Oxygen-17 NMR study of aqueous peroxotungstates.
Aqueous peroxotungstates have been studied from pH 0.5 to 9.0, over a range of peroxide concentrations. Although equilibria are not always established, many anions can be identified by 17O NMR because the ratio of deltaO(W anion)/deltaO(known Mo anion) is consistently 79 +/- 3%. They are [WO3(HO2)]-; [WO(OH)(O2)2]-; [WO(OH2)(O2)2]0; [W2O3(O2)4]2-; [W2O3(OH)(O2)4]3-; [W4O12(O2)2]4-; [W7O23(O2)]6- and [W7O22(O2)2]6-. Their pKa values, where measurable, are about 2 units lower than the corresponding peroxomolybdates, e.g. 0.0 for [WO(OH2)(O2)2]0 and 8.0 for [W2O3(O2)4]2-. Other peroxotungstate species are also present but can only be broadly identified. These include Keggin structures with relatively low peroxo content, and a very unsymmetrical anion appearing at pH ca. 7 that bears no obvious structural relationship to any species previously reported. The main product from the reaction of powdered W metal with 30% aqueous peroxide is provisionally identified as the symmetrical anion [W6O13(OH)2(OH2)2(O2)5]2-, although other minor species are also formed, probably having fewer peroxo substituents.


The nosology of sub-acute and chronic fatigue syndromes that follow infectious mononucleosis.
A previous principal components analysis of symptoms occurring after infectious mononucleosis suggested that a discrete fatigue syndrome occurs, which is independent of psychiatric disorder. This work has not been replicated and no latent class analysis of subjects has been published. We prospectively examined a cohort of 150 American primary care patients 2 and 6 months after the onset of corroborated infectious mononucleosis. A subset of 50 subjects was studied 4 years after onset. We performed principal components analyses of both psychological and somatic symptoms and latent class analyses of subjects. Principal components analyses consistently delineated two fatigue factors at 2 and 6 months and one fatigue factor at 4 years. These factors were separate from a mixed anxiety and depressive factor. A four-class solution for the latent class analyses consisted of most subjects with few symptoms, a few with many symptoms, a group with predominantly mood symptoms and some subjects with fatigue symptoms. The symptoms of the principal factors with fatigue were similar to those previously described. Both the factors and classes were independent of an equally delineated mood factor and class. These results support the existence of two discrete chronic fatigue syndromes after infectious mononucleosis, one of which is still demonstrable 4 years after onset.


Prognostic significance of B-cells and pSTAT3 in patients with ovarian cancer.
Several previous studies have identified a strong association between T-cell infiltration and clinical outcome in ovarian cancer. The role of B-cells remains controversial, however. Forty-nine paraffin-embedded omental specimens derived from patients with high grade epithelial ovarian cancer were assessed. Immunohistochemical analyses were performed to characterize expression of CD19(+) B-cells and pSTAT3 as high (>50% positively staining cells [PSCs]) or low (<50% PSCs). The Kaplan-Meier method with log-rank test was used to determine the association between clinicopathologic parameters and overall survival (OS). A multi-variate Cox proportional hazards regression analysis including nature of debulking (primary vs secondary), histology, tumor grade, receipt of prior chemotherapy, B-cell infiltration and pSTAT3 expression was performed. Median OS was 160.6 months in those patients with low B-cell expression vs 47.3 months in those with high B-cell expression (P = 0.0015). Similarly, median OS was improved in those patients with low pSTAT3 expression (160.6 vs 47.9 months, P = 0.02). In a multivariate model to predict survival, only the degree of B-cell infiltration and clinical stage were retained. pSTAT3 expression did not enter the final model, possibly be due to a high positive correlation with B-cell infiltration (r = 0.82, P<0.0001). Increased B-cell infiltration and pSTAT3 expression in omental tissue are associated with poorer survival.


Teleost Metamorphosis: The Role of Thyroid Hormone.
In most teleosts, metamorphosis encompasses a dramatic post-natal developmental process where the free-swimming larvae undergo a series of morphological, cellular and physiological changes that enable the larvae to become a fully formed, albeit sexually immature, juvenile fish. In all teleosts studied to date thyroid hormones (TH) drive metamorphosis, being the necessary and sufficient factors behind this developmental transition. During metamorphosis, negative regulation of thyrotropin by thyroxine (T4) is relaxed allowing higher whole-body levels of T4 that enable specific responses at the tissue/cellular level. Higher local thyroid cellular signaling leads to cell-specific responses that bring about localized developmental events. TH orchestrate in a spatial-temporal manner all local developmental changes so that in the end a fully functional organism arises. In bilateral teleost species, the most evident metamorphic morphological change underlies a transition to a more streamlined body. In the pleuronectiform lineage (flatfishes), these metamorphic morphological changes are more dramatic. The most evident is the migration of one eye to the opposite side of the head and the symmetric pelagic larva development into an asymmetric benthic juvenile. This transition encompasses a dramatic loss of the embryonic derived dorsal-ventral and left-right axis. The embryonic dorsal-ventral axis becomes the left-right axis, whereas the embryonic left-right axis becomes, irrespectively, the dorsal-ventral axis of the juvenile animal. This event is an unparalleled morphological change in vertebrate development and a remarkable display of the capacity of TH-signaling in shaping adaptation and evolution in teleosts. Notwithstanding all this knowledge, there are still fundamental questions in teleost metamorphosis left unanswered: how the central regulation of metamorphosis is achieved and the neuroendocrine network involved is unclear; the detailed cellular and molecular events that give rise to the developmental processes occurring during teleost metamorphosis are still mostly unknown. Also in flatfish, comparatively little is still known about the developmental processes behind asymmetric development. This review summarizes the current knowledge on teleost metamorphosis and explores the gaps that still need to be challenged.


An unusual cause of carpal tunnel syndrome.
Tuberculosis is an uncommon cause of carpal tunnel syndrome. We report a patient with systemic lupus erythematosus who developed hand numbness. Ultrasonic, operative and microbiological findings supported the diagnosis of median nerve compression secondary to a tuberculous abscess. The symptoms resolved with surgical excision and antituberculous chemotherapy.


Sustaining and improving working capacity--programme description and two years follow-up.
In 1991 the Social Insurance Institution Rehabilitation Act introduced a working capacity sustaining and improving training programme (TYK). The goal of this programme is to sustain the physio-psycho-social competences of older workers and employees by creating a chain of in-house rehabilitation phases and training phases at the workplace. We describe the programme in its early state of implementation. Two years after entering the programme 17 patients were working, six were on sick leave, three were out of work, 16 were on pension, and six patients could not be retrieved.


Methodologies for evaluating exoskeletons with industrial applications.
Industrial exoskeletons are globally developed, explored, and increasingly implemented in industrial workplaces. Multiple technical, physical, and psychological aspects should be assessed prior to their daily application in various occupational environments. The methodology for evaluating these aspects is not standardised and differs in terms of focussed research objectives, used types of analyses, applied testing procedures, and use cases. The aim of this paper is to provide a matrix comparing the prevalence of different types of analyses combined with their respective research objective(s). A systematic review in the database 'Web of Science' identified 74 studies, mainly in laboratory settings, with a focus on short-term effects as well as with male-dominated samples being low representative for industrial workforces. The conducted evaluation methodologies are further discussed and compared in terms of testing procedure, sample, and research objectives. Finally, relevant aspects for prospectively evaluating industrial exoskeletons in a more harmonised and comprehensive way are suggested. Practitioner summary: Industrial exoskeletons are still inconsistently and insufficiently evaluated in scientific studies, which might hamper the comparability of systems, threaten the human health, and block an iterative system optimisation. Thus, a comprehensive evaluation methodology is needed with harmonised and multicriteria types of analyses.


Altered expression of basement-membrane components and collagenases in ascitic xenografts of OVCAR-3 ovarian cancer cells.
Ascitic ovarian cancer cells, which derive from solid tumors, complicate the treatment of ovarian cancer by spreading throughout the peritoneal cavity. Because basement-membrane components may influence tumor-cell proliferation and dissemination, the present studies examined the production of (a) basement-membrane attachment and migration factors (laminin, fibronectin and type IV collagen); (b) a laminin receptor, the 32/67-kDa laminin-binding protein, the presence of which correlates with malignancy; and (c) metalloproteinases (types I and IV collagenase and stromelysin), by ascitic and cultured OVCAR-3 cells and solid OVCAR-3 tumors. The cultured cells and solid tumors produced high levels of mRNA encoding attachment factors and metalloproteinases, and low levels of mRNA for the 32/67-kDa laminin receptor. In contrast, the ascitic ovarian cells had low or undetectable levels of mRNA encoding laminin, type IV collagen and metalloproteinases, but higher levels of transcripts for the laminin receptor. Our results suggest that the apparent inability of ascitic OVCAR-3 cells to attach to host-tissue surfaces may be a consequence, in part, of low levels of expression of laminin, type IV collagen and/or type IV collagenase.


Submicron-patterned fibronectin controls the biological behavior of human dermal fibroblasts.
Cell adhesion is an important step in cell survival, and in the proliferation of anchorage-dependent cells, whose dimensions can be controlled by micro-patterning of the cell-adhesive extracellular matrix. To fabricate a micro-patterned fibronectin substrate with spacings ranging from 0.9 microm to 20 microm, we made a replica mold using e-beam lithography. The physiological behavior of human dermal fibroblasts (HDFs) on a substrate with a gradient of pattern spacings from 0.9 microm to 20 microm was evaluated after 4.5 hours and 2 days of culture. The number of proliferating cells on the fibronectin-patterned surface increased as the spacing between strip lines increased to 11 micron. However, the number of cells gradually decreased when the pattern spacing exceeded 11 microm. These findings demonstrate that the submicron-patterned topography of a substrate plays important roles in HDF survival and proliferation.


[Primary hyperparathyroidism. Mechanisms of hypercalcemia].
In primary hyperparathyroidism, hypercalcaemia is due to inappropriate hypersecretion of parathormone (PTH). Yet, the intestinal or osseous origin of the excess in plasma calcium and the symptoms of the disease are largely conditioned by vitamin D reserve and metabolism. In cases with sufficient vitamin D reserve and normal metabolism, the primary disorder is hyperabsorption of calcium by the intestine, and there is a risk of renal stone formation. In patients with vitamin D deficiency, there is a significant increase of bone resorption accompanied by osteoarticular symptoms. In addition, other factors, as yet unidentified, seem to intervene in the reabsorption of calcium by the renal tubule, which commands the degree of hypercalcaemia. Hypersecretion of parathormone may be due either to a reduced sensitivity of parathyroid cells to calcium (as in adenomas) or to an increase of the PTH-secreting thyroid mass (as in hyperplasia and some adenomas).


Trauma, workfare and the social contingency of precarity and its sufferings: the story of Marius, a street-youth.
Based on ethnographic fieldwork in London, Ontario, Canada, with homeless and street-involved youth in a youth drop-in shelter that I call "At Home", this paper is an ethnographically grounded narrative analysis of interview content and participant observation with a centre focus on my key informant, a youth from Eastern Europe whom I call "Marius". Like many other street youth, Marius lives a life marked by precarity. His daily life is marked by traumatic memories of abandonment and abuse, which has lead to an inability to work; and structural violence facilitated by Ontario's workfare program called Ontario Works, especially its mandate that all "participants" (i.e. those in receipt of social assistance, such as Marius) seek employment or face termination of their social assistance check. For Marius, the recounting of traumatic memories at At Home opened up a shared rhetorical space from which he could narratively align himself vis-à-vis other street youth as a victim of precarity and trauma and therefore absolve himself of the onus to find employment. Regardless of his narrative positioning, he is constantly terminated from Ontario Works for not submitting proof of citizenship and proof of job-seeking activities. In conclusion, the only way for Marius to find any form of solace from his past and the constraints of OW is through isolation: a cultural stance that serves as a coping mechanism, and allows Marius to muddle through each day, all the while holding precarity and its pursuant anxiety and depression at bay.


In vivo role of glucocorticoids in barotrauma vascular repair and fibrosis.
To determine the important repair events leading to vascular collagen accumulation following barotrauma, in vivo changes were assessed during dexamethasone (DEX) treatment, as well as physiological healing. Hypercholesterolemic rabbits underwent bilateral iliac artery endothelial denudation, followed by angioplasty. Messenger ribonucleic acid (RNA) (procollagen types I, III and transforming growth factor [TGF]beta1), and bio-histometric composition of iliac arteries of animals treated with DEX (2, 7 and 7 days; 1 mg/kg1/day1), were compared to that in controls 2, 7 and 30 days after angioplasty. Type I and III procollagen mRNA transcripts were up-regulated following injury in either group. Similarly, TGFbeta1 mRNA levels were also elevated; however, treatment with DEX led to down-regulation at day 30 post-angioplasty. Linear regression and correlation of the densitometric ratios of procollagen alpha1(I) and TGFbeta1 mRNA during repair were observed significantly in either group (DEX-treated, r2= 0.84; non-treated, r2=0.79). Biochemically derived total vascular RNA concentration decreased transiently (7 days), with DEX-treatment (P = 0.003). Arterial lumen cross-sectional area was reduced between days 2 and 30 (P=<0.02), accompanied by an increase in fibrillar collagen concentration in both groups of animals post-angioplasty. These results suggest that during barotrauma repair, administration of DEX (approximately 1 week), does not affect vascular intimal hyperplasia or fibrosis, and that despite treatment, significant production of type I procollagen mRNA continues, influencing subsequent collagen deposition. The data also confirm a strong correlation between TGFbeta1 and type I procollagen mRNA expression, and modestly with type III procollagen during post-angioplasty repair.


Electrospinning of Cellulose Nanocrystal-Reinforced Polyurethane Fibrous Mats.
We report the electrospinning of mechanically-tunable, cellulose nanocrystal (CNC)-reinforced polyurethanes (PUs). Using high-aspect ratio CNCs from tunicates, the stiffness and strength of electrospun PU/CNC mats are shown to generally increase. Furthermore, by tuning the electrospinning conditions, fibrous PU/CNC mats were created with either aligned or non-aligned fibers, as confirmed by scanning electron microscopy. PU/CNC mats having fibers aligned in the strain direction were stiffer and stronger compared to mats containing non-aligned fibers. Interestingly, fiber alignment was accompanied by an anisotropic orientation of the CNCs, as confirmed by wide-angle X-ray scattering, implying their alignment additionally benefits both stiffness and strength of fibrous PU/CNC nanocomposite mats. These findings suggest that CNC alignment could serve as an additional reinforcement mechanism in the design of stronger fibrous nanocomposite mats.


Validation of a supplemental reading intervention for first-grade children.
This experimental study was designed to validate a short-term supplemental reading intervention for at-risk first-grade children. Although substantial research on long-term supplemental reading interventions exists, less is known about short-term interventions. Thirty first-grade children were randomly assigned to intervention or control conditions. Students in the intervention received 16 hours of instruction. Analyses of pre- and posttest data and growth measures suggest that short-term supplemental reading intervention had a significant effect on children's reading skills; however, effects were not consistent across measures. Parent and teacher ratings moderated significant effects. Findings support the validity of a brief intervention for students at risk for reading failure that may inform Tier 2 interventions within a Response to Intervention framework.


Gasless laparoscopy-assisted colon surgery utilizing mini-laparotomy and a subcutaneous abdominal wall lift system.
This study was performed to investigate the technical aspects and perioperative results of using a subcutaneous abdominal wall lift system for laparoscopy-assisted colectomy. We attempted a laparoscopy-assisted colectomy for 19 patients and completed 16 cases using mini-laparotomy and a subcutaneous abdominal wall lift system, observing monitor images via laparoscopy or direct views through mini-laparotomy. All 5 surgeons had no experience of laparoscopy-assisted colectomy but considerable experience of laparoscopic cholecystectomy. The operating time ranged from 120 to 360 minutes with an average of 188. Intraoperative blood loss ranged from 20 to 300 mL with an average of 116 mL. No postoperative major complications occurred, but 5 cases suffered wound infection. Laparoscopy-assisted colon surgery utilizing a subcutaneous abdominal wall system and mini-laparotomy was feasible as minimally invasive surgery for colorectal diseases, even for surgeons with little previous experience.


Freshly isolated bone marrow cells induce death of various carcinoma cell lines.
In some carcinomas such as digestive tract carcinomas, bone marrow infiltration by tumor cells is a frequent event but usually remains a micrometastatic disease and rarely induces overt bone lesions. The mechanisms responsible for the control of these metastases in the bone marrow remain poorly known. We show that freshly isolated bone marrow cells from human, murine and rat origin rapidly kill a wide range of syngeneic or xenogeneic carcinoma cell lines in culture. Further analysis of this cytotoxic process in the rat indicated that neither resident bone marrow macrophages nor NK cells were responsible for this cytotoxic effect that was restricted to a subpopulation of bone marrow cells expressing CD90 (Thy-1), a marker of hemopoietic precursors. The tumoricidal activity of these cells did not require long-term culture nor addition of exogenous cytokines or growth factors. A subset of CD90+ cells that rapidly differentiates into CD163(ED2)-expressing macrophages was observed to be responsible for tumor cell killing. These macrophages induced a non-apoptotic death of tumor cells, a process that required both a direct interaction with the tumor cell and nitric oxide (NO) production through the activation of inducible nitric oxide-synthase (iNOS). This ability of pluripotent hemopoietic stem cells to rapidly differentiate into macrophages capable of killing invasive tumor cells may account for the limited expansion of micrometastases of some carcinomas in the bone marrow.


Control of hypobiotic and benzimidazole-resistant nematodes of sheep.
In studies comprising a total of 117 naturally infected crossbred lambs, it was found that lambs turned out to spring pasture were exposed to immediate infection with overwintered Ostertagia, Nematodirus, and Trichostrongylus spp, but did not acquire Haemonchus contortus infection until July. With all species, there appeared to be only one major disease-producing generation of worms per year; it was responsible for serious worm burdens and clinical disease from July onward. High frequencies of hypobiosis (arrested development) were demonstrated in H contortus (98% to 100%), Ostertagia circumcincta (89% to 96%), and Nematodirus filicollis (77% to 90%) by late November; Trichostrongylus spp comprised most of the adult (egg-laying) worm population at that time. The onset of hypobiosis appeared to be induced by seasonal stimuli rather than by host-immune responses. The results of these studies showed benzimidazole resistance to be a major problem. In the first year, fenbendazole (5 mg/kg) reduced worm burdens by 46% and 20% in September and December, respectively. In December of the second year, levamisole (8 mg/kg) reduced worm burdens by 99%, thiabendazole (44 mg/kg) by 55%, fenbendazole (5 mg/kg) by 47%, and fenbendazole (15 mg/kg) by 11%. Levamisole was highly efficient (99%) against adult worms, hypobiotic worms, and benzimidazole-resistant worms. Ostertagia circumcincta was strongly resistant to the benzimidazole drugs at all dosages tested, while H contortus and Trichostronglylus spp were partially resistant. There was no evidence of reversion of resistant worms to susceptibility on this farm, even though benzimidazole drugs had not been used for 9 years.


DExSI: a new tool for the rapid quantitation of 13C-labelled metabolites detected by GC-MS.
Stable isotope directed metabolomics is increasingly being used to measure metabolic fluxes in microbial, plant and animal cells. Incorporation of 13C/15N isotopes into a wide range of metabolites is typically determined using gas chromatography-mass spectrometry (GC/MS) or other hyphenated mass spectrometry approaches. The DExSI (Data Extraction for Stable Isotope-labelled metabolites) pipeline is an interactive graphical software package which can be used to rapidly quantitate isotopologues for a wide variety of metabolites detected by GC/MS. DExSI performs automated metabolite annotation, mass and positional isotopomer abundance determination and natural isotope abundance correction. It provides a range of output options and is suitable for high throughput analyses. DExSI is available for non-commercial use from: https://github.com/DExSI/DExSI/. For Microsoft Windows 7 or higher (64-bit). firstname.lastname@example.com or firstname.lastname@example.com. Supplementary data are available at Bioinformatics online.


Ponatinib dose-ranging study in chronic-phase chronic myeloid leukemia: a randomized, open-label phase 2 clinical trial.
In PACE (Ponatinib Ph+ ALL and CML Evaluation), a phase 2 trial of ponatinib that included patients with chronic-phase chronic myeloid leukemia (CP-CML) resistant to multiple prior tyrosine kinase inhibitors (TKIs), ponatinib showed deep and durable responses, but arterial occlusive events (AOEs) emerged as notable adverse events. Post hoc analyses indicated that AOEs are dose dependent. We assessed the benefit/risk ratio across 3 ponatinib starting doses in the first prospective study to evaluate a novel, response-based, dose-reduction strategy for TKI treatment. Adults with CP-CML resistant to or intolerant of at least 2 prior BCR-ABL1 TKIs or with a BCR-ABL1 T315I mutation were randomly assigned 1:1:1 to 3 cohorts receiving ponatinib 45, 30, or 15 mg once daily. In patients who received 45 or 30 mg daily the dose was reduced to 15 mg upon response (BCR-ABL1IS transcript levels ≤1%). The primary end point was response at 12 months. From August 2015 through May 2019, 283 patients were randomly assigned to the cohorts: 282 (94 per dose group) received treatment (data cutoff, 31 May 2020). The primary end point (98.3% confidence interval) was achieved in 44.1% (31.7-57.0) in the 45-mg cohort, 29.0% (18.4-41.6) in the 30-mg cohort, and 23.1% (13.4-35.3) in the 15-mg cohort. Independently confirmed grade 3 or above treatment-emergent AOEs occurred in 5, 5, and 3 patients in the 45-, 30-, and 15-mg cohorts, respectively. All cohorts showed benefit in this highly resistant CP-CML population. Optimal benefit/risk outcomes occurred with the 45-mg starting dose, which was decreased to 15 mg upon achievement of a response. This trial is registered on www.clinicaltrials.gov as NCT02467270.


Attenuation of oxidative stress and alteration of hepatic tissue ultrastructure by D-pinitol in streptozotocin-induced diabetic rats.
The present study was aimed to investigate the effect of D-pinitol on hyperglycaemia mediated oxidative stress by analysing the hepatic antioxidant competence, pro-inflammatory cytokines and ultrastructural changes in liver tissues of streptozotocin-induced diabetic rats. Oral administration of D-pinitol (50 mg/kg b.w.) resulted in significant (p < 0.05) attenuation in blood glucose, glycosylated haemoglobin and pro-inflammatory markers such as TNF-alpha, IL-1beta, IL-6, NF-kappaB p65 unit and NO and significant (p < 0.05) elevation in the plasma insulin level. In addition, D-pinitol instigated a significant escalation in the levels of hepatic tissue non-enzymatic antioxidants and the activities enzymatic antioxidants of diabetic rats with significant (p < 0.05) decrease in lipid peroxides and hydroperoxides formation, thus demonstrating the protective role of D-pinitol on the hepatic tissues from oxidative stress-induced liver damage. These biochemical observations were complemented by histological and ultrastructural examination of liver section. Thus, the present study demonstrates the hepatoprotective nature of D-pinitol by attenuating hyperglycaemia-mediated pro-inflammatory cytokines and oxidative stress.


Methods for the detection of trichothecenes.
The trichothecenes are a group of fungal metabolites with a tetracyclic, sesquiterpenoid ring system and include a number of compounds which are highly toxic. These compounds are produced by various species of the imperfect fungi including members of the following genera: Calonectria, Fusarium, Myrothecium, Stachybotrys, Trichoderma, and Trichothecium. Both biological and chemical methods for detection of various trichothecenes are reviewed. Some of the bioassay techniques in use for the detection of the various trichothecenes include the rabbit dermal toxicity tests, cytotoxicity, and inhibition of protein synthesis tests; these are highly sensitive but lace specificity. The sensitivity of these tests for the T-2 toxin are 0.005 mug for rabbit skin toxicity, 0.03 mug/ml for inhibition of protein synthesis in rabbit reticulocytes, and less than 1 mug/ml for cytotoxicity to human karyoblast cells. In the present state of development of the chemical assay methods, thin layer and gas-liquid chromatography are specific for various trichothecenes but lack sensitivity. The lower detection limit of the trichothecenes on thin layer plates varies from 0.2 to 2-3 mug/spot while gas-liquid chrommatography has a reported sensitivity of approximately 0.05 mug/injection.


Whole-cell configuration of the patch-clamp technique in the hERG channel assay to predict the ability of a compound to prolong QT interval.
In vitro electrophysiological safety studies have become an integral part of the drug development process since, in many instances, compound-induced QT prolongation has been associated with a direct block of human ether-a-go-go-related gene (hERG) potassium channels or its native current, the rapidly activating delayed rectifier potassium current (I(Kr)). Therefore, the in vitro hERG channel patch-clamp assay is commonly used as an early screen to predict the ability of a compound to prolong QT interval. The protocol described in this unit is designed to assess the effects of new chemical entities after acute or long-term exposure on the amplitude of I(Kr) in human embryonic kidney 293 (HEK293) cells stably transfected with the hERG channel (whole-cell configuration of the patch-clamp technique). Examples of results obtained with terfenadine, arsenic, pentamidine, erythromycin, and sotalol are provided for illustrative purposes.


[Application characteristics and situation analysis of volatile oils in database of Chinese patent medicine].
Aromatic traditional Chinese medicines have a long history in China, with wide varieties. Volatile oils are active ingredients extracted from aromatic herbal medicines, which usually contain tens or hundreds of ingredients, with many biological activities. Therefore, volatile oils are often used in combined prescriptions and made into various efficient preparations for oral administration or external use. Based on the sources from the database of Newly Edited National Chinese Traditional Patent Medicines (the second edition), the author selected 266 Chinese patent medicines containing volatile oils in this paper, and then established an information sheet covering such items as name, dosage, dosage form, specification and usage, and main functions. Subsequently, on the basis of the multidisciplinary knowledge of pharmaceutics, traditional Chinese pharmacology and basic theory of traditional Chinese medicine, efforts were also made in the statistics of the dosage form and usage, variety of volatile oils and main functions, as well as the status analysis on volatile oils in terms of the dosage form development, prescription development, drug instruction and quality control, in order to lay a foundation for the further exploration of the market development situations of volatile oils and the future development orientation.


The Effect of Anaesthesia Management with Different Fresh Gas Flows on Cognitive Functions of Geriatric Patients: A Randomized Double-blind Study.
The present study aimed to compare the effects of two different fresh gas flows (FGFs) (0.5 L min-1 and 2 L min-1) applied during maintenance of anaesthesia on recovery from anaesthesia and early cognitive functions in geriatric patients. In this prospective, randomised, double-blind study, sixty patients were divided into two groups according to the amount of FGF. Minimal-flow anaesthesia (0.5 L min-1 FGF) was applied to group I and medium-flow anaesthesia (2 L min-1 FGF) was applied to group II during maintenance of anaesthesia. Following the termination of inhalation anaesthesia, recovery times were recorded. The evaluation of cognitive functions was performed using the Addenbrooke's Cognitive Examination (ACE-R). There was no significant difference between the two groups in terms of demographic characteristics and recovery (P > 0.05). There was no significant difference between the two groups in terms of the preoperative day, the first postoperative day, and the third postoperative day; ACE-R scores (P > 0.05). In group II, on the third postoperative day ACE-R scores were found to be significantly lower than the preoperative ACE-R scores (P=0.04). In group II, third postoperative day ACE-R memory sub-scores (14.53 ± 3.34) were found to be significantly lower than preoperative ACE-R memory sub-scores (15.03 ± 3.57) (P=0.04). In geriatric patients, minimal-flow anaesthesia was not superior to medium-flow anaesthesia in terms of recovery properties and cognitive functions. Keeping in mind that hypoxaemia and changes in anaesthesia levels may occur with the reduction of FGF, both minimal- and medium-flow anaesthesia can be applied with appropriate monitoring without adverse effects on recovery and cognitive functions.


Effect of Various Polyols on the Acid-Denatured States of Champedak Galactose-Binding Lectin.
Champedak galactose-binding (CGB) lectin is a tetrameric protein with noncovalently bound monomers, isolated from Artocarpus integer fruit seeds. We had previously reported existence of a structured monomer and an unfolded monomer of CGB lectin at pH 2.5 and pH 1.5, respectively. Polyols are known to induce significant refolding in denatured proteins and stabilize proteins against environmental stresses. Studies on the effect of various polyols on the acid-denatured states of CGB lectin are lacking. The objective of this study was to investigate the effects of four different polyols, namely, ethylene glycol, erythritol, xylitol and sorbitol on the acid-denatured states of CGB lectin. CGB lectin was subjected to acid denaturation at pH 2.5 and pH 1.5, both in the absence and presence of 30% (w/v) polyols, i.e. ethylene glycol, erythritol, xylitol and sorbitol. Thermal denaturation of the acid-denatured states was also studied in the absence and presence of these polyols. Different spectroscopic probes such as tryptophan fluorescence, ANS fluorescence and far-UV CD spectral signal were used to monitor structural changes in the acid-denatured states of CGB lectin in the presence of polyols. Presence of erythritol, xylitol and sorbitol in the incubation mixture was found to stabilize the lectin at both pH 2.5 and pH 1.5, as evident from the burial of the hydrophobic clusters and decreased polarity around Trp residues. These polyols also stabilized the acid-denatured states of CGB lectin against thermal denaturation by shifting the thermal transition curves towards higher temperatures. Exposure of the acid-denatured states of CGB lectin, obtained at pH 2.5 and pH 1.5 to 61°C and 51°C, respectively, induced formation of non-native β-structures, compared to that present at 25°C, and this phenomenon was significantly suppressed in the presence of these polyols. Based on the spectral data, both sorbitol and erythritol appeared to exude better stabilizing effect. On the other hand, ethylene glycol was shown to destabilize the aciddenatured states of CGB lectin. Thermal stabilization of the lectin was noticed in the presence of erythritol, xylitol and sorbitol at both pH 2.5 and pH 1.5. These polyols also stabilize the secondary and tertiary structures of the acid-denatured CGB lectin at 25°C. Ethylene glycol was proved to be a destabilizer of the acid-denatured CGB lectin.


Estrogen transiently increases delayed rectifier, voltage-dependent potassium currents in ovine gonadotropes.
Treatment of gonadotropes with estrogen (E) changes the electrophysiological response to gonadotropin-releasing hormone (GnRH) such that the cells are hyperpolarised immediately after stimulation with GnRH and then generate action potentials more frequently than non-E-treated cells. We investigated the role of K+ current in this altered response to GnRH using cultures of ewe pituitary cells enriched for gonadotropes. K+ current density was measured using nystatin-perforated whole-cell recordings in the voltage clamp mode. Treatment of cells with E for 16-20 h significantly (p < 0.01) increased the unit K+ current to 180% of that in vehicle-treated cells. Outward current in these cells flows predominantly through voltage-dependent, delayed rectifier K+ channels (IK), and E alters the magnitude of this current. The effect of E to increase the K+ current was dose- and time-dependent and was maximal after 16-20 h. The unit K+ current values returned to pre-treatment levels after 36 h of E treatment. Several cells were studied both before and after E treatment and the average effect of E on these cells was to increase the unit K+ current by 90%. The time-course of the effect of E on K+ current density is the same as the effect of E to increase LH release in vitro and in vivo. We conclude that the increase in K+ current may be an important part of the mechanism whereby E acts on gonadotropes to facilitate the LH surge which triggers ovulation.


Imaging of leiomyomas arising from Müllerian remnants in a case of Mayer-Rokitansky-Küster-Hauser syndrome.
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a rare congenital abnormality characterised by varying degrees of aplasia or hypoplasia of the uterus and vagina. Very rarely, leiomyomas or adenomyosis can develop in the Müllerian remnant tissue or rudimentary uterus. We present a case of a 43-year-old woman with MRKH syndrome, who presented with primary amenorrhoea and lower abdominal pain. On examination, a large pelvic mass was palpated and a provisional diagnosis of ovarian tumour was made. MRI showed multiple large leiomyomas arising from the Müllerian remnant tissue, and chronic torsion of the right ovary.


Meningococcal core and accessory phasomes vary by clonal complex.
Neisseria meningitidis is a Gram-negative human commensal pathogen, with extensive phenotypic plasticity afforded by phase-variable (PV) gene expression. Phase variation is a stochastic switch in gene expression from an ON to an OFF state, mediated by localized hypermutation of simple sequence repeats (SSRs). Circulating N. meningitidis clones vary in propensity to cause disease, with some clonal complexes (ccs) classified as hypervirulent and others as carriage-associated. We examined the PV gene repertoires, or phasome, of these lineages in order to determine whether phase variation contributes to disease propensity. We analysed 3328 genomes representative of nine circulating meningococcal ccs with PhasomeIt, a tool that identifies PV genes by the presence of SSRs and homologous gene clusters. The presence, absence and functions of all identified PV gene clusters were confirmed by annotation or blast searches within the Neisseria PubMLST database. While no significant differences were detected in the number of PV genes or the core, conserved phasome content between hypervirulent and carriage lineages, individual ccs exhibited major variations in PV gene numbers. Phylogenetic clusters produced by phasome or core genome analyses were similar, indicating co-evolution of PV genes with the core genome. While conservation of PV clusters is high, with 76 % present in all meningococcal isolates, maintenance of an SSR is variable, ranging from conserved in all isolates to present only in a single cc, indicating differing evolutionary trajectories for each lineage. Diverse functional groups of PV genes were present across the meningococcal lineages; however, the majority directly or indirectly influence bacterial surface antigens and could impact on future vaccine development. Finally, we observe that meningococci have open pan phasomes, indicating ongoing evolution of PV gene content and a significant potential for adaptive changes in this clinically relevant genus.


Cancer diagnosis by discrimination between normal and malignant human blood samples using attenuated total reflectance-Fourier transform infrared spectroscopy.
FTIR spectroscopy is a common technique for cancer diagnosis. Applied tissue samples are heterogeneous and may be damaged in preparation procedures. Easier sampling, more available samples and also easier process with assured results would be interesting. Whole blood samples include all of these qualifications and our hypothesis was the bio-molecular changes in blood which manifest themselves in different optical signatures, detectable by FTIR spectroscopy. Noncancerous blood samples were differentiated from cancerous ones using ATR-FTIR spectroscopy and LDA classification method. Procedure was 100 percent and 90 percent accurate in prediction of cancerous or noncancerous situation for 33 known and 10 unknown samples, respectively.


Effectiveness of L-asparaginase-based regimens compared to anthracycline-based regimens in newly diagnosed extranodal NK/T-cell lymphoma, nasal type: a single Mexican center experience.
Extranodal NK/T-cell lymphoma, nasal type (ENKTCL) has a high prevalence in Asia and Latin American countries, such as Mexico, where it encompasses 40% of all T-cell non-Hodgkin lymphomas. Historically, responses to anthracycline-based therapies have been disappointing. Since data about the effectiveness of L-asparaginase-based regimens in Mexico are limited, we compared both therapies in our center. We performed a retrospective cohort of patients with newly diagnosed ENKTCL, who were divided into two groups for treatment and analysis (group 1: L-asparaginase-based regimen and group 2: anthracycline-based regimen) between 2001 and 2016. Of 36 patients with newly-diagnosed ENKTCL, 33 received at least one cycle of chemotherapy (22 in group 1 and 11 in group 2). Over a median follow-up interval of 17 months (range, 0-167), a complete response (CR) was observed in 45.5% of patients in group 1, compared to 27% of group 2 (P=0.45). Progression was more frequently observed in group 2 than in group 1 (54.5% vs. 18.4%, P=0.04). The median overall survival (OS) was 44 months in group 1, compared to 5 months in group 2 (P=0.012). The multivariate analysis showed that failure to achieve a CR after first-line therapy was the only significant factor for OS (HR, 3.04; 95% CI, 1.4-6.5; P=0.005). L-asparaginase-based regimens for patients with newly-diagnosed ENKTCL confer a survival advantage over anthracycline-based regimens.


Comparative analysis of immunodeficiency in patients with monoclonal gammopathy of undetermined significance and patients with untreated multiple myeloma.
The objectives of this study were firstly, to compare the immunophenotype of patients with monoclonal gammopathy of undetermined significance (MGUS) with that of patients with newly diagnosed, untreated multiple myeloma (Unt. MM). Our second objective was to determine which variables might distinguish patients with MGUS and early MM. The CD4/CD8 ratio in both patient groups differed significantly from normal as a result of a decrease in the proportion of CD4+ cells. Similarly, surface immunoglobulin-positive (Ig+) B cells were significantly reduced in both groups. Also, some impairment of Ig secretion was observed. An in vitro specificity study of B cells showed an enriched proportion of B cells specific for tetanus toxoid (which may be indicative of enrichment for memory B cells) in both MGUS and Unt. MM patients. Further to this, in MM patients but not in MGUS patients, there was an enriched proportion of B cells specific for determinants on the F(ab')2 fragment of Ig. This suggests an anomalous auto-immune reactivity to polyclonal Ig molecules. In one of the two patients studied, who progressed from MGUS to MM, disease progression was accompanied by an increase in this anti-Ig reactivity. In both patients there was a decrease in CD4/CD8 ratio.


Embryonic neural retina collagen: in vitro synthesis of high molecular weight forms of type II plus a new genetic type.
Chicken neural retina cells from 6- to 7-day embryos were labeled with [(3)H]proline for 24 and 72 hr and the collagenous proteins of the medium were analyzed. Ninety percent of the collagenous proteins eluted from DEAE-cellulose columns as a peak near the middle of the gradient. Upon sodium dodecyl sulfate/polyacrylamide gel electrophoresis, this material consisted predominantly of a slowly migrating procollagen, a smaller amount of an intermediate migrating form, and some alpha-chain material. Limited enzymatic digestion of this DEAE peak material plus mapping of its CNBr peptides identified this material as a type II precursor. The remaining 10% of the collagenous proteins eluted from DEAE-cellulose at the end of the gradient. Electrophoresis of this fraction showed four major bands. Two migrated near the type II precursors, a third migrated somewhat more slowly, and the fourth was near beta-chain dimers. In addition, there were two minor bands. Limited pepsin digestion of this DEAE peak material produced two bands: one migrated slightly more slowly than alpha1, and the second, considerably more slowly. The CNBr peptide pattern of this material appears to be different from any previously described. Thus, neural retina cells in culture synthesize at least two genetically distinct classes of collagenous proteins. One represents precursors to type II. The second is composed of multiple, very high molecular weight forms which may represent precursors (procollagens) of a new genetic type(s) of collagen.


Recent Advances on Macrocyclic Trichothecenes, Their Bioactivities and Biosynthetic Pathway.
Macrocyclic trichothecenes are an important group of trichothecenes bearing a large ring. Despite the fact that many of trichothecenes are of concern in agriculture, food contamination, health care and building protection, the macrocyclic ones are becoming the research hotspot because of their diversity in structure and biologic activity. Several researchers have declared that macrocyclic trichothecenes have great potential to be developed as antitumor agents, due to the plenty of their compounds and bioactivities. In this review we summarize the newly discovered macrocyclic trichothecenes and their bioactivities over the last decade, as well as identifications of genes tri17 and tri18 involved in the trichothecene biosynthesis and putative biosynthetic pathway. According to the search results in database and phylogenetic trees generated in the review, the species of the genera Podostroma and Monosporascus would probably be great sources for producing macrocyclic trichothecenes. Moreover, we propose that the macrocyclic trichothecene roridin E could be formed via acylation or esterification of the long side chain linked with C-4 to the hydroxyl group at C-15, and vice versa. More assays and evidences are needed to support this hypothesis, which would promote the verification of the proposed pathway.


Hesitancy towards COVID-19 vaccines on social media in Canada.
To effectively end the pandemic, the acceptance of effective vaccines against COVID-19 is critical. Comments posted in online platforms act as a barometer for understanding public concerns regarding vaccination and can be used to inform communication strategies for the 'moveable middle'. The aim of this exploratory study was to identify online dialogue regarding the nature of vaccine hesitancy related to COVID-19 vaccine(s). We analyzed user comment threads in response to news reports regarding COVID-19 vaccines on the Canadian Broadcasting Corporation national news website (with as many as 9.4 million unique visitors per day). User comments (n = 1145) were extracted from 19 articles between March 2020 and June 15th, 2020. Comments were then coded inductively for content to establish a coding framework that was subsequently applied to the dataset. Our data provide empirical support for misrepresentation as a form of misinformation and further demonstrate the utility of social media content as data for social research that informs public health communication materials. The data point to the need for, and value of, rapid communication interventions to foster vaccine acceptance. False information will continue to create challenges for delivering COVID-19 vaccines. Communication strategies to get ahead of the pace of misinformation are critical, particularly in light of boosters and the possibility of COVID-19 vaccination on an annual basis.


Cross-Cultural Validation of the Polish Version of the ADI-R, Including New Algorithms for Toddlers and Young Preschoolers.
Autism Diagnostic Interview-Revised (ADI-R) is one of the most widely used standardized diagnostic instruments for autism spectrum disorder (ASD). This article presents findings from the validation of the Polish version of the Autism Diagnostic Interview-Revised (ADI-R-PL), including new algorithms for toddlers and preschoolers. The validation group consisted of 125 participants: 65 with Autism Spectrum Disorder (ASD group) and 60 in the control group, including individuals with non-ASD disorders and typical development. The normalization group consisted of 178 participants, including 118 with ASD. The ADI-R-PL was found to have good psychometric properties. Confirmatory factor analysis supported both a bifactor structure and three-factor model. The study has generated preliminary information about the psychometric properties of the new algorithms for toddlers and young preschoolers. To the best of our knowledge, this paper is the first to propose new cutoffs in three ADI-R domains for a non-English-speaking population.


Purification and Properties of a Soluble Methane Monooxygenase from Methylocystis sp. M.
A soluble methane monooxygenase (sMMO: EC 18.104.22.168) was purified from a type II obligate methanotroph, Methylocystis sp. M. Ion exchange chromatography elution separated the sMMO into three components, I, II, and III. Components II and III were purified to homogeneity and were essential for the sMMO activity. Components II and III had molecular masses of approximately 233,000 and 39,000, respectively. Component II consisted of three subunits with molecular masses of 55,000, 44,000, and 21,000, which appeared to be present in stoichiometric amounts, suggesting a (αβγ)2 configuration in the native protein. Component II contained 1-4 mol of iron and was considered to be a hydroxylase. Component III was a flavoprotein, which contained 1 mol of FAD as well as 1-2mol of iron. It catalyzed the reduction of K3Fe(CN)6 and 2,6-dichloroindophenol by NADH. Component I, which was partially purified and not essential for sMMO activity, stimulated the activity by about 11-fold. Its stimulation could be replaced by addition of Fe(2+). The molecular mass of the partially purified component I was estimated to be from 35,000 to 40,000 based on gel filtration, which suggested the presence of a new type of regulatory protein of sMMO.


Targeted deletion of Atg5 in chondrocytes promotes age-related osteoarthritis.
It has been suggested that the lysosomal recycling process called macro-autophagy plays a role in osteoarthritis development. We thus decided to genetically ablate the autophagy-indispensable Atg5 gene specifically in chondrocytes and analyse the development of osteoarthritis upon aging and in a post-traumatic model. Mice lacking the Atg5 gene in their chondrocytes (Atg5cKO) were generated by crossing Atg5-floxed mice with transgenic mice that expressed cre recombinase driven by the collagen type 2 promoter. Animals were analysed at the age of 2, 6 and 12 months for age-related osteoarthritis or underwent mini-open partial medial meniscectomy at 2 months of age and were analysed 1 or 2 months after surgery. We evaluated osteoarthritis using the Osteoarthritis Research Society International (OARSI) scoring on safranin-O-stained samples. Cell death was evaluated by terminal deoxy-nucleotidyl-transferase-mediated deoxy-UTP nick end labelling (TUNEL) and by immunostaining of cleaved caspases. We observed the development of osteoarthritis in Atg5cKO mice with aging including fibrillation and loss of proteoglycans, which was particularly severe in males. The ablation of Atg5 was associated with an increased cell death as assessed by TUNEL, cleaved caspase 3 and cleaved caspase 9. Surprisingly, no difference in the development of post-traumatic osteoarthritis was observed between Atg5cKO and control mice. Autophagy protects from age-related osteoarthritis by facilitating chondrocyte survival.


Streamlined duplex live-dead microplate assay for cultured cells.
A duplex fluorescence assay to assess the viability of cells cultured in multi-well plates is described, which can be carried out in the original culture plate using a plate reader, without exchanges of culture or assay medium, or transfer of cells or cell supernatant. The method uses freshly prepared reagents and does not rely on a proprietary, commercially supplied kit. Following experimental treatment, calcein acetoxymethyl ester (CaAM) is added to each well of cultured cells; after 30 min, the fluorescence intensity (emission λmax ∼ 530 nm) is measured. The signal is due to formation of calcein, which is produced from CaAM by action of esterase activity found in intact live cells. Since live cells may express plasma membrane multidrug transport proteins, especially of the ABC transporter family, the CaAM incubation is carried out in the presence of an inhibitor of this efflux process, thereby improving the dynamic range of the assay. Next, SYTOX® Orange (SO) is added to the culture wells, and, after a 30-min incubation, fluorescence intensity (emission λmax ∼ 590 nm) is measured again. SO is excluded from cells that have an intact plasma membrane, but penetrates dead/dying cells and can diffuse into the nucleus, where it binds to and forms a fluorescent complex with DNA. The CaAM already added to the wells causes no interference with the latter fluorescent signal. At the conclusion of the duplex assay, both live and dead cells remain in the culture wells and can be documented by digital imaging to demonstrate correlation of cellular morphology with the assay output. Two examples of the application of this method are provided, using cytotoxic compounds having different mechanisms of action.


Ex vivo Culture and Contractile Force Measurements of Non-human Primate Heart Slices.
Cardiovascular diseases are the leading cause of death and morbidity worldwide. Patient mortality has been successfully reduced by nearly half in the last four decades, mainly due to advances in minimally invasive surgery techniques and interventional cardiology methods. However, a major hurdle is still the translational gap between preclinical findings and the conversion into effective therapies, which is partly due to the use of model systems that fail to recapitulate key aspects of human physiology and disease. Large animal models such as pigs and non-human primates are highly valuable because they closely resemble humans but are costly and time intensive. Here, we provide a method for long-term ex vivo culture of non-human primate (NHP) myocardial tissue that offers a powerful alternative for a wide range of applications including electrophysiology studies, drug screening, and gene function analyses.


Prevalence and Correlates of Preschool Overweight and Obesity Amidst the Nutrition Transition: Findings from a National Cross-Sectional Study in Lebanon.
There is increasing evidence linking early life adiposity to disease risk later in life. This study aims at determining the prevalence and correlates of overweight and obesity among preschoolers in Lebanon. A national cross-sectional survey was conducted amongst 2-5 years old children (n = 525). Socio-demographic, lifestyle, dietary, and anthropometric data were obtained. The prevalence of overweight and obesity was estimated at 6.5% and 2.7%, respectively. Based on stepwise logistic regression for the prediction of overweight and obesity (combined), the variance accounted for by the first block (socioeconomic, parental characteristics) was 11.9%, with higher father's education (OR = 5.31, 95% CI: 1.04-27.26) and the presence of household helper (OR = 2.19, 95% CI: 1.05-4.56) being significant predictors. The second block of variables (eating habits) significantly improved the prediction of overweight/obesity to reach 21%, with eating in front of the television (OR = 1.07, 95% CI: 1.02-1.13) and satiety responsiveness (OR = 0.83, 95% CI: 0.70-0.99) being significantly associated with overweight/obesity. In the third block, fat intake remained a significant predictor of overweight/obesity (OR = 2.31, 95% CI: 1.13-4.75). This study identified specific risk factors for preschool overweight/obesity in Lebanon and characterized children from high socioeconomic backgrounds as important target groups for preventive interventions. These findings may be of significance to other middle-income countries in similar stages of nutrition transition.


The biosynthesis of dicoumarol.
Micro-organisms have been isolated that can utilize o-coumaric acid as a sole carbon source with the subsequent production of 4-hydroxycoumarin and dicoumarol. One of these organisms, Penicillium jenseni, has been used to examine the biosynthesis of dicoumarol. Certain thermophilic fungi have also been found that can convert o-coumaric acid into dicoumarol.


Nutritional status, management and clinical outcomes in patients with esophageal and gastro-oesophageal cancers: A descriptive study.
The aims of this study were to investigate the nutritional management practice and nutritional status of patients with oesophageal and gastro-oesophageal cancers, and to propose strategies for improving their nutritional and clinical outcomes. All patients diagnosed with oesophageal and gastro-oesophageal cancers and treated with chemotherapy and/or radiotherapy at the Liverpool Cancer Therapy Centre (between August 2010 and February 2014) were included in this retrospective study. Patient and tumour characteristics, nutritional status and management were compared to clinical outcomes. A total of 69 patients met the inclusion criteria. The median weight loss prior to treatment commencement was 10.5% (Interquartile Range (IQR) = 6.6-15.4). A decline in nutritional status continued throughout the treatment course. The median percentage of weight loss during treatment was 3.53% (IQR = 0.00-6.84). Seven and 19 patients required nutrition intervention using a feeding tube or stent insertion to manage dysphagia, respectively. In patients treated with a curative intent, radiotherapy was completed in 100% of those with a nasogastric tube insertion as compared to 80% who had a stent insertion. There was a higher percentage of patients from culturally and linguistically diverse (CALD) background, experiencing significant weight loss when compared with their non-CALD counterparts (P = 0.04). Patients with oesophageal and gastro-oesophageal cancers commonly present with significant weight loss and this continues during the course of their anti-cancer treatment. A standardised protocol of nutrition management for these cancer patients is recommended, focusing on assisting patients from CALD backgrounds.


Cystic lymphangioma of the mesentery causing intestinal obstruction.
Mesenteric cystic lymphangioma is a rare lesion that is not often described in the literature. A four-year-old boy, who presented with abdominal distension and pain, is reported. At surgery, a huge mesenteric cyst was found to be the cause of the intestinal obstruction and was completely excised. Histology was consistent with a cystic lymphangioma. Abdominal lymphangioma is a rare cause of bowel obstruction. Clinical presentation varies and may be misleading due to a lack of awareness of the clinical condition. Occasionally, the diagnosis is made during surgery. General awareness of this entity with a high index of suspicion is needed to avoid complications.


Epigallocatechin-3-Gallate Therapeutic Potential in Cancer: Mechanism of Action and Clinical Implications.
Cellular signaling pathways involved in the maintenance of the equilibrium between cell proliferation and apoptosis have emerged as rational targets that can be exploited in the prevention and treatment of cancer. Epigallocatechin-3-gallate (EGCG) is the most abundant phenolic compound found in green tea. It has been shown to regulate multiple crucial cellular signaling pathways, including those mediated by EGFR, JAK-STAT, MAPKs, NF-κB, PI3K-AKT-mTOR, and others. Deregulation of the abovementioned pathways is involved in the pathophysiology of cancer. It has been demonstrated that EGCG may exert anti-proliferative, anti-inflammatory, and apoptosis-inducing effects or induce epigenetic changes. Furthermore, preclinical and clinical studies suggest that EGCG may be used in the treatment of numerous disorders, including cancer. This review aims to summarize the existing knowledge regarding the biological properties of EGCG, especially in the context of cancer treatment and prophylaxis.


MCPH1 patient cells exhibit delayed release from DNA damage-induced G2/M checkpoint arrest.
Mutations in the MCPH1 gene cause primary microcephaly associated with a unique cellular phenotype of misregulated chromosome condensation. The encoded protein contains three BRCT domains, and accumulating data show that MCPH1 is involved in the DNA damage response. However, most of this evidence has been generated by experiments using RNA interference (RNAi) and cells from non-human model organisms. Here, we demonstrate that patient-derived cell lines display a proficient G2/M checkpoint following ionizing irradiation (IR) despite homozygous truncating mutations in MCPH1. Moreover, chromosomal breakage rates and the relocation to DNA repair foci of several proteins functioning putatively in an MCPH1-dependent manner are normal in these cells. However, the MCPH1-deficient cells exhibit a slight delay in re-entering mitosis and delayed resolution of γH2AX foci following IR. Analysis of chromosome condensation behavior following IR suggests that these latter observations may be related to hypercondensation of the chromatin in cells with MCPH1 mutations. Our results indicate that the DNA damage response in human cells with truncating MCPH1 mutations differs significantly from the damage responses in cells of certain model organisms and in cells depleted of MCPH1 by RNAi. These subtle effects of human MCPH1 deficiency on the cellular DNA damage response may explain the absence of cancer predisposition in patients with biallelic MCPH1 mutations.


Reconstruction of traumatic nasal deformity in Orientals.
The application of rhinoplasty in the treatment of traumatic nasal deformity remains one of the most challenging problems for surgeons. Not only is the skeletal structure severely deformed, but the soft tissue may also be disfigured by a previous injury. Although autogenous bone and cartilage have been the primary choice for nasal reconstruction, synthetic material is desirable for various reasons. This article presents our experiences in the reconstruction of traumatic nasal deformity by using porous polyethylene (Medpor) implant in Orientals. From May 1998 to January 2005, 32 patients, including 15 males and 17 females, underwent augmentation rhinoplasty for the correction of traumatic nasal deformity. Of these, 30 patients had experienced associated midfacial bone fractures. The surgical procedures employed consisted of the open-tip approach that was followed by implant carving, placement and fixation. Twenty patients received lateral nasal osteotomies, and septoplasty procedures were performed in nine patients, simultaneously. External taping was done, and nostril tampons were placed postoperatively and left in situ for 3 days. The outcome was assessed by an independent investigator and the patients themselves. The patients were, on average, 22 years old at the time of reconstruction and were followed up for an average period of 25.4 months. The interval from injury to the rhinoplasty procedure was 304 days, on average. The average length of dorsal grafts was 44.9 mm. The overall aesthetic-improvement rate was 90.6%, and the patient-satisfaction rate was 84.4%. There were three complications, including an implant-tip exposure and two implant infections. A porous polyethylene (Medpor) implant is an effective alternative to autograft for correction of traumatic nasal deformity in Orientals to achieve a pleasing appearance of the nose without donor-site morbidity. A meticulous execution of concomitant procedures and impregnation of the implant by submerging it in an antibiotics solution prior to use were helpful in decreasing the complications.


Yeast growth selection system for detecting activity and inhibition of dimerization-dependent receptor tyrosine kinase.
Receptor tyrosine kinases (RTKs) play an important role in the control of fundamental cellular processes, including cell proliferation, migration, differentiation, and survival. Deregulated RTK signaling is critically involved in the development and progression of human cancer. Here, we present an assay for monitoring RTK activities in yeast, which provides an ideal heterologous cellular system to study these mammalian proteins in a null background environment. With our system, we have reconstituted aspects of the epidermal growth factor receptor (EGFR) signaling pathway as a model. Our approach is based on the Ras-recruitment system, in which membrane localization of a constitutively active human Ras achieved through protein-protein interactions can rescue growth of a temperature-sensitive yeast strain (cdc25-2). We show that co-expression of a dimerizing membrane-bound EGFR variant with specific adaptor proteins fused to the active Ras rescues growth of the cdc25-2 mutant yeast strain at the nonpermissive temperature. Using kinase-defective RTK mutants and selective EGFR kinase inhibitors, we demonstrate that growth rate of this yeast strain correlates with kinase activity of the EGFR derivatives. The RTK cellular assay presented here can be applied in high-throughput screens for selecting RTK-specific inhibitors that must be able to permeate the membrane and to function in an eukaryotic intrecellular environment.


Prevalence of plant beneficial and human pathogenic bacteria isolated from salad vegetables in India.
The study aimed at enumerating, identifying and categorizing the endophytic cultivable bacterial community in selected salad vegetables (carrot, cucumber, tomato and onion). Vegetable samples were collected from markets of two vegetable hot spot growing areas, during two different crop harvest seasons. Crude and diluted vegetable extracts were plated and the population of endophytic bacteria was assessed based on morphologically distinguishable colonies. The bacterial isolates were identified by growth in selective media, biochemical tests and 16S rRNA gene sequencing. The endophytic population was found to be comparably higher in cucumber and tomato in both of the sampling locations, whereas lower in carrot and onion. Bacterial isolates belonged to 5 classes covering 46 distinct species belonging to 19 genera. Human opportunistic pathogens were predominant in carrot and onion, whereas plant beneficial bacteria dominated in cucumber and tomato. Out of the 104 isolates, 16.25% are human pathogens and 26.5% are human opportunistic pathogens. Existence of a high population of plant beneficial bacteria was found to have suppressed the population of plant and human pathogens. There is a greater potential to study the native endophytic plant beneficial bacteria for developing them as biocontrol agents against human pathogens that are harboured by plants.


Microbiology and visual outcome of bleb-associated endophthalmitis.
To identify the microbiological spectrum and visual outcome of bleb-associated endophthalmitis. The medical records of patients treated for bleb-associated endophthalmitis were reviewed. Seventy-five patients were identified. Vitreous cultures were positive in 48 (64%) patients. The most common isolates were Streptococcus species in 24 (50%) eyes, gram-negative bacteria in 10 (20.8%) eyes, and Staphylococcus epidermidis in 7 (14.6%) eyes. Good visual outcome was achieved in 33 (44%) patients. On univariate analysis, shorter interval from onset of symptoms and treatment (p = .005), better initial visual acuity (p = .004), clear cornea at presentation (p = .048), isolation of less virulent organisms (p < .001), and absence of diabetes mellitus (p = .048) were significant positive predictors for good visual outcome. Bleb-associated endophthalmitis is associated with severe visual impairment. Clinical features associated with better visual outcome include early presentation, better presenting visual acuity, clear cornea at presentation, culture of a less virulent organism, and absence of diabetes mellitus.


Issues of electric shock in forensic medical practice.
The authors summarize the current state of knowledge of electric shock as a minority group of injuries in forensic practice. Initially, they deal with electric current as a physical quantity and its effect on the human body, how it enters and moves in the body, which tissues due to their electrical activity and properties are the best conductors and which, on the contrary, due to their high resistance, practically do not conduct current. Subsequently, different pathways of current passage through the body are mentioned, leading to different types of damage, the most serious of which appears to be damage to the cardiovascular system, which can lead to immediate death due to disturbed heart rhythm with subsequent arrest, but is also likely to leave permanent effects leading to late health complications. The effect of electric current at the cellular level is demonstrated in experimental animal models exposed to both low- and high-voltage electric current, with damage described not only at the site of entry but also by microscopic examination in organs distant from the site of direct electric current. Since the effect of electric current on the organism is not fully understood and experimental studies have produced results indicating damage mainly to the cardiovascular system, this opens up certain possibilities for improving not only the diagnosis of deaths due to electric shock but also the follow-up care of patients who survive these injuries.


[Hormone receptors and breast cancer prognosis].
Estradiol and progesterone assays in breast cancer have been developed for ten years and their clinical significance investigated in primary and metastatic tumors. The presence of estradiol and/or progesterone receptor is not related to the extension of the disease, the age of the patient or hormonal status. It seems to be related to the grade of histological differentiation. 1) Clear relationship exists between the presence of estradiol receptor and hormone dependency. 2) Estrogen receptor positive tumors demonstrate a more favorable outcome than the estrogen receptor negative one. According to recent data the presence of progesterone receptor is a better criteria than ER for long term pronostic.


Inhibition of Aldehyde Dehydrogenase-Activity Expands Multipotent Myeloid Progenitor Cells with Vascular Regenerative Function.
Blood-derived progenitor cell transplantation holds potential for the treatment of severe vascular diseases. Human umbilical cord blood (UCB)-derived hematopoietic progenitor cells purified using high aldehyde dehydrogenase (ALDHhi ) activity demonstrate pro-angiogenic functions following intramuscular (i.m.) transplantation into immunodeficient mice with hind-limb ischemia. Unfortunately, UCB ALDHhi cells are rare and prolonged ex vivo expansion leads to loss of high ALDH-activity and diminished vascular regenerative function. ALDH-activity generates retinoic acid, a potent driver of hematopoietic differentiation, creating a paradoxical challenge to expand UCB ALDHhi cells while limiting differentiation and retaining pro-angiogenic functions. We investigated whether inhibition of ALDH-activity during ex vivo expansion of UCB ALDHhi cells would prevent differentiation and expand progeny that retained pro-angiogenic functions after transplantation into non-obese diabetic/severe combined immunodeficient mice with femoral artery ligation-induced unilateral hind-limb ischemia. Human UCB ALDHhi cells were cultured under serum-free conditions for 9 days, with or without the reversible ALDH-inhibitor, diethylaminobenzaldehyde (DEAB). Although total cell numbers were increased >70-fold, the frequency of cells that retained ALDHhi /CD34+ phenotype was significantly diminished under basal conditions. In contrast, DEAB-inhibition increased total ALDHhi /CD34+ cell number by ≥10-fold, reduced differentiation marker (CD38) expression, and enhanced the retention of multipotent colony-forming cells in vitro. Proteomic analysis revealed that DEAB-treated cells upregulated anti-apoptotic protein expression and diminished production of proteins implicated with megakaryocyte differentiation. The i.m. transplantation of DEAB-treated cells into mice with hind-limb ischemia stimulated endothelial cell proliferation and augmented recovery of hind-limb perfusion. DEAB-inhibition of ALDH-activity delayed hematopoietic differentiation and expanded multipotent myeloid cells that accelerated vascular regeneration following i.m. transplantation in vivo. Stem Cells 2018;36:723-736.


Iterated Learning Models of Language Change: A Case Study of Sino-Korean Accent.
Iterated learning models of language evolution have typically been used to study the emergence of language, rather than historical language change. We use iterated learning models to investigate historical change in the accent classes of two Korean dialects. Simulations reveal that many of the patterns of historical change can be explained as resulting from successive generations of phonotactic learning. Comparisons between different iterated learning models also suggest that Korean learners' phonotactic generalizations are guided by storage of entire syllable-sized units, and provide evidence that perceptual confusions between different forms substantially impacted historical change. This suggests that in addition to accounting for the evolution of broad general characteristics of language, iterated learning models can also provide insight into more detailed patterns of historical language change.


Endoscopic ultrasound guided thrombin injection of angiographically occult pancreatitis associated visceral artery pseudoaneurysms: Case series.
Pseudoaneurysm is a known complication of pancreatitis associated with significant mortality and morbidity. Imaging plays an important role in the diagnosis and management. Computed tomography (CT) helps localize the lesion and the severity of the background pancreatitis but digital subtraction angiography with coil embolization is recommended to avoid bleeding and inadvertent surgery. However, in cases where angiographic coil embolization is not feasible due to technical reasons, thrombin injection via CT or ultrasound guidance remains a viable option and often described in literature. In this series, effort has been made to highlight the role of endoscopic ultrasound guided thrombin instillation especially in patients with poorly visualized pseudoaneurysm on ultrasound thereby avoiding surgery and the associated mortality and morbidity.


[On the morphology of flagella and fimbriae of Escherichia strains (author's transl)].
100 Escherichia-strains, isolated from urine and faeces, were investigated with regard to flagella and fimbriae by electron-microskopy. The flagella had a length of 3-6 mu and a diameter of ca 0.02 mu. The flagellation was different not only between to the single bacteria of the same strain, but also in the separated isolates. Of 50 strains from urine had 27 and of 50 strains from feces had 28 no flagella. Different Escherichia-strains contained fimbriae, the number of which was much higher with regard to the flagella. The length of the fimbriae differed between 0.25 and 2 mu, the diameter was constantly ca 8 nm. 21 strains of 100 (4 from 50 urine strains and 17 from 50 faeces strains) had no fimbriae.


Pretreatment proliferation parameters do not add predictive power to clinical factors in cervical cancer treated with definitive radiation therapy.
To examine the prognostic value of tumor proliferation measurements in women with carcinoma of the uterine cervix. We report an update of a prospective study focusing on whether pretreatment proliferation parameters are associated with clinical outcome, relative to other established clinical factors. One hundred and one patients were recruited into the study from years 1991 to 1999. The LI for in vivo bromodeoxyuridine incorporation by the tumor and the potential doubling time (T(pot)) were determined by flow cytometry (fc). LI and its staining pattern were also assessed by immunohistochemistry (ih) using tissue sections. Apoptosis was assessed histologically using morphological criteria. Patients were treated with definitive radiation therapy. A successful fc measurement for LI-fc and T(pot) was possible in 95 patients (94%). The median/mean LI-fc was 6.6/7.6% (range 1.4-36.1%), and for LI-ih, 10.8/11.5%. To date, 43 patients have died of disease, and the median follow-up for alive patients is 6.2 years (range 1.3-9.3 years). Among 88 patients who completely responded to treatment, 40 patients have relapsed (14 pelvic, 23 distant, and 3 pelvic and distant). In univariate analysis, the significant factors for adverse disease-free survival were large tumor size (P = 0.0001), low hemoglobin (P = 0.001), pelvic lymph node status (P = 0.004), stage (P = 0.013), and overall treatment time (P = 0.0008). In multivariate analysis, only tumor size, pelvic lymph node status, and overall treatment time remained significant for disease-free survival. LI-fc, LI-ih, T(pot), ploidy, pattern of bromodeoxyuridine staining, and apoptosis were not significantly associated with clinical outcome in univariate or multivariate analyses. These mature data indicate that none of the pretreatment proliferation parameters have prognostic significance in the radical radiotherapy of carcinoma of the uterine cervix, despite the significance of overall treatment time for treatment outcome.


Trauma registry methodology: a survey of trauma registry custodians to determine current approaches.
The global burden of injury is enormous, especially in developing countries. Trauma systems in highincome countries have reduced mortality and disability. An important component of trauma quality improvement programmes is the trauma registry which monitors the epidemiology, processes and outcomes of trauma care. There is a severe deficit of trauma registries in developing countries and there are few resources to support the development of trauma registries. Specifically, publicly available information of trauma registry methodology in developed trauma registries is sparse. The aim of this study was to describe and compare trauma registries globally. A survey of trauma registry custodians was conducted. Purposive sampling was used to select trauma registries following a structured review of the literature. Registries for which there were at least two included abstracts over the five-year period were defined as active and selected. Following piloting and revision, a detailed survey covering physical and human resources, administration and methodology was distributed. The survey responses were analysed; single hospital and multi-hospital registries were compared. Eighty-four registries were emailed the survey. Sixty-five trauma registries participated, giving a response rate of 77%. Of the 65 participating registries, 40 were single hospital registries and 25 were multi-hospital registries. Fifteen countries were represented; more than half of the participating registries were based in the USA. There was considerable variation in resourcing and methodology between registries. A trauma registry most commonly had at least three staff, reported to both the hospital and government, included more than 1000 cases annually, listed admission, death and transfer amongst inclusion criteria, mandated collection of more than 100 data elements, used AIS Version 2005 (2008 update) and used age, the Glasgow Coma Scale and the Injury Severity Score for injury severity adjustment. Whilst some characteristics were common across many trauma registries, the resourcing and methodology varied markedly. The common features identified may serve as a guide to those looking to establish a trauma registry. However much remains to be done for trauma registries to determine the best standardised approach.


Conformational changes in rhodopsin probed by surface plasmon resonance spectroscopy.
Surface plasmon resonance (SPR) spectroscopy has been used to follow incorporation and light-induced conformational changes in bovine rhodopsin reconstituted into an egg phosphatidylcholine bilayer deposited on a thin silver film. The magnitude of the SPR spectral changes caused by light varies with pH in a manner paralleling that in flash photolysis experiments, which monitor formation of metarhodopsin II. Irradiation produces an increase of approximately 4 A in the average thickness of the proteolipid layer, consistent with exposure of recognition sites for the G protein. The results demonstrate that the SPR technology described herein may be used to monitor conformational events in membrane-associated receptors such as rhodopsin.


HIV education and the law: a critical review.
So far, the law has been used more to limit than to encourage effective HIV education. In this article, I will discuss how the law has largely failed as a tool for compelling the government to educate effectively, and, indeed, has provided only lukewarm protection against the chilling effect of official ambivalence about explicit education. I will begin with a review of current approaches to HIV education and the education efforts of the first decade of the epidemic. I will conclude with a discussion of the role of courts and legislatures as health educators.


Clinical and immunomodulating effects of ketamine in horses with experimental endotoxemia.
Ketamine has immunomodulating effects both in vitro and in vivo during experimental endotoxemia in humans, rodents, and dogs. Subanesthetic doses of ketamine will attenuate the clinical and immunologic responses to experimental endotoxemia in horses. Nineteen healthy mares of various breeds. Experimental study. Horses were randomized into 2 groups: ketamine-treated horses (KET; n = 9) and saline-treated horses (SAL; n = 10). Both groups received 30 ng/kg of lipopolysaccharide (LPS, Escherichia coli, O55:B5) 1 hour after the start of a continuous rate infusion (CRI) of racemic ketamine (KET) or physiologic saline (SAL). Clinical and hematological responses were documented and plasma concentrations of tumor necrosis factor-α (TNF-α) and thromboxane B(2) (TXB(2)) were quantified. All horses safely completed the study. The KET group exhibited transient excitation during the ketamine loading infusion (P < .05) and 1 hour after discontinuation of administration (P < .05). Neutrophilic leukocytosis was greater in the KET group 8 and 24 hours after administration of LPS (P < .05). Minor perturbations of plasma biochemistry results were considered clinically insignificant. Plasma TNF-α and TXB(2) production peaked 1.5 and 1 hours, respectively, after administration of LPS in both groups, but a significant difference between treatment groups was not demonstrated. A subanesthetic ketamine CRI is well tolerated by horses. A significant effect on the clinical or immunologic response to LPS administration, as assessed by clinical observation, hematological parameters, and TNF-α and TXB(2) production, was not identified in healthy horses with the subanesthetic dose of racemic ketamine utilized in this study.


National surveillance of dialysis-associated diseases in the United States, 2001.
In December 2001, all U.S. chronic hemodialysis (HD) centers were surveyed regarding selected patient care practices and dialysis-associated diseases. The results were compared with similar surveys conducted in previous years. During 1997-2001, the percentage of patients vaccinated against hepatitis B virus (HBV) infection increased from 47% to 60% and the percentage of staff vaccinated increased from 87% to 89%. In 2001, an estimated 65% of patients had been vaccinated for influenza and 26% for pneumococcal pneumonia. In 2001, routine testing for antibody to hepatitis C virus (anti-HCV) was performed on staff at 42% of centers and on patients at 62% of centers; anti-HCV was found in 1.5% of staff and 8.6% of patients. In 2001, the incidence of HBV infection was higher among patients in centers where injectable medications were prepared at the dialysis station, and both HCV prevalence and incidence were higher among patients in centers where injectable medications were prepared at the dialysis station compared to a dedicated medication room. During 1995-2001, the percentage of patients who received dialysis through central catheters increased from 13% to 25%; this trend is worrisome, as infections and antimicrobial use are higher among patients receiving dialysis through catheters. However, during the same period, the percentage of patients receiving dialysis through fistulas increased from 22% to 30%. In 2001, 25% of catheters were used for new patients awaiting an arteriovenous (AV) access, 28% for established patients with a failed access awaiting new AV access, 40% as an access of last resort, and 6% for other reasons, including patient preference. The percentage of centers reporting one or more patients infected or colonized with vancomycin-resistant enterococcus (VRE) increased from 12% in 1995 to 31% in 2001.


gamma-Glutamyl transpeptidase activity in mice: age dependent changes and effect of cortisol.
gamma-Glutamyl transpeptidase (gamma-GT) activity in various organs of mice during ontogenesis has been determined. The activity profile in foetus, neonates and the adult animal were compared to ascertain the functional significance of the enzyme. In addition, the effect of cortisol on gamma-GT activity in adult kidney is presented.


Effect of titanium oxide nanoparticle incorporation into nm thick coatings deposited using an atmospheric pressure plasma.
This study reports on the use of an atmospheric plasma technique to incorporate metal oxide nanoparticles into nm thick siloxane coatings. Titanium dioxide (TiO2) particles with diameters of 30-80 nm, were mixed with a number of different siloxanes-polydimethylsiloxane, hexamethyldisiloxane and tetraethylorthosilicate (TEOS). The TiO2/TEOS mixture was found to give the most stable suspension, possibly due to the higher surface tension of TEOS compared with the other siloxanes. TiO2/TEOS mixtures with 2 to 10% by weight of the metal oxide were prepared and were then nebulised into a helium/oxygen atmospheric plasma. Polyethylene terepthalate (PET) and silicon wafer substrates were passed through this plasma using a reel-to-reel substrate manipulation system. SEM combined with EDX was used to examine the distribution of the metal oxide particles in the resultant coatings. The TEOS coating thickness without TiO2 addition was 9 nm. The composite coating consisted of a relatively homogeneous distribution of small agglomerates of the TiO2 nanoparticles in TEOS. A linear increase in the titanium surface concentration was observed with increase in the quantity of TiO2 added into the siloxane precursor. The chemical functionality of the siloxane coating was examined using FTIR spectroscopy and no significant spectrum differences was observed with the incorporation of the different concentrations of TiO2 into the polymer. There were also no changes observed in coating surface energy with TiO2 incorporation. Coating morphology was examined using optical profilometry and surface roughness (Ra) values increased from typical values of 0.8 nm for the TEOS coating to 4.1 nm for the TiO2/TEOS coating. The adhesion of the deposited coatings was compared using fragmentation tests. These were carried out through uniaxial tensile loading. The coating cracking pattern after applied strain of 20% was not observed to change significantly with the addition of TiO2 into the siloxane.


Fentanyl and other New Psychoactive Synthetic Opioids. Challenges to Prevention and Treatment.
Synthetic opioids have played a significant role in the current opioid crisis in the United States (U.S.) and Canada and are a matter of concern worldwide. New psychoactive opioids (NPOs) are classified in the internationally recognized new psychoactive substances (NPSs) category. This group comprises compounds that may have been synthesized decades ago but appeared only recently in the illicit drug market. Such is the case of fentanyl, fentanyl analogs, and non-fentanyl opioids. Most NPOs have effects similar to morphine, including euphoria and analgesia, and can produce fatal respiratory depression. Here, we present an overview of the systemic and molecular effects of main NPOs, their classification, and their pharmacological properties. We first review the fentanyl group of NPOs, including the four compounds of clinical use (fentanyl, alfentanil, sufentanil, and remifentanil) and the veterinary drug carfentanil. We also provide essential information on non-medical fentanyl analogs and other synthetic opioids such as brorphine, etonitazene, and MT-45, used as adulterants in commonly misused drugs. This paper also summarizes the scarce literature on the use of NPOs in Mexico. It concludes with a brief review of the challenges to prevention and treatment posed by NPOs and some recommendations to face them.


Race between virus and inflammasomes: inhibition or escape, intervention and therapy.
The inflammasome is a multiprotein complex that further regulates cell pyroptosis and inflammation by activating caspase-1. The assembly and activation of inflammasome are associated with a variety of diseases. Accumulative studies have shown that inflammasome is a key modulator of the host's defense response to viral infection. Indeed, it has been established that activation of inflammasome occurs during viral infection. At the same time, the host has evolved a variety of corresponding mechanisms to inhibit unnecessary inflammasome activation. Therefore, here, we review and summarize the latest research progress on the interaction between inflammosomes and viruses, highlight the assembly and activation of inflammosome in related cells after viral infection, as well as the corresponding molecular regulatory mechanisms, and elucidate the effects of this activation on virus immune escape and host innate and adaptive immune defenses. Finally, we also discuss the potential therapeutic strategies to prevent and/or ameliorate viral infection-related diseases via targeting inflammasomes and its products.


Maternal and infant health of Eastern Europeans in Bradford, UK: a qualitative study.
This qualitative study aimed to investigate maternal and infant health needs within Eastern European populations in Bradford. Evidence suggested that migrants from Eastern Europe had poor maternal and child health and increased rates of infant mortality. Health visitors, community midwives and specialist voluntary workers were involved. Eleven interviews took place. They were semi-structured and analysed using a thematic approach. A number of health needs were identified in Eastern European populations, including high rates of smoking and poor diet. Wider determinants of health such as poverty and poor housing were cited as commonplace for Eastern European migrants. There were numerous cultural barriers to health, such as discrimination, mobility, cultural practices regarding age at pregnancy, and disempowerment of women. Lastly, access to health services was identified as a significant issue and this was impacting on staff working with this population. This study demonstrated the complexity and interaction of health and social factors and their influence on utilisation of health services.


Interaction of human alpha fetoprotein with bilirubin.
Human alpha fetoprotein (AFP) binds bilirubin with an affinity somewhat lower than albumin. Free bilirubin was found to have an extinction maximum at 440 nm with an extinction coefficient of 4.97 x 10(4) M-1cm-1. AFP binding with the bile pigment elicits a blue shift while albumin interaction produced red spectral shift.


Phase separation of binary mixtures in thin films: Effects of an initial concentration gradient across the film.
We study the kinetics of phase separation of a binary (A,B) mixture confined in a thin film of thickness D by numerical simulations of the corresponding Cahn-Hilliard-Cook (CHC) model. The initial state consisted of 50% A:50% B with a concentration gradient across the film, i.e., the average order parameter profile is Ψav(z,t=0)=(2z/D-1)Ψg,0≤z≤D, for various choices of Ψg and D. The equilibrium state (for time t→∞) consists of coexisting A-rich and B-rich domains separated by interfaces oriented perpendicular to the surfaces. However, for sufficiently large Ψg, a (metastable) layered state is formed with a single interface parallel to the surfaces. This phenomenon is explained in terms of a competition between domain growth in the bulk and surface-directed spinodal decomposition (SDSD) that is caused by the gradient. Thus, gradients in the initial state can stabilize thin-film morphologies which are not stable in full equilibrium. This offers interesting possibilities as a method for preparing novel materials.


Beyond simple adaptation: Incorporating other evolutionary processes and concepts into eco-evolutionary dynamics.
Studies of eco-evolutionary dynamics have integrated evolution with ecological processes at multiple scales (populations, communities and ecosystems) and with multiple interspecific interactions (antagonistic, mutualistic and competitive). However, evolution has often been conceptualised as a simple process: short-term directional adaptation that increases population growth. Here we argue that diverse other evolutionary processes, well studied in population genetics and evolutionary ecology, should also be considered to explore the full spectrum of feedback between ecological and evolutionary processes. Relevant but underappreciated processes include (1) drift and mutation, (2) disruptive selection causing lineage diversification or speciation reversal and (3) evolution driven by relative fitness differences that may decrease population growth. Because eco-evolutionary dynamics have often been studied by population and community ecologists, it will be important to incorporate a variety of concepts in population genetics and evolutionary ecology to better understand and predict eco-evolutionary dynamics in nature.


Deep learning-derived 12-lead electrocardiogram-based genotype prediction for hypertrophic cardiomyopathy: a pilot study.
Objective: Given the psychosocial and ethical burden, patients with hypertrophic cardiomyopathy (HCMs) could benefit from the establishment of genetic probability prior to the test. This study aimed to develop a simple tool to provide genotype prediction for HCMs.Methods: A convolutional neural network (CNN) was built with the 12-lead electrocardiogram (ECG) of 124 HCMs who underwent genetic testing (GT), externally tested by predicting the genotype on another HCMs cohort (n = 54), and compared with the conventional methods (the Mayo and Toronto score). Using a third cohort of HCMs (n = 76), the role of the network in risk stratification was explored by calculating the sudden cardiac death (SCD) risk scorers (HCM risk-SCD) across the predicted genotypes. Score-CAM was employed to provide a visual explanation of the network.Results: Overall, 80 of 178 HCMs (45%) were genotype-positive. Using the 12-lead ECG as input, the network showed an area under the curve (AUC) of 0.89 (95% CI, 0.83-0.96) on the test set, outperforming the Mayo score (0.69 [95% CI, 0.65-0.78], p < 0.001) and the Toronto score (0.69 [95% CI, 0.64-0.75], p < 0.001). The network classified the third cohort into two groups (predicted genotype-negative vs. predicted genotype-positive). Compared with the former, patients predicted genotype-positive had a significantly higher HCM risk-SCD (0.04 ± 0.03 vs. 0.03 ± 0.02, p <0.01). Visualization indicated that the prediction was heavily influenced by the limb lead.Conclusions: The network demonstrated a promising ability in genotype prediction and risk assessment in HCM.


Enlargement of the ampullary gland and seminal vesicle, but not the prostate in int-2/Fgf-3 transgenic mice.
Expression of the int2/Fgf-3 gene occurs during normal embryonic development and is associated with mammary cancer in mice. Overexpression of this gene under the control of the mouse mammary tumor virus long terminal repeat (MMTV-LTR) in males was reported to result in prostatic enlargement. In this report male Fgf-3-overexpressing mice were shown to have enlarged ampullary glands, seminal vesicles, and ductus deferens; there was extensive epithelial hyperplasia in the ampullary glands and seminal vesicles. The prostates of these animals were of normal size and histology. The transgene was expressed in all of the enlarged organs, which are derived exclusively from the Wolffian duct. Male secondary sex organs derived from the urogenital sinus, e.g., the ventral prostate, coagulating gland, and bulbourethral glands, were normal and did not express the MMTV-LTR-driven Fgf-3 transgene. A dorsolateral prostate was also morphologically normal but did express the transgene. This study underscores the importance of careful organ identification in transgenic models in which gross organ enlargement or distortion occurs. It also highlights the heterogeneity of the response to Fgf-3 among the secondary sex organs and even within the prostate itself.


Microendoscopic discectomy compared with standard microsurgical discectomy for treatment of uncontained or large contained disc herniations.
Minimally invasive spinal techniques have been developed for years in an attempt to minimize trauma. However, most endoscopic techniques have been unable to address uncontained or large contained disc herniations. The aim of this prospective study was to compare the results of microendoscopic discectomy (MED) and microsurgical discectomy in the treatment of patients with uncontained or large contained disc herniations. An independent observer reviewed the treatment of 28 patients. The study group included 14 consecutive patients who underwent MED and 14 consecutive patients who underwent microsurgical discectomy for radicular pain secondary to uncontained or large contained disc herniations during the same period. Patients were followed up for an average of 12 months. They were assessed by use of Oswestry disability questionnaire and low back pain outcome score. The average outcome score improvement was of clinical significance in both patient groups. No difference in the scores was found between the two groups. Patients in the MED group required less postoperative analgesia during their stay. One patient in the MED group had a dural tear. MED is at least as effective as microsurgical discectomy for treatment of uncontained or large contained disc herniations, although the advantages over the open technique are short lived and did not reach significance. Nonetheless, for the surgeon accustomed to endoscopic techniques, MED seems to be a safe procedure.