53. Compared to cases with favorable prognosis, the adverse-prognosis tumor samples had significantly increased expression of INPP4B, which was confirmed with traditional immunohistochemistry. The analysis of microRNA profiles revealed that, out of 798 microRNAs assessed, 228 were overexpressed and 134 downregulated in the adverse prognosis group. Significant over-expression of oncogenic/tumor suppressor miR-3144-3p, miR-612, miR-302d-3p, miR-421, miR-548ar-5p and miR-548y (p < 0.05) was noted in the adverse prognosis group. This study highlights the utility of NanoString digital profiling methods in RMS, where it can detect distinct molecular signatures with the expression of signaling pathways and microRNAs from FFPE tumor tissue that may help identify prognostic biomarkers of interest. The overexpression of INPP4B and miR-3144-3p, miR-612, miR-302d-3p, miR-421, miR-548y and miR-548ar-5p may be associated with worse overall survival in ERMS and SRMS.


Elevated CO2 concentration modifies the effects of organic fertilizer substitution on rice yield and soil ARGs.
Antibiotic resistance and rising CO2 levels are considered among the most significant challenges we will face in terms of global development over the following decades. However, the impact of elevated CO2 on soil antibiotic resistance has rarely been investigated. We used a free-air CO2 enrichment system to investigate the potential risks posed by applying mineral and organic fertilizers to paddy soil at current CO2 concentration (370 ppm) and future elevated CO2 (eCO2, 570 ppm predicted for 2100). Organic fertilizer substitution (substituting the mineral fertilizer by 50% N) alone increased the plant uptake and soil residue of sulfamethazine, and enriched sulfonamide resistance genes (sul1, sul2), tetracycline resistance genes (tetG, tetM) and class 1 integron (intl1). But it decreased the rice grain yield (by 7.6%). Comparatively, eCO2 decreased the sul2, tetG and intl1 gene abundances by organic fertilizer substitution, and meanwhile increased grain yield (by 8.4%). Proteobacteria and Nitrospirae were potential hosts of antibiotic resistance genes (ARGs). Horizontal gene transfer via intl1 may play an important role in ARGs spread under eCO2. Results indicated that future elevated CO2 concentration could modify the effects of organic fertilizer substitution on rice yield and soil ARGs, with unknown implications for future medicine and human health.


Recognizing the causes of in-hospital cardiac arrest--A survival benefit.
The in-hospital emergency team (ET) may or may not recognize the causes of in-hospital cardiac arrest (IHCA) during the provision of cardiopulmonary resuscitation (CPR). In a previous 4.5-year prospective study, this rate of recognition was found to be 66%. The aim of this study was to investigate whether survival improved if the cause of arrest was recognized by the ET. The difference in survival if the causes were recognized versus not recognized was estimated after propensity score matching patients from these two groups. Overall survival to hospital discharge was 25%. After propensity score matching, the benefit of recognizing the cause regarding 1-hour survival of the episode was 29% (p<0.01), and 19% regarding hospital discharge, respectively. Variables commonly known to affect the outcome after cardiac arrest were found to be balanced between the two groups. The largest difference was found in patients with non-cardiac causes and non-shockable presenting rhythms. Patient records and pre-arrest clinical symptoms were the information sources most frequently utilized by the ET to establish the causes of arrest. Patients suffering an IHCA showed a substantial survival benefit if the causes of arrest were recognized by the ET. Patient records and pre-arrest clinical symptoms were the sources of information most frequently utilized in these instances.


[Investigation and management of patients presenting with thrombocytosis].
Thrombocytosis is a common finding when performing a blood count. It is often consecutive to an underlying condition and then does not lead to thrombotic complications. If a reactive thrombocytosis is eliminated, thrombocytosis is primitive, rarely hereditary and most often associated with hematological malignancies. Essential thrombocythemia must be recognized, by eliminating the differential diagnoses that are myelodysplastic syndromes associated with thrombocytosis and other myeloproliferative disorders. The treatment is based on the prevention of thrombotic risk and the possible introduction of a cytoreductive therapy. Life expectancy is close to that of the general population and mainly depends on the occurrence of myelofibrosis or transformation to acute myeloid leukemia.


Is phenytoin metabolism dose-dependent by enzyme saturation or by feedback inhibition?
The suggestion from animal experiments that phenytoin metabolism may be dose-dependent in man due to feedback inhibition by the major metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin, was examined in 3 normal subjects by measuring phenytoin clearance during an intravenous infusion of the metabolite and during a control infusion of solvent. Clearance was measured using both carbon-labeled and unlabeled phenytoin. The infusion of metabolite did not produce any consistent change of phenytoin clearance, suggesting that feedback inhibition does not occur in man.


Qualitative and quantitative parameters on hepatobiliary phase of gadoxetic acid-enhanced MR imaging for predicting pathological response to preoperative systemic therapy in colorectal liver metastases.
To explore the value of parameters of the on hepatobiliary phase (HBP) of pre-treatment gadoxetic acid-enhanced magnetic resonance imaging (MRI) for predicting pathological response to systemic therapy in colorectal liver metastases (CRLMs), compared with response evaluation criteria in solid tumors, version 1.1 (RECIST 1.1). A total of 96 patients with CRLMs who underwent gadoxetic acid-enhanced MRI prior to treatment and then liver resection from January 2017 to December 2021 were enrolled. The pathological response was assessed by the percentage of residual tumors (RTs), and CRLMs were classified into two groups according to the pathological response grade (PRG): (1) strong response (including PRG2 and PRG3, RTs ≤ 10%), and weak response (PRG1, RTs > 10%). Two radiologists evaluated the enhancement pattern and degree of CRLMs on the HBP. The diameter, mean and standard deviation (SD) value of signal intensity (SI) of CRLMs on pre-contrast and HBP images were recorded. Relative tumor enhancement (RTE) and the SD ratio (SDR) were calculated. These parameters were analyzed in terms of pathological response on a lesion-by-lesion basis. Totally, 263 CRLMs were classified into: the strong response group (PRG2, n = 57; PRG3, n = 7) and the weak response group (PRG1, n = 199). RTE and SDR values were significantly higher in the strong response group than in the weak response group (P < 0.001). RTE values (P < 0.001) and SDR values (P = 0.031) were independent factors for predicting strong response. The area under curve (AUC) of RTE and SDR values were 0.725 and 0.652, respectively. The combination of these parameters was 0.750, which performed better than RECIST 1.1 (0.750 vs 0.531; P < 0.001). RTE and SDR values on HBP are potential features in predicting pathological response to systemic therapy in CRLMs.


Thermo-responsive Hercosett/Poly(N-isopropylacrylamide) films: a new, fast, optically responsive coating.
Poly(N-isopropylacrylamide) (PNIPAM) is a common thermo-responsive, water-soluble polymer, while Hercosett is a cationic resin commonly employed in the paper industry. In this paper, Hercosett™ and poly(N-isopropylacrylamide) (PNIPAM) nanoparticles were used to prepare composite films that show thermo-responsive behavior and swelling-shrinking properties in water. First, size-controlled PNIPAM hydrogel nanoparticles were synthesized. These were then embedded within a matrix of the cationic resin Kymene 577H by film casting. The distribution of nanoparticles in the resin film was investigated. The thermo-responsive properties of the as-synthesized PNIPAM hydrogel nanoparticles and of the composite films were characterized together with the repeatability of the swelling-shrinking cycles. The presence of nanoparticles endowed the film with highly enhanced water retention (in comparison with resin-only films) and, most importantly, thermo-responsiveness. A very fast optical and morphological response was in fact observed. Due to the dual (optical and morphological) response, this new system is suitable for applications in optical or morphological actuation and gating.


Coordinated control of bone cutting for a CT-free navigation robotic system in total knee arthroplasty.
Robots are gradually becoming intelligent tools for surgeons in computer assisted orthopedic surgery. A hands-on robot combining CT-free navigation software and coordinated control has been designed for total knee arthroplasty. The hands-on robot is under bilateral force control so that the robot not only follows the force commands from the operator but also shapes the reflected force back to the operator. The proposed coordinated control also defines three operating modes to fulfill intelligent bone cutting by tuning appropriate scaling to the admittance gains. Experimental results demonstrated assistive, resistant and emergent actions to meet various bone cutting conditions by the coordinated controller. The proposed coordinated controller enables the robot to perform bone cutting more safely, rapidly and accurately compared with being performed by manual bone saw. The intelligent bone cutting has been successfully verified by a cadaver test.


Immunogold labelling of tumour cells during NK/target cell interactions.
Using a system of immunocolloidal gold labelling, we have monitored the expression and distribution of transferrin receptors (TfRs) within the K562 cell line, during NK/target cell interactions. An indirect method of immunolabelling was used to effectively immunolabel tumour cells without disrupting the natural effector:target interactions. Successful localization of TfRs demonstrates the potential of the described technique for discerning antigenic distribution of other cell:cell interactions. Immunolabelling has also provided a useful method for demonstrating receptor down-regulation within NK target cells, as a proposed cause of reduced receptor expression by TPA-treated cells. Following 30 and 60 min incubation periods with TPA, approximately 15 and 30%, respectively, of the gold/antibody complexes were relocated from the surface membrane to an intracellular location within endocytotic vesicles. The demonstration of receptor down-regulation is important as a proposed cause of TPA-induced tumour cell resistance to NK-mediated cytolysis.


Madingley, Madding, Mad scenarios: an exercise in futurology.
The Madingley scenarios were created to suggest potential contrasting futures (around year 2020) that could develop from the same driving forces. Those contrasting futures are named 'Trust their Guidance' and 'Find my Way', respectively. Trust their Guidance depicts a world where institutions have succeeded in adapting to the changing world and have strengthened their power and control on nations. Find my Way depicts a world where empowered individuals have taken responsibility for optimising their own lives. The discussion of these scenarios raised a number of questions including the purpose and role of governments, differences between societies, fundamental vs superficial change and, applied to the area of homeopathy, the role and responsibility of the homeopathic community in shaping the future of this medical approach.


Effect of an 8-hour holding period on in vivo and in vitro properties of red cells and factor VIII content of plasma after collection in a red cell additive system.
Extension of the holding time for whole blood units from 6 to 8 hours at ambient temperature should provide enhanced flexibility in the preparation of platelet concentrates (PCs). A paired study was conducted to evaluate the characteristics of stored red cells (RBCs) and plasma prepared from whole blood collected into a red cell additive system (CPD-ADSOL) after an extended holding time. An individual donated a unit of whole blood on two occasions; 1 unit was held for 6 hours before processing and the other for 8 hours. Autologous RBC 24-hour survival levels after 42 days of storage were comparable. Laboratory A, using a 99mTc-51Cr technique, found mean survival levels of 79 percent (6-hour hold) and 78 percent (8-hour hold) (n = 8). Analysis by the single-label procedure found the mean levels to be 82 and 81 percent. Laboratory B, using an albumin 125I-51Cr technique, found mean survival levels of 74 and 72 percent (n = 10). Mean hemolysis and ATP levels were found to be comparable after 42 days of storage following 6- and 8-hour holding periods. 2,3 DPG levels were reduced to a greater degree during the longer hold. The factor VIII levels in plasma frozen for at least a month after 6- and 8-hour holding periods were comparable; thawed plasma contained mean levels of 0.77 and 0.76 units per mL (n = 21). These studies indicate that components prepared by using a CPD-ADSOL system after holding periods of 6 and 8 hours have comparable properties.


Swin-UNet++: A Nested Swin Transformer Architecture for Location Identification and Morphology Segmentation of Dimples on 2.25Cr1Mo0.25V Fractured Surface.
The precise identification of micro-features on 2.25Cr1Mo0.25V steel is of great significance for understanding the mechanism of hydrogen embrittlement (HE) and evaluating the alloy's properties of HE resistance. Presently, the convolution neural network (CNN) of deep learning is widely applied in the micro-features identification of alloy. However, with the development of the transformer in image recognition, the transformer-based neural network performs better on the learning of global and long-range semantic information than CNN and achieves higher prediction accuracy. In this work, a new transformer-based neural network model Swin-UNet++ was proposed. Specifically, the architecture of the decoder was redesigned to more precisely detect and identify the micro-feature with complex morphology (i.e., dimples) of 2.25Cr1Mo0.25V steel fracture surface. Swin-UNet++ and other segmentation models performed state-of-the-art (SOTA) were compared on the dimple dataset constructed in this work, which consists of 830 dimple scanning electron microscopy (SEM) images on 2.25Cr1Mo0.25V steel fracture surface. The segmentation results show Swin-UNet++ not only realizes the accurate identification of dimples but displays a much higher prediction accuracy and stronger robustness than Swin-Unet and UNet. Moreover, efforts from this work will also provide an important reference value to the identification of other micro-features with complex morphologies.


Comparison of mesiodistal space measurements of single-implant sites on panoramic and oblique images generated by cone-beam CT.
To compare the mesiodistal space measurements of single-implant sites on panoramic and oblique images generated by cone-beam CT (CBCT). CBCT images for 101 single-implant sites of 66 patients referred for pre-surgical radiographic implant planning were selected for the study; 15-mm-thickness panoramic images were reformatted and used for measuring mesiodistal space dimensions. The measurements were repeated and compared with those of thin oblique images (200-300 μ) using Wilcoxon signed rank test. The correlation between measurements in addition to intra-observer agreement was evaluated by Pearson's correlation coefficients. All mesiodistal space measurements on panoramic and oblique images generated by CBCT were strongly correlated and there were no statistically significant differences between them (P < 0.05). Both panoramic and oblique images generated by CBCT can be used for measuring mesiodistal space dimensions of single-implant sites.


Biomechanical properties of abdominal organs under tension with special reference to increasing strain rate.
Currently, abdominal finite element models overlook the organs such as gallbladder, bladder, and intestines, which instead are modeled as a simple bag that is not included in the analysis. Further characterization of the material properties is required for researchers to include these organs into models. This study characterized the mechanical properties of human and porcine gallbladder, bladder, and intestines using uniaxial tension loading from the rates of 25%/s to 500%/s. Small differences were observed between human and porcine gallbladder elastic modulus, failure stress, and failure strain. Strain rate was determined to be a significant factor for predicting porcine gallbladder elastic modulus and failure stress which were found to be 9.03 MPa and 1.83 MPa at 500%/s. Human bladder was observed to be slightly stiffer with a slightly lower failure stress than porcine specimens. Both hosts, however, demonstrated a strain rate dependency with the elastic modulus and failure stress increasing as the rate increased with the highest elastic modulus (2.16 MPa) and failure stress (0.65 MPa) occurring at 500%/s. Both human and porcine intestines were observed to be affected by the strain rate. Failure stress was found to be 1.6 MPa and 1.42 MPa at 500%/s for the human and porcine intestines respectively. For all properties found to be strain rate dependent, a numerical model was created to quantify the impact. These results will enable researchers to create more detailed finite element models that include the gallbladder, bladder, and intestines.


Directional transport and active retention of Dpp/BMP create wing vein patterns in Drosophila.
The bone morphogenetic protein (BMP) family ligand decapentaplegic (Dpp) plays critical roles in wing vein development during pupal stages in Drosophila. However, how the diffusible Dpp specifies elaborate wing vein patterns remains unknown. Here, we visualized Dpp distribution in the pupal wing and found that it tightly reflects the wing vein patterns. We show that Dpp is directionally transported from the longitudinal veins (LVs) into the posterior crossvein (PCV) primordial region by the extracellular BMP-binding proteins, short gastrulation (Sog) and crossveinless (Cv). Another BMP-type ligand, glass bottom boat (Gbb), also moves into the PCV region and is required for Dpp distribution, presumably as a Dpp-Gbb heterodimer. In contrast, we found that most of the Dpp is actively retained in the LVs by the BMP type I receptor thickveins (Tkv) and a positive feedback mechanism. We provide evidence that the directionality of Dpp transport is manifested by sog transcription that prepatterns the PCV position in a Dpp signal-independent manner. Taken together, our data suggest that spatial distribution of Dpp is tightly regulated at the extracellular level by combination of long-range facilitated transport toward the PCV and short-range signaling by active retention in the LVs, thereby allowing diffusible ligands to form elaborate wing vein patterns.


Bis(4-phenyl-2-sulfanyl-idene-2,3-di-hydro-1,3-thia-zol-3-ido-κ2 S 2,N)(4-phenyl-1,3-thia-zole-2-thiol-ato-κS 2)bis-muth.
The title compound, [Bi(C9H6NS2)3], was prepared by reacting BiCl3 and 2-mercapto-4-phenyl-thia-zole (LH) at room temperature in a stoichiometric ratio of 1:4. The mol-ecular structure reveals a slightly distorted square-pyramidal environment around the BiIII atom. Two of the three monoanionic ligands L - coordinate in an N,S-bidentate mode, while one shows a monodentate mode through an S atom. There are no significant inter-molecular inter-actions present in the crystal.


The effects of dihydropyridines on neurotransmitter release from cultured neuronal cells.
Depolarizing stimuli increase the release of transmitter substances from cultured PC12 pheochromocytoma cells and reaggregate cultures of mouse mesencephalic dopamine neurones. We measured the stimulated release of (3H) norepinephrine and (3H) dopamine from these systems respectively. In the cultured mouse dopaminergic neurones, several organic calcium channel blockers including nitrendipine, D-600, verapamil and diltiazem were unable to inhibit potassium-evoked transmitter release. However, release was blocked by 3 mM cobalt. The novel dihydropyridine calcium channel agonist BAY K8644 also had no effect on basal or evoked dopamine release. In contrast, BAY K8644 greatly stimulated the potassium-evoked release of (3H) norepinephrine from PC12 cells. The BAY K8644 enhanced release could be blocked by the dihydropyridine antagonist nitrendipine. These results indicate that while stimulus-secretion coupling in the PC12 cell line involves dihydropyridine sensitive calcium channels, this is not the case in primary cultured neurones.


Immune responses and inorganic ion transport regulations of Epinephelus coioides in response to L321_RS13075 gene of Pseudomonas plecoglossicida.
Pseudomonas plecoglossicida is a well-known pathogen of viscera granulomas disease in fish, which has led to severe economic losses. In our previous study, L321_RS13075 was predicted to be a key virulence gene of P. plecoglossicida during the host-pathogen interaction with Epinephelus coioides. To investigate the role of L321_RS13075 in the regulation of virulence in P. plecoglossicida, a L321_RS13075 knock-down strain was constructed. And a significant reduction in the ability of colonization, intracellular survival, motility, biofilm formation, and adhesion was detected in the L321_RS13075 knock-down strain. Compared with the wild-type strain, the silence of L321_RS13075 in P. plecoglossicida resulted in a significant change in the transcriptome of infected Epinephelus coioides (E. coioides). Results of COG and GO analysis on E. coioides showed that genes related to immune responses and inorganic ion transport were significantly affected by L321_RS13075 of P. plecoglossicida. Meanwhile, the interactions of the genes related to immune responses and inorganic ion transport were predicted, and the important hub genes were identified. Taken together, the results indicated that L321_RS13075 was a virulent gene of P. plecoglossicida, which significantly affected the immune responses and inorganic ion transport in E. coioides.


Assessing the gold standard: a review of 253 two-stage revisions for infected TKA.
Periprosthetic joint infection has been the leading cause of failure following TKA surgery. The gold standard for infection control has been a two-staged revision TKA. There have been few reports on mid- to long-term survivorship, functional outcomes, and fate of patients with a failed two-stage revision TKA. Therefore, we determined (1) the mid-term survivorship of two-stage revision TKA, (2) the function of patients in whom infection was controlled, and (3) the outcome of patients with a failed two-stage revision due to recurrent infection. We retrospectively reviewed 239 patients who underwent 253 two-stage revision TKAs for periprosthetic infection. There were 239 patients (253 knees), 104 men and 135 women, with a mean age of 70 ± 10 years at the time of two-stage revision and a mean BMI of 31.53 ± 6.74 kg/m2. During followup, we obtained WOMAC and The Knee Society Clinical Rating Scores and radiographs. The minimum followup was 1 year (median, 4 years; range, 1-17 years). Thirty-three patients experienced a failed two-staged TKA. Sixteen patients experienced failure due to recurrent sepsis. There were 17 failures for aseptic causes. The overall infection-free survivorship for two-stage revision TKA was 85% at 5 years and 78% at 10 years. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.


Restitution of the NHS breast reconstruction service during the recovery phase of the Covid 19 pandemic.
During the recovery restitution phase of the coronavirus pandemic, breast reconstruction teams have faced particular challenges to restarting this essential service. This is due to the length and complexity of the surgery, along with the demands on healthcare staff. The Royal College of Surgeons have classified immediate breast reconstruction as priority 2 and the National Institute for Health and Care Excellence have provided a pre-operative pathway for resumption of elective procedures. We therefore describe our experience in restarting our service for providing a breast reconstruction service from the 29th June 2020.


The effect of growth temperature on the nanoscale biochemical surface properties of Yersinia pestis.
Yersinia pestis, the causative agent of plague, has been responsible for several recurrent, lethal pandemics in history. Currently, it is an important pathogen to study owing to its virulence, adaptation to different environments during transmission, and potential use in bioterrorism. Here, we report on the changes to Y. pestis surfaces in different external microenvironments, specifically culture temperatures (6, 25, and 37 °C). Using nanoscale imaging coupled with functional mapping, we illustrate that changes in the surfaces of the bacterium from a morphological and biochemical standpoint can be analyzed simultaneously using atomic force microscopy. The results from functional mapping, obtained at a single cell level, show that the density of lipopolysaccharide (measured via terminal N-acetylglucosamine) on Y. pestis grown at 37 °C is only slightly higher than cells grown at 25 °C, but nearly three times higher than cells maintained at 6 °C for an extended period of time, thereby demonstrating that adaptations to different environments can be effectively captured using this technique. This nanoscale evaluation provides a new microscopic approach to study nanoscale properties of bacterial pathogens and investigate adaptations to different external environments.


Unusual metastases from tall cell variant of papillary thyroid cancer.
Tall cell variant (TCV) cancer is considered more aggressive than the classic variant of papillary thyroid cancer (PTC). Distant metastases are more common among this variant and affect survival. Little is known about the molecular pattern of this histotype. This is a report of 2 cases of unusual metastases from TCV, BRAF V600E-positive. A 38-year-old woman developed subcutaneous metastases during short-term follow-up; at medium-term follow-up, the patient showed detectable stimulated serum thyroglobulin without disease evidence at imaging. A 33-year-old man presented incidental thymic metastases at time of surgical treatment; this is the first case of not ectopic thymic metastases from PTC. TCV may present with unusual metastases already during early follow-up. The more aggressive behavior could be linked to the higher prevalence of BRAF point mutations, but only a long-term follow-up might clarify if this association could worsen the prognosis. Moreover, skin metastases have been predictive factors of worse outcome in our patients, but not thymic metastases.


Analytical methodology for metabolomics study of adherent mammalian cells using NMR, GC-MS and LC-HRMS.
We developed a methodology for the analysis of intracellular metabolites using nuclear magnetic resonance spectrometry (NMR), gas-chromatography coupled with mass spectrometry (GC-MS), and liquid chromatography coupled with high resolution mass spectrometry (LC-HRMS). The main steps for analysis of adherent cells in order to recover the widest possible range of intracellular compounds are blocking metabolic activity by quenching and extraction of intracellular metabolites. We explored three protocols to quench NSC-34 cell metabolism and four different extraction methods, analyzed by NMR. On the basis of the number of metabolites extracted and their relative standard deviation (RSD) analyzed by NMR, the most reproducible protocol [quenching by MeOH at -40 °C and extraction with CH2Cl2/MeOH/H2O (3:3:2)] was used to obtain intracellular media to be analyzed by GC-MS and LC-HRMS. GC-MS analysis was optimized by three oximation procedures followed by silylation derivatization and these were compared to silylation alone. Using reversed-phase liquid chromatography (C18), four different gradients for LC-MS were compared. The analytical protocols were determined to establish the reliability and suitability of sample treatments required to achieve the correct biological analysis of untargeted mammalian cell metabolomics.


pCLE detects mucosal neoplastic vascular pattern in gastric linitis plastica.
Linitis plastica (LP) is a very aggressive and rare carcinoma with a scirrhous stroma that affects the submucosal and muscular layers of the stomach even without mucosal alterations. Lack of timely diagnosis is a crucial problem related to its prognosis and treatment. In this study, we investigated the LP-associated vascular pattern as a possible means to improve the diagnosis of these patients. During standard endoscopy, mucosal architecture, tortuosity and enlargement of vessels, as well as the presence of vascular leakage and efficiency of the blood flow were assessed in six LP patients using probe-based Confocal Laser Endomicroscopy (pCLE). In all LP patients, we detected abnormal changes in vasculature. The aberrant features of the vascular network were common to all LP patients examined and consisted of vessel enlargement, tortuosity, and leakage associated with the affected submucosal layer. This is the first study to highlight the presence of marked vascularization associated with LP, characterized by the presence of abnormal and non-functional vessels, similar to what is observed in neoplastic tissues. Therefore, the analysis of LP by pCLE may provide a new endoscopic approach and strategy to better define these patients.


A Systematic Review of Risk Factors for Hepatitis C Virus Infection Among Low-Risk Population in India.
Identification of risk factors for hepatitis C virus (HCV) transmission will help in targeted screening of people who are at risk for HCV. Indian studies, published between January 1989 and June 2020, were systematically reviewed to identify the relevant studies. We searched electronic databases including PubMed/Medline, Embase, Scopus, and Google scholar to identify the original data published in English language. The full-text studies, published in any form, which reported data on risk factors for HCV transmission among low-risk population were selected. The studies which exclusively included high-risk groups were excluded. Data were extracted from 31,176 participants included in 25 studies (median [range] 40 [7-20,113). The participants were HCV infected patients who visited the hospital (n = 10), community population (n = 6), pregnant women (n = 5), blood donors (n = 2), people with diabetes mellitus (n = 1), army recruits (n = 1), or slum dwellers (n = 1). These studies provided data on blood transfusion, use of unsafe injections, minor or major surgery, unsafe dental procedures, tattooing, body piercing, obstetrical procedures, unsafe shaving, intravenous drug use, and unsafe sexual practices as risk factors for HCV transmission. Unsafe injections, body piercing, unsafe dental procedure, unsafe shaving, and tattooing were identified as major risk factors for reported by HCV population participants.More data are needed to identify the risk factors for HCV in Indian population. Risk-factor-targeted screening may increase the yield and reduce the cost of HCV screening in India.


Paramedian supracerebellar transtentorial approach for a medial tentorial meningioma with supratentorial extension: technical case report.
The choice of surgical approach to treat medial tentorial meningiomas is crucial and sometimes difficult to make. Although the subtemporal approach is most commonly used for lesions that extend mostly supratentorially, it risks injury to the vein of Labbé or the veins coursing along the subtemporal surface. To avoid venous injury, a medial tentorial meningioma was removed transtentorially through the infratentorial space via the paramedian supracerebellar transtentorial (PSCTT) approach. A 35-year-old right-handed woman presented with a generalized convulsion. Magnetic resonance imaging scans revealed a left medial tentorial meningioma with supratentorial extension at the dominant hemisphere. The main venous drainage route from the ipsilateral temporal lobe was a sphenopetrosal vein. An operation was performed with the patient in a sitting position, and the tumor was resected totally via the paramedian supracerebellar transtentorial approach without perioperative complications. The paramedian supracerebellar transtentorial approach is useful for supratentorially located medial tentorial meningiomas without retraction of the temporal lobe and without damage to the vein of Labbé or the sphenopetrosal vein.


Painless aortic dissection presenting as spinal cord ischemia.
A 67-year-old woman developed a transient paraplegia as the initial manifestation of acute aortic dissection. Chest or abdominal pain was not present. Magnetic resonance imaging of the thorax demonstrated dissection of the aortic root, aortic arch, and descending aorta as well as pericardial effusion. Ultrasonography of the abdomen revealed an intimal flap in the region of the artery of Adamkiewicz. During aortic dissection, temporary obstruction of spinal arteries may result in transient paraplegia. Painless aortic dissection should be considered in patients who present with transient myelopathy.


Smoking Cessation in Individuals With Serious Mental Illness: A Randomized Controlled Trial of Two Psychosocial Interventions.
Smoking among individuals with serious mental illness is a critical public health problem. Although guidelines recommend bupropion for these smokers, many do not want to use medications for smoking cessation, express ambivalence about identifying a "quit date," and do not have access to behavioral smoking cessation services integrated with mental health care. Individuals with serious mental illness who smoked 10 or more cigarettes per day (N = 178) were randomized to either a multifaceted behavioral group intervention or a supportive group intervention, both of which were integrated within outpatient mental health services at three VA medical centers. Participants attended twice-weekly meetings for 12 weeks, provided information on their smoking at each meeting, and completed baseline and post-treatment assessments conducted by an assessor who was blind to condition. Primary outcomes collected at post-treatment included 1-week abstinence, number of cigarettes smoked per day during the last week, and number of quit attempts during the treatment period. Outcomes examined for a subset of participants who attended at least one intervention meeting (n = 152) included smoking abstinence for 1-, 2-, and 4-week blocks during the treatment period. Analyses conducted on those participants who attended three or more intervention meetings (n = 127) included time to 50% reduction in the number of cigarettes smoked and time to first quit attempt. Sixteen participants achieved abstinence (11.8%), smoking quantity was significantly reduced (baseline M = 15.2, SD = 9.8 to post-treatment M = 7.5, SD = 7.7, p <.0001), and most reported making a quit attempt (n = 88, 72.7%). There were no differences by study condition on any abstinence or reduction outcomes. Significant reductions in number of cigarettes smoked generally took place within the first two weeks; however, these reductions did not often translate into abstinence. Many participants reduced their smoking and sampled quitting during the study. Implementing smoking cessation services in mental health treatment settings is feasible and, if delivered in line with best practices, either a behavioral or a supportive approach can be helpful. Future research should examine ways to facilitate the transition from reduction to abstinence. This study was part of a clinical trial registered as NCT #00960375 at www.clinicaltrials.gov.


Dietary sodium restriction exacerbates age-related changes in rat adipose tissue and liver lipogenesis.
To investigate the effects of prolonged dietary sodium restriction on lipid metabolism, male rats weighing 35 to 40 g (just weaned) were fed either a low-salt (LSD) or a normal salt diet (NSD) and used in metabolic experiments after 1, 2, or 3 months of diet consumption. After 2 and 3 months on the diet, LSD rats showed increased amounts of lipid in carcass and retroperitoneal tissue. In both LSD and NSD, extending the feeding period from 2 to 3 months resulted in a marked reduction in the in vivo rates of adipose tissue fatty acid synthesis that was accompanied by increases in liver lipogenesis and in the activity of adipose tissue lipoprotein lipase (LPL). However, these increases were more marked in LSD rats. Thus, in vivo rates of liver fatty synthesis and LPL activity in LSD rats, which were already higher (by about 35% and 20%, respectively) than in controls after 2 months, attained levels 50% higher than those in NSD animals after another month on the diet. Brown adipose tissue (BAT) thermogenic capacity, estimated after 2 and 3 months by the tissue temperature response to norepinephrine (NE) injection and by guanosine diphosphate (GDP) binding to BAT mitochondria, did not change in controls, but was significantly reduced in LSD rats. This raises the possibility that a decrease in overall energy expenditure, together with an LPL-induced increased uptake of preformed fatty acids from the circulation, may account for the excessive lipid accumulation in LSD rats. Taken together, the data indicate that prolonged dietary sodium restriction exacerbates normal, age-related changes in white and BAT metabolism.


Higher response with bone mineral density increase with monthly injectable ibandronate 1 mg compared with oral risedronate in the MOVER study.
We examined response to bone mineral density (BMD) gains in the MOVER study following treatment with intravenous (IV) ibandronate 1 mg/month, and investigated the characteristics of a non-responder group. At 1 year, responder rates for patients with BMD increases >0 % were similar with IV ibandronate 0.5 or 1 mg/month and oral risedronate 2.5 mg/day. However, after 3 years, responder rates with BMD increases ≥3 % were highest with ibandronate 1 mg at all bone sites (>80 % at the lumbar spine [L2-L4] and >50 % at all femur sites, which was significantly higher than with risedronate). Non-responders were defined by BMD increases ≤3 % at L2-L4 or ≤0 % at total hip, and ≤50 % reduction in creatinine-corrected urinary collagen type 1 cross-linked C-telopeptide (uCTX) from baseline to 1 year. There were a small number of non-responders in the ibandronate 1 mg group: 3.3 % (10/299) with ≤0 % total hip BMD increase and ≤50 % uCTX reduction from baseline. These non-responders had lower 25-hydroxyvitamin D (25[OH]D) levels than responders, but no differences in kidney function, L2-L4 BMD or bone turnover marker baseline values. Throughout the study, non-responders failed to show any increases in BMD. Our analysis demonstrates significantly higher responder rates with IV ibandronate 1 mg/month than with risedronate at 3 years. A small number of non-responders in the ibandronate group had lower 25(OH)D baseline levels than responders, suggesting that 25(OH)D levels could be a useful indicator of BMD response to therapy.


Large-Scale Preparation for Multicolor Stimulus-Responsive Room-Temperature Phosphorescence Paper via Cellulose Heterogeneous Reaction.
The large-scale preparation of sustainable room-temperature phosphorescence (RTP) materials, particularly those with stimulus-response properties, is attractive but remains challenging. This study develops a facile heterogeneous B─O covalent bonding strategy to anchor arylboronic acid chromophores to cellulose chains using pure water as a solvent, resulting in multicolor RTP cellulose. The rigid environment provided by the B─O covalent bonds and hydrogen bonds promotes the triplet population and suppresses quenching, leading to an excellent lifetime of 1.42 s for the target RTP cellulose. By increasing the degree of chromophore conjugation, the afterglow colors can be tuned from blue to green and then to red. Motivated by this finding, a papermaking production line is built to convert paper pulp reacted with an arylboronic acid additive into multicolor RTP paper on a large scale. Furthermore, the RTP paper is sensitive to water because of the destruction of hydrogen bonds, and the stimuli-response can be repeated in response to water/heat stimuli. The RTP paper can be folded into 3D afterglow origami handicrafts and anti-counterfeiting packing boxes or used for stimulus-responsive information encryption. This success paves the way for the development of large-scale, eco-friendly, and practical stimuli-responsive RTP materials.


Regulation of galactose-1-phosphate uridyltransferase gene expression.
Analysis of both the human and rat galactose-1-phosphate uridyltransferase (GALT) genes reveal 5' regulatory consensus sequences suggestive of a housekeeping gene. This is in accord with the finding of GALT activity in all tissues. However, the complications seen in galactosemia, in particular ovarian dysfunction and verbal dyspraxia, suggest organ-specific sensitivity to lack of GALT activity. Analysis of steady-state GALT mRNA and specific activity levels in adult rat organs reveals a marked difference between organs that correlates with the degree of organ dysfunction in humans with galactosemia. The organ variation in GALT mRNA and activity thus appears to be due to genetic regulation. Discernment of the pathophysiologic basis for the organ-specific complications requires an understanding of the basis for the differences in organ regulation. The present state of knowledge of the regulation of the Leloir enzymes in general, GALT in particular, from prokaryotes to mammals is discussed.


Glomerular hemodynamics in cyclosporine nephrotoxicity following uninephrectomy.
Experiments were performed to determine the cause of the reduced glomerular filtration rate (GFR) in cyclosporine nephrotoxicity during compensatory renal growth. Sprague-Dawley rats were uninephrectomized and given daily injections of cyclosporine (30 mg/kg, i.m.) or vehicle (olive oil), and studied 7 or 14 days later. In cyclosporine treated rats GFR was lower seven days (1.34 +/- 0.10 vs. 1.68 +/- 0.07 ml/min) and 14 days (1.19 +/- 0.08 vs. 1.58 +/- 0.04, P less than 0.025) following uninephrectomy. Arterial blood pressure, cardiac output and renal blood flow (RBF) were not different in cyclosporine and control rats. Kidney mass increased to the same extent in cyclosporine and control rats. Micropuncture of the glomerular microcirculation in similarly prepared Munich-Wistar rats demonstrated low whole kidney GFR (1.10 +/- 0.07 vs. 1.55 +/- 0.13 ml/min, P less than 0.01), and single nephron GFR (31.07 +/- 2.27 vs. 42.36 +/- 2.47 nl/min, P less than 0.005) in cyclosporine treated rats as compared to controls. Single nephron plasma flow, afferent and efferent arteriolar resistance, the transglomerular hydrostatic pressure gradient, and arterial blood pressure were the same in both groups. The glomerular capillary ultrafiltration coefficient (Kf) was lower in cyclosporine treated rats compared to controls [0.039 +/- 0.002 vs. 0.075 +/- 0.013 nl/(sec.mm Hg), P less than 0.025]. We conclude that in this model of cyclosporine nephrotoxicity the low GFR is caused solely by a reduction in Kf, and that cyclosporine can reduce GFR without causing renal vasoconstriction.


Temperature screening has negligible value for control of COVID-19.
To report the incidence of fever among patients who tested positive for SARS-CoV-2. Retrospective cohort study of patients who tested positive for SARS-CoV-2 at a single centre. Temperature at time of testing and on repeat testing within 24 h were collected. At the time of testing, fever was detected (sensitivity) in 16 of 86 (19%; 95% confidence interval 11-28) episodes of positive tests for SARS-CoV-2. With repeat testing, fever was detected in 18 of 75 (24%; 95% confidence interval 15-35) episodes. In an Australian hospital, screening for fever lacked sensitivity for detection of patients with SARS-CoV-2.


Ultrasensitive detection of pepsinogen I and pepsinogen II by a time-resolved fluoroimmunoassay and its preliminary clinical applications.
A fast and highly sensitive assay for pepsinogen I (PG I) and pepsinogen II (PG II) by using time-resolved fluoroimmunoassay (TRFIA) detection technique has been developed for the determination of serum PG I and PG II against gastrointestinal diseases. On the noncompetitive assay, one monoclonal antibody (McAb) coated on wells was directed against a specific antigenic site on the PG I or PG II. The McAb, called as labelling McAb, was prepared with the europium-chelate of N-(p-isothiocyanatobenzyl)-diethylenetriamine-N,N,N,N-tetraacetic acid and directed against a different antigenic site on the PG I or PG II molecule. After bound/free separation by washing, the fluorescence counts of bound Eu(3+)-McAb were measured. The levels of PG in sera from patients or healthy volunteers were determined by PG I and PG II TRFIA using the autoDELFIA(1235) system. The measurement ranges of PG I-TRFIA were 3.5-328.0 microg L(-1) and those of PG II-TRFIA were 2.0-55.0 microg L(-1). The within-run and between-run CVs of the PG I-TRFIA were 1.9% and 4.7%, respectively, and those of PG II-TRFIA were 2.1% and 3.8%, respectively. The recovery rates of PG I-TRFIA and PG II-TRFIA were 102.7% and 104.6%, respectively. The detection limitations of PG I and PG II were 0.05 microg L(-1) and 0.02 microg L(-1), respectively. The dilution experiments showed the percentage of expected value of PG I-TRFIA was 93.2-102.3% and of PG II-TRFIA was 97.3-110.6%. The cross-reacting rate between PG I and PG II was negligible. The linear correlation of radioimmunoassay (RIA) and TRFIA measurements resulted in a correlation coefficient as 0.926 of PG I and as 0.959 of PG II. The europium-labelling McAbs were stable for at least one year at -20 degrees C, and the results of the TRFIA with same reagents were reproducible over one year as well. The means of 1600 healthy volunteers were 162.4+/-52.1 microg L(-1) for serum PG I, 11.7+/-6.8 microg L(-1) for serum PG II, and 13.8+/-7.4 for the PG I/PG II ratio. The normal ranges of Serum PG I levels for healthy volunteers were 58.2-266.6 microg L(-1), and those of serum PG II levels were less than 25.3 microg L(-1). The availability of a highly sensitive, reliable, and convenient PG-TRFIA method for quantifying PG will allow investigations into the possible diagnostic value of this analysis in various clinical conditions, including gastric carcinoma, duodenal ulcer, gastric ulcer and gastritis. The sensitivity and reproducibility of the assay were satisfactory for clinical applications.


Primary Stability of Collared and Collarless Cementless Femoral Stems - A Finite Element Analysis Study.
Primary stability of the femoral stem is important for the long-term results of cementless total hip arthroplasty. Cementless collared stems have been known to have higher stability than collarless stems when there is a contact between the collar and the calcar. The purpose of this study was to compare the stabilities of collared stem and collarless stem in 2 loading conditions: 1) flat walking and 2) stair climbing. We constructed 3 finite element models. In the first model, the collar had contact with the calcar. The second model had a 1 mm gap between the calcar and the collar. The third model was constructed with a collarless stem. The proximal femur around the stem was divided into 3 zones: the upper zone (Gruen zones 1 and 7), the middle zone (Gruen zones 2 and 6), and the lower zone (Gruen zones 3 and 5). The micromotion at the stem/bone interface was measured at each zone of the 3 models under the 2 loading conditions. The results showed that collared stems were more stable when the collar was in contact with the calcar than when a gap was left between the collar and the calcar. In particular, collar contact was highly effective in suppressing the micromotion proximal to the stem. Compared to the collarless stem, the collared stem had comparable stability when there was a gap at the collar and calcar interface and higher stability when there was contact between the collar and the calcar.


The correlation of the phi function of the difference score with performance and its relevance to laterality experiments.
It is shown that there is a generic correlation between the phi functions of differences in pairs of scores and the averages of pairs of scores. This correlation can be approximated extremely accurately given only the means, variances, and covariance of the two scores in the sample data. Thus, even when difference scores are transformed into their phi equivalents, these are still not independent of performance level.